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Biomedical subjects

T Kajiwara

Publications and source records attributed to T Kajiwara.

At least 163 records · Page 9Linked to original sources

[Clinical trial of cisplatin in the treatment of ovarian carcinoma].

Cisplatin (cis-diamminedichloroplatinum) was administered to 20 patients with histologically proven ovarian cancer. Ten of 20 patients were evaluable. They consisted of 1 patient by single use and 9 by combined use. The dose of cisplatin in single administration was 50 mg/m2, and the schedule for combined administration was as follows: cisplatin (50mg/m2, i.v. day 1), adriamycin (40 mg/m2, i.v. day 1), cyclophosphamide (350 mg/m2, i.v. day 1) and 5-FU (350 mg/m2, i.v. day 1-5). This was repeated every three weeks. The side effects of cisplatin and in its combination use were relatively severe. All of 20 patients showed severe nausea and vomiting, but fortunately there were no signs of hepatotoxicity, bone marrow or renal impairments during these courses. As the result, according to the response criteria of Koyama-Saito's group, out of 10 evaluable patients, the response rate consisting of partial and complete responses was 50% (CR: 3 cases, RP: 2 cases). It is shown that cisplatin is effective and useful in chemotherapy for the patients with ovarian carcinoma.

Adenocarcinoma↗

Mammary tumorigenic effect of a new nitrosourea, 1,3-dibutyl-l-nitrosourea (B-BNU), in female Donryu rats.

Four groups (groups 1-4) of female Donryu rats were given continuously 400, 200, 100, or 0 ppm solution of 1,3-dibutyl-l-nitrosourea (B-BNU) as their drinking water, and were studied for the development of tumors. The incidence of mammary tumors was 15/19 (79%), 20/24 (83%), 21/26 (81%), and 8/25 (32%) in groups 1, 2, 3, and 4, respectively. In addition, hematopoietic neoplasms, uterine tumors, and vaginal tumors developed in 13, 11, and six rats, respectively in 69 treated rats. Other tumors were infrequent.

Animals↗

[Effect of D-penicillamine on vitamine B6 and collagen metabolism (author's transl)].

Although D-Penicillamine (D-PeA) administration is getting popular in the treatment of rheumatoid arthritis (RA), the mechanism by which D-PeA produced therapeutic effect has not been fully elucidated. D-PeA had been shown to exert an antivitamine B6 effect. However, it has not been precisely confirmed if clinical dose of D-PeA induces vitamine B6 (VB6) deficiency. In order to clarify these questions, biochemical analyses of bone and skin collagens and determination of VB6 content in soft tissues have been performed in the rats administrated therapeutic dose of D-PeA. VB6 deficiency was not observed in the brain and skin from rats fed on normal diet containing D-PeA (13.0--33.5 mg/kg wt). There were no significant changes in the stability of collagen from bone and skin. On the other hand, significant VB6 deficiency and reduced stability of collagen were observed in rats fed on VB6 deficient diet containing the same amount of D-PeA. Aldehyde formation of collagen molecule and cross-link formation of collagen were also found to be suppressed. The same results were obtained from analyses in rats fed on VB6 deficient diet without D-PeA administration. These data indicate that D-PeA is not capable of producing VB6 deficiency in the dosage employed in patients. However, in the treatment for patients who are not taking enough nutrition, the possibility of VB6 deficiency can not be neglected. Once VB6 deficiency is induced by D-PeA administration, severe connective tissue disorder may be produced, since VB6 is required for enzymic activity of lysyl oxidase. It is unlikely that the therapeutic effects of D-PeA in the treatment of RA are produced the the disturbance of collagen cross-link formation as discussed before. Immunologic reactions of D-PeA may play more important role in the improvement of clinical symptoms of this disease.

Aldehydes↗

Hepatic changes in male ACI/N rats on low dietary levels of sterigmatocystin.

Three groups, each consisting of 36 male ACI/N rats, were fed a diet containing 10, 1, or 0.1 ppm sterigmatocystin for life span. There was no dose--effect relationship on tumor incidence or mean survival time. Toxic and preneoplastic changes of the parenchyma such as hyperplastic foci were observed in the liver of experimental groups with dose--effect relation, but hepatocellular carcinoma was observed only in one rat of 10 ppm group. In addition to these lesions, hemangiosarcomas of the liver were also observed in the highest and middle-dose groups, 3/26 and 1/29, respectively. There was not significant difference in the incidence of other tumors in experimental or control groups.

Animals↗

Functional alteration of islet cells after jejunal or ileal resection in dogs.

Functional alteration of the islet cells was investigated in dogs after the resection of different parts of the small intestine. Three weeks after jejunal or ileal resection, when the dogs might still have been in a catabolic state, insulin and pancreatic glucagon release in response to intravenously infused glucose and arginine was reduced. Three months after jejunal resection, both intravenous glucose tolerance and insulinogenic index in the intravenous glucose tolerance test were significantly below the preoperative values (P less than 0.001, P less than 0.05), while pancreatic glucagon release in response to arginine infusion release. This functional alteration three months after jejunal resection was similar to that seen in diabetes mellitus. On the other hand, three months after ileal resection, insulin and pancreatic glucagon release was almost normal. We conclude that the jejunum plays a more important role in the enteroinsular system than the ileum and that prolonged interruption of this enteroinsular axis can cause insular disorder and what could hypothetically be called enterogenic chemical diabetes, in view of the altered glucose tolerance test and the alteration in insulin secretory response.

Animals↗

Effects of penicillamine on distribution of B6 vitamens in rat urine.

