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Biomedical subjects

S Saitoh

Publications and source records attributed to S Saitoh.

At least 217 records · Page 12Linked to original sources
PubMed1996

Effects of expansive force on the differentiation of midpalatal suture cartilage in rats.

In an attempt to clarify the effects of biomechanical tensional force on chondrogenic and osteogenic differentiation of secondary cartilage, the midpalatal sutures of 4-week-old Wistar male rats were expanded by orthodontic wires which applied 20 g force for 4, 7, 10, and 14 days. The differentiation pathways in the midpalatal suture cartilage were examined by immunohistochemistry for osteocalcin, type I and type II collagen, and von Kossa histochemistry. Although the midpalatal sutures of the control animals consisted mainly of two separate secondary cartilages with mesenchyme-like cells at their midlines, type I collagen-rich fibrous tissue began to appear at day 4 and increased at the midline of the cartilage with days of experiment. At the end of the experiment, type I collagen-rich and calcified bone matrix appeared at the boundary between the precartilaginous and the cartilaginous cell layers. Most of the cartilaginous tissues were separated from each other and the midpalatal suture was replaced by osteocalcin-positive intramembranous bone and fibrous sutural tissue. These results strongly suggest that tensional force changed the phenotypic expression of collagenous components in secondary cartilage, which may reflect the differentiation pathway of osteochondro progenitor cells.

Animals↗
PubMed1996

Long-term results of vein grafts interposed in arterial defects using the telescoping anastomotic technique and fibrin glue.

Fibrin glue has been applied in the anastomosis of vein grafts placed in rat femoral arteries using the telescoping technique at both ends of the graft. 34 out of 35 grafts which were patent 1 to 3 weeks post-operatively were kept for 3 months to assess the long-term patency, and the effect of the glue on the diameters of the graft and femoral artery. All 34 grafts were patent 3 months post-operatively. Excessive enlargement of the graft diameter was alleviated by the fibrin glue without affecting the diameter of the femoral artery. The diameter at the proximal anastomosis was 66% and that at the distal anastomosis was 87% of the diameter of the femoral artery.

Anastomosis, Surgical↗
PubMed1996

High frequency of p53 gene mutations in primary breast cancers in Japanese women, a low-incidence population.

The pattern of acquired mutations in the p53 tumour-suppressor gene is potentially useful for determining factors contributing to carcinogenesis in diverse populations differing in incidence and/or mortality from the disease. We previously reported differences in mutational patterns of the p53 gene in primary breast cancers from Midwest US Caucasian, African-American and Austrian women. Herein, we report 16 mutations in 27 primary breast cancers from Japanese women from Hirosaki, a population with a low incidence of breast cancer. The frequency of 59.3% of p53 mutations is the highest reported in breast cancers from a particular ethnic group thus far. A relatively high number of mutations (7/16) were heterozygous in at least some tumour cell clusters. Intergroup comparisons of the mutational pattern between this population and several other US, European and Japanese populations do not show any statistically significant differences. There were recurrent mutations at two sites, codon 273 (R --> H; three mutations), a common hotspot of mutations in breast and other cancers, and codon 183 (S --> Stop; two mutations), a very rare location for p53 mutations. These mutations were shown to be independent and presumably not in the germ line. The highest frequency of p53 mutations raises the possibility that p53 mutagenesis is a predominant factor for breast cancer development in this low-risk Japanese group, whereas in other cohorts different mechanisms are likely to account for the higher proportion of breast cancer. Further studies are needed to confirm the present observations.

Adult↗
PubMed1996

Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene.

Imprinting on human chromosome 15 is regulated by an imprinting centre, which has been mapped to a 100-kb region including exon 1 of SNRPN. From this region we have identified novel transcripts, which represent alternative transcripts of the SNRPN gene. The novel exons lack protein coding potential and are expressed from the paternal chromosome only. We have also identified intragenic deletions and a point mutation in patients who have Angelman or Prader-Willi syndrome due to a parental imprint switch failure. This suggests that imprint switching on human chromosome 15 may involve alternative SNRPN transcripts.

Alternative Splicing↗
PubMed1996

A pilot study of corticosteroid priming for lymphoblastoid interferon alfa in patients with chronic hepatitis C.

