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Biomedical subjects

M Hirano

Publications and source records attributed to M Hirano.

At least 199 records · Page 11Linked to original sources

Spaceflight modulates insulin-like growth factor binding proteins and glucocorticoid receptor in osteoblasts.

Rat osteoblasts were cultured for 4 or 5 days during a Space Shuttle mission. After 20-h treatment with 1alpha,25-dihydroxyvitamin D3, conditioned media were harvested and cellular DNA and/or RNA were fixed on board. The insulin-like growth factor binding protein (IGF BP)-3 levels in the media were three- and tenfold higher than in ground controls on the fourth and fifth flight days, as quantitated by Western ligand blotting and radioimmunoassay, respectively. The increased IGF BP-3 protein levels correlated with two- to threefold elevation of IGF BP-3 mRNA levels, obtained by reverse transcription-polymerase chain reaction. The IGF BP-5 mRNA levels in flight cultures were 33-69% lower than in ground controls. The IGF BP-4 mRNA levels in flight cultures were 75% lower than in ground controls on the fifth day but were not different on the fourth day. The glucocorticoid receptor mRNA levels in flight cultures were increased by three- to eightfold on the fourth and fifth days compared with levels in ground controls. These data suggest potential mechanisms underlying spaceflight-induced osteopenia.

Animals↗

Electron microscopic investigation of sulcus vocalis.

This investigation was carried out to determine the histopathologic findings of sulcus vocalis in two human adult larynges. Observations were made by light and transmission electron microscopy. The results are summarized as follows. Sulcus was confined to the squamous epithelium area. The basement membrane thickness increased at the sulcus. The sulcus was situated in the superficial layer of the lamina propria, which was thin around the bottom of the sulcus. Collagenous fibers were dense, and fibrous long-spacing collagen was seen around the bottom of the sulcus. Elastic fibers decreased in number and were composed predominantly of microfibrils and reticular amorphous substances. In the maculae flavae, the fibroblasts were decreased in number and degenerated. Collagenous and elastic fibers, synthesized by fibroblasts in the maculae flavae, were decreased. There were many abnormal elastic fibers in the maculae flavae. The quality and quantity of the fibrous components were changed in the mucosa of sulcus vocalis, owing in part to dysfunction of the fibroblasts and abnormal fibrogenesis in the maculae flavae.

Basement Membrane↗

Age-related changes in the human laryngeal glands.

The present study was conducted to determine age-related changes in the human laryngeal glands by means of excised human adult larynges. Scanning and transmission electron microscopic observations were made. The results obtained are summarized as follows. 1) Granular endoplasmic reticulum and Golgi apparatus were sparse in the cytoplasm of serous and mucous cells. 2) Secretory granules in serous cells had decreased in number. 3) Secretory granules were less electron-dense compared to those in younger adult specimens, but were electron-lucent. 4) Mucigen droplets in mucous cells were not as numerous as those in younger adults. 5) Discharge of secretory granules and mucigen droplets had decreased. 6) Age-related morphologic changes in the laryngeal glands influenced not only the amount but also the quality of secretions. 7) The above changes lessened lubrication of the vocal folds, thus causing aging of the voice to some extent. 8) Local immunity and mucociliary transport were also affected. 9) Age-related changes in the laryngeal glands partially altered laryngeal function.

Adult↗

Multiple mtDNA deletions features in autosomal dominant and recessive diseases suggest distinct pathogeneses.

Multiple mitochondrial DNA (mtDNA) deletions have been described in patients with autosomal dominant progressive external ophthalmoplegia (AD-PEO) and in autosomal recessive disorders including mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and autosomal recessive cardiomyopathy ophthalmoplegia (ARCO). The pathogenic bases of these disorders are unknown. We studied three patients with AD-PEO and three patients with autosomal recessive (AR)-PEO (two patients with MNGIE and one patient with ARCO). Histochemistry and Southern blot analyses of DNA were performed in skeletal muscle from the patients. Muscle mtDNA was used to characterize the pattern and amounts of the multiple mtDNA rearrangements; PCR analysis was performed to obtain finer maps of the deleted regions in both conditions. The patients with AD-PEO had myopathic features; the patients with AR-PEO had multisystem disorders. The percentage of ragged-red and cytochrome c oxidase-negative fibers tended to be higher in muscle from the patients with AD-PEO (19% +/- 13.9, 29.7 +/- 26.3) than in muscle from the patients with AR-PEO (1.4% +/- 1.4, 3.3% +/- 3.2; p < 0.10). The sizes of the multiple mtDNA deletions ranged from approximately 4.0 to 10.0 kilobases in muscle from both groups of patients, and in both groups, we identified only deleted and no duplicated mtDNA molecules. Patients with AD-PEO harbored a greater proportion of deleted mtDNA species in muscle (31% +/- 5.3) than did patients with AR-PEO (9.7% +/- 9.1; p < 0.05). In the patients with AD-PEO, we identified a deletion that included the mtDNA heavy strand promoter (HSP) region, which had been previously described as the HSP deletion. The HSP deletion was not present in the patients with AR-PEO. Our findings show the clinical, histologic, and molecular genetic heterogeneity of these complex disorders. In particular, the proportions of multiple mtDNA deletions were higher in muscle samples from patients with AD-PEO than in those from patients with AR-PEO.

