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T Kosaka

Publications and source records attributed to T Kosaka.

At least 19 recordsLinked to original sources
PubMed1992

Induction of thromboxane synthase and prostaglandin endoperoxide synthase mRNAs in human erythroleukemia cells by phorbol ester.

The effects of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the mRNA levels of two enzymes, thromboxane synthase (TXS) and prostaglandin endoperoxide synthase (PES), responsible for the synthesis of thromboxane A2 from arachidonic acid, were studied in human erythroleukemia (HEL) cells by RNA blot analysis. TPA induced both TXS and PES mRNAs in HEL cells in a dose-dependent manner at 36 h. The half-maximal and maximal effects for the induction of both mRNAs were at approximately 3 x 10(-9) M and at 10(-8) M, respectively. TXS and PES mRNA levels increased in a time-dependent fashion by TPA, and reached to 7- and 3.5-fold of the control, respectively after 48 h of TPA treatment. These results suggest that expression of TXS and PES genes in HEL cells were simultaneously stimulated by TPA.

Cyclooxygenase Inhibitors↗
PubMed1992

Expression of human pituitary adenylate cyclase activating polypeptide (PACAP) cDNA in CHO cells and characterization of the products.

cDNA encoding human PACAP precursor was expressed in non-neuroendocrine Chinese hamster ovary cells, CHO-K1, The cells were transfected with expression vector (pTS705) containing the human PACAP cDNA by electroporation. A cell line which produced more than 80 ng/ml of immunoreactive PACAP (ir-PACAP) into the conditioned medium was established. RP-HPLC analysis of culture medium of this established cell line exhibited the presence of two types of PACAP, i.e. PACAP38 and PACAP27. At the same time, it was also revealed that immunoreactive PACAP-related peptide (ir-PRP) was secreted into the cultured medium. The ir-PACAPs were confirmed to ahve biological activities such as induction of cAMP and neurite outgrowth in rat pheochromocytoma PC12h cells.

Adenylyl Cyclases↗
PubMed1992

Monoclonal antibody 473 selectively stains a population of GABAergic neurons containing the calcium-binding protein parvalbumin in the rat cerebral cortex.

Monoclonal antibody (MAb) 473 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 preembedding immunocytochemistry at the light microscopic level. About 90% of MAb 473 stained cells in the rat parietal cortex were PV immunoreactive. Thus we compared MAb 473 staining with that of three chemical probes, previously shown to stain selectively a subpopulation of PV-containing GABAergic neurons in this brain region, namely, a lectin, Vicia villosa agglutinin (VVA), with a specific affinity for terminal N-acetyl-galactosamine, MAb 3B3 which is specific for chondroitin sulfate proteoglycan and MAb HNK-1 which is specific for some types of carbohydrate epitope containing a sulfated derivative of glucuronic acid. About 85% of MAb 473 immunoreactive cells were shown to be stained with VVA. Furthermore about 90% of MAb 473 immunoreactive cells were also stained with MAb 3B3. Thus MAb 473 positive cells were almost included into VVA and/or MAb 3B3 positive cells. On the other hand only about 34% of MAb 473 positive cells were HNK-1 positive, whereas about 44% of HNK-1 positive cells were MAb 473 positive. Thus these two MAbs defined different, though partially overlapping, subsets of PV-containing GABAergic neurons in the rat parietal cortex.

Animals↗
PubMed1992

Postnatal X-ray irradiation effects on glomerular layer of rat olfactory bulb: quantitative and immunocytochemical analysis.

