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M Hirano

Publications and source records attributed to M Hirano.

At least 19 recordsLinked to original sources
PubMed1992

Tissue-specific expression and chromosome assignment of genes specifying two isoforms of subunit VIIa of human cytochrome c oxidase.

Subunit VIIa of mammalian cytochrome c oxidase (COX; EC 1.9.3.1) exists in at least two isoforms, one present in all tissue types ('liver' isoform; COX VIIa-L) and the other specific for cardiac and skeletal muscle (COX VIIa-M). We have isolated a full-length cDNA encoding human COX VIIa-M. The deduced polypeptide represents the human ortholog of COX VIIa-M, as it shares 78% identity with bovine COX VIIa-M, but only 63% identity with human COX VIIa-L. Northern-blot analysis of primate tissues demonstrated that COXVIIa-M mRNA is present only in muscle tissues; in contrast, the COXVIIa-L mRNA is present in both muscle and nonmuscle tissues. Southern-blot hybridization of human-rodent cell hybrid genomic DNA indicates that the COXVIIa-M gene maps to a single locus on chromosome 19, designated COX7AM. In contrast, COXVIIa-L cDNA probes hybridized to fragments from two COX7AL loci, on chromosomes 4 and 14.

Amino Acid Sequence↗
PubMed1992

Differential expression of genes specifying two isoforms of subunit VIa of human cytochrome c oxidase.

Subunit VIa of mammalian cytochrome c oxidase (COX; EC 1.9.3.1) exists in two isoforms, one present ubiquitously ('liver' isoform; COX VIa-L) and the other present only in cardiac and skeletal muscle (COX VIa-M). We have now isolated a full-length cDNA specifying human COX VIa-M. The deduced mature COX VIa-M polypeptide is 62% identical to the human COX VIa-L isoform, but is approximately 80% identical to the bovine and rat COX VIa-M isoforms, suggesting that the two COX VIa isoform-encoding genes arose prior to the mammalian radiation. Transcriptional analysis showed a tissue-specific pattern: whereas COXVIa-L is transcribed ubiquitously, COXVIa-M is transcribed only in heart and skeletal muscle. The cDNA specifying COX VIa-M is a prime candidate for use in investigations of Mendelian-inherited COX deficiencies with primary involvement of muscle.

Amino Acid Sequence↗
PubMed1992

Phase II study: treatment of non-Hodgkin's lymphoma with an oral antitumor derivative of bis(2,6-dioxopiperazine).

BACKGROUND: Although razoxane (ICRF-159), a derivative of bis(2,6-dioxopiperazine), has shown significant antitumor activity in several murine tumors, inadequate bioavailability has limited its clinical efficacy. Sobuzoxane (MST-16), another derivative of bis(2,6-dioxopiperazine), has shown activity against a broad spectrum of murine tumors and human tumor xenografts in nude mice and a lack of cross-resistance to vincristine, doxorubicin, cyclophosphamide, fluorouracil, etoposide, and mitomycin C. These findings suggest that MST-16 has a mode of cytocidal activity different from that of other antitumor agents. PURPOSE: The present late phase II study was conducted to evaluate the clinical efficacy and toxicity of MST-16 in non-Hodgkin's lymphoma (NHL). METHODS: As part of a multi-institutional cooperative study, we conducted a study of MST-16 in 27 patients with NHL who were assessable for drug efficacy and toxicity. MST-16, a bis(2,6-dioxopiperazine) analogue and an inhibitor of topoisomerase II, was administered orally at a dose of 1600 mg/m2 a day for 5-7 days at intervals of 2-3 weeks. RESULTS: Response consisted of one complete remission and seven partial remissions in 27 assessable patients. Response was achieved at a median of 13 days (range, 9-62 days) after initiation of therapy and lasted a median of 46 days (range, 29-155 days). Major toxic effects were leukopenia in 70% of the patients, thrombocytopenia in 44%, and gastrointestinal disorders in 37%. CONCLUSIONS: MST-16 was shown to be effective in NHL and deserves further clinical trial, since the drug shows little cross-resistance to available antitumor drugs. IMPLICATIONS: Phase II clinical studies of MST-16 in treatment of breast cancer, gastric cancer, and adult T-cell leukemia and lymphoma are also being conducted in Japan. Future trials of combination chemotherapy using MST-16 with other antitumor drugs are warranted in view of the additive effects observed in studies of MOLT-3 cells and studies of L1210 leukemia in mice.

Administration, Oral↗
PubMed1992

Alternating non-cross-resistant chemotherapy for non-Hodgkin's lymphoma of intermediate-grade and high-grade malignancy. A pilot study.

