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S Wilson

Publications and source records attributed to S Wilson.

At least 109 records · Page 6Linked to original sources
PubMed2001

Hypoglycemia activates orexin neurons and selectively increases hypothalamic orexin-B levels: responses inhibited by feeding and possibly mediated by the nucleus of the solitary tract.

Orexins are novel appetite-stimulating peptides expressed in the lateral hypothalamic area (LHA), and their expression is stimulated by hypoglycemia in fasted rats. We investigated activation of orexin and other neurons during insulin-induced hypoglycemia using the immediate early gene product Fos. Insulin (50 U/kg) lowered plasma glucose by >50% after 5 h and stimulated feeding sixfold compared with saline-injected controls. Hypoglycemic rats allowed to feed and normoglycemic controls both showed sparse Fos-positive (Fos+) neurons in the LHA and the paraventricular nucleus (PVN) and arcuate nucleus (ARC) and showed none in the nucleus of the solitary tract (NTS), which relays visceral feeding signals to the LHA. In the LHA, total numbers of Fos+ neurons were comparable in fed hypoglycemic and control groups (60 +/- 6 vs. 52 +/- 4 cells/mm2, P > 0.05), as were Fos+ neurons immunoreactive for orexin (1.4 +/- 0.4 vs. 0.6 +/- 0.4 cells/mm2, P > 0.05). By contrast, hypoglycemic rats that were fasted showed significantly more Fos+ nuclei in the LHA (96 +/- 10 cells/mm2, P < 0.05, vs. both other groups) and Fos+ orexin neurons (8.4 +/- 3.3 cells/mm2, P < 0.001, vs. both other groups). They also showed two- to threefold more Fos+ nuclei (P < 0.001) in the PVN and ARC than both fed hypoglycemic rats and controls and showed strikingly abundant Fos+ neurons in the NTS and dorsal motor nucleus of the vagus. In parallel studies, whole hypothalamic orexin-A levels were not changed in hypoglycemic rats, whether fasted or freely fed, whereas orexin-B levels were 10-fold higher in hypoglycemic fasted rats than in control and hypoglycemic fed groups. These data support our hypothesis that orexin neurons are stimulated by falling glucose levels but are readily inhibited by signals related to nutrient ingestion and suggest that they may functionally link with neuronal activity in the NTS. Orexin-A and -B may play specific roles in behavioral or neuroendocrine responses to hypoglycemia.

Animals↗
PubMed2001

Effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency.

OBJECTIVE: To determine effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency. ANIMALS: 32 cats. PROCEDURE: Renal mass was surgically reduced, and cats were assigned to 1 of 4 eight-cat groups. Group 1 received placebo, whereas groups 2, 3, and 4 received benazepril hydrochloride orally once daily for approximately 6.5 months at the following doses: group 2, 0.25 to 0.50 mg/kg of body weight; group 3, 0.50 to 1.00 mg/kg; and group 4, 1.00 to 2.00 mg/kg. Arterial blood pressures, glomerular filtration rate (GFR), and renal plasma flow were determined before treatment and during the treatment period. Other determinants of renal hemodynamics were measured by use of micropuncture techniques. Renal biopsy specimens were examined microscopically. RESULTS: Compared with cats that received placebo, mean systolic arterial blood pressure was significantly less and GFR significantly greater in cats that received benazepril. Glomerular capillary pressure and the ratio of efferent to afferent arteriolar vascular resistance were also significantly less in treated cats. However, histologic differences in renal specimens were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with benazepril sustained single nephron GFR in remnant nephrons of cats with induced renal insufficiency. Administration of benazepril was also associated with a small but significant reduction in degree of systemic hypertension and an increase in whole kidney GFR. Benazepril may be an effective treatment to slow the rate of progression of renal failure in cats with renal disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

A novel assay for fungal ketol-isomerase activity.

2-Deoxy-D-glucose-6-phosphate ketol-isomerase (EC 2.6.1.16) forms glucosamine-6-phosphate and glutamate from fructose-6-phosphate and glutamine and plays an important role in chitin synthesis in fungi. We have established a new assay for fungal ketol-isomerase activity that is amenable to high throughput screening to identify enzyme inhibitors. Aspergillus fumigatus crude lysate was incubated with substrates and after incubation, reactions were terminated. Glutamate dehydrogenase, nitro blue tetrazolium chloride, phenazine methosulfate and beta-NAD were added and the amount of glutamate formed by ketol-isomerase activity was determined by measuring OD585nm. A feedback inhibitor, UDP-N-acetylglucosamine, of fungal ketol-isomerase was successfully detected by this assay (IC50=0.48 mM). In a pilot scale screening, an active extract from an extremophilic bacterium was found, and the extract showed antifungal activity against A. fumigatus, Candida albicans and C. glabrata.

