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Biomedical subjects

J Thompson

Publications and source records attributed to J Thompson.

At least 559 records · Page 31Linked to original sources

Low background scintillation counting.

Counting radioactive samples with Beckman Instrument's Ready Caps, using a restricted energy window, LL-UL = 400-1000, resulted in machine backgrounds of under 2 cpm and efficiencies of counting relative to liquid scintillation cocktails (LSC) of 51%, 65%, 57%, 62%, and 1% for 32P, 125I, 14C, 35S and 3H, respectively. Signal-to-noise ratios from a quantitative molecular hybridization technique were increased 8-10 fold. There may be a general application for this product in experiments yielding low amounts of radioactivity in liquid samples.

Animals↗

Colchicine toxicity: a case report.

A 59-year-old male was admitted to the Intensive Care Unit from the Emergency Department approximately 12 hr after the ingestion of 30 to 40 mg of colchicine, TYLENOL with codeine, IMODIUM, DESYREL and ethanol. He suffered severe systemic manifestations and succumbed approximately 36 hr post-ingestion. Although this is a case of a mixed ingestion, the complications seen suggest that colchicine was responsible for the fatality.

Acetaminophen↗

Effects of coumarin (1,2-benzopyrone) and cimetidine on peripheral blood lymphocytes, natural killer cells, and monocytes in patients with advanced malignancies.

The combination of coumarin and cimetidine has yielded objective tumor regressions in patients with metastatic renal cell carcinoma and malignant melanoma. While the mechanism of action of cimetidine appears to be immunomodulatory, coumarin appears to have direct effects on tumor cells as well as immunomodulatory activity. We utilized monoclonal antibody labeling techniques to monitor peripheral blood lymphocyte, natural killer (NK) cell, and monocyte phenotypes in patients treated with coumarin and cimetidine. Patients received coumarin 100 mg orally daily for 14 days; on day 15 cimetidine 300 mg four times daily was added and both drugs were continued until disease progression. Studies were performed pre treatment and at 2, 4, and 8 weeks on therapy. There were no alterations in T-cells, helper/inducer T-cells, cytotoxic/suppressor T-cells, B-cells, Ia + lymphocytes, or NK cells. However, an increase was noted by 2 weeks on therapy in the percentage of monocytes and the percentage of DR+ monocytes. This change in the monocyte population occurred in the presence of coumarin alone, before the institution of cimetidine. While this treatment appears to increase DR expression by monocytes, further studies with larger numbers of patients are needed to determine if this observed change is related to antitumor response.

Adult↗

Alternative splicing generates a secreted form of N-CAM in muscle and brain.

A number of different membrane associated isoforms of the neural cell adhesion molecule (N-CAM) have previously been identified. Here the structure of a novel secreted isoform of N-CAM is established by analysis of a cDNA corresponding to an N-CAM mRNA from human skeletal muscle. The mRNA incorporates a novel sequence block into the extracellular domain, which introduces an in-frame stop codon and thus prematurely terminates the coding sequence, generating a truncated N-CAM polypeptide. Analysis of genomic clones indicates that the inserted sequence is present as a discrete exon within the human N-CAM gene, and Northern analysis shows it to be associated specifically with a 5.2 kb mRNA species from skeletal muscle and brain. Stable transfectants expressing the secreted isoform accumulate it in the cytoplasm and release it to the culture medium. In contrast, cells transfected with cDNA encoding lipid-tailed N-CAM express it predominantly at the cell surface. The existence of a secreted isoform may further expand the spectrum of N-CAM function beyond its known involvement in intercellular adhesion to extracellular matrix interactions.

Amino Acid Sequence↗

Site-directed mutagenesis of Escherichia coli 23 S ribosomal RNA at position 1067 within the GTP hydrolysis centre.

Site-directed mutagenesis has been used to change, specifically, residue 1067 within 23 S ribosomal RNA of Escherichia coli. This nucleoside (adenosine in the wild-type sequence) lies within the GTPase centre of the larger ribosomal subunit and is normally the target for the methylase enzyme responsible for resistance to the antibiotic thiostrepton. The performance of the altered ribosomes was not impaired in cell-free protein synthesis nor in GTP hydrolysis assays (although the 3 mutant strains grew somewhat more slowly than wild-type) but their responses to thiostrepton did vary. Thus, ribosomes containing the A to C or A to U substitution at residue 1067 of 23 S rRNA were highly resistant to the drug, whereas the A to G substitution resulted in much lesser impairment of thiostrepton binding and the ribosomes remained substantially sensitive to the antibiotic. These data reinforce the hypothesis that thiostrepton binds to 23 S rRNA at a site that includes residue A1067. They also exclude any possibility that the insensitivity of eukaryotic ribosomes to the drug might be due solely to the substitution of G at the equivalent position within eukaryotic rRNA.

