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Biomedical subjects

J A Roth

Publications and source records attributed to J A Roth.

At least 451 records · Page 25Linked to original sources

Improved graft patency in patients treated with platelet-inhibiting therapy after coronary bypass surgery.

One hundred forty-seven consecutive coronary bypass patients were enrolled in a randomized, double-blind, risk-stratified, placebo-controlled prospective trial evaluating the effect on graft patency of 325 mg tid aspirin (ASA) plus 75 mg tid dipyridamole (DP) or ASA alone. One hundred twenty-seven patients (399 total grafts) underwent surgery, initiation of drug therapy 67 +/- 27 (SD) hr postoperatively, five clinic visits, and repeat angiography at 1 year. A logistic regression statistical model was used to determine the effects of 28 different measured variables on graft patency and to adjust for these effects in determining the relationship between antiplatelet therapy and graft occlusion. No patient-specific variable contributed significantly to the prediction of occlusion in either the placebo or the treated group. Six graft-specific variables (arterial diameter, severity of stenosis, graft flow, reactive hyperemia, presence or absence of collaterals, and graft type) did contribute and were included in the model. Twenty-one percent of placebo-treated grafts became occluded. Compared with placebo, the relative risk of graft occlusion with ASA was 0.47 (p = .04); with ASA + DP, it was 0.50 (p = .04). This benefit was principally due to reduction of occlusion in the most common and presumably most important groups of grafts, those in which flow exceeded 40 ml/min, or supplying arteries having luminal diameters greater than 1.5 mm. Grafts lacking reactive hyperemia had a 32% occlusion frequency in placebo-treated patients; relative risk of their occlusion averaged 0.26 (p less than .01) with platelet-inhibiting therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Detection of pulmonary metastases in patients with osteogenic and soft-tissue sarcomas: the superiority of CT scans compared with conventional linear tomograms using dynamic analysis.

A prospective serial evaluation in 19 patients with soft-tissue and osteogenic sarcomas was performed to determine whether computerized tomography (CT) or conventional linear tomography (LT) detected pulmonary metastases earlier. Analysis of the metastatic nodules was performed radiographically with histologic confirmation by obtaining serial CTs and LTs followed by metastasectomy. Nodules were classified as stable, growing, or developing and by detection on CT and/or LT. CT was the first positive study in a significantly greater number of patients (13 CT, 1 LT; P less than .005), and CT detected the nodules earlier than LT (56 CT first v 7 LT first; P less than .0001). Ninety of 166 nodules resected were detected by CT, LT, or both (54%). The median size of metastatic nodules documented at surgical exploration and first detected by CT was significantly smaller than that first detected by LT (7.6 mm for CT v 13.2 mm for LT; P less than .05). Of 55 histologically documented metastases detected initially either by CT or LT, CT was markedly superior to LT with 50 (91%) first detected only by CT (P less than .001). These data reveal that CT detects more pulmonary metastases earlier than LT and that developing or growing nodules in patients with sarcomas are usually metastases. Decisions regarding metastasis resection in sarcoma patients, therefore, should be based primarily on CT findings.

Adolescent↗

A large scale method of separating multiple lymphokines secreted by the murine EL-4 thymoma.

The in vivo administration of lymphokines is a new approach to immunotherapy with possible applications to the treatment of tumors and infectious processes. These lymphokines are produced in very small quantities and purification of these molecules has proven difficult. A rapid two step method was used to isolate different lymphokines from large quantities of conditioned media produced by the murine EL-4 cell line. Interleukin-2 (IL-2), colony stimulating factor (CSF) and macrophage activating factor (MAF) are lymphokines with distinct biologic activities and are secreted by the EL-4 cell line. Their isolation involved initial batch purification on trimethylsilyl-controlled pore glass beads followed by reversed phase high pressure liquid chromatography. Recovery of IL-2 activity was greater than 100% of initial activity. The specific activity of the purified IL-2 ranged from 2 X 10(6) to 3.6 X 10(7) U/mg protein. Colony stimulating factor (CSF) and macrophage activating factor (MAF) were also separated on the chromatographic columns. This technique is useful for the purification of large quantities of these lymphokines which have potential in vivo applications.

Animals↗

Enhancement of lymphocyte blastogenesis and neutrophil function by avridine in dexamethasone-treated and nontreated cattle.

