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Biomedical subjects

T Shibuya

Publications and source records attributed to T Shibuya.

At least 271 records · Page 15Linked to original sources

Micronucleus test with 6-mercaptopurine monohydrate administered intraperitoneally and orally.

The effect of route of administration on the induction of micronucleated polychromatic erythrocytes (MNPCEs) was examined. 6-Mercaptopurine monohydrate (6-MP) was administered intraperitoneally (i.p.) or orally (p.o.) to 2 strains of mice, MS/Ae and CD-1. From the results of an acute toxicity test and a pilot micronucleus test, the doses selected for the final micronucleus test were 12.5-100 mg/kg for the i.p. route and 25-200 mg/kg for the p.o. route. The sampling time was 48 h. Frequencies of MNPCEs increased dose-dependently by the i.p. route but peaked at 50 or 100 mg/kg for the p.o. route. 6-MP induced MNPCEs more efficiently after p.o. administration than after i.p. treatment in both strains.

Administration, Oral↗

New percutaneous transluminal coronary angioscope.

A new percutaneous transluminal coronary angioscopic catheter has been developed for visualization of the coronary artery. A specially made balloon, fixed at the catheter tip, and an angulation mechanism made a precise coaxial alignment possible in the coronary lumen. This angioscopic catheter, 1.22 mm in outer diameter, has four channels, one for irrigation in which a 0.36 mm (0.014 in.) angioplasty guide wire can be used. With the use of this angioscope, coronary lumens in 8 dogs, thrombi that were produced with copper coils in the left anterior descending coronary artery in 11 dogs, atherosclerotic coronary arteries in 20 patients during cardiac catheterization and the sequence of transluminal coronary angioplasty in 1 patient were observed. The angioscopic catheter was introduced into the coronary artery by an 8F guide catheter. The steerable guide wire enabled the angioscopic catheter to be accurately and safely inserted into the target lesion in all cases. The inflated balloon and angulation mechanism allowed a curved coronary lumen and atheroma to be seen with a limited volume of irrigation fluid. Visualization was good (complete visualization of the inner lumen) in 46% (10 of 22 lesions), moderate (visualization of greater than 50% of the inner lumen) in 36% (8 of 22 lesions) and poor (visualization of less than 50% of the inner lumen) in 18% (4 of 22 lesions) in humans. There were no major complications. These preliminary experiences in closed chest cardiac catheterization in dogs and in humans indicate the feasibility of this angioscope. The information yielded by angioscopy may be clinically useful in the study of the pathophysiologic changes in coronary disease that are not detected by coronary arteriography.

Aged↗

Prostaglandin-mediated suppression of in vitro growth of erythroid progenitor cells.

In vitro hematopoiesis was evaluated in 37 patients with chronic renal failure (CRF) who developed moderate to severe anemia in order to clarify the relationship between the growth of erythroid progenitor cells and CRF-associated anemia. Bone marrow cells from these patients were cultured in the presence of recombinant erythropoietin. Both early and late erythroid progenitor cells (BFU-E and CFU-E) were significantly suppressed in patients with CRF compared to those in normal controls, while myeloid progenitor cells (GM-CFC) remained normal. Suppression of CFU-E was shown to be mediated by prostaglandin(s) secreted from bone marrow adherent cells. Furthermore, the suppression of CFU-E was inversely correlated with concentrations of uremic serum or parathyroid hormone added to the assay system. These observations suggest a possibility that late erythroid progenitor cells may be preferentially suppressed by the network consisting of parathyroid hormone, bone marrow adherent cells and prostaglandin(s).

Anemia↗

Development of drug resistance in cultured clonogenic leukemic blast cells during the clinical course of myeloblastic leukemia.

We studied changes in the drug sensitivity of clonogenic leukemic blast cells from patients with acute myeloblastic leukemia during clinical courses. These cells were assayed using the colony formation technique in methylcellulose culture. Various doses of each of two chemotherapeutic agents, daunorubicin and aclarubicin, were added at the start of culture, and drug sensitivities were measured in terms of percentage inhibition of leukemic blast colony formation. Clonogenic leukemic blast cells became less sensitive to the drugs which were administered to the patients during the course of the disease, suggesting that development of drug resistance in vivo may reflect the presence of dominant resistant populations of clonogenic leukemic blast cells in vitro.

Aclarubicin↗

Structural elucidation of aculeximycin. I. Further purification and glycosidic bond cleavage of aculeximycin.

A new insecticidal antibiotic, aculeximycin (ACM), was produced by an actinomycete identified as Streptosporangium albidum. ACM has been successfully isolated from culture filtrate by a combination of Diaion HP-20, Amberlite CG-50, reversed phase silica gel and Sephadex LH-20 chromatographies. It was found that ACM is a basic glycosidic antibiotic with a molecular weight of 1,672 including five monosaccharide units, three double bonds and a hemiketal ring by preliminary spectral analyses. Treatment of ACM with 1,8-diazabicyclo[5,4,0]undecene-7 caused a glycosidic bond cleavage to give aculexitriose, pseudoaglycones I and II.

