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Biomedical subjects

S Igarashi

Publications and source records attributed to S Igarashi.

At least 73 records · Page 4Linked to original sources
PubMed1999

Bilirubin pigmentation of human teeth caused by hyperbilirubinemia.

This study was conducted to identify bilirubin in deciduous teeth obtained from two patients with a history of severe liver dysfunction. Teeth were histologically analyzed and bilirubin was extracted and quantified spectrophotometrically. Histological analysis revealed a green line in the dentine running parallel to the incremental lines. A chloroform/methanol/acetic acid (30:10:0.5, v/v) extract of the teeth was evaporated and the residue dissolved in chloroform. Absorption spectra were prepared before and after the diazo reaction. The absorption maximum shifted from 450 nm before to 540 nm after the diazo reaction and was higher than that of normal deciduous teeth. These results indicate that the discolouration of teeth in patients with severe liver dysfunction is due to bilirubin deposition.

Bilirubin↗
PubMed1999

Role of salivary mucin in the protection of rat esophageal mucosa from acid and pepsin-induced injury.

The mucosal defensive mechanisms of the esophagus against acid and pepsin remain to be elucidated. In the present study, we investigated the contribution of the salivary mucin in maintaining the integrity of the esophageal mucosa. When an everted esophageal sac, isolated from normal rat, was treated with N-acetyl-L-cysteine, a mucolytic agent, the amount of glycoprotein in the gel layer adherent to the epithelium was completely depleted and the susceptibility of the mucosa against acidified pepsin-induced digestion increased. In sialoadenectomized rats, 7 days after extirpation, the amount of glycoprotein adherent to the esophageal epithelium was definitely reduced, and the esophageal mucosa was significantly vulnerable to acidified pepsin-induced digestion compared with the sham-operated rats. Induction of regurgitation of the gastric juices into the esophagus resulted in the development of severe hemorrhagic esophageal lesions only in the sialoadenectomized rats but not in the sham-operated rats. In conclusion, the glycoprotein in the adherent gel layer in rat esophagus, which mainly derives from salivary glands, plays an important role in the preepithelial defense to maintain the integrity of the esophageal mucosa against acid and pepsin.

Acetylcysteine↗
PubMed1999

Endometriosis and free radicals.

Recent studies have shown that synthase for nitric oxide or scavenger enzymes is distributed throughout the endometrium. We have reported that endothelial nitric oxide synthase, originally identified in vascular endothelial cells, is distributed in glandular epithelial cells in the endometrium, peaking in the midsecretory phase. In addition, it is known that superoxide dismutase is distributed throughout the endometrium, varying with the menstrual cycle. Yet it is not clear how these enzymes are committed in the reproductive processes. Endometriosis is often complicated by infertility and miscarriage. Of particular interest is that these enzymes are overexpressed in the disease throughout the menstrual cycle. These findings strongly suggest that excessive amounts of free radicals are produced in endometriosis. Copyrightz1999S.KargerAG,Basel

Adult↗
PubMed1999

A novel class of inhibitors for human steroid 5 alpha-reductase: phenoxybenzoic acid derivatives. I.

In a search for novel nonsteroidal inhibitors of human prostatic 5 alpha-reductase, we found a new series of phenoxybenzoic acid derivatives to be potent human prostatic 5 alpha-reductase inhibitors. Among them, 4-(biphenyl-4-yloxy)benzoic acid derivatives (2n, YM-31758), 2o and 2s showed more potent inhibitory activities than finasteride with IC50 values of 0.87, 0.67 and 0.56 nM, respectively. The optimized structures for the phenoxybenzoic acid derivatives 2d-2i were calculated by molecular modeling analysis, and the favorable distance between the carbon of the carboxyl group and the centroid of the phenyl group (benzene ring C) was found to be in the 9-11 A range.

5-alpha Reductase Inhibitors↗
PubMed1999

[Molecular analyses of intergenerational instability of CAG repeat in SCA2 gene].

Spinocerebellar Ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat, and the intergenerational change in the number of CAG repeat units has been shown to result in genetic anticipation of SCA2. To elucidate the molecular mechanism of intergenerational instability of CAG repeat, 16 affected parent-affected offspring pairs were studied. The mean intergenerational changes of CAG repeat were 5.3 +/- 6.9 repeat in paternal transmission (n = 11) and 2.8 +/- 3.1 repeat in maternal transmission (n = 5). Two CAA insertion pattern (CAG)8CAA(CAG)4CAA(CAG)8 and (CAG)13CAA(CAG)8 were found in normal alleles, and there was no significant correlation CAA insertion pattern of parents normal allele and the intergenerational change of CAG repeat.

