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Biomedical subjects

S A Smith

Publications and source records attributed to S A Smith.

At least 145 records · Page 8Linked to original sources
PubMed1997

Plasma leptin concentrations and OB gene expression in subcutaneous adipose tissue are not regulated acutely by physiological hyperinsulinaemia in lean and obese humans.

OBJECTIVES: To determine the effects of obesity on fasting plasma leptin levels and assess the effects of feeding on plasma leptin and OB gene expression in subcutaneous adipose tissue in non-diabetic subjects. DESIGN: Blood and subcutaneous adipose tissue needle biopsy samples were obtained after an overnight fast and 1, 2 and 3 h following a mixed meal (606 kcal). SUBJECTS: Eighteen female subjects: eight lean with a mean age of 40.1 yr (range 20-65) and mean body mass index of 22.24 kg/m2 (range 18.6-26.6) and ten obese subjects with a mean age of 48.6 yr (range 29-71) and body mass index of 33.53 kg/m2 (range 28.7-41.7). RESULTS: Apart from obesity the only significant difference between groups was a 2.6 fold higher fasting plasma leptin concentration in obese subjects compared to leans (26.9 +/- 2.9 vs 10.2 +/- 2.22 (P < 0.05) respectively). Adipose tissue OB mRNA levels were not significantly higher in the obese group. Plasma leptin correlated with BMI and visceral fat weight in lean subjects only. No significant association between plasma leptin and adiposity was evident in obese patients. In addition, there was no association between plasma leptin and the insulin: glucose ratio (an index of insulin sensitivity). Following a mixed meal, post-prandial plasma insulin levels were significantly increased, with a concomitant significant reduction in plasma NEFA levels in both groups. Despite the large increase in plasma insulin, there were no post-prandial changes in either plasma leptin concentrations or subcutaneous adipose tissue OB mRNA levels in either lean or obese subjects. CONCLUSIONS: The data indicate that plasma leptin levels are correlated with the degree of adiposity, especially in lean subjects, and confirm that circulating leptin levels are greater in obese subjects than lean subjects. The present study also failed to show a significant association between plasma leptin and insulin sensitivity in lean and obese women. Furthermore, plasma leptin and subcutaneous adipose tissue OB gene expression are not under short term regulation following feeding in fasted lean or obese female subjects.

Adipose Tissue↗
PubMed1997

Unilateral eye enucleation in adult rats causes neuronal loss in the contralateral superior colliculus.

Several studies have reported the morphological changes induced by unilateral enucleation during early neonatal life on the developing visual system. This study has examined cellular changes in the superior colliculi by removal of a single eye in adult rats. Anaesthetised male hooded rats aged 90 d had their right eyes removed. Groups of nonenucleated control and enucleated rats were killed when aged either 150 or 390 d. The brains were removed and both the right and left superior colliculi dissected out. The volume of the stratum griseum superficiale (SGS) within these colliculi was estimated stereologically by light microscopy, as well as the numerical density and total number of neurons within this cell layer. The volume of the cell layer was reduced by about 40% on the side contralateral to the enucleated eye but not on the ipsilateral side at both survival periods examined. The numerical density of neurons within the SGS was unaffected by the enucleation so that the colliculi contralateral to the enucleated eye showed a substantial loss of neurons within this cells layer. This study demonstrates the importance of the retinal ganglion cell input, even in adult animals, for maintaining the viability of neurons in the SGS layer of the superior colliculus.

Animals↗
PubMed1997

Antidiabetic efficacy of BRL 49653, a potent orally active insulin sensitizing agent, assessed in the C57BL/KsJ db/db diabetic mouse by non-invasive 1H NMR studies of urine.

