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Biomedical subjects

J L Thomas

Publications and source records attributed to J L Thomas.

At least 127 records · Page 7Linked to original sources
PubMed1984

Reactivation of human placental 17 beta, 20 alpha-hydroxysteroid dehydrogenase: affirmation of affinity labeling principles.

Human placental 17 beta, 20 alpha-hydroxysteroid dehydrogenase was completely inactivated by the affinity alkylator, 3-bromoacetoxy-1,3,5(10)-estratrien-17-one (estrone 3-bromoacetate). The inactivated enzyme was then reactivated to 100% of the enzyme activity by base-catalyzed hydrolysis of the steroidalester-enzyme conjugate. After the reactivated enzyme was repurified by dialysis, re-inactivation studies were performed on it. The reactivated enzyme could not be re-inactivated by the original alkylator, estrone 3-bromoacetate. However, 16 alpha-bromoacetoxyestradiol-17 beta 3-methyl ether caused a loss of reactivated enzyme activity at a rate comparable to that for the native enzyme. These observations demonstrate that a specific amino acid modification within the enzyme active site was produced by estrone 3-bromoacetate alkylation and suggest that the conformation of the active center was essentially unaltered. Thus, these successful reactivation studies of 17 beta, 20 alpha-hydroxysteroid dehydrogenase affirm the specificity of affinity labeling. This methodology also offers a new tool to investigate the steroid binding regions of macromolecular proteins.

20-Hydroxysteroid Dehydrogenases↗
PubMed1984

Effects of propranolol and of verapamil on heart rate and blood pressure in hyperthyroidism.

Cardiac manifestations of hyperthyroidism have been attributed to enhanced sympathoadrenal activity, but thyroid hormones also have a direct positive chronotropic effect on sinoatrial cells, in which there are slow calcium channels. We evaluated the effects of verapamil on heart rate, PR and QT intervals, and blood pressure in eight patients with hyperthyroidism and compared them to those effects of propranolol. Three doses of propranolol (0.05, 0.1, and 0.2 mg/kg) and verapamil (0.1, 0.2, and 0.4 mg/kg) were injected intravenously after a 72-hr withdrawal period in a double-blind, crossover fashion. Propranolol increased the RR interval from 581 +/- 51 to 734 +/- 65 msec, whereas verapamil did not have any negative chronotropic effect despite prolonging the PR interval. Systolic blood pressure decreased from 134 +/- 5 to 119 +/- 8 mm Hg after verapamil and was not affected by propranolol. Diastolic blood pressure was depressed equally by both drugs. We conclude that verapamil is not a good alternative drug to propranolol in hyperthyroidism. Our data cannot confirm the possibility of an interaction between thyroid hormones and slow calcium channels in patients with hyperthyroidism.

Adult↗
PubMed1984

Behaviour of thyroid tissue from patients with Graves' disease in nude mice.

Thyroid tissue from five patients with hyperthyroidism due to Graves' disease was transplanted into nu/nu mice (2 to 4 mice per thyroid) in order to assess whether the tissues would remain hyperfunctional. Before surgery, the patients received only propranolol and iodine for ten days. Transplants were removed from the mice after 10, 20, 30 or 57 days, and compared to the initial tissue, as well as toxic nodules from two patients and thyroid tissue from two normal subjects grafted similarly. All transplants survived, as proven by histology and autohistoradiography with 131I uptake, while all signs of hyperfunction and dysimmunity disappeared. Conversely, both transplanted toxic nodules remained hyperfunctional. These results indicate that, in spite of the in situ presence of most factors of auto-immune reactions, thyroid tissue from patients with Graves' disease is not autonomous and depends on the extra-thyroid environment.

Adult↗
PubMed1983

Inactivation of human placental 17 beta,20 alpha-hydroxysteroid dehydrogenase by 16-methylene estrone, an affinity alkylator enzymatically generated from 16-methylene estradiol-17 beta.

