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Biomedical subjects

J A Roth

Publications and source records attributed to J A Roth.

At least 487 records · Page 27Linked to original sources

Survival following aggressive resection of pulmonary metastases from osteogenic sarcoma: analysis of prognostic factors.

Between 1975 and 1982, 80 patients with osteogenic sarcoma were entered into prospective trials in the Surgery Branch of the National Cancer Institute. In 43 of these patients, pulmonary metastases developed as the initial site of recurrence, and 39 underwent one or more thoracotomies for resection of the disease. The actuarial five-year survival for the group of 43 patients with pulmonary metastases was 40%. Various prognostic factors were analyzed for their influence on survival after thoracotomy. Age, sex, location of primary tumor, tumor doubling time, and involvement of one or both lungs (bilaterality) were not significant in predicting survival. Prognostic factors that influenced survival, calculated by regression analysis, included the number of nodules on preoperative lung tomograms (negative correlation, p = 0.0004), disease-free interval (positive correlation, p = 0.0136), resectability (positive correlation, p = 0.002), and the number of metastases resected at thoracotomy (negative correlation, p = 0.0032). The presence of 3 nodules or less on preoperative full-lung linear tomography was found to be the single most useful preoperative prognostic factor. The application of these prognostic factors preoperatively may identify patients who will benefit optimally from thoracotomy.

Actuarial Analysis↗

Distinct cellular localization of membrane-bound and soluble forms of catechol-O-methyltransferase in brain.

The cellular localization of the two forms of catechol-O-methyltransferase (COMT) was investigated by measuring their activities in rat striatum following unilateral stereotaxic injection of kainic acid, which causes degeneration of striatal neurons followed by proliferation of astroglial cells. Membrane-bound COMT activity was decreased in the lesioned striatum, while soluble COMT activity was increased. There was a statistically significant correlation between the ratio of lesioned to control activity for membrane-bond COMT and the neuronal marker enzyme glutamate decarboxylase. Similarly the increase in soluble COMT activity paralleled that of the astroglial marker enzyme, glutamine synthetase. These results indicate that the low-Km membrane-bound catechol-O-methyltransferase may be localized predominantly in neurons, whereas the high-Km soluble enzyme is found in glial cells.

Animals↗

Localization of membrane-bound catechol-O-methyltransferase.

Previous studies of the distribution of catechol-O-methyltransferase (COMT) have concentrated on the soluble enzyme activity. In this study the activity of the membrane-bound enzyme was determined in different brain regions and peripheral tissues of the rat. Membrane-bound COMT, like the soluble enzyme, has a general distribution with high levels in liver, kidney, and vas deferens. However, the ratio of membrane-bound to soluble activity varies almost 30-fold in different tissues, with the highest ratio in brain. Membrane-bound activity varies twofold within brain. In view of their different localization and kinetic properties, it seems likely that the two forms of COMT have different functions in vivo.

Animals↗

Immunoregulatory factors derived from human tumors. II. Partial purification and further immunobiochemical characterization of a human sarcoma-derived immunosuppressive factor expressing HLA-DR and immunoglobulin-related determinants.

An immunoregulatory factor (IRF) that suppresses Con A-mediated peripheral blood mononuclear cell (PBM) proliferative responses was partially purified by DEAE anion exchange chromatography and affinity chromatography from a 3 M KCl extract of a human liposarcoma. The factor (m.w. = 70K) co-purified with albumin, monitored by two-dimensional gel electrophoresis, and demonstrated a heterogeneous isoelectric point (pI 7.6-7.8). Xenoantisera produced against the DEAE-purified fraction and coupled to Affigel 10 removed suppressive activity that could subsequently be eluted by glycine-HCl, pH 3.5. An anti-albumin column partially removed activity, but the unbound 70K factor could still be detected in the column effluent. A xenoantiserum to this 70K effluent coupled to acrylamide beads completely removed the immunosuppressive activity in immunodepletion experiments. Further direct binding enzyme-linked immunoassays (ELISA) and solid-phase immunoabsorption experiments with monoclonal antibodies to human anti-HLA-DR framework determinants and a constant region of the IgM mu-chain demonstrated determinants on the 70K factor recognized by these antibodies.

Cells, Cultured↗

Suppression of neutrophil and lymphocyte function induced by a vaccinal strain of bovine viral diarrhea virus with and without the administration of ACTH.