Thirty-two patients with advanced non-Hodgkin's lymphoma (NHL) with aggressive histologic findings were treated with cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide, and prednisolone (CAMBO-VIP), in which presumably non-cross-resistant myelosuppressive and nonmyelosuppressive agents were administered during alternate weeks for 12 weeks. To ensure the high-dose intensity of the protocol, dose reduction and delay in treatment were minimized. Three patients were treated inadequately. Twenty-six (89.7%) of 29 evaluable patients had a complete response, and three had a good partial response. Relapse occurred in four patients, with a median follow-up of 29 months. The actuarial overall survival and disease-free survival were estimated to be 87.6% and 75.9%, respectively. The CAMBO-VIP treatment was well tolerated; myelosuppression was severe but transient and caused no serious infections. Side effects that affected dose intensity were oral ulceration, occurring in 28 patients, and blister formation under the thickened skin of palms and/or soles, followed by desquamation (5 patients). Hepatic toxicity was generally mild to moderate; it was severe in one patient. A 12-week regimen of CAMBO-VIP was effective for advanced NHL with aggressive histologic findings.

Adolescent↗
PubMed1992

MELAS: clinical features, biochemistry, and molecular genetics.

We studied 23 patients with clinically defined mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 25 oligosymptomatic or asymptomatic maternal relatives, and 50 mitochondrial disease control subjects for the presence of a previously reported heteroplasmic point mutation at nt 3,243 in the transfer RNA(Leu(UUR)) gene of mitochondrial DNA. We found a high concordance between clinical diagnosis of MELAS and transfer RNA(Leu(UUR)) mutation, which was present in 21 of the 23 patients with MELAS, all 11 oligosymptomatic and 12 of 14 asymptomatic relatives, but in only five of 50 patients without MELAS. The proportion of mutant genomes in muscle ranged from 56 to 95% and was significantly higher in the patients with MELAS than in their oligosymptomatic or asymptomatic relatives. In subjects in whom both muscle and blood were studied, the percentage of mutations was significantly lower in blood and was not detected in three of 12 asymptomatic relatives. The activities of complexes I + III, II + III, and IV were decreased in muscle biopsies harboring the mutation, but there was no clear correlation between percentage of mutant mitochondrial DNAs and severity of the biochemical defect.

Acidosis, Lactic↗
PubMed1992

Effects of medicinal plants on hemopoietic cells.

It has been found that Juzentaihoto (TJ-48), one of the traditional Japanese kampo (herbal) medicines, improves the general condition of cancer patients receiving chemotherapy and radiation therapy. We analyze how TJ-48 elicits such effect, and show that oral administration of TJ-48 accelerates recovery from hemopoietic injury induced by radiation and the anti-cancer drug mitomycin C. The effects are found to be due to its stimulation of spleen colony-forming units. Based on the present findings, we propose that the administration of TJ-48 should be of benefit to patients receiving chemotherapy, radiation therapy or bone marrow transplantation.

Adjuvants, Immunologic↗
PubMed1992

Effect of hepatic collateral hemodynamics on gastric mucosal blood flow in patients with liver cirrhosis.

The dependence of the gastric mucosal change in liver cirrhosis on the extrahepatic collaterals is still unknown. Therefore we studied the influence of these collateral hemodynamics on gastric mucosal blood flow and gastric mucosal lesions. The subjects were 23 cirrhotic patients and were divided into two groups by the findings of percutaneous transhepatic portography. The first group consisted of 14 cases whose extrahepatic collaterals were via esophageal varices (group I). The second group included 9 cases having collaterals other than esophageal varices (group II). Multiple red spots were observed in 13 of 14 cases in group I, and two of nine cases in group II. Gastric mucosal blood flow was 2.0 +/- 0.9 volts (mean +/- SD) in group I, 4.0 +/- 1.2 in group II. A statistically significant difference was observed between groups I and II. Gastric mucosal blood flow was not significantly correlated with portal venous pressure in group I. It is concluded that, in liver cirrhosis, gastric mucosal blood flow is changeable according to the types of the extrahepatic collaterals.

Aged↗
PubMed1992

Abnormality of background EEG determined by the entropy of power spectra in epileptic patients.

Relationships between epileptiform discharges and background activity were examined by power spectral entropy (PSE), measuring a degree of EEG irregularity. The EEGs were recorded from 10 electrodes placed at F3, F4, C3, C4, T3, T4, P3, P4, O1 and O2 in 11 epileptic patients with widespread lateralized spike and wave complexes (SWCs). Bipolar records were also made from the antero-posterior derivations. The locations of the maximum PSE coincided with those of the maximum amplitude of SWC in most of the patients. Bipolar derivations with the maximum PSE always included the locations with the maximum PSE obtained from a linked ears reference. Pearson's correlation coefficient between PSE and SWC amplitude was 0.62 +/- 0.14 (mean +/- S.D.) in 11 patients, thus indicating that the scalp distribution of PSE was closely related to that of the amplitude of SWC. These findings suggest that the background EEG is disorganized in or near the epileptogenic focus. A focal background abnormality can therefore be estimated by PSE.

