Search PubMed⌕ Search

Biomedical subjects

S Miyake

Publications and source records attributed to S Miyake.

At least 127 records · Page 7Linked to original sources
PubMed1997

[Two cases of toluene embryopathy with severe motor and intellectual disabilities syndrome].

We reported two patients with severe motor and intellectual disabilities syndrome, who were born to mothers having inhaled organic solvents during pregnancy. They had microcephaly, cerebral palsy, mental retardation, seizures, growth failure and minor craniofacial anomalies, variable growth deficiency including a small midface, narrow bifrontal diameter, low-set ears, thin upper lips and micrognathia. Patient 1, a male, died at 8 years and 8 months. The autopsy of his brain revealed marked cerebral atrophy and destruction of bilateral temporal lobes with ventricular enlargements. Microscopic examination revealed migration disorders with polymicrogria at the remaining cerebrum and the cerebellum as well as very thin white matter. Much hemosiderin was found around ventricles, suggesting recurrent minimal bleedings which led to more brain atrophy. Patient 2, a 5 months old male infant, had infantile spasms. On CT and MRI, he had bilateral temporal lobe defect, which might be due to the infarction of bilateral middle cerebral arteries at the prenatal period. These clinical findings are similar to those of other embryopathies, caused by alcohol, phenytoin and other agents. Hersh et al. reported five cases of toluene embryopathy in 1985 and 1988, but they did not report such central nervous system abnormalities. The pathogenesis of toluene embryopathy remains to be solved, but our cases suggested the possible teratogenesis of toluene.

Abnormalities, Drug-Induced↗
PubMed1997

[A survey of radioactive levels of agricultural products in Saitama Prefecture].

Past atmospheric nuclear testing which have been conducted frequently, have caused environmental pollution due to the diffusion of radioactive substances into the atmosphere and from the radioactive fallout. The environmental pollution from nuclear testing into the atmosphere has resulted in the radioactive contamination in agricultural products and has continued for a long time. The radioactive contamination of agricultural products occurs through air, water and soil which were contaminated by radioactive fallout. In this paper, for the purpose of analyzing the extent of the radioactive contamination levels in the agricultural products of Saitama Prefecture, spinach, green soybeans, dried shiitake and welsh onion, were selected among products, as the amount of the harvest is abundant in all of Japan. Radioactivity concentration was investigated by gamma ray spectrometry and radiochemical analysis. The radioactivity concentrations of artificial radioactive nuclides, cesium-137 (137Cs) and strontium-90 (90Sr), were detected in the range which is considered to be the result of radioactive fallout. Moreover, in order to examine the effect on radioactivity concentrations in agricultural products by culinary processing, the raw agricultural products were boiled, and their radioactivity concentrations were compared with the raw produce. The radioactivity concentrations in the boiled were lower than those in the raw produce.

Cesium Radioisotopes↗
PubMed1996

Identification of two Xenopus laevis genes, xMCM2 and xCDC46, with sequence homology to MCM genes involved in DNA replication.

The Schizosaccharomyces pombe genes, nda1 and nda4, are essential for the normal regulation of DNA replication and belong to the MCM gene family. This gene family includes Saccharomyces cerevisiae MCM2, MCM3, MCM5/CDC46 and CDC47, S. pombe nda1, nda4, cdc21 and mis5, and genes encoding human BM28, P1MCM3 and P1.1MCM3 and mouse P1MCM3, most of which are considered to be required for the initiation of DNA replication. We isolated two homologues of the MCM genes, xMCM2 and xCDC46, from a Xenopus laevis cDNA library using the polymerase chain reaction (PCR) method. The predicted amino acid (aa) sequences of xMCM2 and xCDC46 are most similar to those of human BM28 (78% identity) and S. pombe Nda4 (48% identity), respectively. By Western blot analysis using anti-xMCM2 and anti-xCDC46 polyclonal antibodies (Ab) raised against glutathione S-transferase (GST)::xMCM2 or GST::xCDC46 fusion proteins, xMCM2 and xCDC46 were identified as 120- and 95-kDa proteins, respectively. When either xMCM2 or xCDC46 was immunoprecipitated with the specific Ab, the other was also co-precipitated. These results suggest that xMCM2 and xCDC46 physically interact with each other.

