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G Williams

Publications and source records attributed to G Williams.

At least 361 records · Page 20Linked to original sources

Cytokine-induced expression of nitric oxide synthase in C2C12 skeletal muscle myocytes.

Nitric oxide (NO) is an important mediator of diverse physiological and pathological responses. To determine whether NO production can be induced in skeletal muscle, we stimulated C2C12 mouse skeletal muscle myocytes with putative inducers of nitric oxide synthase (NOS). Neither lipopolysaccharide (LPS), interleukin-1 alpha (IL-1), tumor necrosis factor-alpha (TNF), nor interferon-gamma (IFN) was able to stimulate nitrite production by C2C12 cells when administered alone. However, combinations of IFN with either TNF or IL-1 resulted in significant nitrite production; simultaneous stimulation of cells with all three cytokines resulted in significantly increased nitrite production compared with any combination of two cytokines. Northern analysis of RNA obtained from stimulated C2C12 cells revealed induction of a single mRNA band that precisely coincided with the mRNA band of mouse macrophage-inducible NOS (iNOS). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis followed by sequencing of the 5' 765 bases of the skeletal muscle iNOS cDNA demonstrated exact homology with mouse macrophage iNOS. These findings indicate that combinations of cytokines stimulate NO production in skeletal muscle cells via induction of the macrophage-type iNOS gene.

Amino Acid Oxidoreductases↗

Effect of fibrous glass on rat pleural mesothelium. Histopathologic observations.

Female Fisher 344 rats (n = 25) were inoculated intrapleurally with a single 20-mg dose of (JM-100) fibrous glass. The mean length (2.2 microns) and width (0.15 microns) of the fibrous glass particles was within respirable range. Following inoculation, the rats were killed at timed intervals ranging from 2 to 430 d from inoculation. The pleural histopathologic changes were independently observed by a panel of three pathologists blinded to the time elapsed from inoculation. Fibrous adhesions, nodular lesions, and grossly evident tumor were noted in 15, 2, and 1 rat, respectively. In 1 rat there were combined adhesive and nodular changes, and in 6 there were no grossly detectable abnormalities. Chronic inflammation, fibrosis, and foreign body reaction were found in 9, 18, and 10 rats, respectively. Mesothelial hyperplasia and dysplasia were observed in 16 and 9 rats, respectively. Of 16 rats with the severest degree of hyperplasia and dysplasia, 3 developed malignant mesothelioma. This study suggests that a spectrum of rat pleural mesothelial histopathologic changes occurs before development of mesothelioma. The association of severe dysplasia in 3 rats with fully developed mesothelioma suggests that there may be a gradual progression from mesothelial hyperplasia or dysplasia to mesothelioma. Multivariate analysis further suggests that gross pleural nodular lesions and dysplasia may be significantly associated with the development of mesothelioma in this experimental model.

Animals↗

The cost effectiveness of combined rapid tests (Multistix) in screening for urinary tract infections.

Urinary tract infections (UTI) are relatively common in the urology outpatient's department and the renal transplant unit. Clinical diagnosis is imprecise and laboratory methods take time and are costly. Combined rapid tests (Multistix) were used to screen 400 consecutive mid stream specimens of urine: 200 from urology outpatients and 200 from renal transplant patients. All specimens were also tested in the laboratory. The negative predictive value for excluding UTI was excellent (> 98%) but positive predictive value for confirming presence of UTI was only 50%. However, with this simple screening method, up to 75% of urines can be excluded from laboratory analysis. Since there is a 20-fold difference in cost between dipstix and laboratory testing, the potential savings from this simple screening test is considerable.

Cost-Benefit Analysis↗

Effects of chronic vanadate administration in the STZ-induced diabetic rat. The antihyperglycemic action of vanadate is attributable entirely to its suppression of feeding.