Effects of a modified live vaccine (MLV) strain of bovine viral diarrhea virus (BVD) on lymphocyte and neutrophil function were determined in cattle with and without increased plasma cortisol (hydrocortisone) concentrations. Cattle were given MLV-BVD vaccine IM and intranasally. Cattle given ACTH received 200 IU every 12 hours for 10 doses. The MLV-BVD virus when administered alone caused no apparent clinical signs or body temperature response. Of 4 MLV-BVD-treated calves that were also given ACTH, 2 developed increased body temperature and respiratory distress. The MLV-BVD virus caused a decrease in circulating lymphocytes and neutrophils, whereas administration of ACTH and MLV-BVD induced a neutrophilia and lymphopenia. The MLV-BVD virus and ACTH when administered separately or in combination caused a depression of lymphocyte blastogenesis in response to selected mitogens. Neutrophils were separated from the peripheral blood and their function was evaluated, using the following procedures: (i) random migration under agarose, (ii) ingestion of 125I-labeled Staphylococcus aureus, (iii) quantitative nitroblue tetrazolium reduction, (iv) iodination, and (v) antibody-dependent cell-mediated cytotoxicity (ADCC). The MLV-BVD virus produced a significant (P less than 0.05) suppression of neutrophil iodination and ADCC. Neutrophils from cattle given MLV-BVD virus and ACTH had enhanced random migration, enhanced S aureus ingestion, suppressed iodination, and suppressed ADCC activity.

Adrenocorticotropic Hormone↗

Depression of polymorphonuclear leukocyte function associated with experimentally induced Escherichia coli mastitis in sows.

In a study of susceptibilities of sows from 2 herds to experimentally induced Escherichia coli mastitis, a marked difference was seen. The "susceptible" sows were from a conventional herd and "resistant" sows were from a specific-pathogen-free herd. The purpose of the study was to determine whether deficient neutrophil function was associated with increased susceptibility to E coli-induced mastitis. Four in vitro procedures were used to evaluate polymorphonuclear leukocyte (PMN) function: (i) random migration under agarose, (ii) ingestion of 125I-iododeoxyuridine-labeled Staphylococcus aureus, (iii) quantitative nitroblue tetrazolium reduction, and (iv) iodination. After parturition and intramammary inoculation with E coli, sows from the susceptible herd were neutropenic and the neutrophils which were present in the peripheral blood had reduced function. Specifically, there were depressed random migration under agarose, S aureus ingestion, and iodination when compared with PMN function in resistant sows. These data indicate that susceptibility to E coli mastitis was associated with deficiencies in PMN numbers and function. Potential causes of the neutrophil dysfunction are discussed and include possible systemic hormonal aberrations or the presence of an inapparent viral or bacterial infection.

Animals↗

Association of increased estradiol and progesterone blood values with altered bovine polymorphonuclear leukocyte function.

Polymorphonuclear leukocyte (PMN) function and serum concentrations of estradiol, progesterone, and cortisol (hydrocortisone) were monitored concurrently in clinically normal cows during the estrous cycle. Five parameters were used to evaluate PMN function: (i) random migration under agarose, (ii) ingestion of 125I-labeled Staphylococcus aureus, (iii) nitroblue tetrazolium (NBT) reduction, (iv) iodination, and (v) antibody-dependent cell-mediated cytotoxicity. Increased serum estradiol concentrations were associated with enhanced random migration, but had no apparent effect on NBT reduction, iodination, or ingestion of S aureus by bovine PMN. Increased serum estradiol was also associated with increased serum cortisol. Increased serum progesterone values were associated with a depression of NBT reduction and iodination by PMN, but with enhanced random migration and antibody-dependent cell-mediated cytotoxicity. These results indicate that physiologic changes in steroid hormone values during the normal estrous cycle of the cow are associated with alterations in PMN function.

Animals↗

Carcinoma arising in an ileostomy stoma: an unusual complication of adenomatous polyposis coli.

A patient with adenomatous polyposis coli (APC) without extraintestinal lesions is presented. The clinical course was complicated by rectal adenocarcinoma following subtotal colectomy. A primary adenocarcinoma arising in a villous adenoma within the ileostomy stoma developed seven years later. The varied pathology of gastric and small intestinal involvement in APC/Gardner's syndrome is reviewed. Greater awareness of these lesions has implications for further management.

Abdominal Muscles↗

Kinetic studies on the O-methylation of dopamine by human brain membrane-bound catechol O-methyltransferase.

