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Biomedical subjects

K M Thomas

Publications and source records attributed to K M Thomas.

46 records · Page 3Linked to original sources

Molecular cloning of the fMet-Leu-Phe receptor from neutrophils.

The bacterial chemotactic peptide fMet-Leu-Phe (fMLP) activates neutrophils upon binding to surface receptors. In a previous communication we reported the functional reconstitution of the fMLP receptor in Xenopus laevis oocytes (Coats, W. D., and Navarro, J. (1990) J. Biol. Chem. 265, 5964-5966). In this work we report the isolation of the cDNA encoding the fMLP receptor from neutrophils. A rabbit neutrophil cDNA library was screened with an oligonucleotide probe deduced from the nucleotide sequence of G-protein-coupled receptors, and a cDNA encoding the fMLP receptor was isolated. This cDNA was characterized according to the following criteria: 1) Analysis of the deduced amino acid sequence revealed that the clone belongs to a G-protein-coupled receptor. 2) Tissue distribution analysis of the mRNA indicated that the message is only found in neutrophils. 3) In vitro translation of the message revealed a protein corresponding in size to the deglycosylated fMLP receptor. 4) X. laevis oocytes injected with the fMLP receptor message exhibited fMLP-dependent calcium mobilization and specific binding to the fMLP analog 125I-labeled fNle-Leu-Phe-Nle-Tyr-Lys (where Nle is norleucine and fNle is formylnorleucine). The molecular cloning of the fMLP receptor should provide the framework to analyze the relationship between structure, function, and regulation of this receptor.

Amino Acid Sequence↗

Urinary interleukin-2 inhibition in patients with cystitis.

An inhibitor of interleukin-2 activity (IL-2-IN) is present in the urine of most patients during the acute phase of untreated bacterial cystitis (UTI). We measured urinary IL-2-IN activity in 30 adults with uncomplicated UTIs and followed the patients for an additional 6 months. Urinary IL-2-IN activity ranged between 0 and 1.97 units/mg urine creatinine (U/mg u.c.). Relatively low levels of IL-2-IN (less than 0.5 U/mg u.c.) correlated with a prior history of recurrent UTIs (p less than 0.01), and also were predictive of a subsequent UTI during the 6 month follow-up, regardless of the prior medical history (p less than 0.01). Measurement of urinary IL-2-IN during the untreated phase of a UTI may prove helpful for directing antibiotic prophylaxis against subsequent UTIs.

Bacterial Infections↗

Measurement of serum interleukin-2 activity.

The accurate measurement of serum interleukin-2 activity is crucial for assessing the efficacy and toxicity of systemic immunotherapy with recombinant interleukin-2. Incubation of serum at 56 degrees C for 30 minutes facilitates the bioassay for interleukin-2 activity by destroying the interleukin-2 inhibitory activity native to human serum. As this report will demonstrate, however, 30% to 50% of interleukin-2 activity in serum taken from patients or normal volunteers was destroyed by heating at 56 degrees C. No loss of recombinant interleukin-2 activity occurred during heating in serum-free media. The percentage of interleukin-2 activity lost at 56 degrees C varied from patient to patient and also varied with the time of exposure. Native serum interleukin-2 inhibitory activity can be removed, and interleukin-2 activity can be assessed accurately in serial dilutions of the serum beyond 1:64.

Chromatography, High Pressure Liquid↗

Effects of trenbolone acetate on adrenal function and hepatic enzyme activities in female rats.

The effects of the anabolic steroid trenbolone acetate (TBA) on adrenal function and hepatic enzyme activity have been studied in growing female rats. Treatment with TBA resulted in a decrease in the peak of plasma corticosterone concentration which occurred during the afternoon. The enzymes tyrosine aminotransferase (TAT) and phosphoenolpyruvate carboxykinase were measured in the livers of treated and control rats. Activities of both enzymes were maximal at 22.00 h, but that of TAT was reduced in TBA-treated rats. After injection of ACTH, TBA-treated rats showed a smaller increase in plasma corticosterone than did controls. Treatment with TBA did not affect the induction of TAT activity after corticosterone treatment. All TBA-treated rats grew significantly faster than controls and the possible relevance of this reduced adrenal function to the increased growth rate is discussed.

Adrenal Glands↗

Salivary gland tumors in Malawi.

