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Biomedical subjects

M Hoshi

Publications and source records attributed to M Hoshi.

At least 217 records · Page 12Linked to original sources

[Preoperative role of angiotensin II induced hypertension chemotherapy (IHC) in advanced gastric carcinoma].

To investigate the role of preoperative IHC in advanced gastric carcinoma, clinical, surgical and pathological stagings of 13 patients were analysed retrospectively. These patients were treated with a 3-drug combination of adriamycin, 5-fluorouracil and mitomycin C under angiotensin II induced hypertensive state. The response rate was 69.2% and mean survival time was 850.2 days. "Down staging" in surgical stage was observed in 5 out of 13 cases (38.3%), and in pathological stage 7 cases (53.8%) "down staging" was achieved. Mean survival time of "pathological down-staging" cases was significantly longer than that of "non-down-staging" cases (1039.6 vs 322.1 days, p less than 0.01, generalized Wilcoxon test). IHC brings selective increase of drug delivery to tumor tissue, and will be useful as preoperative chemotherapy in advanced gastric carcinoma in terms of "down staging".

Adult↗

Purification and characterization of a GTP-binding protein serving as pertussis toxin substrate in starfish oocytes.

In response to a meiosis-inducing hormone, 1-methyladenine (1-MA), starfish oocytes undergo reinitiation of meiosis with germinal vesicle breakdown. The 1-MA-initiated signal is, however, inhibited by prior microinjection of pertussis toxin into the oocytes (Shilling, F., Chiba, K., Hoshi, M., Kishimoto, T., and Jaffe, L.A. (1989) Dev. Biol. 133, 605-608), suggesting that a pertussis-toxin-sensitive guanine-nucleotide-binding protein (G protein) is involved in the 1-MA-induced signal transduction. Based on these findings, we purified a G protein serving as the substrate of pertussis toxin from the plasma membranes of starfish oocytes. The purified G protein had an alpha beta gamma-trimeric structure consisting of 39-kDa alpha, 37-kDa beta, and 8-kDa gamma subunits. The 39-kDa alpha subunit contained a site for ADP-ribosylation catalyzed by pertussis toxin. The alpha subunit was also recognized by antibodies specific for a common GTP-binding site of many mammalian alpha subunits or a carboxy-terminal ADP-ribosylation site of mammalian inhibitory G-alpha. An antibody raised against mammalian 36-/35-kDa beta subunits strongly reacted with the 37-kDa beta subunit of starfish G protein. The purified starfish G protein had a GTP-binding activity with a high affinity and displayed a low GTPase activity. The activity of the G protein serving as the substrate for pertussis-toxin-catalyzed ADP-ribosylation was inhibited by its association with a non-hydrolyzable GTP analogue. Thus, the starfish G protein appeared to be similar to mammalian G proteins at least in terms of its structure and properties of nucleotide binding and the pertussis toxin substrate. A possible role of the starfish G protein is also discussed in the signal transduction between 1-MA receptors and reinitiation of meiosis with germinal vesicle breakdown.

Amino Acid Sequence↗

Activation of MAP kinase and enhanced phosphorylation of the 350-kDa protein by mitogenic stimuli in quiescent Balb/c 3T3 cells.

In quiescent Balb/c 3T3 cells, competence factors such as platelet-derived growth factor and 12-O-tetradecanoylphorbol-13-acetate (TPA) activated MAP kinase, whereas progression factors such as insulin did not. Insulin was, however, capable of activating MAP kinase in cells pretreated with TPA. Moreover, TPA plus insulin activated MAP kinase more strongly and for a longer time period than did TPA alone. Treatment of Balb/c 3T3 cells with competence factors stimulated phosphorylation of the 350-kDa protein which was immunoprecipitated with antibodies against brain high-molecular-weight microtubule-associated protein MAP1, whereas insulin treatment did not stimulate the phosphorylation. Insulin could induce, however, further increase in the phosphorylation of the 350-kDa protein, when added simultaneously with TPA or added to the TPA-treated cells. The enhanced phosphorylation of the 350-kDa protein thus correlated with the MAP kinase activation. As insulin acts synergistically with TPA to induce initiation of DNA synthesis in the quiescent Balb/c 3T3 cells, it seems that activation of MAP kinase and enhanced phosphorylation of the 350-kDa protein are accompanied by the initiation of DNA synthesis.