High resolution 1H nuclear magnetic resonance (NMR) spectroscopic analysis of biofluids is a recently established tool for evaluating inherited and acquired errors in metabolic control. In the present study 1H NMR analysis of urine was used to monitor efficacy of BRL 49653, a potent and selective antihyperglycaemic agent, following oral administration for up to 36 weeks to the genetically diabetic C57BL/KsJ db/db mouse. The effects of BRL 49653 on carbohydrate and fatty acid metabolism were monitored by determination of changes in concentrations of low molecular weight urinary metabolites. A qualitative comparison of the NMR spectra of urine from untreated diabetic mice with those of lean littermates and literature examples revealed several abnormalities, the majority of which could be explained in terms of the non-insulin dependent diabetes syndrome exhibited by these animals. Quantitatively the most prominent was the extreme glycosuria of both young (8-12 weeks; 0.9 g glucose kg-1 h-1) and older (42 weeks; 2 g glucose kg-1 h-1) diabetic mice. This was accompanied by the excretion of a number of unassigned sugar derivatives and by ketone bodies. Administration of BRL 49653 (3 mumol kg-1) to db/db mice for 24 days reduced blood glucose concentrations to values comparable with non-diabetic lean littermates and reduced glycosuria by > 90%. BRL 49653 significantly reduced excretion of unassigned sugars, acetate, lactate, and the ketone bodies, acetoacetate, 3-D-hydroxybutyrate and acetone. The anti-diabetic efficacy of BRL 49653, assessed from the pattern of urinary metabolites, was maintained over a 36-week treatment period. These results demonstrate the value of 1H NMR to evaluate non-invasively the efficacy of novel therapeutic agents.

Administration, Oral↗
PubMed1997

Effects of temperature on hematologic and serum biochemical profiles of hybrid striped bass (Morone chrysops x Morone saxatilis).

OBJECTIVE: To investigate the effect of water temperature on hematologic and biochemical analytes in hybrid striped bass. ANIMALS: Hybrid striped bass (reciprocal cross: female Morone chrysops x male M saxatilis) maintained in 2,000-L tanks with undergravel filters. PROCEDURE: Fish were acclimated to 10, 18, 24, and 29 C water for 6 weeks prior to sample collection. Hematologic and serum biochemical profiles were then determined. Values were compared among the various temperatures, and with reference intervals previously determined. RESULTS: Most values were within or slightly outside the established reference intervals. The following analytes deviated notably from the reference interval: leukocyte, lymphocyte, and monocyte counts were lower than the reference intervals at 10 C; glucose values were lower at 10 and 18 C; calcium values were higher at 10 and 18 C; and total protein, albumin, globulin, and chloride values were higher at 29 C. CONCLUSION: Separate reference intervals should be developed for analytes which, because of temperature, deviate notably from the reference interval. Modifications of the established reference intervals, by including fish from varied temperatures, should allow use of one reference interval for analytes, with only slight variation attributable to temperature. CLINICAL RELEVANCE: Determining the effects of temperature on the hematologic and biochemical values helps develop clinical pathology as a diagnostic tool in fish.

Acclimatization↗
PubMed1997

Effects of ammonia and nitrate concentration on hematologic and serum biochemical profiles of hybrid striped bass (Morone chrysops x Morone saxatilis).

OBJECTIVE: To investigate the effects of poor water quality on hematologic and biochemical analytes in hybrid striped bass. ANIMALS: Hybrid striped bass (reciprocal cross: female Morone chrysops x male M saxatilis) maintained in 2,000-L tanks with undergravel filters. PROCEDURE: Fish were acclimated to high ammonia (0.15 mg/L) and nitrate (200 mg/L) concentrations for 6 weeks prior to sample collection. Hematologic and biochemical profiles were determined for these fish and for fish kept under normal conditions (control). Comparisons were made among the 3 water qualities and with reference intervals determined previously. RESULTS: Significant differences in hematologic and biochemical analytes were observed between fish in the various groups; however, most of the values were within established reference intervals. All values from fish in the high ammonia concentration tank were either within the reference interval or not significantly different from control values. Fish from the high nitrate concentration tank had higher serum creatinine values and lower chloride values than did control fish, and both analytes were substantially outside the reference intervals. CONCLUSION: High ammonia concentration of 0.15 mg/L did not affect any of the blood analytes measured. The hypercreatininemia and hypochloremia observed in fish from the 200 mg of nitrate/ml tank were considered to be pathologic changes associated with the high nitrate concentration. CLINICAL RELEVANCE: Determining the effects of water quality on hematologic and biochemical values helps to develop clinical pathology as a diagnostic tool in fish.