Km values for dopamine and S-adenosylmethionine (AdoMet) of human brain membrane-bound catechol O-methyltransferase are 3.3 microM and 3.1 microM, respectively. S-Adenosylhomocysteine is a very potent competitive inhibitor with respect to AdoMet with a Ki value of 1 microM. Product inhibition patterns strongly support a steady-state compulsory-order ternary complex mechanism in which AdoMet binds to the enzyme before dopamine. Inhibition of membrane-bound COMT by tropolone is competitive with respect to dopamine (Ki = 5 microM) and uncompetitive with respect to AdoMet and is consistent with this type of mechanism. The mechanism proposed is different from that suggested for soluble catechol O-methyltransferases.

Brain↗

Catecholamine-thyroid hormone interactions: II. Thyroid hormone and platelet MAO activity in patients with thyroid disorders.

Platelet monoamine oxidase (MAO) activity and serum thyroxine indices were determined in 62 children and adolescents currently undergoing medical treatment for various thyroid disorders. The platelet MAO activity of these patients was similar to that of control and contrast groups previously reported, and there were no differences when patients were grouped according to specific thyroid disorders. Estimated free thyroxine and total thyroxine levels were generally in the upper normal or slightly elevated range and were not significantly related to MAO activity.

Adolescent↗

A black hepatocellular carcinoma with Dubin-Johnson-like pigment and Mallory bodies: a histochemical and ultrastructural study.

A hepatocellular carcinoma which was predominately black was surgically excised from a noncirrhotic, asymptomatic 62-year-old white man. Brown-black, pigment granules, found only in the tumor cells, were histochemically and ultrastructurally identical to the hepatocellular pigment found in Dubin-Johnson syndrome. The latter pigment is thought to accumulate as a consequence of a genetically determined abnormality in the excretion of catecholamines and related substances. It is postulated that the pigment formation in this tumor developed via a similar, though epigenetic, mechanism. This occurrence has not been previously described. Unusual PAS-negative, globular cytoplasmic inclusions were also found in the tumor cells and these proved to be Mallory bodies by electron microscopy.

Carcinoma, Hepatocellular↗

Contribution of sulfate conjugation, deamination, and O-methylation to metabolism of dopamine and norepinephrine in human brain.

The kinetic constants were determined for dopamine (CA) and norepinephrine (NE) metabolism by phenolsulfotransferase (PST), type A and B monoamine oxidase (MAO), and membrane-bound and soluble catechol-O-methyltransferase (COMT) in frontal lobe preparations of human brain. PST and membrane-bound COMT were found to have the lowest Km values for both catecholamines. By means of the appropriate rate equations and the calculated kinetic constants for each enzyme, the activity of each enzymatic pathway was determined at varying concentrations of DA and NE. Results indicate that deamination by MAO is the principal pathway for the enzymatic inactivation of DA whereas NE is largely metabolized by MAO type A and membrane-bound COMT under the in vitro assay conditions used. At concentrations less than 100 microM, soluble COMT contributes less than 5% to the total catabolism of either catecholamine. PST can contribute up to 15% of the total DA metabolism and 7% of NE metabolism.

Arylsulfotransferase↗

Effect of estradiol and progesterone on lymphocyte and neutrophil functions in steers.

Polymorphonuclear leukocyte function and lymphocyte blastogenesis in response to mitogens were evaluated in castrated male cattle after the repeated administration of estradiol or progesterone. Polymorphonuclear leukocyte function was evaluated with the following five parameters: (i) random migration under agarose, (ii) ingestion of 125I-labeled Staphylococcus aureus, (iii) nitroblue tetrazolium reduction, (iv) iodination, and (v) antibody-dependent cell-mediated cytotoxicity. The administration of high dosages of estradiol cypionate produced no measurable effect on the total or differential leukocyte count, neutrophil function, lymphocyte blastogenesis, or blood cortisol levels. The administration of high dosages of progesterone caused a significant enhancement of random migration by neutrophils and a depression of the activity of the myeloperoxidase-H2O2-halide antibacterial system (iodination) of the neutrophil. Progesterone administration did not cause a measurable effect on the lymphocyte blastogenic response to mitogens or the ability of polymorphonuclear leukocytes to ingest S. aureus, reduce nitroblue tetrazolium, or mediate antibody-dependent cell-mediated cytotoxicity. Progesterone did not cause a change in blood cortisol concentrations; therefore, the observed effects on polymorphonuclear leukocyte function were not due to alterations in blood cortisol concentrations. Impairment of the iodination reaction indicates that high dosages of progesterone interfere with an important bactericidal mechanism of the neutrophil.

Animals↗