The lipoidal amine, N,N-dioctadecyl-N',N'-bis (2-hydroxyethyl) propanediamine (avridine or CP 20,961), formulated in liposomes, was evaluated for its effect on leukocyte kinetics, lymphocyte blastogenesis, and polymorphonuclear leukocyte (PMN) function in dexamethasone-treated and nontreated cattle. In the 1st experiment, cattle were given avridine in a single IM injection of 0.1, 1.0, or 10 mg/kg of body weight. All doses induced swelling at the injection site, a febrile response, and a leukocytosis due to a neutrophilia. Mononuclear cell numbers were normal. All 3 groups of avridine-treated animals had a higher mean lymphocyte blastogenic response to mitogens on the 4 days after administration than did the control nontreated animals. Avridine administration was associated with an enhanced ability of PMN to ingest Staphylococcus aureus and to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). The highest dose (10 mg/kg) was associated with a depression of the ability of PMN to iodinate protein. An effect of avridine on PMN random migration under agarose or nitroblue tetrazolium (NBT) reduction was not observed. In a 2nd experiment, cattle were given no treatment, 0.04 mg of dexamethasone/kg IM, or 10 mg of avridine/kg IM followed 24 hours later by 0.04 mg of dexamethasone/kg. Dexamethasone administration caused a leukocytosis due to a neutrophilia with normal mononuclear cell numbers, an enhancement of PMN random migration under agarose, and an inhibition of NBT reduction, iodination, and ADCC activity of PMN. Dexamethasone did not have a detectable effect on lymphocyte blastogenesis or on ingestion of S aureus by PMN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vivo effect of ascorbic acid on neutrophil function in healthy and dexamethasone-treated cattle.

Ascorbic acid (20 mg/kg of body weight) administered subcutaneously to otherwise nontreated cattle resulted in enhancement of neutrophil oxidative metabolism and capability of neutrophils to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). Random migration, bacterial ingestion, and iodination by neutrophils was unaffected. Three dosage levels of ascorbic acid (10 mg/kg, 20 mg/kg, and 40 mg/kg) were examined for their effects on neutrophil function in cattle treated with dexamethasone (0.04 mg/kg). Dexamethasone administration caused an enhancement of neutrophil random migration and a suppression of neutrophil oxidative metabolism, iodination, and ADCC. None of the dosage levels of ascorbic acid had an effect on the alterations in the WBC count induced by dexamethasone. The ascorbic acid did tend to reverse the effects of dexamethasone on neutrophil random migration, oxidative metabolism, and ADCC in a dose-dependent manner, with the lowest dose having no discernible effect. Ascorbic acid administration also tended to enhance Staphylococcus aureus ingestion by bovine neutrophils. These results indicate that ascorbic acid should be further investigated for its potential to reduce the susceptibility of stressed or glucocorticoid-treated cattle to infective processes.

Animals↗

Late occurrence of malignancy in a ganglioneuroma 19 years following radiation therapy to a neuroblastoma.

Neuroblastoma is a common solid tumor of childhood. Maturation to a ganglioneuroma or regression has been reported to occur spontaneously or following minimal treatment. Malignant degeneration of such a ganglioneuroma is extremely rare. We present a report of a malignant tumor arising in a ganglioneuroma 19 years following abdominal radiation therapy for neuroblastoma.

Abdominal Neoplasms↗

Attempts to use thiabendazole to improve the immune response in dexamethasone-treated or stressed cattle.

Thiabendazole was evaluated in two separate experiments for its ability to enhance the immune response in dexamethasone-treated or stressed cattle. In the first experiment the cattle received either no drug treatment (controls), dexamethasone intramuscularly (IM), or dexamethasone IM plus thiabendazole orally. All animals were inoculated with heat-killed Brucella abortus strain 19, equine ferritin, tetanus toxoid, and live Corynebacterium equi at the time dexamethasone therapy was initiated. Dexamethasone (0.04 mg/kg/day IM for 3 days) significantly (p less than 0.05) inhibited the lymphocyte blastogenic response to mitogens and the antibody response to ferritin and tetanus toxoid. Thiabendazole given orally (16 mg/kg/day) beginning 24 h prior to antigen and dexamethasone administration and continued for 6 days failed to prevent the dexamethasone-induced suppression of the lymphocyte blastogenic or antibody responses. In the second experiment 51 cattle were divided into a control group and a thiabendazole-treated group. The animals were stressed by weaning, injection of antigen (equine ferritin, tetanus toxoid, B. abortus strain 19 and killed bovine viral diarrhea virus) and castration of the bulls on the day that thiabendazole therapy was started. Thiabendazole administered orally for 5 days at a dosage of 20 mg/kg did not enhance the antibody response to any of the antigens, and was associated with a significantly lower antibody response to B. abortus.

