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Biomedical subjects

L Thomas

Publications and source records attributed to L Thomas.

At least 307 records · Page 17Linked to original sources

The predictive value of the time course of ST segment depression during exercise testing in patients referred for coronary angiograms.

We studied the time course of ST segment depression during and after exercise testing in 462 subjects who also had coronary angiograms. Sixty-three percent of patients with late onset-early offset ST depression, previously reported to be likely to have false positive tests, had significant coronary artery disease, and 32% had three-vessel disease. Those with early onset and late offset ST depression and those with resting ST depression that was accentuated with exercise had a high prevalence of significant coronary artery disease and three-vessel disease. We found that observation of the time course of ST depression during and after exercise adds significantly to the information gained during exercise testing.

Aged↗

Epithelioid sarcoma in a dog.

A tumour in an 11-year-old male crossbred Fox Terrier, showing the clinical and pathological features of epithelioid sarcoma in man is reported. Clinical aspects, location, peculiar pattern of spread and evolution, together with histopathological and immunohistological findings of this rare tumour simulating a granuloma are described. Controversial histogenesis is discussed.

Animals↗

Is human papillomavirus associated with cervical neoplasia in the elderly?

There have been no studies in the United States of human papillomavirus (HPV) in elderly women. This paper presents cross-sectional data on HPV and cervical neoplasia among 232 women age 65 or more. HPV deoxyribonucleic acid (DNA) testing was performed using a modified dot-blot hybridization technique. The prevalence of HPV DNA positivity was 3.5% (95% confidence interval (CI) 0.9%, 6.0%). There were six cases of histologic cervical neoplasia. The crude odds ratio for cervical neoplasia among HPV DNA positives was 18.3 (95% CI 2.8, 120.3). The adjusted odds, controlling for age, prior screening history, current sexual activity, and past contraception use, were 12.2 (95% CI 1.2, 122.9). Ever having had a Papanicolaou smear was protective, and there was a trend for the odds of having neoplasia to increase with age. Additional studies with larger samples of elderly women are needed. If confirmed, the results suggest that, independent of past screening, HPV may increase the risk of having cervical neoplasia for elderly women.

Aged↗

CD44H regulates tumor cell migration on hyaluronate-coated substrate.

CD44 is a broadly distributed cell surface glycoprotein expressed in different isoforms in various tissues and cell lines. One of two recently characterized human isoforms, CD44H, is a cell surface receptor for hyaluronate, suggesting a role in the regulation of cell-cell and cell-substrate interactions as well as of cell migration. While CD44H has been shown to mediate cell adhesion, direct demonstration that CD44H expression promotes cell motility has been lacking. In this work we show that a human melanoma cell line, stably transfected with CD44H, displays enhanced motility on hyaluronate-coated surfaces while transfectants expressing an isoform that does not bind hyaluronate, CD44E, fail to do so. Migration of CD44H-expressing transfectants is observed to be blocked by a soluble CD44-immunoglobulin fusion protein as well as by anti-CD44 antibody, and to depend on the presence of the cytoplasmic domain of CD44. However, cells expressing CD44H cytoplasmic deletion mutants retain significant binding capacity to hyaluronate-coated substrate. Taken together, our results provide direct evidence that CD44H plays a major role in regulating cell migration on hyaluronate-coated substrate.

Base Sequence↗

Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human immunodeficiency virus type 1.

Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) are produced by leukocytes and play a role in immune responses. They also function in normal brain physiology as well as in pathological conditions within the central nervous system, where they are produced by brain macrophages (microglia) and brain astrocytes. In this study, we document the ability of human immunodeficiency virus type 1 (HIV-1) to induce TNF alpha and IL-1 in primary rat brain cultures. While productive infection did not occur in these cells, it was not required for cytokine induction. Using monocyte/macrophage-tropic (JRFL) and T-cell-tropic (IIIB) strains of HIV-1, we were able to induce cytokines in both microglia and astrocytes. In addition to whole virus, recombinant envelope proteins also induced these cytokines. The induction of IL-1 and TNF alpha could be blocked by a panel of antibodies recognizing epitopes in the gp120 and gp41 areas of the envelope. Soluble recombinant CD4 did not block TNF alpha and IL-1 production. If TNF alpha and IL-1 can be induced in brain tissue by HIV-1, they may contribute to some of the neurologic disorders associated with AIDS.

Animals↗

Maintenance of wakefulness test and multiple sleep latency test. Measurement of different abilities in patients with sleep disorders.