Humans↗
PubMed1999

[Familial amyotrophic lateral sclerosis associated with mutant Cu/Zn superoxide dismutase as a conformational disease].

To investigate the molecular mechanism of mutant Cu/Zn superoxide dismutase (SOD) associated with familial amyotrophic lateral sclerosis (FALS), mutant (A1a4Thr, Gly85Arg, Gly93Ala, and two base-pair deletion in the 126th codon), as well as wild-type (wt), Cu/Zn SODs were expressed in COS7 cells. The formation of granular cytoplasmic aggregates accompanied by collapse of the cytoplasm was observed in cells expressing mutant Cu/Zn SODs, but not in cells expressing mutant Cu/Zn SODs. The aggregates contained ribosome-like particles and endoplasmic reticulum. These results suggest the possibility that mutant Cu/Zn SODs promote the formation of aggregates which are toxic to cells.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Formation of granular cytoplasmic aggregates in COS7 cells expressing mutant Cu/Zn superoxide dismutase associated with familial amyotrophic lateral sclerosis.

To investigate the molecular mechanisms of the 'gain of toxic function' of mutant Cu/Zn superoxide dismutase (SOD) associated with familial amyotrophic lateral sclerosis (FALS), mutant (Ala 4 --> Thr, Gly 85 --> Arg, Gly 93 --> Ala, and two base-pair deletion in the 126th codon), as well as wild-type (wt), Cu/Zn SODs were expressed in COS7 cells. The formation of granular cytoplasmic aggregates accompanied by collapse of the cytoplasm was observed in cells expressing mutant (mt) Cu/Zn SODs, but not in cells expressing wt Cu/Zn SOD. The aggregates contained ribosome-like particles and endoplasmic reticulum. These results suggest the possibility that mt Cu/Zn SODs promote the formation of aggregates which are toxic to cells.

Amino Acid Substitution↗
PubMed1998

Phenotype variation correlates with CAG repeat length in SCA2--a study of 28 Japanese patients.

Spinocerebellar ataxia-2 (SCA2) is an autosomal dominant ataxia caused by an abnormal CAG repeat expansion in a novel gene on chromosome 12q24.1. The size of the mutant allele is unstable during transmission, and correlates inversely with age at onset. We studied eight Japanese SCA2 families, including 28 patients, to assess the effect of repeat length on the phenotype features of SCA2. Frequencies of slow eye movements (SEM), reflex activity, dementia, choreiform movements, and axial tremor correlated significantly with CAG repeat size. Parkinsonism was seen in a man homozygote for SCA2 mutation. The clinical variety of SCA2 is apparently influenced by the size of the mutant allele, as is the case in other CAG repeat disorders.

Adolescent↗
PubMed1998

Molecular cloning, structural organization, sequence, chromosomal assignment, and expression of the mouse alpha-N-acetylgalactosaminidase gene.

Alpha-N-acetylgalactosaminidase (2-acetamido-2-deoxy-alpha-d-galactoside acetamidodeoxy-galactohydrolase, NAGA; EC 3.2.1.49) deficiency is a recently recognized autosomal recessive lysosomal disease. As a prerequisite for the generation of an animal model, the mouse NAGA gene was cloned and characterized. The NAGA gene was assigned to mouse chromosome 15 band E3, syntenic to the region encompassing the human gene, and NAGA-deficient mutant human cells transfected with the cosmid clone containing the mouse NAGA gene expressed NAGA activity. Comparison of the mouse NAGA nucleotide sequence with the human NAGA sequence predicted that the mouse NAGA gene contains an open reading frame of 1245bp, comprising nine coding exons and spanning a genomic region of 8258bp, and a 3' untranslated region of 0.5kb. The 5' untranslated region was determined in primer extension studies to be 235bp in length. Nucleotide identity between the human and mouse NAGA exons ranged from 67.4 to 89.5%, with better matches for exons 1-7 than for 8 and 9. The overall amino acid identity between the mouse and human deduced NAGA polypeptides was 82.0%, between those of mouse and chicken 72.9%. Homology was found to only one other mouse gene, i.e. the alpha-galactosidase A (GALA; EC 3.2.1. 22) gene. The amino acid identity ranged from 51.6 to 62.1% in the polypeptide regions corresponding to NAGA exons 2-7 and GALA exons 1-6, but little, if any, in the remainder. These analyses gave emphasis to the strong conservation of the NAGA gene and its origin from an ancestor common with the GALA gene, with NAGA exons 8 and 9 and GALA exon 7 being the most divergent regions in the evolution of the two genes.

