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Biomedical subjects

M Hirano

Publications and source records attributed to M Hirano.

At least 109 records · Page 6Linked to original sources
PubMed2000

Mitochondrial encephalomyopathies: therapeutic approaches.

Therapy of mitochondrial encephalomyopathies (defined restrictively as defects of the mitochondrial respiratory chain) is woefully inadequate, despite great progress in our understanding of the molecular bases of these disorders. We review available and experimental therapeutic approaches, which fall into seven categories: (1) palliative therapy; (2) removal of noxious metabolites; (3) administration of artificial electron acceptors; (4) administration of metabolites and cofactors; (5) administration of oxygen radical scavengers; (6) gene therapy; and (7) genetic counseling. Progress in each of these approaches provides some glimmer of hope for the future, although much work remains to be done.

Electron Transport↗
PubMed2000

Direct observation of specific messenger RNA in a single living cell under a fluorescence microscope.

We observed the expression of human c-fos mRNA in a living transfected Cos7 cell under a fluorescence microscope by detecting hybrid formed with two fluorescently labeled oligodeoxynucleotides (oligoDNAs) and c-fos mRNA in the cytoplasm. Two fluorescent oligoDNAs were prepared, each labeled with a fluorescence molecule different from the other. When two oligoDNAs hybridized to an adjacent sequence on the target mRNA, the distance between the two fluorophores became very close and fluorescence resonance energy transfer (FRET) occurred, resulting in changes in fluorescence spectra. To find sequences of high accessibility of c-fos RNA to oligoDNAs, several sites that included loop structures on the simulated secondary structure were selected. Each site was divided into two halves, and the pair of fluorescent oligoDNAs complementary to the sequence was synthesized. Each site was examined for the efficiency of hybridization to c-fos RNA by measuring changes in fluorescence spectra when c-fos RNA was added to the pair of oligoDNAs in solution. A 40 mer specific site was found, and the pair of oligoDNAs for the site were microinjected into Cos7 cells that expressed c-fos mRNA. To block oligoDNAs from accumulating in the nucleus, oligoDNA was bound to a macromolecule (streptavidin) to prevent passage of nuclear pores. Hybridization of the pair of oligoDNAs to c-fos mRNA in the cytoplasm was detected in fluorescence images indicating FRET.

Animals↗
PubMed2000

Endoscopic injection sclerotherapy for esophageal varices prolonged survival of patients with hepatocellular carcinoma complicating liver cirrhosis.

BACKGROUND: A prospective controlled study was performed between 1982 and 1991 to evaluate the efficacy of endoscopic injection sclerotherapy (EIS) in patients with esophageal varices complicated by hepatocellular carcinoma and liver cirrhosis. METHODS: The study included 83 patients with esophageal varices, hepatocellular carcinoma, and liver cirrhosis. Forty-three patients (group 1) underwent prophylactic EIS or emergent EIS for bleeding varices. EIS was performed weekly 4 to 6 times until the varices disappeared. The remaining 40 patients (group 2) underwent conservative therapy and did not undergo EIS. Survival rates were compared between the 2 groups. RESULTS: During the 5-year observational period, all patients who did not undergo EIS died. Sixteen in group 2 (40.0%) died of gastrointestinal bleeding including ruptured esophageal varices. In contrast, patients treated with EIS survived significantly longer (p<0.001). Nine patients (20.9%) treated with EIS experienced gastrointestinal bleeding as a result of which 5 (11.6%) died. EIS prolonged survival in patients classified as Child's A or B but did not affect survival in patients with Child's C hepatic function. EIS was effective in prolonging survival in patients with hepatocellular carcinomas smaller than 5 cm. However, EIS had no effect in patients with hepatocellular carcinomas that were larger than 5 cm. EIS prolonged survival only for patients with nodular hepatocellular carcinoma and had no effect in patients with massive and diffuse hepatocellular carcinoma. Further, EIS prolonged survival only for patients who did not have portal vein thrombosis. CONCLUSION: Based on this prospective study, we concluded that EIS was effective in prolonging the survival period of a select subset of patients with hepatocellular carcinoma.

Aged↗
PubMed2000

Missense mutants inactivate guanosine triphosphate cyclohydrolase I in hereditary progressive dystonia.

