Biomedical subjects

K Kawamoto

Publications and source records attributed to K Kawamoto.

At least 19 recordsLinked to original sources

PubMed1992

Cytocidal effects of bromocriptine, somatostatin analog, and heat on growth hormone-secreting pituitary adenoma in vitro.

The effects of bromocriptine (BC), a somatostatin analog (SMS), and heat on the secretion of growth hormone (GH) and prolactin (PRL), and on the morphologic features of human GH-secreting pituitary adenoma were studied in vitro. The treatment with BC, SMS, or heat (41.5 degrees C and 42.5 degrees C) markedly suppressed the secretion of GH and PRL from the adenoma cells and reduced the number of cells immunoreactive with GH or PRL. The combined treatment with BC and heat induced a marked reduction in the number of GH and PRL cells consistent with the effect on the secretion of GH and PRL. These results suggest that BC, SMS, and heat treatments produced the cytotoxic effects on pituitary adenoma cells, and that the simultaneous treatment of BC and heat enhanced this effect.

Adenoma↗

PubMed1992

An androgen-dependent subclone derived from a mouse mammary tumor, Shionogi carcinoma 115, secretes a heparin-binding growth factor having an apparent molecular weight of 31,000 in response to androgen.

An androgen-dependent cell line denoted SC2G is a clone of an androgen-dependent mouse mammary tumor, Shionogi Carcinoma 115. Fibroblast growth factors (FGFs), epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are stimulatory for the growth of SC2G cells in the absence of androgen. This clone was found to secrete an androgen-induced growth factor mostly eluting at 1.8 M NaCl on a heparin-Sepharose column. This factor was partially purified by chromatography on two consecutive heparin-Sepharose columns followed by cation-exchanging chromatography on an S-Sepharose column from the chemically defined serum-free medium conditioned by SC2G cells in the presence of androgen. The factor was a heat- and acid-labile cationic protein that was inactivated by reduction with dithiothreitol. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, most of the growth-promoting activity of this factor was found at approx. 31 kDa under non-reduced conditions. Neither neutralizing antibody against basic-FGF nor that against EGF inhibited the growth-promoting activity of this factor in cell culture, suggesting the factor was distinct from basic FGF or EGF. However, the possibility that the factor was another FGF- or EGF-like growth factor was not excluded.

Animals↗

PubMed1992

Experimental and clinical evaluation by flow cytometry for the mechanism of combination therapy (cisplatin and peplomycin).

Pharmacologic effects of cisplatin (CDDP) and peplomycin (PEP) on tumor cell kinetics were studied both in vitro and in vivo with the aid of flow cytometry (FCM). Double staining with propidium iodide (PI) and fluorescein isothiocyanate (FITC)-labeled bromodeoxyuridine (BrdU) was used to analyze the cell cycle, and the number of viable cells was determined with fluorescein diacetate (FDA). Effects of combining the 2 agents were also studied to establish the most effective method of combination therapy. Furthermore, these agents were tried clinically on the basis of experimental results. Results showed that CDDP exerted its action at the S and G2M phases in the cell cycle and PEP at the G2M phase. Among the combination regimens in the experiments with CDDP, PEP, and CDDP + PEP as analyzed by FCM, the strongest block on the G2M phase was shown in the one at a 2-day interval, resulting in the most effective killing of the tumor cells. Clinical trial of the combination therapy showed the same results as the in vitro experiment; the therapy proved useful for improving the patient's clinical condition and the results obtained with CT imaging and pathology.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Photodestruction of fluorophores and optimum conditions for trace DNA detection by automated DNA sequencer.

