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Biomedical subjects

D Williams

Publications and source records attributed to D Williams.

At least 271 records · Page 15Linked to original sources
PubMed1995

Effect of rapid correction of hyponatremia on the blood-brain barrier of rats.

Brain demyelination sometimes follows rapid correction of hyponatremia, especially if the hyponatremia is chronic. During correction brain water decreases and the brain shrinks. The present study examined whether such shrinkage might be sufficient to disrupt the tight junctions of the blood-brain barrier. Barrier intactness was evaluated using magnetic resonance imaging and intravenous gadolinium contrast administration. Hypertonic saline infusion rapidly increased the plasma sodium concentration and caused barrier disruption more frequently in chronic than in acute hyponatremic rats. Similar increases in plasma sodium concentration did not disrupt the barrier in normonatremic rats. The disruption appeared to be due to altered plasma osmolality since infusion of hypertonic mannitol, which raised plasma osmolality without changing the plasma sodium concentration, disrupted the barrier in hyponatremic but not normonatremic rats. Moreover, the osmotic threshold for barrier disruption was lowest in chronic hyponatremia, intermediate in acute hyponatremia, and highest in normonatremia. The greater susceptibility to osmotic disruption in chronic hyponatremia suggests that blood-brain barrier disruption may play a significant role in causing the demyelination sometimes found following too rapid correction of hyponatremia, possibly through exposure of oligodendrocytes to plasma macromolecules such as complement.

Animals↗
PubMed1995

Crystallization and preliminary crystallographic study of human CksHs1: a cell cycle regulatory protein.

The cell cycle regulatory protein CksHs1 has been crystallized in a form suitable for X-ray studies. CksHs1 crystals were grown in the presence of vanadate, a phosphatase inhibitor, but were also obtained with phosphate or tungstate as a cofactor. They belong to the hexagonal space group P6(1)22 with unit cell dimensions: a = b = 94 A, c = 131.6 A, and gamma = 120 degrees. The crystals grown in the presence of vanadate diffract X-rays to at least 2.8 A. Molecular replacement results from the homologous human CksHs2 structure reveal that a dimer forms the crystal habit, giving the unusual Vm value of 4.4 A3/Da or a solvent content of 72%.

CDC2-CDC28 Kinases↗
PubMed1995

A double mutant allele, csr1-4, of Arabidopsis thaliana encodes an acetolactate synthase with altered kinetics.

A comparison is made of the kinetic characteristics of acetolactate synthase (EC 4.1.3.18) in extracts from Columbia wild type and four near-isogenic, herbicide-resistant mutants of Arabidopsis thaliana (L.) Heynh. The mutants used were the chlorsulfuron-resistant GH50 (csr1-1), the imazapyr-resistant GH90 (csr1-2), the triazolopyrimidine-resistant Tzp5 (csr1-3) and the multiherbicide-resistant, double mutant GM4.8 (csr1-4), derived from csr1-1 and csr1-2 by intragenic recombination (G. Mourad et al. 1994, Mol. Gen. Genet. 243, 178-184). Kmapp and Vmax values for the substrate pyruvate were unaffected by any of the mutations giving rise to herbicide resistance. Feedback inhibition by L-valine (L-Val), L-leucine (L-Leu) and L-isoleucine (L-Ile) of acetolactate synthase extracted from wild type and mutants fitted a mixed competitive pattern most closely. Ki values for L-Val, L-Leu and L-Ile inhibition were not significantly different from wild type in extracts from csr1-1, csr1-2, and csr1-3. Ki values were significantly higher than wild type by two- and five-fold, respectively, for csr1-4 with L-Val and L-Leu but not L-Ile. GM4.8 (csr1-4) plants were also highly resistant in their growth to added L-Val and L-Leu.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetolactate Synthase↗
PubMed1995

Insulin sensitization in diabetic rat liver by an antihyperglycemic agent.