Animals↗

Effects of thiabendazole on dexamethasone-induced suppression of lymphocyte and neutrophil function in cattle.

Seven dosage levels of thiabendazole were evaluated for their ability to normalize lymphocyte or neutrophil function in dexamethasone-treated cattle. Dexamethasone administration (0.04 mg/kg intramuscularly daily for 3 days) significantly suppressed the lymphocyte blastogenic response to phytohemagglutinin, concanavalin A, and pokeweed mitogen. The lymphocyte blastogenic response to allogeneic lymphocytes was also suppressed in dexamethasone-treated cattle, but this effect was not statistically significant. Neutrophils from dexamethasone-treated cattle had a significantly enhanced ability to migrate under agarose, and significantly suppressed ability to reduce nitroblue tetrazolium, iodinate protein, and mediate antibody-dependent cell-mediated cytotoxicity. Thiabendazole when administered concurrently with dexamethasone in the dosage range from 1.0 to 25.0 mg/kg (orally) did significantly enhance lymphocyte blastogenic responsiveness to phytohemagglutinin, concanavalin A, pokeweed mitogen and allogeneic cells (in dexamethasone-treated cattle). This immunonormalizing effect was not observed at the 50 or 100 mg/kg dosage levels. Thiabendazole did not produce a consistent significant enhancement of any parameter of neutrophil function in dexamethasone-treated cattle.

Animals↗

Effect of Rhodococcus equi on equine polymorphonuclear leukocyte function.

A procedure was developed for isolating large numbers of purified polymorphonuclear leukocytes (PMNs) from the peripheral blood of horses. Equine PMN function was evaluated by three procedures: 1) Staphylococcus aureus ingestion, 2) nitroblue tetrazolium reduction, and 3) iodination. Four preparations of R. equi were added to polymorphonuclear leukocytes (PMNs) in each test system. Live bacteria, heat-killed bacteria, the washed pellet from heat-killed bacteria, and the supernatant fluid from heat-killed bacteria were evaluated for effects on equine PMN function. None of the R. equi preparations had an effect on S. aureus ingestion by equine PMNs. Nitroblue tetrazolium reduction by PMNs, a measure of oxidative metabolism, was suppressed by pellet and supernatant fractions. Values for the iodination reaction were depressed by all R. equi preparations, indicating decreased activity of the myeloperoxidase-H2O2-halide system of the PMN. Further evaluation of the supernatant from heat-killed R. equi showed that it retained its inhibitory effect on iodination following autoclaving and/or passage through a 10,000 MW filter. R. equi fractions did not alter the enzymatic conversion of 125I to a protein-bound form in a PMN-free assay developed to evaluate this reaction. The presence of a surface component capable of inhibiting bactericidal mechanisms of the PMN may play an important role in intracellular survival of R. equi.

Animals↗

Radical forequarter amputation with chest wall resection.

Forequarter amputation with resection of the chest wall is indicated for primary bony and soft tissue tumors involving the shoulder girdle, axilla, and chest wall, as well as for recurrent breast cancer in the axilla after irradiation. We describe a modification of this procedure that includes an initial thoracotomy for intraoperative staging and a median sternotomy, which avoids individual division of the anterior ribs and clavicle.

Adult↗

Staff-inmate bargaining tactics in long-term treatment institutions.

The field notes of four studies of long-term treatment institutions are examined for patterns of staff-inmate bargaining. The main focus is on the conditions which enhance the bargaining power of staff and of inmates in relation to each other. A list of such conditions with examples is provided.

England↗

Characterization of membrane-bound and soluble catechol-O-methyltransferase from human frontal cortex.

