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Biomedical subjects

N Hall

Publications and source records attributed to N Hall.

At least 55 records · Page 3Linked to original sources
PubMed1991

The substrate-specificity of human lysosomal alpha-D-mannosidase in relation to genetic alpha-mannosidosis.

The specificity of human liver lysosomal alpha-mannosidase (EC 3.2.1.24) towards a series of oligosaccharide substrates derived from high-mannose, complex and hybrid asparagine-linked glycans and from the storage products in alpha-mannosidosis was investigated. The enzyme hydrolyses all alpha(1-2)-, alpha(1-3)- and alpha(1-6)-mannosidic linkages in these glycans without a requirement for added Zn2+, albeit at different rates. A major finding of this study is that all the substrates are hydrolysed by non-random pathways. These pathways were established by determining the structures of intermediates in the digestion mixtures by a combination of h.p.t.l.c. and h.p.l.c. before and after acetolysis. The catabolic pathway for a particular substrate appears to be determined by its structure, raising the possibility that degradation occurs by an uninterrupted sequence of steps within one active site. The structures of the digestion intermediates are compared with the published structures of the storage products in mannosidosis and of intact asparagine-linked glycans. Most but not all of the digestion intermediates derived from high-mannose glycans have structures found in intact asparagine-linked glycans of human glycoproteins or among the storage products in the urine of patients with mannosidosis. However, the relative abundances of these structures suggests that the catabolic pathway is not the same as the processing pathway. In contrast, the intermediates formed from the digestion of oligosaccharides derived from hybrid and complex N-glycans are completely different from any processing intermediates and also from the oligosaccharides of composition Man2-4GlcNAc that account for 80-90% of the storage products in alpha-mannosidosis. It is postulated that the structures of these major storage products arise from the action of an exo/endo-alpha(1-6)-mannosidase on the partially catabolized oligomannosides that accumulate in the absence of the main lysosomal alpha-mannosidase.

Chromatography, High Pressure Liquid↗
PubMed1991

Thymic peptides, stress, and depressive symptoms in older men: a comparison of different statistical techniques for small samples.

Thymic peptides play an important role in aging and immune regulation, but little is known about their relationship to psychosocial factors. One thymic fraction, thymosin-alpha 1 (TSN-alpha 1) may be of particular interest given its hypothesized role in the differentiation of immature T cells into functional, mature T cells. We examined the relationships among stress, psychological symptoms, and TSN-alpha 1 levels in two conditions; before and after a glucose challenge test. The sample consisted of 18 men, aged 48-80, participants in the Normative Aging Study. While none of the correlations reached significance in the baseline condition, life events and depressive symptoms were significantly correlated with TSN-alpha 1 in the postchallenge condition (r's = .57, and .62, respectively). Hierarchical regression analyses with cross-product interaction terms suggested that individuals who were high in both life events and depression showed the highest levels of postchallenge TSN-alpha 1, with the psychosocial variables accounting for 65% of the variance. Given the small sample size, we replicated these analyses using jackknife and bootstrap techniques, which generally confirmed these findings. Thus, these preliminary results suggest that psychosocial factors may be related to abnormal TSN-alpha 1 responses to a challenge.

Aged↗
PubMed1991

Factors influencing choice of specialty and location of residency.

Students recently graduating from the University of Oklahoma College of Medicine are leaving the state for their postgraduate training and entering nonprimary care fields in increasing numbers. This study identifies the major determinants for training location as having to do with the anticipated quality of the program, and for specialty as having to do with positive experiences on clerkship and the perceived characteristics of the field, including potential controllability of practice. Other factors of significance include lifestyle, standard of living and opinions of others. A striking finding was the negative view of Oklahoma held by our graduates.

Adult↗
PubMed1990

Effect of ursodeoxycholic acid (UDCA) on pancreatic enzyme secretion and gallbladder emptying.

We have used a duodenal perfusion technique to study the effect of chronic administration of ursodeoxycholic acid (UDCA) on postprandial pancreatic enzyme secretion and gallbladder emptying. Duodenal output and hepatic secretion rate of bile acid were also measured. Six gallstone subjects were studied during an evening meal and an overnight fast before and during UDCA administration (675 mg/day for 6 weeks). During the first postprandial hour, the duodenal trypsin output was reduced from 253 to 164 IU/kg/h (p less than 0.05), and mean gallbladder ejection fraction from 38 to 20% (p less than 0.05). The peak response to the meal was delayed from 30 to 50 min for trypsin output (NS) and from 25 to 45 min for gallbladder ejection fraction (p less than 0.05). Area under the curve during the first postprandial hour was decreased for trypsin output from 225 to 119 IU/kg (p less than 0.025), and for gallbladder ejection fraction from 43 to 19% (NS); but areas for the second postprandial hour were increased, so that total values were unchanged. We conclude that the pattern of response for both end organs during chronic UDCA is better described as an attenuated response to food, rather than as a simple reduction in response; and that, since the effects were unaccompanied by any quantitative changes in hepatic bile acid secretion rate, they were probably mediated via the qualitative change in biliary bile acid composition known to accompany chronic UDCA administration.

