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Biomedical subjects

S Negoro

Publications and source records attributed to S Negoro.

191 records · Page 11Linked to original sources
PubMed1980

Depressed immunological defence mechanisms in mice with experimentally induced diabetes.

Persistent diabetes mellitus with marked hyperglycemia was induced in mice by the administration of streptozotocin. In these streptozotocin-induced diabetic mice, resistance to tubercle bacillus challenge and primary as well as secondardy humoral immune responses against foreign erythrocytes were markedly depressed. The T-cell function in delayed hypersensitivity to 2,4-dinitro-1-fluorobenzene and bacterial phagocytic activity or peritoneal macrophages were markedly depressed. In contrast, the B-cell function in antibody production against T-independent antigen and the intracellular killing of bacteria in peritoneal macrophages were intact. We concluded that depression of the T-cell function or the phagocytic activity of macrophages or both may be the main immunological defect in these mice.

Animals↗
PubMed1980

Plasmid control of 6-aminohexanoic acid cyclic dimer degradation enzymes of Flavobacterium sp. KI72.

Flavobacterium sp. K172, which is able to grow on 6-aminohexanoic acid cyclic dimer as the sole source of carbon and nitrogen, and plasmid control of the responsible enzymes, 6-aminohexanoic acid cyclic dimer hydrolase and 6-aminohexanoic acid linear oligomer hydrolase, were studied. The wild strain of K172 harbors three kinds of plasmid, pOAD1 (26.2 megadaltons), pOAD2 (28.8 megadaltons), and pOAD3 (37.2 megadaltons). The wild strain K172 was readily cured of its ability to grow on the cyclic dimer by mitomycin C, and the cyclic dimer hydrolase could not be detected either as catalytic activity or by antibody precipitation. No reversion of the cured strains was detected. pOAD2 was not detected in every cured strain tested but was restored in a transformant. The transformant recovered both of the enzyme activities, and the cyclic dimer hydrolase of the transformant was immunologically identical with that of the wild strain. All of the strains tested, including the wild, cured, and transformant ones, possessed identical pOAD3 irrespective of the metabolizing activity. Some of the cured strains possessed pOAD1 identical with the wild strain, but the others harbored plasmids with partially altered structures which were likely to be derived from pOAD1 by genetic rearrangements such as deletion, insertion, or substitution. These results suggested that the genes of the enzymes were borne on pOAD2.

Amidohydrolases↗
PubMed1979

Regulatory mechanism of autoantibody production in mice to bromelin-treated isologous red blood cells.

In the spleen of mice immunized with bromelin treated rat red blood cells (RBC), the number of PFC against bromelin treated isologous RBC increased, although immunization with non-treated rat RBC or bromelin treated isologous RBC gave no increase in number of these PFC. This immune response was found to be T-independent and the PFC developed are exclusively of direct or Ig-M type. In the secondary immune response, production of these PFC was depressed rather than increased. This can be thought of as one of the defence mechanisms against overproduction of autoantibodies in confrontation to foreign antigens cross-reactive with self antigenic determinants. This depressed secondary immune response can be adoptively transferred by primed spleen cells but no active suppressor effect was found. We concluded that clonal elimination by exhaustive differentiation may be operative in this depressed secondary immune response.

Animals↗
PubMedDate not supplied

Phase I and pharmacologic study of oral (E)-2'-deoxy-2'-(fluoromethylene) cytidine: on a daily x 5-day schedule.

(E)-2'-deoxy-2'-(fluoromethylene)cytidine (FMdC), one of the most potent inhibitors of ribonucleoside diphosphate reductase, was selected for clinical development because of its novel mechanisms of action, and strong antitumor activity against experimental tumor models. This study was designed to determine the toxicities, maximum-tolerated dose (MTD), and pharmacokinetic profile of FMdC. FMdC was given orally for 5 consecutive days every 3 or 4 weeks in patients with advanced solid tumors. The starting dose was 8 mg/m2/day. Pharmacokinetic studies were carried out on days 1 through 5 of the first cycle. Ten patients with non-small cell lung cancer received 15 courses of FMdC at doses which were de-escalated from 8 mg/m2/day to 2 mg/m2/day because of unexpected severe toxicities at the starting dose level. Neutropenia was the dose-limiting toxicity. Thrombocytopenia and anemia were mild. Flu-like symptoms and fever were the common non-hematologic toxicities. The MTD was 4 mg/m2/day, since four of six patients developed grade 3-4 neutropenia. At the 4 mg/m2/day dose level, the mean terminal half-life, maximum plasma concentration (Cmax), plasma clearance, and mean residence time on day 1 were 3.20 h, 15.8 ng/ml, 2.91 l/h/kg, and 4.03 h, respectively. The recommended dose for phase II studies with this schedule is also 4 mg/m2/day for 5 days. Further investigations are necessary to establish optimal dosing schedules and routes for the administration of FMdC.

