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Biomedical subjects

M Hagiwara

Publications and source records attributed to M Hagiwara.

At least 163 records · Page 9Linked to original sources

Discrepancy of protein kinase C translocation and platelet aggregation--immunocytobiochemical evidence.

We searched for possible relationships between platelet aggregation induced by 12-O-tetradecanoyl phorbol 13-acetate (TPA) or thrombin and the translocation of protein kinase C. Using monoclonal antibodies against subspecies of protein kinase C, we noted a predominant expression of the isozyme, type II, in human platelets (M. Watanabe, M. Hagiwara, K. Onoda, and H. Hidaka, 1988, Biochem. Biophys. Res. Commun. 152, 642). Analysis of the subcellular distribution of protein kinase C revealed that 65% of the kinase activity was present in the cytosolic fraction in unstimulated platelets, with the remaining activity in the membrane fraction. Treatment of platelets with 100 nM TPA resulted in a greater than 60% decrease in protein kinase C activity in the cytosolic fraction and a greater than 200% increase in the activity in the membrane fraction, within 10 min after treatment. Translocation of the enzyme was also found after treatment of platelets with thrombin, although the response was of lower magnitude than that induced by TPA. Similar results were obtained by immunoblotting using MC-2a, an anti-type II protein kinase C monoclonal antibody. We also examined localization of the enzyme, by electron microscopic immunocytochemistry. The presence of type II protein kinase C seemed to be localized mostly in hyaluromeres and not in granulomeres. When platelets were fixed just after the addition of TPA (within 1 min), protein kinase C was localized at the submembranal region with no remarkable change in shape but there was a decrease in the number of granules in the cytoplasma and the open canalicular system was dilated. We then investigated the effects of cytochalasin B, W-7, ML-9, and H-7 on TPA-induced platelet aggregation and the translocation of protein kinase C. W-7 and ML-9 potently inhibited platelet aggregation but none of these compounds hampered the translocation. Thus, activation of protein kinase C may not be a complete requirement for the initiation of platelet aggregation.

Antibodies, Monoclonal↗

Expression of protein kinase C isozyme in epidermal Langerhans cells of the mouse.

Protein kinase C (PKC) is encoded by a complex of a gene family, and its multiple isozymes are expressed in various mammalian tissues. We examined whether PKC is expressed in epidermal Langerhans cells (LC) of the mouse by using monoclonal antibodies specific to PKC I, PKC II, and PKC III isozymes (respective products of PKC genes gamma, beta, and alpha). Immunohistochemical and immunoblotting studies revealed that LC of adult C57BL/6 mice express PKC II, while PKC I and PKC III were not detected. In keratinocytes, none of the isozymes were detected. These results suggest that PKC II is a novel marker of LC and that it possibly plays a regulatory role in epidermal LC of the mouse in vivo.

Animals↗

Different expression of protein kinase C isozymes in pancreatic islet cells.

To elucidate differential roles of protein kinase C isozymes in pancreatic islet cells, the precise localization of the isozymes in rabbit and rat islet endocrine cells was investigated using monoclonal antibodies specific for three types of the enzyme. We detected strong immunoreactivity for the type III protein kinase C in B cells. Immunoreactivity for the type II enzyme was seen in A cells, and no apparent immunoreactivity for type I was observed in the islet cells. The expression of the type III protein kinase C in B cells was confirmed using rat insulinoma cells. The predominant expression of the type III enzyme in these cells was shown by immunoblotting. Moreover, on the basis of an enzyme-linked sandwich immunoassay, the levels of protein kinase C isozymes were determined in these cells. The significant amounts of the type III enzyme was detected, but the contents of the type I and II enzyme were under detectable level. These results suggest that the type III protein kinase C is involved in the regulation of insulin release in pancreatic B cells.

Adenoma, Islet Cell↗

Pharmacological activities of synthetic human cholecystokinin-33 of which tyrosine was sulfated by arylsulfotransferase.

The pharmacological activities of synthetic human CCK-33, in which a tyrosine molecule was sulfated by arylsulfotransferase, were investigated in the rat and the guinea-pig. The activities were compared with those of non-sulfated CCK-33 (CCK-33NS), CCK-8 and CCK-4. CCK-33 was about 100 fold more potent than non-sulfated CCK-33(CCK-33NS) but was about 20 fold less potent than CCK-8 in the contraction of the isolated gallbladder of the guinea-pig. In rat pancreatic secretion, intravenous CCK-33 and CCK-8 showed almost the same activity. The potency of each was about 1000 fold more than the individual potency of CCK-33NS, non-sulfated CCK-8 (CCK-8NS) and CCK4. There were no significant differences in gastric acid stimulatory activities among CCK-33, CCK-8, CCK-4, but the activities of CCK-33NS and CCK-8NS were less than those of CCK-33 and CCK-8, respectively. CCK-33 and CCK-8 produced a reduction in the intake of powder chow in doses of 10(-8) and 3 x 10(-8) mol/kg i.p., but CCK-33NS, CCK-8NS and CCK-4 did not. In conclusion, the activities of synthetic human CCK-33 are almost the same as those of CCK-8 on exocrine pancreatic secretion, gastric acid secretion and food intake, but less than CCK-8 on isolated gallbladder contraction.

