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Biomedical subjects

Y Hata

Publications and source records attributed to Y Hata.

At least 343 records · Page 19Linked to original sources

The effect of cimetidine on adaptive cytoprotection by mild irritant dose of HCl in the rat gastric mucosa.

While cimetidine (CIM) is strikingly effective in inhibiting gastric acid secretion, its effect on the defensive mechanisms of the gastric mucosa has been controversial. The aims of the present study were to test if administration of CIM at an antisecretory dose is protective against acid-induced injury and to assess its effect on adaptive cytoprotection induced by non-necrotizing concentrations of HCl in rats. A dose of 100 mg/kg of CIM was administered once, or twice a day for 5 days intraperitoneally. To study the effect of CIM on HCl-induced damage, 0.6 N HCl was given orally one hour after the last administration of CIM. To study the effect of CIM on adaptive cytoprotection, 0.35 N HCl was given orally one hour after the last administration of CIM. Fifteen minutes later, 0.6 N HCl was given orally. Thirty minutes after the administration of 0.6 N HCl, the stomach was removed and ulcer indices were calculated. Pretreatment with CIM did not prevent 0.6 N HCl induced gastric damage. Prior administration of 0.35 N HCl significantly reduced ulcer indices caused by 0.6 N HCl. Short or long term treatment with CIM did not have significant effects on the reduction of ulcer indices. These results suggest that CIM at an antisecretory dose neither acts as a protective agent nor modulates the protective process of the gastric mucosa.

Adaptation, Physiological↗

The glucoamylase cDNA from Aspergillus oryzae: its cloning, nucleotide sequence, and expression in Saccharomyces cerevisiae.

A cDNA for Aspergillus oryzae glucoamylase was cloned, using oligodeoxyribonucleotide probes derived from amino sequences of peptide fragments of the enzyme. The glucoamylase cDNA, when introduced into Saccharomyces cerevisiae, directed the secretion of active glucoamylase into the culture medium. The complete nucleotide sequence of the cDNA contained an open reading frame encoding 612 amino acid residues. Comparative studies with other fungal glucoamylases showed homologies of 67% with A. niger and 30% with Rhizopus oryzae of the deduced amino acid sequences. In the five conserved regions reported in other fungal glucoamylases, the levels of homologies between those regions of A. oryzae and A. niger enzymes were much higher (78-94%). A. oryzae glucoamylase contained no peptide region abundant in threonine and serine residue (TS-region), like that proposed to adsorb onto raw starch in A. awamori var. kawachii glucoamylase.

Amino Acid Sequence↗

Establishment and biochemical properties of cis-diamminedichloroplatinum(II)-resistant A549 lung cancer cells.

A 6.2-fold cis-diamminedichloroplatinum(II) (CDDP) resistant human lung cancer cell line (A549/CDDP5), which was capable of proliferating in the presence of 5 microM CDDP, was developed. Compared to the parent cell line, A549/CDDP5 subline had a significantly longer doubling time, increased population of S phase, enhanced sensitivity to 5-FU and elevated activities of dTMP synthase (EC 2.1.1.45) and thymidine kinase (EC 2.7.1.21) by 5.4- and 2.0-fold of the parent cells. These results suggest that the capacity of dTMP synthesis might have an important role in the acquisition of CDDP resistance of A549 cells.

Cell Division↗

[Adriamycin, cisplatin and etoposide combination chemotherapy in non-small cell lung cancer].

Nineteen patients with non-small cell lung cancer (eight patients with adenocarcinoma, nine patients with squamous cell carcinoma, one patient with large cell carcinoma and one patient with sarcoma) who had not received previous chemotherapy were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cisplatin (80 mg/m2, i.v., on day 1) and etoposide (70 mg/m2, i.v., on day 1-5). This chemotherapy regimen was repeated as long as possible for patients in whom PR was induced. Among all patients, CR was induced in none and 6 showed a PR (response rate 32%). However, 4 (56%) squamous cell carcinoma patients also showed PR. The median response duration in 6 PR patients was 28 weeks, and the median survival time in all patients was also 28 weeks. Mild to severe hematologic toxicities were induced and one patient died during myelosuppression. However almost all cases were reversible. Other toxicities included alopecia, nausea/vomiting, diarrhea, stomatitis, peripheral neuropathy and myocardial infarction which were reversible and manageable. The APVp therapy may be a valuable regimen for non-small cell lung cancer, especially squamous cell carcinoma.

Adult↗

[Therapeutic approach and associated problems of advanced liver tumors in children based on nuclear DNA ploidy pattern].

