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Biomedical subjects

T Smith

Publications and source records attributed to T Smith.

At least 541 records · Page 30Linked to original sources

Growth and characterization of fibroblasts obtained from bronchoalveolar lavage of patients with scleroderma.

We describe the detection and the growth of fibroblasts with human smooth muscle cell differentiation features from bronchoalveolar lavage (BAL) fluid of 53% of patients with scleroderma, but not from healthy controls. The binding of alpha-actin, vimentin and desmin antibodies by scleroderma lung fibroblasts exceeded that of normal adult lung fibroblasts, indicating that scleroderma lung fibroblasts express some markers of human smooth muscle cell differentiation (myofibroblasts), which may account for differences in biological behavior. A mesenchymal cell phenotype was documented by mRNA analysis, showing high expression of collagen type I and fibronectin in these cells. Fibronectin is also released in significantly higher amounts by scleroderma alveolar macrophages than by macrophages from healthy donors.

Actins↗

Metabolism of carcinogenic nitrosamines by rat nasal mucosa and the effect of diallyl sulfide.

Rat nasal cavity is one of the target organs for carcinogenesis induced by N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The present work investigated the metabolism of these nitrosamines by rat nasal microsomes, as well as the possible modulating factors. Microsomes prepared from rat nasal mucosa were efficient in metabolizing these nitrosamines. In general, the metabolism of the nitrosamines was slightly higher in 9-week-old rats than in 4-week-old animals, and there was no sex-related difference. Fasting of rats for 48 h, which is known to induce hepatic cytochrome P450IIE1 and NDMA metabolism, did not increase the nasal metabolism of NDMA, NDEA, or NNK. Pretreatment of rats with acetone, another inducer of hepatic P450IIE1, did not increase the metabolism of NDMA. Furthermore, it decreased the nasal metabolism of NDEA and NNK. Immunoinhibition studies suggest that, in the nasal mucosa, P450IIE1 is only partially responsible for the oxidation of NDMA and other P450 isozymes are responsible for the metabolism of NDEA. A single p.o. pretreatment of male rats with diallyl sulfide (DAS), a component of garlic oil, caused a significant decrease in the oxidative metabolism of NDEA and NNK in rat nasal mucosa. Whereas the nasal metabolism of NDMA was reduced by DAS pretreatment, there was no change in the amount of the nasal microsomal proteins immunoreactive with the antibodies against P450IIE1. The inhibitory effect of DAS on the nasal oxidative metabolism of NDMA, NDEA, and NNK was also observed in experiments in vitro. The results demonstrate the ability of nasal mucosa to metabolically activate these nitrosamines and the inhibition of this process by DAS, suggesting that DAS may be effective in inhibiting the related nasal tumorigenesis.

Acetone↗

Upper extremity function in spina bifida.

Poor upper extremity function is often recorded in meningomyelocele patients. Only 2 of the 25 patients we assessed, 5 to 19 years old, showed normal upper extremity function in the clinical neurological examination and a timed hand function test simulating daily activities. Slow performance with unsystematic variability was typical. Poor hand function correlated strongly with hydrocephalus. A trend towards better performance with increasing age may indicate that the difficulties are overcome in some patients. While patients without hydrocephalus showed a near-normal distribution in the seven subtests, patients with hydrocephalus needed more time than normal children. Patients with shunt-treated hydrocephalus did not cope as well as patients without a shunt. Mean age in the three groups differed and may partly explain the differences.

Adolescent↗

Localization of donor nuclei in skeletal muscle grafts by in situ hybridization to a cDNA probe.

The development of therapies, based upon implantation of normal muscle cell precursors, for the treatment of skeletal muscle diseases such as Duchenne Muscular Dystrophy is in its infancy. Detailed analysis of the genetic and phenotypic contribution made by donor myoblasts to the regenerated muscle is critical. Using non-radioactive in situ hybridization of a Y chromosome-specific DNA probe to sections of muscle, we have localized the position of male donor nuclei within female host muscles after myoblast implantation. These results were compared with the distribution of immunocytochemically-localized dystrophin and the expression of donor-specific glucose phosphate isomerase by isoelectric-focussing. We found consistent male-specific nuclear hybridization and a close spatial relationship between the distribution of male donor nuclei and dystrophin-positive muscle fibres within female, dystrophin-negative host muscles. This approach will be useful in the further analysis of myoblast implantation experiments.

Animals↗

Biogenesis as an evolutionary process [letter].

The earliest fossil stromatolites present evidence of a complex ecosystem of photosynthetic organisms. Because the origin of present life can be dated within a few hundred million years prior to these fossils, their complexity poses a problem. A heuristic model outlines the first radiation leading to the universal ancestor.

Biological Evolution↗

Host genetic factors do not account for variation in parasite loads in Strongyloides fuelleborni kellyi.