Hereditary progressive dystonia (HPD) with marked diurnal fluctuation is caused by mutant guanosine triphosphate (GTP) cyclohydrolase I (GCH). The clinical presentation of dominant HPD varies considerably. We proposed the hypothesis that a relative increase of mutant GCH capable of inhibiting normal GCH is responsible for heterogeneous phenotypic manifestations. In a Japanese family with a novel G90V mutation, an affected heterozygote had a higher mutant/normal mRNA ratio than an unaffected heterozygote. Co-expression analysis showed that mutant enzyme (GCH-G90V) inactivated the normal enzyme in the COS cells. Similarly, GCH-G203R showed the dominant negative effects. These results supported our proposed hypothesis.

Adult↗
PubMed2000

Progressive cardiac dysfunction in adriamycin-induced cardiomyopathy rats.

Cardiotoxicity is a limiting factor in the treatment of cancer with adriamycin. We administered adriamycin by a method which minimizes the risk of peritonitis in an adriamycin-induced cardiomyopathy rat model. Sixty male Wistar rats were given 1 mg/kg of adriamycin intraperitoneally 15 times over a 3-week period (total dose, 15 mg/kg) to induce the cardiomyopathy model. Fifteen control rats received 10 ml/kg body wt. saline 15 times over 3 weeks. The animals were observed for 12 weeks and assessed for mortality, and cardiac volume and function was analyzed by echocardiography at 4, 8, and 12 weeks. In rats treated with adriamycin, the cumulative mortality was 35.8% while in the controls, none of the rats died. Left ventricular diameter of the systole (LVDs) was significantly increased at 4 weeks (4.5 vs. 3.3 mm; P<0.001). Left ventricular diameter of the diastole (LVDd) was significantly increased at 12 weeks (7.9 vs. 7.0 mm; P<0.01) and the % fractional shortening (FS) was significantly decreased at 8 weeks (33.4% vs. 50.0%; P<0.01) in the adriamycin-treated rats. This administration method appears to be useful for investigating the cardiac effect of adriamycin while avoiding the influence of peritonitis typically caused by an intraperitoneal injection of higher single doses of adriamycin.

Animals↗
PubMed2000

CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) regimen with granulocyte colony-stimulating factor (G-CSF) for patients with aggressive non-Hodgkin's lymphoma: a pilot study. The Adult Lymphoma Treatment Study Group (ALTSG).

We conducted a multi-institutional collaborative study to examine the usefulness and safety of third-generation chemotherapy CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) combined with granulocyte colony-stimulating factor (G-CSF) in the treatment of aggressive non-Hodgkin's lymphoma (NHL). Subjects included patients with aggressive NHL who were 60 yr of age or younger and had been diagnosed as having a low-intermediate, high-intermediate, or high risk using the International Prognostic Index (IPI). A total of 24 patients were enrolled in the study between May 1997 and March 1998, including 9 low-intermediate-risk cases, 13 high-intermediate-risk cases and 2 high-risk cases. Although all 24 patients were originally enrolled in the study, one adult T-cell leukemia/lymphoma case was subsequently excluded. Thus, in the end, 23 cases were evaluated. Evaluation of the efficacy of therapy revealed complete remission in 20 patients (87%). Of these 20 patients, 8 were low-intermediate-risk cases (89%) and 12 were either high-intermediate- or high-risk cases (86%). Partial remission was achieved in 2 patients (8.7%). The 2-yr survival rate was 91.3%, and the 2-yr disease-free survival rate was 81.8%. Grade 3 or higher adverse reactions were granulocytopenia (87%), thrombocytopenia (17.4%) and liver dysfunction (4.3%). CyclOBEAP therapy has been associated with a high remission rate for aggressive NHL. When combined with G-CSF, a high relative dose intensity was maintained for each drug administered (0.94-0.97). Furthermore, although the observation period was short, both the survival rate and disease-free survival rate were good. Hence, we concluded that there were no problems associated with the procedure in terms of safety.

Adolescent↗
PubMed2000

Relation of lifestyle factors to metacarpal bone mineral density was different depending on menstrual condition and years since menopause in Japanese women.