Adult↗

A novel mutation of the GTP-cyclohydrolase I gene in a patient with hereditary progressive dystonia/dopa-responsive dystonia.

We report a 37-year-old Japanese woman with hereditary progressive dystonia with marked diurnal fluctuation and dopa-responsive dystonia. She developed dystonia in the lower limbs at the age of 11 years, followed by spasmodic torticollis and resting tremor of the feet, which responded remarkably to low doses of levodopa (100 mg/day). Concentrations of biopterin and neopterin in CSF were decreased. Polymerase chain reaction analysis of the guanosine 5'-triphosphate cyclohydrolase I gene revealed a novel mutation (Thr186-->Lys).

Adult↗

Missense mutation in the mtDNA cytochrome b gene in a patient with myopathy.

A patient with progressive exercise intolerance, proximal weakness, and complex III deficiency in skeletal muscle had a missense mutation in the cytochrome b gene of mitochondrial DNA (G15762A). The mutation, which leads to the substitution of a highly conserved amino acid (G339E), was heteroplasmic (85%) in the patient's muscle and was not present in 100 individuals of different ethnic backgrounds. These data strongly suggest that this molecular defect is the primary cause of the myopathy.

Adult↗

NC-1900, a [pGlu4,Cyt6]AVP(4-9) analogue, facilitates the learning performance of rats on delayed nonmatching to sample task in Y-water maze.

The effect of a novel peptide, NC-1900 (pGlu-Asn-Ser-Pro-Arg-Gly-NH2) on learning behavior in normal animals was studied in delayed nonmatching to sample tasks in rats using a Y-water maze. In the acquisition tests, a nonmatching to sample task, a delayed nonmatching to sample task with a delay time of 10 min (10-min DNMTS task), and a 20-min DNMTS task were performed for 15 sessions. NC-1900 was administered subcutaneously 1 h prior to the start of the acquisition test once a day. In the retention tests, the 10-min DNMTS task (on days 3, 10 and 17) and 20-min DNMTS task (on days 4, 11, 19 and 26) were conducted over time in the absence of administration of NC-1900 following completion of the acquisition test of the 10-min DNMTS task. In the acquisition of the 10- and 20-min DNMTS tasks, the NC-1900 100 pg/kg group exhibited significantly higher correct choice percentages or percentages of rats that achieved the criteria (mean correct choice percentage for 3 days of 90% or higher) in comparison with the control group. In the retention tests, in contrast to the correct choice percentages on each test day for the 20-min DNMTS task of the control group being approximately 50%, rats administered NC-1900 demonstrated high correct choice percentages at all dose levels, although there were some variations on each test day. These results demonstrate that NC-1900 clearly facilitated acquisition and retention of DNMTS tasks in rats using a Y-water maze.

Animals↗

Utility of measuring serum parathyroid hormone-related protein concentration in leukemic patients with hypercalcemia for assessing disease status.

OBJECTIVE: To evaluate serum parathyroid hormone-related protein (PTHrP) as a marker of hypercalcemia in leukemic patients. DESIGN AND METHODS: We measured the serum levels of PTHrP, lactate dehydrogenase (LDH) and calcium in three patients with hypercalcemia due to leukemia. RESULTS: Serum levels of PTHrP, LDH and calcium were elevated at admission in all patients, and these levels were reduced to within the normal range after chemotherapy. However, normalization of serum PTHrP concentration occurred more rapidly than normalization of serum LDH levels after chemotherapy. The increase in serum PTHrP concentration accompanied leukemic cell proliferation and preceded the increases in serum LDH and calcium. Serum LDH concentration increased, but serum PTHrP concentration did not after administration of granulocyte colony-stimulating factor. CONCLUSION: These findings suggest that serum PTHrP may be a more useful marker than serum LDH or calcium in assessing the status of leukemic patients with hypercalcemia.