Administration, Oral↗
PubMedDate not supplied

Evolutionary adaptation of plasmid-encoded enzymes for degrading nylon oligomers.

Flavobacterium sp. KI72 metabolizes 6-aminohexanoic acid cyclic dimer, a by-product of nylon manufacture, through two newly evolved enzymes, 6-aminohexanoic acid cyclic dimer hydrolase (EI) and 6-aminohexanoic acid linear oligomer hydrolase (EII). These enzymes are active towards man-made compounds, the cyclic dimer and linear oligomers of 6-aminohexanoic acid respectively, but not towards any of the natural amide bonds tested. The structural genes of EI (nylA) and EII (nylB) are encoded on pOAD2, one of three plasmids harboured in Flavobacterium sp. KI72. This plasmid contains two kinds of repeated sequence (RS-I and RS-II); one of the two RS-II sequences, RS-IIA, contains the nylB gene, while the other, RS-IIB, contains a homologous nylB' gene. From comparisons of the nucleotide sequences and gene products of the nylB and nylB' genes, we now conclude that EII enzyme is newly evolved by gene duplication followed by base substitutions on the same plasmid.

Amidohydrolases↗
PubMedDate not supplied

The CA125 regression rate to predict overall survival differ between paclitaxel-containing regimen and nonpaclitaxel regimen in patients with advanced ovarian cancer.

In this study, we compare the time to normalization of CA125 after cytoreductive surgery between a paclitaxel-containing regimen and a non-paclitaxel regimen. This study demonstrates that CA125 regression in a paclitaxel-containing regimen was slower than that in a non-paclitaxel regimen. When we determine the CA125 regression rate to predict overall survival in ovarian cancer, we should take into account the kind of chemotherapy regimen, especially the use of paclitaxel.

Adult↗
PubMedDate not supplied

Intrapleural administration of cisplatin and etoposide to treat malignant pleural effusions in patients with non-small cell lung cancer.

BACKGROUND: To determine the efficacy, toxicity and pharmacokinetics of intrapleural cisplatin (CDDP) and etoposide as a treatment for malignant pleural effusions (MPE) in patients with non-small cell lung cancer (NSCLC). METHODS: Seventy patients with MPE associated with NSCLC were enrolled in this study. In 68 patients, a catheter was inserted into the pleural cavity, within 24 h after complete drainage of the pleural effusion, CDDP (80 mg/m2) and etoposide (80 mg/m2) were simultaneously administered successfully via the catheter and the catheter was clamped. Seventy-two hours later, the catheter was unclamped to allow drainage. The catheter was removed when the accumulated intrapleural fluid decreased to 20 ml or less per day. RESULTS: The pharmacokinetic profiles showed high maximum concentrations of CDDP (free form, 88 microg/ml) and etoposide (182. 4 microg/ml) in intrapleural fluids. CDDP did not remain for a long period (free form, beta-phase half-life = 10.51 h) in the fluids, while etoposide persisted for a long period (beta-phase half-life = 62.53 h). The overall response rate was 46.2%, the median survival time 32.3 weeks, the 1-year survival rate 28.7% and the 2-year survival rate 12.8%. The most serious adverse reactions were WHO grade 3 anemia (3 patients), grade 3 nausea and vomiting (17 patients), grade 3 constipation (1 patient), grade 3 pulmonary toxicity (1 patient), grade 4 fever (1 patient), grade 3 infection (1 patient) and grade 3 mental disorder (1 patient). CONCLUSION: Intrapleural administration of CDDP and etoposide was an effective and acceptable regimen for patients with MPE due to NSCLC.

Adenocarcinoma↗
PubMedDate not supplied

Prognostic factors in elderly patients with unresectable non-small cell lung cancer.

BACKGROUND: The number of elderly patients with lung cancer is rapidly increasing and their management is an important issue. PATIENTS AND METHODS: 109 patients aged over 75 years with unresectable non-small cell lung cancer were assessed to define the prognostic factors. The median age was 80 years in a range of 76 to 95. The overall median survival time was 6.3 months. Fifty-one patients underwent chemotherapy and/or thoracic radiotherapy whilst the others received best supportive care. RESULTS: Multivariate Cox regression model showed performance status (PS) (p = 0.0063) and stage of disease (p = 0.0158) to be independent prognostic factors for survival. In seventy-six patients with a good PS of 0-1, choice of treatment (p = 0.0225) and hyponatremia (p = 0.0302) were the predictors for survival. CONCLUSIONS: PS, treatment and serum sodium level were important factors for survival, and most patients with good PS were able to undergo the treatment and have a good outcome.

Aged↗