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Biomedical subjects

D Bennett

Publications and source records attributed to D Bennett.

At least 217 records · Page 12Linked to original sources

The influence of genetic background and the homologous chromosome 17 on t-haplotype transmission ratio distortion in mice.

Transmission ratio distortion is a characteristic of complete t-haplotypes, such that heterozygous males preferentially transmit the t-haplotype bearing chromosome 17 to the majority of their progeny. At least two genes contained within the t-haplotype have been identified as being required for such high transmission ratios. In this study we examine the effects of the genetic background and the chromosome homologous to the t-haplotype on transmission ratio distortion. We use two different congenic lines: BTBRTF/Nev.Ttf/t12, in which the t12 haplotype has a transmission ratio of 52%, and C3H/DiSn.Ttf/t12, in which the t12 haplotype has a transmission ratio of 99%. By intercrossing these two strains to produce reciprocal F1 and F2 generations, we have isolated the effects of the homologous chromosome 17 from the effects of the genetic background. We demonstrate that both the homologous chromosome and the genetic background have profound effects on t-haplotype transmission ratio distortion. Furthermore, it is evident that the t-haplotype transmission ratio behaves as a quantitative character rather than an intrinsic property of t-haplotypes.

Analysis of Variance↗

OSHA work-practice guidelines for personnel dealing with cytotoxic (antineoplastic) drugs. Occupational Safety and Health Administration.

Work-practice guidelines for personnel dealing with cytotoxic drugs (CDs) are presented. Current practices in the preparation, storage, administration, and disposal of CDs may expose pharmacists, nurses, physicians, and other health-care workers to high environmental levels of these drugs. OSHA has developed these guidelines to protect health-care workers from unnecessary exposure to CDs. A brief summary of the short-term and long-term hazards known to be associated with these drugs is presented. The risks to workers handling CDs are a combined result of the drugs' inherent toxicity and the extent to which workers are directly exposed to CDs via inhalation, absorption, and ingestion. Work-practice guidelines that can limit the exposure of workers to CDs and the equipment necessary to carry out these practices properly are described.

Antineoplastic Agents↗

Analysis of major histocompatibility complex haplotypes of t-chromosomes reveals that the majority of diversity is generated by recombination.

t-chromosomes are natural polymorphisms in feral populations of mice that are thought to be descended from a single ancestral chromosome. They carry an inversion of at least 10 cM surrounding the major histocompatibility complex (MHC) that effectively prevents recombination between a t-bearing chromosome and wild type chromosomes. However, on the rare occasion when two different t-chromosomes meet in a wild female, recombination occurs at an apparently normal rate. Since they contain the highly polymorphic MHC, their limited origin and restricted chances for recombination make t-chromosomes a valuable tool for studying the relative contributions of mutation and recombination to the generation of diversity. Using 13 different serological reagents to class I antigens, and studying restriction enzyme polymorphisms detected with three molecular probes for class II genes examined with three endonucleases, we present data indicating that the major factor responsible for the diversity of class I antigens is recombination, but that for class II genes, mutation must play an important role in addition to recombination.

Animals↗

Definitive chromosomal location of the H-2 complex by in situ hybridization to pachytene chromosomes.

Chromosome 17 of the mouse carries the H-2 complex and the T/t complex. An understanding of the organization of this region and an accurate genetic map of chromosome 17 would be of great value for both immunologists and developmental biologists. Until now the only maps available have been derived solely from recombinational studies using several translocations, an inherently inaccurate method. We have found the definitive location of the H-2 complex by the use of in situ hybridization. Our results show that both the T/t complex and the H-2 complex map to positions far more distal than the generally accepted map positions. This proves that recombination in Robertsonian chromosomes underestimates physical map distances on chromosome 17.

Animals↗

Contamination and effects in freshwater ditches resulting from an aerial application of cypermethrin.

Cypermethrin (Ripcord) was applied at 25 g ai ha-1 by fixed-wing aircraft to a large field (11.6 ha) of winter wheat bordered on three sides by drainage ditches. About 60% of the nominal application rate was deposited on the crop and about 6% (maximum) was deposited over the water surface. The amount of spray drift deposited upwind declined sharply with increasing distance from the treated field. Downwind, the spray drift was small but occurred over a much greater distance. Very low (0.03 micrograms liter-1 maximum) concentrations of cypermethrin were found in subsurface water samples and these declined rapidly after spraying. Bioassay tests, using a sensitive indicator species, confirmed that only a small amount of cypermethrin contamination had occurred in the ditch adjacent to the downwind perimeter of the field. Frequent sampling of the zooplankton and macroinvertebrate fauna of the ditches indicated that there were no marked biological effects resulting from the cypermethrin application. Only a few air-breathing corixids and the highly susceptible water mites showed minor short-term reductions in abundance after spraying. No effects were observed on either caged or indigenous fish stocks and no significant residues of cypermethrin were found in fish tissues.

