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Biomedical subjects

M Shimoyama

Publications and source records attributed to M Shimoyama.

At least 109 records · Page 6Linked to original sources
PubMed1995

ADP-ribosylation of Arg28 and Arg206 on the actin molecule by chicken arginine-specific ADP-ribosyltransferase.

We reported previously on ADP-ribosylation of actins by chicken arginine-specific ADP-ribosyltransferase in vitro and in situ and the inhibition of actin polymerization by this modification [Terashima, M., Mishima, K., Yamada, K., Tsuchiya, M., Wakutani, T. & Shimoyama, M. (1992) Eur. J. Biochem. 204, 305-311]. In the present study, we determined amino acid residues of ADP-ribosylation site(s) in globular (G-) and filamentous (F-) actins and examined the molecular basis of the modification of actin. Arginine-specific ADP-ribosylation occurred at Arg28 and Arg206 in G-actin, but only at Arg28 in F-actin. ADP-ribosylation of Arg206, located on the pointed end of the actin molecule, significantly blocked the interaction with deoxyribonuclease I. These results indicate that Arg206 in G-actin may be involved in actin polymerization. ADP-ribosylation of Arg28, located on the outer surface of actin molecule, did not affect the binding activity with myosin subfragment-1, that is thought to interact through the N-terminal amino acid residues of G-actin. ADP-ribosylation at both Arg28 and Arg206 of G-actin had no apparent effect on the intrinsic ATPase activity. We concluded from this study that ADP-ribosylation of Arg206 in G-actin causes the inhibition of actin polymerization, and that ADP-ribosylation of Arg28 occurs in F-actin.

Actins↗
PubMed1995

Assay of arginine-specific adenosine-5'-diphosphate-ribosyltransferase by capillary electrophoresis.

Using high-voltage capillary electrophoresis we detected ADP-ribosylarginine, a product of ADP-ribosylation reaction catalyzed by arginine-specific ADP-ribosyltransferase in the presence of NAD and L-arginine. The authentic ADP-ribosylarginine, detected by its ultraviolet absorbance at 254 nm, had a different retention time from NAD or nicotinamide. When the ADP-ribosylation reaction products were analyzed, the peak corresponding to ADP-ribosylarginine increased with incubation time and in an enzyme-dose-dependent manner. The lower limit of detection was 0.3 pmol, a value 100 times lower than that obtained with the reversed-phase high-performance liquid chromatography assay described previously. Using the capillary electrophoresis system, a thiol-independent ADP-ribosyltransferase activity was detected in chicken spleen cell membrane. Since the capillary electrophoresis assay for ADP-ribosylarginine is simpler, faster, and less expensive than the high-performance liquid chromatography assay, determination of arginine-specific ADP-ribosyltransferase activity in animal tissues will be facilitated.

ADP Ribose Transferases↗
PubMed1995

Low-dose granulocyte colony-stimulating factor enables the efficient collection of peripheral blood stem cells after disease-oriented, conventional-dose chemotherapy for breast cancer, malignant lymphoma and germ cell tumor.

Peripheral blood stem cells (PBSCs) were collected from 29 adult patients (median age 42 years, range 14-59 years) with breast cancer, germ cell tumor and malignant lymphoma after disease-oriented, conventional-dose chemotherapy combined with daily subcutaneous injections of low-dose (50 micrograms/m2 or 2 micrograms/kg) granulocyte colony-stimulating factor (G-CSF). The median number of colony-forming units-granulocyte macrophage (CFU-GM) collected in an apheresis was 2.37 (range 0-60.6) x 10(4)/kg body weight. Taking into consideration the minimum number of CFU-GM for hematopoietic reconstitution (at least 1 x 10(5) CFU-GM/kg), it was suggested that sufficient PBSCs could be collected by a few leukaphereses, although the cell yields of PBSCs tended to differ among the chemotherapeutic regimens. Twelve patients subsequently received high-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT), including four receiving PBSCT alone and eight both PBSCT and autologous bone marrow transplantation (BMT). When compared with the 20 patients who received high-dose chemotherapy followed by autologous BMT alone, the median day of recovery of a neutrophil count > 0.5 x 10(9)/l and a platelet count > 20 x 10(9)/l was significantly shortened in those who received PBSCT (9 vs 12 days; P < 0.01 and 14 vs 30.5 days; P < 0.001), resulting in a lower platelet transfusion requirement (4.5 vs 9; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