Although automated DNA sequencers are becoming popular, their sensitivity in detecting DNA bands is still around 10(-17) mole/band. The sensitivity of a system depends on the laser power, labeling fluorophore, and the fluorescence-collecting yield. The emission and photodestruction cross-sections of the fluorophores are critical in optimizing the irradiated laser power and the migration speeds of DNA fragments to achieve high sensitivity. We investigated photodestruction cross-sections of various fluorophores to optimize the irradiation laser power. In addition, we used a cylindrical lens system to improve the fluorescence-collecting yield of a DNA sequencer using side entry laser irradiation. Fluoresceine isothiocyanate (FITC) commonly used in fluorescence studies, is very photo-destructive, the cross-section of the destruction being about 3.8 x 10(-20) cm2 in buffer solution while that of Texas Red is 1.5 x 10(-21) cm2. When the time for DNA fragments to transit through the irradiated region is 11 s, the optimum laser powers are 0.9 mW, with an Ar laser (488 nm) for FITC-DNA, and 18 mW, with an He-Ne laser (594 nm) for Texas Red DNA. We have developed a DNA sequencer, with a cylindrical lens system which improves the fluorescence-collecting efficiency by a factor of 4, and an He-Ne laser (5 mW). Although the sequencer uses a slab gel, an ultra-high sensitivity of 5 x 10(-20) mole/band (S/N-4) was achieved under optimized conditions.

Autoanalysis↗

PubMed1992

Three cell lines showing androgen-dependent, -independent, and -suppressed phenotypes, established from a single tumor of androgen-dependent Shionogi carcinoma 115.

We investigated the heterogeneity of cells in terms of androgen responsiveness within a single tumor mass of Shionogi carcinoma SC-115 showing androgen-dependent growth. After cloning of the tumor by the limiting dilution method in the presence of androgen, we isolated 40 clones at random. Twenty-two clones required androgen for growth (androgen-dependent phenotype), 16 did not (androgen-independent phenotype), and the remaining two clones showed growth inhibition when androgen was added (androgen-suppressed phenotype). In addition, 22 androgen-dependent clones showed heterogeneity in growth factor sensitivity in the absence of androgen. All clones were sensitive to both acidic and basic fibroblast growth factor (FGF), 7 of 22 clones were sensitive to epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha, and 2 of 22 clones were sensitive to TGF-beta. This preexisting heterogeneity may be partly responsible for the growth of androgen-dependent tumor under hormone-deprived circumstances. Three typical clones, SC2G, SC1G, and SC4A, were selected from androgen-dependent, -independent, and -suppressed phenotypic groups, respectively. These clones, as well as original solid tumors, were found to produce heparin-binding growth factors of heterogeneous elution positions. The molecular nature of these growth factors is not yet known. Neither anti-basic FGF antibody nor anti-EGF antibody inhibited the cell growth when added in cell culture, suggesting the factors were distinct from basic-FGF and EGF.

Androgens↗

PubMed1992

Epidemiological study of peptic ulcer disease among Japanese and Koreans in Japan.

Peptic ulcer among Japanese and Koreans in Japan has rarely been studied. In this 10-year study of hospital-based endoscopy, we focused on the epidemiology of peptic ulcer among these ethnic groups in Japan. Between 1980 and 1990, 81.2% of all patients examined via endoscopy at Saikyo Hospital in Kyoto completed a life-style questionnaire: 1,264 Japanese (70.5%), 503 Koreans (28.1%), and 25 persons of unknown ethnicity (1.4%). Characteristics of ulcer disease were almost identical for Koreans and Japanese. Like other world-wide patterns, the male to female ratio was 2.3:1. Unlike results from Western countries, however, the overall gastric ulcer rate was 1.5 times higher than for duodenal ulcer. This higher rate was due to the relatively high rate of gastric ulcer in the older age groups; among persons less than 40 years of age, duodenal ulcer was diagnosed more often than gastric ulcer. The mean age at diagnosis of duodenal ulcer (40.7 years) was significantly lower (p less than 0.005) than that for gastric ulcer (53.7 years). Multivariate-adjusted odds ratios were calculated using a multiple logistic regression model. Cigarette smoking significantly increased the risk for both gastric ulcer (odds ratio = 3.10, 95% confidence interval [CI] 2.1-4.6) and duodenal ulcer (odds ratio = 1.9, 95% CI 1.2-2.9). Age greater than or equal to 40 years (odds ratio = 2.3, 95% CI 1.6-3.3) and consumption of salty foods (odds ratio = 1.5, 95% CI 1.0-2.1) also significantly increased the risk for gastric ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Enhancing effect of cyclodextrins on nasal absorption of insulin and its duration in rabbits.