Biomarkers↗

Dissociation between specific personal episodes and other aspects of remote memory in a patient with hippocampal amnesia.

In this paper, we describe some features of remote memory in a single-case, Y.K., with amnesic syndrome. His ability to access remote memory was investigated through a variety of tests and then analyzed in terms of specific aspects of remote memory, i.e., public events, personal semantic memory, and specific personal episodes. Although Y.K. showed relatively good performance in recalling public events, personal semantic memory, and general personal events, he was not able to recall specific personal episodes over his entire life span. That is, there appears a clear dissociation between recalling specific personal episodes and other aspects of remote memory. This suggests he lacks "richness" in his remote memory, which is probably necessary to maintain one's own identity.

Amnesia↗

New medicinal treatment for severe gingivostomatitis.

We formulated de novo a poraprezinc-sodium alginate suspension (P-AG) as a specific treatment for severe gingivostomatitis and administered it to 15 patients who had developed such inflammation while on chemotherapy. Very high utility of P-AG was demonstrated and the response was classified as excellent in 10 patients and good in 5 patients. The mechanism of the beneficial effect of P-AG in treatment of severe gingivostomatitis accompanied by hemorrhagic erosion and ulcers is considered to involve the mucosal protective effect, free radical scavenging activity and tissue repair promoting action of poraprezinc together with the hemostatic action of sodium alginate.

Adult↗

The treatment of periocular and facial pain with topical capsaicin.

This article describes the effects of topically applied capsaicin (a nociceptive substance-P suppressor) in patients with neuropathic periocular or facial pain. Peripheral neuropathic pain is a major cause of periocular or facial discomfort and usually follows injury to a subcutaneous peripheral nerve. Though the damage is local, the pain tends to radiate. We studied three patients who complained of a 2- to 30-year history of fluctuating pain in the periocular area. All three had an area of point tenderness that responded to the topical application of capsaicin cream.

Administration, Topical↗

Mitochondria and heart disease.

Because the myocardium depends heavily on oxidative metabolism, it is not surprising that genetic errors of mitochondrial function often result in cardiomyopathies. The emphasis of this review is on disorders of the respiratory chain, the only area of cell metabolism that is under dual genetic control: 1) the mitochondrial genome (mtDNA) encodes 13 subunits of respiratory chain complexes, and 2) the nuclear genome not only encodes all other respiratory chain proteins, but also mitochondrial translocases, components of the mitochondrial protein transport machinery, and factors that are essential for mtDNA transcription, translation, and replication. Mitochondrial cardiomyopathies due to mutations in the nuclear DNA are inherited as mendelian traits involving structural or enzyme proteins of the respiratory chain, mitochondrial protein importation, or the dialogue between the two genomes. Mitochondrial cardiomyopathies due to mtDNA mutations can be sporadic or inherited as maternal traits and follow the rules of "mitochondrial genetics," which are outlined briefly. MtDNA mutations can cause isolated cardiomyopathies or, more often, multisystem disorders of which cardiac involvement is a major component. We review recent advances in this rapidly expanding field and briefly discuss pathogenetic problems and the mitochondrial theory of presbycardia.

Age Factors↗

Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes.

In an unprecedented finding, Davis et al. [Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N. & Parker, W. D., Jr. (1997) Proc. Natl. Acad. Sci. USA 94, 4526-4531] used an unusual DNA isolation method to show that healthy adults harbor a specific population of mutated mitochondrial cytochrome c oxidase (COX) genes that coexist with normal mtDNAs. They reported that this heteroplasmic population was present at a level of 10-15% in the blood of normal individuals and at a significantly higher level (20-30%) in patients with sporadic Alzheimer's disease. We provide compelling evidence that the DNA isolation method employed resulted in the coamplification of authentic mtDNA-encoded COX genes together with highly similar COX-like sequences embedded in nuclear DNA ("mtDNA pseudogenes"). We conclude that the observed heteroplasmy is an artifact.

Adult↗

Serum protein determination by high-performance gel-permeation chromatography.

A general high-performance gel-permeation chromatography (HPGPC) method was developed to determine protein in human serum with improved sensitivity and speed. The optimum UV wavelength for protein detection was found to be 210 nm, by comparing the protein values obtained by varying the UV wavelength of the HPLC detection system with the protein values obtained from spectrophotometric protein assays, i.e., the bicinchoninic acid (BCA) method and the biuret method. The analysis time was less than 1 min. Since this HPGPC serum protein assay method is simple and rapid, it is expected to be particularly well adapted for use in clinical laboratories.

Adolescent↗