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Biomedical subjects

T Kosaka

Publications and source records attributed to T Kosaka.

At least 235 records · Page 13Linked to original sources

[A study on 29 patients with cancers of the gastric remnant--a speculation on a remnant cancer-promoting factor from the aspect of tumor location].

We reviewed 29 patients who developed carcinomas of the gastric remnant more than 10 years after the initial gastrectomy. The median age was 59 years (29-75), with a male-to-female ratio of 3.8:1. The reason for previous operation was stomach ulcer in 16 patients, chronic gastritis in 2, stomach polyp in 2, duodenal ulcer in 5 and stomach cancer in 4 patients. Regarding the type of the original operations, Billroth's operation I (B-I) was performed for 10 patients, Billroth's II (B-II) for 18 and Roux-en Y operation for one. The site of tumor was classified into three groups, stoma (gastroenterostomy), stump (gastric cut-end except stoma) and others (the site except stoma and stump). The patients reconstructed with B-II developed significantly more carcinomas in the stoma than those reconstructed with B-I, with the incidence of 10/18 and 0/10, respectively (p less than 0.05). The interval between the initial operation and the second one was significantly longer in patients with stomal cancer than in those with stump cancer (p less than 0.05). There were no significant difference in the frequency and degree of histologic change, such as intestinal metaplasia or glandular cystification in noncancerous areas, between the B-I and B-II patients. This study suggested that cancers of the gastric remnant, especially those developed in the stoma after B-II were different from the other remnant cancers in terms of carcinogenesis or cancer promotion, and that they were probably induced by duodenogastric reflux to the gastrojejunostomized area.

Adult↗

[Proliferative activity as a marker for lymph node metastases on early gastric cancers--in vitro bromodeoxyuridine labeling for clinical use].

We estimated the clinical significance of the DNA ploidy pattern and S-phase fraction (SPF) with in vivo administration of bromodeoxyuridine (BrdU) and flow cytometry on 61 early gastric cancers. Aneuploid tumors or tumors with high SPF had high incidence of lymph node metastases than diploid tumors or tumors with low SPF, respectively. Thirty cases of human gastric cancers were examined with both in vivo and in vitro labeling of BrdU. In early gastric cancers, DNA ploidy pattern was same in 11 cases out of 13 cases and SPF was correlated with in vivo and in vitro (p less than 0.01). However, in advanced gastric cancers, DNA ploidy pattern was same in only 3 cases out of 17 cases and SPF was not correlated with in vivo and in vitro. The reasons for no correlation with in vivo and in vitro was reduced to the existence of DNA ploidy heterogeneity which was observed 22.2% and 70.6% in early and advanced cancers, respectively. From the results, we considered that DNA ploidy pattern and SPF were useful marker for lymph node metastases and the preoperative in vitro BrdU labeling method was useful for the marker of lymph node metastasis in early gastric cancers.

Bromodeoxyuridine↗

[Metastasis and its relation to cell kinetics in human colorectal cancers].

The difference of the cell kinetics between primary tumor and its metastasis was studied on six cases of human colorectal cancers (four cases at synchronous liver metastases and two metachronous) with migration chase method using flow cytometry in vivo. The bromodeoxyuridine labeling indices (LI), DNA synthesis time (Ts), and generation time (Tg) were measured in normal colonic mucosae, primary tumors, lymph node metastases, and liver metastases. The LI, Ts, and Tg were 4.9 +/- 2.2%, 11.6 +/- 1.4 hours, and 11.3 +/- 3.7 days, respectively, in normal mucosa. In cancer, they were 13.9 +/- 7.1%, 16.9 +/- 4.8 hours, and 6.0 +/- 2.5 days, respectively. LI was higher and Ts was longer in cancer than in normal mucosa. Tg was shorter in cancer than in normal mucosa. In lymph node metastases, LI, Ts, and Tg were 12.0 +/- 4.5%, 14.4 +/- 6.0 hours and 5.0 +/- 0.5 days, respectively. Ts was faster in lymph node metastases than in primary tumors. In liver metastases, they were 30.1 +/- 18.1%, 28.0 +/- 10.2 hours, and 4.8 +/- 2.1 days, respectively. LI was higher and Ts was longer in liver metastases than in primary tumors. In both metastatic lesions, Tg was shorter than in primary tumors. The proliferation rate correlated with LI/DNA index significantly (r = 0.7868, p less than 0.00001). From the results, it was revealed that the proliferation rate was higher in metastatic lesions than primary tumors in vivo. The application of this method for clinical and experimental use would be expected.

Bromodeoxyuridine↗

Proliferative activity of early gastric cancer measured by in vitro and in vivo bromodeoxyuridine labeling.