The absorption of insulin (from porcine pancreas) in rabbits after the nasal administration of aqueous preparations containing insulin and five kinds of cyclodextrins (CyDs) in phosphate buffer solution at pH 7.0 was investigated. Without CyD, the insulin and glucose levels in plasma were unchanged, whereas a marked increase in the plasma levels of insulin and a decrease in glucose concentrations were observed following the simultaneous administration of insulin and CyD such as alpha- and heptakis (2,6-di-O-methyl)-beta-CyD (DM-beta-CyD). The largest enhancing effect on the nasal absorption of insulin was obtained by DM-beta-CyD. To evaluate the duration of the absorption-enhancing effect of CyDs, preadministration (administration of CyD 0.5, 6, 12 and 24 h before insulin administration) was performed. The area under plasma concentration-time curve (AUC) and Cmax of insulin significantly decreased with the preadministration of DM-beta-CyD 6, 12 and 24 h before nasal administration. The absorption-enhancing effect disappeared 24h after the preadministration. These findings demonstrate that CyDs enhance the nasal absorption of insulin, and the recovery of the membrane transport barrier function in nasal mucosa is achieved, at the latest, 24 h after the administration of CyDs.

Absorption↗

PubMed1992

[The influence of paraquat on cell cycle--analysis of cell kinetics using DNA/BrdU staining].

We examined the in vitro and in vivo effects of paraquat on the cell cycle. After we exposed paraquat to the cultured cell (MDCK), we examined cell kinetics by flow cytometry with BrdU-PI double staining. And we administered paraquat intravenously to the rats, we collected and separated rat's liver and pulmonary cells, and we examined the cell kinetics by same method. Consequently our study found that the cells in the S-phase were noted to be abundant, and we suggested that paraquat apparently arrested the cell cycle at S time, and that DNA damage was importance in the mechanism of paraquat toxicity.

Animals↗

PubMed1992

[Pedunculated hepatocellular carcinoma suspected of right adrenal tumor: a case report].

We report a rare case of extrahepatic growing hepatocellular carcinoma which was clinically diagnosed as right adrenal tumor. A 61-year-old woman was admitted for further examination of right flank pain and hypertension. Abdominal computed tomographic scan and echogram revealed a suprarenal mass. Hypercatecholaminemia was suspected from urinary analysis. Preoperative diagnosis was right adrenal tumor; suspected pheochromocytoma. On operation, we found the tumor was pedunculated from right lobe of liver and compressing normal right adrenal gland. Its clinical diagnosis was hepatocellular carcinoma. Ten months after operation she is still alive. We discuss the difficulty of differential diagnosis between extrahepatic growing hepatocellular carcinoma and adrenal tumor.

Adrenal Gland Neoplasms↗

PubMed1992

Studies on antitumor effects and mechanism of action of l-hexylcarbamoyl-5-fluorouracil by DNA/BrdU double staining using flow cytometry.

An investigation was carried out to elucidate the mechanism of action of the oral antitumor agent 1-hexylcarbamoyl-5-fluorouracil (HCFU) by determining its effects on the growth and cell cycle of epipharyngeal carcinoma cells (KB cell) by DNA/BrdU double staining using flow cytometry (FCM). As a result, it was found that HCFU stimulates KB cells in the S phase to proliferate for the first 3 days of treatment in a low concentration (8 micrograms/ml) and caused cell accumulation in the later G2M phase. On the other hand, when administered in the concentration (20 micrograms/ml) that produces a 50 per cent cell kill, as determined from the cell growth curve, HCFU appeared to exhibit a cytocidal effect by blocking cells in S and G2M for the first 3 days after exposure. It was revealed by FCM for the first time that HCFU operates by a similar mechanism to that of 5-FU. This method seems to be of significance to therapeutic schemes that take into consideration the mechanism of action of antitumor drugs.

