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S Shaw

Publications and source records attributed to S Shaw.

At least 91 records · Page 5Linked to original sources
PubMed2000

Failure to establish linkage on the X chromosome in 301 families with schizophrenia or schizoaffective disorder.

The hypothesis that a gene for susceptibility to psychosis (specifically in the X-Y homologous class) is located on the sex chromosomes has been proposed. Such a gene would account for the excess of sex chromosome anomalous males and females in populations of patients with psychosis, a tendency towards concordance by sex within families, and sex differences associated with psychosis and its underlying brain pathology. In earlier studies we observed small positive LOD scores in Xp11, and in a more recent and larger cohort of 178 sibling pairs, a peak multipoint nonparametric LOD score of 1. 55 at the locus DXS8032 in Xq21. The present study with a new set of markers extended the cohort to 301 ill sibling pairs and their parents. Despite the increase in sample size, the LOD score did not increase. A peak NPL of 1.55 was observed at the locus DXS1068 in proximal Xp, a region remote from the previous report. Separating families into those who were more likely to have X chromosome inheritance (maternal with no male to male transmission) did not yield stronger findings. In spite of the evidence that psychosis is related to a sex-dependent dimension of cerebral asymmetry, it is concluded that no consistent linkage of schizophrenia to the X chromosome can be demonstrated. In the context of the general failure of replication of linkage in psychosis, the possibility that the genetic predisposition to psychosis is contributed to by epigenetic modification rather than variations in the nucleotide sequence has to be considered.

Chromosome Mapping↗
PubMed2000

Dissociation of mitochondrial malate dehydrogenase into active soluble subunits.

Gel exclusion chromatographic studies demonstrate that cytosolic and mitochondrial malate dehydrogenases (cMDH and mMDH) dissociate into subunits in the presence of 0.1% of the non-ionic detergent Triton X-100 (TX-100). The presence of cofactor and catalytically competent cofactor-substrate pairs does not protect mMDH against this dissociation. In contrast, cMDH dimers resist dissociation in the presence of either addition. Since steady state kinetic studies indicate both enzymes are fully active in the presence of 0.1% TX-100, we conclude that quaternary structure is not a kinetically important feature of mMDH structure and cooperativity does not account for mMDH kinetic anomalies. In contrast, cooperativity is a reasonable explanation for cMDH kinetic properties even in the presence of 0.1% TX-100, since this enzyme's subunits associate in the presence of active site ligands. The existence of fully active mMDH subunits raises the possibility that this species rather than the dimer may be a constituent of proposed multi-enzyme complexes of the mitochondrion. Preliminary chromatographic experiments involving gently disrupted mitochondria have found MDH activity in differently sized complexes, all with molecular weights larger than the mMDH dimer but smaller than complexes anticipated for multi-enzyme complexes involving other enzymes and the mMDH dimer.

Animals↗
PubMed2000

Lack of evidence for linkage to chromosomes 13 and 8 for schizophrenia and schizoaffective disorder.

A previous report [Blouin et al., 1998: Nat Genet 20:70-73] suggesting linkage to chromosomes 13q32 and 8p21 in families with schizophrenia led us to investigate these regions in a large set of 301 multiplex families with schizophrenia. Multipoint analyses failed to reveal evidence for linkage to any portion of chromosome 13, while only a weakly positive score was present on 8p using the identical marker reported in the earlier report. Failure to confirm the Blouin et al claims in a substantially larger cohort adds emphasis to the inconsistency of the findings concerning linkage in schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:235-239, 2000.

Chromosomes, Human, Pair 13↗
PubMed2000

Stimulated response of peripheral lymphocytes may distinguish cyclosporine effect in renal transplant recipients receiving a cyclosporine+rapamycin regimen.

BACKGROUND: Clinically, cyclosporine (CSA, Neoral) is titrated to concentrations, and not to pharmacological effect. METHODS: Intracellular interleukin- (IL) 2 was measured in phorbol myristic acid-ionomycin-stimulated peripheral lymphocytes by flow cytometry, after isolation from 14 renal transplant recipients receiving CSA+prednisone, and double-blind rapamycin (rapamycin:placebo=4:1). RESULTS: The proportion (%) of CD4+IL-2+ lymphocytes corresponding to CSA levels (mean+/-SD ng/ml) measured preoperatively (TO=O), and on postoperative day 8, before (356+/-63), and 2 hr after the morning dose (Cmax=1567+/-669), decreased from 39+/-16 to 15+/-8 and 3+/-1.6, respectively. Reciprocally, unresponsive lymphocytes (%CD4+IL-2-) increased with increasing CSA levels and predicted an EC50 of 249 ng/ml (CSA concentration at which CD4+IL-2- cells increased by 50% over baseline) in an Emax pharmacodynamic model. CONCLUSIONS: Clinically, the pharmacological effect of CSA is quantifiable, and lies in the upper end of the predicted range. In our Neoral-treated sample population, Cmax was associated with the least variable "cyclosporine effect." Such information could potentially individualize immunosuppression, and lead to rational dosing strategies.