OBJECTIVE: To examine whether the relation between lifestyle and metacarpal bone mineral density (BMD) varied with life-stages. DESIGN: Cross-sectional study. SETTING: Taking questionnaires related to lifestyle and examining metacarpal BMD by computed X-ray densitometry at a local health care center. SUBJECTS: Out of 750 Japanese women aged 40-69 y old who underwent screening for osteoporosis, we selected 535 healthy subjects without medical conditions or lifestyle factors known to affect bone metabolism. RESULTS: A cross-sectional comparison of BMD and years since menopause (YSM) resulted in a logarithmic regression model (BMD=2. 539-0.149xloge YSM, r2=0.418), indicating that a prominent reduction in metacarpal BMD appears up to 4-6 y after menopause. In premenopausal women with regular menstruation, those who engaged in regular physical activity during adolescence showed significantly greater BMD than those who did not. In 1-5-y postmenopausal women, those with current calcium intake of more than 800 mg/d, current milk intake greater than 900 ml/week, daily consumption of milk and/or dairy products, or frequent consumption of small fish showed significantly greater BMD. In 6-15-y postmenopausal women, those who took more than 6000 or 8000 steps/day showed significantly greater BMD. CONCLUSIONS: The relation between lifestyle and BMD differed with life-stages in Japanese women. It was suggested that to perform lifestyle modifications for the prevention of osteoporosis, life-stages should be taken into consideration. SPONSORSHIP: Grant for Research on Health Service from Ministry of Health and Welfare, Japan and grant from The National Dairy Promotion and Research Association of Japan. European Journal of Clinical Nutrition (2000) 54, 9-13

Adult↗
PubMed2000

Endoscopic surgery for a parathyroid functioning adenoma resection with the neck region-lifting method.

Recently, endoscopic surgery has been applied to cervical exploration. We have developed new techniques for endoscopic neck surgery. We reported on a 53-year-old Japanese man with functioning parathyroid adenoma resected by endoscopic surgery with a neck region-lifting method. A 10-mm midline trocar for the endoscope and two 5-mm lateral trocars were inserted from the anterior chest wall to avoid neck scars. There were no intraoperative complications. The incisions were completely covered by the patient's undergarments.

Adenoma↗
PubMed2000

Fibroblasts in geriatric vocal fold mucosa.

Fifty fibroblasts in the macula flava (MF) and 50 fibroblasts in the Reinke's space (RS) of geriatric vocal folds were studied by transmission electron microscopy. Five larynges from autopsy cases in the age range 74-83 years were included in the study. The results were compared with those obtained previously from younger adults. The majority of fibroblasts in RS were spindle-shaped and those in MF were stellate. This was the case with younger adults. The nucleus/cytoplasm (N/C) ratio was 0.5-2.0 in most fibroblasts in RS and MF. Again, this was in common with the findings in younger adults. The development of rough endoplasmic reticulum (rER) and Golgi apparatus (GA) in MF was less marked in the geriatric group than in adults. Glycogen particles were observed in 28 fibroblasts in MF. Lipofuscin granules were found in 12 fibroblasts of RS and 9 cells of MF. The findings suggest a decrease in activities and the presence of ageing processes in fibroblasts of geriatric vocal fold mucosa, to which geriatric changes in the vocal ligament can be attributed.

Aged↗
PubMed2000

Efficacy of temporal musculopericranial flap for reconstruction of the anterior base of the skull.

Since March 1988 the temporal musculopericranial (TMP) flap has been used as our flap of choice to reconstruct defects of the anterior base of the skull that are larger than 2 x 3 cm, including the dura mater, in 33 patients. The primary diseases were malignant head and neck tumours (n = 16), trauma (n = 15), meningioma (n = 1), and teratoma (n = 1). The dura mater was reconstructed with a unilateral TMP flap, after which the cranial and nasal cavities were closed with the opposite TMP flap. In addition, bone was grafted by sandwiching the bone between the two flaps and fixing it to the surrounding residual bone. When a large area was resected, making it impossible to use a TMP flap, a frontal musculopericranial (FMP) flap or a free flap (usually the rectus abdominis myocutaneous flap) was used to close the cranial and nasal cavities. Thirty of the 33 patients recovered with no postoperative complications. Two patients developed extradural abscesses in the anterior base of the skull and one developed mild meningitis, but they were successfully treated conservatively. When bilateral TMP flaps were used for the reconstruction, no patient had aesthetic problems in the forehead region. The TMP flap is extremely effective for the reconstruction of the anterior base of the skull because it is minimally invasive and causes few aesthetic problems in the forehead region.