Binding Sites↗

Randomized study of the duration of treatment with interferon alfa-2B in patients with hairy cell leukemia.

Several previous studies have demonstrated that both partially purified and recombinant alpha-interferons (alpha-IFNs) have high response rates in advanced hairy cell leukemia. However, the optimal dose and duration of therapy have not yet been defined. In this study, 90 patients were randomized after 12 months of IFN alfa-2b therapy with a standard dose of 2 X 10(6) U/m2 sc three times weekly to either no further therapy or an additional 6 months of therapy (18 mo total). There was no significant difference in the peripheral blood cell counts between the two groups (when analyzed) dating from the end of IFN therapy rather than from the time of randomization. Eighteen evaluable patients relapsed and were re-treated with IFN: 11 in the no-further-therapy group and 7 in the treated group. No patient was resistant to re-treatment with IFN. There was a significantly greater incidence of fatigue in the treated group (44% vs. 21%; P = .02) during the first 6 postrandomization months. We conclude that the duration of IFN therapy does not influence the clinical course after therapy is discontinued, but responses are maintained while patients receive therapy. However, because of a high incidence of fatigue with prolonged therapy and the ability to reinduce a second response, we recommend that IFN therapy be discontinued after 12 months in asymptomatic patients.

Clinical Trials as Topic↗

N6-(1-carboxyethyl)lysine formation by Streptococcus lactis. Purification, synthesis, and stereochemical structure.

During growth in an arginine-deficient (chemically defined) medium, cells of Streptococcus lactis K1 formed significant amounts of a previously undetected ninhydrin-positive compound. This intracellular compound did not cochromatograph with any of a wide range of amino acids or amino acid analogs tested. However, by two-dimensional thin layer chromatography, the unknown compound migrated close to the recently discovered N5-(1-carboxyethyl)ornithine (Thompson, J., Curtis, M. A., and Miller, S. P. F. (1986) J. Bacteriol. 167, 522-529; Miller, S. P. F., and Thompson, J. (1987) J. Biol. Chem. 262, 16109-16115). The purified compound behaved as a neutral amino acid and eluted between valine and methionine in the amino acid analyzer. The results of 1H NMR spectroscopy suggested the presence of a lysine backbone and a coupled methyl-methine unit in the molecule, and 13C NMR showed that there were nine carbon atoms, of which two (C-1 and C-7) were carboxyl carbons. The simplest structure compatible with the physicochemical data was that of an alkylated derivative of lysine. The identity of this new amino acid, N6-(1-carboxyethyl)lysine, was confirmed by chemical synthesis. In vivo labeling experiments conducted using L[U-14C]lysine and [epsilon-15N]lysine showed that exogenous lysine served as the precursor of intracellular N6-(1-carboxyethyl)lysine and that the epsilon-amino N atom was conserved during biosynthesis of the lysine derivative. Of the two possible diastereomers (2S,8S or 2S,8R) of N6-(1-carboxyethyl)lysine, comparative 13C NMR spectroscopy established that the amino acid produced by S. lactis K1 was exclusively of the 2S,8S configuration.

Amino Acids↗

Focal intestinal heating with regional abdominal hyperthermia.

The effect of regional abdominal heating on the small and large bowel was evaluated in three female research pigs. The BSD Annular Phased Array was used for heating. Blind-end catheters and a free peritoneal probe were surgically attached to small bowel, large bowel, liver, and kidney. Each pig underwent 4-8 heating sessions and was subsequently autopsied. There was no histologic evidence of acute bowel, liver, or kidney damage. There were significant differences in temperatures at the various sites. The average small bowel temperature was significantly higher than predicated by the free peritoneal probe or than seen in the liver or kidney. The large bowel temperatures averaged higher than the free peritoneal probe temperatures, but the difference was not significant. Liver and kidney temperatures approximate whole body temperature due to extensive vascular network. Although the elevated small bowel temperatures may be due in part to different position in relation to isotherms, the frequent occurrence of a large temperature difference suggests focal heating of fluid pockets in the small bowel.

Abdomen↗

The respiratory Vco2/Vo2 exchange ratio during maximum exercise and its use as a predictor of maximum oxygen uptake.