CD4-Positive T-Lymphocytes↗
PubMed2000

Enzymatic synthesis of cephalothin by penicillin G acylase*

Enzymatic synthesis of cephalothin from 7-aminocephalosporanic acid (7-ACA) and amide derivatives of 2-thienylacetic acid (2-TA) using penicillin G acylase (pen G acylase) was studied. Two amide derivatives of 2-TA namely 2-thienylacetamide (2-TAA) and 2-thienylacetohydroxamic acid (2-TAH) were used in this study. The main reason for choosing amide but not the methyl ester derivative of 2-TA for the enzymatic synthesis was to increase their solubilities in water. The solubility of 2-TA methyl ester (2-TAM), 2-TAA, and 2-TAH in aqueous solution is 8 +/- 0.05 mM, 87 +/- 0.75 mM and 120 +/- 1.65 mM, respectively. Enzymatic conversion of 2-TAH to cephalothin yielded side products but they were not found in the conversion of 2-TAA to cephalothin. The side products were derived from reactions between hydroxyamine and 7-ACA. The effects of pH, temperature, initial substrate concentrations and reaction time on the conversion of 2-TAA and 7-ACA to cephalothin were examined. The optimum reaction condition was determined at pH 6.5 and 10 approximately 15 degrees C. The best conversion yield of 72% was obtained when the initial concentration of 2-TAA and 7-ACA was at 0.4 M and 0.1 M, respectively. Furthermore, a one-step method was developed to purify cephalothin from the enzymatic reaction mixture with the purity of 91% and the recovery yield of 96%.

Journal Article↗
PubMed2000

Type A, but not type B, endothelin receptor antagonists significantly decrease portal pressure in portal hypertensive rats.

BACKGROUND/AIM: Endothelin-1 plays an important role in the regulation of portal hypertension; endothelin antagonists have been extensively studied in portal hypertensive animals. We aimed to evaluate the efficacy of highly selective endothelin antagonists in partial portal vein ligated (PPVL) rats. METHODS: Four groups of 7 male Sprague-Dawley rats were administered orally ABT-627 (ET(A)-selective), A-192621 (ET(B)-selective), or A-182086 (non-selective), with the fourth group serving as control. On the 3rd day after beginning treatment animals underwent PPVL. On the 11th day hemodynamics were studied and portal vein ET-1 was measured. RESULTS: In the control group portal pressure was 13.4+/-SD 0.2 mmHg; this increased to 14.9+/-1.8 (p<0.05) in the ET(B) blocked group. In contrast, ET(A) blockade improved portal hypertension (11.7+/-1.1, p<0.05), while the treatment with the non-selective antagonist had no effect (12.3+/-0.7 n.s.). Mean arterial pressure was not significantly affected by any treatment. Portal vein ET-1 was increased in all groups compared to controls; this increase was limited to the pre-stenotic area (79+/-43 vs 194+/-76 in the pre- and post-stenotic portal vein; p<0.0025). CONCLUSIONS: Oral administration of an ET(A) antagonist ameliorated portal hypertension; we suggest that long-term therapy of portal hypertension with selective ET(A) antagonists may be more beneficial than mixed antagonists.

Animals↗
PubMed2000

Ultrasound criteria in the diagnosis of polycystic ovary syndrome (PCOS).

Not all women with the polycystic ovary syndrome (PCOS) on ultrasound (US) will have the syndrome, and clinical and biochemical features of PCOS may be present without US features. The sensitivity of US in detecting PCOS was, therefore, prospectively determined in 72 women (32 PCOS and 40 controls). The most sensitive features were the presence of 10 or more follicles (82% and 69% in the left and right ovary) and a peripheral distribution of follicles (81.8% and 71.9% in the left and right ovary). Although ovarian enlargement and stromal brightness were not as sensitive as the previous criteria, stromal brightness was most specific. Combining all the criteria predicted a diagnosis of PCOS or control correctly in 86.4% of cases. This study shows that established US criteria of polycystic ovaries remain of value in the diagnosis of PCOS; however, the discrepancy between the left and right ovaries is an interesting but unexplained finding.