Antifungal Agents↗
PubMed2001

The influence of fluid shear and AICI3 on the material properties of Pseudomonas aeruginosa PAO1 and Desulfovibrio sp. EX265 biofilms.

An understanding of the material properties of biofilms is important when describing how biofilms physically interact with their environment. In this study, aerobic biofilms of Pseudomonas aeruginosa PAO1 and anaerobic sulfate-reducing bacteria (SRB) biofilms of Desulfovibrio sp. EX265 were grown under different fluid shear stresses (tau g) in a chemostat recycle loop. Individual biofilm microcolonies were deformed by varying the fluid wall shear stress (tau w). The deformation was quantified in terms of strain (epsilon), and the relative strength of the biofilms was assessed using an apparent elastic coefficient (Eapp) and residual strain (epsilon r) after three cycles of deformation. Aluminium chloride (AlCl3) was then added to both sets of biofilm and the tests repeated. Biofilms grown under higher shear were more rigid and had a greater yield shear stress than those grown under lower shear. The addition of AlCl3 resulted in a significant increase in Eapp and also increased the yield point. We conclude that the strength of the biofilm is in part dependent on the shear under which the biofilm was grown and that the material properties of the biofilm may be manipulated through cation cross-linking of the extracellular polysaccharide (EPS) slime matrix.

Aluminum Chloride↗
PubMed2001

Factors associated with frequent admission to hospital for patients with chronic airflow limitation.

BACKGROUND: Chronic airflow limitation (CAL) is a common cause of admission and readmission to hospital. This study has explored associated factors with repeat hospital admission in patients with CAL. METHOD: A retrospective file review of patients admitted more than once to hospital during the 1999 calendar year, with a diagnosis of CAL. RESULTS: Two hundred and two patients admitted with CAL accounted for 284 admissions and 1815 bed days. Of these, 46 patients were admitted more than once accounting for 115 (40.5%) admissions and 730 (39.8%) bed days. The study found evidence of general practice involvement in 35 (30.5%) admissions immediately before presentation at the hospital emergency department (ED). The discharge summary following that admission revealed only 67 (54%) were referred back to their general practitioners for follow up. The number of admissions attending the ED between the hours of 9.00 am and 5.00 pm were 62 (53.9%) and 96 (83.5%) between the hours of 7.00 am and 10.00 pm. CONCLUSION: Treatments given in hospital were similar, in most cases, to what could be provided at home with appropriate community based support. General practitioners were involved in approximately one-third of those patients requiring admission or re-admission to hospital.

Female↗
PubMed2000

Cost effectiveness of initial endoscopy for dyspepsia in patients over age 50 years: a randomised controlled trial in primary care.

BACKGROUND: Dyspepsia can be managed by initial endoscopy and treatment based on endoscopic findings, or by empirical prescribing. We aimed to determine the cost effectiveness of initial endoscopy compared with usual management in patients with dyspepsia over age 50 years presenting to their primary care physician. METHODS: 422 patients were recruited and randomly assigned to initial endoscopy or usual management. Primary outcomes were effect of treatment on dyspepsia symptoms and cost effectiveness. Secondary outcomes were quality of life and patient satisfaction. Total costs were calculated from individual patient's use of resources with unit costs applied from national data. Statistical analysis of uncertainty on incremental cost-effectiveness ratio (ICER) was done along with a sensitivity analysis on unit costs with cost-effectiveness acceptability curves. FINDINGS: In the 12 months following recruitment, 213 (84%) patients had an endoscopy compared with 75 (41%) controls. Initial endoscopy resulted in a significant improvement in symptom score (p=0.03), and quality of life pain dimension (p=0.03), and a 48% reduction in the use of proton pump inhibitors (p=0.005). The ICER was Pound Sterling1728 (UK Pound Sterling) per patient symptom-free at 12 months. The ICER was very sensitive to the cost of endoscopy, and could be reduced to Pound Sterling165 if the unit cost of this procedure fell from Pound Sterling246 to Pound Sterling100. INTERPRETATION: Initial endoscopy in dyspeptic patients over age 50 might be a cost-effective intervention.

