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Biomedical subjects

M Shimoyama

Publications and source records attributed to M Shimoyama.

At least 127 records · Page 7Linked to original sources

Comparison of acceptor protein specificities on the formation of ADP-ribose.acceptor adducts by arginine-specific ADP-ribosyltransferase from rabbit skeletal muscle sarcoplasmic reticulum with those of the enzyme from chicken peripheral polymorphonuclear cells.

We compared acceptor-protein specificities on the formation of ADP-ribose.acceptor adducts by arginine-specific ADP-ribosyltransferase (EC 2.4.2.31) purified from rabbit skeletal muscle sarcoplasmic reticulum (SR) with those of the enzyme purified from chicken peripheral polymorphonuclear cells (heterophils). Major differences are as follows: (1), p33 and beta/gamma-actin, preferential endogenous acceptor proteins for the modification by the heterophil enzyme (Mishima, K., Terashima, M., Obara, S., Yamada, K., Imai, K and Shimoyama, M. (1991) J. Biochem. 110, 388-394 and Terashima, M., Mishima, K., Yamada, K., Tsuchiya, M., Wakutani, T. and Shimoyama, M. (1992) Eur. J. Biochem. 204, 305-311) were not modified by the SR enzyme. (2), The modification of p33 by the heterophil enzyme was enhanced by addition of polyanions such as DNA while the protein did not function as acceptor for modification by the SR enzyme even in the presence of DNA. (3), To ADP-ribosylate endogenous substrate Ca(2+)-transporting ATPase (EC 3.6.1.38) of rabbit skeletal muscle SR, the SR ADP-ribosyltransferase required polycations such as poly(L-lysine), whereas the heterophil enzyme modified the ATPase in the absence of poly(L-lysine). These results suggest that vertebrate arginine-specific ADP-ribosyltransferase prefers its own acceptor protein for the modification. Some other properties of the SR and the heterophil ADP-ribosyltransferases were also compared.

Adenosine Diphosphate Ribose↗

Effect of low-power He-Ne laser on deformability of stored human erythrocytes.

This study was designed to investigate the effect of the He-Ne laser (continuous wave, lambda = 632.8 nm, 8.5 mW in power) irradiation on human erythrocyte deformability. Blood samples were obtained from hematologically normal adult donors by venipuncture. Red cells were washed and adjusted to 30% Ht with 0.9% NaCl solution (pH 7.00). Red cell solution samples were assigned to three groups. Each sample was divided into seven 3-ml working aliquots. The aliquots in Group I were irradiated for 0 (control), 1, 3, 5, 10, 15, and 30 min within 2 hr after sampling. The aliquots in Group 2 and Group 3 were stored at 5 degrees C for 24 and 36 hr, respectively, and received similar irradiations after 12 hr (in both groups), 24 hr (in Group 2), and 36 hr (in Group 3) from sampling. Red cell deformability was measured by the Nuclepore filter filtration and presented as the filter filtration rate (FFR). The deformability shown as FFR was unchanged in Group 1 (fresh cell group) from the control value, but improved significantly in Groups 2 and 3 (damaged cell groups) after the irradiation. These results suggested that the irradiation of low-powered He-Ne lasers improved cytoskeletal protein activities in damaged erythrocytes.

Cytoskeletal Proteins↗

Do low-power lasers change phase transition temperature of dipalmitoyl phosphatidylcholine (DPPC) membrane?

This study was designed to investigate the effects of the He-Ne laser (632.8 nm of wavelength, 8.5 mW in power, Senko Med. Co. Ltd., Tokyo, Japan) on the phase transition temperature of dipalmitoyl phosphatidylcholine (DPPC) membranes. Liposomal bilayers of DPPC (12.5 mM) were obtained with ultrasonification for 45 min at 40 degrees C and refrigerated for 2-3 days at 5 degrees C. The bilayers vesicle solution was divided into 3-ml working aliquots, which were assigned to three groups. The aliquots in Group 1 were used as controls without irradiation and the aliquots in Groups 2 and 3 were irradiated in 37 degrees C baths for 15 to 30 min, respectively. To determine phase transition temperature, optical density (%T; percent of permittance) of each aliquot was measured spectrophotomechanically at a wavelength of 440 nm while increasing its temperature at a rate of 0.5 degrees C every minute. Main phase transition temperatures in Groups 1, 2, and 3 were 41.54 +/- 0.23 degrees C (n = 10), 41.50 +/- 0.27 degrees C (n = 10), and 41.30 +/- 0.36 degrees C (n = 10), respectively. No significant difference between the nonirradiation and irradiation groups was established. These results suggest that irradiations of low-power He-Ne lasers up to 30 min do not change important physical characteristics of artificial DPPC membranes.