Female↗
PubMed2000

CNS oxidative stress associated with the kainic acid rodent model of experimental epilepsy.

The role of oxidative stress in seizure-induced brain injury was investigated in a kainic acid model of experimental epilepsy. Kainic acid (12.5 mg/kg) or saline was injected intraperitoneally into 12-week-old male Fischer 344 rats and sacrificed by decapitation at 4 and 24 h after injection. Markers of oxidative stress including protein carbonyls, thiobarbituric acid reactive material (TBARs), glutathione (GSH) and glutathione disulfide (GSSG) were measured in hippocampus, cortex, cerebellum and basal ganglia. Four hours after treatment, protein carbonyls were elevated by 103, 55, 52 and 32% in cortex, hippocampus, basal ganglia and cerebellum, respectively. TBARs were increased by 30-45% in all areas. After 24 h, elevated protein and lipid oxidative markers persisted in the hippocampus and cerebellum; by contrast, in the cortex, TBARs almost normalized to control values and protein carbonyls trended downward by one-half compared with measurements at 4 h, although this reduction relative to the 4 h timepoint did not reach statistical significance. In the basal ganglia, protein carbonyls approached control values at 24 h. GSSG levels were only increased statistically in the cortex after 4 h, GSH levels in all the regions were unchanged after treatment with kainic acid. However, in cortex, GSH levels correlated negatively with increases in protein and lipid oxidation (r = -0.69, P < 0.002). In contrast, significant correlations between GSH, protein carbonyls and TBARs measured in the hippocampus or cerebellum were not observed. Our data suggests that kainic acid induced similar oxidative stress in all of the brain regions that were examined, and that GSH plays a major antioxidant role in the cerebral cortex but not the hippocampus.

Animals↗
PubMed2000

Patch testing with corticosteroid mixes in Europe. A multicentre study of the EECDRG.

This study investigated whether a corticosteroid mix containing tixocortol pivalate, budesonide, and hydrocortisone-17-butyrate could detect contact allergy to corticosteroids. 2 corticosteroid mixes, 1 with a high (mix I) and 1 with a low (mix II) concentration and the 3 individual constituents, each at 2 concentrations, were inserted into the standard series of 16 participating clinics. Tests were read on day (D) 3 or 4. 5432 patients were tested, and 110 (2.0%) had positive reactions to at least 1 of the 8 test preparations. Of the 8 preparations, mix I identified most allergic patients, followed by mix II, budesonide 0.10%, budesonide 0.002%, and tixocortol pivalate, both concentrations (1.0 and 0.10%) tracing the same number. With the mixes, 53.2-59.6% of tixocortol pivalate allergy was missed. 47 patients were allergic to either concentration of tixocortol pivalate, 25% of these only to 1.0% and another 25% only to 0.10%. Testing with mix I and tixocortol pivalate 0.10% picked up 98/110, testing with tixocortol pivalate 1.0% and 0.10% and budesonide 0.10% picked up 105/110. 3379 patients were read on both D3 or D4 as well as on D7. Without a late reading (D7), up to 30% of contact allergy to corticosteroid markers was missed.

Administration, Topical↗
PubMed2000

Raised plasminogen activator inhibitor-1 (PAI-1) is not an independent risk factor in the polycystic ovary syndrome (PCOS).