Animals↗

Pharmacological activity of angiotensin-II modified by tyrosine sulfation.

An angiotensin-II analogue with a sulfated tyrosine residue was prepared by arylsulfotransferase treatment of synthetic human angiotensin-II. Its biological activities were studied in isolated smooth muscles, and its effect on blood pressure was determined. The sulfated angiotensin-II (AII-S) was about 15-30 fold less potent than angiotensin-II (AII) for ileum contraction and gallbladder contraction. The hypertensive potency of AII-S was about 30-fold less than that of AII.

Angiotensin II↗

Vasoactive intestinal polypeptide (VIP) stimulates fibrinolytic system in the rat.

We have studied the fibrinolytic effect of VIP in rats. Intravenous injection of VIP enhanced blood fibrinolytic activity in a dose-related manner. The euglobulin fraction obtained from intact rat plasma incubated with VIP did not produce an increase in fibrinolytic activity, while dextran sulfate (DS) and urokinase (UK) showed the activity. VIP solution placed on a plasminogen-rich fibrin plate did not show fibrinolysis. VIP had neither a plasminogen activator nor plasmin activity. VIP may release plasminogen activators into the blood.

Animals↗

[A clinical study on the usefulness of CT and MRI imaging in evaluating differential diagnosis and the degree of dementia in vascular dementia].

For the evaluation of differential diagnosis and estimation of the functional prognosis for vascular dementia (VD), the usefulness of computed tomography (CT) and magnetic resonance imaging (MRI) in detecting cerebro-vascular lesions was compared. Then the correlations between the degrees of mental function (Hasegawa's dementia rating scale: HDRS, activity of daily living: ADL, troublesome behaviors: TB) and the CT findings of vascular dementia were examined retrospectively. A hundred and seventeen dementia patients (male: 79 cases, female: 38 cases; mean-age 69.5 +/- 10.9 years old), diagnosed using DSM-III criteria, were scored according to Hachinski's ischemic score (I.S.) by clinical course and symptoms. Both MRI and CT were carried out on 56 dementia cases (male: 21 cases, female: 35 cases; mean-age 78.0 +/- 7.4 years old) at the chronic stage of the cerebro-vascular accidents to compare the detectiveness of vascular lesions. In 90 vascular dementia patients on whom only CT was carried out, the imagings were classified according to number, size, and localization. The correlation between these parameters and the degree of dementia were examined retrospectively. MRI was more useful and sensitive than CT for differentiating VD from DAT (dementia of Alzheimer type), since MRI was superior to CT in detecting small infarcts or lacunaes on the perforating area or white matter. Cases with positive findings on CT or MRI but clinically diagnosed as DAT by I.S. showed poorer ADL.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Relation between articulatory function and prosthesis. II-1. Longitudinal changing aspect of experimental palatal plate on muscular discharge of intrinsic muscles, tongue movement and mandibular movement before pronunciation].

As the first step of evaluating the kinematic function and the coordinative movement among articulatory organs, attention was focused on the palatal form in various factors related to the function of pronunciation on complete denture. After the experimental palatal plate was inserted into 13 natural dentitions in the age ranging from 21-24 years old, muscular discharge of intrinsic muscles, tongue movement and mandibular movement before pronunciation were recorded longitudinally. These data were comparatively evaluated with those before insertion of the experimental palatal plate, and the following conclusion were obtained. It has been made clear in this study that from the change of muscular discharge of intrinsic muscles, tongue movement and mandibular movement before pronunciation between before and after the insertion of the experimental palatal plate, correction aspect of the kinematic function and the coordinative movement among articulatory organs varied with point and method of articulation on each sound. And these facts suggested that it was necessary to diagnose and treat under consideration of the relation between the palatal form and articulatory function of tongue and mandible in removable prosthodontic treatment.

Adult↗

[Clinical evaluation on differential quantitation of human chorionic gonadotropin in testicular cancer].