Adolescent↗
PubMed1992

Antagonism of ceruletide, a cholecystokinin analog, to the neurochemical effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, phencyclidine and MK-801, on regional dopaminergic neurons in the rat brain.

In the present study, we investigated the effects of ceruletide (CL), a cholecystokinin analog, on the neurochemical response to non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, phencyclidine (PCP) and MK-801, of the dopaminergic neuron systems in the discrete regions of the rat brain. Systemically administered PCP (7.5 mg/kg, i.p.) or MK-801 (1.0 mg/kg, i.p.) produced significant increases in the tissue contents of dopamine metabolite, homovanillic acid (HVA), in the prefrontal cortex, the nucleus accumbens and the olfactory tubercle but not in the nucleus caudatus putamen after 60 min. The effects of NMDA receptor antagonists in the nucleus accumbens and the prefrontal cortex were partially antagonized by pretreatment with CL (80 and 400 micrograms/kg, i.p., at 60 min prior to the drugs). While CL alone decreased the dopaminergic metabolism only in the nigrostriatal pathways in naive rats, the present results indicated that CL also attenuates the activities of the meso-limbic and meso-cortical dopaminergic neuron systems when these are enhanced by either PCP or MK-801.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Melas: an original case and clinical criteria for diagnosis.

We describe the full history and postmortem findings in one of the first identified cases of mitochondrial encephalomyopathy with stroke-like episodes (MELAS). To clarify diagnostic criteria, we analyzed 69 reported cases. The syndrome should be suspected by the following three invariant criteria: (1) stroke-like episode before age 40 yr; (2) encephalopathy characterized by seizures, dementia, or both; and (3) lactic acidosis, ragged-red fibers (RRF), or both. The diagnosis may be considered secure if there are also at least two of the following: normal early development, recurrent headache, or recurrent vomiting. There are incomplete syndromes in relatives of patients with the full syndrome and incomplete syndromes might also be encountered in sporadic cases. Some MELAS patients have features of the Kearns-Sayre syndrome (KSS) or myoclonic epilepsy with ragged-red fibers (MERRF), but none had the full KSS syndrome. In partial or confusing cases, analysis of mitochondrial DNA (mtDNA) may point to the correct diagnosis; however, not all patients with clinical MELAS have had the typical mtDNA point mutation and some patients with the mutation have clinical syndromes other than MELAS.

Brain↗
PubMed1992

Cristospinal reflex in circular walking.

This study comprised 22 normal adults, 12 males and 10 females. Electromyograms of the bilateral gastrocnemius muscle were recorded during circular walking under two conditions: no caloric stimulation and immediately after irrigating the right auditory canal with 20 degrees C water for 20 s with the horizontal semicircular canal maintained in vertical position. With no caloric stimulation, gastrocnemius muscle activity on the right side exceeded that on the left during dextrorotation and vice versa during sinistrorotation. Following irrigation of the right auditory canal, the activity was greater on the left side than on the right during sinistrorotation, but no consistent differences in muscle activity were observed during dextrorotation. Dextrorotation was associated with ataxic gait in all cases. Thus ampullopetal lymphatic flow in the semicircular canal due to circular walking causes increased antigravity muscle tonus of the ipsilateral leg. This gives the ipsilateral leg assistance for supporting body weight which shifts to the inner side of circular walking.

Adult↗
PubMed1992

Intracellular Ca2+ concentration and pHi during metabolic inhibition.

To study the changes in intracellular Ca2+ concentration ([Ca2+]i) and pH (pHi) during metabolic inhibition, rat ventricular myocytes were dual loaded with the acetoxymethyl esters of fura-2 (fura-2/AM) and 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF/AM) and perfused with 2 mM sodium cyanide (NaCN). The percent of rod-shaped cells was 30% of the control after 30 min NaCN in the absence of glucose. [Ca2+]i increased from 82 +/- 8 to 151 +/- 25 (SE) nM (P less than 0.05) when cells were shortened, and to 421 +/- 106 nM (P less than 0.05) when cells were rounded. There was a positive relationship between pCai and pHi (r = 0.425, P less than 0.01). When 50 mM glucose was added during NaCN, there were no significant changes in [Ca2+]i and the percent of rod-shaped cells after 30 min. The pHi of rod-shaped cells, however, decreased to 6.95 +/- 0.03 (P less than 0.01). Although the acidic solution (70% O2-30% CO2) decreased pHi to 6.90 +/- 0.05 (P less than 0.01), there were no changes in the cell shape or [Ca2+]i. The addition of NaCN for 30 min decreased the rod-shaped cells to 18% of the control. Mild acidosis did not cause the changes in cell shape or [Ca2+]i. There was also no protection of the NaCN-induced changes in cell shape by intracellular acidosis. It is likely that the changes in cell shape during metabolic inhibition were related to the depletion of metabolic energy and the increase in [Ca2+]i.

