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Biomedical subjects

M Hirano

Publications and source records attributed to M Hirano.

At least 469 records · Page 26Linked to original sources

Exonic point mutations in NADH-cytochrome B5 reductase genes of homozygotes for hereditary methemoglobinemia, types I and III: putative mechanisms of tissue-dependent enzyme deficiency.

We analyzed the NADH-cytochrome b5 reductase gene of hereditary methemoglobinemia type I and type III, by using PCR-related techniques. The mutation in type I is a guanine-to-adenine substitution in codon 57 of exon 3 of the NADH-cytochrome b5 reductase gene, and the sense of this codon is changed from arginine to glutamine. In type III the mutation is a thymine-to-cytosine transition in codon 148 of exon 5, causing leucine-to-proline replacement in type III. The former mutation abolishes the MspI recognition site. Homozygosity for the former mutation in a patient with type I was confirmed by restriction analysis of PCR-amplified fragments and by dot blot hybridization of amplified products with allele-specific oligonucleotide probes. The latter mutation generates a recognition site for MspI. Amplification of exon 5 by PCR followed by digestion with MspI revealed homozygosity for this mutation in patients with type-III. Putative mechanisms of tissue-dependent enzyme defects in hereditary methemoglobinemia are discussed.

Adult↗

Clinical syndromes associated with ragged red fibers.

Among 40 patients with ragged red fibers in muscle biopsy, all but two met criteria for one of the recognized mitochondrial myopathies: Kearns-Sayre syndrome (6 patients); other ophthalmoplegias (17): MELAS (3); MERRF (2); limb myopathy (5); and exercise intolerance (3). Two patients had MNGIE (mitochondrial myopathy with neuropathy, gastrointestinal symptoms and encephalopathy) and one had spinal muscular atrophy. The myopathy had features of facioscapulohumeral dystrophy in 4 patients. This analysis provides 4 lines of evidence to reinforce the view that, despite occasional "overlap" cases, distinct syndromes can be recognized. First, there are clinical differences. Second, KSS is almost never familial but MELAS and MERRF are often familial. Third, in this series, as in others, all deletions of mtDNA were found in patients with either KSS or non-familial PEO. With a possible single exception, none of the familial cases had KSS and no familial cases included a deletion of mtDNA. Others have found evidence of mtDNA point mutations in MERRF, and maternal inheritance suggests that point mutations will be found in MELAS. Finally, postmortem findings differ in KSS, MELAS, and MERRF. For all of these reasons, we believe it is useful to separate cases on clinical grounds. Deletions and point mutations of mtDNA are becoming defining characteristics of these syndromes.

Adult↗

[Three cases of catamenial pneumothorax].

Three cases of catamenial pneumothorax were presented. A 42-year-old woman with intrapelvic endometriosis had recurrent right-sided pneumothorax with menstruation more than six times. At the operation only a bleb was noted at the apex of the right lung. In a 16-year-old woman who already had been operated on for recurrent right-sided pneumothorax one year ago, left-sided pneumothorax occurred on the day of the beginning of each menstruation four times. A small bleb was noted at the apex. A 29-year-old woman with cesarean section at the age of 25 had recurrent right-sided pneumothorax occurring on the day before the beginning of menstruation three times. Though the operation was performed during her menstrual period, neither air leakage nor any lesions were found. In all cases each lesion was resected and did not prove endometriosis, and partial parietal pleurectomy was performed for pleurodesis. No pneumothorax has recurred.

Adolescent↗

[A clinical study in postoperative bile excretion of cefuzonam].

We investigated the postoperative bile excretion and serum concentration of cefuzonam (CZON) in 6 cholecystectomized patients with postsurgical biliary drainage. CZON was administered intravenously by infusion at a dose of 1.0 g immediately following the operation. Serum and bile concentrations of CZON were determined on the day of the operation and the second day after the operation. The following results were obtained. 1. Serum concentrations of CZON were at their highest levels at 30 minutes after administration of CZON. Levels were 45.8 +/- 13.8 micrograms/ml on the day of the operation and 60.9 +/- 12.2 micrograms/ml on the second postsurgical day. 2. Bile concentration peaked 1 hour after administration (4,083 +/- 1,427 micrograms/ml on the day of the operation and 4,376 +/- 630 micrograms/ml on the second postsurgical day). In particular, bile concentrations of CZON at 6 hours (259 +/- 140 micrograms/ml and 154 +/- 23 micrograms/ml) exceeded MIC80 of CZON against Gram-negative bacteria except for Pseudomonas aeruginosa. 3. Serum and bile concentrations were higher on the second postsurgical day than on the day of the operation, but the differences between these 2 days were not significant. These results have indicated that CZON is a useful drug with excellent bile excretion following cholecystectomy, and that bile concentrations of CZON are maintained at high levels for 6 hours after intravenous administration.

Adult↗

[A case of left lung cancer associated with an aneurysm of the thoracic aorta].