Forty seven patients with early gastric cancer received a 30-minute intravenous injection of bromodeoxyuridine (BrdU), 1000 mg each 1 hour before laparotomy, to label tumor cells in the S phase. In 13 of 47 patients, specimens obtained by endoscopic biopsy were cultured in vitro at 37 degrees C for 1 hour under three times the atmospheric pressure in a vial with 400 microM BrdU. Labeled cells were detected in the resected specimen and the cultured specimen by immunohistochemical staining procedure. The BrdU labeling index (LI, defined as the percentage of labeled cells in relation to the 1000 tumor cells) was calculated for each specimen. All patients without lymph node metastasis had an in vivo BrdU LI of less than 12%. In contrast, 31% of patients with early gastric cancer with an in vivo BrdU LI greater than 12% had lymph node metastasis. There was a correlation between the in vivo and the in vitro LI. Therefore, the in vitro BrdU LI of specimens obtained by endoscopic biopsy may be a useful indicator of lymph node status in patients with individual early gastric cancers before operations. If the in vitro BrdU LI is less than 12% lymph node dissection may not be necessary.

Bromodeoxyuridine↗

Synthesis of the vasoconstrictor peptide endothelin in kidney cells.

The expression plasmid containing human prepro-endothelin cDNA was constructed and introduced into COS-7 cells. Mature endthelin, consisting of 21 amino acid residues, was secreted into the culture medium of the transfected cells and was also synthesized by non-transfected COS-7 cells. Normal kidney cells derived from other species also synthesized and secreted endothelin. Partial characterization of endothelins produced by kidney cells suggested that existence of new types of endothelin. This is the first report of the vasoconstrictor peptide endothelin being synthesized in kidney cells.

Animals↗

Selective staining of a population of parvalbumin-containing GABAergic neurons in the rat cerebral cortex by lectins with specific affinity for terminal N-acetylgalactosamine.

Lectins with specific affinity for terminal N-acetylgalactosamine, Vicia villosa agglutinin (VVA) and Glycine max agglutinin (soybean agglutinin; SBA), are shown to stain selectively a subpopulation of GABAergic neurons in the rat cerebral cortex. About 90% of VAA- and/or SBA-stained cells are also parvalbumin-immunoreactive, but no VVA-stained cells showed somatostatin-28-like or cholecystokinin-8-like immunoreactivities.

Acetylgalactosamine↗

Three-dimensional morphometrical study of dendritic spines of the granule cell in the rat dentate gyrus with HVEM stereo images.

Number, length, and diameters of dendritic spines of the granule cell in the dorsal leaf of the rat dentate gyrus were measured by using high-voltage electron microscope stereo images of 5-micron-thick Golgi preparations with the aid of a three-dimensional image analyzer system. Spine densities of 2.02 +/- 0.28, 2.28 +/- 0.33, and 3.36 +/- 0.35 per 1 micron at distal, middle, and proximal portions of the dendrite were obtained. These values were about 1.6-fold of the previous light microscopical report. Mean three-dimensional spine length were 1.244 +/- 0.506 micron, 1.262 +/- 0.563 micron, and 1.254 +/- 0.584 micron at distal, middle, and proximal portions, respectively, which were about 1.4 times longer than those measured in two dimensions. By using measured morphometrical parameters of spines such as lengths, diameters, and population densities, total spine surface areas of 2.401 micron 2, 2.806 micron 2, and 4.180 micron 2 per 1 micron of the dendrite at distal, middle, and proximal portions, respectively, were obtained. The total surface area of dendrite was about doubled by the addition of the spines at each dendritic portion. The advantageous features and the problems of the present method are discussed.

Animals↗

Correlation of DNA ploidy and clinical outcome in Borrmann type 4 gastric carcinoma.

The correlation between DNA ploidy pattern and clinical outcome was studied in 76 patients with Borrmann type 4 gastric carcinomas. Twenty-six tumors were diploid, and 50 tumors were aneuploid. There was no correlation among DNA ploidy and histologic type, lymph-node status, wall invasion, or clinical stage. The incidence of vascular invasion in the aneuploid tumors was significantly higher than that in the diploid tumors. Five year survival was achieved in 28% of the patients with diploid tumors and 8% of those with aneuploid tumors, respectively. Among the patients undergoing curative resection, 5 year survival rate was 54% in the patients with diploid tumors compared to 28% with aneuploid tumors. There was a significant survival advantage in patients with diploid tumors. These results indicate that DNA ploidy might be an important prognostic factor in Borrmann type 4 gastric carcinomas.

Adult↗

Monoclonal antibody VC1.1 selectively stains a population of GABAergic neurons containing the calcium-binding protein parvalbumin in the rat cerebral cortex.

