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Biomedical subjects

M Matsuo

Publications and source records attributed to M Matsuo.

At least 307 records · Page 17Linked to original sources
PubMed1995

[Problems found in genetic diagnosis of DMD/BMD].

The method to understand the result of the multiplex PCR amplification of the dystrophin gene has been discussed. In dystrophin Kobe, a very small intra-exon deletion was identified in exon 19 when the amplified product was not detected in its corresponding position. Also, an insertion mutation was identified in exon 44 of the dystrophin gene named dystrophin Yakumo. In this case the amplified product from exon 44 was not localized to the its expected position, but a larger fragment was identified. In one case of BMD all exons were amplified by multiplex PCR. However, thorough examination disclosed the presence of point mutation at the last nucleotide of exon 13.

Dystrophin↗
PubMed1994

Studies on neurokinin antagonists. 4. Synthesis and structure-activity relationships of novel dipeptide substance P antagonists: N2-[(4R)-4-hydroxy-1-[(1-methyl-1H-indol-3-yl)carbonyl]-L-prolyl]-N- methyl-N-(phenylmethyl)-3-(2-naphthyl)-L-alaninamide and its related compounds.

As an extension of our studies on discovering a novel substance P (SP) antagonist, we modified the previously reported dipeptide, N2-[N2-(1H-indol-3-ylcarbonyl)-L-lysyl]-N-methyl-N-(phenyl-methyl) -L- phenylalaninamide (2b). The lysine part in 2b was first optimized to a (2S,4R)-hydroxyproline derivative (3h), which is 2-fold more potent than 2b in [3H]SP binding assay using guinea pig lung membranes. Next we modified the 1H-indol-3-ylcarbonyl part in 3h. Introduction of a methyl group at the indole nitrogen enhanced the oral activity, while retaining the binding activity. Finally, we modified the phenylalanine part to culminate in the most potent compound 7k (FK888), which is a potent SP antagonist with NK1 selectivity as well as oral activity.

Animals↗
PubMed1994

Synthesis and anticholinergic activity of the four stereoisomers of 4-(dimethylamino)-2-phenyl-2-(2-pyridyl)pentanamide.

The four stereoisomers of 4-(dimethylamino)-2-phenyl-(2-pyridyl)pentanamide were synthesized, and the absolute configurations were determined by X-ray crystallography. Pharmacological testing for anticholinergic activity revealed great differences in potency among 10 (2R,4R,IC50 = 0.40 microM), 11 (2S,4S,31 microM), 12 (2R,4S,170 microM), and 13 (2S,4R,0.13 microM). A new drug application for the racemate 8 (FK176, vamicamide) has been filed in Japan for the treatment of overactive detrusor syndrome.

Animals↗
PubMed1994

The correlation of serum luteinizing hormone levels with the induction of Leydig cell tumors in rats by oxolinic acid.

Studies were performed to examine the mechanism by which testicular Leydig cell tumors are induced in rats by administration of the antimicrobial agent oxolinic acid (1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxo-3-quinolinecarboxylic acid). In these studies, the effects of oxolinic acid on serum levels of luteinizing hormone (LH), testosterone, and prolactin and the binding of testosterone to prostatic androgen receptors were examined. In a long-term hormonal study, male Wistar rats were fed a diet containing oxolinic acid at 0, 100, 1000, or 3000 ppm for 104 weeks. A statistically significant increase in serum LH levels was observed at 1000 and 3000 ppm, but no dose of oxolinic acid had a significant effect on serum testosterone levels. Serum LH levels were no longer elevated above control levels within 2 weeks of cessation of the administration of oxolinic acid. Oxolinic acid was found to have no effect on the rate of clearance of exogenous LH from the circulation. Serum prolactin levels were decreased by the administration of oxolinic acid. The increase in serum LH induced by oxolinic acid was completely blocked by the intraperitoneal injection of the dopamine antagonist haloperidol (2 mg/kg). In addition, no significant affinity of oxolinic acid for androgen receptors was found in an in vitro study. These findings suggest that: (1) oxolinic acid induces Leydig cell tumors in rats by chronically stimulating the release of LH from the pituitary, (2) the mechanism of stimulating the release of LH involves facilitation of the dopaminergic systems in the hypothalamus-pituitary axis, and (3) oxolinic acid has no effect on androgen-mediated feedback inhibition.