Analysis of Variance↗
PubMed1992

Dysphagia following various degrees of surgical resection for oral cancer.

Postoperative swallowing problems were investigated in 20 patients who had undergone various degrees of surgical resection for oral cancer. The swallowing problems were evaluated on the basis of type of food, degree of aspiration, and duration of postoperative nasogastric tube feeding. Two patients with tongue cancer who had had hemiglossectomy without reconstruction ate normal food without aspiration within a week after operation. Eight patients who had undergone two- to three-quarter glossectomy for tongue cancer ate gruel with no or occasional liquid aspiration. Among 4 patients who had had near-total or total glossectomy for tongue cancer, 3 ate thin gruel or liquid with occasional aspiration. The other could not eat orally because of consistent severe aspiration. One patient with mouth floor cancer underwent resection of the mouth floor in combination with hemiglossectomy and she ate gruel without aspiration. Among 5 patients with mouth floor cancer who had had surgical removal accompanied by near-total or total glossectomy, 3 ate gruel with no or occasional liquid aspiration, 1 ate thin gruel with no aspiration, and the other could not eat orally. A diagnosis of T4 lesions, extensive removal of the tongue base, removal of the geniohyoid and mylohyoid muscles, and removal of the lateral pharyngeal wall were significantly related to poor swallowing function.

Aged↗
PubMed1992

Acute quadriplegic myopathy: a complication of treatment with steroids, nondepolarizing blocking agents, or both.

We studied two patients who were given high-dose intravenous steroid therapy and were intubated for status asthmaticus. Both became quadriplegic and wasted within 2 weeks. EMG had myopathic abnormalities. Muscle biopsy revealed severe atrophy of most muscle fibers, with disorganization of myofibrils and selective loss of thick (myosin) filaments. Immunohistologic stains for myosin isoforms confirmed the decrease or absence of this protein. Both patients clinically improved over several months.

Acute Disease↗
PubMed1992

Multifocal motor neuropathy with conduction block: is it a distinct clinical entity?

We studied 169 patients with motor neuron disease. Seventeen showed abnormal amplitude reduction of the compound muscle action potential. Ten had focal loss of both amplitude and area across a specific segment (conduction block). Eight of the 10 had slowing of conduction across that segment. Nine were men and had prominent hand involvement. Six had probable or definite upper motor neuron signs. Five of the 10 showed immunologic abnormalities (elevated GM1 antibody titers or paraproteinemia), and eight had had symptoms for more than 4 years. Seven of the 17 patients showed loss of amplitude without corresponding loss of area and focal slowing of conduction (temporal dispersion). Five of the seven were men, five had prominent hand involvement, and five had definite or probable upper motor neuron signs. Two had immunologic abnormalities, and ony one had had symptoms for longer than 4 years. Among 152 patients with no abnormality of conduction, 64% wee men, hands were dominantly involved in 34%, upper motor neuron signs were definite or probable in 72%, and 3% had immunologic abnormalities. None had symptoms for more than 4 years. Because there were so many exceptions, we could not define a unique syndrome by criteria involving conduction block, GM1 antibodies, or lack of upper motor neuron signs. The clinical syndrome associated with multifocal conduction block seemed uniform, however, and patients with conduction block had slower progression if there were no upper motor neuron signs.

Action Potentials↗
PubMed1992

[Disseminated varicella-zoster virus infection without vesicles in a patient with malignant lymphoma].

A 76-year-old man was diagnosed as having malignant lymphoma (non-Hodgkin's lymphoma, diffuse medium cell-sized, B cell type). He was treated with CHOP therapy but with no response. In the terminal stage, he had continuous high temperature despite the administration of anti-bacterial and anti-fungal agents. Paralytic ileus, liver and pancreas dysfunction, and gastrointestinal bleeding developed. No skin eruptions occurred throughout the clinical course. He died on day 36 of treatment. Postmortem examination revealed foci of hemorrhagic necrosis containing many multinuclear giant-cells some of which with intranuclear inclusion bodies (Cowdry type A), in the liver, pancreas, gastrointestinal tract, bone marrow and other organs. Electron microscopy showed viral particles in the cytoplasm but not the nuclei of infected cells which were covered with a capsule, which was characteristic of varicella-zoster virus infection. Cells of the above organs were positive for immunohistochemical staining using antivaricella-zoster antibodies. The multiorgan failure seen in the terminal stage was considered to be due to disseminated varicella-zoster infection.

Aged↗