Aged↗
PubMed1987

Measurement of outcomes of general practice: comparison of three health status measures.

The broad range of medical problems seen in general practice means that the assessment of health outcomes shares much with the assessment of health status in the general community. The last two decades have seen considerable progress in health status measurement for this purpose. This paper reports the use of three such measures in a general practice setting. The 'Rand health insurance study battery', the 'sickness impact profile' and the 'general health questionnaire' were tested in two general practices in Sydney, Australia, to determine patient compliance, to assess the range of scores and discriminative ability of the instruments, and to compare the different instruments. There was a high degree of acceptance of the questionnaires, showing that patients visiting their general practitioners are prepared to complete such questionnaires. The range of scores obtained was less skewed for the Rand measures than for the sickness impact profile or the general health questionnaire, suggesting that the Rand measures should be the preferred general health status measure.

Australia↗
PubMed1985

Decreased mitochondrial creatine kinase activity in dystrophic chicken breast muscle alters creatine-linked respiratory coupling.

Dystrophic chicken breast muscle mitochondria contain significantly less mitochondrial creatine kinase than normal breast muscle mitochondria. Breast muscle mitochondria from normal 16- to 40-day-old chickens contain approximately 80 units of mitochondrial creatine kinase per unit of succinate:INT (p-iodonitrotetrazolium violet) reductase, a mitochondrial marker, while dystrophic chicken breast muscle mitochondria contain 36-44 units. Normal chicken heart muscle mitochondria contain about 10% of the mitochondrial creatine kinase per unit of succinate:INT reductase as normal breast muscle mitochondria. The levels in heart muscle mitochondria from dystrophic chickens are not affected significantly. Evidence is presented which shows that the reduced level of mitochondrial creatine kinase in dystrophic breast muscle mitochondria is responsible for an altered creatine linked respiration. First, both normal and dystrophic breast muscle mitochondria respire with the same state 3 and state 4 respiration. Second, the post-ADP state 4 rate of respiration of normal breast muscle mitochondria in the presence of 20 mM creatine continues at the state 3 rate. However, the state 4 rate of dystrophic breast muscle mitochondria and mitochondria from other muscle types with a low level of mitochondrial creatine kinase, such as heart muscle and 5-day-old chicken breast muscle, is slower than the state 3 rate. Third, dystrophic breast mitochondria synthesize ATP at the same rate as normal breast muscle mitochondria but rates of creatine phosphate synthesis in 20-50 mM Pi are reduced significantly. Finally, increasing concentrations of Pi displace mitochondrial creatine kinase from mitoplasts of normal and dystrophic breast muscle mitochondria with the same apparent KD, indicating that the outer surface of the inner mitochondrial membrane and the mitochondrial creatine kinase from dystrophic muscle are not altered.

Adenosine Triphosphate↗
PubMed1984

The effect of inorganic phosphate on creatine kinase in respiring rat heart mitochondria.

The ability of creatine to stimulate the respiration of rat heart mitochondria in vitro is reversibly affected by the concentration of inorganic phosphate. The rate of oxygen consumption due to post-ADP state-4 respiration in the presence of 20 mM creatine is reduced significantly when the potassium phosphate concentration is raised from 5 to 20 mM. State-3 respiration is reduced only by potassium phosphate concentrations higher than 20 mM. The rate of synthesis of creatine phosphate is also affected by phosphate concentration, and the apparent Km of the coupled reactions for ADP is significantly higher at 25 mM phosphate as compared to that at 5 mM phosphate. These observations are consistent with the hypothesis that inorganic phosphate acts as an effector molecule, regulating creatine phosphate synthesis by favoring the dissociation of mitochondrial creatine kinase from the mitochondrial membrane. Such regulation may be important in the case of cells undergoing partial or severe ischemia, where changes in phosphate concentration within this range have been reported.

Adenosine Diphosphate↗
PubMed1983

Development and validation of a self-scoring test for coronary heart disease risk.