In 113 patients with testicular germ cell tumor, the authors determined human chorionic gonadotropin (hCG) and the free beta subunit levels in sera by differential quantitation using homologous hCG-beta radioimmunoassay (RIA) and hCG enzyme immunoassay (EIA), respectively. In 59 patients with seminoma, intact hCG was positive in 6 patients (10.1%), whereas free hCG-beta was positive in 23 patients (39.0%). Syncytiotrophoblastic giant cells were detected in 4 cases out of 6 patients with positive intact hCG seminoma. Seventeen cases (28.8%) revealed positive free hCG-beta only without elevation of intact hCG. In 54 patients with nonseminoma, both intact hCG and free hCG-beta were positive in 36 cases (66%). In some cases, hCG-beta/hCG ratio increased up to 275% when recurrence of tumor developed. Molecular heterogeneity of hCG is closely related to proliferation and differentiation of hCG producing cells. The differential quantitation of intact hCG and hCG-beta using these two assays is valuable for clinical detection of molecular heterogeneity of hCG in testicular tumor.

Adolescent↗

[Continent urinary reservoir (CUR) for supravesical diversion. Pouchmetric properties of the colonic CUR and role of detubularization].

Eight patients underwent pouchmetry at 12 months after creation of the colonic continent urinary reservoir (CUR) for supravesical diversion. Pouchmetry revealed a volume-dependent tonic and phasic increase in pouch pressure in 3 patients who had undergone pouch construction using the partially detubularized right colon (Heineke-Mikulicz type closure after splitting the transverse and ascending colon at the antimesenteric border), whereas the volume-dependent phasic increase in pouch pressure was much less remarkable in 5 patients whose pouch was constructed using the totally detubularized right colon (Heineke-Mikulicz type closure after splitting the whole colonic segment including the cecum). The maximum pouch pressure at the pouch volume of 400 to 500 ml was significantly higher (p less than 0.05) in the partial detubularization group (46 +/- 6.0 cmH2O, mean +/- S.D.) than in the total detubularization group (12 +/- 1.6 cmH2O). In creation of the low-pressure pouch using the right colon, detubularization should extend to the whole portion of the isolated colonic segment.

Colon↗

[Intravesical bacillus Calmette-Guerin (BCG) in the treatment of superficial bladder cancer. Prospective randomized study for prophylactic effect].

We report the results of prospective randomized study which was designed to evaluate prophylactic effects of intravesical bacillus Calmette-Guerin (BCG) in the treatment of superficial transitional cell carcinoma of the bladder. A total of 44 cases who had no previous treatment of bladder cancer were randomly assigned to BCG or control groups after TUR. BCG group (23 cases) received intravesical instillation of 80 mg BCG (Tokyo strain) at one week intervals for 6 weeks, at two week intervals for 12 weeks, and at one month intervals for 20 months. In BCG groups, 3 cases had recurrence at 6 months and 1 case at 9 months, while the other 19 cases had no recurrent disease for 3 to 34 months (average 20.3 months) of follow-up. Control group (21 cases) had no further treatment after TUR. In control group, recurrence was seen at 3 months in 3 cases, at 6 months in 5 cases, at 9 months in 2 cases, at 12 months in 3 cases and at 21 months in 1 case. Only 7 cases in the control group were free of recurrence for 8 to 45 months (average 32.3 months) of follow-up. One and two year-recurrence rates in BCG group (18.4%, 18.4%) was significantly (p less than 0.01) lower than those in control group (63.2%, 68.9%). Among the complications of intravesical BCG were cystitis (76.2%), low grade fever (13.0%), and several days' persistent gross hematuria (13.0%). Most of these signs were self-limited and only in 2 cases instillation of BCG was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗

New analogues of rosaramicin isolated from a Micromonospora strain. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties.

Antibiotics 6108 A1, B, C and D, a new series of analogues of rosaramicin, were found together with rosaramicin, juvenimicin A4 and M-4365 A1 from the cultured broth of strain BA06108 which was assigned to be a new species of Micromonospora. 6108 A1 and C showed inhibitory activity against Gram-positive and some Gram-negative bacteria as potent as rosaramicin and exhibited low acute toxicity in mice. However, 6108 B showed less potent antimicrobial activity and 6108 D showed higher toxicity than those two antibiotics.

Animals↗

Expression of protein kinase C isozyme in human Langerhans' cells.

Protein kinase C is a key molecule controlling signal transduction into the cell. We recently reported that protein kinase C II isoenzyme, but neither I nor III isozyme, was expressed in epidermal Langerhans' cells of the adult mouse, and that none of these isozymes was detected in keratinocytes. In this study, we examined the expression of protein kinase C isozymes in human Langerhans' cells in vivo to see whether the expression of protein kinase C II isozyme in Langerhans' cells is a mouse-specific trait. Immunohistochemical studies revealed that protein kinase C II isozyme, but neither I nor III isozyme, was expressed in epidermal Langerhans' cells. None of these isozymes was detected in keratinocytes. These results suggest that the expression of protein kinase C II isozyme in epidermal Langerhans' cells in vivo is not a mouse-specific trait and that protein kinase C II isozyme is a novel phenotypic marker for epidermal Langerhans' cells in human as well as mouse skin.

