Search PubMed⌕ Search

Biomedical subjects

H Hirai

Publications and source records attributed to H Hirai.

At least 73 records · Page 4Linked to original sources

TT virus in hematological disorders and bone marrow transplant recipients.

TT virus (TTV) was cloned as a possible causative agent for non A to C posttransfusion hepatitis. Determination of the entire sequence of the virus revealed that the virus is the first human circovirus. The nucleotide sequence of TTV has a wide range of diversity and at least sixteen genotypes have been discovered to date. The prevalence of TTV infection in the normal population differs among countries, but exceeds 10% in several countries. Most of TTV infections are not associated with hepatitis, although there is evidence of TTV-induced hepatitis, especially caused by TTV of genotype I. To determine whether TTV is replicated in the liver is important in order to show that TTV is really a hepatitis virus, because results of a study in bone marrow transplant (BMT) recipients suggested that TTV might be replicated mainly in the hematopoietic cells. The prevalence of TTV infection in patients with hematological disorders who regularly require blood products was extremely high, but most of the infections did not cause liver injury, even in BMT recipients.

Bone Marrow Transplantation↗

Early relapse after high-dose chemotherapy rescued by tumor-free autologous peripheral blood stem cells in acute lymphoblastic leukemia: importance of monitoring for WT1-mRNA quantitatively.

A 24-year-old woman who suffered from ALL with MLL gene rearrangement received high-dose chemotherapy followed by autologous PBSC transplantation during complete remission (CR). Reverse transcriptase-polymerase chain reaction (RT-PCR) used to detect MLL/LTG4 chimeric mRNA showed no minimal residual disease (MRD) in the graft or bone marrow at the transplantation. However, the leukemia relapsed four months after transplantation. Retrospective analysis of quantitative measurement of Wilms tumor gene (WT-1) mRNA showed an increased level in the bone marrow although it was within the normal range. These observations suggest that careful monitoring of MRD by quantitative measurement of WT-1 mRNA in addition to disease-specific chimeric mRNA is required to predict relapse.

Adult↗

CJ-13,981 and CJ-13,982, new squalene synthase inhibitors.

Two new squalene synthase (SSase) inhibitors, CJ-13,981 (I) and CJ-13,982 (II), were isolated from the fermentation broth of an unidentified fungus CL 15036. They inhibited human liver microsomal SSase with IC50s of 2.8 and 1.1 microM, respectively, but showed no inhibitory activity against human brain protein farnesyltransferase (PFTase) at 100 microM. Based on FAB-MS and NMR analyses, the structures of I and II were determined to be 3-hydroxy-3,4-dicarboxy-15-hexadecenoic acid and 3-hydroxy-3,4-dicarboxyhexadecanoic acid, respectively.

Alkyl and Aryl Transferases↗

CJ-19,784, a new antifungal agent from a fungus, Acanthostigmella sp.

A new antifungal agent, CJ-19,784 (I), was isolated from the fermentation broth of a fungus, Acanthostigmella sp. CL12082. Based on spectroscopic analyses, structure of I was determined to be 3'-bromo-2',5-dihydroxy-3,7,8-trimethoxy-flavone. Compound I inhibits the growth of pathogenic fungi, Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus with IC50 values of 0.11, 20 and 0.54 microg/ml, respectively.

Antifungal Agents↗

CJ-15,801, a novel antibiotic from a fungus, Seimatosporium sp.

A novel antibiotic, CJ-15,801 (I), was isolated from the fermentation broth of a fungus, Seimatosporium sp. CL28611. The structure was determined to be a pantothenic acid analog having an alpha,beta-unsaturated carboxylic acid moiety by spectroscopic analyses. The compound inhibits the growth of multi-drug resistant (MDR) Staphylococcus aureus strains with MIC ranging from 6.25 to 50 microg/ml.

Anti-Bacterial Agents↗

Cytokine production inhibitors produced by a fungus, Oidiodendron griseum.

A series of diterpenes were isolated from the fermentation broth of a fungus, Oidiodendron griseum CL37215. The diterpenes were identified as LL-Z1271alpha, LL-Z1271gamma, CJ-14,445, PR 1388, CJ-14,604 and a new diterpene, CJ-14,515. They inhibited both lipopolysaccharide-induced interleukin-1beta and tumor necrosis factor-alpha production in human whole blood with IC50s of the range from 0.049 to 100 microM.

Ascomycota↗

Novel cytokine production inhibitors produced by a basidiomycete, Marasmiellus sp.

New cytokine production inhibitors, CJ-14,877 (I) and CJ-14,897 (II), were isolated from the fermentation broth of a basidiomycete, Marasmiellus sp. CL21624. Their structures were determined to be methyl-(7S,8S)-5-(7,8-dihydroxypropyl)pyridine-2-carboxylate and methyl-(7S,8S)-5-(8-acetoxy-7-hydroxypropyl)pyridine-2-carboxylate [corrected], respectively, by spectroscopic analyses. These compounds showed inhibitory activities for lipopolysaccharide-induced production of interleukin-1beta and tumor necrosis factor-alpha in human whole blood with IC50 values of the range from 0.059 to 2.6 microM.

Agaricales↗

CJ-15,183, a new inhibitor of squalene synthase produced by a fungus, Aspergillus aculeatus.

A new squalene synthase (SSase) inhibitor, CJ-15,183 (I) was isolated from the fermentation broth of a fungus, Aspergillus aculeatus CL38916. The compound potently inhibited rat liver and Candida albicans microsomal SSases and also inhibited the human enzyme. It also showed antifungal activities against filamentous fungi and a yeast. The structure was determined to be an aliphatic tetracarboxylic acid compound consisting of an alkyl gamma-lactone, malic acid and isocitric acid moieties by spectroscopic studies.