Administration, Oral↗
PubMed1994

Twenty seven nucleotide deletion within exon 11 of the erythrocyte band 3 gene in Indonesian ovalocytosis.

We here report the molecular characterization of an Indonesian ovalocytosis. The analysis of genomic gene by polymerase chain reaction shows that the individual has two amplified products from a region encompassing exon 11 of the erythrocyte band 3 gene. The sequence of the larger product matched completely with that of normal individuals. In the sequence of the smaller product, 27 nucleotides within exon 11 disappeared. The deletion removes a total of nine amino acids in the boundary of cytoplasmic and membrane domains of band 3 protein, a membrane anion transporter protein. This is the first report to confirm the heterogeneous presence of an altered membrane band 3 protein in Indonesian ovalocytosis.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1994

Phospholipid hydroperoxides are significantly less toxic to cultured endothelial cells than fatty acid hydroperoxides.

Optically active hydroperoxides of phospholipids including phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, and phosphatidic acid were synthesized, and their cytotoxicity to cultured bovine pulmonary artery endothelial cells was examined. Phospholipid hydroperoxides were readily incorporated into cells during the incubation in a medium containing each hydroperoxide. Phospholipids with a linoleic acid hydroperoxide residue showed no toxicity, whereas phosphatidylcholine with an arachidonic acid hydroperoxide residue was somewhat toxic. When hydroperoxyarachidonoylphosphatidylcholine was reduced to hydroxyarachidonoylphosphatidylcholine, the reduction product was found to have no toxicity. It appears that phospholipid hydroperoxides, unless converted into more reactive compounds, are significantly less toxic to endothelial cells than fatty acid hydroperoxides.

Animals↗
PubMed1994

Carcinogenicity studies of oxolinic acid in rats and mice.

A chronic feeding study was conducted to determine the carcinogenic potential of oxolinic acid, an antimicrobial agent, in rats and mice. Oxolinic acid was administered in the diet to Wistar rats (0, 30, 100, 300 or 1000 ppm; 50 rats/dose/sex) for 104 wk and to ICR mice (0, 50, 150 or 500 ppm; 50 mice/dose/sex) for 78 wk. Clinical signs, body weight, food consumption, autopsy findings and histopathological data were noted. Mortality was unaffected by oxolinic acid administration in neither species. In rats, body weight gain was suppressed in both sexes at 1000 ppm. Histopathological examinations conducted after autopsy at 104 wk revealed a slight increase in benign Leydig cell tumours of the testis at 1000 ppm, which did not appear until late in the lifetime of rats. No other treatment-related neoplastic lesions were observed in rats. Non-neoplastic lesions in males at 1000 ppm included Leydig cell hyperplasia and tubular atrophy of the testes. In mice, decreased body weight gain was observed in both sexes at 500 ppm, but no non-neoplastic or neoplastic lesions attributable to the treatment with oxolinic acid occurred in either sex. In conclusion, oxolinic acid induced benign Leydig cell tumours of the testis in rats at the highest dose level tested (1000 ppm). The no-effect level for tumour induction was confirmed to be 300 ppm (10.9 mg/kg/day) in rats. None was induced in mice.

Animals↗
PubMed1994

Protection of linoleic acid hydroperoxide-induced cytotoxicity by phenolic antioxidants.

The protective effects of phenolic antioxidants on linoleic acid hydroperoxide (LOOH)-induced toxicity to cultured human umbilical vein endothelial cells were examined. Our previous results were confirmed that for tocopherol homologs, lipophilicity and the presence of a phenolic hydroxyl group and two alkyl groups at its ortho positions are critical for protection against LOOH-induced cytotoxicity. Probucol and butylated hydroxytoluene (BHT) were more effective than other simple alkylated phenols. It was found that the protective effects of alkylated phenols were depended on by the presence of two alkyl groups; in particular, two tert-butyl groups, at positions ortho to a hydroxyl group and an alkyl group at the para position. Among alpha-tocopherol, 2,2,5,7,8-pentamethylchroman-6-ol, and BHT, the relative effectiveness of protection against the cytotoxicity (1.0:0.86:0.58, respectively) was inconsistent with the previously reported, relative antioxidant activity in homogeneous solution (1.0:1.2:0.004, respectively). Probably, the effectiveness of protection by phenolic antioxidants against the cytotoxicity depend primarily on their incorporation rate into cells due to their lipophilicity, secondly on their antioxidant activity, and thirdly on their orientation in biomembranes.