Animals↗

Activation of microtubule-associated protein kinase by microtubule disruption in quiescent rat 3Y1 cells.

Treatment of quiescent rat fibroblastic cells (3Y1) with colchicine, a microtubule-disrupting agent, which could induce the initiation of DNA synthesis [Y. Shinohara, E. Nishida, and H. Sakai (1989) Eur. J. Biochem. 183, 275-280], activated a serine/threonine-specific protein kinase activity in cell extracts that preferentially phosphorylated exogenous microtubule-associated protein 2 (MAP2). Vinblastine treatment also activated the kinase activity, and taxol pretreatment inhibited the colchicine-induced activation of this kinase activity. The detailed biochemical characterization indicated that this microtubule disruption-activated MAP2 kinase was very similar or identical to the mitogen-activated MAP kinase in the substrate specificity and chromatographic behaviors on phosphocellulose, DEAE-cellulose, gel filtration, and phenyl-Sepharose. Pretreatment of the cells with protein synthesis inhibitors did not prevent the MAP2 kinase activation by colchicine. Moreover, phosphatase treatment inactivated the colchicine-activated MAP2 kinase activity. These data suggest that microtubule disruption activates MAP kinase through phosphorylation.

Animals↗

Microbial sensor system for nondestructive evaluation of fish meat quality.

A microbial sensor system consisting of the bacterium (Alteromonas putrefaciens) immobilized within membranes, a flow cell, an oxygen electrode, peristaltic pumps, a buffer tank, a thermostatically controlled bath and a recorder, was constructed for the nondestructive quality evaluation of bluefin tuna. The chemical compounds on fish meat surfaces which are the indicators of fish meat quality were rapidly determined by using the proposed sensor system. Fish meat quality was determined from the rate of current decrease of the sensor. Good correlations were obtained between fish meat quality and sensor response. One assay could be completed within one minute.

Animals↗

In vitro fertilization and development of bovine oocytes matured in serum-free medium.

This study was undertaken to investigate the effects of supplementation of serum (fetal calf serum), gonadotropins (LH, FSH, prolactin) and estradiol-17 beta (E2) to culture medium during in vitro maturation of bovine cumulus oocyte complexes on subsequent fertilization and development to the blastocyst stage in vitro. Serum supplementation during bovine oocyte maturation was not required but hormonal supplementation, gonadotropins (LH + FSH) and E2, enhanced the fertilizability and developmental ability of bovine oocytes matured in vitro. The addition of prolactin to maturation medium containing LH, FSH, and E2 did not further enhance frequencies of fertilization and development.

Animals↗

Studies of radioactivity produced by the Hiroshima atomic bomb: 1. Neutron-induced radioactivity measurements for dose evaluation.

This review summarizes measurements made of 152Eu and 60Co radioactivity induced by neutron radiation from the Hiroshima atomic bomb (A-bomb) with the goal of estimating the neutron dose released by the bomb. Prior to these measurements, A-bomb-irradiated specimens such as rocks and pieces of concrete, which had not been shielded were collected. The specific radioactivity obtained (in bequerels per gram of Eu or Co) were compared with those calculated from DS86 neutrons. Findings of usefulness of 152Eu data within 700 m ground range are reported and systematic differences between measured activities and calculations are discussed. The 152Eu data were also useful for the discussion of circular asymmetry, and there was no asymmetry within the experimental errors. This review also covers the similar difference found in 32P data, which were measured immediately after the A-bomb, along with the other 152Eu and 60Co data. The need for more measurements of 152Eu activity in samples farther away from the hypocenter in order to verify the DS86 calculations is also discussed.

Humans↗

Studies of radioactivity produced by the Hiroshima atomic bomb: 2. Measurements of fallout radioactivity.