This study aimed to demonstrate directly that the thiazolidinedione pioglitazone acts as an insulin sensitizer. We tested the hypothesis that pioglitazone treatment of diabetic rats alters liver function such that responsiveness of selected genes to subsequent insulin regulation is enhanced. Although flux through gluconeogenic/glycolytic pathways involves regulation of many enzymes, we presently report the effects of insulin on expression of two key enzymes in these metabolic pathways, ie, phosphoenolpyruvate carboxykinase (PEPCK) and glucokinase (GK). Rats were either studied as nondiabetic controls or injected with streptozotocin as a model for insulin-deficient diabetes. Diabetic animals were treated without or with pioglitazone and subsequently examined for acute responses to insulin. Pioglitazone treatment of diabetic animals significantly enhanced the effects of insulin to reverse elevated blood glucose. Although the mean level of liver mRNA transcripts encoding PEPCK was increased to nearly 300% in diabetic animals as compared with nondiabetic controls (100%), it was significantly lower in pioglitazone-treated diabetic rats (119% of control) than in diabetic rats without pioglitazone (223% of control) after insulin treatment. By contrast, mRNA transcripts encoding GK were not detectable in diabetic animals, but were increased markedly by insulin treatment in all animal groups. Insulin-enhanced expression of GK was significantly greater in liver from animals that were treated earlier with pioglitazone (291% of control) than in liver from those that were untreated (214% of control). An amplified acute response of liver to insulin thus established pioglitazone as an insulin sensitizer. Our findings further showed that such sensitization can be developed even in the insulin-deficient state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Amantadine does not reduce cocaine use or craving in cocaine-dependent methadone maintenance patients.

We tested the efficacy of amantadine to reduce cocaine use or craving in cocaine-dependent methadone maintained patients. Two doses of amantadine (200 mg p.o. daily, n = 16, and 200 mg p.o. bid, n = 21) were tested against placebo, n = 22, in a random assignment, double-blind clinical trial lasting nine weeks. Amantadine was well tolerated. However, neither dose of amantadine was more effective than placebo in reducing cocaine use and craving.

Adult↗
PubMed1995

Pre-hospital care--current concepts.

After a brief outline of past developments in the training of ambulance personnel, this paper traces the adoption in the UK of Pre-Hospital Trauma Life Support (PHTLS) courses from the US. The 1991 World Student Games in Sheffield, UK led to liaison between training staff from South Yorkshire Metropolitan Ambulance and Paramedic Service (SYMAPS) and from Western New York Medical Training Institute. As a result, the trauma care policy of SYMAPS was altered from aiming to stabilise the patient at the scene of the accident to emphasising rapid and thorough assessment, packaging and transport. This is a resume of the scope of the PHTLS provider course. The course concentrates on the principles of PHTLS for the multisystems trauma victim.

Emergency Medical Services↗
PubMed1995

Macrosocial and environmental influences on minority health.

Ethnic minority populations show patterns of health, health care use, and mortality that differ from the overall U.S. population. Each of the broad groups of minorities (Asian Hispanic, Native, and African Americans) has a unique background of sociocultural factors that influence these patterns. Thus, the larger social environment for ethnic populations, including political, environmental, historical, and economic factors, is a major variable in possible health outcomes. The individual portions in this panel report of the conference seek to identify such factors for each ethnic group and to suggest those macrosocial influences that are most important for observed health effects.

Black or African American↗
PubMed1995

The relationship between age and cutaneous aryl hydrocarbon hydroxylase (AHH) activity.

Aryl hydrocarbon hydroxylase (AHH), a component of the mixed-function oxygenase system, has been identified in liver and in many extrahepatic tissues, including the skin. In this study, the effect of ageing on cutaneous AHH activity in both male and female Wistar and Brown Norwegian rats of two age groups (average ages being 44 and 130 weeks) was assessed using benzo(alpha)pyrene as substrate and by measuring the formation of the fluorescent metabolite 3-hydroxybenzo(alpha)pyrene. Results show that cutaneous metabolism of polycyclic aromatic hydrocarbons does not change between young adulthood and senescence in either male or female rats. Sex-related differences did occur, however, and may be explained, partly, by the existence of different molecular forms of cyt-P450. In conclusion, age does not appear to be a major determinant of basal cutaneous AHH activity in rats.