Aged↗
PubMed2000

Receptor for the pain modulatory neuropeptides FF and AF is an orphan G protein-coupled receptor.

Opiate tolerance and dependence are major clinical and social problems. The anti-opiate neuropeptides FF and AF (NPFF and NPAF) have been implicated in pain modulation as well as in opioid tolerance and may play a critical role in this process, although their mechanism of action has remained unknown. Here we describe a cDNA encoding a novel neuropeptide Y-like human orphan G protein-coupled receptor (GPCR), referred to as HLWAR77 for which NPAF and NPFF have high affinity. Cells transiently or stably expressing HLWAR77 bind and respond in a concentration-dependent manner to NPAF and NPFF and are also weakly activated by FMRF-amide (Phe-Met-Arg-Phe-amide) and a variety of related peptides. The high affinity and potency of human NPFF and human NPAF for HLWAR77 strongly suggest that these are the cognate ligands for this receptor. Expression of HLWAR77 was demonstrated in brain regions associated with opiate activity, consistent with the pain-modulating activity of these peptides, whereas the expression in adipose tissue suggests other physiological and pathophysiological activities for FMRF-amide neuropeptides. The discovery that the anti-opiate neuropeptides are the endogenous ligands for HLWAR77 will aid in defining the physiological role(s) of these ligands and facilitate the identification of receptor agonists and antagonists.

Amino Acid Sequence↗
PubMed2000

N-acylated alpha-(3-pyridylmethyl)-beta-aminotetralin antagoinists of the human neuropeptide Y Y5 receptor.

Alpha-(3-Pyridylmethyl)-beta-aminotetralins were acylated with amino-piperidinyl and-pyrrolidinyl acetic acids, and with (aminomethyl)cyclohexanecarboxylic acid. Reaction with acyl chlorides, chloroformates, and isocyanates gave amides 8e, carbamates 9, and ureas 10, which bound to the Y5 receptor with nanomolar affinity. Congeners 11a and 11d containing a terminal benzimidazolone group were shown to be functional Y5 antagonists.

2-Naphthylamine↗
PubMed2000

Identification of an EDG7 variant, HOFNH30, a G-protein-coupled receptor for lysophosphatidic acid.

We have identified a cDNA, designated HOFNH30, which encodes a 354 amino acid G-protein-coupled receptor (GPCR). This receptor has 96% amino acid identity to the Jurkat-T cell-derived EDG7 and could be a splice variant. RT-PCR analysis demonstrated that HOFNH30 mRNA is expressed in placenta whereas EDG7 mRNA shows highest expression in prostate. The HOFNH30 gene is localized to human chromosome 1p22. 3-1p31.1. When HOFNH30 was expressed in RBL-2H3 cells, LPA and phosphatidic acid (PA) induced a calcium mobilization response with EC(50) values of 13 nM and 3 microM, respectively. LPA also induced phosphorylation of mitogen-activated protein kinase (p42(MAPK) and p44(MAPK)) in HOFNH30-transfected but not vector-transfected RBL-2H3 cells. In the present study, we have identified a novel variant from the EDG receptor family, a GPCR for which LPA is a high-affinity endogenous ligand.

Amino Acid Sequence↗
PubMed2000

Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3.

Neuromedins are a family of peptides best known for their contractile activity on smooth muscle preparations. The biological mechanism of action of neuromedin U remains unknown, despite the fact that the peptide was first isolated in 1985. Here we show that neuromedin U potently activates the orphan G protein-coupled receptor FM3, with subnanomolar potency, when FM3 is transiently expressed in human HEK-293 cells. Neuromedins B, C, K, and N are all inactive at this receptor. Quantitative reverse transcriptase-polymerase chain reaction analysis of neuromedin U expression in a range of human tissues showed that the peptide is highly expressed in the intestine, pituitary, and bone marrow, with lower levels of expression seen in stomach, adipose tissue, lymphocytes, spleen, and the cortex. Similar analysis of FM3 expression showed that the receptor is widely expressed in human tissue with highest levels seen in adipose tissue, intestine, spleen, and lymphocytes, suggesting that neuromedin U may have a wide range of presently undetermined physiological effects. The discovery that neuromedin U is an endogenous agonist for FM3 will significantly aid the study of the full physiological role of this peptide.

