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Biomedical subjects

T Kosaka

Publications and source records attributed to T Kosaka.

At least 217 records · Page 12Linked to original sources
PubMed1990

One of the endothelin gene family, endothelin 3 gene, is expressed in the placenta.

A cDNA encoding human endothelin 3 (ET-3) precursor was cloned from a cDNA library from the placenta, and its nucleotide and deduced amino acid sequences were determined. This ET-3 cDNA was found to contain 2.3 kb pairs and encode prepro-ET-3 protein consisting of 224 amino acid residues. The putative big-ET-3 seems to consist of 42 amino acid residues. Two of the intron insertion sites were determined with information from nucleotide sequences of the cloned genomic ET-3 gene. This is the first direct evidence that the ET-3 gene is transcribed and expressed in the placenta.

Amino Acid Sequence↗
PubMed1990

Retrospective analysis of the prognostic significance of DNA ploidy patterns and S-phase fraction in gastric carcinoma.

Paraffin-embedded tumor samples from 493 gastric carcinoma patients were analyzed by DNA flow cytometry. The results were correlated with clinicopathological findings and S-phase fractions measured by in vivo bromodeoxyuridine (BrdUrd) labeling. Of the 493 patients, 183 (37%), 225 (46%), and 85 (17%) showed diploidy, single DNA-aneuploidy, and DNA-multiploidy patterns, respectively. When the DNA histogram and all the clinicopathological parameters were entered simultaneously into the Cox regression model, DNA ploidy, liver metastasis, peritoneal dissemination, and nodal status emerged as independent prognostic parameters. The relative risk of death was twofold higher in single DNA-aneuploid and threefold higher in DNA-multiploid tumors than in DNA-diploid tumors. BrdUrd labeling indices (LIs) also proved to be an independent prognostic factor. Multiploid tumors showed the highest median BrdUrd LI associated with the most frequent peritoneal dissemination and liver metastasis. The simultaneous evaluation of DNA ploidy patterns and BrdUrd LIs gave more prognostic information than the determination of tumor DNA ploidy only. Namely, DNA diploid, together with low BrdUrd LIs, was associated with favorable prognosis, whereas DNA aneuploid with high BrdUrd LIs was related to the poorest prognosis. These results indicate that DNA ploidy and BrdUrd labeling indices may be possibly useful prognostic factors for gastric carcinoma.

Aneuploidy↗
PubMed1990

Relation of proliferative activity to survival in patients with gastric carcinoma.

The prognostic significance of proliferative activity in 167 gastric carcinomas was studied by means of an in vitro labeling method with bromodeoxyuridine (BrdU), using specimens obtained by endoscopic biopsy, and the results were correlated with conventional prognostic factors. The BrdU labeling indicates (BrdU LI) varied from 2.1 to 45%. When the in vitro BrdU LI were plotted against in vivo BrdU LI, a significant correlation was found between in vitro and in vivo BrdU LI (P less than .01). These results show that the in vitro BrdU LI of specimens obtained by endoscopic biopsy indicate accurate proliferative activities of gastric cancers. The BrdU LI were closely correlated with nodal status, vessel invasion, and tumor size. With regard to the correlation of BrdU LI and prognosis, patients whose tumors had a high BrdU LI (BrdU greater than LI less than 10%). When the BrdU LI and all the pathologic findings were entered simultaneously into the regression model, nodal status, tumor size, serosal involvement, and BrdU LI emerged as independent prognostic parameters. The present studies demonstrated the usefulness of the in vitro BrdU-labeling method to estimate the malignancy of gastric cancer preoperatively, and this method may be useful in designing the operative procedure and multimodal therapy for individual patients.

Antibodies, Monoclonal↗
PubMed1990

Monoclonal antibody HNK-1 selectively stains a subpopulation of GABAergic neurons containing the calcium-binding protein parvalbumin in the rat cerebral cortex.