Animals↗

Ultrastructural observations on the effect of azelaic acid on normal human melanocytes and a human melanoma cell line in tissue culture.

Azelaic acid has been shown clinically to have a cytotoxic effect on the abnormally active and malignant human melanocyte, but it has no apparent effect upon normal melanocytes. This difference in reactivity between normal and abnormal cells in vivo is further examined here in vitro. The disodium salt of azelaic acid (C(9)2Na) was added to pure and mixed cultures of normal human melanocytes and to cultured human melanoma cells, at 10(-3) M, 10(-2) M, 5 X 10(-2) M, and 10(-1) M for 1 and 6 h. Control cultures and cultures exposed to the same concentrations of the disodium salt of adipic acid (C(6)2Na) were also examined. No damage to cells of any line was observed with diacids at 10(-3) M or 10(-2) M up to 6 h. At 5 X 10(-2) M some mitochondria of melanoma cells appeared swollen. With C(6)2Na at 10(-1) M for I and 6 h, minimal swelling of mitochondria was observed in some cells of all lines. Pure normal melanocytes and melanocytes of mixed cultures exhibited greater swelling of mitochondria with 10(-1) M C(9)2Na at 1 and 6 h, but the mitochondria of the malignant melanocytes were massively swollen with destruction of cristae. Plasma and nuclear membranes and membranes of rough endoplasmic reticulum were intact, but Golgi membranes exhibited vesiculation. These results provide further evidence that azelaic acid damages the human malignant melanocyte and that one of its targets is the mitochondrion. Damage to normal melanocytes, found here, may be due to the fact that, in culture, they are more active than in intact epidermis.

Cell Line↗

A preliminary double-blind study of intravenous nitroglycerin in acute myocardial infarction.

A preliminary double-blind, placebo-controlled study of the effects of a 48-h intravenous infusion of nitroglycerin (NG) in 140 patients with acute myocardial infarction has been carried out. The patients were randomised to placebo or active treatment within 12 h of the onset of symptoms. Those patients treated with nitroglycerin showed a significant reduction on both days in systolic blood pressure, haemoglobin concentration, and packed cell volume. There was also a significant reduction in diamorphine usage in the first 24 h. There was a higher incidence (non-significant) of dysrhythmia in the placebo group despite an increased usage of antidysrhythmic therapy. The mortality rate in the placebo group was 13%, and 7.8% in the active treatment group, but this difference was not significant. At the 3-month follow-up, 83% of treated patients as opposed to 60% of placebo group were able to resume normal or near-normal activities. Preliminary findings suggest that intravenous NG may be useful treatment for patients with acute myocardial infarction and a larger-scale trial is warranted.

Adult↗

Gene mapping within the T/t complex of the mouse. IV: The inverted MHC is intermingled with several t-lethal genes.

Using a combination of classical genetics, serology, and molecular genetics, we have mapped as many as possible of the MHC components in t haplotypes. Results indicate that the whole MHC is included in a simple inversion with the relative positions of its genes being intact. Furthermore, some of the t-lethal mutations map very near to, or are intermingled with, components of the MHC. At the centromeric end the t12 lethal maps between TL and H-2D in the Qa region, and distally the tw5 lethal is inseparable from H-2K.

Alleles↗

Fate and biological effects of methyl parathion in outdoor ponds and laboratory aquaria. I. Fate.

Three outdoor ponds were treated with methyl parathion (MEP) applied beneath the water surface at a concentration of 100 micrograms liter-1. Laboratory aquaria containing either tap water, pond water, tap water plus plants, tap water plus sediment, or tap water plus sediment and plants were similarly treated. Samples of water, sediment, and fish were analyzed for residues of MEP. The rate of loss from water and concentrations found in sediment were compared with predictions based on a calculated rate of biodegradation and a sediment:water partition coefficient. The rate of loss of MEP from pond water isolated in an aquarium was similar to the predicted rate. However, the rate of loss from outdoor ponds, or from aquaria containing plants and sediment, was greater than predicted. MEP was not detected in sediment even though predicted concentrations far exceeded the limit of detection. These results are discussed and it is suggested that the rate of biodegradation in shallow bodies of water may be determined predominantly by bacteria attached to sediments and plants, rather than by planktonic bacteria. Bioaccumulation in fish was predicted from empirical equations based on the octanol:water partition coefficient. Observed values were in good agreement with predictions.

Animals↗

Atrial fibrillation.

Atrial fibrillation is a common arrhythmia and one which may cause pilot incapacitation. In many cases there may be no more than one episode and there will be no organic heart disease. Prediction of the risk of recurrence is not possible. Atrial fibrillation in both paroxysmal and persistent forms should be disqualifying for Class I or unrestricted Class III certification. Individuals with a single episode of atrial fibrillation related to a reversible toxic cause but with no evidence of organic heart disease could be considered for restricted duty subject to echocardiographic and ambulatory electrocardiographic follow up. Atrial flutter and atrial tachycardia should disbar from aircrew duties.