Adolescent↗

[A case of complete remission obtained with etoposide cis-platinum combination chemotherapy in advanced testicular cancer].

A 49-year-old male patient was admitted to our hospital complaining of right scrotal mass. Serum tumor markers, HCG, beta-HCG and AFP, were all elevated. After right high inguinal orchiectomy, a pathological report revealed a mixed-type germ cell tumor, which was composed of choriocarcinoma, embryonal carcinoma and seminoma. Because of persistent elevation of these tumor markers, RPLND was performed. There were viable tumor cells in the dissected lymph node specimens. As pulmonary metastases developed after RPLND, the patient was treated with 3 courses of VAB-6 combination chemotherapy (vinblastine, actinomycin-D, cyclophosphamide, bleomycin and cis-platinum). Pulmonary metastases disappeared and tumor markers returned to normal range except for moderate elevation of serum HCG. Two months later, pulmonary metastases developed again with re-elevation of tumor markers. Four courses of EP salvage chemotherapy (etoposide and cisplatinum) were given. After EP chemotherapy, the patient was given etoposide orally for about 7 months. During this period, no abnormality was found except for slight elevation of serum HCG. Five months after discontinuing chemotherapy, serum HCG returned to normal and complete remission was obtained.

Antineoplastic Combined Chemotherapy Protocols↗

[The effect of cepharanthin on adjuvant chemotherapy induced bone marrow suppression in patients with breast cancer].

We studied the effect of Cepharanthin on bone marrow suppression induced by adjuvant chemotherapy in primary breast cancer patients in our hospital. The 36 patients with breast cancer were divided into two groups. Both groups were administered of MMC 20 mg intravenously on the day of radical operation. One group (23 patients) was administered of Cepharanthin 60 mg every day, but the other (13 patients) group was not administered. In the leukocyte count at 3 weeks after post operation, 82.6% (19 out of 23) of the patients who were administered cepharanthin kept more than 70% of pre-operation's leukocyte. On the other hand, only 46.1% (6 out of 13) of the patients who were not administered Cepharanthin kept more than 70% of pre-operation's leukocyte. The number of thrombocyte was not decreased in both groups. Side effects by Cepharanthin were not observed in this study.

Alkaloids↗

[An esophageal cancer with a renal metastasis that was detected and resected as the only focus of recurrence].

Reported is the case of an esophageal cancer presenting a renal metastasis, which was detected and resected as the only recurrent focus. The patient was a 62-year-old male. Five months after an esophagectomy, a left renal mass was detected by abdominal computerized tomography, and a rise in the SCC antigen. The urinary cytology suggested a renal metastasis of the esophageal cancer. Thus, chemotherapy and irradiation was performed, followed by a resection. The histology of the resected mass showed a squamous cell carcinoma, similar to the findings at the primary site. A renal metastasis of an esophageal carcinoma usually is latent, but not rarely found on postmortem examination. A nephrectomy for a renal metastasis of an esophageal cancer is rare, and only 8 cases are reported in the literature.

Antigens, Neoplasm↗

Beneficial effects of a new 5-lipoxygenase inhibitor on occlusion- and occlusion-reperfusion-induced myocardial injury.

Effects of a new 5-lipoxygenase inhibitor TZI-41127 (2-(4-hydroxy-3,5-dimethylphenyl)-5-methoxy-3-methylindole) on occlusion- and occlusion-reperfusion-induced myocardial injury were examined in rats and dogs. The occlusion-reperfusion-induced myocardial injury was produced by the occlusion of the left anterior descending (LAD) coronary artery for 90 min following 22 h reperfusion in Beagle dogs. The drug was orally administered twice in a dose of 30 mg/kg. The first administration was 2 h before the occlusion and the second one was 1 h after the start of the occlusion. Eighteen dogs were divided into two groups. Nine were for control which were administered the vehicle, and the other were for the drug treatment. One animal of each group died because of ventricular fibrillation. The risk area and the infarct area were measured 22 h after reperfusion. The risk area as percent of total ventricle was not different between the two groups. However, the infarct area as percent of the risk area was significantly less in the drug-treated group. Although the ventricular arrhythmias immediately after the reperfusion were not prevented by the drug treatment, the ventricular arrhythmias 22 h after the reperfusion were significantly less in the drug-treated group. The arterial blood pressure, the heart rate and the double product were not significantly different between the two groups. The infarct size induced by LAD occlusion in rats was also reduced by the pretreatment with TZI-41127. Thus, TZI-41127 has beneficial effects on occlusion- and occlusion-reperfusion-induced myocardial injury.

Animals↗