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Biomedical subjects

M Hino

Publications and source records attributed to M Hino.

At least 91 records · Page 5Linked to original sources

A practical quick staining method using hydrochloric acid-fast metachromatic dye for megakaryocytes.

A specific stain using violet polymethine dye (VPM stain) for megakaryocytes was first developed by Kass (1995). We have modified this method for practical use in bone marrow specimens. The modified VPM stain labels megakaryocytes very well, while other marrow cells are poorly colorized. This staining procedure was more stable, and its color intensity was finer and clearer than the original. Using this stain, morphologic classification of megakaryocytes in bone marrow specimens from 11 normal and 8 myelodysplastic syndrome (MDS) patients was performed. Many megakaryocytes observed in MDS patients were juvenile compared with normal subjects according to their morphology. Blasts from acute megakaryoblastic leukemia (M7) and from a megakaryoblastic cell line (Mo7e) were also clearly stained with our method. This staining method is practical and very useful for rapid identification of megakaryocyte distribution and morphology.

Bone Marrow Examination↗

C19 odd-chain polyunsaturated fatty acids (PUfas) are metabolized to C21-PUfas in a rat liver cell line, and curcumin, gallic acid, and their related compounds inhibit their desaturation.

It was demonstrated that the rat liver cell line BRL-3A converted exogenous C19 odd chain-polyunsaturated fatty acids (PUFAs) into the corresponding C21- and C23-PUFAs as follows: 21:3n-8, 21:4n-8, 23:3n-8, and 23:4n-8 (from 19:3n-8); 21:4n-5, 21:5n-5, 23:4n-5, and 23:5n-5 (from 19:4n-5); 21:5n-2, 21:6n-2, 23:5n-2, and 23:6n-2 (from 19:5n-2). It presumed that these C19 PUFAs were converted through the mimic route to docosahexaenoic acid (22:6n-3) from eicosapentaenoic acid (20:5n-3). In addition, the characterization of the change of fatty acid composition of cellular lipids in rat liver cells were examined, using 19:4n-5 and several fatty acid desaturation inhibitors. Curcumin related compounds, curcumin, capsaicin, isoeugenol, 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one, and gallic acid esters with near five carbon numbered alcohol had great changes of fatty acid composition of cellular lipids based on inhibition of the A6 desaturation of C24-PUFAs in rat liver cells.

Alkylation↗

Expression and mutational analysis of amino acid residues involved in catalytic activity in a ribonuclease MC1 from the seeds of bitter gourd.

The ribonuclease MC1 (RNase MC1) from seeds of bitter gourd (Momordica charantia) consists of 190 amino acids and belongs to the RNase T2 family, including fungal RNases typified by RNase Rh from Rhizopus niveus. We expressed RNase MC1 in Escherichia coli cells and made use of site-directed mutagenesis to identify essential amino acid residues for catalytic activity. Mutations of His34 and His88 to Ala completely abolished the enzymatic activity, and considerable decreases in the enzymatic activity were observed in cases of mutations of His83, Glu84, and Lys87, when yeast RNA was used as a substrate. Kinetic parameters for the enzymatic activity of the mutants of His83, Glu84, and Lys87 were analyzed using a dinucleoside monophosphate CpU. Km values for the mutants were approximately like that for wild-type, while k(cat) values were decreased by about 6 to 25-fold. These results suggest that His34, His83, Glu84, Lys87, and His88 in RNase MC1 may be involved in the catalytic function. These observation suggests that RNase MC1 from a plant catalyzes RNA degradation in a similar manner to that of fungal RNases.

Amino Acids↗

Leptin receptor and leukemia.

The receptor for leptin, the gene product of the obese gene, is expressed in hematopoietic stem cells. Leptin stimulates normal myeloid and erythroid development, and is secreted from bone marrow adipocytes, which occupy most of the marrow cavity in humans. Leptin might thus play an important role in the control of the expansion and differentiation of primitive hematopoietic cells through paracrine interaction in the bone marrow microenvironment. Leukemic cells of some patients with acute myeloblastic leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia (CML) also express the leptin receptor. In cases of CML, higher expression of leptin receptor is observed during blast crisis than in chronic phase. Leptin alone and in combination with other cytokines has stimulative effects on proliferation of leukemia cells as well as anti-apoptotic effects. These findings suggest the possibility that leptin plays roles in the pathophysiology of leukemia.

Carrier Proteins↗

A new antimitotic substance, FR182877. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

Using the characteristic morphological changes of mammalian cells, we screened novel antimitotic substances and found that a strain of Streptomyces sp. No.9885 produced FR182877. This substance was isolated from the culture broth by ethyl acetate extraction, silica gel column chromatography and ODS column chromatography. Structural studies on FR182877 suggested that it had a unique hexacyclic structure encompassing its highly strained double bond. FR182877 exhibited potent antitumor activities against murine ascitic tumor and solid tumor in vivo.

Animals↗

FR191512, a novel anti-influenza agent isolated from a fungus strain No.17415. I. Taxonomy, fermentation, isolation, physico-chemical properties and structure elucidation.

