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M Shimoyama

Publications and source records attributed to M Shimoyama.

At least 145 records · Page 8Linked to original sources

[Immunologic phenotype of malignant lymphoma].

Recent advances in clinical research on surface marker analysis of malignant lymphoma cells are reviewed. Malignant lymphoma can be classified into T-cell malignancy or B-cell malignancy, using flow cytometry or immunohistochemical analysis. Based on recent results of immunophenotypic analysis and clinical data, a new clinicopathologic classification of lymphoid malignancy is proposed. T-cell malignancy bearing T-cell receptor of gamma delta-type is discussed. Other recent topics on malignant lymphoma, such as B-cell lymphoma of the pleural cavity developing from long-standing pyothorax, mediastinal large-B-cell lymphoma with sclerosis, HIV-related B-cell lymphoma, and EB-virus genome carrying B-cell lymphoma in ATL are also discussed.

Antigens, Surface↗

Phase I study of YK-176 (2'-deoxycoformycin) in patients with adult T-cell leukemia-lymphoma. The DCF Study Group.

YK-176 is a newly isolated 2'-deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase, produced by Aspergillus nidulans. In a cooperative phase I study, YK-176 was administered to 22 patients, comprising 18 with adult T-cell leukemia-lymphoma (ATL), two with cutaneous T-cell lymphoma (CTCL), one with lymphoblastic lymphoma of T-cell type and one with carcinoma of the uterine cervix. Doses of YK-176 ranged from 3.0 to 9.0 mg/m2 and were given intravenously for three consecutive days. General malaise, anorexia, nausea, vomiting and low grade fever were frequently encountered, but were transient and not dose-related. At all dose levels hematological toxicities were mild. Two of seven patients receiving 7.0 mg/m2 for three consecutive days developed hepatocellular enzyme elevations (grade 2) and one patient, proteinuria (grade 2). One of two patients given 9.0 mg/m2 for three consecutive days manifested a life-threatening (grade 4) disturbance of consciousness and dyspnea, presumably ascribable to the drug-related toxicity of YK-176. The results suggest that 7.0 mg/m2 i.v. for three consecutive days is the maximum acceptable dose of YK-176. Central nervous system, pulmonary and possibly renal toxicities appeared to be dose-limiting. Out of the 20 patients evaluable for therapeutic response, partial remissions were observed in four, three with ATL and one with CTCL, who received less than 7.0 mg/m2 for three consecutive days. We conclude that YK-176 is an active agent against ATL at doses that may not be associated with prohibitive toxicity. A starting dose of 5.0 mg/m2 for three consecutive days is recommended for further phase II studies on ATL.

Adult↗

Localization of an endogenous ADP-ribose acceptor, p33, in polymorphonuclear cell granules in chicken liver interlobular connective tissue.

We investigated immunohistochemically the localization of p33, an endogenous substrate protein for an arginine-specific ADP-ribosyltransferase in chicken liver. Polymorphonuclear-pseudo-eosinophilic granulocytes (heterophils) in interlobular connective tissues of the liver were exclusively and strongly stained with the antibody against p33. Strong reactivity was associated with granules in cytoplasm of the heterophils. When the chicken liver nuclear fraction was washed, the transferase activity was released into the 600 x g supernatant fraction while a nuclear enzyme poly(ADP-ribose) synthetase was retained in the pellet fraction. These results indicate that p33 and probably also ADP-ribosyltransferase, found in the liver nuclear fraction [Tanigawa et al. (1984) J. Biol. Chem. 259, 2022-2029, Mishima et al. (1988) Eur. J. Biochem. 179, 267-273], originate from interlobular heterophils of the chicken liver.

Animals↗

Deoxyadenosine triphosphate acting as an energy-transferring molecule in adenosine deaminase inhibited human erythrocytes.

