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Biomedical subjects

Y Fukushima

Publications and source records attributed to Y Fukushima.

At least 163 records · Page 9Linked to original sources
PubMed1998

Successful surgical treatment for hepatic encephalopathy caused by a pancreatic siphon: report of a case.

We report herein the case of a 39-year-old man with cirrhosis of the liver who developed hepatic encephalopathy and progressive diabetes caused by a pancreatic siphon after undergoing a distal splenorenal shunt (DSRS) for a variceal hemorrhage. Radiologic occlusion was judged to be inappropriate because of the extensive DSRS. The DSRS was surgically closed 6 years after the operation to restore portal perfusion. To alleviate the portal hypertension, splenectomy and gastric devascularization were performed, which proved successful, as the encephalopathy disappeared completely, the ammonia levels decreased, liver function improved, and the diabetes subsided. Our experience indicates that a small percentage of cirrhotic patients who undergo DSRS with longterm followup may develop various undesirable complications, although some of these patients benefit from a combination of surgical shunt occlusion, splenectomy, and gastric devascularization.

Adult↗
PubMed1998

Role of JTT-501, a new insulin sensitiser, in restoring impaired GLUT4 translocation in adipocytes of rats fed a high fat diet.

JTT-501 is an insulin-sensitising compound with an isoxazolidinedione rather than a thiazolidionedione structure. Sprague-Dawley rats fed a high fat diet for 2 weeks were used as an animal model of insulin resistance, and JTT-501 was administered for the final week of the diet. An euglycaemic glucose clamp study showed that the glucose infusion rate (GIR) required to maintain euglycaemia was 57% lower in rats fed a high fat diet than in control rats, and that JTT-501 treatment restored the reduction in GIR produced by the high fat diet. To explain the mechanisms underlying the effects of a high fat diet and JTT-501 treatment, epididymal fat pads were excised and used in the analysis of insulin action. The high fat diet caused: (1) a 58% decrease in insulin receptor substrate-1 (IRS-1) content with a 58% decrease in IRS-1 tyrosine phosphorylation; (2) reductions of 56% and 73% respectively in insulin-induced maximal PI 3-kinase activation in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates; (3) a 46% reduction in the glucose transporter protein, GLUT4 content and, consequently, (4) severely impaired insulin-induced GLUT4 translocation to the plasma membrane and glucose uptake in adipocytes. JTT-501 treatment restored appreciably the protein content and tyrosine phosphorylation level of IRS-1. Insulin-stimulated PI 3-kinase activation was also restored in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates. As reflected by these improvements in insulin signalling, JTT-501 treatment improved considerably insulin-induced GLUT4 translocation to the plasma membrane as well as insulin-induced glucose uptake. However, JTT-501 had no effect on the decrease in GLUT4 content produced by the high fat diet. These observations suggest that JTT-501 enhances insulin signalling and may be effective in reducing insulin resistance.

Adipocytes↗
PubMed1998

Urinary metabolites of sarin in a patient of the Matsumoto sarin incident.

Sarin metabolites were measured in urine from a patient with sarin poisoning. Two metabolites, methylphosphonic acid (MPA) and isopropylmethylphosphonic acid (iPMPA), were detected by gas chromatography after conversion to volatile derivatives with N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide in the urine from the victim collected on the first day of hospitalization. iPMPA was detected in the urine on the seventh day, but MPA could not be detected in the urine sample. MPA was narrowly detected in the urine collected on the third day. The concentration of iPMPA was estimated on the assumption that the sensitivity of phosphorus was the same as that of MPA. The total excretion of iPMPA and MPA in the urine was 2.1 mg and 0.45 mg, respectively. When all the sarin inhaled was excreted within a week as these two metabolites, the subject was considered to have been exposed to 2.79 mg (0.05 mg/kg) sarin at the incident. Thus, the measurement of sarin metabolites in urine is a useful tool for the biological monitoring of exposure to sarin.

Adult↗
PubMed1998

Alterations in tumour suppressor gene p53 correlate with inhibition of thrombospondin-1 gene expression in colon cancer cells.

If activation of the p53 gene is involved in the progression or metastasis of colon cancer, it may affect the angiogenic phenotype in vivo. To verify this hypothesis, we studied the correlation between p53 accumulation and expression of thrombospondin-1 (TSP1) in colon cancer specimens. Levels of TSP1 gene expression were estimated by Northern blotting in 65 colon cancers. Accumulation of p53 and the distribution of TSP1 protein were evaluated immunohistochemically. Various levels of TSP1 gene expression were seen in colon cancers, while p53 accumulation was confirmed in 42 of the 65 colon cancers. The level of TSP1 gene expression demonstrated a significant inverse correlation with p53 accumulation in colon cancer. Colon cancer cells expressed TSP1 protein and p53 accumulation reciprocally in the same nests. These results suggest that alterations in the tumour suppressor gene p53 may inhibit TSP1 expression in colon cancer.

