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Biomedical subjects

Y Matsubara

Publications and source records attributed to Y Matsubara.

At least 109 records · Page 6Linked to original sources
PubMed1998

A one-base deletion (183delC) and a missense mutation (D276H) in the T-protein gene from a Japanese family with nonketotic hyperglycinemia.

Two novel mutations in the gene encoding T-protein, a component of the glycine cleavage system, were identified in a Japanese family with nonketotic hyperglycinemia. The proband had two affected sibs, and enzymatic analysis of the liver sample from the proband revealed the T-protein deficiency. The first mutation, 183delC, was found in exon 1. One of six cytidine residues (base position 183-188) was deleted. The deletion was located in a coding region of the mitochondrial leader peptide and was deduced to create a truncated peptide with 94 amino acids. The second mutation was a base substitution from G to C at position 955 in exon 7. The G955C substitution caused an amino acid change from aspartate to histidine at position 276 (D276H). Aspartic acid at position 276 is evolutionarily conserved among human, bovine, chicken, and pea genes, and replaced by glutamic acid in Escherichia coli, suggesting that the presence of an acidic amino acid at 276 may be crucial for the enzymatic function. No base change other than the 183delC and the G955C was observed in the sequencing analysis. Familial analysis revealed that the 183delC and the D276H mutations were inherited from the father and the mother, respectively. This is the first report of T-protein gene mutation in Oriental patients with nonketotic hyperglycinemia.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Establishment of a novel cell line (TS-2) of pre-B acute lymphoblastic leukemia with a t(1;19) not involving the E2A gene.

The t(1;19)(q23;p13) translocation involving the E2A gene on chromosome 19p13.3 is a nonrandom translocation that is often seen in childhood pre-B-cell acute lymphoblastic leukemia (ALL). However, recent studies have demonstrated the presence of immunophenotypic and molecular heterogeneity among patients with the cytogenetically identical chromosome translocation. Here we report a novel pre-B ALL cell line, TS-2, with t(1;19) translocation not involving the E2A gene. The breakpoint of t(1;19) in TS-2 was demonstrated to be at 19p13.3, a region indistinguishable from the locus of the E2A gene, by cytogenetic study and fluorescence in situ hybridization. However, rearrangement of the E2A gene was not detected in TS-2 by Southern blot analysis. Moreover, the expressions of PBX1 or E2A/PBX1 fusion genes were not detected by an extensive study with Northern blot analysis and reverse transcription-polymerase chain reaction. These findings suggest that TS-2 may have a genetic abnormality involving uncharacterized gene(s) at 19p13.3 distinct from the E2A gene and, therefore, may be useful for investigating the heterogeneity of molecular pathogenesis in leukemias with t(1;19)(q23;p13) translocation.

Adenovirus E2 Proteins↗
PubMed1998

Extracellular poly(alpha-L-guluronate)lyase from Corynebacterium sp.: purification, characteristics, and conformational properties.

Extracellular alginate lyase was purified from the culture supernatant of Corynebacterium sp. isolated from the sewage of a sea tangle processing factory in order to elucidate the structure-function relationship of alginate lyase. The electrophoretically homogeneous enzyme was shown to have a molecular mass of 27 kDa by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) and by gel filtration, with an isoelectric point of 7.3. The molecular mass from amino acid analysis was 28.644 kDa. The optimal pH and temperature for the enzyme reaction were around 7.0 and 55 degrees C, respectively. Metal compounds such as MnCl2 and NiCl2 increased the enzyme activity. The enzyme was identified as the endolytic poly(alpha-L-guluronate)lyase, which was active on poly(alpha-L-1,4-guluronate) and caused a rapid decrease in the viscosity of alginate solution. Measurement of the far-UV circular dichroic spectrum of the enzyme molecule gave a spectrum with a deep trough at 215 nm accompanied by a shallow one at around 237 nm, and with a high peak at 197 nm and a much lower one at 230 nm. This spectrum was most likely to be that of the beta-form of the enzyme molecule and resembled poly(beta-D-mannuronate)lyase from Turbo cornutus (wreath shell) and poly(alpha-L-guluronate)lyase from Vibrio sp. (marine bacterium). The near-UV circular dichroic spectrum was characteristic for aromatic amino acid residues. In the presence of 6 M urea, these spectra changed drastically in the near-UV and a little in the far-UV with the disappearance of the enzyme activity. Removal of the denaturant in the enzyme solution by dialysis restored both the activity and inherent circular dichroic spectra. The beta-sheets observed in alginate lyases as the major ordered structure seem to be a common conformation for the lyases.