Deoxyadenosine triphosphate (dATP) is present in adenosine deaminase (ADA)-deficient or ADA-inhibited human red cells and in the red cells of the opossum Didelphis virginiana. In order to investigate the functions of dATP in the red cell, red cells were treated with 2'-deoxycoformycin (dCf), a powerful inhibitor of ADA, and incubated with phosphate, deoxyadenosine and glucose. These red cells in which ATP was almost completely replaced by dATP, had the same shape, lactate production, nucleotide consumption, stability of reduced glutathione, osmotic fragility and cell deformability as red cells containing ATP. Cells merely depleted of ATP showed reduced viability. This indicates that dATP compensates well for the absence of ATP and acts as an energy-transferring molecule to maintain cell viability. These results indicate that the accumulation of dATP or the reduction of ATP is not the cause of the hemolysis observed after dCf administration.

Adenosine Deaminase↗

Evidence for the endogenous GTP-dependent ADP-ribosylation of the alpha-subunit of the stimulatory guanyl-nucleotide-binding protein concomitant with an increase in basal adenylyl cyclase activity in chicken spleen cell membrane.

We investigated the endogenous GTP-dependent ADP-ribosylation of the alpha-subunit of the stimulatory guanyl-nucleotide-binding protein (Gs alpha) concomitant with an increase of basal adenylyl cyclase activity in chicken spleen cell membranes. When these membranes were incubated with [adenylate-32P]NAD, there was significant incorporation of [32P]ADP-ribose into a 45-kDa acceptor protein in the membranes. This reaction was inhibited when 20 mM arginine was present during the incubation. When the membranes were incubated with unlabelled NAD, subsequent ADP ribosylation by cholera toxin was diminished significantly. Thus, chicken spleen cell membranes have the potential to endogenously ADP-ribosylate the arginine residue of Gs alpha. The endogenous ADP-ribosylation Gs alpha was enhanced by the addition of 0.1 mM GTP or 0.1 mM guanosine 5'-[gamma-thio]triphosphate (GTP[S]), but not 0.1 mM GDP, 0.1 mM ATP or 0.1 mM ADP. The endogenous GTP-dependent ADP-ribosylation of Gs alpha stimulated basal adenylyl cyclase activity. Furthermore, NAD-induced stimulation of basal adenylyl cyclase activity was suppressed, when the membranes were incubated with NAD in the presence of novobiocin, an inhibitor of arginine-specific ADP-ribosyltransferase. These data represent the first demonstration that a eukaryotic cell membrane contains an ADP-ribosyltransferase which can catalyze the endogenous GTP-dependent ADP-ribosylation of the arginine residue of Gs alpha and that this modification enhances basal adenylyl cyclase activity in the membrane. In light of this evidence, the possible control of basal adenylyl cyclase activity via endogenous GTP-dependent ADP-ribosylation in eukaryotic cells warrants further attention.

Adenosine Diphosphate Ribose↗

Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer.

Between April 1985 and May 1988, we conducted a randomized study comparing two standard chemotherapy regimens with the same regimens given on an alternating basis in patients with small-cell lung cancer. The patients were randomly assigned to receive cyclophosphamide at a dose of 800 mg/m2 intravenously (IV) on day 1, doxorubicin at 50 mg/m2 IV on day 1, and vincristine at 1.4 mg/m2 IV on day 1 (CAV); cisplatin at 80 mg/m2 IV on day 1 and etoposide at 100 mg/m2 IV on days 1, 3, and 5 (PE); or CAV alternating with PE (CAV/PE). Each regimen was repeated every 3-4 weeks. Three hundred patients were entered in the study, and 288 of them were eligible for analysis (97 for CAV, 97 for PE, and 94 for CAV/PE). The response rates for PE (78%) and CAV/PE (76%) were significantly higher than the rate for CAV (55%), while the complete response rates were similar (14%, 16%, and 15%, respectively). Nine (23%) of 39 patients who failed to respond to the initial CAV regimen responded to PE when they were crossed over. In contrast, only one (8%) of 13 patients responded to CAV after failing to respond to the PE regimen, suggesting that these two regimens were partially non-cross-resistant. The response duration on CAV/PE was significantly longer than that with CAV (P = .004). The survival time with CAV/PE (11.8 months) was superior to that with CAV (9.9 months) (P = .027) or that with PE (9.9 months) (P = .056). In patients with limited disease, the survival in the alternating arm was significantly superior to the survival in the CAV arm (P = .014) or the survival in the PE arm (P = .023). The toxic effects were acceptable in all three chemotherapy regimens. These results favor the alternating chemotherapy over either standard chemotherapy, such as CAV and PE, although the differences are not dramatic.