Adenocarcinoma↗
PubMed1998

Microphthalmia with linear skin defects syndrome in a mosaic female infant with monosomy for the Xp22 region: molecular analysis of the Xp22 breakpoint and the X-inactivation pattern.

This paper describes a female infant with microphthalmia with linear skin defects syndrome (MLS) and monosomy for the Xp22 region. Her clinical features included right microphthalmia and sclerocornea, left corneal opacity, linear red rash and scar-like skin lesion on the nose and cheeks, and absence of the corpus callosum. Cytogenetic studies revealed a 45,X[18]/46,X,r(X)(p22q21) [24]/46,X,del(X)(p22)[58] karyotype. Fluorescence in situ hybridization analysis showed that the ring X chromosome was positive for DXZ1 and XIST and negative for the Xp and Xq telomeric regions, whereas the deleted X chromosome was positive for DXZI, XIST, and the Xq telomeric region and negative for the Xp telomeric region. Microsatellite analysis for 19 loci at the X-differential region of Xp22 disclosed monosomy for Xp22 involving the critical region for the MLS gene, with the breakpoint between DXS1053 and DXS418. X-inactivation analysis for the methylation status of the PGK gene indicated the presence of inactive normal X chromosomes. The Xp22 deletion of our patient is the largest in MLS patients with molecularly defined Xp22 monosomy. Nevertheless, the result of X-inactivation analysis implies that the normal X chromosomes in the 46,X,del(X)(p22) cell lineage were more or less subject to X-inactivation, because normal X chromosomes in the 45,X and 46,X,r(X)(p22q21) cell lineages are unlikely to undergo X-inactivation. This supports the notion that functional absence of the MLS gene caused by inactivation of the normal X chromosome plays a pivotal role in the development of MLS in patients with Xp22 monosomy.

Chromosome Mapping↗
PubMed1998

Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia.

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are common skeletal dysplasias with impaired enchondral ossification and premature degenerative joint disease. The two disorders were in the past considered to be distinct clinical entities; however, recent studies have proven that both diseases can result from mutations of the gene encoding cartilage oligomeric matrix protein (COMP). To characterize further COMP mutations and investigate phenotype-genotype relationships, we screened this gene in 15 patients with PSACH or MED by directly sequencing polymerase chain reaction products from genomic DNA. We identified ten mutations involving conserved residues among the eight calmodulin-like repeats of the gene product: seven were novel missense mutations in exons 9, 10, 11, 13 or 14, and the other three resulted from deletion of one of the five GAC repeats in exon 13. We have found that the GAC repeats in the 7th calmodulin-like repeat in exon 13 represent a hot-spot for mutation, and that mutations in the 7th calmodulin-like repeat produce severe PSACH phenotypes while mutations elsewhere in the gene exhibit mild PSACH or MED phenotypes. These genotype-phenotype correlations may facilitate molecular diagnosis and classification of PSACH and MED, and provide insight into the relationship between structure and function of the COMP gene product.

Achondroplasia↗
PubMed1998

The gene for mesomelic dysplasia Kantaputra type is mapped to chromosome 2q24-q32.

Mesomelic dysplasia Kantaputra type (MDK) (MIM *156232) is a new autosomal dominant skeletal dysplasia characterized by dwarfism, shortening of the forearms/lower-legs, carpal/tarsal synostosis, and dorsolateral foot deviation. We studied a Thai family in which 15 members in 3 generations were affected with MDK. With reference to the breakpoints of a balanced translocation [t(2;8)(q31;p21)] in patients from a previously reported Italian family with a skeletal dysplasia that appears similar to MDK, a linkage analysis was performed in the Thai family using 50 CA-repeat markers mapped to nearby regions (2q22-q34 and 8p24-p21) of the translocation breakpoints. The results clearly ruled out a linkage of MDK to marker loci at the 8p24-p21 region, whereas all nine affected members available for the study shared a haplotype at four loci (D2S2284, D2S326, D2S2188, and D2S2314) spanning about 22.7 cM in the 2q24-q32 region. The computer-assisted two-point linkage analysis revealed maximum logarithm of odds (lod) scores of 4.82, 4.21, 4.82, and 4.21 (theta = 0) at these loci, respectively. These data indicated that the MDK locus is in the vicinity of D2S2284 and D2S2188 loci that are most likely mapped to 2q24-q32.

