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Biomedical subjects

S Leonard

Publications and source records attributed to S Leonard.

At least 127 records · Page 7Linked to original sources

Iowa Agricultural Health and Safety Service Project.

A model community-based comprehensive agricultural occupational health and safety service program has been implemented in Iowa. The functional center of coordination is based in the College of Medicine at the University of Iowa. The community-based hub of the service is the community hospital, where the majority of the direct client services originate. The University provides training of hospital staff, programming, direction, consultation, and referral. The services offered include primary care, health surveillance, industrial hygiene and safety, and education. Through a detailed evaluation of the project's objectives we will be able to evaluate, modify, and disseminate a model agricultural health and safety services delivery program. This model should be effective in changing the farming population's health and safety attitudes and behaviors through a community-based program.

Accidents, Occupational↗

Primary polycythaemia: positive diagnosis using the differential response of primitive and mature erythroid progenitors to erythropoietin, interleukin 3 and alpha-interferon.

Forty adult subjects were studied with the aim of establishing positive diagnostic criteria in primary proliferative polycythaemia (polycythaemia vera, PPP). These comprised 14 patients with PPP, eight secondary polycythaemia (SP), five idiopathic erythrocytosis, and 13 normal subjects, classified under standard criteria following comprehensive investigation for causes of SP. Erythroid colony formation from peripheral blood in a serum-free system was assayed with the addition of recombinant human erythropoietin (Epo), interleukin 3 (IL3), or alpha-interferon (alpha-IFN). The differential sensitivity of primitive and mature progenitors (BFU-E) was assessed by counting the number of clusters ('sub-colonies') comprising each erythroid burst. 'Endogenous' erythroid colonies were found in both PPP (56%) and controls (17%). In Epo containing cultures, the mean number of clusters per burst was lower in PPP than controls, and the percentage of small (less than or equal to 8 clusters) bursts was higher. In PPP primitive BFU-E demonstrated greater dependence on IL3 than controls, and mature BFU-E greater inhibition by alpha-IFN. These findings suggest an abnormal response to several growth factors, rather than dysfunction of a single growth factor receptor. Regression analysis of these data defined a discriminant of high diagnostic sensitivity and specificity. This discriminant accurately predicted diagnosis in a further nine polycythaemic patients.

Adolescent↗

Somatic cell genetics and the study of cholesterol metabolism.

The regulation of cholesterol biosynthesis by extracellular cholesterol occurs both in whole animal tissue and in permanent somatic cell lines in culture. Permanent mammalian cells lines, under optimized growth conditions, are easily manipulated both biochemically and genetically. The Chinese hamster ovary cell line (CHO-K1) is the most widely used cell line for genetic studies. CHO-K1 is a pseudo-diploid mammalian cell exhibiting a short doubling time and a relatively high plating efficiency. Somatic cell mutants can be generated through mutagenesis and also by drug adaptation. Following mutagenesis, auxotrophs may be isolated either by selection or by screening. Most selection procedures for mutants of cholesterol metabolism must be done in serum depleted of cholesterol which requires the endogenous biosynthetic pathway to be intact. Mutants failing to produce cholesterol do not replicate their DNA and exhibit reduced concentrations of cholesterol in their membranes. BUdR and polyene antibiotics have both been used to select against the wild-type cells which incorporate these compounds and are killed, allowing the survival of the mutant cells. Both mevalonate and cholesterol auxotrophs have been isolated with the BUdR technique and have proven useful for elucidation of the early steps in cholesterol biosynthesis, particularly for the ratelimiting enzyme HMG-CoA reductase. Somatic cell fusion of a mutant and wild-type cell followed by chromosomal segregation, routinely used to map human genes, has also been used to map the human gene for HMG-CoA synthase. Such hybrids also provide valuable information on the dominance or recessivity of a specific lesion. DNA-mediated gene transfer into somatic cell mutants allows the selection of DNA sequences which complement the mutation, and is also useful for analysis of regions of regulatory significance. Mutants, resistant to the regulatory effects of oxygenated sterols, can be isolated following mutagenesis. Mutants of this type vary the lipid content of their membranes in response to cholesterol concentration in the medium. All such mutants tested exhibit a pleiotropic regulatory effect on more than one enzyme in the cholesterol biosynthetic pathway. Adaptation to drugs such as compactin and mevinolin, which inhibit HMG-CoA reductase, have been used to produce mutants which overexpress enzymes in the pathway. These amplified cells are useful sources of specific mRNAs for construction of cDNA libraries and gene isolation. Structure-function relationships of membrane sterols can be studied in cholesterol auxotrophs where changes in acyl-chain ordering can be manipulated by exogenous sterols in the medium.