Adult↗

Peripheral T-cell lymphoma in Japan: recent progress.

T-lymphoma, including adult T-cell leukemia-lymphoma (ATL) accounted for 75% of non-Hodgkin's lymphoma in the Kyushu district of Japan and for 43% in the nation as a whole. Human T-cell leukemia/lymphoma virus type I (HTLV-I) is closely associated with ATL; however, 11 (7.5%) of 147 patients with ATL were HTLV-I negative. The cumulative percentage incidence of anti-HTLV-I seropositive ATL patients can be simply described by a Weibull model of the typical tear-off type, suggesting that ATL leukemogenesis may be the result of accumulation of approximately five critical events, most likely somatic mutations within HTLV-I-infected T-cells. ATL is still a difficult disease to treat successfully, while peripheral non-ATL T-lymphoma responded to standard chemotherapy in the same way as B-lymphoma. The disease entity of immunoblastic lymphadenopathy (IBL)-like T-lymphoma was also described. Morphological recognition of focal or sheetlike proliferation of atypical neoplastic pale cells and immunoblasts of T-cell nature were important findings for the diagnosis. Major prognostic factors differed greatly among ATL, peripheral non-ATL T-lymphoma and B-lymphoma. Pathology was not associated with treatment outcome and survival in T-cell diseases. These results indicate that the terms ATL, peripheral non-ATL T-lymphoma, and B-lymphoma should be used instead of the all-inclusive term non-Hodgkin's lymphoma, because of differences in cellular origin, clinical features, treatment outcome, prognosis, prognostic factors, chromosomal aberrations, and etiology.

Adult↗

Epstein-Barr virus (EBV) genome carrying monoclonal B-cell lymphoma in a patient with adult T-cell leukemia-lymphoma.

A Japanese patient with adult T-cell leukemia-lymphoma (ATL) showed a disease progression from the smoldering type to the chronic type and finally to the acute type. The patient was variously treated, including 2'-deoxycoformycin, with some beneficial effects. During the chronic type he developed a composite lymphoma consisting of T-cell lymphoma (ATL) of medium-sized cells and B-cell lymphoma of diffuse large cell type. At that time, he also suffered from miliary tuberculosis and adenovirus type 11-induced hemorrhagic cystitis, indicating that he was in a marked immunodeficient state. Southern-blot analysis revealed that the two malignancies have distinct clonal origin on the basis of the following results: (1) clonally rearranged T-cell receptor beta-chain gene (TcR-beta gene) and germline configuration of immunoglobulin heavy chain gene (IgH gene) in ATL leukemic cells, (2) clonal rearrangement of IgH gene in lymphoma cells, indicating a monoclonal B-cell lymphoma, (3) monoclonal integration of HTLV-I provirus in ATL leukemic cells, (4) definite presence and monoclonal origin of EBV genome in lymphoma cells. This is the first report of secondary EBV genome carrying monoclonal B-cell lymphoma in an ATL patient. It is suggested that the immunodeficient state in the patient with ATL allows the emergence of EBV-related B-cell lymphoma.

Adult↗

Evaluation of analgesic effect of low-power He:Ne laser on postherpetic neuralgia using VAS and modified McGill pain questionnaire.

In order to investigate the efficacy of low-power He:Ne laser in treatment of pain, we irradiated 18 outpatients with severe postherpetic neuralgia. The efficacy of the low-power laser treatment was evaluated using a four-grade estimation, visual analog scale (VAS), and modified McGill pain questionnaire (m-MPQ) after every 10 of as many as 50 irradiations. The efficacy rate using a four-grade estimation at the end of 50 treatments was 94.4%. VAS decreased from 6.2 before irradiation therapy to 3.6 after 50 treatments, and the degree of pain relief was reduced to 44.6% and correlated with the number of treatments. The total numbers of words and the total scores of the m-MPQ decreased as the number of treatments increased. No complications attributable to the laser therapy were observed. These results suggest that repeated irradiation with low-power He:Ne laser is an effective and safe therapy for postherpetic neuralgia.