Interferon treatment reduces the serum level of hepatitis C virus (HCV) and improves inflammatory activity, but relapse is frequently observed. In an attempt to develop a new therapeutic strategy that may reduce relapse and cure the disease, we evaluated the effect of corticosteroid priming on lymphoblastoid interferon alfa in an open randomized clinical trial. The level of HCV RNA increased significantly during corticosteroid priming (from 5.60 [median] to 21.0 x 10(5) Eq/mL; P = .0004) but decreased to the pretreatment level 4 weeks after cessation of corticosteroid (7.0 x 10(5) Eq/mL; P = .07). Sustained normalization of alanine transaminase (ALT) level and virus clearance, confirmed by negative results for HCV RNA using reverse-transcription nested polymerase chain reaction (PCR), were observed over a period of 6 months in 8 of 19 (42.1%) corticosteroid-primed patients, compared with 6 of 19 patients (31.6%) treated with interferon only. A "rebound" of ALT after the withdrawal of corticosteroid was observed in only 2 of 19 patients primed with corticosteroid, but both showed sustained responses. Multivariate analysis for factors predictive of the sustained response indicated that HCV titers measured immediately before interferon therapy and HCV genotype were statistically significant (P = .006 and P = .025, respectively). Our results indicated that corticosteroid priming has a marginal benefit over treatment with interferon alone and that large-scale clinical trials are necessary to determine whether interferon with corticosteroid priming is more effective than interferon alone.

Adult↗
PubMed1996

Aberrant mitosis in fission yeast mutants defective in fatty acid synthetase and acetyl CoA carboxylase.

Two fission yeast temperature-sensitive mutants, cut6 and lsd1, show a defect in nuclear division. The daughter nuclei differ dramatically in size (the phenotype designated lsd, large and small daughter). Fluorescence in situ hybridization (FISH) revealed that sister chromatids were separated in the lsd cells, but appeared highly compact in one of the two daughter nuclei. EM showed asymmetric nuclear elongation followed by unequal separation of nonchromosomal nuclear structures in these mutant nuclei. The small nuclei lacked electron-dense nuclear materials and contained highly compacted chromatin. The cut6+ and lsd1+ genes are essential for viability and encode, respectively, acetyl CoA carboxylase and fatty acid synthetase, the key enzymes for fatty acid synthesis. Gene disruption of lsd1+ led to the lsd phenotype. Palmitate in medium fully suppressed the phenotypes of lsd1. Cerulenin, an inhibitor for fatty acid synthesis, produced the lsd phenotype in wild type. The drug caused cell inviability during mitosis but not during the G2-arrest induced by the cdc25 mutation. A reduced level of fatty acid thus led to impaired separation of non-chromosomal nuclear components. We propose that fatty acid is directly or indirectly required for separating the mother nucleus into two equal daughters.

Acetyl-CoA Carboxylase↗
PubMed1996

Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.

A patient with Prader-Willi syndrome (PWS) was found to carry a de novo balanced reciprocal translocation, t(15;19)(q12;q13.41), which disrupted the small nuclear ribonucleoprotein N (SNRPN) locus. The translocation chromosome 15 was found to be paternal in origin. Uniparental disomy and abnormal DNA methylation were ruled out. The translocation breakpoint was found to have occurred between exon 0 (second exon) and 1 (third exon) of the SNRPN locus outside of the SmN open reading frame (ORF), which is intact. The transcriptional activities of ZNF127, IPW, PAR-1, and PAR-5 were detected with RT-PCR from fibroblasts of the patient, suggesting that these genes may not play a significant role in the PWS phenotype in this patient. Transcription from the first two exons and last seven exons of the SNRPN gene was also detected with RT-PCR; however, the complete mRNA (10 exons) was not detected. Thus, the PWS phenotype in the patient is likely to be the result of disruption of the SNRPN locus.

Autoantigens↗
PubMed1996

Decidua as a site of extrathymic V gamma I T-cell differentiation.