Adolescent↗
PubMed2000

Current status of SOD1 mutations in familial amyotrophic lateral sclerosis.

Twenty percent of cases of familial amyotrophic lateral sclerosis (FALS) have identifiable mutations in the gene for Cu, Zn superoxide dismutase (SOD1) located on the long arm of chromosome 21. SOD1 mutations are thought to cause a yet unknown toxic gain of function resulting in motor neuron damage. Seventy-one mutations, located in all five exons of SOD1, have been reported. Identified mutations are predominantly heterozygous mis-sense mutations, although rare nonsense mutations, deletions, and insertions exist. While gene dosage has an effect on the age of onset, genotoype/phenotype correlation is better defined for progression of symptoms than for disease onset.

Amino Acid Substitution↗
PubMed2000

Maintenance of human rearranged mitochondrial DNAs in long-term cultured transmitochondrial cell lines.

Large-scale rearrangements of mitochondrial DNA (mtDNA; i.e., partial duplications [dup-mtDNAs] and deletions [Delta-mtDNAs]) coexist in tissues in a subset of patients with sporadic mitochondrial disorders. In order to study the dynamic relationship among rearranged and wild-type mtDNA (wt-mtDNA) species, we created transmitochondrial cell lines harboring various proportions of wt-, Delta-, and dup-mtDNAs from two patients. After prolonged culture in nonselective media, cells that contained initially 100% dup-mtDNAs became heteroplasmic, containing both wild-type and rearranged mtDNAs, likely generated via intramolecular recombination events. However, in cells that contained initially a mixture of both wt- and Delta-mtDNAs, we did not observe any dup-mtDNAs or other new forms of rearranged mtDNAs, perhaps because the two species were physically separated and were therefore unable to recombine. The ratio of wt-mtDNA to Delta-mtDNAs remained stable in all cells examined, suggesting that there was no replicative advantage for the smaller deleted molecules. Finally, in cells containing a mixture of monomeric and dimeric forms of a specific Delta-mtDNA, we found that the mtDNA population shifted towards homoplasmic dimers, suggesting that there may be circumstances under which the cells favor molecules with multiple replication origins, independent of the size of the molecule.

Cell Culture Techniques↗
PubMed2000

Identification and characterization of a molecule, BAM11, that associates with the pleckstrin homology domain of mouse Btk.

Bruton's tyrosine kinase (Btk) is required for normal B cell development and signal transduction through cell surface molecules, and its defects lead to X-linked immune deficiency in mice and X-linked agammaglobulinemia in humans. In this report, we will describe the identification and characterization of a molecule, BAM11, which binds to the pleckstrin homology domain of Btk. A sequence homology search revealed that BAM11 has 89% homology, at the amino acid level, to human LTG19/ENL, that was originally identified as one of the fusion partners involved in chromosomal translocations of 11q23, MLL/ALL-1/HRX, in leukemia cells. Deletion mutants demonstrated that the region of BAM11 required for binding to Btk was localized between amino acid residues 240 and 256. Forced expression of a truncated form of BAM11 (amino acids 246-368) inhibited IL-5-induced proliferation by 50%, whereas forced expression of full-length BAM11 in Y16 cells did not affect the IL-5 responsiveness. We have also shown that BAM11 (amino acids 246-368) inhibited the kinase activity of Btk. These results suggest that the binding of BAM11 to Btk plays a regulatory role in the Btk signal transduction pathway. A cell fractionation study and analysis using EGFP-fused Btk protein demonstrated that a proportion of Btk is present within the nucleus.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2000

Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). The Lymphoma Study Group of the Japan Clinical Oncology Group.