Adult↗

Red and green low-powered He-Ne lasers protect human erythrocytes from hypotonic hemolysis.

The effect of low-powered He-Ne lasers (red beam, 632.8 nm, 10.2 mW, and green beam, 543.5 nm, 0.44 mW) on hypotonic hemolysis in human red cells was investigated. Red cell solutions (0.9% NaCl, pH 7.00) were centrifuged and the sediments were irradiated with the red or the green beam for 0 (control), 1, 3, 5, 7, 10, 15 and 30 minutes. Each of the 40 irradiated samples were transferred into hypotonic solution (0.405% NaCl, pH 7.00). After leaving the samples at room temperature for 10 minutes, optical density of every suspension was measured spectrophotomechanically at a wavelength of 545 nm to determine hemoglobin content. Hemolysis percentages of the control samples in hypotonic solution were 52.2 +/- 10.7% (mean +/- SD, N = 20) in the red group and 55.0 +/- 12.0% (N = 20) in the green group. Relative values of hemolysis in the hypotonic solution after irradiation with the red or the green beam decreased significantly between the 7- and 30-minute irradiation. These results demonstrate that low-powered He-Ne lasers have a protective effect on red cell membranes from hypotonic hemolysis and stabilize the cell membranes.

Erythrocyte Membrane↗

Arginine-specific ADP-ribosyltransferase and its acceptor protein p33 in chicken polymorphonuclear cells: co-localization in the cell granules, partial characterization, and in situ mono(ADP-ribosyl)ation.

We have reported the purification and characterization of arginine-specific ADP-ribosyltransferase from hen liver nuclei [Tanigawa, Y. et al. (1984) J. Biol. Chem. 259, 2022-2029] and the DNA-dependent mono(ADP-ribosyl)ation of p33, an acceptor protein in the nuclei [Mishima, K. et al. (1989) Eur. J. Biochem. 179, 267-273]. In the present study, we obtained evidence that among various tissues and cells from chicken, polymorphonuclear cells, so-called heterophils, possess both the ADP-ribosyltransferase and p33 at high levels. Percoll density gradient centrifugation of the postnuclear fraction of the heterophils revealed the co-localization of ADP-ribosyltransferase with p33 in the granule fraction. The enzyme and p33 were purified approximately 219- and 3.77-fold, respectively, from postnuclear pellet fraction to apparent homogeneity. The properties of heterophil ADP-ribosyltransferase and p33 were compared with those of the liver enzyme and p33. The molecular mass of the heterophil enzyme was estimated by SDS-polyacrylamide gel electrophoresis to be 27.5 kDa. The enzyme activity was stimulated by a sulfhydryl agent and inhibited by lysolecithin, NaCl, and inorganic phosphate. The mono(ADP-ribosyl)ation of p33 was markedly enhanced by polyanion, such as DNA, RNA, or poly(L-glutamate). SDS-polyacrylamide gel electrophoretic analysis after limited trypsin proteolysis of p33s, purified from chicken heterophils and liver, showed much the same pattern. Thus, it appears that ADP-ribosyltransferase and p33 present in heterophils are identical to those in the liver, respectively. p33 is considered to be an in situ substrate for ADP-ribosyltransferase, since it was specifically mono(ADP-ribosyl)ated in permeabilized heterophils.(ABSTRACT TRUNCATED AT 250 WORDS)

ADP Ribose Transferases↗

Genetic alteration of p53 in some patients with adult T-cell leukemia.

Abnormalities of p53 mRNA in adult T-cell leukemia (ATL) were analyzed using reverse transcription-polymerase chain reaction-single strand conformation polymorphism analysis. Mutations were present in two of 12 ATL patients studied, but not in 3 cell lines immortalized by human T cell leukemia virus type 1 (HTLV-1) infection in vitro. Direct sequencing analysis of the p53 gene from these two patients revealed missense point mutations at codon 153 (arginine to histidine) or codon 220 (cysteine to tyrosine), respectively. Immunohistochemical analysis revealed the elevated expression of p53 proteins in ATL cells from a patient carrying the mutated p53 gene at codon 158. Neither gross rearrangement of p53 gene nor abnormal size of mRNA for the gene was demonstrated by Southern or Northern blot analyses. Thus, there is a mutated p53 in some patients with ATL. The involvement of abnormalities in some suppressor oncogenes may play a role in the development of ATL.