Amino Acids↗
PubMed1998

Induction of precocious pepsinogen synthesis by glucocorticoids in fetal rat gastric epithelium in organ culture: importance of mesenchyme for epithelial differentiation.

Glucocorticoids significantly affect both proliferation and differentiation of gastric epithelial cells in vivo. Here we examined the mechanism of action of glucocorticoids on the cells in vitro, with special reference to the epithelial-mesenchymal interaction. When 16.5-day fetal rat gastric explants were maintained in organ culture, the epithelial cells began to invaginate into mesenchyme on days 3 to 4, and formed glandular structures on days 5 to 6 in culture. Immunohistochemical analysis with specific antibodies revealed that pepsinogen-synthesizing cells first appeared on day 2, and they increased in number with epithelial morphogenesis to about 20%-30% of total epithelial cells on days 4 to 6, and that these cells were localized at the base of glandular structures in control media. When the explants were treated with hydrocortisone (1 microgram/ml), epithelial morphogenesis was mostly suppressed, but epithelial cytodifferentiation was significantly stimulated, indicating that epithelial morphogenesis is not necessary for their cytodifferentiation. In glucocorticoid-treated explants, pepsinogen-synthesizing cells first appeared on day 1, and more than 90% of the cells were positively stained with the antibodies from days 3 to 5 in culture. Biochemical analysis showed that much higher acid protease activity could be detected in glucocorticoid-treated explants than in controls from days 2 to 6 in culture, and analysis by zymography indicated that the synthesis of pepsinogen 1 but not cathepsin E was stimulated by the hormone. Northern blotting analysis showed that the level of pepsinogen 1 mRNA was greatly increased by glucocorticoids. Examination of the effect of the hormone on the epithelial proliferation showed that hydrocortisone (1 microgram/ml) significantly inhibited the epithelial growth from days 1 to 3 in culture. To investigate the role of epithelial-mesenchymal interaction in the glucocorticoid-induced differentiation of the gastric epithelial cells, effects of the hormone on the proliferation and differentiation of the cells in the absence of mesenchyme were examined, using a recently established primary culture system. The epithelial cells synthesized cathepsin E but not pepsinogen in cell culture, irrespective of glucocorticoid treatment, and the level of acid protease activity was not affected by the hormone, indicating that mesenchyme is necessary for the hormone to induce pepsinogen gene expression in the epithelial cells. In the cell culture system, glucocorticoids did not inhibit but significantly stimulated epithelial proliferation. This suggests that the hormone indirectly inhibited epithelial proliferation in organ culture, probably via mesenchyme. The mechanism of action of glucocorticoids on the epithelial-mesenchymal interaction in the fetal glandular stomach is discussed.

Animals↗
PubMed1998

Genetic polymorphisms and risk of coronary artery disease.

The fact that certain ethnic groups and specific populations residing in certain geographic areas carry an increased risk for thrombosis and that thrombosis occurs in young patients without established risk factors indicates the presence of new, previously unrecognized inherited conditions predisposing to thrombosis. We are now aware that interindividual variations within the loci coding for proteins relevant to lipid and vascular metabolisms as well as blood coagulation are universally found. Platelets play central roles in cerebrovascular diseases and acute coronary syndromes, as demonstrated by histopathological findings and clinical observations showing the efficacy of antiplatelet therapies for these disorders. In this article, we show our recent findings on the association between coronary artery disease (CAD) and polymorphisms in platelet membrane glycoproteins. The glycoprotein (GP) Ib/IX complex is a receptor for von Willebrand factor, which mediates shear stress-dependent platelet activation. It has recently been implicated in the pathogenesis of acute coronary syndromes. We have determined genotypes of the "size-polymorphism" of GPIb alpha--i.e., the variable number (1-4) of a 13 amino acid sequence (399-411)--in angiographically proven Japanese CAD patients with myocardial infarction or angina pectoris as well as in individuals from the general population with no history of angina or other heart diseases and normal resting electrocardiograms (ECG). We have found that the genotypes having at least one 4-repeat allele (4R) are more frequently found in patients than in controls. Logistic regression analyses for the adjustment of age, sex, and other acquired coronary risk factors provided an odds ratio of 7.94 (p=0.0043) for those with 4R vs. those without 4R, suggesting that the presence of 4R is an independent risk factor for CAD. The molecular mechanisms underlying this association are currently under investigation. Relationships between arterial thrombosis and polymorphisms in other platelet GPs (collagen receptor and fibrinogen receptor), blood coagulation factors, fibrinolytic factors, vasoactive substances, and factors relevant for lipid metabolisms are also discussed.