Vanadate treatment can lower glycemia in diabetic rats. This action is generally attributed to vanadate's insulinomimetic properties, but vanadate also inhibits feeding, which could lower blood glucose. We therefore assessed the contribution of hypophagia to vanadate's antihyperglycemic action in a 3-week study of streptozocin-induced (STZ) diabetic rats. Untreated diabetic rats (n = 8) ate 54% more food than nondiabetic control rats (P < 0.001). Diabetic rats given sodium metavanadate (0.5 mg in 0.5 ml of water by gavage twice daily; n = 8) had significantly lower food intakes (P < 0.001) than untreated diabetic rats. In vanadate-treated diabetic rats, blood glucose levels were significantly lower than in untreated diabetic rats (P < 0.001). Untreated diabetic rats pair-fed to the food intake of the vanadate-treated diabetic rats (n = 8) showed virtually identical blood glucose falls (P > 0.05 vs. vanadate-treated diabetic rats). Vanadate treatment did not affect plasma insulin concentrations in diabetic rats. In nondiabetic rats (n = 8), vanadate treatment significantly reduced food intake (P < 0.05) and also lowered plasma insulin concentrations (P < 0.05) without significantly affecting glycemia. To investigate the mechanism of vanadate's hypophagic effect, we also measured regional hypothalamic levels of neuropeptide Y (NPY), a potent central appetite stimulant that is thought to drive hyperphagia in STZ-induced diabetes. Hypothalamic NPY concentrations rise markedly in diabetes and are normalized by insulin replacement. Unlike insulin, vanadate treatment did not normalize regional hypothalamic NPY concentrations in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The prediction of diabetic neuropathic plantar foot ulceration by liquid-crystal contact thermography.

OBJECTIVE: To assess whether the development of plantar foot ulceration could be predicted from the mean plantar foot temperature (MFT), as assessed by liquid-crystal contact thermography (LCT), in patients with peripheral neuropathy. RESEARCH DESIGN AND METHODS: Fifty patients with painful diabetic sensorimotor neuropathy were studied prospectively. Initially, 30 patients had no significant peripheral vascular disease (PVD) (ankle:brachial systolic blood pressure ratio > 1.0). LCT was used to assess the MFT from eight standard plantar sites. RESULTS: Initial MFT was higher in the patients without PVD (28.2 +/- 2.9 degrees C, mean +/- SD) than in patients with PVD (25.6 +/- 1.9 degrees C, P < 0.001) and in nondiabetic control subjects (25.7 +/- 2.1 degrees C, P < 0.001). At review, on average 3.6 (range 3.0-4.1) years later, 11 patients had died (6 of whom had PVD), and one was lost to follow-up. Six patients (seven feet) from the group without PVD had developed neuropathic plantar foot ulcers. The initial MFT was significantly higher in these seven feet (30.5 +/- 2.6 degrees C) than in the 38 feet of the 19 survivors in this group (27.8 +/- 2.3 degrees C, P < 0.01). Only one patient with PVD developed a plantar ulcer, although four required foot surgery for ischemic feet. CONCLUSIONS: LCT is a simple, inexpensive, and noninvasive method of identifying the neuropathic foot at increased risk of ulceration. Patients with high plantar foot temperatures are at increased risk of neuropathic foot ulceration. A normal or low MFT in the neuropathic foot is a marker of PVD, which confers an increased risk of ischemic foot disease.

Blood Pressure↗

Charge distribution of plasma IgG and IgG immune complexes in IgA nephropathy.

IgA nephropathy is characterized by a predominant deposition of IgA in the glomerular mesangium. However, in many cases, deposition of IgG also occurs and the concentration of circulating IgG immune complexes is higher than that in controls. To examine further the possible role of the charge of immunoglobulins in the pathogenesis of IgA nephropathy, we used isoelectric focusing (IEF) and densitometry to investigate the charge distribution of plasma IgG and IgG immune complexes in patients with this disease. Blood samples were taken from patients and healthy adults, and plasma and samples treated with 7.0% polyethylene glycol (PEG) were used. All samples were focused with a Multiphor II flatbet electrofocusing unit apparatus on an agarose gel, then immunofixed with polyclonal goat anti-human IgG, and stained with Coomassie blue R 250. The stained gels were analyzed by densitometry. 1. In plasma, the areas of PI 10-8.9 and PI 10-8.6 in IgA nephropathy were higher in the patients than in the controls. 2. In the 7.0% PEG precipitation, the area PI 8.1-6.1 was higher in the patients than in the controls. These findings suggest that a change in charge distribution of IgG and IgG immune complexes may contribute to the pathogenesis of IgA nephropathy.

Adult↗

Cortical area in the rat that mediates visual pattern discrimination.