Base Sequence↗

Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87).

The following diagnostic criteria are proposed to classify four clinical subtypes of HTLV-1 associated adult T-cell leukaemia-lymphoma (ATL): (1) Smouldering type, 5% or more abnormal lymphocytes of T-cell nature in PB, normal lymphocyte level (less than 4 x 10(9)/l), no hypercalcaemia (corrected calcium level less than 2.74 mmol/l), lactate dehydrogenase (LDH) value of up to 1.5 x the normal upper limit, no lymphadenopathy, no involvement of liver, spleen, central nervous system (CNS), bone and gastrointestinal tract, and neither ascites nor pleural effusion. Skin and pulmonary lesion(s) may be present. In case of less than 5% abnormal T-lymphocytes in PB, at least one of histologically-proven skin and pulmonary lesions should be present. (2) Chronic type, absolute lymphocytosis (4 x 10(9)/l or more) with T-lymphocytosis more than 3.5 x 10(9)/l, LDH value up to twice the normal upper limit, no hypercalcaemia, no involvement of CNS, bone and gastrointestinal tract, and neither ascites nor pleural effusion. Lymphadenopathy and involvement of liver, spleen, skin, and lung may be present, and 5% or more abnormal T-lymphocytes are seen in PB in most cases . (3) Lymphoma type, no lymphocytosis, 1% or less abnormal T-lymphocytes, and histologically-proven lymphadenopathy with or without extranodal lesions. (4) Acute type, remaining ATL patients who have usually leukaemic manifestation and tumour lesions, but are not classified as any of the three other types. A total of 818 ATL patients with a mean age of 57 years, newly diagnosed from 1983 to 1987, were analysed by this criteria. There were 448 males and 370 females, and 253 were still alive with a median follow-up time of 13.3 months from diagnosis, while 565 were dead with a median survival time (MST) of 5.4 months. MST was 6.2 months for acute type, 10.2 months for lymphoma type, 24.3 months for chronic type, and not yet reached for smouldering type. Projected 2- and 4-year survival rates were 16.7% and 5.0% for acute type, 21.3% and 5.7% for lymphoma type, 52.4% and 26.9% for chronic type, 77.7% and 62.8% for smouldering type, respectively. Distinct clinical features and laboratory findings of each clinical subtype are described.

Adult↗

[Tumor markers--personal experience. A case of advanced extragonadal germ-cell tumor showing complete remission by high-dose combination chemotherapy with autologous bone marrow transplantation].

A twenty-four-year-old male patient with stage III advanced extragonadal germ-cell tumor obtained complete remission after comprehensive treatment including high-dose combination chemotherapy with autologous bone marrow transplantation. He had massive tumors in cervical, mediastinal, abdominal and inguinal lymph nodes, bilateral lungs and liver. Ascites, plural effusion and pericardial effusion were also noted. Cancer cells were demonstrated from his bloody sputum, pericardial drainage and an aspirate from supraclavicular tumor. His tumor produced hCG, AFP, placental ALP and LDH, and hCG was the best marker for the diagnosis and monitoring. The initial serum hCG level was high at 460,000 mIU/ml, but fell to 13 mIU/ml after 3 courses of PVP therapy. However, it rose ten-fold in a week. After ultra-high dose combination chemotherapy with autologous BMT, the patient's hCG fell to 1.8 mIU/ml and remained at that level thereafter. He has remained well with no sign of recurrence after 25 months.

Adult↗

Non-Hodgkin's lymphoma in patients under twenty years of age. A clinicopathological study.