A study of 190 tumors of major and minor salivary glands seen in Malawi over a nine-year period showed an overall incidence rate similar to that in Western countries. However, submandibular and palatal tumors are relatively more common, parotid tumors more likely to be malignant, and submandibular tumors less likely to be malignant than in Western countries. No adenolymphomas were seen. Despite the long history given by many patients with pleomorphic adenomas, the rate of malignant change in these tumors was not high; the majority of carcinomas (16% of all tumors) appeared to rise de novo. Histologic features were similar to those of tumors from other countries but the occurrence of tyrosine crystals in 20% of the pleomorphic adenomas was unusual. Melanocyte colonization of a mucoepidermoid tumor and a carcinoma, both in the primary site and in metastases of a salivary gland tumor, has not been previously reported.

Adolescent↗

Platelet monoamine oxidase activity in schizophrenia. Relationship to disease, treatment, institutionalization and outcome.

A study was made of platelet monoamine oxidase (MAO) activity in non-medicated, newly-admitted schizophrenics and institutionalized chronic schizophrenics both on and off medication. These patients were compared to two control groups: normal subjects and brain-damaged institutionalized patients. No relationship was found between platelet MAO activity and the severity or duration of illness, duration of psychotropic medication, presence of auditory hallucinations or institutionalization. Mean platelet MAO activity did not differ significantly between the schizophrenic subgroups and control groups. Thirty-one patients studied before and after treatment with phenothiazines showed no significant change in platelet MAO activity. The findings did not indicate a relationship between schizophrenia, its treatment or outcome and platelet MAO activity.

Antipsychotic Agents↗

Structural chemistry of 1,2 dilauroyl-DL-phosphatidylethanolamine: molecular conformation and intermolecular packing of phospholipids.

Crystals of 1,2 dilauroyl-DL-phosphatidyl-ethanolamine:acetic acid are monoclinic with a = 46.2, b = 7.77, c = 9.95 A, beta = 92.0 degrees ; space group P2(1)/c. The structural analysis, based on the visual estimates of 1467 reflection intensities, was achieved by direct methods, and least squares analysis convergence was to R(1) = 0.28. There are marked differences between the observed molecular conformation and those that have been predicted theoretically. The mean planes containing the lipid chains are essentially parallel to one another; the phosphodiester moiety has a double gauche conformation, while intermolecular hydrogen bonding modifies the conformation that could be anticipated for an isolated phosphatidylethanolamine molecule. The intermolecular packing produces the classical lipid bilayer structure, adjacent lipid bilayers being separated by acetic acid molecules of crystallization. The hydrocarbon chain packing can be considered either as a quasi-hexagonal type or as a complex orthorhombic subcell arrangement. One-dimensional electron density profiles across the lipid bilayer at increasing resolution clearly demonstrate the origin of features present on the low resolution profiles of both model and natural membranes.

Fatty Acids↗

[Characteristics of natural strains of naphthalene-utilizing bacteria of the genus Pseudomonas].

Sixty-three strains of bacteria capable of utilizing naphthalene as the sole source of carbon and energy were isolated from 137 samples of soil taken in different sites in Belarus. All isolated bacteria contained extrachromosomal genetic elements of 45 to 150 kb in length. It was found that bacteria of 31 strains contained the IncP-9 incompatibility group plasmids, bacteria of one strain carried a plasmid containing replicons IncP-9 and IncP-7, and bacteria of 31 strains contained unidentified plasmids. Primary identification showed that the hosts of plasmids of naphthalene biodegradation are fluorescent bacteria of the genus Pseudomonas (P. putida and P. aeruginosa; a total of 47 strains) and unidentified nonfluorescent microorganisms (a total of 16 strains). In addition to the ability to utilize naphthalene, some strains exhibited the ability to stimulate the growth and development of the root system of Secale cereale.

Biodegradation, Environmental↗

Measurement and partial characterization of an interleukin-2 inhibitor (IL-2-IN) in human urine.

We observed a human urine-derived protein complex (IL-2-IN) which competitively inhibits interleukin-2 (IL-2) dependent murine lymphocyte proliferation. Measurements of urinary IL-2-IN have been used to stratify the immune response of patients to bacteria in the bladder. Partial characterization of IL-2-IN indicates that it is a heat-stable, 75 kDa complex comprised of interleukin-2 bound to another protein(s). Although the IL-2-IN complex is stable in physiologic buffers, the complex can be disrupted using acidic or low-ionic strength buffers, thereby liberating IL-2. IL-2-IN activity is susceptible to bacterial and endogenous urinary proteolysis. The IL-2 bound in the IL-2-IN complex cannot be detected using a double monoclonal antibody radioimmunoassay for IL-2. Unlike other IL-2 binding proteins, the IL-2 binding protein of the IL-2-IN complex is not a soluble interleukin-2 receptor. A modification of the bioassay for interleukin-2 activity is the method of choice for the detection and quantification of urinary IL-2-IN.

Chromatography, Gel↗