[Proton MR spectroscopy in patients with unilateral temporal lobe epilepsy].

The authors assessed proton magnetic resonance spectroscopy (1H-MRS) in patients with unilateral refractory temporal bole epilepsy. The subjects consisted of 20 patients (those with brain tumors, trauma, malformations or definite organic lesions were excluded) and 10 normal volunteers. 1H-MRS and MRI were performed using a 1.5 tesla machine. 1H-MRS was achieved using point-resolved spectroscopy (PRESS) or the stimulated echo acquisition mode (STEAM), and a 3 x 3 x 3 cm volume of interest was positioned at the hippocampus. N-Acetyl-aspartate (NAA) and choline-containing substance (Cho) signals were evaluated. The results showed decreased NAA and elevated Cho or asymmetry of both NAA and Cho in the epileptogenic focus in 19/20 cases. The reductions in NAA presumably reflect neuronal loss, while the elevation of Cho probably represents membrane break down within the lesion. These abnormalities were observed in 19/20 cases (95%), whereas abnormal magnetic resonance imaging was detected in only 6/20 (30%) of the patients. Thus, 1H-MRS appears to be a useful, non-invasive modality for evaluating metabolic changes in epileptogenic foci, and these metabolic changes can serve as a more sensitive indicator than magnetic resonance imaging.

Adolescent↗
PubMed1995

[Remnant-like particles-cholesterol (RLP-C) assay and its clinical application to lipid tests in a postprandial as well as fasting state].

It was during the past few years that postprandial hyperlipidemia is believed to be more closely related to a risk for coronary artery disease. However, the high variability in the postprandial triglyceride (TG) levels could have made overlooked such diagnostic value in estimating an individual's risk for coronary artery disease. To minimize the impact of such variability, the remnant lipoproteins, TG-rich lipoproteins, might be measured in cholesterol using remnant-like particles (RLP-C) assay as a more reliable marker. In place of the previous cholesterol reagent (CHOD-Iodine) in RLP-C assay, the RLP-C assay was improved by employing a new cholesterol reagent (POD-EMSE). The correlation between these two assays was high (r = 0.978). The variations in RLP-C levels in healthy normolipidemic subjects was within 7.5mg/dl in a day. In oral-fat loading test, the variations of RLP-C levels in healthy subjects were also within 7.5mg/dl. However, patients with coronary artery disease showed much higher levels (over 7.5mg/dl) of RLP-C during the test. In conclusion the RLP-C assay can be used for the measurement of remnant lipoproteins in serum prepared from the fasting as well as postprandial states for predicting subjects who may be at risk of coronary artery disease.

Adult↗
PubMed1995

Role of Epstein-Barr virus in pleural lymphomagenesis.