In the rat olfactory bulb, the majority of interneurons in the glomerular layer (GL) are supposed to be generated during first postnatal week. Low and repeated doses of X-rays (200 rad x 4 and 200 rad x 6) were used during this period to impair the development of interneurons. The resulting effects of olfactory bulb neurons were examined stereologically and immunocytochemically in animals of 4 and 12 weeks of age. Quantitative analysis showed that, 1) the volume of the GL decreased to 55% (1200 rad) - 70% (800 rad) of control, 2) numerical cell densities in GL decreased to 40% (1200 rad) - 60% (800 rad) of control, thus resulting in 3) a decrease of the total cell number in GL to 20% (1200 rad) - 40% (800 rad) of control in irradiated olfactory bulbs of animals 4 weeks old. In comparison, mitral cells, which are generated prenatally, were much less affected (total cell number: 70-80% of control), indicating a selective loss of cells generated during the first postnatal week in GL. Effects on somata and processes immunoreactive for GABA, tyrosine hydroxylase (TH), calbindin D-28K and parvalbumin (PV) were examined in irradiated bulbs of both 4 and 12 week-old rats. All of these immunoreactive elements showed a drastic decrease in all layers. Semiquantitative analysis showed that in the GL, calbindin D-28K immunoreactive (calbindin D-28K(+)) neurons decreased more extensively than TH immunoreactive (TH(+)) and GABA-like immunoreactive (GABA(+)) neurons; that is, TH(+) and GABA(+) neurons decreased to 20% (1200 rad) - 40% (800 rad) of control, whereas calbindin D-28K(+) neurons decreased to 10% (1200 rad) - 30% (800 rad) of control in the GL of irradiated bulbs. These findings indicated that larger proportions of calbindin D-28K(+) neurons might be generated during the first postnatal week than those of GABA(+) and TH(+) neurons. Furthermore, in irradiated bulbs the proportion of GABA(-)TH(+) cells in TH(+) cells increased to about twice of control, and the estimated total numbers of GABA(-)TH(+) cells in irradiated rats were 95% (800 rad) and 40% (1200 rad) of control. These observations suggest that the majority of GABA(-)TH(+) neurons were less affected by X-ray irradiation during the first postnatal week and thus that they might be generated in the prenatal period. Since during the first 2 postnatal weeks, neurons showing GABA(-)TH(+) were not seen in GL (Kosaka et al. 1987a), the majority of GABA(-)TH(+) neurons in adult olfactory bulb were assumed to change their phenotype at some postnatal developmental period.

Animals↗
PubMed1992

Quantitative analysis of neurons and glial cells in the rat somatosensory cortex, with special reference to GABAergic neurons and parvalbumin-containing neurons.

The number of neuronal and glial cells in the rat somatosensory cortex (barrel area) has been estimated by a stereological method, the disector, using pairs of toluidine blue-stained, plastic-embedded 0.5-microns-thick sections, 1.5 microns distant from each other. Chemical properties of those disector-counted cells were further analyzed by postembedding immunocytochemical methods on adjacent semithin sections. Thus we were able to analyze quantitatively number, distribution, and proportion of five cell types: (1) gamma-aminobutyric acid-(GABA)-negative neurons; (2) GABA-like immunoreactive (GABA-LIR) neurons; (3) a specific calcium-binding protein parvalbumin-immunoreactive (PV-IR) neurons, a subpopulation of GABA-LIR neurons; (4) S-100 beta-LIR glial cells (astrocytes); and (5) S-100 beta-negative glial cells (oligodendrocytes and microglia). The densities of total cells, glial cells, and neurons in the rat somatosensory cortex were 85.4 +/- 10(3)/mm3, 30.5 x 10(3)/mm3, and 54.9 x 10(3)/mm3, respectively. Of all neurons 25% and 14% were GABA-LIR and PV-IR, respectively; all PV-IR neurons are GABA-LIR, and thus about 54% of GABA-LIR neurons are PV-positive. The number of total cells under a unit surface area of 1 mm2 through the thickness of the somatosensory cortex was 171.6 x 10(3); the number of neurons and glial cells were 110.2 x 10(3) and 61.4 x 10(3), respectively. There were 27.7 x 10(3) GABA-LIR neurons and 15.0 x 10(3) and 12.7 x 10(3) PV-IR neurons and PV-negative GABA-LIR neurons, respectively. The laminar distribution of each group of cells shows prominent differences, indicating that the cellular composition was different from layer to layer. The density of GABA-LIR neurons was highest in layer IV. The numerical density of PV-IR neurons was 2-4 times higher in layer IV than in layers II/III, V, and VI, whereas that of PV-negative GABA-LIR neurons was almost constant throughout the layers.