BACKGROUND: It has been postulated that an insulin-driven increase in plasminogen activator inhibitor-1 (PAI-1) levels may link insulin resistance to anovulatory infertility in women with PCOS and that it may place them at increased risk of thromboembolic disease. However, previous studies have been conflicting because many have failed to control for body mass index (BMI) which may affect PAI-1. The aim of this study was to investigate PAI-1 activity in women with PCOS and to compare it with unaffected controls of a similar BMI. DESIGN AND PATIENTS: 41 women with PCOS and 25 weight-matched controls participated in this cross-sectional study. Patients were evaluated clinically and by pelvic ultrasound and fasting blood samples were taken for haematological and biochemical tests. MEASUREMENTS: PAI-1 activity, insulin, glucose, triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, FSH, LH, PRL, testosterone, SHBG, 17-hydroxyprogesterone, plasminogen, fibrinogen (alpha2 antiplasmin, blood pressure and insulin sensitivity with a homeostasis model assessment (HOMA) computer programme. RESULTS: There was no significant difference in BMI or in (log) PAI-1 activity in women with PCOS compared with controls (BMI 29.5 +/- 5.6 vs. 28.4 +/- 6.3 kg/m2, P = 0.25 and PAI-1 2.56 (SD 0.85) vs. 2.14 (SD 0.98) au/ml, P = 0.07). The median fasting insulin level was significantly higher (17 (4.6-134.5) vs. 9.6 (3.7-41.5) mU/l, P < 0.01), and insulin sensitivity significantly lower in the PCOS group, ( 43.17% (5. 48-160) vs. 82.8% (21.8-193), P < 0.01). Women with PCOS also had a significantly higher free androgen index, LH/FSH ratio and a lower HDL/total cholesterol ratio. However blood pressure and all other lipid and haematological measurements were not significantly different between both groups. There were significant positive correlations between (log) PAI-1 activity and BMI (rho = 0.61), triglycerides (rho = 0.49) and fasting insulin (rho = 0.60) and a negative correlation with HDL cholesterol (rho = - 0.46). Triglyceride concentrations showed the most significant relationship with (log) PAI-1 activity on multiple regression. 29% of PCO women (12/41) gave a positive family history of thrombosis compared to 8% (2/25) in the control group. CONCLUSION: Plasminogen activator inhibitor-1 activity is not raised in women with PCOS independent of obesity and these results do not support the hypothesis that it may contribute to their anovulatory infertility, or increase their risk of thrombosis. The only significant metabolic features of the PCOS independent of obesity are insulin resistance, hyperinsulinaemia and lower HDL/total cholesterol ratio. The higher frequency of a positive family history of thrombosis in these women nevertheless requires further explanation.

Adult↗
PubMed2000

Comparison of three methods to recover vancomycin-resistant enterococci (VRE) from perianal and environmental samples collected during a hospital outbreak of VRE.

OBJECTIVE: To establish an efficient and sensitive technique for recovering vancomycin-resistant enterococci (VRE) from perianal and environmental samples collected during implementation of control measures for an outbreak of VRE. DESIGN: Perianal and environmental samples were collected in triplicate on sterile swabs. One swab was used to inoculate a selective broth medium containing 6 pg of vancomycin and 8 pg of ciprofloxacin per mL, one to inoculate Campylobacter agar containing 10 microg/mL of vancomycin, and one to inoculate Enterococcosel agar containing 8 microg/mL of vancomycin. SETTING: Samples were collected in the intensive care units of a 600-bed university hospital over a period of 2 months. SAMPLE SELECTION: Patients and their immediate environment were sampled if they resided in a ward with a patient known to be colonized or infected with VRE. RESULTS: Of the 88 perianal samples obtained from 63 patients, 37 were positive for VRE by broth culture, with 36 also recovered on both types of solid media (sensitivity, 97.3%; negative predictive value, 98.1%). Of the initial samples collected from each of the 63 patients, 20 were positive for VRE by all methods. Of the 500 environmental samples cultured, 139 were positive for VRE in broth, with only 33 recovered on Campylobacter agar (sensitivity, 23.7%; negative predictive value, 77.2%) and 22 on Enterococcosel agar (sensitivity, 15.8%; negative predictive value, 75.2%). CONCLUSIONS: Our data indicate that, when performing surveillance cultures during an outbreak of VRE, use of an enrichment broth medium is required to recover VRE contaminating environmental surfaces; however, direct inoculation to selective solid medium is adequate to recover VRE in patient perianal specimens.

Agar↗
PubMed2000

Endothelin in atherosclerosis: importance of risk factors and therapeutic implications.

Endothelin (ET)-1, a potent vasoconstrictor peptide, is primarily released abluminally from endothelial cells and exerts its biological effect through the activation of specific ET receptors. Endothelin subtype A receptors (ET(A)) are involved in constriction and proliferation of vascular smooth muscle cells, whereas endothelin subtype B receptors (ET(B)) on endothelial cells mediate the formation of nitric oxide, which acts as vasodilator and inhibits platelet aggregation. Cardiovascular risk factors such as hypertension and aging, as well as hypercholesterolemia, which are precursors of atherosclerosis, and elevated ET-1 levels are found. The best approach to determine the contribution of endogenous ET to vascular structural and functional alterations can be achieved by chronic inhibition of ET receptors with ET receptor antagonists. Recent studies showed favourable effects of selective ET(A)-antagonists on vascular alterations in different experimental models of hypertension, hypercholesterolemia and atherosclerosis, suggesting that activation of the local ET system importantly contributes to endothelial dysfunction and vascular remodeling, mainly through ET(A) receptors. Chronic blockade of ET(A) receptors may be a new therapeutic approach for the treatment of atherosclerosis and its risk factors.