Alkenes↗

A new antibiotic CJ-17,665 from Aspergillus ochraceus.

A new antibiotic, CJ-17,665 (I) was isolated from the fermentation broth of Aspergillus ochraceus, CL41582. It inhibits growth of multi-drug resistant Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, with MICs of 12.5, 12.5 and 25 microg/ml, respectively. The structure contains a diketopiperazine and an indole N-oxide moiety that is unusual in natural products.

Anti-Bacterial Agents↗

New pyrrolizidinone antibiotics CJ-16,264 and CJ-16,367.

Two new antibiotics, CJ-16,264 (I) and CJ-16,367 (II), were isolated from the fermentation broth of an unidentified fungus CL39457. These antibiotics have a pyrrolizidinone skeleton, first discovered in fungi. Compounds I and II inhibit the growth of Gram-positive multi-drug resistant bacteria and some Gram-negative strains such as Moraxella catarrhalis and Escherichia coli with altered permeability (imp). Comparison of an antibacterial profile between the two compounds suggested that the gamma-lactone portion of I is important for the activity.

Anti-Bacterial Agents↗

[Therapy-related myeloid leukemia following platinum-based chemotherapy for ovarian cancer].

A 40-year-old woman, who had suffered from AML (M1) in 1983, developed ovarian cancer (stage IIIc) in December 1996 after long-term remission. She underwent surgical resection of the cancer, 10 courses of standard chemotherapy and tandem PBSCT (total dose: CBDCA 6,750 mg, CDDP 200 mg, CPA 16,000 mg, THP-ADR 450 mg). After receiving the last course of chemotherapy in June 1998, she was referred to our hospital in September 1998 because of pancytopenia. Laboratory findings showed pancytopenia with 34% leukemic cells, which were positive for alpha NBE and negative for POX and CAE. Surface-marker analysis of the leukemic cells showed positivity for CD11c, CD33, CD56, and DR, and chromosome analysis revealed 47, XX, +8. The patient was diagnosed as having AML (M5a), and received induction therapy consisting of IDR and Ara-C, which led to complete remission. As she had not received etoposide, this case was thought to have been therapy-related leukemia due to the platinum agents used for treating the ovarian cancer.

Adult↗

[Successful therapy of cyclosporin A in a case with idiopathic interstitial pneumonia].

Seventy-one-year-old woman was visited to our hospital because of dry cough and dyspnea on effort. Fine crackle was audible on both lower lung fields. Joints and skin were normal. Laboratory examination revealed elevation of serum LDH and CRP level. Both anti-nuclear antibody and Jo-1 antibody were negative. Blood gas analysis showed hypoxia after exercise. Chest X-ray film showed reticular shadow in both lower lung fields. Chest CT finding showed patchy area of ground glass attenuation, air-space consolidation, and reticular shadow. Scintigram showed diffuse uptake of Gallium-67 in both lung. Transbronchial biopsy specimen revealed alveolar wall thickness, lymphocyte infiltration and swelling of type II pneumocytes. Bronchoalveolar lavage fluid analysis revealed elevation of CD4/CD8 ratio. She was given a diagnosis of idiopathic interstitial pneumonia. Combination therapy of cyclosporin A and steroid was performed. After therapy, her chest CT findings and her data of pulmonary function test were improved. Then therapy of cyclosporin A was continued and dose of prednisolone was gradually decreased. After that, she was suffered from respiratory tract infection. After administration of antibiotics and cyclosporin A, she was getting well without acute exacerbation of interstitial pneumonia. Since then, she was treated with cyclosporin A only and her pulmonary function test data were gradually improved more. It suggests that cyclosporin A may be useful for the treatment of idiopathic interstitial pneumonia.

Aged↗

Relationship of telomere sequence and constitutive heterochromatin in the human and apes as detected by PRINS.

Hitherto, hominoid telomere sequences have been localized only at essential telomere regions of chromosome ends using ordinary FISH. In the present study, however, a PRINS technique revealed the new insight that chromosomes of humans and apes have many internal locations of the sequence. Moreover, a combination of PRINS and post-PRINS C-banding elucidated that the internal telomeric repeats corresponded with regions of constitutive heterochromatin. The PRINS reaction appeared more sensitive than the standard FISH technique, as it provided greater resolution of FITC signals. Furthermore, G- and R-like bands yielded by post- PRINS counter-staining with DAPI and PI, respectively, were informative in identification of chromosomes as well as the detailed characterization of those chromosomal structures signaling positive for the PRINS reaction. The combined efforts of FITC signals, DAPI-, PI-, and C-bands are most precisely analyzed through the use of a microscope mounted with a cooled CCD camera and an auto-wheel fluorescence filter set regulated by a computer.

Animals↗

Nonredundant roles of the elongation factor MEN in postimplantation development.

The MEN/ELL gene was cloned as a fusion partner of the MLL gene in the t(11;19)(q23;p13.1) translocation, which is found in adult myeloid leukemia. MEN belongs to a family of RNA polymerase II elongation factors and dysregulated production of MEN through the MLL promoter could cause malignant transformation of myeloid cells. To pursue the physiological role and determine the requirement of the MEN gene product in mouse development, we generated knockout mice (MEN-/-) by gene targeting in embryonic stem cells. After intercrossing heterozygous mice to generate homozygous mutants, we identified no homozygotes (MEN-/-) even at E9.5, as well as after birth, by Southern analysis. Moreover, histological examinations revealed degenerative changes in nearly one-fourth of E6.5 embryos, which were gradually resorbed by E8.5. Our findings demonstrated that MEN-/- mice are embryonic lethal, and die before E6.5 and after implantation. MEN should play a nonredundant role in postimplantation development of mice.

Adult↗