The multiple sleep latency test and the maintenance of wakefulness test were administered on the same day to 258 consecutive patients whose clinical presentation required evaluation for excessive sleepiness. While the MSLT is the standard test for assessing excessive daytime sleepiness, the MWT may have some clinical advantage over the MSLT when the assessment of daytime alertness is the primary goal. To explore further the relationship between alertness and sleepiness, we have conducted a thorough analysis of the similarities, differences, and correlations between MWT and MSLT. The results of this study show that the coefficient of correlation between MSLT and MWT (r = 0.41), although statistically significant, accounts for less than 17 percent of the variability between the two tests. Factor analysis suggests that two factors, alertness and sleepiness, account for 91 percent of all variance. Our data demonstrate that patients with diagnosable disorders of excessive somnolence may be discordant on the two tests (eg, having low sleep latency on MSLT but high sleep latency on MWT). Specifically, we found that some patients with abnormally low MSLT scores were able to stay awake when asked to do so on the MWT, and conversely, some patients who failed to stay awake when asked to do so on the MWT were unable to fall asleep quickly on the MSLT. We conclude that the MWT and MSLT measure different abilities and that the MWT may be a useful adjuvant daytime test in many clinical situations.

Adult↗

Disorders of excessive sleepiness. Treatment improves ability to stay awake but does not reduce sleepiness.

A total of 47 patients with sleep disorder (36 male and 11 female) with a mean age of 47.5 +/- 15 years were evaluated for daytime symptoms with a Multiple Sleep Latency Test (MSLT) and a Maintenance of Wakefulness Test (MWT) given on the same day--once at the time of their diagnostic evaluation and again after one to six months of treatment. The MSLT and MWT data are consistent with the notion that sleep tendency, as measured by the MSLT and ability to remain awake, as measured by the MWT, represent different physiologic processes. Data show a marked treatment-related improvement in ability to stay awake as measured by the MWT and no treatment-related improvement in sleepiness as measured by the MSLT. We conclude that there is a heterogeneous subpopulation of patients with sleep disorders whose symptoms of daytime sleepiness will show no treatment-related improvement in daytime symptoms if they are evaluated only by the MSLT. We suggest that, since ability to stay awake (and not ability to fall asleep) is a requisite for all job-related duties, an objective, physiologically based test such as the MWT should be used to assess the impact of sleep disorders in cases where there is a clinical concern about fitness to drive or work.

Antidepressive Agents, Tricyclic↗

[Acquired atrophic pigmented band-like lesions following Blaschko's lines].

Over a seventeen years period we observed 5 patients presenting with very similar lesions the equivalent of which we could not find in the literature. These were pigmented and more or less atrophic bands which exactly followed Blaschko's lines. The lesions appeared during childhood or adolescence, between the ages of 6 and 20 years and always were unilateral. In all cases they were located on the trunk where they formed a recumbent "S" pattern characteristic of Blaschko's lines. They often started 3 to 6 cm away from the posterior midline and ended precisely on the anterior midline. These bands varied in number and in 3 out of 5 cases they were associated with pigmented atrophic bands or lines on the limbs of the same side. The intensity of pigmentation and atrophy was variable. The lesions were asymptomatic and only caused a cosmetic prejudice. They were perfectly fixed, and during a 2 to 30 years observation period they remained unmodified. The five skin biopsies performed on 3 patients showed no abnormality of the epidermis other than irregular and moderate hyperpigmentation of its deep part. In the dermis, there was no distinct pigment incontinence, no inflammation and no alteration of connective tissue texture; the elastic network was invariably normal. The impression of skin atrophy was not due to true dermal hypoplasia and perhaps corresponded to atrophy of the subcutaneous cellular tissue. No biological disturbance was observed. These lesions can easily be distinguished from epidermic naevi, incontinentia pigmenti and areas of hypoplastic dermis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A multicentre evaluation of the Ektachem DT60-, Reflotron- and Seralyzer III systems.