In the course of our screening for anti-influenza agents of microbial origin, FR191512 was isolated from the cultured broth of fungus strain No. 17415 as colorless powder. The structure of FR191512 was determined by several spectroscopic experiments as a novel polyphenolic compound. This compound showed potent antiviral activity against influenza A virus.

Antiviral Agents↗

WF14865A and B, new cathepsins B and L inhibitors produced by Aphanoascus fulvescens. I. Taxonomy, production, purification and biological properties.

WF14865A and B, novel cathepsins B and L inhibitors, were produced and isolated separately from the culture mycelium of a fungal strain Aphanoascus fulvescens No. 14865. Spectroscopic analysis revealed that both WF14865A and B were composed of trans-epoxysuccinyl moieties, 1-H-imidazole-2-ylamine, and isoleucine or leucine. These compounds inhibited human cathepsins B and L with IC50 values in the range of 8.4 approximately 72nM in vitro. Though their in vitro properties were typical as trans-epoxysuccinyl type inhibitors, they exerted strong bone resorption inhibitory effects in low-calcium-diet-fed mouse model at 3.2 approximately 10 mg/kg.

Animals↗

FR901469, a novel antifungal antibiotic from an unidentified fungus No.11243. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological properties.

FR901469 is a novel antifungal antibiotic produced by an unidentified fungus No.11243. This compound was isolated from the culture broth by solvent extraction, HP-20 and YMC ODS gel column chromatography, and lyophilization. FR901469 is a white powder which melts at 182 approximately 187 degrees C and possesses the molecular formula C71H116N14O23. This compound has good water solubility. FR901469 inhibited the activity of 1,3-beta-glucan synthase from Candida albicans with an IC50 value of 0.05 microg/ml, and displayed greater inhibitory activity than other 1,3-beta-glucan synthase inhibitors such as, WF11899A, echinocandin B, aculeacin A, and papulacandin B.

Animals↗

FR901469, a novel antifungal antibiotic from an unidentified fungus No.11243. II. In vitro and in vivo activities.

FR901469 is a water-soluble macrocyclic lipopeptidolactone (C71H116N14O23) that has inhibitory activity against 1,3-beta-glucan synthase and exhibits in vitro and in vivo antifungal activity against both Candida albicans and Aspergillus fumigatus. The MICs of FR901469 against Candida albicans FP633 and Aspergillus fumigatus FP1305 in a micro-broth dilution test were 0.63 and 0.16 microg/ml, respectively. FR901469 showed excellent efficacy by subcutaneous injection against both Candida albicans and Aspergillus fumigatus in a murine systemic infection mode, with ED50s of 0.32 and 0.2 mg/kg, respectively. This compound also showed potent anti-Pneumocystis activity in the nude mice model with experimental Pneumocystis pneumonia. The hemolytic activity of FR901469 towards mouse red blood cells, is about 30-fold weaker than that of amphotericin B.

Animals↗

Identification of cytochrome P-450 isoform(s) responsible for the metabolism of pimobendan in human liver microsomes.

Pimobendan, 4, 5-dihydro-6-(2-(4-methoxyphenyl)-1H-benzimidazol-5-yl)-5-methyl-3( 2-H )-pyridazinone, is a new inotropic drug that augments Ca(2+) sensitivity and inhibits phosphodiesterase in cardiomyocytes. Pimobendan is well absorbed after oral administration and is metabolized in the liver to the O-demethyl metabolite, which is also active. This study was conducted to identify the cytochrome P-450 (CYP) isoform(s) responsible for the pimobendan O-demethylation in human liver microsomes. Pimobendan O-demethylase activity in human liver microsomes was significantly correlated with phenacetin O-deethylase activity. CYP1A2 antibody and specific inhibitors of CYP1A2 strongly inhibited the metabolism of pimobendan. CYP1A2 was the only one of 10 recombinant human CYP isoforms tested that catalyzed pimobendan O-demethylation at the substrate concentration of 1 microM. At a high substrate concentration (100 microM), recombinant CYP3A4 also catalyzed the reaction, and antibody to CYP3A4 partially inhibited the activity in human liver microsomes. The contribution of CYP1A2 to pimobendan O-demethylation in human liver microsomes varied in the range of 18 to 76%, whereas CYP3A4 accounted for less than 10%, as calculated using the relative activity factor method. We conclude that CYP1A2 is one of the major enzymes responsible for the O-demethylation of pimobendan and CYP3A may make a minor contribution at clinically relevant concentrations of the drug.

Adolescent↗

[Seven cases of brain metastasis from papillary thyroid carcinoma].