PROBLEM: Decidual tissue is an interface between the host and fetus, which is regarded as a natural allograft. We have reported the possible presence of extrathymic T cells in human decidua through the expression of recombinase-activating genes in the decidual CD16-CD56bright large granular lymphocytes. METHODS: In this study we analyzed expression of TCR V gamma delta gene segments in peripheral lymphocytes and decidual and nonpregnant endometrial samples using RT-PCR and oligonucleotide hybridization. RESULTS: Interestingly, a limited repertoire of V gamma gene segments were discovered in decidual lymphocytes of normal pregnancy when compared with peripheral lymphocytes, whereas usage of V delta gene segments were ubiquitous in peripheral and decidual lymphocytes. Strong expression of V gamma I gene segment, often exceeding 50% of total V gamma, were noted in all (13/13) pregnant decidual tissues obtained at different gestational stages. Interestingly, this predominance of V gamma I gene is also noted in nonpregnant endometrial samples and the decidua of patients with ectopic pregnancies. CONCLUSIONS: Our results suggest the nature of decidual V gamma I T cells as possible suppressors of rejective maternal cytotoxic T cells during the maintenance of normal pregnancies.

Adult↗
PubMed1996

Demonstration of borna disease virus RNA in peripheral blood mononuclear cells derived from domestic cats in Japan.

Borna disease virus (BDV) naturally infects horses, sheep, and several other species, including humans, and it is believed to be related to neurological disorders. BDV infection in domestic cats has also been demonstrated by serological assays. We demonstrated for the first time BDV RNA in peripheral blood mononuclear cells from 11 of 83 (13.3%) randomly selected domestic cats in Japan by nested reverse transcriptase-PCR. The BDVs from cats were similar to but slightly different from those from horses and humans, as shown by sequencing the reverse transcriptase-PCR products. None of the cats was positive for both BDV RNA and anti-BDV antibodies.

Amino Acid Sequence↗
PubMed1996

Effects of cardiac contraction and coronary sinus pressure elevation on collateral circulation.

Controlled coronary sinus occlusion was shown to retard necrosis of ischemic myocardium. To elucidate this mechanism, regional myocardial blood flow measurement was performed with and without coronary sinus pressure elevation to 30 mmHg (CS30). Colored microspheres were injected into left and right coronary arteries after coronary perfusion of the left anterior descending (LAD) coronary artery was stopped in seven isolated canine hearts with induced atrioventricular block, either paced at 120 beats/min by direct right ventricular stimulation [beating heart (B)] or during asystole induced by stopping pacing [nonbeating heart (NB)]. Regional myocardial blood flow in the LAD perfused area in the control state in the NB with normal coronary sinus pressure (NB-CScont; 0.27 +/- 0.13 ml.min-1.g-1, means +/- SE) was significantly greater than those in B-CScont (0.19 +/- 0.09 ml.min-1.g-1; P < 0.05) and in NB with CS30 (NB-CS30; 0.19 +/- 0.09 ml.min-1.g-1; P < 0.05). Regional myocardial blood flow of the LAD area in B with CS30 (B-CS30; 0.23 +/- 0.10 ml.min-1.g-1) was significantly greater in comparison with that at B-CScont and NB-CS30 (P < 0.05). The augmentative effect of the LAD area regional myocardial blood flow was observed only in the periphery of the ischemic region but not in its center. Cardiac contraction and CS30 impede regional myocardial blood flow in the ischemic bed independently. The coexistence of these two factors enhances regional myocardial blood flow. In conclusion, coronary sinus pressure elevation in B may participate in augmenting collateral flow.

Animals↗
PubMed1996

Ovariectomy-evoked increase in gonadotropin releasing hormone receptor parallels its messenger RNA level, but does not correlate with stimulated gonadotropin release.

The amount of gonadotropin releasing hormone receptor (GnRH-R) in the anterior pituitary changes during the rat estrous cycle; in addition, it is chronically increased for several weeks in response to ovariectomy. The present study was undertaken to investigate these changes in relation to the concentrations of GnRH-R mRNA, gonadotropins and luteinizing hormone-beta (LH-beta) subunit in serum and the pituitary gland, as well as hypothalamic GnRH. GnRH-R concentrations on the day of estrus were significantly lower than that at diestrus (30% lower during 2 d), its mRNA decreased even further (by 60%), but there were no significant changes in gonadotropin. Ovariectomy increased GnRH-R significantly (by 30% during 2 wk) in parallel with receptor mRNA and with pituitary LH and LH-beta, but induced an earlier increase in serum gonadotropins. Our results suggest that transcriptional activity is more intimately linked to the number of GnRH-R in the long-term increase after ovariectomy than in the short-term change during the estrous cycle, and that the increased GnRH-R is not a major factor in ovariectomy-stimulated gonadotropin release.