Animals↗
PubMed1996

A novel phosphotyrosine-binding domain in the N-terminal transforming region of Cbl interacts directly and selectively with ZAP-70 in T cells.

The protooncogene product Cbl has emerged as a novel signal transduction protein downstream of a number of cell surface receptors coupled to tyrosine kinases. Recently, we and others have reported the activation-dependent association of Cbl with the Syk and ZAP-70 tyrosine kinases through presently undefined mechanisms. Potential Src homology 2 and 3 domain binding sites within the C-terminal half of Cbl mediate in vivo interactions with several signaling proteins; however, the N-terminal transforming region (Cbl-N) lacks recognizable catalytic or protein interaction motifs. Here, we show that in vitro Cbl-N (amino acids 1-357) but not Cbl-C (amino acids 358-906) binds to ZAP-70 in a T cell-activation-dependent manner. A point mutation in Cbl-N, G306E, corresponding to a loss-of-function mutation in the Caenorhabditis elegans Cbl homologue, SLI-1, severely compromised Cbl-N/ZAP-70 binding. Cbl-N/ZAP-70 binding was direct and phosphotyrosine-dependent, thus identifying a phosphotyrosine-binding domain within the transforming region of Cbl. In vivo, Cbl-N expressed in T cells selectively associated with the ZAP-70/zeta complex. These results identify a novel mechanism for the direct participation of the N-terminal region of Cbl in ZAP-70 signal transduction, and suggest a biochemical mechanism for the leukemogenicity of the oncogene v-cbl through potential interaction with proliferation-related phosphotyrosyl proteins.

Cell Line↗
PubMed1996

Improved visualization of pulmonary venous flow Doppler signal by intravenous injection of sonicated albumin.

Color Doppler signal of pulmonary venous flow was enhanced, and the optimal recordings could be detected in most cases after intravenous injection of sonicated albumin. Improved visualization of pulmonary venous flow Doppler signal by intravenous injection of sonicated albumin should have important clinical implications for the assessment of left ventricular diastolic function by using Doppler technique.

Adult↗
PubMed1996

Tyrosine phosphorylation of Cbl upon epidermal growth factor (EGF) stimulation and its association with EGF receptor and downstream signaling proteins.

We and others have shown that Cbl, the protein product of the c-cbl proto-oncogene, is an early target of tyrosine phosphorylation upon stimulation through the immune cell surface receptors, which signal through noncovalently associated cytoplasmic tyrosine kinases. Using human mammary epithelial cells that express a natural epidermal growth factor (EGF) receptor and require EGF as an essential growth factor, we demonstrate here that Cbl is a prominent target of tyrosine phosphorylation upon stimulation through the EGF receptor tyrosine kinase. Phosphorylation of Cbl was EGF dose-dependent, rapid (detectable as early as 5 s and maximal by 2 min), and relatively sustained (detectable even after 1 h). Co-immunoprecipitation studies demonstrated that Cbl became associated with the EGF receptor in an EGF-dependent manner. Cbl was basally associated with the adaptor protein growth factor receptor-binding protein 2 (Grb2), and this interaction was further enhanced by EGF stimulation; however, the interaction was entirely mediated via the Grb2 Src homology 3 (SH3) domains, suggesting that binding of Grb2 SH2 domain to EGF receptor provides one mechanism of Cbl's association with the EGF receptor. EGF stimulation also induced the association of Cbl with Src homology and collagen (Shc) protein, p85 subunit of the phosphatidylinositol 3-kinase and Crk proteins, in particular with the CrkL isoform. Interactions of Cbl with the EGF receptor and multiple downstream signaling proteins suggest a role for this proto-oncogene product in mitogenic signaling through growth factor receptor kinases.

Adaptor Proteins, Signal Transducing↗
PubMed1996

p120cbl is a major substrate of tyrosine phosphorylation upon B cell antigen receptor stimulation and interacts in vivo with Fyn and Syk tyrosine kinases, Grb2 and Shc adaptors, and the p85 subunit of phosphatidylinositol 3-kinase.