A retrospective clinicopathological study was performed on 149 patients who developed malignant lymphoma at under 20 years of age and were diagnosed and treated at the National Cancer Center Hospital between 1962-1986. Using the Japanese Lymphoma Study Group classification (and Working Formulation), we reclassified the 84 evaluable tissue specimens as follows: follicular large and mixed lymphoma (two cases), diffuse lymphoblastic lymphoma (40 cases), Burkitt's lymphoma (small noncleaved, SNC) (12 cases), diffuse large and mixed cell lymphoma (25 cases), and unclassified (five cases). The age of the patients ranged from 6 months to 20 years, with a median of 11 years. The clinical characteristics were found to depend upon the histological diagnosis, as reported previously. To evaluate the influence of various clinical and morphological parameters on survival, univariate analysis was performed for each histological subtype. In lymphoblastic lymphoma, patients with a mediastinal mass had significantly earlier development of leukemic conversion and a shorter survival than patients without a mass. Because of the small number of patients and their short survival, no significant prognostic factors were found in Burkitt's lymphoma (SNC). In large and mixed cell lymphoma, response to therapy was the most significant prognostic factor. As therapy became more intense and systematic throughout the study period, the complete remission rate and survival improved steadily. Autopsy findings confirmed that lymphoblastic lymphoma and Burkitt's lymphoma (SNC) spread systemically earlier than large and mixed cell lymphoma.

Adolescent↗

Severe herpes simplex virus hepatitis following autologous bone marrow transplantation: successful treatment with high dose intravenous acyclovir.

A 17-year-old male patient with T-cell type lymphoblastic lymphoma in complete remission underwent high dose chemotherapy (busulfan 16 mg/kg and cyclophosphamide 120 mg/kg) followed by autologous bone marrow transplantation (ABMT). The patient had been taking oral acyclovir (200 mg x 5) daily from seven days prior to the ABMT (day -7). On day +24, he complained of epigastralgia and general malaise, and the next day his GOT and GPT rose to 570 U/l and 397 U/l, respectively. Although he had no mucocutaneous lesions, hepatitis caused by a herpes virus was suspected, and high dose intravenous acyclovir (10 mg/kg x 3/day) was immediately started. His GOT, GPT and total bilirubin reached peaks of 2,870 U/l on day +26, 1,830 U/l on day +27 and 10.3 mg/dl on day +39, respectively, and rapidly improved thereafter. Serological analyses on IgG antibody titers to herpes simplex virus type 1 using an enzyme-linked immunosorbent assay revealed specific increases (454-fold before transplantation to 3,830-fold on day +46). Antiviral antibody titers to cytomegalovirus, varicella-zoster virus and Epstein-Barr virus showed no significant changes. The serologic markers of hepatitis B virus, hepatitis A virus and hepatitis C virus were all negative. The results indicate the patient's severe icteric hepatitis to have been caused by a reactivation of herpes simplex virus type 1 due to immunosuppression after high dose chemotherapy with ABMT. It is suggested that prompt commencement of high dose intravenous acyclovir is required to treat severe herpes simplex virus hepatitis affecting immunocompromised patients.

Acyclovir↗

Prognostic factors for pleural lymphoma patients.

Prognostic factors in 47 patients with pleural lymphocytic lymphoma developing in chronic tuberculous pyothorax were evaluated using Cox's proportional hazards model. There were 41 men and six women, aged 44-80 (median 61) years. Approximately 70% of the patients had localized disease in Stages I and II, and 30% advanced disease in Stages III and IV. Histologically, 27 patients had the diffuse large, immunoblastic type and 12 had others. In the other seven patients, histological subtyping of the lymphocytic lymphoma was impossible because of degenerative or necrotic changes in the histologic specimens. A diagnosis of lymphocytic lymphoma of B-cell type was made in one case using combined cytologic and surface maker findings on a cell suspension. In addition, immunologic and immunohistochemical studies revealed another 40 cases to be proven B-cell lymphomas. Poor performance status and elevated levels of BUN and GPT were significantly associated with shortened survival in a Cox's proportional hazards model. A poor performance status and high levels of serum BUN and GPT suggested a marked deterioration in a patient's condition. When compared with previous literature describing prognostic factors in patients with B-cell lymphomas and with lymphocytic lymphomas with unfavorable histologies or associated with long-standing inflammations, the only common prognostic factors was performance status. The significance of primary site in predicting survival from lymphocytic lymphoma is discussed.

Adult↗