Amino Acid Sequence↗
PubMed1998

Maternal anticipation in Machado-Joseph disease (MJD): some maternal factors independent of the number of CAG repeat units may play a role in genetic anticipation in a Japanese MJD family.

We studied the relationship between the number of CAG repeat units in the MJD1 gene and clinical features of Machado-Joseph disease (MJD) in eight patients from two generations of a Japanese MJD family. Because of lack of characteristic clinical signs of MJD such as dystonia, bulging eyes or facial myokymia, clinical diagnosis of MJD in this family was difficult to make prior to molecular testing for the CAG repeat expansion in the MJD1 gene. All the patients exhibited maternal transmission of MJD, and the intergenerational change in the number of CAG repeat units in the MJD1 gene was very small (+0.5+/-0.3, mean+/-S.E.M., n=4) in spite of marked genetic anticipation (-17.0 years/generation). In the present family, the degree of anticipation per repeat unit in maternal transmissions was much larger than that in maternal transmissions in the other six MJD families. This indicates that some maternal factors other than the increase of the number of CAG repeat units, which is known to be the basis of anticipation, may play a role in genetic anticipation in this MJD family.

Adult↗
PubMed1998

Progressive atrophy of cerebellum and brainstem as a function of age and the size of the expanded CAG repeats in the MJD1 gene in Machado-Joseph disease.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia associated to varying degrees with pyramidal signs, extrapyramidal signs, or peripheral amyotrophy. It is caused by unstable expansion of the CAG repeat in the MJD1 gene on chromosome 14q32.1. To determine how the neurodegenerative process in the central nervous system of patients with MJD correlates with the size of expanded CAG repeats in the MJD1 gene and other factors, we performed detailed quantitative analyses of findings of magnetic resonance imaging of the central nervous system of 21 patients with MJD of various ages and with various sizes of expanded CAG repeats. We found that atrophy of the brainstem and cerebellar vermis in MJD patients is closely correlated not only with the size of expanded CAG repeat in the MJD1 gene but also with patient age, which suggests that the neurodegenerative process in MJD is regulated by the size of expanded CAG repeats as well as by the patient age.

Adult↗
PubMed1998

Hereditary dentatorubral-pallidoluysian atrophy: detection of widespread ubiquitinated neuronal and glial intranuclear inclusions in the brain.

We examined the brains and spinal cords of seven patients with clinicopathologically and genetically confirmed hereditary dentatorubral-pallidoluysian atrophy (DRPLA) using an antibody against ubiquitin, and found small, round immunoreactive intranuclear inclusions in both neurons and glial cells in various brain regions. Ubiquitinated neuronal intranuclear inclusions (uNIIs) were consistently found in the striatum, the pontine nuclei, the inferior olivary complex, the cerebellar cortex and the dentate nucleus. Ubiquitinated glial intranuclear inclusions (uGIIs) were found less frequently than uNIIs. Most of the inclusion-bearing nuclei were of an astrocytic nature. Immunostaining with an antibody against DRPLA protein revealed similar immunoreactive neuronal and glial intranuclear inclusions, but in much smaller in numbers compared with uNIIs and uGIIs. Electron microscopy showed that such inclusions were composed of granular and filamentous structures. These findings strongly suggest that, in DRPLA, the occurrence of uNIIs and uGIIs is directly related to the causative gene abnormality (an expanded CAG repeat encoding polyglutamine), that neurons are affected much more widely than previously recognized and that glial cells are also involved in the disease process.

Adult↗
PubMed1998

Endothelial nitric oxide synthase in the endometrium during the menstrual cycle in patients with endometriosis and adenomyosis.

OBJECTIVE: To determine the expression of endothelial nitric oxide synthase in the endometrium during the menstrual cycle in endometriosis and adenomyosis. DESIGN: Immunohistochemical identification of endothelial nitric oxide in endometrial tissues using the monoclonal antibody. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): The subjects were divided into three groups: 35 patients with endometriosis, 33 patients with adenomyosis proven histologically, and 46 fertile controls. MAIN OUTCOME MEASURE(S): Semiquantitative immunostaining (evaluation nomogram) score in endometrial cells. RESULT(S): The analyses revealed phase-dependent changes in the expression of endothelial nitric oxide synthase in the surface and glandular epithelia during the menstrual cycle in the fertile controls. The expression was weakest in the early proliferative phase, gradually increased, was most marked in the midsecretory phase, and decreased thereafter. In contrast, stromal cells did not change throughout the cycle. Contrary to expectations, the expression of endothelial nitric oxide synthase in endometriosis and adenomyosis was persistently greater than the control levels throughout the menstrual cycle. CONCLUSION(S): This study has shown that endothelial nitric oxide synthase is changed in a phase-dependent manner during the menstrual cycle. The exaggerated expression of endothelial nitric oxide synthase in the endometrium throughout the cycle suggests some pathologic role in endometriosis and adenomyosis.