Animals↗

Further characterization of a somatic cell mutant defective in regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Two enzymes of mammalian cellular mevalonate biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and HMG-CoA reductase, have been shown to be regulated by exogenous sterols. It has been demonstrated that these enzymes are regulated, at least in part, by transcriptional control of their synthesis. We have previously described a somatic cell mutant (CR1) of the CHO-K1 cell line that is defective in regulation of the activity of these enzymes in response to exogenous sterols. In this report, we demonstrate that this mutant is defective in regulation of the mRNA levels for HMG-CoA reductase and HMG-CoA synthase by 25-hydroxycholesterol and mevinolin. In the case of HMG-CoA reductase, this loss of apparent transcriptional control is not accompanied by a comparable loss in regulation of synthesis of this enzyme. This observation is consistent with prior studies suggesting that HMG-CoA reductase can be regulated translationally. We also show that CR1 cells exhibit a constitutively rapid rate of degradation of HMG-CoA reductase.

Animals↗

Autologous blood donation during pregnancy: analysis of safety and blood use.

Forty-eight women in the third trimester of pregnancy who requested autologous blood donations were enrolled in an experimental protocol to evaluate the safety of this procedure. Risk factors suggesting the possible need for postpartum transfusion were present in 17 women, including previous history of transfusion, scheduled cesarean section, placenta previa, and previous pregnancy-induced hypertension. Nine women were unable to meet donation criteria. Thirty-nine participants donated one to three units each. There was one vasovagal reaction among 61 donations. Fetal monitoring performed during each donation to assess cardiovascular and neurologic effects of maternal hypovolemia revealed no abnormalities. Three women with symptomatic postpartum anemias were transfused with autologous blood; two of these patients were identified antepartum as being at risk for possible transfusion. Autologous donation during pregnancy was safe for both mother and fetus. However, the likelihood of postpartum transfusion, while possibly predictable based on antepartum history, was low in this study.

Blood Transfusion, Autologous↗

Localization of the gene encoding 3-hydroxy-3-methylglutaryl-coenzyme A synthase to human chromosome 5.

A series of hybrids between primary human cells and a Chinese hamster somatic cell mutant (Mev-1), defective in expression of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase [(S)-3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating, EC 4.1.3.5], has been prepared that complements the mutant defect. A technique based on differential sensitivity of this enzyme activity to inhibition by magnesium ion is described that allows the discrimination of expression of human and hamster HMG-CoA synthase in these hybrids. The results indicate a structural gene defect in expression of HMG-CoA synthase activity in Mev-1 cells. Segregation of human chromosomes that do not possess the complementing marker have allowed the assignment of human HMG-CoA synthase activity to chromosome 5. This is the second demonstrably transcriptionally regulated enzyme of cholesterologenesis to be assigned to chromosome 5, the other being HMG-CoA reductase.

Chromosome Mapping↗

Effect of selenium supplementation on selenium balance in the dependent elderly.

Although trace minerals are necessary constituents of enzymes, dietary requirements of these nutrients for the elderly are unknown. This study measured selenium balance in six dependent elderly men before and after five weeks daily administration of 200 micrograms organically-bound selenium; dietary selenium intake averaged 62.1 +/- 7 micrograms/day during both study periods. Selenium status was assessed not only chemically but also biologically as red cell and platelet glutathione peroxidase activities. Plasma selenium averaged 8.8 +/- 0.8 micrograms% (normal: 10 +/- 2 micrograms %) when intake derived from dietary sources alone and increased during medicinal supplementation to an average of 12.8 +/- 1.9 micrograms %. The rise in plasma selenium was not associated with an increase in red cell or platelet glutathione peroxidase activity. The effect of selenium supplementation on in vivo platelet aggregability was studied by measuring plasma levels of beta-thromboglobulin and platelet factor 4, two proteins secreted concomitant with aggregation. beta-thromboglobulin diminished 7.5 +/- 11.0 ng/ml and platelet factor 7.6 +/- 11.0 ng/ml during selenium supplementation despite no change in platelet glutathione peroxidase activity. These data support the concept that selenium nutritional status should be assessed not only by blood selenium content but also by selenium-dependent enzyme activity or selenium-dependent biologic effect.