Monoclonal antibody HNK-1 is shown to outline selectively a subpopulation of GABAergic neurons containing a specific calcium-binding protein parvalbumin (PV) in the adult rat parietal cortex, using pre- and postembedding immunocytochemistry at light microscopic level. About 98% of HNK-1 stained cells in the rat parietal cortex were PV immunoreactive. About 95% of HNK-1 immunoreactive cells were also shown to be stained with a lectin, Vicia villosa agglutinin (VVA), with a specific affinity for terminal N-acetylgalactosamine, which has been previously shown to stain selectively a subpopulation of PV-containing GABAergic neurons in this region. Furthermore almost all HNK-1 immunoreactive cells were also stained with a monoclonal antibody, 3B3, which is specific for chondroitin sulfate proteoglycan. 3B3 was shown in the present study to stain selectively a subpopulation of PV-immunoreactive neurons in the adult rat parietal cortex. In addition, a direct comparison of two monoclonal antibodies HNK-1 and VC1.1 revealed that these two were identical in their staining properties and that they defined the same subset of PV-containing GABAergic neurons in the rat parietal cortex.

Animals↗
PubMed1990

Two-year oral chronic toxicity and carcinogenicity study in rats of diets fumigated with methyl bromide.

A chronic toxicity and carcinogenicity study was conducted by feeding diets containing 80, 200 or 500 ppm total bromine following fumigation with methyl bromide, a diet containing 500 ppm potassium bromide, or a basal diet alone to groups of 60 male and 60 female Fischer (F344) rats for up to 2 yr. Ten males and ten females from each group were killed after wk 52 and 104 for urinalysis, haematology, blood biochemistry and pathology. Rats that were killed in extremis or found dead during the study and all rats that survived to the end of the study were also subjected to pathological examinations. In rats fed the diets fumigated with methyl bromide there were no marked toxic changes, except for a slight depression of body-weight gain from wk 60 onwards in males of the 500-ppm group, and tumour incidence was unaffected. Rats given a diet containing potassium bromide did not show any treatment-related changes. It was concluded that residues of up to 500 ppm total bromine in diets fumigated with methyl bromide are not carcinogenic in F344 rats of either sex and that the maximum no-effect level is 200 ppm (6.77 mg total bromine/kg body weight/day) in males. The maximum no-effect level could not be determined in females.

Animals↗
PubMed1990

The "recall effect" in radiotherapy: is subeffective, reparable damage involved?

It has been proposed that lethal mutations among the progeny of a surviving cell could be the basis for the recall effect when chemotherapy is applied subsequent to the repair of normal-tissue injury resulting from a course of radiation therapy. Because radiotherapy is usually multifractionated, the possibility exists that repair of heritable injury of this type could occur between fractions as is the case for sublethal damage. To examine this possibility, the endpoint small-colony formation was used--an endpoint which integrates the effects of a number of radiation-induced aberrancies including lethal mutations--and low-dose-rate irradiation. It was found that, even after net surviving fractions comparable to those sought in radiotherapy were reached, little damage remained expressible as a deficiency in the size of the colony generated from a surviving cell. We conclude that the damage expressible as a lethal mutation is reparable and therefore the recall effect must be attributed to some other cellular mechanism.

Animals↗
PubMed1990

Detection of the growth fraction in colorectal tumours by a monoclonal antibody against DNA polymerase alpha.

The cell kinetics of 54 colorectal tumours were examined by immunohistochemical methods, using the monoclonal antibody DNA polymerase alpha which reacts with an antigen found only in proliferating cells. The rate of DNA polymerase alpha positive cells in colorectal cancer was 44.8%, a figure that was significantly higher than the 21.9% found in colorectal adenomas. The rate of DNA polymerase alpha positive cells tended to rise as the degree of differentiation decreased according to the standard histological grading criteria for colorectal cancer. Positive cells were detected in much greater numbers in tumours with liver metastasis (55.4%) than in those without metastasis (41.7%). The rate of DNA polymerase alpha positive cells for aneuploid lesions was higher than that for lesions with a diploid pattern. The determination of growth fractions with a monoclonal antibody (DNA polymerase alpha) may be a biological marker of great prognostic significance.

Adenocarcinoma↗
PubMed1990

Correlation between non-repairable DNA lesions and fixation of cell damage by hypertonic solutions in Chinese hamster cells.