Previous work in Papua New Guinea has shown considerable variation in egg counts between different people infected with Strongyloides fuelleborni kellyi, although individual egg loads remained relatively constant over a 14-month period. Possible explanations include genetic predisposition, a surprising longevity of the worms, or external auto-infection. We have now analysed the pedigrees of 177 individuals for whom egg counts were available, and find no evidence for polygenic inheritance of factors related to egg counts. The use of genetic models postulating the segregation of a single unknown susceptibility gene did not enable us, using the data available, to distinguish between this hypothesis and environmental determination of egg counts; nor did we find any association between egg load and the class 1 HLA genotype of the host.

Animals↗

The use of the Karnofsky Performance Scale in determining outcomes and risk in geriatric outpatients.

The Karnofsky Performance Scale (KPS) was evaluated in a geriatric outpatient population with regard to three issues: its strength of association with widely used and validated geriatric instruments; its ability to predict patient outcomes; and its ability to serve as an identifier of high-risk patients. The 134-patient sample was given a comprehensive geriatric assessment which included the KPS, the Activities of Daily Living (ADL) scale, the Instrumental Activities of Daily Living (IADL) scale, and other psychosocial and sensory tests. The KPS, ADL, and IADL were significantly correlated with each other, and the KPS showed the strongest associations with other functional measures. The KPS was also highly predictive of outcomes, performing better or equally well as the ADL and IADL. The KPS designation of high- and low-risk groups resulted in statistically significant score differences between groups in all but one assessment area, demonstrating better ability to discriminate than either the ADL or IADL. Thus, the KPS was shown to serve as an effective proxy score for a patient's health and functional status. It also was a significant predictor of hospitalizations, survival time, community residence, and institutionalization. Finally, the KPS was shown to adequately distinguish risk groups to aid in the targeting of services to ambulatory geriatric patients.

Activities of Daily Living↗

Effects of Furegrelate (Upjohn 63557A) on patency and platelet deposition after canine carotid endarterectomy.

Platelet deposition upon endarterectomy sites is a likely cause for early postoperative thrombosis, embolism and restenosis. Platelets aggregate by the thromboxane-prostacycline mechanism. Thromboxane synthetase inhibitors which have been safely administered to humans should reduce platelet deposition after surgical therapy and therefore reduce peri-operative mortality and the prevalence of stroke. A randomized prospective controlled trial was designed to determine vessel patency and platelet deposition associated with the use of 3 mg/kg and 30 mg/kg of Furegrelate (Upjohn U63557A) daily in dogs, who were to have carotid endarterectomy. The 46 treated and 46 control dogs had total carotid patency of 96% and 76% respectively (P less than 0.01). Fourteen dogs treated with 30 mg/kg Furegrelate had no occlusions, compared with a 19% prevalence in 13 controls (P less than 0.02). Furegrelate 10 mg/kg significantly lowered platelet aggregation. Platelet deposition was not significantly changed, however. The reason for this disparity was a probable persistence of vessel wall factors which promoted platelet deposition. This approach might therefore lower rates of peri-operative thrombosis but it would be very unlikely to alter the incidence of restenosis or embolism. Further research could be directed towards modifying the stimuli for platelet deposition upon the endarterectomy site.

Animals↗

Reduced cerebral grey matter observed in alcoholics using magnetic resonance imaging.

Twenty-eight chronic alcoholics and 36 age- and sex-matched non-alcoholic controls were examined with magnetic resonance imaging and brain morphometric analyses. Results confirmed large increases in subarachnoid cerebrospinal fluid (CSF) volume and mild ventricular enlargement in the alcoholics and revealed associated volume reductions of localized cortical and subcortical cerebral structures. Volume losses in the diencephalon, the caudate nucleus, dorsolateral frontal and parietal cortex, and mesial temporal lobe structures were the most prominent. Significant correlations between increments in cortical and ventricular CSF and decrements in the volume of cortical and subcortical grey matter were noted. Although there was little evidence for relationships between performance on neuropsychological tests and volume of grey matter structures, significant correlations between some cognitive measures and subcortical and cortical fluid volumes were found. The parallels between this pattern of affected structures and recent neuropathological findings are discussed.

Adult↗

Cognitive performance of alcoholics: a longitudinal evaluation of the role of drinking history, depression, liver function, nutrition, and family history.

To assess the role of drinking history, depression, liver function, nutrition, and family history on cognitive performance, 171 detoxified male alcoholics were administered a brief neuropsychological examination at admission and discharge from an inpatient treatment program and at a 3-month follow-up evaluation. Regression analyses showed that at admission, depression and liver function were significant predictors of neuropsychological performance, whereas at discharge 3 to 4 weeks later only age and an estimate of premorbid intelligence were significant predictors. At the 3-month follow-up, estimates of drinking following discharge and severity of depressive symptoms were major significant predictors of neuropsychological performance. Indices of drinking prior to admission to the treatment program, nutrition, and family history for alcoholism did not predict performance on any of the three test occasions. These findings indicate that in addition to the chronic neurotoxic effect of alcohol a number of different medical and psychiatric factors, as well as the acute effects of alcohol, contribute to the cognitive scores of patients at various points in the clinical course.

Adult↗