Adult↗
PubMed1998

Action of poly (alpha-L-guluronate)lyase from Corynebacterium sp. ALY-1 strain on saturated oligoguluronates.

A kinetic analysis of degradation of saturated oligoguluronates by poly(alpha-L-guluronate)lyase from Corynebacterium sp. ALY-1 strain was done. The saturated oligoguluronates were prepared by hydrolyzing poly alpha-1,4-L-guluronate from alginate with HCl, and then by gel filtration on a Bio-Gel P-6 column. The saturated pentaguluronate or above were rapidly degraded by the enzyme, while tetraguluronate was slowly degraded. From the dependency of the catalytic rate constant (kcat) on the degree of polymerization of substrates, the enzyme was found to have a subsite size corresponding to hexaguluronate units. The action pattern of the enzyme on hexaguluronate suggested that the catalytic site of the enzyme was matched to the linkage between the second and third uronic residue from the non-reducing end, since the substrate was mainly split into a unsaturated tetramer and a saturated dimer from a HPLC analysis.

Amino Acid Sequence↗
PubMed1998

[Limited operation for stage I lung cancer: a retrospective study].

Although lobectomy is standard therapy for Stage I non-small cell lung cancer, it often cannot be performed in poor-risk patients. In this report, we describe the results of a retrospective study to assess the usefulness of limited operation for stage I lung cancer. Over a 21-year period, 1,286 lung cancers were resected at our center. Among the 497 patients with stage I lung cancer, 36 sublobar resections were performed. There was only one surgery-related death, and the 5-year survival rate was 46% for all patients. At 5 years, survival was 69.2% for patients with squamous cell carcinoma and 33.7% for patients with adenocarcinoma. Survival rates were higher in patients who underwent mediastinoscopy than those who did not, and depended on histological findings and accurate pathological staging.

Adenocarcinoma↗
PubMed1998

[A case of pulmonary sarcoidosis with multiple cavitation and pneumothorax].

We describe a rare case of pulmonary sarcoidosis with multiple cavitation and pneumothorax. A 32-year-old woman was admitted to our hospital with a dry cough and an interstitial shadow with dense infiltrates in both upper lungs and cavitation in the right upper lung on chest roentgenogram and CT. Laboratory tests revealed an elevated level of serum lysozyme. BAL fluid demonstrated a high proportion of lymphocytes with an increased CD4/CD8 ratio, compatible with sarcoidosis. Transbronchial lung and skin biopsies showed evidence of noncaseating epithelioid-cell granuloma, and a diagnosis of sarcoidosis was made. Although pneumothorax appeared in the left lung on chest roentgenogram during clinical observation conservative treatment without corticosteroids or any other therapy for a follow-up period of 3 years resulted in improvement of her clinical condition and abnormal X-ray findings.

Adult↗
PubMed1998

[Cytokines produced by cells in bronchoalveolar lavage fluid from a patient with primary pulmonary cryptococcosis].

Cytokines in the culture supernatant of concanavalin A-stimulated macrophages/lymphocytes isolated from bronchoalveolar lavage (BAL) fluid in a 29-year-old patient with primary pulmonary cryptococcosis were evaluated to study the immune reaction against Cryptococcus neoformans in the lung. Before fungicidal therapy, levels of interferon-gamma and interleukin-10 were markedly elevated, and declined after therapy. There were no changes in interleukin-2 or interleukin-4 throughout the clinical course. This result suggests that IFN-gamma and IL-10 may be involved in the immune reaction against pulmonary cryptococcosis.