Actinomycetales↗

Structural elucidation of aculeximycin. II. Structures of carbohydrate moieties.

Treatment of aculeximycin with 2% 1,8-diazabicyclo[5,4,0]undecene-7 (DBU)-methanol yielded three products, aculexitriose, pseudoaglycones I and II. The structural elucidation of aculexitriose was carried out by spectral analyses (MS, NMR (1H-1H 2D NMR spectroscopy, nuclear Overhauser effect] and chemical degradations of aculexitriose and its derivatives. The structure of aculexitriose was established to be a branched trisaccharide, O-6-deoxy-beta-D-glucopyranosyl-(1----2)-O-[3-amino-2,3,6-trideoxy-beta- D- arabino-hexopyranosyl-(1----3)]-6-deoxy-D-glucopyranose. On the other hand the pseudoaglycones I and II were stereoisomers with respect to a chiral center newly formed by the DBU reaction. The pseudoaglycones contain one neutral sugar and one amino sugar, which turned out to be D-mannose and L-vancosamine, respectively.

Acetylation↗

Chironomidae as a cause of IgE-mediated histamine release in patients with asthma.

The present study was undertaken to assess the importance of Chironomidae as an allergen causing bronchial asthma in Japan, and to evaluate histamine release as an allergy test in chironomid-midge allergic patients. Extracts of Chironomidae (T. akamusi and C. Yoshimatsui) caused the release of histamine in six out of 13 allergic patients with positive skin tests. In contrast, histamine release induced by these allergens was not observed in leukocytes from two asthmatic patients and five control subjects without IgE antibody as evidenced by negative skin tests and RAST. There was a significant correlation between maximal histamine release and IgE antibody levels. Furthermore, a significant inverse relationship between the concentration of allergen causing 25% histamine release (HR25) and IgE antibody levels was observed. The correlation coefficients, however, between histamine release and RAST were not high, and there were discrepancies between the two tests in some cases. These results suggest that Chironomidae induce histamine release from leukocytes via IgE-mediated mechanism but histamine release cannot be replaced by RAST and also suggest that chironomid midge is one of the important allergens in Japan.

Allergens↗

[Sézary syndrome associated with hepatocellular carcinoma and monoclonal gammopathy--a case report].

We treated 54-year-old Japanese man with a large cell type of Sézary syndrome. He had generalized erythrodermia, superficial lymphadenopathy, atypical lymphocytes in the peripheral blood, anti-HTLV-I antibody negativity and chromosomal abnormality. The patient was a hepatitis B virus carrier, and was complicated with hepatocellular carcinoma and monoclonal gammopathy of IgG, lambda type. Sézary syndrome is a T cell malignancy, the clinical course of which is relatively mild and chronic; accordingly, this case showed no crisis under chemotherapy. However, the patient died due to rapid growth of the hepatoma. Although case reports of Sézary syndrome complicated with other malignancies are very few, the occurrence of malignancies is possible because of decreased immunological function in the patients. In this case, hepatitis B virus might participate in the hepatic oncogenesis under dysfunction of helper/inducer cells. In addition, the complication of monoclonal gammopathy was also interesting from the standpoint of the helper function of Sézary cells.

Carcinoma, Hepatocellular↗

Herpes simplex virus in oral mucosal ulcers in patients with hematological malignancy.

Developments of oral mucosal ulcers induced by herpes simplex virus (HSV) were studied in patients with hematologic malignancy. Herpes simplex virus type-1 (HSV-1) was identified by immunological staining using virus-specific monoclonal antibodies in the epithelial cells of such ulcers from two patients with malignant lymphoma (ML), three with acute myeloblastic leukemia (AML), one with refractomy anemia with excess blasts, two with chronic myelocytic leukemia (CML), one with acute lymphoblastic leukemia (ALL) and one with aplastic anemia (AA). Herpes simplex virus type-2 (HSV-2) was also identified in an ulcer from a patient with AML. Isolation of HSV-1 was successful in the two patients with ML, one with CML, one with AML, the one with ALL and the one with AA. The ulcers developed on the tongue (four cases), buccal membrane (five cases), hard palate (one case), soft palate (one case), soft palate (one case) and gingiva (two cases). Only one patient with CML and one with AML had accompanying labial vesicular lesions. All patients except the one with AA had previously been given combination chemotherapy with anti-neoplastic agents. The results indicate that HSV may have an important role to play in the development of chemotherapy-related oral mucosal ulcers in patients with hematological malignancy.

Adult↗

Allergenicity of Chironomidae in asthmatic patients.

In order to clarify the relation between asthma and Chironomidae, we examined the cross-reactivity between Chironomidae and other common allergens. We noted significant correlations between positive skin tests with Chironomidae and with other allergens. The radioallergosorbent inhibition test, however, suggested that there may be no cross-reactivity or, if any, only very low cross-reactivity between midge allergens and mite, house dust (HD), silk, shrimp, or mosquito allergens.