Self-administered tests to assess an individual's coronary heart disease risk are common in the popular press. However, delusion and inaccuracy in self-scoring may impair their utility as educational tools. Self-assessment questions concerning dietary cholesterol, weight, cigarette smoking, and blood pressure were administered several days prior to risk measurement to 246 randomly selected adults aged twenty-five to sixty-four. A standard risk score combining measured blood pressure, cigarette smoking on blood cholesterol level was calculated for each participant using a multiple logistic equation. The self-scoring test was derived by multiple regression, using the standard risk score as the dependent variables and the self-assessment responses, age, and sex as independent variables. The multiple R2 of the resulting equation was 0.48. For 86 percent of the participants, the decile of self-assessed risk was within two deciles of the decile of risk calculated from logistic equation. We tested the validity of the self-scoring test in a separate and independent population (n-247) with comparable results. We conclude that the test indicated risk status and sources of elevated risk for many individuals. Such a test can be a valid health education tool.

Adult↗
PubMed1983

Legionnaires' disease associated with a hospital water system: a cluster of 24 nosocomial cases.

Over a 10-month period, 24 cases of Legionnaires' disease pneumonia occurred among patients admitted to an Iowa hospital, most of whom were immunosuppressed. Eleven patients died. Twenty-one patients were admitted to a recently completed hospital addition, 16 of these to a new hematology-oncology unit. Legionella pneumophila serogroup 1 was isolated from the patients, water outlets, and hot water in the new addition. Water quality variables in the hospital addition were adequate. Shock chlorination, temporary elevation of the hot water temperature, and continuous chlorination of hospital water decreased the frequency of isolation of Legionella. Water use by patients in the hematology-oncology unit was restricted until the water was free of Legionella. The incidence of Legionnaires' disease decreased. Indirect evidence supports an hypothesis of water-borne disease in this cluster of cases. Current variables of acceptable water potability may not guarantee water free of L. pneumophila.

Cross Infection↗
PubMed1982

Effects of various catecholamine receptor antagonists, muscle relaxation and physical hindrance on shuttlebox self-stimulation.

Certain drugs, particularly clozapine and clonidine, have been reported to increase selectively the latency to initiate brain stimulation (the ON latency) in a shuttlebox test of self-stimulation, suggesting a preferential attenuation of the "reward" component. The pharmacological selectivity of this reported effect was systematically evaluated. At doses that blocked bar-pressing self-stimulation, metoclopramide (3 mg/kg), prazosin (3 mg/kg) clonidine (0.1mg/kg), clozapine (3 mg/kg)and haloperidol (0.3 mg/kg), all elevated the ON latency to a greater extent than the OFF latency. Methocarbamol (200 mg/kg), and a muscle relaxant, also elevated the ON latency preferentially but the magnitude of this preferential effect was smaller than that produced by the other drugs. A hurdle in the center of the shuttlebox increased the ON and OFF latencies nonselectively. The shuttlebox procedure does not clearly discriminate among various substances that interfere with noradrenergic or dopaminergic neurotransmission, but the common profile produced by the these substances is distinguishable to some degree from simple motor disruption.

Adrenergic alpha-Antagonists↗
PubMed1982

Trauma-induced glial proliferation: possible involvement of the immune system.

Rat neurologlial cells proliferate following trauma to the frontal cortex. Since previous reports have indicated that activated T-lymphocytes secrete a factor which can induce the proliferation of glial cells in vitro, we investigated the effects of immunosuppression on the trauma-induced proliferation of glial cells in the rat. Animals were treated with either methotrexate (2.5 and 10 mg/kg/day), hydrocortisone (100 mg/kg/day), or saline for five days prior to lesioning of the cortex. Immunocompetence was estimated by measuring sheep red blood cell hemagglutination titers at the time of killing. On the last day of drug treatment, rats were mechanically lesioned on the frontal cortex, and the incorporation of intraventricularly injected 3H-thymidine (3H-TdR) into cortical DNA, a measure of glial cell proliferation, was determined two days after lesioning. Intraperitoneal treatment with methotrexate before the lesioning depressed 3H-TdR incorporation into brain DNA, and reduced hemagglutination titers and thymus and spleen weight. However, intramuscular hydrocortisone pretreatment, which had immunosuppressive actions similar to methotrexate, had a much smaller effect on 3H-TdR incorporation into brain DNA following trauma. Methotrexate given acutely after lesioning did not depress thymidine utilization in the lesioned rat cortex, apparently because of poor penetration of the folate analog into the brain. Thus, we conclude that inhibition of glial cell proliferation resulting from methotrexate pretreatment had been produced indirectly, probably by its severe immunosuppressive effects.

Animals↗