We and others have demonstrated that the c-cbl proto-oncogene product is one of the earliest targets of tyrosine phosphorylation upon T cell receptor stimulation. Given the similarities in the B and T lymphocyte antigen receptors, and the induction of pre-B leukemias in mice by the v-cbl oncogene, we examined the potential involvement of Cbl in B cell receptor signaling. We demonstrate prominent and early tyrosine phosphorylation of Cbl upon stimulation of human B cell lines through surface IgM. Cbl was associated in vivo with Fyn and, to a lesser extent, other Src family kinases. B cell activation also induced a prominent association of Cbl with Syk tyrosine kinase. A substantial fraction of Cbl was constitutively associated with Grb2 and this interaction was mediated by Grb2 SH3 domains. Tyrosine-phosphorylated Shc, which prominently associated with Grb2, was detected in association with Cbl in activated B cells. Thus, Grb2 and Shc adaptors, which associate with immunoreceptor tyrosine based activation motifs, may link Cbl to the B cell receptor. B cell activation also induced a prominent association between Cbl and the p85 subunit of phosphatidylinositol (PI) 3-kinase resulting in the association of a substantial fraction of PI 3-kinase activity with Cbl. Thus, Cbl is likely to play an important role to couple the B cell receptor to the PI 3-kinase pathway. Our results strongly suggest a role for p120cbl in signaling downstream of the B cell receptor and support the idea that Cbl participates in a general signal transduction function downstream of the immune cell surface receptors.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Efficient generation of recombinant adenoviruses using adenovirus DNA-terminal protein complex and a cosmid bearing the full-length virus genome.

An efficient method of constructing recombinant adenoviruses (Ads) has been established. The expression unit to be introduced into recombinant Ad was first inserted into the unique Swa I site of the full-length Ad genome cloned in a cassette cosmid. The cassette bearing the expression unit was then cotransfected into human embryonic kidney 293 cells together with the Ad DNA-terminal protein complex digested at several sites with Eco T22I or Ase I/EcoRI. The use of the parent Ad DNA-terminal protein complex instead of the deproteinized Ad genome DNA allowed very efficient recovery of the desired recombinant Ad, and the above restriction digestion drastically reduced regeneration of the parent virus. Several hundred virus clones were readily obtained in each experiment, and about 70% of the clones were the desired recombinant viruses. Furthermore, because the cassette contained the full-length Ad genome, any position of the genome could be easily modified to develop a new vector design. We established construction systems for two types of Ad vectors, the E1-substitution type and the E4-insertion type. This method may greatly facilitate the application of recombinant Ads and should be useful for further improvement of Ad vectors.

Adenovirus E4 Proteins↗
PubMed1996

Short- and long-term clinical effects of primary directional coronary atherectomy for acute myocardial infarction.

We performed primary directional coronary atherectomy (DCA) without antecedent thrombolytic therapy in 21 of 67 patients with acute myocardial infarction within 24 hr of onset between June 1993-March 1994. Reperfusion with primary DCA was successful in 18 patients (85.7%, group D). Results were compared with those of primary balloon angioplasty patients treated between June 1992-May 1993 (group P). Minimum lumen diameter (MLD) values both immediately after reperfusion and in predischarge angiograms were significantly larger in group D than in group P, but were similar in late follow-up angiograms. Although a larger MLD in group D than in group P contributed to the prevention of reocclusion of the coronary artery before discharge in DCA patients, a high rate of restenosis at late follow-up canceled the beneficial effects of primary DCA.

Aged↗
PubMed1996

Soluble Fas molecule in the serum of patients with systemic lupus erythematosus.

The serum level of soluble Fas (sFas) molecules in 35 patients with SLE was determined by enzyme-linked immunosorbent assay (ELISA) and its relation to other lymphocyte activation markers and clinical parameters was examined. The level of sFas increased significantly compared to that in normal subjects, consistent with previous reports. There was a significant correlation between the level of sFas and that of sCD4, suggesting some relation between sFas and activation of CD4+ T cell. Patients with lymphopenia tended to have low levels of sFas, making it possible to hypothesize that sFas protects against apoptosis. Although the change in the level of sFas protects steroid therapy was variable, some relation to the differential activation of T cell subsets was suggested.