1,2-Dipalmitoylphosphatidylcholine↗

Artificial pneumothorax as a risk factor for development of pleural lymphoma.

An etiologically important role of chronic tuberculous empyema for development of pleural lymphocytic lymphoma of B-cell type has been suggested. To examine risk factors for development of pleural lymphoma in patients with chronic tuberculous empyema, a case-control study was carried out. Onset age of lung tuberculosis and empyema, presence of chemotherapy, surgical treatment, extent of empyema, presence of fistula, history of smoking, and height and weight of patients at first admission were compared in patients with empyema alone (70 controls) and empyema complicated with lymphoma (42 cases): the date of birth and sex were matched by group. The patients receiving artificial pneumothorax showed a significant increase in risk for development of pleural lymphoma (relative risk = 4.92, P < 0.05). We could not find any report describing development of pleural neoplasias in patients with chronic empyema receiving surgical resection of pleural pyogenic membrane. From these findings, it is suggested that artificial pneumothorax left chronic non-healing inflammation in the pleural cavity, which resulted in development of pleural lymphoma.

Adult↗

Differences in clinicopathological characteristics and major prognostic factors between B-lymphoma and peripheral T-lymphoma excluding adult T-cell leukemia/lymphoma.

A total of 541 consecutive patients treated between 1975 and 1985, 449 with B-lymphoma and 92 with peripheral T-lymphoma, excluding adult T-cell leukemia/lymphoma (ATL), termed peripheral non-ATL T-lymphoma, were analysed. Clinicopathological features that were predominantly associated with B-lymphoma were low and intermediate grades (defined by the Working Formulation), diffuse large cell type, stage II disease, bulky disease, favourable extranodal sites that are defined as a group of primary tumors such as the eye, Waldeyer's ring, thyroid, and stomach, while other features predominantly associated with peripheral non-ATL T-lymphoma were high grade pathology, diffuse mixed-cell and immunoblastic type, systemic "B" symptoms, poor performance status (PS), generalized lymphadenopathy, involvement of organs such as liver, skin, and nose, leucocytosis, and a high levels of serum alkaline phosphatase. The survival curve for B-lymphoma was better (P < 0.01) than that for peripheral non-ATL T-lymphoma. Multivariate analysis revealed that the major prognostic factors were pathology, stage, and primary site for B-lymphoma, while stage, PS, and total protein levels were important for peripheral non-ATL T-lymphoma. These results indicate that B- and peripheral non-ATL T-lymphomas appear to have different biological characteristics.

Adult↗

[Japan Clinical Oncology Group for cooperative cancer clinical trials and role of the statistical center in the management of cancer clinical trials].

In 1978, clinical investigators decided to collaborate on clinical trials through a "cooperative group" mechanism in order to promote multidisciplinary treatment of cancer under the auspices of a Grant-in-Aid for Cancer Research from the Ministry and Health and Welfare. This cooperative study group was formally renamed in 1990 and became "The Japan Clinical Oncology Group (JCOG)," and its Statistical Center was housed in the National Cancer Center Hospital. This paper introduces various JCOG activities and the role of the Statistical Center.

Clinical Protocols↗

[HTLV-I negative adult T cell leukemia; a case report of acute type].

We described a case of adult T cell leukemia (ATL) not associated with human T-cell leukemia virus type I (HTLV-I), a clinical entity that was first reported by Shimoyama et al. A 79-year-old male was admitted with anorexia and fever in October, 1989. Physical examination revealed marked hepatosplenomegaly and superficial lymphadenopathies. Hematological examination revealed marked leukocytosis (136,300/microliters) with abnormal lymphoid cells showing highly lobulated nuclei. Hypercalcemia (11.2 mg/dl) and elevation of lactic dehydrogenase were also recognized. Surface marker analysis showed that the abnormal lymphoid cells in the peripheral blood were positive for CD2 and CD4 but negative for CD8. Southern blot analysis of the DNA from peripheral blood leukemic cells revealed monoclonal rearrangement of T-cell receptor beta-chain gene. The clinical and hematological findings of the patient were compatible with those of acute type ATL, however, serum anti-HTLV-I antibody was negative and HTLV-I proviral DNA was not detected in the leukemic cells by Southern blot analysis. Furthermore, the polymerase chain reaction showed no integration of the HTLV-I proviral DNA in the leukemic cells.