Allergens↗

[Allergen tests with midge allergens in Moriyama City, located on the south coast of Lake Biwa].

The main species of midge which emerge from the Lake Biwa, the biggest lake in Japan, are Tokunagayusurika akamusi (TA) and Chironomus pulmons. In order to determine how the existence of Lake Biwa affects the positivity to allergen tests with midge allergens, randomly selected asthmatic patients were examined by skin test and RAST. Out of 129 patients, 35 (27%) were positive to scratch tests with an extract of Chironomus yoshimatsui (CY). Out of 64 patients, 16 (25%) were positive to TA RAST and 12 (19%) were positive to CY RAST. The positive rate of skin tests was highest in the patients aged between 20 and 39. The positive rate of TA RAST was not significantly higher than the rates reported in other districts of Japan.

Adolescent↗

Re-evaluation of the phagocytic respiratory burst in the physiological or inflammatory state and in aging.

We studied the differences in oxygen metabolite generation, using a chemiluminescence (CL) assay, in peripheral blood phagocytic cells from various donors including healthy young volunteers, patients with acute or chronic inflammation, pregnant women, and elderly persons. The CL response of polymorphonuclear leukocytes (PMN) after stimulation with serum-opsonized zymosan was increased in patients with acute inflammation due to infection and in pregnant women as compared with that in controls. Monocytes from those patients also showed a slight increase of the CL response. In contrast, CL of monocytes from patients with chronic inflammation (Crohn's disease patients) and elderly persons was significantly enhanced, whereas that of their PMN remained in the range of control values. The significance of these results was discussed.

Adolescent↗

Expression of cytokine genes in hematological malignancies.

A substantial number of leukemic blast colonies were formed when conditioned medium of human bladder carcinoma cell line 5637 was added as a stimulator. Recombinant colony-stimulating factor (CSF) also stimulated leukemic blast cell proliferation, leading to colony formation. Furthermore, serum CSF levels in some patients with acute myelogenous leukemia (AML), as detected by sensitive enzyme-linked immunosorbent assay (ELISA), were high. These observations prompted us to study further the expressions of hematopoietic growth factor genes. Granulocyte-macrophage CSF (GM-CSF) mRNA was detected in the leukemic blast cells from about 30% of patients with AML by Northern blot analysis using strict hybridization conditions with or without in vitro blast cell enrichment. These findings suggest that the expression of cytokine genes including the GM-CSF gene reflects in vivo phenomena, although no clear relationship between expression of the genes and serum CSF level has been established. Gene encoding tumor necrosis factor alpha (TNF-alpha), lymphotoxin (LT) and transforming growth factor beta (TGF-beta) were sometimes expressed in some malignant hematological cell lines and also some fresh leukemic cells.

Biological Factors↗

[Thrombocytosis in chronic myelogenous leukemia (CML) controlled by interferon alpha (IFN-alpha)].

A 39-year-old Japanese female who had been followed as chronic myelogenous leukemia (CML) since 1984 was admitted to our hospital because of dizziness. On admission, platelet count markedly increased (245 X 10(4)/microliters) in spite of daily administration of busulfan 2 mg. She was diagnosed as accelerated phase CML with thrombocytosis. So we tried to use interferon alpha (IFN-alpha) finally given in a dose of 9 X 10(6) U daily by subcutaneous injection. After that, platelet count decreased to 70 X 10(4)/microliters and megakaryocyte count in bone marrow decreased from 887.5/microliters to 395.7/microliters. But we had to stop IFN-alpha because of severe side effects.

Adult↗

Effects of Ca2+ antagonists on 45Ca2+ uptake by rat whole brain P1 and P2 fractions.

Voltage-dependent 45Ca2+ uptake into rat whole brain P1 (nonsynaptosomal) and P2 (synaptosomal) fractions was measured after 60-s KCl-stimulated depolarization to investigate possible inhibitory effects of Ca2+ antagonists, nitrendipine, diltiazem, verapamil and ifenprodil tartrate. All drugs (10(-5)M) had little influence on 45Ca2+ uptake by whole brain P1 fraction in both nondepolarizing and depolarizing mediums. Diltiazem (10(-5)M) had no influence on 45Ca2+ uptake by whole brain P2 fraction under both conditions. However, nitrendipine (10(-5)M) verapamil (10(-5)M) and ifenprodil tartrate inhibited depolarization-dependent 45Ca2+ uptake by whole brain P2 fraction, while nondepolarization-dependent 45Ca2+ uptake was not affected by these drugs. The inhibitory sequence of depolarization-dependent 45Ca2+ uptake by P2 fraction was: ifenprodil tartrate greater than nitrendipine greater than verapamil. These results suggest that ifenprodil tartrate, nitrendipine and verapamil specifically inhibit depolarization-dependent synaptosomal 45Ca2+ uptake, but that diltiazem has little influence on it.

Animals↗