Three studies of fallout measurements were reviewed for the discussion of possible radioactivity intake from the Hiroshima atomic bomb. The first study discussed correlations between enriched 234U and 137Cs specific activities from the measurement of soil samples collected in the "black rain" area. The second study measured 137Cs activity on the rock and roof tile samples collected in the hypocenter area immediately after the explosion. Some of the rock and roof tile samples collected near the hypocenter had a small but detectable amount of 137Cs activity. However, it has been determined that 137Cs exposure, for example, was negligible compared with DS86 dose estimates, since these activity levels were low. The third study detected 90Sr activity in some of the specimens of human bones exhumed on Ninoshima Island. This study compared the difference in activity between the bone head and shaft, with higher activities obtained in the bone head. This fact suggests a short intake period for this activity, however, the levels of 90Sr contamination were too low to allow a discussion of the exposure risks.

Humans↗

Thermoluminescence dosimetry of gamma rays using ceramic samples from Hiroshima and Nagasaki: a comparison with DS86 estimates.

This study reports gamma-ray doses measured using thermoluminescence (TL) dosimetry of atomic-bomb-exposed ceramic samples from Hiroshima and Nagasaki. Advances in the dosimetry of TL-sensitive minerals in the field of TL dating of archaeological and geological materials made it possible to measure a radiation dose of 10(-2) Gy. Ceramic samples such as tiles and bricks were collected from locations between 523 and 2,453 m from the hypocenter in Hiroshima and from between 731 and 1,565 m in Nagasaki. The gamma-ray dose estimates derived from these samples are compared with estimates from DS86. A significant discrepancy was noted between the doses measured for samples from Hiroshima and DS86 values. One possible cause of this discrepancy might be a secondary gamma-ray dose related to the neutron dose.

Ceramics↗

[Evaluation of induced hypertension chemotherapy (IHC) in ambulatory cancer patients].

To evaluate ambulatory cancer chemotherapy (ACC), the clinical response, dose intensity of anticancer drugs, toxicities, ambulatory periods (AP) and survival days (SD) were analysed among 20 outpatients with various types of advanced cancer who were continuously treated by angiotensin II-IHC for the past 10 years. ACC was assessed with a questionnaire by the patients themselves or their families. In advanced cancer, at first, it was essentially to obtain a get clinical response or to stabilize the condition for a while, and secondly, to upgrade the performance status in better grade. Although AP and SD were so differed with the individuals: AP/SD = 1692.2 +/- 1450.2 days/2075.0 +/- 1348.0 days for CR (n = 5); 1086.0 +/- 1160.2 days/1344.3 +/- 1143.7 days for PR (n = 10); and 197.3 +/- 129.2 days/471.7 +/- 362.5 days for PD (n = 3). Alopecia, nausea/vomiting and appetite loss were the most frequent side effects, though these were almost completely controllable by ACC. Patients and their families could be cooperated and allow receiving ACC. The key in fighting cancer is the formation of good human relationship between medical oncologists and patients (including their families) mutual confidence, and giving a sufficient explanation for therapies.

Adult↗

[Randomized controlled trial of induced hypertension chemotherapy (IHC) using angiotensin II human (TY-10721) in advanced gastric carcinoma (TY-10721 IHC Study Group Report)].

A randomized controlled trial was carried out to elucidate the enhancement of chemotherapeutic effect of induced hypertension chemotherapy (IHC) using newly synthesized angiotensin II human (TY-10721) in advanced gastric carcinoma under multi-institutional cooperation. In IHC, the drugs were administered under the hypertensive state induced and maintained by the continuous infusion of TY-10721. The regimen for the trial was as follows: adriamycin (33 mg/m2, day 3), 5-fluorouracil (330 mg/m2/day through day 1 to 3, 8 to 10) and mitomycin C (5 mg/m2, day 8). It was repeated every 4 weeks. Of 67 registered cases, 62 eligible patients were randomized to either IHC arm or control arm (non-IHC) in which the drugs were administered by an ordinary i.v. injection. According to the Criteria of Japanese Society for Cancer Treatment, the response rate of IHC group was 31.3% and that of non-IHC was 6.7% with statistically significant difference (p less than 0.05; chi 2c). There were 4 CR and 6 PR in 32 eligible cases of IHC and 2 PR in 30 of non-IHC. Clinical characteristics of patients and toxicities were not different in both groups. Clinical advantage of IHC was confirmed by increase of the response rate in this trial.