In Chinese hamster HA-1 cells, killing induced by gamma-rays was enhanced by post-irradiation treatment with hypertonic solution (0.5 mol/l NaCl in phosphate buffered saline, pH 7.2) for 20 min. The initial DNA double-strand breaks (dsb) induced by gamma-rays were repaired during post-irradiation treatment with hypertonic solution. However, hypertonic treatment following gamma-irradiation enhanced the frequency of non-repairable dsb, as compared with the frequency after incubation at 37 degrees C following gamma-irradiation. Hypertonic treatment did not affect the initial half-time for rejoining of dsb. Hypertonic treatment did not enhance cell killing, nor did it enhance the non-repairable dsb when the irradiated cells were incubated at 37 degrees C for 2 h. These results suggest that fixation of gamma-ray-induced potentially lethal damage by hypertonic treatment results from inhibition of the rejoining of dsb.

Animals↗
PubMed1990

Time-lapse microscopy and DNA double-strand breakage of Chinese hamster cells under conditions promoting or preventing PLD repair after irradiation with 60Co gamma rays.

We have confirmed previous time-lapse microscopic observations (Suzuki 1985) using Chinese hamster hai and V79 cells. The proportion of non-dividing to dividing cells was the same under conditions of potentially lethal damage (PLD) repair and non-PLD repair after irradiation with 60Co gamma-rays. This finding suggested that the radiation-induced damage to cellular DNA was similarly repaired so that cells undergo a first division to the same extent under both sets of conditions. In fact, direct measurement of double-strand breaks (dsb) in DNA from the two cell lines by the neutral elution technique showed no differences either in the initial amount of damage or in the time-course under conditions promoting or preventing PLD repair. These results indicate that PLD repair (i.e. an increase in cell survival) cannot be simply explained by a difference in the repair of dsb, but it can perhaps be explained by assuming that DNA damage is repaired with either fewer or more errors in the presence or absence of PLD repair respectively.

Animals↗
PubMed1990

Correlation of DNA ploidy and clinical outcome in early gastric carcinomas.

The nuclear DNA content was measured in 120 early gastric carcinomas and the results correlated with histologic findings and S-phase fractions measured by in vivo bromodeoxyuridine (BrdU) labeling. Forty-six cases (38%) were diploid and 74 cases were aneuploid. In aneuploid tumors, incidence of submucosal invasion, vascular invasion, and lymph node involvement were significantly higher than that in diploid tumors. In addition, the S-phase fractions in aneuploid tumors were significantly higher than those in diploid tumors. There was no recurrence in diploid tumors; whereas 21% of cases with aneuploid tumors recurred. These results indicate that DNA content may be a prognostic factor in early gastric carcinoma.

Adult↗
PubMed1990

Flow-cytometric analysis of colorectal cancer with hepatic metastases and its relationship to metastatic characteristics and prognosis.

Studying the DNA ploidy patterns of 52 primary tumors, diploid tumors accounted for 48.1% and aneuploid tumors for 51.9%. Out of 31 patients with liver metastases, 35.5% had diploid tumors and 64.5%, aneuploid tumors. Heterogeneity (difference in DNA ploidy pattern between the primary lesion and liver metastases) was found in 20% of the patients examined. In 28 of the patients, the liver metastases were unresectable, and their prognoses were such that the 1- and 2-year survival rates from the diploid tumors were 42.9 and 14.3%, respectively, while 1-year survivors from aneuploid tumors died within 2 years. In resected cases of hepatic metastases, the DNA ploidy pattern of the metastatic lesions did not correlate with the metastasis period, extent of spread or number of lesions. The recurrence rate of aneuploid tumors in the residual livers was 50%, which was slightly higher than the rate of 36.4% for diploid tumors. The prognoses in patients with diploid tumors were significantly better than those in patients with aneuploid tumors: 5-year survival was 71.1% in diploid tumor patients, compared with 21% in aneuploid tumor patients.

Colorectal Neoplasms↗
PubMed1990

Effect of radical scavengers on canine peripheral blood mononuclear lymphocyte-mediated cytotoxicity and production of active oxygen.