The antivitamin B6 effect of DL- and D-penicillamine has been studied in rats. A considerable elevation in the urinary excretion of vitamin B6 activity (pyridoxal and its thiazolidine derivative) has been shown as a parameter of B6 antagonism. Both DL- and D-pencillamine have been shown to have an antivitamin B6 effect in rats, although that induced by the DL-form is considerably greater, as would be expected from previous studies. We suggest that B6 supplementation should be included in any long term penicillamine therapy, regardless of the isomer that is employed.

Animals↗

Effect of biliary diversion on exocrine pancreas.

An experimental study was conducted on the effect of bile diversion on exocrine pancreatic function. Twelve dogs were divided into three groups, one group consisting of a choledochojejunostomy; one, a choledochoduodenostomy, and one, a choledochocholedochostomy. In each group, exocrine pancreatic function was observed before and two months after the operation. With combined secretin and pancreozymin infusion, a significant decrease in the rate of flow, bicarbonate concentration and amylase output was seen only after choledochojejunostomy. The function of the exocrine pancreas was markedly decreased late in the period of stimulation. Contrariwise, no pancreatic dysfunction was noted after choledochoduodenostomy or choledochocholedochostomy. The high incidence of peptic ulcer formation after choledochojejunostomy might be closely connected with the postoperative impairment of exocrine pancreatic function.

Amylases↗

Electron spin resonance studies on the lipoxygenase reaction by spin trapping and spin labelling methods.

The rate of oxygenation and that of trapping linoleic acid free radicals in the lipoxygenase [EC 1.13.11.12] reaction were measured in the presence of linoleic acid, oxygen, and nitrosobenzene at various concentrations, with a Clark oxygen electrode and ESR spectroscopy. The results were interpreted under the assumption that the free radical of linoleic acid, an intermediate of the lipoxygenase reaction, reacts competitively with oxygen or nitrosobenzene. The oxidation of the iron in the active site of lipoxygenase caused by the spin label reagent, 2-(10-carboxydecyl)-2-hexyl-4,4-dimethyl-3-oxazolidinyloxyl, was also observed by ESR- and fluorescence-spectroscopy.

Electron Spin Resonance Spectroscopy↗

Follow-up study of gastrin response after resection of the jejunum and the ileum.

An experimental study was conducted on the effect of resection of the jejunum and ileum on gastrin release. The intravenous infusion of L. arginine in a dose of 0.5 g per kg body weight for 30 minutes proved to be most practical in evaluating gastrin release in addition to insulin and glucagon release. Serum gastrin levels in response to this dose of arginine were determined before and three weeks, three months and one year after resection of the jejunum and of the ileum. At three weeks, a significant increase in gastrin levels occurred in bothe the fasting state and after stimulation in dogs with either jejunum or ileum resection. At three months, the elevated gastrin response persisted only in those with jejunum resection. By one year, the gastrin levels had fallen in almost all dogs to approximately the preoperative levels.

Animals↗

Urine plasmin-like substances as an index of kidney allograft rejections.

Using solid state radioimmunoassays developed by the first author, changes in the urine level of plasmin-like substances (PLS) and fibrin degradation products (FDP) before and after human kidney transplantation were determined in 49 transplant patients. Averages of urine PLS and FDP in a normal population of 51 persons were 0.13+/-0.10 (SD) and 0.14+/-0.07 microng/ml, respectively. In all transplant patients there was an initial rise of both PLS and FDP in urine immediately after transplantation. This elevation peaked on days 4 and 5 and the PLS and FDP levels returned to normal range within 2 weeks in patients without evidence of rejeciton. A secondary rise of urine PLS was detected before or with a rise in serum creatinine in all of the patients experiencing rejections. Of 11 patients who showed a rejection episode within 2 weeks of transplantation, the secondary rise of urine PLS was detectable in 55% of the patients slightly before the serum creatinine level changes; of 6 patients with a rejection episode more than 2 weeks after transplantation, 100% showed a secondary PLS rise 6.7+/-2.3 (SE) days before the serum creatinine increased. The appearance of the secondary rise of urine FDP in the rejecting recipients was slightly later than the rise of PLS. Serial determination of urine PLS levels following human kidney transplantation appears to be an early index of rejections which occurs more than 2 weeks after transplantation, although the clinical usefulness of this measurement is probably limited.

Creatinine↗

Modification of lipoxygenase by hydrogen peroxide and photooxidation.

The kinetic study of fluorescence stopped-flow method suggested that the interaction between lipoxygenase and H2O2 is consistent with a simple irreversible one-step mechanism. The activation energy of the reaction was 7.2 kcal/mol. Participation of an ionizable group with pK about 8.8, possibly a histidine residue, was suggested from the pH-dependence of the rate constant. No further fluorescence quenching of lipoxygenase was observed when the product was added to the lipoxygenase solution before mixing the lipoxygenase and H2O2 solutions. The fluorescence quenching of lipoxygenase by H2O2 was in parallel with the inactivation of the enzyme. Hydroperoxylinoleic acid strongly protects the inactivation of lipoxygenase caused by H2O2. These results are consistent with an interpretation that OH- and/or O- - are produced when the iron of the enzyme is oxidized by H2O2, which in turn will attack some amino acid essential for the enzyme activity. The pH-dependence of the inactivation rate constant of photooxidation of lipoxygenase sensitized by methylene blue indicated that an ionizable group with pK about 8.8 is concerned with the enzymatic activity. In contrast to the inactivation of lipoxygenase by H2O2, the product protected the inactivation of the enzyme by photooxidation only at high concentration.

Fluorescence↗