Adult↗

[The effect of induced hypertension chemotherapy using angiotensin II human in patients with advanced gastric carcinoma--a histopathological evaluation on the excised stomachs].

In an attempt to evaluate the effect of induced hypertension chemotherapy (IHC) using angiotensin II human, histopathological analysis was performed on stomachs excised from thirteen patients who had advanced gastric carcinoma and were submitted to presurgical cancer chemotherapy. IHC was introduced in randomly chosen eight patients and, in the remaining five patients, chemotherapy was designed under conventional conditions. A common regimen comprising 5-fluorouracil, adriamycin, mitomycin C was applied in both the IHC and non-IHC groups. The clinical effect in these patients, assessed prior to surgery, gave rise to the confirmation of three CR patients in the IHC group, while in the non-IHC, PR was the highest score. Histological examination illuminated a patient in the IHC group in whom no viable carcinoma cell proved to remain in the excised stomach, a state meeting the requirements for the highest (Grade 3) effectiveness according to the standard given by the Japanese Research Society for Gastric Cancer. In another two patients of the same group, the effect was Grade 2, i.e., the degeneration and loss of carcinoma cells in the major part of tumor. In contrast, the effect in the non-IHC group was Grade 1b at the highest, where chemotherapy-associated degeneration and necrosis did not predominate over one third of tumor area. Thus, the mean histological score was apparently higher in the IHC than in the non-IHC group, with a difference significant at p less than 0.05 by Wilcoxon's test. Patients clinically evaluated as effective tended to be so pathologically as well, as shown by Spearman's rank correlation test which gave a significant correlation between the clinical and pathological scores.

Adenocarcinoma↗

Microtubule-associated-protein (MAP) kinase activated by nerve growth factor and epidermal growth factor in PC12 cells. Identity with the mitogen-activated MAP kinase of fibroblastic cells.

Treatment of PC12 cells with either nerve growth factor (NGF), a differentiating factor, or epidermal growth factor (EGF), a mitogen, resulted in 7-15-fold activation of a protein kinase activity in cell extracts that phosphorylated microtubule-associated protein (MAP) 2 on serine and threonine residues in vitro. Both the NGF-activated kinase and the EGF-activated kinase could be partially purified by sequential chromatography on DEAE-cellulose, phenyl-Sepharose and hydroxylapatite, and were identical with each other in their chromatographic behavior, apparent molecular mass (approximately 40 kDa) on gel filtration, substrate specificity, and phosphopeptide-mapping pattern of MAP2 phosphorylated by each kinase. Moreover, both kinases were found to be indistinguishable from a mitogen-activated MAP kinase previously described in growth-factor-stimulated or phorbol-ester-stimulated fibroblastic cells, based on the same criteria. Kinase assays in gels after SDS/polyacrylamide gel electrophoresis revealed further that the NGF- or EGF-activated MAP kinase in PC12 cells, as well as the EGF-activated MAP kinase in fibroblastic 3Y1 cells resided in two closely spaced polypeptides with an apparent molecular mass of approximately 40 kDa. In addition, these MAP kinases were inactivated by either acid phosphatase treatment or protein phosphatase 2A treatment. These results indicate that MAP kinase may be activated through phosphorylation by a differentiating factor as well as by a mitogen. MAP kinase activation by EGF was protein kinase C independent; it reached an almost maximal level 1 min after EGF treatment and subsided rapidly within 30-60 min. On the other hand, NGF-induced activation of MAP kinase was partly protein kinase C dependent and continued for at least 2-3 h.

Adrenal Gland Neoplasms↗

Activation of a serine/threonine kinase that phosphorylates microtubule-associated protein 1B in vitro by growth factors and phorbol esters in quiescent rat fibroblastic cells.