We evaluated the therapeutic approach and its associated problems in 14 hepatoblastomas (HB) and 3 hepatocellular carcinomas (HCC) based on the ploidy patterns determined from paraffin-embedded tissues by flow cytometry. Aneuploid pattern was seen more frequently in the patients with poorly differentiated and immature types of HB, and HCC. It was also observed in patients with tumors showing microscopic vessel invasion, and in patients showing resistance to the therapeutic approach. Among 4 patients with combined epithelial components of HB, 2 patients' tumors revealed both the aneuploid and diploid patterns and their prognoses were poor. The prognoses of patients with tumors showing the aneuploid pattern were significantly poorer. From our study we concluded that careful attention should be pain to the heterogeneity of these tumors and that more aggressive treatment for tumors showing aneuploid pattern should be developed.

Child↗

[Study on the clinical usefulness of NCC-ST-439 in breast cancer].

We investigated the usefulness of NCC-ST-439, a new tumor marker in breast cancer. The positive rate of NCC-ST-439 in cases of primary breast cancer was 46.9%. In cases of primary breast cancer, there were no significant differences in average and positive rate among each group of patient age, tumor size, number of metastatic node, clinical stage and status of hormone receptor (ER, PgR). The positive rate of NCC-ST-439 in early breast cancer was as high as that in advanced case. NCC-ST-439 had better sensitivity than CEA and CA15-3, and decreased in serum level after the curative operation. We concluded that NCC-ST-439 is useful as a screening marker for the detection of early breast cancer and as a post operative monitoring marker for the surveillance of the recurrence.

Antigens, Tumor-Associated, Carbohydrate↗

[Clinical study of eel calcitonin for relief of pain from metastatic bone lesions].

Thirty patients with bone metastasis were treated with eel calcitonin (CT) to relieve severe pain from metastatic bone lesions. Patients were two males and twenty-eight females with a mean age of 52.8. CT was administered intramuscularly in twenty-seven patients and intravenously in three. CT was effective on 55.6% of patients to reduce severe bone pain but did not decrease the amount of analgesics in most patients. Serum Ca and P were not changed markedly. As side-effects, two patients complained of nausea and vomiting after administration of CT but they weren't severe. These results indicate that CT is quite useful drug for relief of severe bone pain from metastatic lesions in patients with breast or digestive tract carcinomas.

Adult↗

[A case of second-degree atrioventricular block caused by high dose cisplatin treatment].

A 56-year-old man was admitted to our hospital because of stage IV squamous cell carcinoma of the lung. He was treated with two courses of high dose cisplatin (40 mg/m2/day, day 1-5). On day 4 of each course, a second-degree atrioventricular block was observed, which disappeared after cisplatin treatment. This case suggests that, although the cardiotoxicity caused by cisplatin is believed to be rare, one should take special care in high dose usage.

Carcinoma, Squamous Cell↗

[Two cases of Trichosporon beigelii pneumonia in immunocompromised hosts].

Two cases of Trichosporon beigelli pneumonia in severely immunocompromised patients are reported. At autopsy, Trichosporon beigelii was detected in all lobes in one patient who had a small cell lung cancer. Polymycotic infection involving Trichosporon beigelii and Aspergillus was proved in the other patient who had a non-Hodgkin's lymphoma. Miconazole therapy was not effective against Trichosporon beigelii infection in both cases. Although diagnosis and management are difficult, Trichosporon beigelii must be considered as a cause of visceral opportunistic fungal infection.

Aged↗

Regulation of reversible binding of smg p25A, a ras p21-like GTP-binding protein, to synaptic plasma membranes and vesicles by its specific regulatory protein, GDP dissociation inhibitor.

We have previously purified from bovine brain cytosol a novel regulatory protein for smg p25A, a ras p21-like GTP-binding protein. This protein, named smg p25A GDP dissociation inhibitor (GDI), regulates the GDP/GTP exchange reaction of smg p25A by inhibiting the dissociation of GDP from and thereby the subsequent binding of GTP to it. We have also previously found that smg p25A is mainly localized in presynaptic plasma membranes and vesicles and moderately in presynaptic cytosol in rat brain synapses. In this paper, we have studied the possible involvement of smg p25A GDI in the localization of smg p25A in the cytosol, plasma membranes, and vesicles in rat brain synapses. Both the GDP- and GTP-bound forms of smg p25A bound to the synaptic membranes and vesicles. smg p25A GDI inhibited the binding of the GDP-bound form of smg p25A, but not that of the GTP-bound form, to the synaptic membranes and vesicles. Moreover, smg p25A GDI induced the dissociation of the GDP-bound form, but not that of the GTP-bound form, of both endogenous and exogenous smg p25As from the synaptic membranes and vesicles. smg p25A GDI made a complex with the GDP-bound form of smg p25A with a molar ratio of 1:1, but not with the GTP-bound or guanine nucleotide-free form. These results suggest that smg p25A reversibly binds to synaptic plasma membranes and vesicles and that this reversible binding is regulated by its specific GDI.