A 61-year-old man was admitted to our hospital because of a left lung cancer. The chest x-ray film showed an irregular mass in the left upper lung field and the ill-defined left upper mediastinal border. A large portion of the aorta seen in the CT section above the aortic arch was understood to be aortic elongation. When a left pneumonectomy was performed, a saccular aneurysm of the distal aortic arch was found and resected under partial aortic clamping. Following the aneurysmectomy mediastinal dissection was performed in the normal way. The patient recovered uneventfully. The pathological specimens showed a pT2N1M0 squamous cell carcinoma with obstructive pneumonia and an arteriosclerotic aneurysm. There was no report of lung cancer associated with aneurysm of the thoracic aorta. In a patient with left lung cancer obliterating the left upper mediastinal border (the "silhouette sign") the aortic arch should be closely examined by MRI and/or angiography.

Aorta, Thoracic↗

In vivo activities of aldose reductase inhibitors having a 1-(arylsulfonyl)hydantoin structure.

Two potent aldose reductase inhibitors, 1-[(2,5-dichlorophenyl)sulfonyl]hydantoin (Di-Cl-PSH) and 1-[beta-naphthyl)sulfonyl]hydantoin (beta-NSH), were tested for usefulness in the treatment of diabetic and galactosemic complications in animal experiments. Both drugs were effective for the treatment of diabetic neuropathy characterized by decreased motor nerve conduction velocity, that is, slowing of tail and sciatic-tibial motor nerve conduction velocities in streptozocin-induced diabetic rats was prevented during 3 weeks by intubating Di-Cl-PSH or beta-NSH at 50 mg/kg/day. Lenticular vacuole formation in rats fed a 30% galactose diet was blocked completely for at least 2 weeks by oral administration of Di-Cl-PSH or beta-NSH at both 30 and 100 mg/kg/day, whereas all of the eyes of vehicle-treated rats showed vacuole formation by day 4 on the galactose diet. The ED50 values of Di-Cl-PSH and beta-NSH for inhibition of sorbitol accumulation in the sciatic nerve and lens of streptozocin-induced diabetic rats were also estimated; the values of Di-Cl-PSH and beta-NSH were 1.1 and 3.4 mg/kg/day, respectively, for inhibition in the sciatic nerve and 4.8 and 16.0 mg/kg/day, respectively, for that in the lens. This study indicates that Di-Cl-PSH and beta-NSH have high potential for future clinical use as aldose reductase inhibitors.

Aldehyde Reductase↗

Fiberscopic estimation of vocal fold stiffness in vivo using the sucking method.

We developed a fiberscopic device for estimating vocal fold stiffness in vivo. A small plastic tube with a hole in the side was connected to the forceps channel of the fiberscope and used as an aspiration tube under constant negative pressure. A basic experiment revealed that the maximum distance at which the vocal fold was sucked to the hole depended on the stiffness of the tissue. A preliminary study was conducted with a normal subject and four patients: one with sulcus vocalis, one with Reinke's edema, and two with carcinoma. The stiffness estimated using this method was 3 to 4 g/cm for the normal vocal fold. The stiffness for carcinoma and sulcus vocalis was significantly greater than that of normal vocal fold tissue. The stiffness of Reinke's edema did not differ markedly from that of normal tissue.

Adult↗

Initiation of meiosis and sporulation in Saccharomyces cerevisiae requires a novel protein kinase homologue.

SME1 was cloned due to its high copy number effect: it enabled MATa/MAT alpha diploid cells to undergo meiosis and sporulation in a vegetative medium. Disruption of SME1 resulted in a recessive Spo- phenotype. These results suggest that SME1 is a positive regulator for meiosis. DNA sequencing analysis revealed an open reading frame of 645 amino acids. An amino terminal peptide of ca 400 amino acids in the deduced protein was similar to known protein kinases. Transcription of SME1 was regulated negatively by nitrogen and glucose and positively by MATa/MAT alpha and IME1, another positive regulator gene of meiosis. By complementation analysis, SME1 was found to be identical to IME2, which had been shown to be important in meiosis. These results suggest that IME1 product stimulates meiosis by activating transcription of SME1 (IME2) and that protein phosphorylation is required for initiation of meiosis.

Amino Acid Sequence↗

Regional distribution of DNA and RNA in rat brain: a sensitive determination using high-performance liquid chromatography with electrochemical detection.

DNA and RNA contents in 20 brain regions or nuclei of the rat were determined by a highly sensitive method using high-performance liquid chromatography with electrochemical detection. The high DNA and RNA contents were found in the hypothalamic nuclei, especially the median eminence-arcuate nucleus. These results may be available for the preparation of nucleic acids as the regional control.

Amygdala↗

Behavioral sensitization to beta-phenylethylamine (PEA): enduring modifications of specific dopaminergic neuron systems in the rat.