Alkaline Phosphatase↗
PubMed1996

The thiazolidinedione insulin sensitiser, BRL 49653, increases the expression of PPAR-gamma and aP2 in adipose tissue of high-fat-fed rats.

The effects of the thiazolidinedione insulin sensitiser BRL 49653 on plasma leptin concentrations and on epididymal fat OB, PPAR-gamma and aP2 mRNA expression were examined in high-fat-fed and high-carbohydrate-fed adult Wistar rats. Diets were given for 4 weeks, with BRL 49653 (10 micromol/kg/day) administered by oral gavage for the last 4 days. Treatment with BRL 49653 reduced plasma leptin concentrations in high-fat-fed rats from 2.34 +/- 0.19 (n=9) to 1.42 +/- 0.09 (n=9) ng/ml (p<0.001). Plasma leptin was unaffected by BRL 49653 in the high-carbohydrate-fed rats. There was no difference in OB mRNA expression between high-fat-fed and high-carbohydrate-fed rats, with or without treatment. PPAR-gamma and aP2 mRNA expression were significantly increased in the high-fat-fed rats treated with BRL 49653 (p < 0.01 and p < 0.001 respectively), but not in carbohydrate-fed rats.

Adipose Tissue↗
PubMed1996

Retinoic acid receptors beta and gamma distinguish retinoid signals for growth inhibition and neuritogenesis in human neuroblastoma cells.

Retinoids induce marked growth inhibition and neuritic differentiation in human neuroblastoma cells. Expression patterns of nuclear retinoic acid receptors (RAR) in embryonic and adult tissues suggests that RAR subtypes alpha, beta and gamma have tissue-specific functions. We have transfected a human neuroblastoma tumor cell line with a vector expressing either human RAR alpha, beta or gamma cDNAs. In the absence of exogenous retinoid, RAR beta transfectants demonstrated marked growth inhibition without morphologic evidence of differentiation, whereas transfectant clones overexpressing RARs alpha and gamma had no significant reduction in cell growth rates. Although RAR gamma transfectants were sensitive to the growth inhibitory effects of exogenous retinoids, these cells demonstrated resistance to the neuritogenic retinoid effects. Only RAR beta transfectants exhibited increased sensitivity to retinoids added in vitro. These results suggest that distinct neuritogenic and growth inhibitory signalling pathways exist in neuroblastoma cells and that RAR beta expression may be necessary for the retinoid growth inhibitory pathway.

Cell Differentiation↗
PubMed1996

Sequence, genomic structure, and chromosomal assignment of human DOC-2.

DOC-2 is a human gene originally identified as a 767-bp cDNA fragment isolated from normal ovarian epithelial cells by differential display against ovarian carcinoma cells. We have now determined the complete cDNA sequence of the 3.2-kb DOC-2 transcript and localized the gene to chromosome 5. A 12.5-kb genomic fragment at the 5'-end of DOC-2 has also been sequenced, revealing the intron-exon structure of the first eight exons (788 bases) of the DOC-2 gene. Translation of the DOC-2 cDNA predicts a hydrophobic protein of 770 amino acid residues with a molecular weight of 82.5 kDa. Comparison of the DNA and amino acid sequences of DOC-2 to publicly accessible sequence databases revealed 83% identify to p96, a murine protein of similar size, thought to be a mitogen-responsive phosphoprotein. In addition, about 45% identity was observed between the first 140 N-terminal residues of DOC-2 and the Caenorhabditas elegans M110.5 and Drosophila melanogaster Dab genes.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Isolation of a gene (DLG3) encoding a second member of the discs-large family on chromosome 17q12-q21.