Aged↗

Evidence against the involvement of chemotaxis in swarming of Proteus mirabilis.

Nonswarming and nonchemotactic mutants of Proteus mirabilis were isolated after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine or ultraviolet light. These mutants were used in experiments to determine if chemotaxis is involved in the swarming of P. mirabilis. Nonchemotactic mutants failed to form chemotactic bands in a semisolid casein hydrolysate medium, yet they swarmed on the same medium containing 1.5% agar. Nonswarming mutants were attracted towards individual amino acids and components of tryptose. In cross-feeding experiments, no evidence was obtained to indicate the production of a diffusable chemical repellent. In studies with the wild-type P. mirabilis, no clear-cut negative chemotaxis was seen even though three different assays were used and numerous chemicals were tested. Additional evidence against the involvement of chemotaxis in swarming comes from finding that dialysis does not interfere with swarming; swarm cells will swarm immediately when transferred to fresh media, and swarm cells will swarm on an agar-water medium supplemented with a surfactant. These data indicate that chemotaxis is not involved in the swarming of P. mirabilis.

Amino Acids↗

Functional status, medical impairments, and rehabilitation resources in 84 females with Rett syndrome: a snapshot across the world from the parental perspective.

PURPOSE: Rett syndrome is a neurological disorder almost exclusively affecting females. Information on its genetic basis has recently become available. However there is little information on the burden and impact of this disorder on the family despite the apparent variability in phenotype. The purpose of this study was to obtain information on the burden and impact of Rett syndrome by examining the functional abilities, medical needs and use of medical, therapy and accommodation services in the sample. METHOD: We used the internet to access an opportunistic sample of parents of 86 females with Rett syndrome. Data on functional status (using the Wee FIM in questionnaire format) morbidity patterns and use of services were collected. RESULTS: The response indicated that the instrument used would be appropriate for tracking these parameters in a population-based cohort. Subjects with Rett syndrome in this pilot sample were completely or partially dependent in all functional domains and significantly more so than children with Down syndrome. CONCLUSION: The complexity of dependency with need for quality medical surveillance throughout adolescence and adulthood requires accessible centres of excellence linking families and skilled professionals. We plan to use this instrument to obtain a more comprehensive profile of the health, functioning and service use of a total population of children with Rett syndrome.

Activities of Daily Living↗

Schizophrenia and nicotinic receptors.

Patients with schizophrenia often cannot respond to important features of their environment and filter out irrelevant stimuli. This dysfunction could be related to an underlying defect in inhibition--i.e., the brain's ability to alter its sensitivity to repeated stimuli. One of the neuronal mechanisms responsible for such inhibitory gating involves the activation of cholinergic nicotinic receptors in the hippocampus. These receptors are diminished in many specimens of hippocampal brain tissue obtained postmortem from schizophrenic patients. In living schizophrenic patients, stimulation of cholinergic receptors by nicotine transiently restores inhibitory gating of evoked responses to sensory stimuli. Many people with schizophrenia are heavy smokers, but the properties of the nicotinic receptor favor only short-term activation, which may explain why cigarette smoking is only a transient symptomatic remedy. This paper reviews the clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function. Inhibitory gating deficits are only partly normalized by neuroleptic drugs and are thus a target for new therapeutic strategies for schizophrenia.

Antipsychotic Agents↗

Jobshares for experienced nurses.

Performance audit from a clinical perspective has been widely accepted. Within Harrogate Health Care NHS Trust, a review of hours worked on day and night duty, coupled with a review of skill mix in one area, led to the successful introduction of a jobshare scheme for experienced nurses.

Humans↗

The expanded role of the registered nurse: studying nurses' perceptions.

Expanded roles for nurses have developed in the UK over the past 25 years and are now commonplace in most clinical settings. However, considerable confusion and difference of opinion exist about the role and its implications for practice. Shelagh Leonard describes a study undertaken to ascertain how the registered nurses who carry out expanded role activities perceive their role.

Attitude of Health Personnel↗

No grain, no pain.

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Aftercare↗