Brain metastases from differentiated thyroid carcinoma are extremely rare and carry a poor prognosis. We describe here clinical details of 7 cases of brain metastases from papillary thyroid carcinoma. Of 153 patients with metastases from differentiated thyroid carcinoma (papillary in 123, follicular in 30) treated at our institution between 1981 and 1999, 7 patients (4.6%) had brain metastases. Histologically, the primary tumor was papillary carcinoma in all 7 cases. Four were males and 3 were females. The median age at first diagnosis of distant metastases was 63 yr (range, 47-76 yr). Of these patients, one had brain metastases only and six had metastases to the lungs as well. Five of these patients were treated with 131I. Three of these 5 patients had marked uptake in the metastases (131I positive) on post-therapy 131I scans and another 2 patients had no significant activity (131I negative) in both pulmonary and brain metastatic lesions. One of 3 patients with 131I positive lesions had intense activity in the brain tumor, but no uptake in multiple pulmonary metastatic tumors. In a patient with 131I positive brain metastases, the tumors progressed rapidly after 131I therapy. In another one patient, acute hemorrhage of the tumor occurred four days after 131I therapy, requiring surgical removal. Loner case of 131I negative 2 patients was treated with radiosurgery (gamma-knife) and complete reduction in tumor volume was observed. On the other hand, one of 2 patients receiving no 131I therapy had radiosurgery (x-knife) and remaining one received conventional external radiation and chemotherapy for small solitary brain and pulmonary metastatic tumors. These therapeutic interventions were useful in both cases. The mean length of survival after the development of brain metastases in the five patients who died of the disease was 30 months. One patient treated with x-knife has been alive at 21 months and another one who has 131I uptake in the brain tumor without uptake in lung lesions has been alive 15 months after diagnosis of brain metastasis. These results indicate that it is important to detect brain metastasis by imaging techniques and Tg measurements and give treatment as early as possible since the brain is the third most common distant metastatic site and the prognosis is poor.

Adolescent↗

Basic and clinical evaluation of a newly-developed enzymatic bilirubin assay.

An enzymatic bilirubin assay using bilirubin oxidase was evaluated. Its repeatability and linearity were excellent, and excellent correlations were observed between the enzyme and the diazo methods in total and conjugated bilirubin. The coefficient of correlation between the conjugated bilirubin fraction obtained with the diazo method and that of HPLC was 0.424, while this coefficient was 0.580 for the diazo method. A multi-laboratory study using 3 serum specimens revealed lower coefficients of variation for the enzymatic method than for the diazo method. Bilirubinuria specimen showed good accord between total bilirubin and conjugate bilirubin levels for the enzymatic method, not for the diazo method. When 12 newborn baby specimens and 34 pediatric specimens were studied, all exhibited increased concentrations of conjugated bilirubin with the diazo method. In an adult case with prolonged jaundice, the diazo method usually yielded higher conjugated bilirubin values than the enzymatic method. The enzymatic method was then concluded to be superior to the diazo method for conjugated bilirubin determination.

Adult↗

Analogues of ethylenediaminetetraacetic acid and sodium fluoride as anticoagulants.

Three analogues of ethylenediaminetetraacetic acid (EDTA), ethyleneglycoltetraacetic acid (EGTA), ethylendiaminedipropionic acid (EDDP), and hexamethylenediaminetetraacetic acid (HDTA), and sodium fluoride (NaF) were evaluated as anticoagulants used for rapid and multi-parametric analysis with minimal amounts of blood. EDDP and HDTA induced rapid blood coagulation (< 30 min), while NaF was not useful for coagulation tests because no coagulation was observed by addition of PT- or APTT-reagents. EGTA could be used for hematology and coagulation tests, although platelet count was significantly decreased in comparison with EDTA treated blood due to platelet aggregation, although prothrombin time was prolonged with EGTA-treated blood. Platelet aggregation could be prevented by addition of kanamycin. In chemistry tests, correlations between serum values and EGTA and kanamycin treated plasma values were good for all items. Based on these findings, we concluded that EGTA could be used for hematology, coagulation, and chemistry tests, although with some limitations.

Adult↗

[High-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of non-Hodgkin's lymphoma].

Findings for 41 patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and/or autologous peripheral blood stem cell transplantation (PBSCT) are reported. Two of the 41 patients were treated with HDC alone without PBSCT. At transplant, 20 patients were in complete remission, while 19 had resistant NHL and had failed to achieve a complete remission (CR) after several courses of conventional chemotherapy. The conditioning regimens used were mainly ACE (cytarabine, cyclophosphamide, etoposide) and MEAC (MCNU, etoposide, cytarabine, cyclophosphamide). The treatment-related mortality rate was 4.9%. Two patients treated with MEAC died from intractable congestive heart failure. Nine of the 19 patients with resistant NHL achieved CR, and at a median follow-up of 26 months (range, 3 to 93 months) the estimated two-year disease-free survival rate for these patients was 44.4%. Four patients in CR at present were in partial remission before HDC and PBSCT. Fifteen of the 20 patients in CR before HDC were transplanted in first CR and 5 in 2nd CR. At a median follow-up of 49 months (range, 3 to 96 months), the estimated 3-year DFS for the group of all patients was 73.7%. Five relapses occurred between 5 and 35 months post-transplantation. In conclusion, HDC and PBSCT as induction therapy was only effective for patients with resistant NHL who responded to conventional chemotherapy, and may improve the survival of patients in CR as consolidation therapy.

Adolescent↗