CD4 Antigens↗
PubMed1996

Hepatic iron contents and response to interferon-alpha in patients with chronic hepatitis C. Relationship to genotypes of hepatitis C virus.

Recent reports have shown that response to interferon treatment is influenced by hepatic iron contents in patients with chronic hepatitis C. In those reports, however, hepatitis C virus (HCV) genotypes and serum HCV-RNA levels were not examined. The aim of the present study was to investigate whether hepatic iron contents influence the response to interferon in patients with chronic hepatitis C and whether HCV genotypes and serum HCV-RNA levels play a role in this relationship. Among 65 patients with chronic hepatitis C, hepatic iron contents were significantly high in patients with a history of excess drinking of alcohol (more than 80 g/day) compared to those without, and significantly low in female patients before menopause. Having excluded these patients, hepatic iron contents were significantly higher in patients with genotype 1b infection than those with genotype 2a and 2b infection. There was no significant correlation between hepatic iron contents and plasma HCV-RNA levels. Among the patients with genotype 1b infection, hepatic iron contents were significantly lower in the responders to interferon than those in the nonresponders (429 +/- 100 vs 875 +/- 110 micrograms/g liver, P < 0.05). From these results, it is concluded that response to interferon is mainly influenced by HCV genotypes, while hepatic iron contents may play an important role in response to interferon in patients with genotype 1b infection.

Adolescent↗
PubMed1996

Induction of antibodies against structural proteins of hepatitis C virus in mice using recombinant adenovirus.

Replication-deficient recombinant adenoviruses expressing structural proteins of hepatitis C virus (HCV) were constructed. Each recombinant lacks adenoviral E1A and E3 genes and bears expression units for HCV structural proteins. The expression units contain HCV cDNAs coding for either the protein or core, one of two envelopes (E1 and E2) or all of these structural proteins (core, E1 and E2) under the control of the SR alpha promoter. In HeLa or HepG2 cells, the recombinants can express efficiently HCV genes after infection without replication of the recombinants. We detected 22-kDa core, 35-kDa E1 and 58-kDa E2 proteins of HCV in these cells. The recombinant expressing all three HCV structural proteins was inoculated into mice. Antibodies to each of the three HCV proteins were detected in all of the ten mice tested. The results indicate that the recombinant adenoviruses efficiently express HCV genes and induce specific antibody against the expressed HCV proteins in animals.

Adenoviridae↗
PubMed1996

Primary stent implantation without coumadin in acute myocardial infarction.

OBJECTIVES: We tested the feasibility and efficacy of primary stent implantation without Coumadin in 74 patients within 8 h of the onset of acute myocardial infarction. BACKGROUND: Although stent implantation in patients with effort angina provides better short- and long-term outcomes than balloon angioplasty, it is not clear whether primary stent implantation is applicable or effective in acute myocardial infarction. METHODS: Primary sent implantation was attempted when 1) the lesion was not located distally in the main coronary branches, 2) the coronary artery did not show any severe calcification or excessive bending proximal to the lesion on fluoroscopy, and 3) the arterial diameter was > or = 2.5 mm. The results (group S) were compared with those of primary balloon angioplasty (group P). Poststenting regimens contained ticlopidine and aspirin without Coumadin. Poststenting inflation was performed with > or = 12 atm. RESULTS: Stent implantation was successful in 72 patients. Stent thrombosis was noted in only one patient who was not given ticlopidine, aspirin or Coumadin. The rates of restenosis and frequency of major clinical events during the hospital period in groups S and P were 0% versus 13.2% (p = 0.007) and 2.8% versus 18.6% (p = 0.009), respectively. Kaplan-Meier analysis demonstrated that cumulative 90-day clinical event-free rates in groups P and S were 98.1 +/- 16.0% versus 79.4 +/- 43.7% (p = 0.0068), and that 180-day rates were 86.5 +/- 38.4% versus 64.2 +/- 49.7% (p = 0.014). CONCLUSIONS: Primary stent implantation can improve clinical outcomes of patients with acute myocardial infarction when the stent is dilated adequately and antiplatelet drugs are used.

Angioplasty, Balloon, Coronary↗