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Biomedical subjects

M Kokubun

Publications and source records attributed to M Kokubun.

71 records · Page 4Linked to original sources
PubMed1987

[Antitumor efficacy of polyamine antimetabolites and mitomycin C under polyamine-free diet].

Treatment of nude mice xenografted with human gastric cancer was carried out by polyamine antimetabolites combined with mitomycin C (MMC) and polyamine-free diet. Polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and ethylglyoxal-bis-guanylhydrazone (EGBG), were given ip in a daily dose of 1,000 mg/kg and 20 mg/kg, respectively, for 6 consecutive days. MMC 2.0 mg/kg was administered every other day. The polyamine-free diet was given from 4 days before start of the treatment through the end of the study. Although the tumor growth rate of the control group given polyamine-free diet was similar to that given normal diet, in the mice treated with EGBG, DFMO plus MMC, the antitumor effect in the polyamine-free diet group was superior to the normal diet group. In comparison with tumor growth suppression due to EGBG plus DFMO or MMC only, the polyamine-free diet group showed better result than the normal diet group to some extent. In mice treated with EGBG, DFMO plus MMC, tumor tissue spermine levels in the polyamine-free diet group were significantly depressed, compared to the normal diet group. Furthermore, marked suppression of DNA biosynthesis was observed in mice given EGBG, DFMO plus MMC together with the polyamine-free diet. These results suggest that combined treatments of polyamine antimetabolites and MMC revealed a marked enhancement of antitumor effects, under conditions of polyamine depletion, which may be responsible for the alteration in DNA structure.

Animals↗
PubMed1986

[Combined efficacy of polyamine antimetabolites and cis-diamminedichloroplatinum].

The combined antitumor effects of the polyamine antimetabolites, alpha-difluoro methylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), with CDDP were studied using human gastric cancer cells xenotransplanted into nude mice. DFMO (1000 mg/kg in two divided doses) and MGBG (50 mg/kg) were given IP for six consecutive days from the time when the xenotransplanted tumor weighted about 100 mg, and CDDP (3.0 mg/kg) was given IP every other day from the same time. Animals treated with DFMO plus MGBG with or without CDDP as well as with CDDP only displayed suppressed tumor growth, compared to untreated mice. In mice treated with these three drugs, however, tumor growth was rather rapid compared to those treated with CDDP only, although tumoral CDDP levels in animals given DFMO, MGBG and CDDP were higher than those given CDDP only. When DFMO, MGBG and CDDP or DFMO and MGBG were administered, tumoral spermidine and spermine levels decreased markedly. On the other hand, tumor DNA biosynthesis in the CDDP only group dropped markedly 24 hours after the termination of therapy. These results suggest that an alteration in the DNA structure caused by polyamine deficiency may prevent cross-link formation in DNA by CDDP.

Animals↗
PubMed1982

Hemoglobin Ai levels in hyperthyroidism.

Hemoglobin AI (HbAI) was studied in 21 cases of hyperthyroidism (H) and 33 control subjects (C). The correlation equations between fasting blood glucose (FBG, mg/dl, x) and HbAI (%, y) in the H and C groups were: y=0.07x+1.26 (r=0.5, p less than 0.05) and y=0.048x+2.23 (r=0.94, p less than p.001), respectively. Five cases in the H group showed a higher level of HbAI far outside the confidence of 5% level of significance calculated from correlation equation for the C group. The correlation equation for the sum of blood glucose (sigma BG, mg/dl, x) during GTT and HbAI (%, y) in the H group was y=0.003x+5.3 (r=0.64, p less than 0.01); in the C group y=0.005x+3.1 (r=0.88, p less than 0.001). sigma BG and HbAI showed a close correlation in both groups. According to the results of the GTT, the subjects, either C or H group, were divided into three sub-groups: normal (n), borderline (b) and diabetic (d). The correlation equation between triiodothyronine (T3, ng/dl, x) and HbAI (%, y) in the H group was calculated as y=0.003x+6.49 (r=0.58, p less than 0.05). T3 in the n subgroup was 331 +/- 90 ng/dl, in the b subgroup 362+/-166 ng/dl and in the d subgroup 621+/-227 ng/dl, and there was a statistical difference between the b and d groups.

