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Biomedical subjects

N Hall

Publications and source records attributed to N Hall.

At least 37 records · Page 2Linked to original sources

Expression of CD44 on rheumatoid synovial fluid lymphocytes.

OBJECTIVES: To investigate the involvement of the adhesion molecule CD44 in the homing of lymphocytes to synovial tissue, by examining the density of expression and molecular mass of CD44 on rheumatoid synovial fluid lymphocytes. METHODS: Twenty patients with rheumatoid arthritis were studied. Peripheral blood and synovial fluid lymphocytes were isolated by Ficoll-Hypaque sedimentation. CD44 expression was analysed by two colour flow cytometry of CD3 positive T lymphocytes with calculation of mean fluorescence intensity. Expression of activation markers M21C5, M2B3, interleukin (IL)-2 receptor and transferrin receptor was quantitated. In addition, CD44 molecular mass was examined by Western blot in six patients. RESULTS: CD44 expression was markedly increased on synovial fluid T lymphocytes of rheumatoid patients relative to peripheral blood lymphocytes from the same individuals. CD44 molecular mass on peripheral blood mononuclear cells was 88 kDa, but that on synovial fluid lymphocytes was only 83 kDa. CD44 expression correlated significantly with expression of activation markers M21C5, M2B3, and the IL-2 receptor. CONCLUSIONS: Alterations in density of expression or of the molecular mass of CD44 could contribute to local tissue injury, either directly by facilitating adhesion, or indirectly through effects on other adhesion molecules.

Arthritis, Rheumatoid↗

Electron paramagnetic resonance investigations of free radical-induced alterations in neocortical synaptosomal membrane protein infrastructure.

Evidence is presented that free radical stress can directly induce physico-chemical alterations in rodent neocortical synaptosomal membrane proteins. Synaptosomes were prepared from gerbil cortical brain tissue and incubated with 3 mM ascorbate and various concentrations of exogenous Fe2+ for 30-240 min at 37 degrees C. Synaptosomes were then lysed and covalently labeled with the protein thiol-selective spin label MAL-6 (2,2,6,6-tetramethyl-4-maleimidopiperdin-1-oxyl) and subjected to electron paramagnetic resonance (EPR) spectrometry. In separate experiments, synaptosomal membranes were labeled with the thiol-specific spin label MTS ((1-oxyl-2,2,5,5-tetramethyl-pyrroline-3-methyl)-methanethiosulfonate), or the lipid-specific spin probe 5-NS (5-nitroxide stearate). Free radical stress induced by iron/ascorbate treatment has a rigidizing effect on the protein infrastructure of these membranes, as appraised by EPR analysis of membrane protein-bound spin label, but no change was detected in the lipid component of the membrane. These results are discussed with reference to potential oxidative mechanisms in aging and neurological disorders.

Animals↗

An evaluation of New Jersey's hospital discharge database for surveillance of severe occupational injuries.

Computerized population-based hospital discharge data in New Jersey offer new opportunities for surveillance of serious work-related injuries. This database was evaluated for its potential in identifying selected injuries that occurred at work during 1985 and 1986. Hospital discharge data were compared with data collected by telephone interview of discharged patients. A total of 1,575 unique hospital discharge records for the selected injuries included finger amputation (1,041), thumb amputation (209), crush injury of the lower limb (208), toxic effects of heavy metals (69), and eye burns (48). Of 809 study subjects sent letters, 445 (55%) could be contacted and 289 (36%) were interviewed for the study. Sixty-one percent (175) said their injury was work related. A comparison was made between self-reported injury at work, and the presence of workers' compensation payer codes on the discharge database. The agreement beyond chance (Kappa) was 0.78 (95% CI = 0.67, 0.89). The sensitivity of this indicator of work relatedness was 83%; specificity was 98%. These data suggest that workers' compensation payment on the hospital discharge database may be a good to excellent proxy indicator of the work relatedness of these injuries. However, this proxy indicator will underestimate the number of work-related injuries by about 20%. Only 11% of hospital discharge records had external cause of injury codes (E-codes), which reduces the utility of the database for understanding the causal mechanisms of work-related injuries.

Accidents, Occupational↗

Hospitalized occupational finger amputations, New Jersey, 1985 and 1986.

About 19,000 finger amputations occur at work each year in the United States. Twenty percent of these injuries are severe enough to require hospitalization. Hospital discharge data from New Jersey (1985, 1986) were used to describe the demographic characteristics of persons with such injuries and to identify potential subjects for telephone interview. A total of 637 persons hospitalized for finger amputations were sent letters asking for their participation. Of 637 persons, 355 (56%) were contacted and 228 (36%) were interviewed, of whom 134 (59%) said their injury occurred at work. The annual rate of finger amputations at work was 9.3 per 100,000 employed persons. The rate was higher for males (14.7) than females (1.9). The age-adjusted rates were higher for Hispanic (52.8) and black (28.9) males than for white males (9.5). Persons working with machines or maintaining them in the manufacturing industry were at highest risk. Unjamming or repairing machinery (e.g., presses, saws, or slicers) while in operation was particularly hazardous. These data can be used to target occupations and industries for specific worksite intervention to prevent finger amputations. One limitation of this study, however, is that hospitalized occupational finger amputations may not be representative of all finger amputations, the majority of which are less severe and do not require hospitalization.

Accidents, Occupational↗

Interaction of tacrine and velnacrine with neocortical synaptosomal membranes: relevance to Alzheimer's disease.

The acridine-based, potential Alzheimer's disease therapeutic agents, tacrine and velnacrine, were incubated with rat or gerbil neocortical synaptosomal membranes. Electron paramagnetic resonance employing a protein-specific spin label was used to monitor this interaction. Analogous to their effects in erythrocyte membranes [Butterfield and Rangachari (1992) Biochem. Biophys. Res. Commun. 185: 596-603], in the present studies both agents decreased segmental motion of spin labeled synaptosomal membrane proteins, consistent with increased cytoskeletal protein-protein interactions (0.001 < P < 0.005), and tacrine was more potent than velnacrine. These results are discussed with possible relevance to molecular actions of the agents and molecular alterations in Alzheimer's disease.

Alzheimer Disease↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