The substrate 16-methylene estra-1,3,5(10)-triene-3,17 beta-diol (16-methylene estradiol-17 beta) and its enzyme-generated alkylating product, 3-hydroxy-16-methylene estra-1,3,5(10)-triene-17-one (16-methylene estrone), were synthesized to study the 17 beta- and 20 alpha-hydroxysteroid dehydrogenase activities which coexist in homogeneous enzyme purified from human placental cytosol. 16-Methylene estradiol, an excellent substrate (Km = 8.0 microM; Vmax = 2.8 mumol/mg/min) when enzymatically oxidized to 16-methylene estrone in the presence of NAD+ (256 microM), inactivates simultaneously the 17 beta- and 20 alpha-activities in a time-dependent and irreversible manner following pseudo-first order kinetics (t1/2 = 1.0 h, 100 microM, pH 9.2). 16-Methylene estradiol does not inactivate the enzyme in the absence of NAD+. 16-Methylene estrone (Km = 2.7 microM; Vmax = 2.9 mumol/mg/min) is an affinity alkylator (biomolecular rate constant k'3 = 63.3 liters/mol-s, pH 9.2; KI = 261 microM; k3 = 8.0 X 10(-4) S-1, pH 7.0) which also simultaneously inhibits both activities in an irreversible time-dependent manner (at 25 microM; t1/2 = 7.2 min, pH 9.2; t1/2 = 2.7 h, pH 7.0). Substrates (estradiol-17 beta, estrone, and progesterone) protect against inhibition of enzyme activity by 16-methylene estrone and 16-methylene estradiol. Affinity radioalkylation studies using 16-methylene [6,7-3H]estrone demonstrate that 1 mol of alkylator binds per mol of inactivated enzyme dimer. Thus, 16-methylene estradiol functions as a unique substrate for the enzymatic generation of a powerful affinity alkylator of 17 beta,20 alpha-hydroxysteroid dehydrogenase and should be a useful pharmacological tool.

20-Hydroxysteroid Dehydrogenases↗
PubMed1983

Human placental 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase. Studies with 6 beta-bromoacetoxyprogesterone.

Two soluble enzyme activities, 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase, copurified from the cytosol fraction of human term placenta, were identically inactivated by 6 beta-bromoacetoxyprogesterone. This affinity alkylating steroid binds at the enzyme-active site (Km = 866 microM; Vmax = 0.073 mumol/min/mg). Enzyme inactivation by four concentrations of 6 beta-bromoacetoxyprogesterone (molar ratio of steroid to enzyme, 71/1 to 287/1) causes irreversible and time-dependent loss of both the 17 beta- and 20 alpha-activities according to first order kinetics and affirms that the alkylating steroid is an active site-directed inhibitor (KI = 2.7 X 10(-3) M; k3 = 1.6 X 10(-3) s-1). Affinity radioalkylation studies using 6 beta-[2'-14C]bromoacetoxyprogesterone indicate that 2 mol of steroid are bound to each mole of inactivated enzyme dimer (Mr = 68,000). Amino acid analyses of the acid hydrolysate of radioalkylated enzyme show that 6 beta-bromoacetoxyprogesterone carboxymethylates cysteine (56%), histidine (22%), and lysine (8%) residues in the active site. These results are identical with those reported for 2-bromo[2'-14C]acetamidoestrone methyl ether radioalkylation of purified "17 beta-estradiol dehydrogenase." The parallel inactivation of 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase by 6 beta-bromoacetoxyprogesterone further shows that both activities reside at a single enzyme-active site. The radioalkylation profile supports our proposed model of one enzyme-active site wherein the bound progestin and estrogen substrates are inverted, one relative to the other.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Graves' disease: in situ localization of lymphoid T cell subpopulations.

An in situ analysis of immunological features in thyroids from 15 Graves' disease patients has been performed. This study included a search for immune complexes visualized near the follicle's basement membranes with fluorescent rabbit antisera to human IgG, IgA, IgM, C1q, C3 and C9. Cellular immunity was investigated on the humoral side by visualization of B cells and plasma cells. Two series of monoclonal antibodies (OKT3, 4 and 8, Leu 1, 2a and 3a) were used to label the infiltrating cells' membrane. These studies demonstrated the prevalence of T cells, a majority of them with OKT8/Leu 2a suppressor/cytotoxic phenotype. No correlation was found between this observation and peripheral blood T cell subsets analysis.

Antibodies, Monoclonal↗
PubMed1982

Percutaneous needle biopsy of soft tissue tumors guided by ultrasound and computed tomography.

Ultrasound and computed tomography (CT) guided percutaneous needle biopsy of soft tissue lesions was performed in 39 patients. A correct diagnosis was obtained in 35 of 42 biopsies, with an overall accuracy rate of 83%. No false-positive diagnoses were obtained, and no complications related to the procedure were encountered. The value of this technique in the management of selected patients with soft tissue masses is detailed.

Adolescent↗
PubMed1982

Computed tomography and routine chest radiography in oat cell carcinoma of the lung.

Computed tomography (CT) scans of the chest and routine postero-anterior and lateral chest films were compared in 32 patients with pathologically proven oat cell carcinoma of the lung. Nineteen of the 32 patients were examined prior to any form of therapy. Overall, CT gave more information about the extent of disease. The significance of this information may be of little value because the routine chest films also demonstrated mediastinal involvement, although to a lesser degree. Computed tomography of the chest should not be the initial diagnostic staging procedure in oat cell carcinoma, but used selectively. It can be quite useful in patients who have a partially opacified lung, possibly for the evaluation of mediastinum after therapy, and for the evaluation of possible abdominal metastases.