Antineoplastic Agents↗

PubMed1992

[Flow cytometric analysis, mechanism of action and evaluation of viability by antineoplastic agents].

Since the cell cycle of tumor cells is evaluable with the aid of flow cytometry, the mechanism of action of antineoplastic agents has readily been analyzed based on the changes of the cell cycle by antineoplastic agents. Propidium iodide had been a conventional staining method for such analysis, but after the introduction of DNA/BrdU double staining method using BrdU, it has become much easier. For evaluating antineoplastic agents, simultaneous measurement by FDA of the viability of the tumor cells is important. In vitro studies of the action mechanism and the antineoplastic effects of 5-FU, ACNU, IFN, PG, CDDP, PEP, and HCFU have been reported previously elsewhere. Similar action mechanism has been confirmed in clinical studies, in which optimal agent was selected by the sensitivity test using flow cytometry, and thus selected agent was actually given to tumor patients. In analyzing antineoplastic agents in vitro, concomitant and total evaluation of DNA-histogram and viability by flow cytometry is needed in the future.

Animals↗

PubMed1992

[Treatment of arteriovenous fistula in the skull base; a case of von Recklinghausen's disease].

We presented a case of neurofibromatosis associated with intractable arteriovenous fistula of the internal carotid artery in the skull base. A 41-year-old man presenting dyspnea and neck swelling was treated with balloon occlusion for arteriovenous fistula. This was followed by its total removal. At operation, we found that arteriovenous fistula was formed by the invasion of the internal carotid arterial wall of a neurofibroma in the skull base, which had been induced by neurofibromatosis. This is a rare case corresponding to vascular neurofibromatosis in the internal carotid artery.

Adult↗

PubMed1992

[Clinical analysis of 46 cases of radiation cystitis].

We experienced 46 cases of radiation cystitis between 1973 and 1990, 10 of which showed intractable bleeding and 17 recurrent bleeding. We clinically analyzed these cases to determine the factors responsible for intractable and recurrent bleeding. Intractable bleeding was suggested to related to the aggravation of the local condition of the urinary tract and recurrent bleeding with an increase of complications, especially diabetes mellitus and hypertension. In conclusion, long-term follow up of local conditions and complications is important in the prevention of intractable and recurrent bleeding of radiation cystitis.

Adult↗

PubMed1992

Comparison of EEG between nasopharyngeal and scalp leads with the aid of an automatic EEG analysis system.

We analyzed the EEG quantitatively with an automatic EEG analysis system, and introduced this system for investigation the relationship between the scalp EEG and nasopharyngeal EEG. The EEG was recorded from healthy volunteers by photic stimulation. We found that components of slow waves like delta and theta were more rich but alpha component was less in the nasopharyngeal EEG than in the scalp EEG. In the analysis of the rate of the appearance of each EEG wave using photic stimulus, a decrease of alpha 1 and an increase of theta 1 are observed in the scalp EEG while there are no specific changes of them in the nasopharyngeal and scalp EEGs. The nasopharyngeal EEG obtained from the vicinity of the base of the brain was thought to originate from the vicinity of the brain stem.

Adult↗

PubMed1991

Glutathione and cellular response of ACNU-resistant rat glioma sublines to drugs and radiation.

Three ACNU-resistant sublines (R1, R3 and R12) from rat glioma 9L cells showed cross-resistance to vinblastine, adriamycin, and VP-16. Among these, the R3 subline also acquired radioresistance under aerobic conditions. Total glutathione levels in these sublines were elevated 2- to 3-fold. Treatment of the cells with BSO, a specific inhibitor of GSH synthesis, resulted in decreased intracellular total glutathione levels in all 4 cell lines to about 10% of control levels. However, sensitivity to radiation or to chemicals did not change accordingly. Treatment of 9L cells with OTZ, a precursor of cysteine, resulted in a rise in intracellular GSH levels but it did not correlate with sensitivity to X-ray or to ACNU. These results suggest that, in terms of cellular sensitivity to radiation or ACNU, total glutathione level alone cannot serve as a predictive indicator.