Aging↗
PubMed2000

Inverse regulation of endothelin-1 and nitric oxide metabolites in tissue with aging: implications for the age-dependent increase of cardiorenal disease.

Aging is an independent risk factor for cardiovascular and renal disease. The study reported here investigated whether aging affects endothelin-1 (ET-1) and tissue levels of the nitric oxide metabolites nitrite/nitrate in the kidney of rodents. Blood pressure was measured by the tail-cuff method, ET-1 protein was determined by radioimmunoassay/high-performance liquid chromatography (RIA/HPLC) and nitrite/nitrate was measured by ion-pairing chromatography. Compared to young male Wistar Kyoto rats (3 months of age), renal ET-1 protein levels in whole kidneys increased 3.6-fold at 24 months of age (from 70 +/- 9 to 253 +/- 43 pg/g tissue, p < 0.05, n = 6 each group). Similarly, renal ET-1 protein increased 1.7-fold in 18-month-old C57BL/6J mice as compared to 8-month-old adult animals (from 188 +/- 18 to 319 +/- 14 pg/g tissue, p < 0.05, n = 5-7). In female RoRo-Wistar rats (6, 18 and 33 months of age), tissue nitrite/nitrate levels in whole kidneys decreased with increasing age (from 232 +/- 25 to 130 +/- 6 micromol/l/g tissue, p < 0.05). Thus, aging in healthy rodents is associated with a marked upregulation of renal ET-1 protein content and a decrease in tissue nitrite/nitrate levels in whole kidneys, independent of blood pressure. Activation of the ET pathway with aging may promote the development of age-dependent diseases such as glomerulosclerosis, hypertension and atherosclerosis.

Aging↗
PubMed2000

Endothelin regulates angiotensin-converting enzyme in the mouse kidney.

Using the orally active endothelin-A- (ET(A)) receptor antagonist LU135252, we determined whether endothelin-1 (ET-1) and/or dietary fat may be involved in angiotensin-converting enzyme (ACE) regulation in vivo. In C57BL6/J mice, renal and pulmonary tissue ACE activity (nmol/l His-Leu/mg protein) was measured and ACE mRNA expression, tissue ET-1 protein content and nitrite/nitrate level were measured in the kidney. Western-type diet increased renal ACE activity by 70% (55 +/- 4 vs 33 +/- 3 nmol/l His-Leu/mg protein, p < 0.05) and increased renal ET-1 levels (267 +/- 19 pg/g vs 190 +/- 18, p < 0.05). Chronic LU135252 treatment completely prevented activation of renal ACE activity (13.3 +/- 0.3 His-Leu/mg protein nmol/l, p < 0.05) independent of ACE mRNA expression or renal ET-1 protein levels. Thus, dietary fat activates renal ACE activity and ET-1 is involved in regulation of tissue ACE activity in vivo independently of ACE mRNA expression.

Animals↗
PubMed2000

Appropriate timing of the 14C-urea breath test to establish eradication of Helicobacter pylori infection.

OBJECTIVE: The aim of this study was to determine the performance characteristics of the 14C-urea breath test (UBT) performed 2 wk after the completion of therapy for Helicobacter pylori using a 4 to 6 wk study as the gold standard. METHODS: Patients with active Helicobacter pylori infection at four medical centers received proton pump inhibitor-based triple or quadruple therapy for 10-14 days. Patients underwent the 14C-UBT 2 and 4-6 wk after the completion of therapy. A positive test was defined as 14CO2 excretion of >200 dpm, a negative test as <50 dpm, and an equivocal test as >50 but <200 dpm. Performance characteristics of the 2-wk UBT were calculated using the 4 to 6-wk result as a gold standard. RESULTS: Eighty-five patients were enrolled and 82 patients (mean +/- SD age, 62 +/- 15 yr; 15 women) completed the protocol. Four patients had equivocal UBT results and were excluded from the analysis. Of the 78 patients, 68 (87%) had a negative 4 to 6-wk UBT. The 2-week UBT yielded a sensitivity of 90% (95% confidence interval 72-100%), specificity of 99% (97-100%), and accuracy of 97% (93-100%). In patients with a persistently positive UBT, 14CO2 excretion at 2 wk was significantly lower than at 4-6 wk after therapy (p = 0.03). CONCLUSIONS: A UBT performed 2 wk after therapy yielded results comparable to 4 to 6 wk testing. Further studies to evaluate the optimal time of confirmatory testing in the age of more effective proton pump inhibitor-based triple therapies are warranted.

Breath Tests↗