Adult↗

Generation of human C3a, C4a, and C5a anaphylatoxins by protein A of Staphylococcus aureus and immobilized protein A reagents used in serotherapy of cancer.

Protein A (SpA) alone or immobilized on bacteria (e.g., Cowan strain I), collodion charcoal, or on Sepharose have been used in serotherapy of cancer in humans and experimental animals. Because SpA forms complexes with IgG that can activate complement, and the physiologic response during treatment often involves hypocomplementemia and reactions that are similar to those induced by anaphylatoxins, we used sensitive and specific radioimmunoassays to test the ability of SpA reagents to generate C3a, C4a, and C5a from human serum. The yield of anaphylatoxins depended on the dose of SpA, with the maximum generation of C3a (47 to 55 micrograms/ml) and C5a (1.4 to 1.9 micrograms/ml) being produced with levels of SpA that were maximally precipitated from serum. Maximum C4a levels (up to 15 micrograms/ml) were obtained at concentrations of SpA equal to or greater than the dose required to give optimal precipitation. The maximum concentrations of anaphylatoxins correspond to essentially quantitative conversions of C3 to C3a, C4 to C4a, and 40% of C5 to C5a after correction for levels found in serum incubated in pyrogen-free saline. Preformed insoluble complexes prepared from either serum or monomeric IgG also were capable of generating anaphylatoxins in fresh whole serum up to levels approximately equal to those observed in serum treated directly with an optimal amount of SpA. The preformed complexes from serum or IgG generated similar high concentrations of anaphylatoxins when carried through four sequential incubations with fresh serum, and complexes that contained approximately 1 microgram SpA were still active. Preincubating the insoluble complexes with chicken anti-SpA serum did not alter their activity. Incubation of serum with collodion charcoal coated with SpA, in a system that models the perfusion technique used to treat cancer, produced complexes that generated significant levels of C3a compared with levels found in serum passaged over albumin charcoal or in untreated serum. The C3a levels in serum from the albumin collodion charcoal were not significantly different from those found in untreated serum. Similar amounts of C3a, C4a, or C5a were observed in serum incubated with differing numbers of bacteria representing a strain of S. aureus rich in cell bound SpA (Cowan strain I) or a strain (Wood 46) deficient in SpA. This suggests that in intact bacteria, cell wall factors other than SpA (e.g., peptidoglycan) are predominantly responsible for generating anaphylatoxins.(ABSTRACT TRUNCATED AT 400 WORDS)

Anaphylatoxins↗

Radioimmunoassays for protein A of Staphylococcus aureus.

Radioimmunoassays have been developed that can detect nanogram amounts of protein A (SpA), a product generated by Staphylococcus aureus that binds selectively to the Fc region of IgG from most mammalian species. Competition assays for fluid phase SpA utilize antibodies produced in chickens, 125I-labeled SpA as the tracer molecule, and either F(ab')2 fragments of rabbit IgG anti-chicken IgG or 40% ammonium sulfate as the precipitating agent to separate antigen-antibody complexes from free antigen. The double antibody assay could be carried out in serum from species that form only soluble complexes with SpA (e.g., rabbit), that react poorly with SpA (e.g., rat), or under appropriate conditions in serum from species (e.g., dog) that show high reactivity with SpA and form precipitating complexes. Chicken antibodies prepared by affinity chromatography on SpA-Sepharose and labeled with 125I were used in a direct binding assay for SpA present either on the cell wall of Cowan strain I or Wood 46 bacteria, in insoluble complexes prepared from SpA and whole serum or purified IgG, or in Clq binding complexes that were formed by passage of serum from normal or tumor bearing humans or dogs over SpA-collodion charcoal. Since both types of assays could detect SpA even in the presence of serum or IgG, they offer advantages over other techniques in which the SpA-Fc interaction may interfere.

Animals↗

Correlation between a learning disorder and elevated brain-reactive antibodies in aged C57BL/6 and young NZB mice.

Previous studies have indicated an increase in brain-reactive antibodies (BRA) in sera of aging mammals and an autoimmune disorder underlying senescence has been suggested. Since New Zealand Black (NZB) mice have a shorter lifespan and greater propensity for autoimmune diseases than C57BL/6 mice, various age groups from both strains of mice were investigated for simultaneous occurrence of BRA serum titer and deficits in learning. NZB mice exhibited a marked learning deficit as well as higher BRA levels at all ages. C57BL/6 mice showed increased BRA and a learning deficit only at advanced ages. The findings of "precocious" BRA titers along with marked learning deficits, both occurring at young ages in NZB mice and both similar to defects seen in the normal mice at senescence and in patients with senile-dementia, suggest that NZB mice may serve as a useful animal model of pre-senile dementia.

Aging↗