Adult↗
PubMed1998

[A pulmonary tumorlet with caseous granuloma associated with atypical mycobacterium].

We encountered a case of pulmonary tumorlet with caseous granuloma associated with atypical mycobacterium. A 73-year-old woman was admitted to the hospital because a chest x-ray film showed enlargement of an abnormal shadow in the middle lobe of the right lung. Primary lung cancer was suspected and right middle lobectomy was performed. Acid-fast bacilli (Gaffky 1) were found in a caseous lesion and examination of intraoperatively obtained frozen specimens showed caseous granulomas. The bacilli were later identified as Mycobacterium avium complex. The permanent specimen showed a minute lesion consisting of small clusters of epithelial cells resembling carcinoid tumor in contact with granulomatous tissue. Histopathological examination revealed argyrophilia on Grimelius stain and immunoreactivity to chromogranin-A in the clusters of epithelial cells. Although these results are consistent with small cell carcinoma or peripheral carcinoid tumor, pulmonary tumorlet was diagnosed because of the lesion's small and minimal cytologic atypia, and because of chronic pulmonary damage around the lesion. Pulmonary tumorlets are minute, usually microscopic, tumor-like lesions mostly found in damaged lung tissue obtained at autopsy or during surgery. Morphological diagnosis is sometimes very difficult, but recently these lesions have been regarded as hyperplastic lesions arising in pulmonary neuroendocrine cells (Kultschitzky cells) and caused by chronic pulmonary damage, such as hypoxia and inflammation. Pulmonary tumorlets must be considered in the differential diagnosis of minute lesions suspected to be small cell carcinoma or peripheral carcinoid tumor.

Aged↗
PubMed1998

[Factors involved in the regeneration of the gastrointestinal tract].

The gastrointestinal mucosal regeneration is a complex process that includes cell migration and proliferation. A wide variety of factors are presumably be involved in the reestablishment of the functional and structural integrity of the mucosa, and different experimental models have been applied to elucidate these factors. Accumulating evidences indicate the importance of soluble factors (e.g. growth factors, cytokines, trefoil peptides) and matrix components in the mucosal healing. Though the interactions of these factors remain to be fully elucidated, the identification of physiologically relevant factors that stimulate mucosal repair and a through description of the mechanisms of action may lead to the development of specific strategy for the promotion of the mucosal healing by exploiting natural mechanisms of regeneration.

Cell Division↗
PubMed1997

Coronary artery disease and polymorphisms in a receptor mediating shear stress-dependent platelet activation.

BACKGROUND: Platelets play pivotal roles in coronary thrombosis, and antiplatelet therapies are widely used for coronary artery disease (CAD). However, the effects of genetic variation in platelets on CAD are poorly understood. We have assessed the association between CAD and polymorphisms in a platelet receptor for von Willebrand factor, the glycoprotein (GP) Ib/IX complex, which mediates shear stress-dependent platelet activation. METHODS AND RESULTS: Genotypes of the alpha-chain of the receptor (GP Ib alpha, 145Thr/Met) were determined in 91 patients with myocardial infarction (MI) or angina pectoris whose lesions were confirmed by coronary angiography as well as in 105 individuals from the general population with no history of angina or other heart diseases and normal resting ECGs. There was no homozygote for Met/Met in either the control or patient groups. The prevalence of the Thr/Met genotype (T/M) in all patients was not significantly different from that in the control group. However, the frequency of T/M was significantly higher in patients aged < or = 60 years (31.8%) than in control subjects aged < or = 60 years (16.0%; P<.05, odds ratio=2.5). An association was also demonstrated between CAD and the other polymorphism of GP Ib alpha, a variable number of tandem repeats of a 13-amino acid sequence, which is known to be linked to the 145Thr/Met polymorphism. There was an association between the frequency of the T/M genotype and the angiographic severity of CAD: 11.1% for Gensini score < 40 versus 50.0% for Gensini score > or = 40 (P=.0015). There was no difference in the distribution of GP Ib alpha genotypes between patients with MI and those with angina pectoris. CONCLUSIONS: This study suggests that the presence of the Met allele in GP Ib alpha is a risk factor for the prevalence and severity of CAD in individuals aged < or = 60 years. The results need to be confirmed in a large-scale study of incident case subjects and matching control subjects.

Adult↗