Adult↗
PubMed1982

Carbohydrate metabolism in thyrotoxicosis, with special reference to its relation to calorie intake.

The effects of two kinds of calorie intake, 30 kcal and 60 kcal per kg of ideal body weight with the same amount of protein, on glucose tolerance and the metabolism of thyrotoxicosis was studied. A diet of 30 kcal per kg of ideal body weight was not sufficient for the thyrotoxicosis, and all the patients lost body weight. On a diet of 60 kcal per kg of ideal body weight, weight reduction was minimal and the urinary nitrogen and blood lactate levels increased. Insulin secretion also increased on a 60 kcal diet, but there was no deterioration of glucose tolerance even in cases of thyrotoxicosis showing mild glucose intolerance. These results suggest that sufficient calories for the thyrotoxicosis are at least 60 kcal per kg of ideal body weight, irrespectively of mild glucose intolerance.

Adult↗
PubMed1980

Urinary excretion of O-hydroxylysylglycosides in diabetes mellitus.

In order to study the metabolism of collagenous proteins in diabetes mellitus, urinary excretion of O-hydroxylysylglycosides, a characteristic component of collagenous protein, was determined in diabetics and controls. There was no significant correlation between urinary excretion rate of O-hydroxylysylglycosides and age (r = -0.40 for diabetics and r = -0.15 for control). In 16 age-matched pairs, urinary excretion of O-hydroxylysylglycosides was less in diabetics than in control (0.78 +/- 0.18 (mean +/- S.D.) mu moles/m2 body surface x hr versus 0.92 +/- 0.18 mu moles/m2 body surface x hr, p less than 0.05). This results suggests that catabolism of collagenous protein decreases in diabetics.

Adolescent↗
PubMed1980

Gluconeogenesis from glycerol and alanine in thyrotoxicosis.

Gluconeogenesis in thyrotoxicosis was studied by oral glycerol-loading test and alanine-loading test performed on 5 normal subjects and 5 cases of thyrotoxicosis. The blood glucose levels in thyrotoxicosis rose after the administration of glycerol deposit elevation of the plasma levels of insulin. After the administration of alanine, the levels of IRI, pyruvate and lactate elevated in thyrotoxicosis. In normal subjects, the plasma levels of glucose, IRI, pyruvate, or lactate did not change significantly after glycerol or alanine load.

Administration, Oral↗
PubMed1979

Effect of tolbutamide on plasma catecholamine in insulin dependent diabetics.

In 4 cases of insulin dependent diabetics, blood levels of glucose, C-peptide reactivity (CPR), free fatty acid, and catecholamines were followed after the intravenous tolbutamide response test. Plasma CPR was low and did not respond to tolbutamide injection, and blood levels of glucose and free fatty acid did not change during the test. Fifteen min after the tolbutamide injection, plasma epinephrine plus norepinephrine and norepinephrine levels fell to 87.5% and 67.4% of the initial values, respectively. These results suggest that decrease in the blood glucose and free fatty acid levels usually observed after tolbutamide injection is not the direct action of drug, but is secondary to insulin secretion, and tolbutamide-induced decrease in catecholamines may contribute to the secretion of insulin from the pancreatic beta-cells.

Catecholamines↗
PubMed1977

Determination of hydroxylysine in urine.

A new method for colorimetric determination of urinary hydroxylysine is described. Approximately one-hundredth of human urine collected for 24 hr was diluted to 25 ml and titrated to pH 2.0 with 2 hcl, and then subjected to column chromatography on Dowex 50 X 4 (H+ form). Amino acids were eluted from the column with 1.5 N NH4OH. Hydroxylysine in the elute with 1.5 N NH4OH was separated from the other amino acids, especially from serine and threonine, by preparative paper chromatography. The paper corresponding to hydroxylysine was cut and eluted with water. An aliquot of the eluate with water was oxidized by sodium metaperiodate, and formaldehyde liberated from hydroxylysine was assayed by chromotropic acid reagents, after removing periodate and iodate with Dowex 1 X 8 (formate form). Excretion rate of hydroxylysine in urine of adults was shown to be approximately 110 mumoles per day.