Animals↗
PubMed1992

Independent clinical and flow cytometric prognostic factors for the survival of patients with stage I gastric cancer.

Paraffin-embedded tumor samples from 151 patients with stage I gastric cancer were analyzed by DNA flow cytometry, and 80 patients received an infusion of bromodeoxyuridine (BrdU) to determine S-phase fraction. S-phase fractions of tumors were measured by the immunohistochemical method using anti-BrdU monoclonal antibody. Of the 151 patients, 81 (54%), and 70 (46%) showed diploid and aneuploid patterns. There was no significant association between DNA ploidy and wall invasion, histologic type, or lymphatic invasion. Aneuploid tumors were associated with positive-vessel invasion. When the DNA ploidy and clinicopathological parameters were simultaneously entered into the Cox regression model, DNA ploidy and wall invasion emerged as independent prognostic parameters. Aneuploid tumors had significantly higher values of BrdU labeling indices than diploid ones. These results indicate that the determination of DNA ploidy patterns may be an important prognostic factor in patients with stage I gastric cancer, and may be useful in deciding the therapeutic schedule of patients with gastric cancer.

Aneuploidy↗
PubMed1992

The succinate dehydrogenase inhibition test for evaluating biopsy specimens and resected tumors of advanced gastric cancer.

An in vitro chemosensitivity study of both biopsy specimens and surgically resected tumors of advanced gastric cancer from 12 patients was evaluated using the succinate dehydrogenase inhibition (SDI) test. A decrease in succinate dehydrogenase (SD) activity as an indicator of chemosensitivity was determined using cisplatin (CDDP), etoposide (VP-16), and mitomycin C (MMC). In this study, 29 of a total 36 experiments were evaluable (80.6%) and significant correlations were found in all three of the antitumor drugs (P < 0.03). This finding suggests that the SDI test using biopsy specimens may prove valuable for assessing the preoperative chemosensitivity of advanced gastric cancer.

Aged↗
PubMed1992

Is bile or are pancreaticoduodenal secretions related to gastric carcinogenesis in rats with reflux through the pylorus?

Male Wistar rats were subjected to one of three types of operative reflux procedure that allowed part or all of the duodenal contents to flow back into the stomach through the pylorus, thus producing models of bile reflux alone, pancreaticoduodenal reflux alone, and combined reflux. All surviving animals were killed 50 weeks after surgery and the development of gastric cancer was assessed. No cancer was seen in 16 animals with pancreaticoduodenal reflux or in 32 control animals with gastrotomy, whereas 2/8 animals with bile reflux and 11/29 animals with combined reflux had gastric carcinoma. Compared with the control group, the incidence of carcinoma in animals with bile or combined reflux was significantly higher (P less than 0.05 and P less than 0.01 respectively). All carcinomas developed in the antral area near the pylorus. Adenomas were observed only in the groups of animals developing carcinoma and occurred in the same region of the stomach. These results suggest that bile, and not pancreaticoduodenal secretions, is the component of the duodenal contents responsible for the development of gastric carcinoma.

Adenocarcinoma↗
PubMed1992

Duodenal reflux through the pylorus induces gastric adenocarcinoma in the rat.