Animals↗
PubMed1996

Gene structure, DNA methylation, and imprinted expression of the human SNRPN gene.

The human SNRPN (small nuclear ribonucleoprotein polypeptide N) gene is one of a gene family that encode proteins involved in pre-mRNA splicing and maps to the smallest deletion region involved in the Prader-Willi syndrome (PWS) within chromosome 15q11-q13. Paternal only expression of SNRPN has previously been demonstrated by use of cell lines from PWS patients (maternal allele only) and Angelman syndrome (AS) patients (paternal allele only). We have characterized two previously unidentified 5' exons of the SNRPN gene and demonstrate that exons -1 and 0 are included in the full-length transcript. This gene is expressed in a wide range of somatic tissues and at high, approximately equal levels in all regions of the brain. Both the first exon of SNRPN (exon -1) and the putative transcription start site are embedded within a CpG island. This CpG island is extensively methylated on the repressed maternal allele and is unmethylated on the expressed paternal allele, in a wide range of fetal and adult somatic cells. This provides a quick and highly reliable diagnostic assay for PWS and AS, which is based on DNA-methylation analysis that has been tested on > 100 patients in a variety of tissues. Conversely, several CpG sites approximately 22 kb downstream of the transcription start site in intron 5 are preferentially methylated on the expressed paternal allele in somatic tissues and male germ cells, whereas these same sites are unmethylated in fetal oocytes. These findings are consistent with a key role for DNA methylation in the imprinted inheritance and subsequent gene expression of the human SNRPN gene.

Adolescent↗
PubMed1996

[Reconstruction of right ventricular outflow tract-pulmonary artery utilizing autologous tissue in extreme tetralogy of Fallot after coil embolization for major aortopulmonary collateral artery: report of a case].

We report a successful surgical treatment for tetralogy of Fallot with pulmonary atresia. A 18-year-old girl was admitted because of increasing exertional dyspnea and cyanosis. She had undergone bilateral classical Blalock-Taussing shunt. Prior to the correction, two major aortopulmonary collateral arteries were embolized using steel coils. Under cardiopulmonary bypass, posterior wall of the pulmonary artery was anastomosed directly to the cranial margin of the ventriculotomy for a floor made of autologous tissue. The roof was reconstructed using a patch with a monocusp. The patient is in a good postoperative condition. A coil embolization is useful and this reconstruction utilizing autologous tissue could prevent a late stenosis of the reconstructed pulmonary artery tract.

Adolescent↗
PubMed1995

Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2).

Thymic shared antigen-1 (TSA-1) is a glycosyl-phosphatidylinositol (GPI)-anchored differentiation Ag expressed on murine lymphocytes, and is identical to stem cell Ag-2 (Sca-2). Using newly established mAb against TSA-1/Sca-2, we have previously shown that surface TSA-1 expression is induced upon activation in T cells, and that anti-TSA-1 inhibits IL-2 production induced by anti-CD3 stimulation in T cell hybridomas. In the present study, we have analyzed the functional role of TSA-1 during T cell activation using normal T cells, T cell hybridomas, and transfected Jurkat cell lines that expressed either GPI-anchored or transmembrane form of TSA-1. Anti-TSA-1 inhibited IL-2 production from normal T cells stimulated with soluble anti-CD3 plus accessory cells. Anti-TSA-1 exhibited the inhibitory effect on T cells, but not on accessory cells, because anti-TSA-1 inhibited IL-2 production in Jurkat cells transfected with TSA-1 cDNA, but not in control transfectant. A transmembrane form of TSA-1 was expressed in Jurkat cells by fusing the extracellular portion of TSA-1 to the transmembrane and cytoplasmic regions of the class 1 Db. The analysis using this transfectant revealed that anti-TSA-1-mediated inhibition of IL-2 production did not require the GPI anchor of TSA-1. Finally, in addition to the inhibition of IL-2 production, tyrosine phosphorylation of CD3 zeta-chains observed following TCR stimulation, one of the important early activation events, was markedly reduced by anti-TSA-1. These results imply that TSA-1/Sca-2 plays an important regulatory role in the TCR signaling pathway of activated T cells in addition to its role in T cell differentiation.

Animals↗