Adult↗
PubMed1998

Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch.

To elucidate the molecular mechanisms whereby expanded polyglutamine stretches elicit a gain of toxic function, we expressed full-length and truncated DRPLA (dentatorubral-pallidoluysian atrophy) cDNAs with or without expanded CAG repeats in COS-7 cells. We found that truncated DRPLA proteins containing an expanded polyglutamine stretch form filamentous peri- and intranuclear aggregates and undergo apoptosis. The apoptotic cell death was partially suppressed by the transglutaminase inhibitors cystamine and monodansyl cadaverine (but not putrescine), suggesting involvement of a transglutaminase reaction and providing a potential basis for the development of therapeutic measures for CAG-repeat expansion diseases.

Animals↗
PubMed1998

Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations.

To test the hypothesis that the frequencies of normal alleles (ANs) with a relatively large number of CAG repeats (large ANs) are related to the prevalences of the dominant spinocerebellar ataxias (SCAs)-SCA types 1, 2, 3 (Machado-Joseph disease), 6, and dentatorubral-pallidoluysian atrophy (DRPLA)-we investigated the relative prevalences of these diseases in 202 Japanese and 177 Caucasian families and distributions of the number of CAG repeats of ANs at these disease loci in normal individuals in each population. The relative prevalences of SCA1 and SCA2 were significantly higher in Caucasian pedigrees (15% and 14%, respectively) than in Japanese pedigrees (3% and 5%, respectively), corresponding to the observation that the frequencies of large ANs of SCA1 (alleles >30 repeats) and of SCA2 (alleles >22 repeats) were significantly higher in Caucasians than in Japanese. The relative prevalences of MJD/SCA3, SCA6, and DRPLA were significantly higher in Japanese pedigrees (43%, 11%, and 20%, respectively) than in Caucasian pedigrees (30%, 5%, and 0%, respectively), corresponding to the observation that the frequencies of large ANs of MJD/SCA3 (>27 repeats), SCA6 (>13 repeats), and DRPLA (>17 repeats) were significantly higher in Japanese than in Caucasians. The close correlations of the relative prevalences of the dominant SCAs with the distributions of large ANs strongly support the assumption that large ANs contribute to generation of expanded alleles (AEs) and the relative prevalences of the dominant SCAs.

Asian People↗
PubMed1998

Morphometric evaluation of stromal vascularization in the endometrium in adenomyosis.

A computerized morphometric investigation of stromal vascularization in the endometrium during adenomyosis was performed retrospectively. Using a polyclonal antibody and a peroxidase-antiperoxidase method, formalin-fixed paraffin sections of the tissue were stained for von Willebrand factor, a marker for endothelium. The subjects were divided into two groups: 42 patients with histologically proven adenomyosis and 29 fertile control subjects, 12 in the proliferative phase and 17 in the secretory phase. Objective quantitative colour image analysis was used to assess the staining intensity and hence the degree of vascularization. In the control group, stromal vascularization increased in the secretory phase. In adenomyosis, vascularization increased markedly, up to 11.6 times that of the controls, in terms of the in total surface area of capillaries per mm2 in the endometrium in the proliferative phase. These findings suggest clinical relevance to severe functional disturbances such as hypermenorrhoea or iron deficiency anaemia.

Adult↗
PubMed1998

Acute cauda equina syndrome secondary to lumbar disc herniation mimicking pure conus medullaris syndrome--case report.

A 49-year-old male presented with a rare case of acute cauda equina syndrome secondary to a sequestrated lumbar disc mimicking pure conus medullaris syndrome. He consulted the emergency room of Otsu Municipal Hospital because saddle anesthesia and complete urinary retention which had started 2 days before admission. Additionally, he complained of constipation and impotence. Abnormality of the deep tendon reflexes, sciatica, and leg weakness were not organized. Emergent myelography and subsequent computed tomography revealed a sequestrated disc in the sacrum compressing the lower cauda equina, but not the conus medullaris. Emergent surgical decompression was performed about 60 hours after the onset. The patient almost fully recovered from sphincter dysfunction, impotence, and saddle anesthesia 3 months after the operation. When a syndrome like conus medullaris compression is encountered, the lower cauda equina should be examined as well as the conus level. Such cases require urgent diagnosis and treatment.

Cauda Equina↗