The purpose of this study was to define carefully the dynamic relationship between oxygen uptake (as % Vo2max) and the respiratory Vco2/Vo2 exchange ratio (R) during maximum progressive treadmill exercise in trained and untrained men, and to determine if this relationship could be used to predict Vo2max. Respiratory gases were continuously monitored and the %Vo2max/R time profile calculated at 15 sec intervals over the final 5 min of each test. Young sedentary men (controls, n = 122) and over-60y sedentary men (n = 30) shared the same %Vo2max/R relationship but the latter group had lower R values at Vo2max (1.06 +/- 0.03 vs 1.08 +/- 0.03, p less than 0.01) than controls. Endurance trained men (n = 45) had a lower %Vo2max/R relationship and higher R at Vo2max (1.11 +/- 0.02, p less than 0.001), team athletes (n = 98) had a lower %Vo2max/R relationship but lower R at Vo2max (1.06 +/- 0.03, p less than 0.001) and the weight trained (n = 19) had a higher %Vo2max/R relationship and lower R at Vo2max (1.01 +/- 0.02, p less than 0.001) all compared to controls. From the %Vo2max/R time profile, the following formulae were devised for the estimation of Vo2max (Vo2maxR): Young Sedentary, Vo2maxR = Vo2R (3.000-1.874 R); Over-60y Sedentary, Vo2maxR = Vo2R (3.457-2.345 R); Endurance Trained, Vo2max = Vo2R (1.980-0.912 R); Team Athletes, Vo2maxR = Vo2R (2.805-1.726 R); Weight Trained, Vo2maxR = Vo2R (4.236-3.191 R).(ABSTRACT TRUNCATED AT 250 WORDS)

Heart Rate↗

The effects of previous severe exercise upon the respiratory Vco2/Vo2 exchange ratio as a predictor of maximum oxygen uptake.

The present study examined the effect of previous severe exercise upon (i) respiratory exchange during maximal exercise, and (ii) the respiratory Vco2/Vo2 exchange ratio (R) as a predictor of maximum oxygen uptake (Vo2max). Thirteen healthy males performed a progressive treadmill test to Vo2max: at rest (T1); after a 1 h run on the level treadmill at a speed corresponding 82.4 +/- 7.3% of their Vo2max (T2); after 1 h recovery (T3); and after 24 h recovery (T4). Respiratory gases were continuously monitored. No changes in average work Vo2, Vo2max or maximum heart rate were found between trials. Average work Vco2 was lower in T2 (2.055 +/- 0.093 1.min-1, p less than 0.001), T3 (2.080 +/- 0.087 1.min-1, p less than 0.001) and T4 (2.337 +/- 0.154 1.min-1, NS) compared with T1 (2.360 +/- 0.147 1.min-1). This resulted in lower average R values in T2 (0.81 +/- 0.02, p less than 0.001), T3 (0.83 +/- 0.02, p less than 0.001) and T4 (0.94 +/- 0.02, NS) in relation to T1 (0.95 +/- 0.02). Analysis of the %Vo2max/R relationship over the final 5 min of each test showed a shift to the left during T2 (p less than 0.001), T3 (p less than 0.001) and T4 (NS) compared with T1. As a result predictions of Vo2max based on R (Vo2max/R) were similar to recorded Vo2max in T1 (+ 0.6%) and T4 (+ 2.2%). But higher in T2 (+ 8.7%, p less than 0.001) and T3 (+ 6.9%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Lactic acid bacteria: model systems for in vivo studies of sugar transport and metabolism in gram-positive organisms.

Lactic acid bacteria provide a model system for the in vivo study of mechanisms pertaining to the regulation of sugar transport and metabolism by microorganisms. Recent studies with resting and growing cells of the homofermentative Streptococci and Lactobacilli have yielded evidence for hitherto unsuspected regulatory mechanisms in this group of industrial and medically important bacteria. These regulatory mechanisms mediate the exclusion and expulsion of sugars, the preferential transport of sugar from sugar mixtures, resistance to non-metabolizable sugar analogs and participate in the establishment of energy-dissipating futile cycles. Transport experiments conducted with novel sugar analogs, data from enzymatic analyses and 31P-NMR spectroscopy studies with wild type and mutant strains of Streptococci, have provided new insight into the fine- and coarse-controls responsible for the modulation of activity of the sugar transport: glycolysis cycle. The purpose of this review is to summarize our current knowledge of these regulatory mechanisms and to suggest avenues for future investigation. Although specifically addressed to the lactic acid bacteria, it seems likely that some of the mechanisms described will be found in other Gram-positive species.

Biological Transport↗

Impact of recurrent otitis media on middle ear function, hearing, and language.

Whether recurrent otitis media in infants and young children is followed by delayed language development was addressed by following 210 normal subjects longitudinally through the first 2 years of life with pneumatic otoscopy and tympanometry performed at every physician encounter. Otitis accounted for 26% of the medical visits. One hundred fifty-six of these children had speech and hearing evaluation at 2 years of age. Thirty percent of the children with recurrent otitis media had a mild or moderate hearing loss. However, after multiple speech and language tests, we could not identify a delay in language acquisition in the otitis-prone children. At 3 to 4 years old, 36 children, including nine with a hearing loss at 2 years of age, were retested; all nine had normal hearing. Recurrent otitis media induced a temporary decrease in hearing sensitivity demonstrable at 2 years of age, which appeared to resolve as the children matured and which was not associated with delay in language acquisition.

Child, Preschool↗