Aged↗

[Acrodystrophic neuropathy in an alcoholic].

The patient was a 48-year-old alcoholic man with no contributory family history. At age 36 he had developed sensory dominant polyneuropathy with highly impaired temperature sensation and deep sensation in the lower extremities, recurrent ulcers of the toes, and sexual impotence. A sural nerve biopsy at this time revealed marked loss of myelinated fibers with relative preservation of the population of unmyelinated fibers. Subsequently, he developed muscle atrophy of the lower thighs, urinary incontinence, and Wernicke's encephalopathy, and became non-ambulatory at age 44. The peripheral nerve conduction findings suggested predominantly axonal degeneration. The entire course was characterized by alternative progression and partial recovery influenced by his alcohol intake and nutritional state. Alcoholic neuropathy is a major cause of solitary acrodystrophic neuropathy (ADN). Manifestations of autonomic and motor neuropathy are more marked in alcoholic ADN than in HSAN-I, and central nervous system involvement is the hallmark of alcoholic ADN. In the treatment of patients with alcoholic ADN, attention should be paid to diabetes mellitus, malnutritional state, and vitamin deficiency, which frequently complicate alcoholism.

Alcoholism↗

Adjuvant chemotherapy for completely resected stage III non-small-cell lung cancer. Results of a randomized prospective study. The Japan Clinical Oncology Group.

Two hundred nine patients with completely resected stage III non-small-cell lung cancer were randomized to receive postoperative cisplatin and vindesine chemotherapy or no further treatment. Before randomization, patients were stratified by the histologic characteristics of their tumors (squamous versus nonsquamous cell carcinoma). Prognostic variables such as histology, performance status, extent of operation, and tumor and nodal status of the eligible patients in chemotherapy (n = 90) and control groups (n = 91) were equally distributed. There was no statistically significant difference in disease-free and overall survival between the two groups. The 3-year disease-free survivals of the chemotherapy and control groups were 37% and 42%, respectively. The median survival times (5-year survival) were 31 months (35%) in the chemotherapy group and 37 months (41%) in the control group. These was no different pattern in the first site of recurrence (local versus systemic) between the two groups. This study failed to demonstrate the therapeutic benefits of postoperative cisplatin and vindesine chemotherapy.

Adenocarcinoma↗

Hemorrhagic cystitis associated with allogeneic and autologous bone marrow transplantation for malignant neoplasms in adults.

We investigated the occurrence of hemorrhagic cystitis in 30 consecutive adult patients undergoing bone marrow transplantation (BMT) for hematological and non-hematological malignancies. Ten patients with hematological malignancies received allogeneic BMT, and twenty patients, seven with hematological and 13 with non-hematological malignancies, received autologous BMT. All 30 patients received high-dose cyclophosphamide-containing regimens (120 mg/kg in 16, 200 mg/kg in one, 6000 mg/m2 in 13) as preparative therapies. They all received 2-mercaptoethane sulphonate sodium (mesna) combined with hyperhydration 3 liter/day as prophylaxis for hemorrhagic cystitis. Bladder irrigation was not performed. Overall, five patients (16.7%) developed hemorrhagic cystitis; early-onset (within 48 hours of the end of the high dose chemoradiotherapy) hemorrhagic cystitis occurred in one (3.3%; 95% confidence interval, 0.6-16.7%) and late-onset occurred in four (13.3%; 95% confidence interval, 5.3-29.7%). In three of the four late-onset cases, adenovirus was isolated from the urine specimens at the onset of the hemorrhagic cystitis. Among the 13 patients with non-hematological malignancies receiving autologous BMT, one with recurrent breast cancer developed late-onset hemorrhagic cystitis associated with adenovirus type 11. We conclude the prophylactic measure with mesna and hyperhydration to be effective enough to prevent cyclophosphamide-induced hemorrhagic cystitis of early onset. Some BMT recipients, however, even those with non-hematological malignancies undergoing autologous BMT, develop late-onset hemorrhagic cystitis in which adenovirus is considered a principal causative agent.