Monoclonal antibody VC1.1 is shown to stain selectively a subpopulation of GABAergic neurons in the rat cerebral cortex. Almost all VC1.1 immunoreactive cells were also GABA-like immunoreactive (GABA-LI) and parvalbumin (PV) immunoreactive, whereas they were about 30% and 65% of GABA-LI and PV-positive cells in the parietal cortex and about 13% and 32% in the occipital cortex, respectively. Although a few VC1.1 positive cells showed somatostatin-like and/or cholecystokinin-like immunoreactivities, they were exceptional (less than 1% of VC1.1 positive cells). Furthermore about 90% of VC1.1 positive cells were also stained with a lectin, Vicia villosa agglutinin, with a specific affinity for terminal N-acetylgalactosamine.

Animals↗

DNA-lesion and cell death by alpha-particles and nitrogen ions.

When the natural logarithm of the surviving fraction is plotted against the dose of radiation, curves with shoulders at relatively high survival levels are obtained after gamma-rays. The curves were practically linear in case of HMV-I and HA-1 cells irradiated by charged particle beams. These cells were derived from human malignant melanoma and Chinese hamster cells, respectively. The amount of DNA single strand breaks (ssb) by gamma-rays or nitrogen-ions (LET=530KeV/micrometers) in HMV-I cells increases linearly with increment in dose, when the ssb is detected using the alkaline elution technique. There is no close relationship between the dose-response curve of the ssb and the dose-survival curves after gamma-rays or N-ions. The amount of DNA double strand breaks (dsb) by gamma-rays increases quadratically with increment of dose, in both HMV-I cells and HA-1 cells, when the dsb is detected using the neutral elution technique. The survival fraction for HA-1 cells is slightly higher than that for HMV-I cells, at the same dose, and the amount of dsb for HA-1 cells is considerably greater than that for HMV-I cells. These results suggest that the radiosensitivities to gamma-rays in different cell lines do not correspond to the number of DNA strand breaks. The amount of both non-repairable ssb and dsb also increases quadratically with increment of dose for gamma-rays and almost linearly with increment of dose for N-ions and alpha-particles (LET=36keV/micrometers for HA-1 cells and LET=77keV/micrometers for HMV-I cells). The dose-response curves for non-repairable dsb in case of these radiations seemed to mirror image the dose-survival curves for these radiations, in both cell lines. The number of non-repairable DNA strand breaks in the two cell lines, at the same level of survival was much the same. These results show the close relationship between the induction of non-repairable DNA strand breaks and cell killing.

Alpha Particles↗

Human chorionic gonadotropin in colorectal cancer and its relationship to prognosis.

The presence of human chorionic gonadotropin in large bowel cancers was studied immunohistochemically using an immunoperoxidase technique. HCG-positive tumour cells were present in 42 of 194 adenocarcinomas examined (22.0% of colon cancer and 21.2% of rectal cancers). On histological grading, the hCG-positive rate tended to rise as the degree of differentiation decreased. HCG was detected more frequently in cancers invading the total bowel wall (27%) than in those invading the partial wall (17.1%). Lymph node, liver or peritoneal metastases were present more frequently in hCG-positive tumours than in hCG-negative tumours. Furthermore, there was an intimate correlation between the presence of hCG-positive tumour cells and CEA doubling times in nine cases with untreated liver metastasis. The survival rate for patients with tissue hCG-positive cells was lower than for those with hCG-negative tumours. Thus, the presence of tissue hCG in colorectal cancers may be a biological marker of prognostic significance.

Adenocarcinoma↗

Effect of pregnant mare's serum gonadotropin on increased ovulation in guinea pigs with synchronized estrous cycle.

An ability of Pregnant Mare's Serum Gonadotropin (PMSG) to induce superovulation was investigated in guinea pigs with synchronized estrous cycle caused by the treatment for 21 days of progesterone tubing. On day 6 later following the removal of progesterone treatment, every animal given saline injection had synchronously ovulated. When compared with saline control, a significant increase of ova ovulated was induced by an injection of PMSG 8 hours before the removal of progesterone tubing, but not by the other PMSG treatment schedule. Present study indicates that PMSG injection given at a fixed stage of synchronized estrous cycle induced superovulation in guinea pigs treated with long-term implantation of progesterone tubing.

Animals↗

[Bromodeoxyuridine labeling index in gastric cancer].

In vivo and in vitro BrdU labeling index (L.I.) were calculated in 97 and 11 gastric cancers, respectively. Biopsied specimens by means of endoscopy were used in vitro method. A comparison of the in vitro and in vivo L.I. showed good correlation (p less than 0.01). Gastric cancer with lymph node metastasis had a significantly higher median in vivo L.I. of 16.2% as compared with a median in vivo L.I. of 13.3% in gastric cancer without lymph node metastasis (p less than 0.05). An in vivo L.I. of gastric cancer with vessel invasion was significantly higher than that without vessel invasion (p less than 0.05). Early gastric cancer with an in vivo L.I. of less than 12% had no lymph node metastasis. On the contrary, 31% in that with an in vivo L.I. of greater than 12% had lymph node metastasis. The in vitro L.I. which was similar to the in vivo L.I. may be useful to decide operative procedure in gastric cancer, specially in early gastric cancer.