Antioxidants↗
PubMed1994

A new method, distribution-analyzing latex immunoassay (DALIA), to measure specific immunoglobulin G against mite and wheat allergen in human sera.

A distribution-analyzing latex immunoassay (DALIA), based on the agglutination of latex particles coupled with mite or wheat allergen, was developed to determine allergen-specific IgG in human sera. The immune complex between chemically coupled-allergen latex and specific IgG was agglutinated specifically and efficiently by employing an IgM-type monoclonal second antibody with strong amplification activity. The extent of agglutination was evaluated by determining the relative ratio of volumes (RV) of agglutinates to residual nonagglutinating particles with a particle counter. This method exhibited a high sensitivity (detection limit < or = 5 units/ml) in the determination of allergen-specific IgG, and no influence of inhibitory factors such as competitive antibodies (specific-IgA, -IgM) and nonspecific IgG (< or = 320 mg/ml) was observed. The concentrations of specific IgG against mite allergen in the sera of 130 allergy patients with atopic dermatitis and 52 normal subjects were 22.3 +/- 12.3 and 16.5 +/- 4.2 units/ml, respectively, and the concentrations of specific IgG against wheat allergen in the same two groups were 5.4 +/- 4.2 and 2.1 +/- 2.2 units/ml, respectively. The coefficients of variation of intra- and interassay ranged from 3.4% to 11.2% in both cases. The present method is an excellent homogeneous immunoassay which may be used as a routine assay that can measure 50 samples per hour without prior treatment.

Allergens↗
PubMed1994

A case of a methylmethacrylate foreign body in the bladder wall.

The authors report a rare case of bone cement protruding into the bladder wall. The patients exhibited an abnormal mass in the bladder wall during ultrasonography and was admitted to our department 21 mo after right hip joint replacement. Partial resection of the urinary bladder including the bone cement was performed. The patient made an uneventful recovery postoperatively. This is the third case reported of a foreign body in the urinary bladder associated with bone cement.

Aged↗
PubMed1994

A variant form of hypobetalipoproteinaemia associated with ataxia, hearing loss and retinitis pigmentosa.

A six-year-old Japanese boy had ataxia, mental retardation, peripheral neuropathy, proximal myopathy, hearing loss, retinitis pigmentosa and deficiencies in apolipoprotein AI, B, CII and CIII. His clinical features except for hearing loss resembled those of abetalipoproteinaemia or symptomatic hypobetalipoproteinaemia, but his apolipoprotein abnormalities were distinct from these disorders. He had apolipoprotein B-100 with a normal molecular weight. Although most of his neurological manifestations were compatible with those of vitamin E deficiency, their early onset and the presence of hearing loss was unusual for that condition. There has been slight deterioration of ataxia during two years follow-up despite high-dose vitamin E supplementation. Other abnormalities in lipid metabolism might be associated with the neurological damage in this case.

Ataxia↗
PubMed1994

Inhibition by dexamethasone of retinoic acid-induced enhancement of leukotriene C4 synthesis in rat basophilic leukemia-1 cells.

We investigated inhibitory actions of dexamethasone (DEX) on retinoic acid (RA)-induced enhancement of leukotriene C4 (LTC4) synthesis in rat basophilic leukemia-1 (RBL-1) cells. Cultured cells were preincubated with RA for 16 h with or without DEX, and generation of LTC4 was measured by high performance liquid chromatography in cell-free and intact cell systems. RA (0.1 microgram/ml) significantly potentiated calcium ionophore-stimulated production of LTC4 synthesis. DEX inhibited the RA-induced enhancement of LTC4 synthesis by up to approximately 95% in intact cells when stimulated with calcium ionophore. RA-induced LTC4 synthase activity, which was determined by enzyme assay, was also inhibited by DEX by 65% in a cell-free system. This discrepancy of inhibition between the intact and cell-free systems was due to a partial inhibition of phospholipase A2 activity by DEX in the intact cells. These results indicate that the production of LTC4 is predominantly regulated at a level of LTC4 synthase. The induction of new LTC4 synthase activity by RA and inhibition of the RA-induced activity by DEX are important regulatory mechanisms of LTC4 synthesis.