We investigated whether duodenal reflux through the pylorus is involved in the development of gastric cancer. Male Wistar rats weighing 230-250 g were subjected to three types of operative procedures: (i) allowing reflux through the pylorus; (ii) allowing reflux through a gastrojejunal stoma; and (iii) gastrotomy. No carcinogens were given, and the animals were killed 50 weeks after surgery. No cancers were detected in any of the 18 animals with gastrotomy. In contrast, seven (41%) of 17 animals with reflux through the pylorus and four (31%) of 13 animals with reflux through the stoma had adenocarcinoma. Differences in the incidence between both reflux groups and the gastrotomy group were significant (P < 0.01 and P < 0.05 respectively). All of the adenocarcinomas developed in the pyloric mucosa near the pylorus in the animals with reflux through the pylorus, and in the oxyntic mucosa near the stoma in those with reflux through the stoma. Adenocarcinomas appeared as a polyploid mass with or without slight central erosion. Most of the adenocarcinomas were of the well-differentiated tubular type, and the others were of the mucinous type. No differences in either the histologic type or depth of invasion of the adenocarcinoma were recognized between the two duodenogastric reflux groups. Precancerous or paracancerous lesions, such as adenoma, adenocystic proliferation, and stomal pseudopyloric metaplasia, were more frequently found in the same region as the adenocarcinomas. These findings suggest that duodenogastric reflux in the rat has potent carcinogenic activities not only in the oxyntic mucosa through the stoma, but also in the pyloric mucosa through the pylorus.

Adenocarcinoma↗
PubMed1992

An immunohistochemical study of the distribution of immunocompetent cells, especially macrophages and Ia antigen-expressing cells of heterogeneous populations, in normal rat molar pulp.

The precise distribution of various immunocompetent cells in rat molar pulp was immunohistochemically examined by use of seven anti-rat monoclonal antibodies. It was demonstrated that rat molar pulp contained many OX6 (anti-Ia antigen)-positive cells and a large number of ED1 (anti-monocytes, macrophages, and dendritic cells)-positive, ED2 (anti-tissue macrophages)-positive, and/or OX35 (anti-macrophages and CD4+ lymphocytes)-positive cells. Macrophage-like cells predominated in the central portion of the pulp, while cells of dendritic appearance usually existed in the periphery of the pulp. Double-immunoperoxidase staining revealed that these cells showed some heterogeneity, but the majority could be classified as ED1+/OX6-/ED2+ cells, which may be Ia-histiocytes. Findings also suggested that true dendritic cells may be included in the ED1+/OX6+/ED2- category of cells. A small number of T lymphocytes and plasma cells were also detected. These results suggest that the normal dental pulp contains a variety of immunocompetent cells, with macrophages as the most dominating. Following the exogenous invasion of pathogenic stimuli in the pulp, these cells may participate in the defense reaction by acting as phagocytes or antigen-presenting cells, which are essential for the initiation of immune responses.

Animals↗
PubMed1992

DNA fragmentation and cytotoxicity by recombinant human tumor necrosis factor in L929 fibroblast cells.

Induction of cell DNA fragmentation by treatment of recombinant human Tumor Necrosis Factor alpha (rhTNF alpha) was examined by using mouse L929 cells derived from mouse fibroblast cells. The amount of DNA fragments derived from rhTNF alpha-treated cells, detected by alkaline elution technique, was smaller than that derived from X-irradiated cells. The rhTNF alpha caused the DNA fragmentation depending on its incubation time and concentration. The DNA damage caused by rhTNF alpha treatment correlated with its cytotoxicity. This result suggested that the DNA fragmentation is one of causes of cell death. The treatment with proteinase K of DNA obtained from rhTNF alpha-treated cells did not increase the amount of DNA fragmentation, which indicates that rhTNF alpha causes DNA-fragmentation but not DNA-protein cross-linking.

Animals↗
PubMed1992

Non-specific natural cytotoxic factor released from bovine peripheral blood lymphocytes.

Natural cytotoxicity against bovine leukemia cells (PC-3 cells) was found in bovine peripheral blood lymphocytes (PBL), and in non-adherent cells but not in adherent cells to nylon-wool column. Natural cytotoxic cells (NCC), which have natural cytotoxic activity, are found in T cell-rich fraction. When NCC were cocultured with PC-3 cells, natural cytotoxic factor (NCF) was released rapidly from NCC, and dose-response curve for NCF was almost linear induction. Cytotoxicity against PC-3 cells by NCC or NCF was increased with an increment of incubation period. Cytotoxicity against K562 cells, CL-1 cells, M1 cells or EL-4 cells by NCF was almost the same level as that against PC-3 cells, but that against those cell lines by NCC was not found. NCF activity in culture fluid from NCC cocultured with K562 cells or CL-1 cells was lower than that from NCC cocultured with PC-3 cells.