Longstanding inflammation in chronic pyothorax (CP) plays a role in the development of pleural lymphoma; therefore, in 1987, the term pyothorax-associated lymphoma (PAL) was proposed. A recent study showed in the tumor cells of a limited number of patients, the presence of the Epstein-Barr virus (EBV) genome together with the expression of latent infection genes in the tumor cells of PAL. The purpose of the present study is to evaluate an association of EBV with PAL in a large number of patients. In addition, the presence of the EBV genome was examined in cases with CP without PAL. Histologic, immunohistochemical studies, and analyses by polymerase chain reaction (PCR) and in situ hybridization method for EBV were performed on 34 PAL and 16 CP collected by nationwide study. Median age of the patients in both diseases was approximately 70 years with a marked preponderance in men. Mean duration of CP in patients with CP alone and with CP complicated with PAL was 33 and 37 years, respectively. Histologically all PAL were non-Hodgkin's lymphoma, with immunoblastic type being the most common. Immunohistochemistry revealed 28 of 34 PAL to be B-cell type. Combined PCR, in situ hybridization method, and immunohistochemistry showed that the EBV genome was detected in lymphoma cells in 85% of PAL with almost constant expression of latent membrane protein-1. The EBV genome was detected by PCR in only one of 16 CP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Cloning and expression of cDNA for arginine-specific ADP-ribosyltransferase from chicken bone marrow cells.

Two arginine-specific ADP-ribosyltransferase cDNAs (designated AT1 and AT2) were cloned from chicken bone marrow cells. Each cDNA encodes a different peptide of 312 amino acid residues. Homology of deduced amino acid sequences between AT1 and AT2 was 78.3%. We found all six combined peptide sequences of 222 amino acid residues derived from purified chicken heterophil ADP-ribosyltransferase (Mishima, K., Terashima, M., Obara, S., Yamada, K., Imai, K., and Shimoyama, M. (1991) J. Biochem. (Tokyo) 110, 388-394) in the deduced amino acid sequence of AT1, with two amino acid mismatches. Arginine-specific ADP-ribosyltransferase activity was detected in culture medium of COS 7 cells transiently transfected with AT1 cDNA, while activity from the cells transfected with AT2 cDNA was found in both culture medium and cell lysate. AT1 transferase required 2-mercaptoethanol for the activity. The activity was inhibited in the presence of NaCl while AT2 enzyme was activated by either agent. On zymographic in situ gel analysis, estimated molecular masses of the AT1, AT2 and purified chicken heterophil transferases were 32, 34, and 27.5 kDa, respectively. Northern blot analysis with specific probes to AT1 or AT2 cDNAs revealed about a 1.5-kilobase message in chicken bone marrow cells but no signals were observed in heterophils, spleen, and liver of chicken or human HL-60 cells. Highly conserved regions were observed among the deduced amino acid sequences of AT1, AT2, rabbit skeletal muscle transferase, and rodent T-cell surface antigen RT6s.

ADP Ribose Transferases↗
PubMed1994

The effect of different routes of administration on the metabolism of morphine: the disposition of morphine and its metabolites after topical application.

The disposition of morphine (MOR) and its metabolites in the rabbit was measured after topical administration of its hydrochloride salt (MOR.HCl), and their time course was compared with those after intravenous and oral administration. The area under the plasma concentration-time curve (AUC) ratio of metabolites/MOR after the topical application of MOR.HCl was similar to that after intravenous injection, but differed from that after oral administration. Pharmacokinetic parameters of the disposition of MOR and its metabolites were obtained by a general curve fitting of the time course of plasma concentrations of these compounds after intravenous injection of MOR.HCl and its metabolites, respectively. On the other hand, the time courses of plasma concentrations of the metabolites after intravenous, oral, and topical administration of MOR.HCl were simulated using a simple compartment model without consideration of enterohepatic circulation and the pharmacokinetic parameters obtained as above. The resulting curves of the metabolites agreed well with the observed values except for those after oral administration. These results suggest that no first-pass metabolism of MOR.HCl occurs after percutaneous administration, and that topical administration of this salt is more advantageous than oral administration in terms of bioavailability.

Administration, Oral↗
PubMed1994

Automodification of arginine-specific ADP-ribosyltransferase purified from chicken peripheral heterophils and alteration of the transferase activity.