The discs-large family is a collection of proteins that have a common structural organization and are thought to be involved in signal transduction and mediating protein-protein interactions at the cytoplasmic surface of the cell membrane. The defining member of this group of proteins is the gene product of the Drosophila lethal (1) discs large (dlg) 1 locus, which was originally identified by the analysis of recessive lethal mutants. Germline mutations in dlg result in loss of apical-basolateral polarity, disruption of normal cell-cell adhesion, and neoplastic overgrowth of the imaginal disc epithelium. We have isolated and characterized a novel human gene, DLG3, that encodes a new member of the discs-large family of proteins. The putative DLG3 gene product has a molecular weight of 66 kDa and contains a discs-large homologous region, a src oncogene homology motif 3, and a domain with homology to guanylate kinase. The DLG3 gene is located on chromosome 17, in the same segment, 17q12-q21, as the related gene, DLG2. The products of the DLG2 and DLG3 genes show 36% identity and 58% similarity to each other, and both show nearly 60% sequence similarity to p55, an erythroid phosphoprotein that is a component of the red cell membrane. We suggest that p55, DLG2, and DLG3 are closely related members of a gene family, whose protein products have a common structural organization and probably a similar function.

Amino Acid Sequence↗
PubMed1996

Central afferent projections of proprioceptive sensory neurons in Drosophila revealed with the enhancer-trap technique.

We have used a GAL4 enhancer-trap line coupled with an upstream activation sequence (UAS)-linked lacZ reporter construct to visualise and describe the central projections of proprioceptive sensory neurons of the thorax and abdomen in Drosophila. In the legs, lacZ expression is restricted to sensory neurons associated with hair plates, a subset of campaniform sensilla, and with the femoral chordotonal organ; whereas, in the wing, expression is seen only in subsets of campaniform sensilla. In the abdomen, expression is seen in Wheeler's organ and in a segmentally repeated array of internal sensory neurons that have not been previously described. The central projections from all of these neurons are described. The results confirm and expand upon our knowledge of the organisation of sensory neuropils in insects. The enhancer-trap technique provides a potentially powerful tool for describing the organisation of the central nervous system of Drosophila.

Afferent Pathways↗
PubMed1996

Amyotrophic lateral sclerosis and occupational history. A pilot case-control study.

OBJECTIVE: To assess the association of a number of occupational and industrial exposures with amyotrophic lateral sclerosis (ALS). DESIGN: A case-control study of ALS cases matched by age and sex to 2 controls each: 1 from a neurologic clinic and 1 from a local community. Exposures were ascertained by questionnaire, and patients were requested before the interview to be to prepared to supply occupational histories. SETTING: Patients with ALS were enrolled at the University of Minnesota ALS Clinic in Minneapolis. PATIENTS: Patients with ALS (n = 25) were from the University of Minnesota ALS clinic, and clinic controls (n = 25) were patients with other neuromuscular diseases from the university's Muscle Disease Clinic, selected on the basis of clinic enrollment date nearest to that of the matched case. Clinic controls were principally patients with myopathies. Community controls (n = 25) were selected from the community using a random-digit-dialing protocol matching on the first 5 digits of the case patient's telephone number. RESULTS: The strongest association with disease was exposure to welding or soldering materials (odds ratio, 5.0) and the welding industry (odds ratio, 5.3). Electric plating showed a high odds ratio of 8 (95% confidence interval, 0.9-72.0), but low statistical significance (P < .07) Several exposures or industries, while not statistically different, showed enough difference that to ignore them might lead to a Type II error, a result of the pilot nature and small sample size. These included paint or pigment manufacturing, the petroleum industry, the printing industry, and shipbuilding. CONCLUSIONS: The association with welding, soldering, and the welding industry is strong and suggests a need for further work. This is despite the small numbers studied, thus making most industrial or occupational exposures too limited to draw conclusions or detect associations. Perhaps the most obvious candidate from the welding, soldering exposure for a common toxin would be lead. Other suggestions of risk were seen for paint or pigment manufacture, shipbuilding, electric plating, and the dairy industry. The degree of association for these, while high, is not statistically significant, and suggests that there may be 1 or more environmental toxins common to those industries that need more precise measurement.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Nonsystemic vasculitic mononeuropathy multiplex, cryoglobulinemia, and hepatitis C.