Animals↗
PubMed1992

[PMUE therapy (CDDP, MMC, UFT, etoposide) for advanced gastric cancer--a case report].

CDDP, MMC, UFT and Etoposide (PMUE)-combined therapy was given to a 62-year-old man with advanced gastric carcinoma. PMUE therapy consists of i.v. injection of CDDP 75 mg/m2 and MMC 10 mg/body on day 1, i.v. injection of Etoposide 50 mg/body on days 3, 4 and 5 and consecutive daily administration of UFT 400 mg/body, with 3 weeks as one course. He was admitted for Borrmann type 3 gastric carcinoma with multiple liver metastasis, lymph node metastases and peritoneal dissemination, the underwent total gastrectomy with R2 lymph node dissection. He was treated four times with this therapy after sensitivity test for carcinostatic agents (SDI test), which resulted in complete remission, as confirmed by CT scan and second-look operation. The patient has currently been free of disease, and we conclude that this PMUE therapy is extremely effective for advanced gastric carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Evaluation of intraoperative intraperitoneal administration on anti-cancer drug for gastric cancer].

This study was undertaken in order to evaluate the effect of intraoperative intraperitoneal (IP) administration of cisplatin (CDDP) and/or mitomycin C (MMC) on patients who underwent an operation for gastric cancer, compared with an untreated group. There were no differences between the effect of CDDP and that of MMC. No differences were found between the survival rate of IP and untreated group in no liver and no peritoneal metastasis cases, nor in non-resection cases. However, the median survival time was longer at 377 days in IP group than at 213 days in the untreated group (p less than 0.1). The free CDDP levels in the serum after 50 mg IP injection remained effective for 15-30 min. On the other hand, the MMC levels in the serum after 20 mg IP proved in effective.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Study on correlation of hematogenous metastasis in advanced colorectal cancer with the morphological mode of tumor invasion in the pm layer].

We studied the influence of the morphological mode of tumor invasion in muscularis propria (pm) layer, in 177 patients who received resection for colorectal carcinoma that invaded beyond the pm layer. Tapering Index (TI = A/B) defined from the ratio between the length of tumor invasion on upper pm layer (A) and that on lower pm layer (B), TI value was significantly lower in cases with hematogenous metastasis than that in cases without hematogenous metastasis. Cases in which TI values were under 1.3 in colon cancer and 1.9 in rectal cancer had higher possibility of synchronous or metachronous hematogenous metastasis and poorer prognosis. Therefore, we suspected that TI value would be an important factor in prediction of hematogenous metastasis.

Adult↗
PubMed1991

Expression of c-erbB-2 oncoprotein in gastric carcinoma. Immunoreactivity for c-erbB-2 protein is an independent indicator of poor short-term prognosis in patients with gastric carcinoma.

Correlations of c-erbB-2 protein expression with clinical outcomes of gastric carcinomas were studied in 189 gastric carcinomas. There were 23 (12.2%) carcinomas with evidence of c-erbB-2 protein in which the reaction was localized to the cell membrane. There was no significant association between c-erbB-2 staining and the macroscopic or histologic type of the carcinomas. c-erbB-2-stained tumors were more likely to be associated with serosal invasion, nodal involvement, and peritoneal metastasis, than c-erbB-2-unstained ones. In addition, c-erbB-2 was stained in none of early gastric carcinomas. The 5-year survival rates of the c-erbB-2 protein-positive and the protein-negative group were 11% and 50%, respectively. When the c-erbB-2 tissue status and seven clinicopathologic variables as conventional prognostic factors were entered simultaneously into the Cox regression model, serosal invasion, hepatic metastasis, peritoneal metastasis, nodal status, and c-erbB-2 tissue status emerged as independent prognostic variables. The results suggested that c-erbB-2 protein expression might be enhanced in advanced stages during the progression of gastric carcinoma. In this particular group of patients, immunoreactivity for c-erbB-2 protein is an indicator of poor short-term prognosis.

Adult↗