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Biomedical subjects

M Shimoyama

Publications and source records attributed to M Shimoyama.

At least 181 records · Page 10Linked to original sources

Genetic and clinical studies of Japanese patients with familial amyloid polyneuropathy.

We examined the DNA analysis of familial amyloid polyneuropathy (FAP) patients and their families from Nagano and Hiroshima prefectures in Japan using recombinant DNA techniques and compared the results with the clinical features. This study indicated that the valine-methionine change prealbumin gene was closely related to the clinical features of type 1 FAP. The DNA analysis was valuable for the definite diagnosis of type 1 FAP even in sporadic and asymptomatic cases. FAP patients from Iiyama city and Ogawa village area in the Nagano prefecture had the same mutation despite differences in clinical features. The onset of the sporadic FAP cases was later than that of the FAP patients who had family histories.

Adult↗

Quantitative autoradiographic localization of the M1 and M2 subtypes of muscarinic acetylcholine receptors in the monkey brain.

The distribution of muscarinic acetylcholine receptors (mAChR) was investigated in the monkey brain by means of quantitative in vitro autoradiography. 3H-QNB, 3H-pirenzepine (PZ) and 3H-AF-DX 116 were used for labelling total mAChR, M1 and M2 receptors, respectively. 3H-PZ and 3H-AF-DX 116 showed specificity to each receptor subtype in the monkey brain. On sections containing the putamen and globus pallidus, the sum of Bmax values of 3H-PZ and 3H-AF-DX 116 binding sites was almost close to that of 3H-QNB binding sites. Autoradiographic distributions of muscarinic subtype receptors in the monkey brain were similar to those reported in the rat brain; that is, M1 receptors were dominant in most areas of the telencephalon, while M2 receptors were richly distributed in the brainstem and cerebellum. However, some nuclei of the brainstem such as the central gray matter, superior colliculus, substantia nigra, nucleus of the oculomotor nerve, pontine nucleus and inferior olivary nucleus, had relatively high ratios of M1 receptors in the monkey brain. In addition, the cortical lamminar distribution of M2 receptors noticed in the rat was not observed in the monkey brain. Knowledge about the localizations of M1 and M2 receptors in various brain regions in the monkey brain will increase our understanding of the functions of the brain cholinergic system in the primate.

Animals↗

[Research into actual conditions and preventive care in periodontal disease. Relationship between questionnaire results and periodontal disease in youth].

The purpose of this study was to determine the prevalence of periodontal disease and the relationship between the results of questionnaire concerning periodontal disease and the actual periodontal condition in youth. The examination was carried out in three parts. In the first part, a questionnaire was conducted on 3,886 junior and senior high school students (12 to 18 years of age) living in Kawagoe, Japan. The questionnaire was composed by of items concerning habits of oral hygiene, periodontal symptoms, understanding of periodontal disease and history of diagnosis by dentist of periodontal disease. Secondary, mass intraoral examination was carried out on all objects. The examination covered gingival inflammation, periodontal probing depth, calculus, dental plaque, dental caries and malalignment. Lastly, we examined the relationship between the results of periodontal examination and questionnaire with the original periodontal classification. The following results were obtained: 1. As an example of items in questionnaire, 83.1% brushed their teeth more than two times daily. The understanding of oral hygiene concerning dental caries was improved, but concerning periodontal disease was still poor. 2. The symptom most frequently reported was gingival bleeding during tooth brushing (18.4%). 3. The percentage of persons with periodontal disease (moderate gingival inflammation and periodontal pocket 4 mm or deeper) was of the highest frequency at 13 years old. The proportion of males increased with the advanced state of periodontal disease. 4. A significant correlation was found (chi 2-test: alpha less than 0.001) between advanced state of periodontal disease and a decrease in tooth brushing time per day. 5. A significant correlation was found between the advance of periodontal disease and gingival bleeding on tooth brushing (chi 2-test: alpha less than 0.001). Similarly, a correlation was found between the advance of periodontal disease and gingival swelling (chi 2-test: alpha less than 0.001). 6. A significant correlation was found (chi 2-test: alpha less than 0.001) between the advance of periodontal disease and aggravation of condition of dental plaque, calculus, dental caries and malalignment.