Catechol-O-methyltransferase (COMT; E.C. 2.1.1.6) from human frontal cortex occurs in both a soluble and membrane-bound form. Attempts to solubilize the membrane-bound transferase by repeated washing or by extraction into solutions of high ionic strength were unsuccessful. The finding that Triton X-100 was capable of solubilizing membrane-bound COMT suggested that the membrane-bound transferase is an integral membrane protein. The membrane-bound and soluble enzymes did not differ in their requirements for magnesium ions or in their pH-activity profiles; both enzymes showed an optimum near pH 8.0 when assayed in phosphate buffer. In addition, the two enzymes did not differ in the degree of inhibition caused by CaCl2, both enzymes displaying 65% inhibition at 2.5 mM CaCl2. The competitive inhibitors tropolone and nordihydroguaiaretic acid displayed Ki values for the membrane-bound transferase five- to 10-fold lower than those observed for the soluble transferase. Solubilization of membrane-bound COMT in Triton X-100 resulted in an increase in the apparent Km value of the membrane-bound transferase for dopamine. The increase in Km appeared to be due to apparent competitive inhibition by Triton X-100 and reached a limiting value of approximately 80 microM. These results confirm that membrane-bound COMT is an integral membrane protein that may be structurally distinct from soluble COMT.

Catechol O-Methyltransferase↗

Sulfate conjugation of dopamine in rat brain: regional distribution of activity and evidence for neuronal localization.

Brain tissue contains at least two forms of phenolsulfotransferase that are involved in the sulfate conjugation of biogenic amines and their metabolites. Two apparent Km values were obtained for p-nitrophenol at pH 7.4 (0.6 microM and 0.3 mM) but only one enzyme had the capacity to conjugate dopamine (Km = 130 microM). Dopamine sulfotransferase activity was found to vary 17-fold in different brain regions, with the highest levels in diencephalon, hippocampus, and striatum. To determine the cellular localization of the enzymes, phenolsulfotransferase activity was measured in striatum following selective destruction of striatal neurons by stereotaxic injection of 2 micrograms kainic acid. Fourteen days after injection the catecholamine sulfotransferase activity in the lesioned striatum was reduced to approximately 40-50% of that in the control contralateral striatum. There was a statistically significant correlation between the ratio of lesioned to control activity for the sulfotransferase and the neuronal marker enzymes glutamate decarboxylase and neuron-specific enolase. p-Nitrophenol sulfotransferase activity was also decreased in the lesioned striatum. These results suggest that PST activity is present within the kainic acid-sensitive neurons of the striatum. The regional variation in activity, together with the results of the kainic acid studies, suggest that sulfate conjugation of biogenic amines and their metabolites in brain may take place within specific types of neurons.

Animals↗

Effect of type A Pasteurella multocida fractions on bovine polymorphonuclear leukocyte functions.

The effect of various Pasteurella multocida fractions on bovine polymorphonuclear leukocyte (PMN) functions was examined in vitro by using two encapsulated strains, P-2383 and P-1062 (both are Carter capsular type A and of bovine origin). The ability of PMNs to ingest Staphylococcus aureus and iodinate protein was significantly inhibited in the presence of live cells, heat-killed whole cells, or saline-extracted capsules but not in the presence of the decapsulated heat-killed cells. None of the fractions of the two strains inhibited nitroblue tetrazolium reduction by PMNs. The saline extract did not inhibit the binding of iodine to protein by a reaction involving xanthine, xanthine oxidase, and horseradish peroxidase. The PMN inhibitory factor was further characterized as a heat-stable capsular material of greater than 300,000 molecular weight.

Animals↗

Effect of levamisole on lymphocyte blastogenesis and neutrophil function in dexamethasone-treated cattle.

Levamisole was evaluated at 6 dose levels for its ability to prevent the dexamethasone-induced suppression of in vitro lymphocyte blastogenesis or neutrophil function in cattle. Dexamethasone (0.4 mg/kg of body weight, IM) and levamisole hydrochloride (0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg orally) were administered to groups of 4 cattle daily for 3 days. Another group of 4 cattle were given the 3-day dexamethasone treatment and 6.0 mg/kg of levamisole (the recommended anthelmintic dose) was given only once on the 1st day that dexamethasone was given. Results obtained from the dexamethasone-levamisole-treated cattle were compared with results obtained from cattle that were given only dexamethasone. Levamisole had no apparent consistent ability to enhance lymphocyte blastogenic responsiveness (to the mitogens phytohemagglutinin, concanavalin A, or pokeweed mitogen or in a 1-way mixed lymphocyte reaction) or to enhance neutrophil function (random migration, nitroblue tetrazolium reduction, iodination, or antibody-dependent cell-mediated cytotoxicity) in dexamethasone-treated cattle.

Adrenocorticotropic Hormone↗