BACKGROUND: The main form of cytotoxic treatment for advanced Hodgkin's disease (HD) is conventional dose multiagents chemotherapy. As HD is not common in Japan, we conducted a phase II study of the commonly used combination chemotherapy (CCT) regimen established in the West for Japanese patients with advanced HD to confirm the efficacy and safety. METHOD: Between October 1989 and February 1993, a multicenter phase II study of alternating CCT C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, vinblastine, bleomycin, dacarbazine) to evaluate its clinical usefulness for clinical stage (cS) II-IV HD was conducted by the Lymphoma Study Group of the Japan Clinical Oncology Group. RESULTS: Seventy-nine previously untreated patients were enrolled in the study. For 67 eligible patients, the response rate was 92.5% with 83.6% complete response (CR). For 40 cS II and 27 cS III/IV patients the response rate was 95.0% with 90.0% CR and 88.9% with 74.1% CR, respectively. The overall 5-year survival rate was 84.8%. Those of cS II and cS III/IV were 92.5 and 73.1%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.1025). The progression-free 4-year survival rate was 72.8%. Those of cS II and cS III/IV were 77.5 and 65.7%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.2483). Grade 4 toxicity by the criteria of the World Health Organization consisted of leukocytopenia in 28.4% of patients. There was GPT elevation in 4.5%, nausea/vomiting in 11.9% and CNS in 1.5% of patients, but there was no treatment-related death. CONCLUSION: The C-MOPP/ABVd regimen for Japanese patients with advanced HD is considered to be one of the effective CCTs according to the results of the present phase II study.

Adolescent↗
PubMed2000

Defects of intergenomic communication: where do we stand?

An expanding number of autosomal diseases has been associated with mitochondrial DNA (mtDNA) depletion and multiple deletions. These disorders have been classified as defects of intergenomic communication because mutations of the nuclear DNA are thought to disrupt the normal cross-talk that regulates the integrity and quantity of mtDNA. In 1989, autosomal dominant progressive external ophthalmoplegia with multiple deletions of mitochondrial DNA was the first of these disorders to be identified. Two years later, mtDNA depletion syndrome was initially reported in infants with severe hepatopathy or myopathy. The causes of these diseases are still unclear, but genetic linkage studies have identified three chromosomal loci for AD-PEO. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), an autosomal recessive disorder associated with both mtDNA depletion and multiple deletions, is now known to be due to loss-of-function mutations in the gene encoding thymidine phosphorylase. Increased plasma thymidine levels in MNGIE patients suggest that imbalanced nucleoside and nucleotide pools in mitochondria may lead to impaired replication of mtDNA. Future research will certainly lead to the identification of additional genetic causes of intergenomic communication defects and will likely provide insight into the normal "dialogue" between the two genomes.

Cell Nucleus↗
PubMed2000

Involvement of two plasmids in fenitrothion degradation by Burkholderia sp. strain NF100.

A bacterium capable of utilizing fenitrothion (O,O-dimethyl O-4-nitro-m-tolyl phosphorothioate) as a sole carbon source was isolated from fenitrothion-treated soil. This bacterium was characterized taxonomically as being a member of the genus Burkholderia and was designated strain NF100. NF100 first hydrolyzed an organophosphate bond of fenitrothion, forming 3-methyl-4-nitrophenol, which was further metabolized to methylhydroquinone. The ability to degrade fenitrothion was found to be encoded on two plasmids, pNF1 and pNF2.

Biodegradation, Environmental↗
PubMed2000

Comparative histology of the maculae flavae of the vocal folds.

A light and electron microscopic comparative investigation of the maculae flavae of the vocal folds was carried out on excised human and canine adult larynges. The structure and functions of human adult maculae flavae (HMF) were found to differ from those of canine adult maculae flavae (CMF). The maculae flavae were composed of fibroblasts, elastic and collagenous fibers, and ground substance in humans and canines. The density of fibroblasts in HMF was found to exceed that in CMF. Fibroblasts in HMF were stellate with processes or spindle-shaped, and the nucleus-cytoplasm (N/C) ratio was small. Rough endoplasmic reticulum and Golgi apparatus were well developed in the cytoplasm. Fibroblasts in CMF were oval, and the N/C ratio was large. Endoplasmic organs were poorly developed in the cytoplasm. Synthesized elastic and collagenous fibers were more numerous in HMF than CMF, and the density of both in HMF was much greater than that in CMF. Ground substance was more abundant in CMF than HMF. Apparently, CMF did not produce elastic and collagenous fibers in amounts sufficient to develop vocal ligaments. The HMF contributes to the formation of the vocal ligaments and the layered structure of human vocal folds.

Adult↗