Adolescent↗

[Detection of multidrug resistant cells in human malignant diseases by monoclonal antibodies and strategy to eradicate resistant malignant cells].

Two monoclonal antibodies of F (ab')2 form, MRK 16 and MRK 20 that recognize P-glycoprotein and P85 kD protein respectively, were useful to detect multidrug resistant cells in human lymphoma, leukemia and gastrointestinal cancer cell lines. They were classified into 4 groups: Group I (4 cell lines) was insensitive to vinca alkaloids, anthracyclines, etoposide (VP-16) and actinomycin-D (ACT-D), and reactive to MRK 16 and MRL 20. Group II (2 cell lines) was insensitive to vincristine (VCR), but not reactive to both antibodies. Group III (3 cell lines) was insensitive to anthracyclines and VP-16, but sensitive to vinca alkaloids and ACT-D, and reactive to MRK 20 but not to MRK 16. Group IV (all other cell lines) was sensitive to these drugs, and not reactive to both antibodies. MRK 16 detects P-glycoprotein-associated multidrug resistance (MDR), while MRK 20 detects P 85kd-associated novel MDR. These monoclonal antibodies were useful for detection of MDR cells in clinical samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Major prognostic factors in patients with T- and B-cell lymphomas].

Major prognostic factors were analyzed by Cox proportional hazard model in 311 patients with B-lymphoma and 141 with T-lymphoma, who were treated with combination chemotherapy as the initial therapy during 1975 to 1987. Poor prognosis was associated with high grade pathology, increasing number of extranodal lesions, advanced stage, initial combination chemotherapy without doxorubicin, low total protein and intestinal lesion in B-lymphoma, but with increasing number of involved lesions, high LDH, low total protein, anemia, skin lesion and patients treated before 1982 in T-lymphoma. First three factors of each disease were the most important with risk ratio more than 2.5. New risk group was made from combination of the factors, which was ordered from low to high hazard rate. The new risk groups for T- and B-lymphoma are usefull for estimation of prognosis and determination of adequate chemotherapy of the patients. The prognostic factors of T-lymphoma were completely different from those of B-lymphoma, suggesting that T- and B-lymphoma are different disease and should be analyzed separately.

Adult↗

[Cross and non-cross resistant anticancer agents to multidrug-resistant cultured cells from hematologic malignancies].

We report here that typical and atypical multidrug resistant (MDR) cells can be identified by monoclonal antibodies, MRK16 and MRK20, respectively. Typical MDR cells were cross-resistant to vinca alkaloids, anthracyclines, mitoxantrone (MXT), etoposide (VP-16) and actinomycin-D (ACT-D), and reactive to MRK16. Atypical MDR cells were cross-resistant to anthracyclines, MXT, VP-16, and bleomycin but sensitive to vinca alkaloids and ACT-D. They were reactive to MRK20, but not to MRK16. Among anthracyclines, aclacinomycin A was not cross-resistant to either typical or atypical MDR cells. Methotrexate was not cross-resistant to doxorubicin, vincristine, Ara-C and cisplatin. Cisplatin was not cross resistant to 5-FU, either. Identification of cross and non-cross resistant anticancer agents may be useful to plan a cure-oriented combination chemotherapy for hematologic malignancies.

Antibodies, Monoclonal↗

[Hodgkin's disease under twenty years of age--clinicopathological study].

Twenty two cases with Hodgkin's disease under 20 years of age who were diagnosed and treated in National Cancer Center during 1962-1986 were studied retrospectively. The most common initial symptom was swelling of lymph nodes (86%) and only 5 cases (23%) showed "B" symptoms. Laboratory findings showed that there were some cases with increased WBC counts but only 2 cases with an elevated LDH value. In 2 out of 4 cases serum copper value correlated well with their clinical state. Histologically lymphocyte predominance type, mixed cellularity type and nodular sclerosis type almost equally occurred in children younger than age 15 years. On the other hand nodular sclerosis type with mediastinal mass was predominantly encountered in older patients (especially female). The ten years' survival rate in stage I and II patients was 59% compared with 21% in stage III and IV patients. As for the results of initial treatment, complete remission and 10 years' survival rate were 91% and 87% in recent 12 years (1975-1986) compared with 55% and 36% in the preceding 13 years (1962-1974) respectively. Autopsy findings revealed rare involvements of the central nervous system and kidneys. Various late effects which may be caused by escalating doses of radiotherapy occurred in 6 out of 9 cases under the age of 15 years who survived. On the basis of these results lower-doses of radiotherapy combined with systemic chemotherapy appeared to be advisable for the treatment of childhood Hodgkin's disease.