Animals↗

Inhibition of the ras p21 GTPase-activating protein-stimulated GTPase activity of c-Ha-ras p21 by smg p21 having the same putative effector domain as ras p21s.

ras p21 GTPase-activating protein (GAP) has been proposed to interact with the putative effector domain of ras p21s, and smg p21, a ras p21-like guanine nucleotide binding protein (G protein), has been shown to have the same amino acid sequence as ras p21s in this region. In the present studies, we examined the effects of ras p21 GAP on the GTPase activity of smg p21 purified from human platelets, of smg p21 on the ras p21 GAP-stimulated GTPase activity of c-Ha-ras p21 purified from Escherichia coli, and of c-Ha-ras p21 on the smg p21 GAP1- or -2-stimulated GTPase activity of smg p21. ras p21 GAP stimulated the GTPase activity of c-Ha-ras p21 but not that of smg p21. The GTP-bound form of smg p21, however, inhibited the ras p21 GAP-stimulated GTPase activity of c-Ha-ras p21 in a dose-dependent manner. The half-maximum inhibition by smg p21 was obtained at 0.4 microM which was more potent than previously observed for ras p21 (2-200 microM). The GDP-bound form also inhibited the ras p21 GAP-stimulated GTPase activity of c-Ha-ras p21, but the efficiency was 40-50% that of the GTP-bound form. smg p21 GAP1 and -2 stimulated the GTPase activity of smg p21 but not that of c-Ha-ras p21. c-Ha-ras p21 did not inhibit the smg p21 GAP1- or -2-stimulated GTPase activity of smg p21. These results indicate that ras p21 GAP interacts with smg p21 without the subsequent stimulation of its GTPase activity.

Blood Platelets↗

Purification and characterization from bovine brain cytosol of a protein that inhibits the dissociation of GDP from and the subsequent binding of GTP to smg p25A, a ras p21-like GTP-binding protein.

A novel regulatory protein for smg p25A, a ras p21-like GTP-binding protein, was purified to near homogeneity from bovine brain cytosol. This regulatory protein, designated here as smg p25A GDP dissociation inhibitor (GDI), inhibited the dissociation of GDP, but not of guanosine 5'-(3-O-thio)triphosphate (GTPgamma S), from smg p25A. smg p25A GDI also inhibited the binding of GTPgamma S to the GDP-bound form of smg p25A but not of that to the guanine nucleotide-free form. GDI did not stimulate the GTPase activity of smg p25A and by itself showed neither GTPgammaS-binding nor GTPase activity. GDI was inactive for other ras p21/ras p21-like GTP-binding proteins including c-Ha-ras p21, rhoB p20, and smg p21. The Mr value of GDI was estimated to be about 54,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, about 65,000 from the S value (4.5 S), and about 82,000 by gel filtration. The isoelectric point of GDI was about pH 5.6. The activities of GDI were killed by tryptic digestion or heat boiling. These results indicate that bovine brain cytosol contains a regulatory protein for smg p25A that inhibits the dissociation of GDP from and thereby the subsequent binding of GTP to this protein.

Animals↗

Release of glutamate and aspartate from the visual cortex of the cat following activation of afferent pathways.

To test the possibility that glutamate (Glu) and aspartate (Asp) are transmitters at geniculo-cortical synapses in the visual cortex of the cat, we studied the release of amino acids from the striate cortex consequent upon visual and electrical stimulation of the dorsal lateral geniculate nucleus (LGN) and of the optic tract, using push-pull cannulae. We perfused a discrete region that included layer IV of the cortex with an artificial cerebrospinal fluid (aCSF) and analysed the amino acid content of these perfusates by high-performance liquid chromatography (HPLC). Significant increases only of Glu and Asp were obtained among all 17 amino acids measured, except for gamma-aminobutyric acid (GABA), during electrical stimulation of the afferent pathways. Visual stimulation by stroboscopic diffuse flashes of light increased the level of Glu released, but did not change that of Asp significantly. The level of GABA released did not change during diffuse flash stimulation, suggesting that the increase in Glu was not derived from cortical neurons. The increases in release of Glu/Asp were not seen when the perfusion medium was replaced with a Ca2(+)-free, high-Mg2(+)-containing solution. The basal (resting) release of Glu/Asp in the absence of stimulation also was decreased during perfusion with Ca2(+)-free/high-Mg2+ solutions. Intraocular injections of a sodium channel blocker, tetrodotoxin (TTX), resulted in a remarkable decrease in the basal release of Glu. These results suggest that Glu is released as in excitatory synaptic transmitter at least from terminals of geniculo-cortical afferents and Asp from axons of a certain type of visual cortical neuron.