Chromatography↗
PubMed1976

Determination of O-hydroxylysyl-glycosides (OHLG) in urine.

A new method for determination of urinary O-hydroxylysyl-glycosides (OHLG) is described. Human urine was extracted with 2 volumes of ethanol, followed by gel-filtration on a column of Sephadex G-10. The presence of OHLG in the alkaline hydrolyzate of the fraction obtained by gel-filtration was proved by paper chromatography and by liquid chromatography. The alkaline hydrolyzate was subjected to Dowex 50 X4 (H+ form) column chromatography, and OHLG were eluted with 1.5N NH4OH. Content of OHLG in the eluate was determined by the anthrone-H2SO4 method in terms of hexose. Excretion rate of OHLG in urine of adults was shown to be 20 mumoles in terms of hexose per day.

Adult↗
PubMedDate not supplied

Augmented antitumour effects of combined treatment with hyperthermia and tumour necrosis factor on human gastric cancer xenotransplanted into nude mice.

Hyperthermia combined with recombinant human tumour necrosis factor (rH-TNF) was evaluated for antitumour efficacy in vivo. Use was made of human gastric cancer tissues xenografted into nude mice. When 100, 300, 600, and 1200 units of rH-TNF (2.4 x 10(6) units/mg protein) were given twice intraperitoneally, tumour regression did not occur in any animal. In contrast, a remarkable suppression of tumour growth was observed when 600 and 1200 units of rH-TNF was given in combination with hyperthermia at 43.5 +/- 0.1 degrees C. No effects were evident with the regimen of 100 and 300 units of rH-TNF plus hyperthermia at the same temperature, as compared with evidence obtained with hyperthermia alone. The tumoral blood flow, determined by the hydrogen diffusion method, decreased immediately after hyperthermia alone or hyperthermia plus 1200 units of rH-TNF, whereas a slight decrease was seen after rH-TNF alone. When hyperthermia plus 1200 units of rH-TNF were given, there was a remarkable delay in reversion to pretreatment values of tumoral blood flow, as compared to findings with rH-TNF only or heat only. These results are discussed in relation to the antitumour and side-effects of rH-TNF.

Animals↗
PubMedDate not supplied

Prevention of scald injury on the peritoneo-serosal surface in advanced gastric cancer patients treated with intraperitoneal hyperthermic perfusion.

In attempts to avoid the side-effects derived from a scald on the peritoneo-serosal surface during intraperitoneal hyperthermic perfusion (IPHP) for advanced gastric cancer, a randomized study using cimetidine, a histamine H2-receptor antagonist, was carried out on 18 patients with advanced gastric cancer. Cimetidine, 50 mg/kg, was administered intravenously and immediately before IPHP. The background characteristics of the patients and the types of surgical treatment used were almost the same between each group of patients, whether or not cimetidine was given. The perfusion time in the cimetidine and control groups was 123 +/- 9 and 117 +/- 9 min, respectively. The inflow and outflow temperatures of the perfusate were 46.3 +/- 0.4 and 44.2 +/- 0.1 degrees C in the cimetidine group, respectively, whereas in the control group the temperatures were 46.0 +/- 0.3 and 44.1 +/- 0.2 degrees C, respectively. In the nine patients who were given cimetidine, the histamine concentrations in the peripheral blood increased significantly, compared to those in the nine controls; this resulted from the release of histamine into the circulating blood. Higher concentrations of protein were observed in the post-hyperthermic intraperitoneal exudate of the control group for 3-24 h after IPHP and, consequently, post-hyperthermic hypoproteinaemia was remarkable in the control group. These data suggest that when pre-IPHP cimetidine was prescribed for patients with gastric cancer treated with IPHP, the peritoneo-serosal surface was protected from scald injury and the side-effects of IPHP were reduced.

Blood Proteins↗