Repeated daily administration of an endogenous trace amine, beta-phenylethylamine (PEA), produces behavioral sensitization such that the intensity of PEA-induced stereotyped behaviors in rats increases gradually during the treatment, and a challenge injection with PEA reinstates the enhanced stereotypy even long after withdrawal. In the present study, we examined the neurochemical changes in the central dopaminergic neurons systems in the rat for 7 drug-free days after repeated treatment with PEA (50 mg/kg, IP day for 14 or 28 days). During withdrawal, a decrease in steady-state levels of tissue dopamine (DA) and its metabolite, dihydroxyphenylacetic acid (DOPAC), was found in the mesolimbic DA nerve terminal areas of the rat brain receiving repeated PEA treatment. Fifteen minutes after challenge administration of PEA at varying doses from 6.3 to 75 mg/kg, the rats with repeated PEA treatment required smaller doses of PEA challenge than the rats with acute PEA treatment in order to obtain a significant decrease in striatal DOPAC content compared to the saline control in each treatment group. These results imply that the behavioral sensitization to PEA is accompanied by enduring modifications of the specific dopaminergic neuron systems in the rat brain. This suggestion was strongly supported by the results of the study using in vivo intracerebral dialysis, which indicated that 25 mg/kg PEA challenge elicited a remarkable increase in the extracellular DA concentrations in striatal perfusates collected from the PEA-pretreated rats, in accordance with the intensity of stereotyped behaviors. These findings argue that the hyper-responsiveness to PEA of the striatal dopaminergic neuron systems persists long after withdrawal from repeated treatment with PEA.

3,4-Dihydroxyphenylacetic Acid↗

Changes in GABA content and turnover in discrete regions of rat brain after systemic administration of caerulein.

The effects of systemically injected caerulein, a cholecystokinin octapeptide analogue, on GABA content and turnover have been studied in various regions of rat brain. Caerulein decreased GABA levels in the nucleus accumbens, tuberculum olfactorium and substantia nigra and diminished GABA turnover rates in the striatum, nucleus accumbens and substantia nigra, as estimated from the rate of GABA accumulation after inhibition of GABA transaminase by aminooxyacetic acid (AOAA). These results indicate the effect of caerulein on the utilization of GABA in specific cerebral regions and suggest that the GABAergic system is involved in the mechanism of action of peripherally administered caerulein.

Animals↗

Chronic toxicity and carcinogenicity of methylmercury chloride in B6C3F1 mice.

A 2-year feeding study of methylmercury chloride (MMC: 0, 0.4, 2, or 10 ppm) was conducted in B6C3F1 mice (60 mice of each sex/group) to compare chronic toxicity and carcinogenicity results with those for ICR mice from our previous study in which males of the 10-ppm group showed an increased incidence of renal tumors without any abnormal in-life parameters. In B6C3F1 mice of the 10-ppm group, neurotoxic signs characterized by posterior paralysis were observed in 33 males after 59 weeks and in 3 females after 80 weeks. In males, a marked increase in mortality and a remarkable decrease in body weight gain were observed after 60 weeks. Toxic encephalopathy consisting of neuronal necrosis of the brain and toxic peripheral sensory neuropathy were induced in both sexes in this group. Chronic nephropathy, testicular atrophy, and glandular stomach ulcer increased in incidence in the males; chronic nephropathy also increased in incidence in females. In proliferative lesions, there were significant increases in the incidence of renal adenoma and/or carcinoma (16/60) and tubular cell hyperplasia (14/60) in males of the 10-ppm group, as compared to the control group. The incidence of chronic nephropathy also increased in males of the 2-ppm group. The results of this study indicate that the susceptibility of B6C3F1 mice to renal toxicity and renal carcinogenicity is comparable to that of ICR mice, and B6C3F1 mice are more sensitive to the chronic neurotoxic effects of MMC than are ICR mice.

Animals↗

Osteoma of the middle ear.

Osteomas involving the middle ear and causing a functional disturbance are rare. We report a case of a patient with an osteoma arising from the lateral semicircular canal. The main symptom was vertigo and to halt this the defect of the canal was obliterated with a bone chip and fibrin glue after removal of the tumour.

Ear Neoplasms↗

Distribution of elastic cartilage in the arytenoids and its physiologic significance.

An investigation of the distribution of the elastic cartilage in the arytenoids was performed on excised human adult and newborn larynges. The distribution of elastic cartilage in the arytenoids was investigated histologically in two serial sections: horizontal and coronal. The behavior of the elastic cartilage portion of the arytenoids was investigated histologically under the conditions of adduction and abduction. The results are summarized as follows. 1) Elastic cartilage is found not only at the tip of the vocal process but at the superior portion of the arytenoid cartilage from the vocal process to the apex. 2) This phenomenon is observed at birth. 3) The vocal process bends at the elastic cartilage portion during adduction and abduction. The sides of the arytenoids come into contact mainly at the elastic cartilage portion. 4) Elastic cartilage appears to play an important role in the physiologic functioning of the arytenoid.

Adult↗