Animals↗
PubMed1994

Identification of a novel first exon in the human dystrophin gene and of a new promoter located more than 500 kb upstream of the nearest known promoter.

The dystrophin gene, which is mutated in patients with Duchenne and Becker muscular dystrophies, is the largest known human gene. Five alternative promoters have been characterized until now. Here we show that a novel dystrophin isoform with a different first exon can be produced through transcription initiation at a previously unidentified alternative promoter. The case study presented is that of a patient with Duchenne muscular dystrophy who had a deletion extending from the 5' end of the dystrophin gene to exon 2, including all promoters previously mapped in the 5' part of the gene. Transcripts from lymphoblastoid cells were found to contain sequences corresponding to exon 3, indicating the presence of new promoter upstream of this exon. The nucleotide sequence of amplified cDNA corresponding to the 5' end of the new transcript indicated that the 5' end of exon 3 was extended by 9 codons, only the last (most 3') of which codes for methionine. The genomic nucleotide sequence upstream from the new exon, as determined using inverse polymerase chain reaction, revealed the presence of sequences similar to a TATA box, an octamer motif and an MEF-2 element. The identified promoter/exon did not map to intron 2, as might have been expected, but to a position more than 500 kb upstream of the most 5' of the previously identified promoters, thereby adding 500 kb to the dystrophin gene. The sequence of part of the new promoter region is very similar to that of certain medium reiteration frequency repetitive sequences. These findings may help us understand the molecular evolution of the dystrophin gene.

Amino Acid Sequence↗
PubMed1994

Amino-terminal deletion of 53% of dystrophin results in an intermediate Duchenne-Becker muscular dystrophy phenotype.

We report a Japanese boy with muscular dystrophy whose clinical symptoms were intermediate between those usually considered typical of Duchenne and Becker muscular dystrophies. The patient had a large inframe deletion extending from exons 3 to 41 of the dystrophin gene, which would be expected to cause the production of a dystrophin protein composing only 53% of the normal polypeptide chain. Such an inframe deletion would be expected to cause Becker muscular dystrophy. We did not obtain evidence for alternative splicing or for RNA editing. Immunocytochemical analysis of skeletal muscle showed that a dystrophin-related polypeptide was detectable with antibody directed against the carboxyl-terminal part of the polypeptide but not with antibodies directed against the amino-terminal part, although labeling by antibody against the carboxyl-terminal was faint and patchy. The severity of the disease in this case may be due to the lack of the amino-terminal, actin-binding domain of dystrophin.

Adolescent↗
PubMed1994

Contents of lecithin and choline in crude drugs.

The determination of lecithin and choline in crude drugs was established by a combination of high performance liquid chromatography (HPLC) with electrochemical detector (ECD) and enzyme reaction. Lecithin in crude drugs extracted with a mixture of chloroform-methanol (2:1) at room temperature was hydrolyzed by phospholipase D. The hydrolyzate was injected to HPLC, and choline was separated from impurities by reverse phase column. The choline was converted to betaine and hydrogen peroxide by passing through column packed with immobilized choline oxidase. This hydrogen peroxide was detected by ECD. The peak area of hydrogen peroxide derived from lecithin was proportional to the concentration of lecithin from 0.10 to 1.52 microgram/ml. Choline in crude drugs was extracted with ethanol under reflux and determined under the same HPLC conditions as lecithin. The peak area of hydrogen peroxide derived from choline was proportional to the concentration of choline from 0.01 to 0.45 microgram/ml. The contents of lecithin and choline in 31 kinds of crude drugs were determined by these established methods. The results showed that Cervi Parvum Cornu, Kokurozin, Foenigraeci Semen and Psoraleae Semen contained more lecithin than other crude drugs, while Angelicae Radix, Foenigraeci Semen, Psoraleae Semen, and especially Hippocampus were found to contain more choline than other crude drugs.

Choline↗