Aging↗
PubMed1995

Genotypic detection of Mycobacterium tuberculosis rifampin resistance: comparison of single-strand conformation polymorphism and dideoxy fingerprinting.

Detection of mutations in the rpoB gene of Mycobacterium tuberculosis can be used as an accurate predictor of rifampin resistance in the majority of strains tested. Simple but highly accurate screening methods must be developed for the detection of these mutations. Either DNA sequence analysis or single-strand conformation polymorphism (SSCP) screening can be used to detect rpoB mutations, but these techniques either are expensive or yield results that may prove difficult to interpret when used in a clinical setting. This report describes the use of dideoxy fingerprinting (ddF) as a postamplification screening method to identify rifampin-resistant genotypes. The ddF protocol was performed on the amplified rpoB fragment with no preparatory steps, thus making ddF practical for laboratories equipped for polyacrylamide gel electrophoresis. When compared with the results of SSCP analysis, ddF results were more easily interpreted and contained more sequence-dependent information that facilitated differentiation of functionally significant and silent mutations. The ddF method was used for genotypic determination of rifampin susceptibility of 20 multidrug-resistant strains of M. tuberculosis. The results of this analysis were concordant with DNA sequence analysis and conventional clinical laboratory methods.

DNA Fingerprinting↗
PubMed1995

Latex allergy in children with spina bifida.

We studied the prevalence of latex-specific IgE among the children in our myelomeningocele clinic and several groups of controls using skin tests, a commercially available ELISA and an in-house RAST. Thirty-nine of 83 (47%) children with myelomeningocele had antibodies directed against latex as did 6 of 40 (15.7%) chronically ill controls, 4 of 105 (3.8%) medical controls and 2 of 75 (2.7%) well controls. Within each study group the likelihood of a positive skin test increased with the number of operations the subject had undergone. Children with myelomeningocele were much more likely to have antibodies to latex than were chronically ill controls with similar surgical histories. A retrospective chart review of 18 years and a total of 646 operations disclosed only one episode of intraoperative anaphylaxis which appeared to be related to latex within our study group.

Adolescent↗
PubMed1995

Development of new nephrons in adult kidneys following gentamicin-induced nephrotoxicity.

Gentamicin-induced nephrotoxicity results in necrosis of proximal tubular epithelial cells. In mammals, the injured nephron can be repaired by migration and division of surviving cells. We examined this repair process in the fresh-water goldfish, Carassius auratus. Fish were given a single intraperitoneal injection of 50 mg/kg gentamicin and sacrificed at 1, 4, 14, and 21 days. Injured nephrons showed regeneration along the basement membrane several days following gentamicin administration. In addition, 2-3 weeks following the injection, entirely new nephrons formed in the renal interstitium. Development of new nephrons in adult fish kidneys provides an excellent model for studying renal development and toxicity, and could provide insights into new therapies for chronic renal disease.

Analysis of Variance↗
PubMed1995

Below the belt: the technology of incontinence.

At a time when advances in so many areas of medicine and surgery mean that hitherto catastrophic diseases can be prevented, diagnosed, or treated with amazing precision and efficiency, the urinary track remains relatively ignored by molecular biology and medical technology. This article addresses some of the reasons underlying this phenomenon and points to major technical and commercial opportunities in this neglected area.

Equipment and Supplies↗
PubMed1995

Polyurethane paranoia flexible friend or deadly foe?

One of the most versatile of all materials used in medical devices has been under a cloud of suspicion for a few years, because of concerns about degradability and carcinogenicity. There is considerable confusion about the exact nature of polyurethanes and the extent of the problem. This article attempts to explain the essentials of polyurethane chemistry and put these concerns into perspective.

Animals↗
PubMed1995

Beyond the barrier: devices inside the brain.

The brain is usually thought of as an extremely sensitive part of the body, which should be entered only with great caution. However, it does appear to be amenable to intervention with treatment involving devices in a number of circumstances. This article describes one such application.

Antineoplastic Agents, Alkylating↗