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Biomedical subjects

T Kamano

Publications and source records attributed to T Kamano.

At least 91 records · Page 5Linked to original sources

Different response of hepatic energy change and adenine nucleotide concentrations to hemorrhagic shock.

The adenine nucleotide and mitochondrial metabolisms of the liver were studied in hemorrhagic shock of rats. In reversible shock, the energy charge (ATP+1/2ADP/ATP+ADP+AMP) levels fell more rapidly than the total adenine nucleotide concentrations and decreased to 64% of controls 2 hours after shock. However, the oxidative phosphorylation of isolated mitochondira was only slightly inhibited. The energy charge levels were restored to normal values immediately when the shed blood was reinfused, while the concentrations of adenine nucleotides increased gradually and reached normal at 2 hours later. In irreversible shock which took up 70% or more of the withdrawn blood to maintain pressure of 40mm. Hg, the energy charge, adenine nucleotide concentrations and mitochondrial oxidative phosphorylation decreased considerably and were not restored by the reinfusion of the remainder of shed blood. It is suggested that the energy charge can respond rapidly to changes in an available oxygen and the adenine nucleotide concentrations and that an impairment of mitochondrial oxidative phosphorylation plays an important role in leading to irreversible hemorrhagic shock.

Adenine Nucleotides↗

Early ductal lesions of pancreatic carcinogenesis in animals and humans.

Two cases of human early pancreatic duct adenocarcinoma were presented, and ductal lesions observed histologically were compared to those induced in hamsters using a rapid-production model of pancreatic carcinoma. In human cases, direct histologic evidence was obtained to suggest that cancerous changes arose from duct epithelial cell hyperplasia, because lesions of hyperplasia and carcinoma coexisted in continuity. In hamster serial-killing studies, it was suggested that carcinoma developed through atypical ductal hyperplasia.

Adenocarcinoma↗

Intratumoural thymidylate synthase and dihydropyrimidine dehydrogenase activities are good predictors of 5-fluorouracil sensitivity in colorectal cancer.

To identify factors that influence the clinical response to 5-fluorouracil (5-FU), we studied the correlation between in vitro sensitivity to 5-FU and the expression of seven biological markers. The markers, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), pyrimidine nucleoside phosphorylase, p53 (wild/mutant), p21, cyclo-oxygenase-2, and inducible nitric oxide synthase were measured in tumour tissues from 32 colorectal cancer patients. The activities of TS and DPD were significantly lower in the tumours sensitive to 5-FU compared with those that were not sensitive to 5-FU. In tumours with TS < 3.7 pmol/min per mg protein and DPD < 98 pmol/min per mg protein, the percentage of cases sensitive to 5-FU (67%) and the mean percentage inhibition of tumour cells by 5-FU (42.8%) were significantly higher than in the other tumours (0% and 13.1%, respectively). The other biological markers did not correlate with in vitro sensitivity to 5-FU. Tumour sensitivity to 5-FU can be more precisely predicted by taking the activities of both TS and DPD into consideration than by using either alone.

Antimetabolites, Antineoplastic↗

Feasibility of measuring 5-fluorouracil catabolic potential by oral loading.

The efficacy of 5-fluorouracil (5-FU) treatment and the incidence of adverse events differ among patients and depend to some extent on individual variations in drug catabolism. This feasibility study aimed to determine the optimum conditions for a 5-FU oral load test, which would allow the simple evaluation of individual differences in 5-FU catabolism. Patients with colon cancer were given oral 5-FU (200 mg/day) for 3 days (n = 36) or a single 100 mg dose (n = 14). Serum concentrations of uracil, dihydrouracil, 5-FU and 5-fluoro-5,6-dihydrouracil were measured before and after 5-FU administration. The results suggested that a decline in 5-FU metabolism was associated with continuous administration and increasing age. We conclude that a continuous load of 5-FU is necessary in order to predict the efficacy and side-effects of the drug. The 3-day regimen, with its ease of administration, merits further study to assess its possible clinical application.

Administration, Oral↗

Abdominal wound dehiscence in patients receiving long-term steroid treatment.

Steroids inhibit primary wound healing and delay the formation of granulation tissue, but it has been controversial whether long-term steroid treatment by itself increases the risk of abdominal wound dehiscence. The aim of this study was to determine whether the pre-operative dose and post-operative total dose of steroids influence abdominal wound dehiscence. Of 28 patients who had surgery while receiving long-term steroid treatment, seven had abdominal wound dehiscence and 21 did not have dehiscence. The two groups differed significantly in the post-operative dose of steroids (404.3 +/- 147.1 and 135.6 +/- 118.7 mg, respectively) and the duration of wound healing (57.3 +/- 18.0 and 12.4 +/- 3.8 days), but no other differences were found. Abdominal wound dehiscence may be influenced by the post-operative rather than the pre-operative steroid dose.