We have previously found and characterized a mitogen-activated, serine/threonine-specific protein kinase that specifically phosphorylates microtubule-associated protein 2 (MAP2) in vitro, which we call here MAP2 kinase [Hoshi, M., Nishida, E. & Sakai, H. (1988) J. Biol. Chem. 263, 5396-5401; Hoshi, M., Nishida, E. & Sakai, H. (1989) Eur. J. Biochem. 184, 477-486]. In this study, we have found another serine/threonine-specific protein kinase that is activated by various mitogens. The activated kinase utilized microtubule-associated protein 1B (MAP1B) as the major substrate in vitro, so we tentatively call it MAP1B kinase (M1BK). M1BK was maximally activated 20-30 min after treatment of quiescent rat fibroblastic 3Y1 cells with epidermal growth factor (EGF), while MAP2 kinase was maximally activated within 5-10 min of EGF treatment. The EGF-activated M1BK was eluted at about 0.15 M NaCl on a DEAE-cellulose column, while the activated MAP2 kinase was eluted at about 0.1 M NaCl under the conditions used. The EGF-activated M1BK was eluted as a single peak just after the activated MAP2 kinase on an HPLC gel-filtration column. Histone, casein and ribosomal protein S6 were very poor substrates for the M1BK, while MAP2 and myelin basic protein were moderate substrates. The M1BK activity in cell extracts was inhibited by Ca2+, glycerol 2-phosphate and Zn2+, and slightly enhanced by heparin. These data suggested that M1BK is distinct from previously described mitogen-activated kinases such as MAP2 kinase, casein kinase II and S6 kinase. Pretreatment with cycloheximide or puromycin did not block the M1BK activation by EGF. Furthermore, incubation of the EGF-activated M1BK with acid phosphatase inactivated the kinase activity. Therefore, M1BK may be activated by phosphorylation in EGF-treated cells. In addition to EGF, 12-O-tetradecanoylphorbol 13-acetate, platelet-derived growth factor and insulin-like growth factor-I also induced the activation of M1BK in quiescent cells.

Animals↗

Trypsin-like hatching protease from mouse embryos: evidence for the presence in culture medium and its enzymatic properties.

Enzymatic properties of a protease involved in hatching of mouse embryos were examined. A trypsin-like protease, which most efficiently hydrolyzed t-butoxycarbonyl-Leu-Ser-Thr-Arg-4-methylcoumaryl-7-amide, was demonstrated in culture medium of mouse hatching embryos. The enzyme was strongly inhibited by diisopropyl fluorophosphate, phenylmethanesulfonyl fluoride, leupeptin, antipain, N alpha-tosyl-L-lysyl-chloromethane, soybean trypsin inhibitor, and Trasylol, but not or weakly inhibited by p-chloromercuribenzoic acid, EDTA, E-64, pepstatin, chymostatin, and bestatin, suggesting a trypsin-like serine proteinase. The protease activity in the medium gradually elevated during the course of hatching, whereas the embryo-associated activity showed no significant change. Furthermore, pyroglutamyl-Leu-argininal, the strongest inhibitor for the enzyme among peptidyl argininals, all of which are potent trypsin inhibitors, showed the strongest inhibition toward hatching. Thus, a trypsin-like protease secreted from hatching embryos into the culture medium may participate in mouse hatching, probably as a hatching enzyme.

Animals↗

Chymotrypsin-like enzymes are involved in sperm penetration through the vitelline coat of Ciona intestinalis egg.

In Ciona intestinalis, sperm penetration through the egg vitelline coat is an essential event of fertilization. We investigated whether trypsin- and chymotrypsin-like enzymes are involved in this event. Inhibitors and peptide substrates for chymotrypsin-like enzymes blocked the overall process of fertilization in a concentration-dependent manner. The inhibitory activity was specifically exerted on the step of sperm penetration. Chymotrypsin-like protease activity was identified in spermatozoa with the fluorogenic synthetic substrate Suc-Ala-Ala-Phe-AMC, which was the most effective substrate in blocking sperm penetration. These data indicate that a chymotrypsin-like protease activity is a sperm lysin of Ciona intestinalis.

Amino Acid Sequence↗