The analytical performance of the three analytical systems Reflotron, Ektachem DT60 and Seralyzer III was studied according to ECCLS guidelines (1) and partly according to a protocol of the Société Francaise de Biologie Clinique (SFBC) (2) in a multicentre evaluation involving four laboratories. The determination of 11 analytes led to more than 180,000 data. With the Ektachem DT60, imprecision was acceptable for all analytes except for sodium. With the Reflotron, imprecision for glucose and creatinine was wider than the acceptable limits. With the Seralyzer III, imprecision for glucose, uric acid, cholesterol, creatinine and potassium was not within acceptance limits. The recovery of system assigned control sera values was acceptable for all analytes, except for glucose, creatinine and sodium with the Ektachem DT60 system, and for all but glucose and cholesterol with the Reflotron. On the Seralyzer III, the limits of acceptance were exceeded only with the creatinine assay. The recovery of the reference method values with Kontrollogen L caused problems with all three systems and for all analytes. Only 30% of the mean values of Kontrollogen L measured with the Ektachem and with the Seralyzer III were within the limits of acceptance. 40% of the mean values determined with the Reflotron were inside these limits. The upper limits of linearity as claimed by the manufacturers were obtained with all analytes and systems with the exception of cholesterol on all systems and the creatinine assay on the Seralyzer III. The systems under test and several different comparison methods showed good agreement for the analysis of patient samples, except in one laboratory for the analysis of sodium and aspartate aminotransferase with the Ektachem system and potassium with the Seralyzer III. Turbidity showed no significant influence on the measurements of all analytes and all systems. Haemolysis, hyperproteinaemia, and bilirubinaemia affected several methods on all three systems. A start time delay of up to 60 s did not affect the results of the Reflotron, except in the case of the triacylglycerol assay, which was affected by start time delays greater than 45 s. The results of 4 assays on the Seralyzer III were decreased considerably by a delayed start time (triacylglycerols and creatinine above 5 s, aspartate aminotransferase above 35 s and creatine kinase above 15 s). For reliable results from all the assays in each of the three analytical systems, it was necessary to use the prescribed sample volume within certain limits. The practicability of all analytical systems tested was found to be very good. A field study was conducted with the Reflotron system. The analyte concentration was determined in venous blood from various patients. In 25 out of 30 experiments, the results of the "field" laboratories showed a greater spread about the fitting line than those obtained in the "expert" laboratories.

Chemistry, Clinical↗

Kex2-like endoproteases PC2 and PC3 accurately cleave a model prohormone in mammalian cells: evidence for a common core of neuroendocrine processing enzymes.

Two mammalian gene products, PC2 and PC3, have been proposed as candidate neuroendocrine-precursor processing enzymes based on the structural similarity of their catalytic domains to that of the yeast precursor-processing endoprotease Kex2. In this report we demonstrate that these two proteases can cleave proopiomelanocortin (POMC) in the secretory pathway of mammalian cells. Similarly to pituitary corticotrophs, PC3 expressed in processing-deficient BSC-40 cells cleaved native mouse POMC at the -Lys-Arg- sites flanking corticotropin. The -Lys-Arg- within beta-lipotropin was less efficiently cleaved to release beta-endorphin. Expression of PC2 together with PC3 resulted in efficient conversion of beta-lipotropin, as occurs in pituitary melanotrophs. Furthermore, coexpression of PC2 together with mouse POMC in bovine adrenomedullary chromaffin cells resulted in conversion of beta-lipotropin to gamma-lipotropin and beta-endorphin in the regulated secretory pathway. Finally, the processing selectivities of PC3 and PC2 expressed together in BSC-40 cells were determined by using a series of mutant mouse POMCs containing all possible pairs of basic residues at certain sites. The observed pattern of cleavage site selectivities mimicked that of the endogenous endoproteases of the insulinoma and bovine adrenomedullary chromaffin cells, suggesting that PC2 and PC3 may represent important core endoproteases in the catalysis of prohormone processing in many neuroendocrine cell types.

Adrenocorticotropic Hormone↗

Drosophila stimulatory G protein alpha subunit activates mammalian adenylyl cyclase but interacts poorly with mammalian receptors: implications for receptor-G protein interaction.

Heterotrimeric guanine nucleotide binding proteins (G proteins) transduce signals from cell-surface receptors to intracellular effector proteins. Two forms of stimulatory G protein (Gs) alpha-like subunit have been described in Drosophila melanogaster. To examine the function of these subunits we have used vaccinia virus vectors to express both proteins in cyc- cells, a murine S49 cell line deficient for Gs alpha activity. Receptor-independent activation of each Drosophila Gs alpha has demonstrated that both forms are capable of activating mammalian adenylyl cyclase and thus have the activity expected of stimulatory G proteins. However, the Drosophila Gs alpha subunits interact poorly with mammalian Gs-coupled receptors. These observations have helped to identify a region of high variability in Gs alpha proteins that may be important for receptor interactions.

Adenylyl Cyclases↗

Effects of salt concentration on bacterial growth on plates with gradients of pH and temperature.

A temperature gradient device has been used to produce pH-temperature gradient plates. The response of Salmonella typhimurium and Bacillus cereus to continuous gradients of pH and temperature has been mapped. A third variable, sodium chloride, was investigated by incorporating it at different concentrations in a series of gradient plates. Both organisms exhibited an optimum temperature and pH range for maximum salt tolerance.

Bacillus cereus↗