Adult↗

p33, an endogenous target protein for arginine-specific ADP-ribosyltransferase in chicken polymorphonuclear leukocytes, is highly homologous to mim-1 protein (myb-induced myeloid protein-1).

We have determined the partial amino acid sequence of p33, an endogenous substrate protein for arginine-specific ADP-ribosyltransferase in chicken polymorphonuclear leukocytes (heterophils), and found that the sequence was completely identical with the regions of amino acid sequences deduced from mim-1 (named for myb-induced myeloid protein-1, which is expressed in chicken promyelocytes) cDNA [(1989) Cell, 59, 1115-1125], except for one amino acid difference (Tyr297-->Ile). These results together with data on cellular and subcellular distributions of p33 in heterophils suggest that mim-1 may encode the precursor protein of p33.

ADP Ribose Transferases↗

ADP-ribosylation of actins by arginine-specific ADP-ribosyltransferase purified from chicken heterophils.

We reported the purification and characterization of an arginine-specific ADP-ribosyltransferase and acceptor protein p33 in granules of chicken peripheral polymorphonuclear leukocytes (heterophils) [Mishima, K., Terashima, M., Obara, S., Yamada, K., Imai, K. & Shimoyama, M. (1991) J. Biochem. (Tokyo) 110, 388-394]. In the present study, we obtained evidence that chicken non-muscle beta/gamma-actin, skeletal muscle alpha-actin and smooth-muscle gamma-actin were ADP ribosylated by the heterophil ADP-ribosyltransferase. The stoichiometry of ADP-ribose incorporation into these actins was 1.2 mol, 1.0 mol and 2.0 mol ADP-ribose/mol of beta/gamma-actin, alpha-actin and gamma-actin, respectively. The optimal pH for the ADP ribosylation was at pH 8.5, with the respective actin. Km values for NAD were calculated to be 30 microM with beta/gamma-actin, 35 microM with alpha-actin and 20 microM with gamma-actin. The Km values for the actin isoforms were 15 microM for beta/gamma-actin, 2.5 microM for alpha-actin and 10 microM for gamma-actin. ADP ribosylation of actin inhibited its capacity to polymerize, as determined by the increase in fluorescence intensity with N-(1-pyrenyl)iodoacetamide-labelled actin. Filamentous actin (F-actin) polymerized with the respective actin isoform was also ADP ribosylated, although the extent of the modification of F-actin was lower than that of globular actin (G-actin). In situ ADP ribosylation of beta/gamma-actin was evidenced with chicken peripheral heterophils permeabilized with saponin. Thus, the endogenous ADP ribosylation of actin in the heterophils may be involved in the cellular processes such as phagocytosis, secretion and migration.

Actins↗

Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase.

Two classes of enzymes, poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferases, catalyze covalent attachment of multiple or single residues, respectively, of the ADP-ribose moiety of NAD+ to various proteins. In order to find good inhibitors of poly(ADP-ribose) synthetase free of side actions and applicable to in vivo studies, we made a large scale survey using an in vitro assay system, and found many potent inhibitors. The four strongest were 4-amino-1,8-naphthalimide, 6(5H)- and 2-nitro-6(5H)-phenanthridinones, and 1,5-dihydroxyisoquinoline. Their 50% inhibitory concentrations, 0.18-0.39 microM, were about two orders of magnitude lower than that of 3-aminobenzamide that is currently most popularly used. A common structural feature among all potent inhibitors, including 1-hydroxyisoquinoline, chlorthenoxazin, 3-hydroxybenzamide, and 4-hydroxyquinazoline, in addition to the four mentioned above, was the presence of a carbonyl group built in a polyaromatic heterocyclic skeleton or a carbamoyl group attached to an aromatic ring. Most of the inhibitors exhibited mixed-type inhibition with respect to NAD+. Comparative studies of the effects on poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase from hen heterophils revealed high specificity of most of the potent inhibitors for poly(ADP-ribose) synthetase. On the other hand, unsaturated long-chain fatty acids inhibited both enzymes, and saturated long-chain fatty acids and vitamin K1 acted selectively on mono(ADP-ribosyl)transferase. The finding of many inhibitors of ADP-ribosyltransferases, especially poly(ADP-ribose) synthetase, supports the view that ADP-ribosylation of proteins may be regulated by a variety of metabolites or structural constituents in the cell.