Adolescent↗

[Heart failure due to rapid right ventricular volume overload in patients with pulmonary hypertension].

We have described three cases of pulmonary artery hypertension (PAH). Two of them developed severe systemic hypotension and cardiac arrest following cardiopulmonary bypass (CPB). Imminent pre-operative right ventricular (RV) failure and subsequent myocardial injury during CPB may have contributed to the insult following CPB. In these cases, RV failure is presumably due to rapid volume overloading, since left atrial pressure (LAP) was essentially unchanged while right atrial pressure (RAP) was markedly elevated during the period of severe hypotension. Furthermore, these events may be attributed to protamine, since the circulatory derangement coincides with its administration. Thus, in these patients with severe PAH, blood transfusion should be carefully titrated under the strict evaluation of both LAP and RAP. Additionally, protamine should be infused at a rate slow enough to avoid concomitant hemodynamic changes. We have also reported a case of over-systemic PAH who was successfully managed intraoperatively by careful monitoring and discreet administration of protamine.

Adult↗

Antitumor activity of quinocarmycin (KW2152) against various cultured leukemia and lymphoma cell lines in vitro.

Growth inhibitory activity of quinocarmycin citrate (KW2152) against 25 human cultured cell lines derived from leukemias and lymphomas was assessed quantitatively by regrowth assay. EC90 values (drug concentration required for 90% growth inhibition of treated cells) measured at 1-h exposure to the drug in vitro were more than 16 micrograms/ml in five of six T-cell lines derived from T-lymphoma/leukemia, hence they were insensitive to KW2152. On the other hand, four of six B-cell lines derived from B-lymphoma and three of four cell lines derived from non-T, non-B acute lymphoblastic leukemia were sensitive to KW2152 with EC90 values of 0.3 to 2.2 micrograms/ml at 1-h exposure. Six myelomonocytoid cell lines derived from acute myelogenous leukemia were also sensitive with EC90 values of 1.8 to 3.0 micrograms/ml on 1-h exposure, but two myeloid cell lines derived from chronic myelogenous leukemia and one cell line derived from erythroleukemia were insensitive with EC90 values of more than 16 micrograms/ml. The EC90 values of most cell lines decreased as exposure time increased, and those measured at 24-h exposure were similarly low and mostly in the 0.02 to 0.06 micrograms/ml range. The kinetics analysis of growth inhibitory activity of KW2152 revealed that the drug showed time-dependent action. These in vitro results, as correlated with in vivo results reported elsewhere (K. Fujimoto, T. Oka, and M. Morimoto, Cancer Res., 47: 1516-1522, 1987), suggest that daily consecutive or continuous dose therapy as well as single or intermittent large-dose therapy would be worthy of testing in the clinical trial of KW2152.

Antibiotics, Antineoplastic↗

Preferential ADP-ribosylation of arginine-3 in synthetic heptapeptide Leu-Arg-Arg-Ala-Ser-Leu-Gly.

Hen liver nuclear ADP-ribosyltransferase modified the synthetic heptapeptide Kemptide (Leu-Arg-Arg-Ala-Ser-Leu-Gly) at arginine-2 and/or arginine-3. Trypsin treatment of ADP-ribosyl-Kemptide revealed that the ADP-ribosylation of arginine-3 was constantly more abundant than that of arginine-2. ADP-ribosylation of Kemptide suppressed the subsequent phosphorylation by cyclic AMP-dependent protein kinase.

Adenosine Diphosphate↗

ADP-ribosylation suppresses phosphorylation of the L-type pyruvate kinase.