Animals↗

PubMed1991

Photodynamic therapy for rat pituitary tumor in vitro and in vivo using pheophorbide-a and white light.

This is the first report on the use of photodynamic therapy (PDT) for rat pituitary tumor in vivo. Rat pituitary tumor (GH3) cells were cultured, GH3 tumor was subcutaneously implanted in nude mice, and pheophorbide-a (Ph-a) and white light were prepared. Photocytotoxicity proportional to Ph-a concentration, intensity of irradiation, and incubation time was observed in vitro. Despite the delay in the disappearance of Ph-a from the tumor, Ph-a in the pituitary gland rapidly decreased after intravenous administration in vivo. Through PDT, the tumor grossly disappeared, the plasma levels of rat growth hormone secreted from the tumor also remarkably decreased, and the development of giantism was inhibited. These results indicate that PDT is effective against rat pituitary tumor.

Animals↗

PubMed1991

Flow cytometric analysis of antineoplastic effects of interferon-alpha, beta and gamma labelled with fluorescein isothiocyanate on cultured brain tumors.

Antineoplastic effects of interferons (IFNs) on brain tumors have often been reported in the literature, however, so far as we know, there are no reports of the study on the antineoplastic effect of IFNs (alpha, beta, and gamma) labelled with fluorescein isothiocyanate (FITC) using flow cytometry (FCM). Three established glioma cell lines and 11 cultured cells of brain tumor from surgical specimens were exposed to IFN-alpha, beta, and gamma at the concentrations of 10(2)-10(5) IU/ml for 24 h, respectively. Using FCM, the viability of the cells was evaluated with fluorescein diacetate stain and the cell cycle was analyzed from the DNA-histogram with propidium iodide stain. Furthermore, FITC-labelled IFN-alpha, beta and gamma were also contacted with each cell to calculate respective positive cells. The viability decreased about 60% on day 1 and day 3, indicating the effect of IFN-alpha and beta on U373MG cells and on some cultured glioma cells from surgical materials, whereas, IFN-gamma had no effects. Antineoplastic effect of each IFN well correlated with FITC-positive rates, demonstrating S phase block in the cell cycle. IFN-gamma had no antineoplastic effects, whereas IFN-alpha and beta showed antineoplastic effects, which fact suggested that IFN-gamma receptor be different from those of IFN-alpha and beta. The method of FITC-labelling for IFNs with the aid of FCM has the advantages as follows: 1) Antineoplasticity of IFN can be simply evaluated with FCM; 2) It is easy to analyze the action mechanism of IFN; 3) Information on the receptor is obtainable; and 4) Sensitivity can be evaluated prior to administration of IFN, suggesting possibilities of clinical application of this method.

Antineoplastic Agents↗

PubMed1991

Central neurocytoma: immunohistochemical and ultrastructural study.

Eight cases of central neurocytomas were studied by immunohistochemistry and electron microscopy. Seven tumors were located in the lateral ventricles and one in the subependymal region. All but one patient had a favorable postoperative course. The tumors were composed of small uniform cells possessing amitotic round nuclei with frequent perinuclear halos, a few Homer Wright rosettes and no ganglion cells; an appearance resembling that of oligodendroglioma. Immunohistochemical studies disclosed neuron-specific enolase and Leu-7 positivity in all tumors, S-100 protein-positive cells were found in six, while glial fibrillary acidic protein--and vimentin-positive cells were confined to the blood vessels. Myelin basic protein as well as neurofilament were not detected in the tumors. Synaptophysin-positive areas were seen in one tumor. Ultrastructural examination showed distinctive neuronal tumor cells which had a cytoplasm with sparse dense-core vesicles and thin cell processes containing parallel microtubules. They were classified into three different types of tumor cells according to the extent of differentiation. The most consistent finding for histological diagnosis was the presence of typical or abortive synapses with clear and dense-core vesicles. Additionally, synaptophysin may be a specific marker for some central neurocytomas.

Adult↗