Animals↗

The clinical features and prognosis of hepatoblastoma: follow-up studies done on pediatric tumors enrolled in the Japanese Pediatric Tumor Registry between 1971 and 1980. Part I. Committee of Malignant Tumors, Japanese Society of Pediatric Surgeons.

Retrospective follow-up studies were conducted on 101 cases of hepatoblastoma enrolled in the registry established by the Committee of Malignant Tumors of the Japanese Society of Pediatric Surgeons between 1971 and 1980. The disease was classified into the following 5 categories; namely, stages I, II, IIIA, IIIB and IV according to local involvement (factor C), vascular invasion (factor V), lymph node involvement (factor N), and distant metastasis (factor M). The results were analysed as the relation between two-year tumor-free survival rate (2YTFSR) and various factors. The overall 2YTFSR of 42 per cent was found to be related to the staging system, age and quality of resection, and our results indicated that cure could be achieved by complete resection of the tumor.

Antineoplastic Combined Chemotherapy Protocols↗

A monolayer culture of gastric mucous cells from adult rabbits.

A new method for the primary monolayer cultures of adult rabbit gastric mucous cells has been developed. Rabbit gastric mucosal cells were isolated with etylenediaminetetraacetic acid and collagenase. Cells were cultured in Coon's modified Ham's F-12 medium supplemented with 10% fetal bovine serum, 15mM HEPES buffer, antibiotics, and antimycotic. The cells reached confluency on days 3-4. Histochemically 92% of the cells contained PAS positive gramules (mucous cells), 3% of cells showed a strong reaction for succinic dehydrogenase activity (parietal cells), 2% of the cells showed positive granules by Bowie staining (chief cells), and G6PDH staining was positive in 5% of the cells (surface mucous cells). Fibroblasts were rarely seen until day 7 (less than 1%). Thus rabbit cultured gastric cells were considered to be mainly comosed of mucous neck cells. These cells produced prostaglandin (PG) E2 and PGI2. Quantitatively cultured cells synthesized 1.475 +/- 0.039 ng/mg protein/hour of PGE2 and 0.244 +/- 0.042 pg/mg protein/hour of PGI2. This relatively simple and convenient technique provides a useful model for the study of cellular functions of gastric mucosa.

6-Ketoprostaglandin F1 alpha↗

Fifteen years' experience of neuroblastoma: a prognostic evaluation according to the Evans and UICC staging systems.

Our policy of preoperative and postoperative adjuvant therapy of advanced neuroblastoma changed from mild to aggressive chemotherapy in 1978. In order to evaluate the clinical effects of this policy, 39 cases before 1977 and 37 cases after 1978 were retrospectively reviewed using the Evans and the International Union Against Cancer (UICC) staging systems. Both clinical stages (CS) and postsurgical histopathological stages (PS) of the UICC staging system showed an almost 100% cure rate in stages I (CSI, PSI) and II (CSII, PSII). The cure rates of CS III, PS IIIA, and PS IIIB cases were remarkably improved after 1978, but those of CS IV and PS IV cases remained extremely low. However, it was found that a disease-free survival rate of advanced neuroblastoma could be produced by complete resection of the tumor accompanied by adjuvant chemotherapy. In these conditions, we found that for predicting the prognosis of advanced neuroblastoma, the UICC staging system, especially the PS staging system, may be more rational than the Evans staging system.

Evaluation Studies as Topic↗

Improvement in prognosis of neuroblastoma through mass population screening.

Since April 1981, the city of Sapporo, Japan, has conducted a mass screening program to measure urinary vanillylmandelic acid and homovanillylic acid using high-performance liquid chromatography. This program was expanded to the entire island of Hokkaido in October 1987. Mass screening proved beneficial, resulting in an increase in patients diagnosed with neuroblastoma under 1 year of age from 17% to 66%, an increase in stage I cases from 9% to 26%, an increase in stage III cases from 9% to 32%, and an increase in the tumor resectability rate from 15.1% to 58%. These improvements raised the 5-year survival rate for neuroblastoma from 23% to 66.7%. An additional study of these mass screening cases using Shimada's classification showed a wide range of histopathological distribution, and it demonstrated the usefulness of such a program in identifying the tumors most in need of early treatment.

Adrenal Gland Neoplasms↗