A 39-year-old man developed sequential acute mononeuropathies involving both median, both ulnar, and the right radial and left peroneal nerves. Electrophysiology demonstrated an asymmetric sensorimotor axonal polyneuropathy; nerve biopsy confirmed a vasculitis. Laboratory evaluation revealed a mixed cryoglobulinemia and active hepatitis C infection. The patient stabilized with prednisone/cyclophosphamide/interferon-alpha. Hepatitis C should be considered in the differential diagnosis of mononeuropathy multiplex. Accurate diagnosis is important, as interferon-alpha may prevent transition to chronic hepatitis/cirrhosis.

Adult↗
PubMed1996

A clinical trial of verapamil in amyotrophic lateral sclerosis.

Seventy-two patients with amyotrophic lateral sclerosis (ALS) were enrolled in a clinical trial of the efficacy of verapamil in the treatment of ALS. In period 1 (pretreatment, months 1-3) and period 3 (posttreatment, months 10-12), patients received no drug. In period 2 (months 4-9), patients received verapamil. The slopes of declining pulmonary function and limb megascores were not significantly different during drug treatment compared to natural history and washout periods. Thus, verapamil was ineffective in slowing the clinical progression in ALS patients. Controlled trials using a natural history period may represent a faster and less expensive method of screening drugs for ALS compared to placebo-controlled trials.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Persistent microvasculopathy in chronic eosinophilia-myalgia syndrome.

Acute eosinophilia-myalgia syndrome (EMS) due to contaminated L-tryptophan (LT) exposure is an inflammatory microangiopathy of the dermis, fascia, and muscle. Select individuals evolve from acute EMS to have persistence of myalgia, fatigue, cramps, and skin changes for years. Many develop memory dysfunction and confusion. The objective of this study is to delineate the pathology in individuals with chronic EMS. Seventeen patients with ongoing symptoms representing chronic EMS are studied by skin, fascia, and muscle biopsies four to five years after exposure to contaminated LT and initial onset of EMS. All have microvascular disease. Most have lymphocytic inflammatory infiltrates. Several have dermal sclerosis. The findings indicate that persistent microvascular disease is present in chronic EMS. The pathologic changes are similar to those of acute EMS but with notable differences. Tissue eosinophil infiltration is rare in the chronic state as compared to acute EMS. The persistence of endothelial pathology indicates continuing microvascular dysfunction.

Arterioles↗
PubMed1996

The effect of temperature and water quality on antibody response to Aeromonas salmonicida in sunshine bass (Morone chrysops x Morone saxatilis).

The kinetics of the antibody response to Aeromonas salmonicida were determined in sunshine bass (hybrid striped bass: female Morone chrysops X male Morone saxatilis) acclimated to 10, 18, 24, 29 degrees C, and to 0.15 mg 1(-1) un-ionized ammonia and 200 mg 1(-1) nitrate levels. Temperature and water quality factors affected the immune response of sunshine bass. Temperatures of 10 degrees C and 18 degrees C decreased the magnitude and delayed the time of the antibody response to A. salmonicida. The antibody response was not affected at 29 degrees C, which is above the optimal temperature for sunshine bass. Elevated un-ionized ammonia concentrations of 0.15 mg 1(-1) also did not affect the antibody response. Elevated nitrate levels of 200 mg 1(-1), however, decreased the antibody response to the same extent as 18 degrees C water.

Aeromonas↗