Auto-ADP-ribosylation of arginine-specific ADP-ribosyltransferase purified from chicken peripheral heterophils was investigated. When the purified ADP-ribosyltransferase was analyzed with sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by Coomassie brilliant blue staining, two protein bands corresponding to the molecular masses of 27.5 and 28.0 kDa were detected. Both proteins were auto-ADP-ribosylated when they were examined by zymographic in situ gel assay without exogenous acceptor for ADP-ribose transfer. The automodification was inhibited by the acceptor, arginine or agmatine, and an inhibitor of arginine-specific ADP-ribosyltransferase, novobiocin. The ADP-ribose-transferase linkage was labile in 0.5 M hydroxylamine (pH 7.5). The automodified transferase was not chased by a large excess of nonradioactive NAD and did not catalyze transfer of its ADP-ribose to p33, an endogenous substrate protein for the transferase in heterophils, therefore, that automodified transferase cannot serve as an intermediate in ADP-ribosylation of other proteins. Auto-ADP-ribosylated transferase showed higher activity than did the unmodified transferase in catalyzing ADP-ribosylation of the basic acceptor such as poly(L-arginine) and p33 while to ADP-ribosylate the acidic proteins such as casein, the modified transferase was less active. Automodification of the transferase decreased polyanion-induced ADP-ribosylation of p33. Automodification of arginine-specific ADP-ribosyltransferase apparently alters the specificity of its own substrate.

Adenosine Diphosphate Ribose↗
PubMed1994

Target protein for eucaryotic arginine-specific ADP-ribosyltransferase.

Among ADP-ribosyltransferases reported in eucaryotes, arginine-specific transferases from turkey erythrocytes, chicken heterophils and rabbit skeletal muscle have been purified and extensively studied. They were reported to modify a number of proteins in vitro. ADP-ribosylation of Ha-ras-p21 and transducin by the turkey erythrocyte transferase inhibits their GTPase and GTP-binding activities. Chicken heterophil enzyme modifies several substrate proteins for protein kinases and decreases the phosphate-acceptor activity. Rabbit skeletal muscle Ca(2+)-ATPase is inhibited by ADP-ribosylation catalyzed by the muscle transferase. Three transferases all ADP-ribosylate small molecular weight guanidino compounds such as arginine, arginine methylester and agmatine and poly-L-arginine and nuclear histones. However, the observation that muscle transferase did not ADP-ribosylate casein or actin, both of which can be modified by the heterophil transferase under the same conditions indicates that substrate specificity of these two enzymes are different. Substrate-dependent effects were observed with polyions of nucleotides such that polyanions stimulate the ADP-ribosylation of possible target protein, p33 by chicken heterophil transferase but has no effect on the modification of casein by the same enzyme.

Animals↗
PubMed1994

Uptake of remnant like particles (RLP) in diabetic patients from mouse peritoneal macrophages.

To investigate whether the remnant like particles (RLP), separated from serum by an immunoaffinity gel mixture of anti-apo B-100 and apo A-I monoclonal antibodies, are relevant to the initiation or progression of atherosclerosis, the incorporation of RLP into mouse macrophages was studied using histochemical and biochemical techniques. Remnant lipoproteins such as RLP are reported to contain a large quantity of chyloniron and very low density lipoprotein (VLDL) remnants, especially in diabetic patients. The RLP separated from the sera of 32 diabetic patients were found to be predominantly taken up into macrophages harvested from mouse abdominal cavities by the staining method applying oil red O. Furthermore, using 14C-oleate to prove the uptake of lipoproteins by macrophages, the uptake of RLP-VLDL, a VLDL fraction of RLP by ultracentrifugation, was the next highest to that of the oxidized LDL, which suggests that RLP-VLDL is also aggressively taken up by macrophages. The degree of uptake of RLP-VLDL by macrophages was positively correlated with HbA1c of these diabetic patients (r = 0.556, p < 0.01), irrespective of the ways of the treatment of diabetes. In conclusion, RLP can contribute to the foaming of macrophages, which in turn may explain the acceleration of atherosclerosis in diabetic patients.