ADP Ribose Transferases↗

Effect of He-Ne laser irradiation on synaptic transmission of the superior cervical sympathetic ganglion in the rat.

The effect of low-power He-Ne laser on synaptic transmission was studied in the superior cervical sympathetic ganglion of Wistar rats. Extracellular and intracellular recordings were made from isolated ganglia before and after laser irradiation. In addition, effects of ganglion irradiation on skin blood flow were observed in in vivo preparations. Irradiation on the isolated ganglion decreased the amplitude of evoked compound action potentials in the extracellular recordings. Intracellular recordings from ganglion cells revealed that the neuronal membrane was hyperpolarized, while threshold potential and latency of response were unchanged. The reduction of skin blood flow during preganglionic nerve stimulation lessened by irradiation on the ganglion. Our results indicate that low-power He-Ne laser depresses sympathetic ganglionic transmission, and hyperpolarization of ganglionic cells takes part in the mechanism of action.

Animals↗

Endogenous arginine-specific ADP-ribosyltransferases and target proteins.

We investigated vertebrate arginine-specific ADP-ribosyltransferases and target proteins for the enzyme. ADP-ribosyltransferase found in each organelle ADP-ribosylated preferentially an endogenous acceptor protein co-localized with the enzyme. We propose that the ADP-ribosylation of tissue-specific target protein by the endogenous ADP-ribosyltransferase may participate in the regulation of cellular processes, including signal transduction.

ADP Ribose Transferases↗

Treatment of hairy cell leukemia with deoxycoformycin (YK-176). The Deoxycoformycin (YK-176) Study Group.

Eleven patients with hairy cell leukemia (HCL) were treated with YK-176 (2'-deoxycoformycin) at a dose of 5 mg/m2 by intravenous injection every week or every other week. Patients received a median of eight (range 4-19) injections of YK-176. Five patients had previously been untreated, four of whom had massive splenomegaly. Six patients had previously been treated, four with interferon-alpha (IFN-alpha) or IFN-alpha and chemotherapy and two with prednisolone. Two patients had had splenectomies. Five patients achieved complete remission (CR) and six, partial remission (PR) according to WHO criteria (remission rate 100%, 95% confidence interval (CI) 74-100%). All six neutropenic patients recovered > 1,500/microliters neutrophils, six of seven anemic patients recovered > 12.0 g/dl hemoglobin and five of nine thrombocytopenic patients recovered > 100,000/microliters platelets following the treatment. According to the response criteria for HLC, five patients achieved CR, two PR and four minor response. The overall remission (CR + PR) rate was 64% (95% CI 35-85%). The CR and PR have lasted from > 30 to > 718 days (median, > 281 days) so far with no relapses. Of four patients previously treated with IFN-alpha, two achieved CR and one, PR. All patients were alive with a median survival time of > 290 days from treatment (range > 50- > 763 days). The treatment was generally well tolerated. Mild to moderate nausea, vomiting, appetite loss and general fatigue were experienced in two patients, skin rash in one and a transient fever in three. YK-176 was a highly active agent in the treatment of HCL.

Adult↗

[High dose chemotherapy with autologous bone marrow transplantation and G-CSF for hematologic malignancies].

High dose chemotherapy (HDCT) followed by autologous bone marrow transplantation (ABMT) is one of the cure-oriented therapies for hematologic malignancies. Colony stimulating factors (CSFs) are currently used to stimulate hematopoiesis in various cytopenic conditions including post BMT. Granulocyte CSF (G-CSF) significantly accelerates granulocyte recovery after ABMT. Earlier recovery of neutrophils is associated with lower incidence of severe infections and shorter duration of reverse barrier nursing and hospitalization. Widespread use of G-CSF in ABMT may contribute to managing this treatment safely in multi-centers. Further prospective clinical study to define the optimal application and timing of HDCT with ABMT in hematologic malignancies is required.

Acute Disease↗