Adolescent↗

Methylenetetrahydrofolate reductase C677T is not associated with expression of pyrimidine metabolic enzyme genes in colorectal cancer.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may influence the chemosensitivity of colorectal cancers to fluorouracil (5-FU) by increasing intracellular 5,10-methylenetetrahydrofolate. The effect of this polymorphism on the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase (TP) in colorectal cancer was investigated. The MTHFR C677T polymorphism was analysed and TS, DPD, OPRT and TP mRNA expression was measured in tumour and adjacent normal mucosal tissue. In all patients, the genotypes of the tumour and normal tissues were identical. No differences were found in the expression of TS, DPD or TP mRNA by genotype in either tumour or normal tissue. Although the OPRT mRNA level in tumour tissue was not associated with the genotype, normal mucosa with the TT genotype showed a significantly higher OPRT mRNA level than mucosa with other genotypes. The MTHFR C667T polymorphism is not associated with intratumoural expression of TS, DPD, OPRT or TP.

Aged↗

Greater development of 1,2-dimethylhydrazine-induced colon cancer in a rat model of type 2 diabetes mellitus.

Several clinical cohort and case-control studies have suggested a link between diabetes and colon cancer. Otsuka Long-Evans Tokushima Fat (OLETF) rats spontaneously develop type 2 diabetes mellitus and Long-Evans Tokushima Otsuka (LETO) rats are non-diabetic. The relationship between type 2 diabetes mellitus and colon cancer was examined in these rats. The carcinogen 1,2-dimethylhydrazine was administered subcutaneously once weekly for 10 weeks, and the animals were killed and necropsied in week 29. All OLETF rats and 80% of the LETO rats developed cancer. The number of colon cancers per rat was significantly greater in the diabetic than in the non-diabetic rats. Although the tumours tended to be larger in diabetic rats, the difference was not statistically significant. No significant differences were observed in the depth of invasion or histological type of cancer in the two groups. Type 2 diabetes mellitus may enhance the generation and growth of colon cancer.

1,2-Dimethylhydrazine↗

Genomic copy-number aberrations related to lymph-node metastasis of colon cancer.

Lymph-node metastasis is an important indicator in the diagnosis of colon cancer. In order to determine the genes involved in metastasis, genomic copy-number aberrations in the primary tumours and lymph-node metastases were analysed in 12 patients using comparative genomic hybridization. This method detects genomic copy-number changes at the chromosomal level and the identification of the regions of aberration on any chromosome. Copy-number gains at 6p12 and losses at 8p12 were observed in a greater number of the primary tumours than in the metastases. These aberrations appear to be involved in lymph-node metastasis of colon cancer, and may allow measurement of the risk of lymph-node metastasis from a given colon cancer.

Adenocarcinoma↗

Analysis of the relationship between sex and chromosomal aberrations in colorectal cancer by comparative genomic hybridization.

Colorectal cancer is thought to be more common in men than in women. The chromosomal locations of DNA gains and losses in surgical specimens of colorectal tumours were detected by comparative genomic hybridization and were compared by gender. Five chromosomal regions, 7p, 8p, 8q, Xp and Xq, contained multiple gains that were significantly more common in males than in females, and within these regions, the differences were significant for Xp21, Xp11.3, Xp11.4 and Xq26. Regions 1p, 3q, 11q, 12p, 12q and 15q contained multiple sites of gain that were significantly more common in females than in males. Tumours from male and female patients showed significantly more losses at 11p and 15q, and at 4q and Xq, respectively. The fact that gains in X-chromosomal regions were detected with a significantly higher frequency in tumours from male patients suggests that the difference between the genders might be explained by X-chromosomal inactivation.

Adenocarcinoma↗

ELISA determination of serum hyocholic acid concentrations in humans and their possible clinical significance.

BACKGROUND/AIMS: Hyocholic acid (HCA), a bile acid isolated from pigs, has a different structure from the predominant bile acids from humans. METHODOLOGY: We prepared an antiserum to HCA in rabbits and developed an enzyme-linked immunosorbent assay (ELISA), which we used to measure serum HCA in healthy subjects and patients with a variety of gastrointestinal and non-gastrointestinal diseases. RESULTS: Patients with hepatic cirrhosis had a mean HCA concentration that was 120-fold greater than that in healthy subjects. Markedly elevated HCA levels were also present in patients with primary hepatoma or pancreatic cancer but not in patients with cancer of the breast, bile duct, duodenum, or stomach. CONCLUSIONS: If these results are confirmed by further study, HCA measurement may prove clinically useful.

Adult↗