Production of active oxygen by canine peripheral blood mononuclear lymphocytes (PBLs) from beagle dog was examined by luminol-dependent chemiluminescence production. The canine PBLs rapidly produced the active oxygen in parallel with the number of cells when PBLs were cocultured with canine leukemia-derived CL-1 cells as target cells. Cytolysis of the target cells and active oxygen production were inhibited linearly by the addition of benzoic acid and n-propyl gallate as hydroxyl radical scavenger. However, superoxide dismutase and tiron which are scavengers of superoxide anion did not inhibit the cytotoxicity so much at low concentrations that inhibited the induction of luminol-dependent chemiluminescence. These results suggest that hydroxyl radical production by stimulated PBLs might be playing a major role of cytotoxic action in the case of canine system.

Animals↗
PubMed1990

[A flow cytometric cell cycle analysis of familial polyposis coli].

The cell cycle of Familial Polyposis Coli (FPC) has been determined by a flow cytometric (FCM) DNA/bromodeoxyuridine (BrdUrd) bivariate analysis. Specimens were obtained from one FPC cancer patient and, for our controls, from 8 single colon cancer patients and from 8 gastric cancer patients who underwent a colectomy. Procedurally, 1 g i.v. injection of BrdUrd was administered 5 to 7 hours before the resection. Later, the BrdUrd-labeling index (BULI) and the potential doubling time (Tpot) were measured by FCM. No significant differences were uncovered between the BULI of the cancer in the FPC patient and that of our controls, or between the BULI of the unaffected mucosa of the FPC patient and that of the controls. Further, with regard to the FPC patient, the mean BULI of the cancer was significantly higher than that of the adenoma and than that of the unaffected mucosa. Also, the mean Tpot of the cancer was significantly shorter than that of the unaffected mucosa. These results suggest that the BULI and the Tpot may change when an adenoma is generated from the unaffected mucosa in FPC patients.

Adenoma↗
PubMed1990

[Flow cytometric analysis in colorectal cancer with hepatic metastases and its relationship to metastatic characteristics and prognosis].

Nuclear DNA ploidy studies were performed by flow cytometry on extracted nuclei from 65 heptic metastases from colorectal cancer. In 25 patients, both primary and metastatic lesions were available for analysis. Primary carcinomas were DNA diploid pattern in 48.1%, DNA aneuploid in 51.9%. Of 31 hepatic metastases, 11 (35.5%) metastases showed a DNA diploid pattern, and 25 (64.5%) showed a DNA aneuploid pattern. Ploidy pattern was constant between primary and metastases in 80% of tumors. No significant relationship between metastatic characteristics and DNA ploidy pattern was found. The DNA aneuploid cancers had a relatively poorer prognosis in patients with unresectable hepatic metastasis. In resected hepatic metastases from colorectal cancer, rate of hepatic recurrence with DNA diploid pattern was lower than that with DNA aneuploid pattern. Survival of patients with DNA diploid metastases (71% alive at 5 years) was significantly better than that of patients with DNA aneuploid metastases (21% alive at 5 years) (p less than 0.05). These results demonstrated that flow cytometric DNA ploidy measurements may have prognostic value for patients with hepatic metastases from colorectal cancer.

Aneuploidy↗
PubMed1990

[Malignancy in gastric cancer, with special reference to the distribution of BrdU-labelled cells].

Analysis of the distribution of BrdU-labelled cells was performed on 50 gastric cancers and the results correlated with histologic findings and DNA ploidy patterns. Patients were administered a intravenous infusion of 1g BrdU 1 hour before laparotomy. The resected specimen was fixed in 70% ethanol, embedded in paraffin, and cut into thin sections. The sections were stained by ABC method. The BrdU labelling index (LI) was calculated by counting 1000 tumor cells in superficial, internal and deep layers, respectively. DNA ploidy was analyzed using flow cytometry. The mean of BrdU LI of superficial layer was 19.6%, which was significantly higher than that of internal layer and deep layer. The distribution patterns were classified into three types (labelling types) as follows: Superficial type, BrdU LI of superficial or internal layer was higher than that of deep layer; deep type, BrdU LI of deep layer was higher than that of superficial or internal layer; diffuse type, BrdU LI of each layer was equal. Thirty of 50 cases were superficial type. But in diffuse type (13 cases), incidence of lymph node metastasis, vessel invasion, larger than 4 cm in tumor size, differentiated type and aneuploid were significantly higher than those in superficial type.

Bromodeoxyuridine↗