Adult↗
PubMed1982

Post-therapy CT-detected mass in lymphoma patients: is it viable tissue?

The demonstration by computed tomography (CT) of enlarged nodes and/or masses in lymphoma patients has been interpreted as indicating that active disease is present. Four cases are presented in which either biopsy or laparotomy of a CT-detected mass after therapy revealed fibrous tissue with no evidence of viable neoplasm. These four cases demonstrate the possible pitfall of diagnosing viable lymphoma in masses detected by CT after therapy.

Adult↗
PubMed1982

CT detection of hepatic metastases with Ethiodized Oil Emulsion 13.

The use of an experimental liposoluble contrast agent-Ethiodized Oil Emulsion 13 (EOE 13)--is described in hepatic computed tomography (CT) of 23 oncologic patients. Without exception, all the hepatic metastases were better delineated in the EOE 13 enhanced scans. The postcontrast scans also detected an increased number of lesions but not all were malignant. There is no specificity to the increased lesion detection. Various splenic abnormalities were detected. Very few minor side effects and no major side effects were caused by the contrast media. We feel that with time, hepatic specific agents such as EOE 13 will become the contrast media of choice in hepatic CT examinations. Also, CT with hepatic specific agents may become the preoperative examination of choice in candidates for partial hepatectomy.

Adult↗
PubMed1982

Hepatic sonography: technical considerations, present applications, and possible future.

Hepatic sonography is improved when static B scanning is combined with a real-time examination, eliminating possible "blind spots" and "pseudolesions." At present, sonography is used to augment radionuclide scanning, to detect masses, and for follow-up. Because of its versatility, sonography should replace radionuclide liver scanning as the initial diagnostic procedure in patients with liver neoplasms. However, if sonography is to retain its utility in the future when compared with computed tomography, significant improvements in equipment are needed. Two other areas in which developments might be made are: (a) data representation other than echo-amplitude, and (b) the availability of liver-specific contrast agents.

Humans↗
PubMed1982

Computed tomographic manifestations of abdominal and pelvic venous collaterals.

Obstruction of blood flow through the inferior vena cava and portal vein may produce venous collaterals. These include the paravertebral venous system and its communications with the ascending lumbar veins and azygous/hemiazygous system; gonadal, periureteric, and other retroperitoneal veins; abdominal wall veins; hemorrhoidal venous plexus; and the portal venous system. The anatomic location of these vessels is discussed. Computed tomography demonstrates them as round or tubular structures that are isodense when compared with other venous structures following contrast material administration. Techniques of examination and methods of differentiation of these vascular structures from other abnormalities, especially lymphadenopathy, are discussed.

Abdomen↗
PubMed1982

EOE-13 in the detection of hepatosplenic lymphoma.

Thirty-nine patients with lymphoma were evaluated prospectively to determine the usefulness of Ethiodol-Oil-Emulsion-13 (EOE-13) in the detection of hepatosplenic lymphoma by computed tomography. The detection rate in the spleen increased from 8% (before EOE-13 infusion) to 92% (after EOE-13 infusion). In ten of 39 patients (25%) in this series, lymphomatous disease was recognized only on the postinfusion computed tomographic scan. The postinfusion EOE-13 study demonstrated additional visceral abnormalities in 38% of the patients. The potential usefulness, limitations, and toxicity of this hepatosplenic-specific imaging agent are discussed.

Ethiodized Oil↗
PubMed1982

Ventral medullary extracellular fluid pH and blood flow during hypoxia.

Vascular responses of the ventral medulla and total brain to 30-60 min of isocapnic hypoxia (PaO2 = 32 +/- 2 Torr) were examined using radioactive microspheres in anesthetized, paralyzed, and artificially ventilated cats. Ventral medullary extracellular fluid (ECF) pH was measured using pH microelectrodes with tip diameters of 1-2 micrometers. Total brain blood flow (Q) increased significantly from a control value of 53 +/- 8 (mean +/- SE) to 160 +/- 42 ml.100 g-1.min-1 following 30-60 min of hypoxia. Ventral medullary Q increased from 28 +/- 5 to 97 +/- 20 ml.100 g-1.min-1 and ECF pH decreased by 0.15 +/- 0.06 pH U. Q responses are attributable to decreased vascular resistance as arterial pressure remained constant. The sensitivity of the ventral medullary vasculature to isocapnic hypoxia did not differ from that of the brain as a whole. The results show that under the conditions of our experiment, the ventral medullary vascular response to hypoxia is not sufficient to stabilize local ECF pH. The observation of simultaneously reduced pH and increased Q is consistent with a role for ECF H+ in mediating the cerebrovascular response to hypoxia.

Animals↗