Aged↗
PubMed1994

Concurrent cisplatin-etoposide chemotherapy plus thoracic radiotherapy for limited-stage small cell lung cancer. Japanese Lung Cancer Chemotherapy Group in Japanese Clinical Oncology Group.

A recent approach in the treatment of limited-stage small cell lung cancer (LDSCLC) has involved a combined modality of chemotherapy and chest irradiation. In using the modality, the study of scheduling methods for combining chemotherapy and radiotherapy should lead to other trials of combined modalities against LDSCLC since it is the most basic issue to be evaluated. We have thus conducted a multicenter phase II trial of concurrent cisplatin-etoposide (PVP) chemotherapy and radiotherapy for LDSCLC to determine the effects of the concurrent administration of a PVP regimen and chest irradiation on response rate, relapse, survival and treatment toxicity. The chemotherapy regimen consisted of a four-week cycle: cisplatin (80 mg/m2, given intravenously on day 1) and etoposide (100 mg/m2, given intravenously on days 1-3). This cycle was given four to six times within six months. Chest irradiation to the primary tumors at both the hili and the mediastinum was administered in standard fractions on days 2-12 in the first cycle of chemotherapy and on days 29-47 in the second cycle, with a total dose of 40-50 Gy. Prophylactic cranial irradiation was performed among complete remission (CR) or good partial remission (PR) patients after completion of the concurrent therapy. A total of 66 patients were entered into the trial and 59 were evaluated. The concurrent therapy induced an overall response rate of 94.9% in 59 patients: 24 patients, 40.7% CR, 32 patients, 54.2% PR. The median response duration was 8.7 months, and the median survival time for all eligible patients was 14.8 months. The percentage of patients with two-year survival periods was 20. A local relapse within the irradiated area was seen in only 22% of relapse patients. Brain metastases occurred in 24% of patients. Four of 32 patients treated with prophylactic cranial irradiation had brain metastases. Toxic effects, chiefly grades 3 and 4 leukopenia, as established by the World Health Organization, were detected in all treated patients. Other toxicities, including radiation-induced esophagitis and pneumonitis, were deemed almost acceptable. We concluded concurrent treatment of a PVP regimen with chest irradiation to be a feasible and beneficial therapy with an efficacy compatible to that of other published reports. The outcome of this protocol warrants further investigation to determine the optimal type of schedule for concurrent chemoradiotherapy against LDSCLC.

Adult↗
PubMed1994

[Late phase II study with 21-consecutive-day oral administration of etoposide for malignant lymphoma].

We conducted a multi-institutional (33 institutes), late phase II study with a 21-consecutive-day oral administration of etoposide for malignant lymphoma. Patient entry criteria were either those refractory to standard therapies or those for whom no appropriate therapy was available. A once-daily dose of 50 mg/body was administered for 21 consecutive days. Of the evaluable 83 among 88 entry patients, the overall response rate was 53.0% (44/83), including 10 CR; 52.5% (42/80, 9 CR) with non-Hodgkin's lymphoma and 100% (2/2, 1 CR) with Hodgkin's disease. Regarding abnormal laboratory findings, myelosuppression was observed; the incidence rates of leukopenia (23.3% with Grade 3), neutropenia (32.6%), hemoglobin decrease (17.4%) and thrombocytopenia (4.7%) were 70.9%, 65.1%, 54.7% and 19.8%, respectively. Major adverse reactions and their incidence were: anorexia 43.0%, alopecia 37.2%, nausea/vomiting 32.6%, fatigue 18.6%, stomatitis 15.1%, fever 7.0% and diarrhea 5.8%. Therefore, a 21-consecutive-day oral administration of 50 mg/body/day or 75 mg/body/day appears to be effective for the treatment of malignant lymphoma.

Administration, Oral↗
PubMed1994

Vortex-mixing-induced inactivation of arginine-specific ADP-ribosyltransferase activity and re-activation of the less-active form by dithiothreitol plus NaCl under anaerobic conditions.