Bromodeoxyuridine↗

[Effect of UFT on nuclear DNA distribution of gastric and colorectal carcinomas].

To evaluate the effect of UFT on nuclear DNA distribution of carcinoma, we measured the DNA content of biopsy specimens and resected specimens obtained from 18 patients by microfluorometry. The tumors consisted of 7 gastric and 11 colorectal carcinomas. Five patients who received administration of 400mg of UFT (400mg of tegafur) were classified as the chemotherapy group and another 13 patients were classified as the control group. 1) DNA indices of biopsy specimens and resected specimens of the same patients showed almost the same values both in the control group (r = 0.81) and in the chemotherapy group (r = 0.89) (p less than 0.05). 2) S and S + G2M fractions of resected specimens showed almost the same values as compared with those of corresponding biopsy specimen in the control group. However, in the chemotherapy group S and S + G2M fractions of resected specimens showed a tendency to be higher than those of corresponding biopsy specimen (0.05 less than p less than 0.1). This study indicates that the biopsy specimens are sufficient for DNA analysis and that UFT-induced DNA change may be increase of S and S + G2M fraction.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical significance of serum NCC-ST 439 as a tumor marker for colorectal cancer].

Clinical significance of preoperative serum NCC-ST 439 level was studied in 119 cases of colorectal cancer (90 of primary, 29 cases of recurrent). The positive rates for serum NCC-ST 439 were 28.9% in primary and 65.5% in recurrent cases. The false positive rates for benign disease were 5.6%. These rates were low when compared with those for other tumor markers. The positive rates for serum NCC-ST 439 exhibited a strong correlation with wall invasion, lymph node and liver metastases. A combination assay of NCC-ST 439, CEA and CA 19-9 produced a high positive rates as 43.3% in primary and 86.2% in recurrent cases. These results demonstrate that measurement of serum NCC-ST 439 may be useful for cancer staging and improves the diagnostic rate in combination with CEA and CA 19-9.

Adenocarcinoma↗

The relationship between the number of synaptic vesicles and the amount of transmitter released.

The relationship between the number of synaptic vesicles and the amount of transmitter released from identified synapses was investigated in the dorsal longitudinal flight muscle (DLM) of the temperature-sensitive endocytosis mutant of Drosophila melanogaster, shibirets-1(shi). In the shi fly at 29 degrees C, vesicle recyling is blocked, but transmitter release proceeds normally. Thus, by inducing transmitter release at 29 degrees C, shi synapses gradually become depleted of synaptic vesicles. In this way it was possible to regulate the number of vesicles in a synapse. Intracellular recordings were made from individual fibers of the DLM in shi flies after various periods at 29 degrees C while stimulating at 0.5 Hz. The amplitude of the evoked excitatory junction potential (ejp), gradually decreased with longer exposure and was brought to various levels. The fiber was then rapidly fixed for electron microscopy. The number of vesicles per synapse was compared with the amplitude of the ejp at the time of fixation. It was observed that the smaller the ejp amplitudes became, the fewer vesicles were in the synapses. Also, as the ejp amplitude decreased, an increased number of synapses contained no vesicles. It is concluded that synaptic vesicles are directly involved in the release process.

Action Potentials↗

[A clinicopathological studies on gastrointestinal leiomyosarcomas, with special reference to prognosis].

Twenty-five cases of gastrointestinal leiomyosarcomas were subjected to clinico-pathological studies in an attempt to correlate the prognosis with tumor size, mitosis, cellularity and DNA ploidy pattern. Leiomyosarcomas greater than 5cm in diameter had poorer prognosis. Those with mitotic index larger than 3.0/mm2, cellularity larger than 3.0/0.0004mm2, DNA aneuploidy had poorer prognosis. By multiple regression analysis, mitotic index was useful for the prediction of tumor recurrence in earlier postoperative period, but cellularity, tumor size were useful for the prediction of recurrence in later postoperative period. As for the type of tumor recurrence, hematogenous metastasis was observed in 7 cases, peritoneal dissemination in 2 and local recurrence in 4. Four cases with local recurrence had all hematogenous metastasis. Two cases of gastric leiomyosarcomas developing local recurrence were greater than 10cm in diameter and gastric local resection was done for them. One case was diagnosed benign leiomyoma in the rectum histologically, but after trans-anal tumor resection local recurrence and metastasis to the lung occurred. We must pay attention to the surgical margin and the surface of tumor dissection during of the tumor, especially in larger tumors. Aggressive surgical resection is efficient for the treatment of recurrent tumors.

Cell Count↗