In Experiment I, bilateral ablations of the caudolateral cortex involving Krieg's area 36 impaired discrimination of visual patterns but not delayed alternation. In Experiment II, the same type of lesions retarded postoperative learning to discriminate embedded visual patterns. In rats from the Experiment II tracers of axonal transport gave no signs of damage of the connections of the primary visual cortex. In agreement with this, Nissl stain of the dorsal lateral geniculate nuclei showed no neuronal loss or gliosis. These results suggest that caudo-lateral cortex in rats corresponds to the inferotemporal cortex of primates.

Animals↗

Comparison of three methods for measuring cigarette smoking in patients with vascular disease.

Although smoking has been identified as an independent risk factor in peripheral vascular disease, smokers do not accurately report their habit. Therefore, a cheap, non-invasive, objective method of measuring smoking behaviour in vascular surgical units is desirable. The value of end-expiratory carbon monoxide monitoring, which is both simple and inexpensive, was compared with two well-established, validated techniques (serum thiocyanate and blood carboxyhaemoglobin levels). Some 33 surgical patients with peripheral vascular disease provided samples of expired air for measurement of carbon monoxide and blood for carboxyhaemoglobin and thiocyanate levels. Carboxyhaemoglobin was the most sensitive test (90%) and had a high specificity (100%). Expired carbon monoxide was the least sensitive (60%) but had a high specificity (100%). The carbon monoxide and carboxyhaemoglobin levels correlated significantly (r = 0.829; P = 0.0001). Serum thiocyanate was relatively sensitive (80%) but had a lower specificity (70%). Conventional methods for assessing smoking behaviour have not gained widespread use because they are time-consuming, relatively invasive and require technical support. Non-invasive measurement of carbon monoxide gives immediate accurate results and is a useful inexpensive method for measuring cigarette smoking in patients attending a follow-up vascular unit.

Aged↗

Effects of antiplatelet therapy with indobufen or aspirin-dipyridamole on graft patency one year after coronary artery bypass grafting.

Saphenous vein coronary artery bypass graft patency can be increased by antiplatelet therapy. Aspirin plus dipyridamole are effective but are associated with tolerability problems. Indobufen is a possible alternative antiplatelet agent that may be better tolerated. A prospective, randomized, double-blind, parallel-group study was undertaken to compare the efficacy and safety of indobufen 200 mg twice daily with aspirin 300 mg thrice daily plus dipyridamole 75 mg thrice daily in preventing occlusion of autologous saphenous vein coronary artery bypass grafts. A total of 803 patients were randomized in the study, of whom 552 had a follow-up coronary angiogram approximately 1 year after operation. All anastomoses were patent in 56% of indobufen-treated patients and 59% of aspirin-dipyridamole recipients (p = 0.384). The percentage of all anastomoses patent was 82% in the indobufen group and 83% in the aspirin-dipyridamole group (p = 0.297). Mean postoperative blood loss was significantly less in the indobufen group (p = 0.043). Patients who received indobufen also had significantly fewer adverse events considered to be treatment-related compared with aspirin-dipyridamole recipients (p = 0.02). At the doses tested indobufen was as effective as aspirin plus dipyridamole in preventing occlusion of saphenous vein grafts and was better tolerated. Because indobufen was associated with less postoperative blood loss it may be used before operation in coronary artery bypass grafting.

Adolescent↗

Levels of matrix metalloproteases in bladder cancer correlate with tumor grade and invasion.

We have used quantitative zymography to measure levels of the type IV collagenases matrix metalloproteinase (MMP)-9 and MMP-2 in 42 biopsies of transitional cell carcinoma and in 7 biopsies of normal bladder. Mean levels of MMP-9 were significantly higher in tumor compared with normal samples (P = 0.08). Levels of MMP-9 and active MMP-2 increased with tumor grade (test for trend, P = 0.002 and P = 0.05, respectively). Levels of MMP-9 and activated MMP-2 were also higher in invasive tumors than in superficial ones (P = 0.001 and P = 0.008, respectively). In situ hybridization studies showed that the mRNAs for both MMP-2 and MMP-9 were located chiefly in the stroma rather than epithelial tumor cells and were concentrated at the interface between the two tissues.

Carcinoma, Transitional Cell↗

Village people.

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England↗