We observed dilution/vortex-mixing-induced inactivation of arginine-specific ADP-ribosyltransferase purified from chicken peripheral polymorphonuclear granulocytes (heterophils) and re-activation of the less active form by dithiothreitol plus NaCl, under anaerobic conditions. The vortex-mixing-induced inactivation of the diluted enzyme was rapid; more than 85% of the enzyme activity was lost with 1-min vortex-mixing at room temperature. When the less-active form of the enzyme was treated with 10 mM dithiothreitol plus 0.2 M NaCl, under anaerobic conditions, more than 50% of the enzyme activity was restored. Putative mechanisms of the vortex-mixing-induced inactivation and dithiothreitol/NaCl-dependent re-activation of the arginine-specific ADP-ribosyltransferase are discussed.

ADP Ribose Transferases↗
PubMed1994

[Recent progress in the treatment of malignant lymphoma].

Recent progress in the chemotherapy for malignant lymphoma is reviewed. From the viewpoint of treatment, malignant lymphoma is classified into five major categories; aggressive lymphoma, indolent B-lymphoma, Hodgkin's disease, T-lymphoblastic lymphoma and adult T-cell leukemia-lymphoma (ATL). Based on the results of the clinical chemotherapy trials conducted by the cooperative oncology groups in Western countries and the Lymphoma Study Group (LSG) in Japan, the state of the art of chemotherapy for malignant lymphoma is described. In aggressive lymphoma of advanced stages, after establishment of CHOP therapy (first generation), better results were reported in the United States for single institute single-arm studies of non-cross resistant alternating multiagent chemotherapy (second generation) and high relative dose intensity chemotherapy (third generation). However, recent multicenter phase III studies, comparing CHOP with third generation regimens, revealed that CHOP remains the best available treatment, because of similar failure-free and overall survival with lower cost and lower severe toxicity. More recently, the results of the International Non-Hodgkin's Lymphoma Prognostic Factors Project were reported. Based on the number of the five unfavorable factors present, such as age, stage, LDH, performance status and the number of extranodal disease sites, a new predictive model "international index" for aggressive lymphoma was developed. Such predictive models based on prognostic factor analyses would be very useful in the design of future clinical trials in patients with aggressive lymphoma and in the selection of appropriate therapeutic approaches for individual patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Loss of poly(ADP-ribose) synthetase activity without change in arginine-specific ADP-ribosyltransferase activity by acid-treatment; application of the treatment to simple assay for transferase in the presence of poly(ADP-ribose) synthetase.

We investigated the effects of acid treatment (pH 3.5) on the activities of arginine-specific ADP-ribosyltransferase (mono(ADP-ribosyl)transferase) (EC 2.4.2.31) and poly(ADP-ribose) synthetase (EC 2.4.2.30) purified from chicken liver, and we observed that the former enzyme retained completely its activity while there was no evidence for activity of the latter enzyme. Kinetic parameters, including Km values for NAD and whole histones in the reaction catalyzed by acid-treated ADP-ribosyltransferase, were the same as those in the reaction catalyzed by non-treated enzyme. The stereospecificities of the reaction forming ADP-ribosylarginine by acid-treated and non-treated ADP-ribosyltransferases were indistinguishable. We made use of this acid treatment to determine ADP-ribosyltransferase activity in chicken and chick-embryo liver extracts, with a filter assay. The enzyme activities (means +/- S.D. for three separate experiments) of 1-year-old chicken and 13-day-old chick embryo livers were 372.7 +/- 80.20 and 110.6 +/- 27.22 nmol ADP-ribose/g wet liver per h, respectively. This acid treatment is useful for filter assay with labelled NAD of arginine-specific ADP-ribosyltransferase in the fraction containing poly(ADP-ribose) synthetase.

ADP Ribose Transferases↗