Calcium↗
PubMed2000

Liver transplantation improves cirrhosis-associated impaired oral glucose tolerance.

BACKGROUND: Thirty-five percent to 80% of cirrhotic patients have impaired glucose tolerance (IGT) or diabetes mellitus (DM). Diabetic cirrhotics have higher morbidity and mortality than nondiabetics. Therefore, it would be worthwhile to determine whether liver transplantation improves glucose homeostasis in these patients. METHOD: A total of 26 patients awaiting liver transplantation were evaluated for impaired glucose homeostasis by fasting blood glucose and/or oral glucose tolerance tests (OGTT). Five patients underwent transplant surgery within 1 year of OGTT and had a repeat OGTT 3-6 months after transplantation. RESULTS: Sixty-five percent (17/26) of the patients had abnormal glucose homeostasis. Twenty-three percent (6/26) met American Diabetes Association criteria for DM, and another 42.3% (11/26) had IGT. All patients had normal HbA1C levels. After transplantation, the 2-hr blood glucose improved in four patients and the mean 2-hr glucose level was reduced (204 +/- 94 vs. 132 +/- 53 mg/dl [mean +/- SD, P=0.051]). CONCLUSION: Liver transplantation can reverse cirrhosis-associated impaired glucose tolerance.

Adult↗
PubMed2000

Vibrio parahaemolyticus infections in the United States, 1973-1998.

Vibrio parahaemolyticus infections are associated with consumption of raw or undercooked shellfish, contaminated food, and exposure of wounds to warm seawater. Foodborne outbreaks and sporadic infections from Vibrio species in 4 Gulf Coast states are reported routinely to the Centers for Disease Control and Prevention (CDC). Between 1988 and 1997, 345 sporadic V. parahaemolyticus infections were reported: 59% were gastroenteritis, 34% were wound infections, 5% were septicemia, and 2% were from other exposures. Forty-five percent of patients suffering from these conditions were hospitalized for their infections, and 88% of persons with acute gastroenteritis reported having eaten raw oysters during the week before their illness occurred. Between 1973 and 1998, 40 outbreaks of V. parahaemolyticus infections were reported to the CDC, and these outbreaks included >1000 illnesses. Most of these outbreaks occurred during the warmer months and were attributed to seafood, particularly shellfish. The median attack rate among persons who consumed the implicated seafood was 56%. To prevent V. parahaemolyticus infections, persons should avoid consumption of raw or undercooked shellfish and exposure of wounds to seawater.

Centers for Disease Control and Prevention, U.S.↗
PubMed2000

Down-regulation of orexin gene expression by severe obesity in the rats: studies in Zucker fatty and zucker diabetic fatty rats and effects of rosiglitazone.

Orexins (hypocretins) are lateral hypothalamic neuropeptides implicated in regulating feeding and the sleep-wake cycle. To study their possible relevance to obesity and diabetes, we measured hypothalamic prepro-orexin mRNA levels in obese, normoglycemic Zucker fatty (fa/fa) and in hyperglycemic, non-obese Zucker diabetic fatty (ZDF) rats. Hypothalamic prepro-orexin mRNA concentrations in Zucker fatty rats were 31% lower than those in lean controls (0. 69+/-0.06 vs. 1.00+/-0.10 arbitrary units, P<0.05), but did not differ between ZDF diabetic rats and non-diabetic controls. Treatment of ZDF diabetic rats with rosiglitazone (1 or 3 mg/kg body weight daily for 13 weeks) normalized plasma glucose and significantly reduced plasma insulin, while leptin levels were 67% higher than in untreated ZDF rats (20.2+/-0.5 vs. 12.1+/-2.5, P<0. 001). Rosiglitazone treatment markedly enhanced weight gain compared with untreated ZDF rats (final weight 732+/-13 g vs. 409+/-13 g, P<0. 001) even though they were restricted to the same food intake. Rosiglitazone-treated ZDF rats had significantly lower hypothalamic prepro-orexin mRNA levels (0.68+/-0.07 arbitrary units) than both non-diabetic lean controls (1.00+/-0.10, P=0.02) and untreated diabetics (1.03+/-0.14, P=0.03). Our data suggest that prepro-orexin gene expression may be suppressed by substantial weight gain. Obesity-related signals that might mediate this effect have not been identified, but plasma leptin, insulin and glucose are not obviously involved.

Animals↗