L-type pyruvate kinase (EC 2.7.1.40) purified from pig liver was ADP-ribosylated by incubation with NAD and ADP-ribosyltransferase purified from hen liver nuclei. Maximal incorporation of the ADP-ribose moiety from NAD into the L-type pyruvate kinase was 0.98 mol/mol of subunit. The Km values for NAD and L-type pyruvate kinase were 0.17 mM and 9.7 microM, respectively. ADP-ribosylation of the L-type pyruvate kinase resulted in suppression of the subsequent phosphorylation catalyzed by cAMP-dependent protein kinase. The ADP-ribosylation-induced suppression of phosphorylation of the L-type pyruvate kinase also resulted in suppression of the phosphorylation-induced inactivation. Amino acid analysis, after exhaustive sequential digestion of ADP-ribosyl-L-type pyruvate kinase with pepsin, aminopeptidase M and carboxy-peptidase B showed arginine to be the ADP-ribose-accepting amino acid. These results together with finding of the ADP-ribosyltransferase activity in mammalian liver cytosol (Moss, J. and Stanley, S.J. (1981) J. Biol. Chem. 256, 7830-7833) suggest that ADP-ribosylation may participate in the regulation of the L-type pyruvate kinase activity through changes in the rate of phosphorylation.

Adenosine Diphosphate Ribose↗

Peripheral T-cell lymphoma.

Since the discovery of human T-cell leukemia virus type 1 (HTLV-1) in patients with adult T-cell leukemia/lymphoma (ATLL), malignant neoplasms of mature (peripheral) T lymphocytes have attracted a great deal of attention. This type of neoplasm is more common in Japan than in Western countries, and may show distinct clinical pictures such as hypergammaglobulinemia, hypercalcemia, etc. T-cell lymphomas are more prone than B-cell lymphomas to become leukemic. Because of a marked intermingling of reactive cells (histiocytes, eosinophils, etc.), the histologic diagnosis of T-cell lymphoma is often difficult. Proliferation pattern and cellular size do not correlate with prognosis as in B-cell lymphoma. Since T-cell lymphomas often manifest with several distinct clinicopathologic settings, their categorization should be based on several parameters, such as the presence or absence of ATLL-associated antigen in serum, histology, phenotype of the neoplastic cell, and clinical features. Since a classification for T-cell lymphomas has not been established, a further multi-disciplinary approach is necessary for a better understanding of this interesting neoplasm.

Chronic Disease↗

Concurrent adult T-cell leukemia and acute myeloblastic leukemia.

A 49-year-old man developed adult T-cell leukemia (ATL) and acute myeloblastic leukemia (AML) at the same time. Using Southern blotting analysis, the leukemic cells of the ATL were found to contain the human T-cell leukemia virus type I (HTLV-I) proviral genome, whereas those of the AML did not, indicating the HTLV-I not to be associated with the AML oncogenesis. At the initial presentation, the serum anti-HTLV-I antibody was judged on screening by a routine particle-agglutination (PA) test and an indirect immunofluorescence assay (IF) to be negative. By Western blotting analysis, however, the serum was proved to be positive for anti-HTLV-I antibody. These results indicate that a routine PA-test and an IF may show false negative reactions on very rare occasions of low antibody titer. This is the first report of a coincidence of ATL with another type of leukemia.

Antibodies, Viral↗

Infectious states of human T lymphotropic virus type I and hepatitis B virus among Japanese immigrants in the Republic of Bolivia.

Serologic tests for human T lymphotropic virus type I (HTLV-I) and hepatitis B virus infections were conducted in 1986 in two Japanese immigrant colonies located in Santa Cruz, Bolivia. A total of 322 adults (283 Japanese and 39 Bolivians) over age 35 years and 305 children (166 Japanese, 124 Bolivians, and 15 of mixed blood) aged 8-17 years were sampled at the time of a routine health checkup. The prevalence of antibody to HTLV-I was 17% in first-generation Japanese immigrants and 6% in second- or third-generation Japanese children. Prevalences among native Bolivians were 3% and 5% in adults and children, respectively. Seropositive Japanese immigrants and mothers showed clustering according to birthplace in endemic areas of Japan. The prevalence of either hepatitis B virus surface antigen (HBsAg) or antibody to HBsAg was 48% in Japanese adults, 21% in Japanese children, 13% in Bolivian adults, and 1% in Bolivian children. Seropositive adults did not show clustering according to birthplace, but children in one colony showed clustering and a narrow age range. A correlation of seropositivity between husbands and wives was found only for HTLV-I. The seropositivity was independent of whether an HTLV-I or a hepatitis B virus infection marker was present.

Adolescent↗