Chromosome Mapping↗
PubMed1998

Novel MEN1 gene mutations in familial multiple endocrine neoplasia type 1.

The recent isolation of the gene responsible for multiple endocrine neoplasia type 1 (MEN 1) has enabled direct genetic diagnosis for people with endocrine tumors and family members of affected patients. Although MEN 1 is rarely recognized in the Japanese population compared to its prevalence in Caucasians, we have previously reported a high prevalence of this disease in a limited area (Nagano Prefecture; population, 2.15 million). In this communication, we report mutations of the MEN1 gene in kindreds living in Nagano Prefecture. The absence of a common mutation among these kindreds indicates that the high prevalence of MEN 1 in this area is not due to a regional accumulation of patients descended from a common ancestor. This result implies that the prevalence of MEN 1 in other areas of Japan could also be higher than had been thought.

Frameshift Mutation↗
PubMed1998

Isolated trigeminal nerve metastases from breast cancer: an unusual cause of trigeminal mononeuropathy.

BACKGROUND: Mononeuropathy of a cranial nerve caused by brain metastases rarely occurs in patients with a malignant neoplasm. Even after the development of computed tomography (CT) and magnetic resonance imaging (MRI), few cases of brain metastases resulting in trigeminal mononeuropathy have been reported. We report a case of trigeminal mononeuropathy caused by a brain metastases that was detected on CT and MRI preoperatively, and was successfully treated by microsurgery and radiation. CASE DESCRIPTION: A 49-year-old woman with a history of breast cancer complained of right facial pain. CT and MRI revealed a brain tumor in the right Meckel's cave and cerebellopontine angle. She underwent surgery, and the diagnosis was metastatic breast cancer. No recurrence was detected on MRI performed 2 years after the resection and radiation of the tumor. CONCLUSIONS: Most of the reported cases of brain metastases causing a mononeuropathy occurred before the availability of CT; the mononeuropathy was diagnosed by neurologic or postmortem examination. Even after the development of CT and MRI, few cases of brain metastases resulting in trigeminal mononeuropathy have been reported. If such patients do not manifest symptoms of brain metastases other than the mononeuropathy, it is difficult to make the correct diagnosis without CT and MRI. Physicians must be aware of mononeuropathy as an uncommon presenting symptom of brain metastases.

Breast Neoplasms↗
PubMed1998

Growth stimulation of non-small cell lung cancer xenografts by granulocyte-macrophage colony-stimulating factor (GM-CSF).

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been suggested to be involved in the carcinogenesis of some types of tumours by autocrine or paracrine mechanisms. We examined GM-CSF/GM-CSF receptor (GM-CSFR) gene expression in 20 human non-small cell lung cancer (NSCLC) xenografts. The stimulatory effects of GM-CSF were examined using GM-CSF transgenic severe combined immunodeficient (SCID) mice (GM-Tg-SCID), which produce abundant human GM-CSF. A NSCLC xenograft (LC11-JCK), expressed GM-CSFR but not GM-CSF, and showed more rapid growth in GM-Tg-SCID than non-GM-CSF transgenic SCID mice (non-Tg-SCID). GM-CSF gene expression was detected in 48 of 90 (53%) primary NSCLC human specimens and GM-CSFR gene expression was detected in 42 specimens (47%). GM-CSF expression was detected in 13 of 30 squamous cell carcinoma specimens (43%) and GM-CSFR expression was detected in 10 specimens (33%). Patients with squamous cell carcinoma coexpressing GM-CSF and GM-CSFR showed significantly poorer prognosis than those expressing neither GM-CSF nor GM-CSFR (P < 0.05, Cox-Mantel test). These results suggest that GM-CSF can have a stimulatory effect on some NSCLC.

Animals↗
PubMed1998

In vitro effect of contrast agents during immunoradiometric assay for tumour-associated antigens.

The aim of this study was to investigate if contrast agents interfere with the performance of an immunoradiometric assay (IRMA) in vitro for serum tumour-associated antigen. Each of five carcinoembryonic antigen (CEA)-positive sera, CA-130-positive sera and tissue polypeptide antigen (TPA)-positive sera was mixed with six contrast agents: Ioversol 350, Iopamidol 370, Iomeprol 300, Iomeprol 400, Iohexol 300 and Gadopenteic acid in 50:50, 50:20, 50:5.0, 50:1.0, 50:0.5 and 50:0.1 microl proportions. Following IRMA, the interference of binding rates in each mixture was calculated, and the serum concentrations of CEA, CA-130 and TPA were estimated and compared with the originals. All contrast agents used were able to inhibit the binding rate with IRMA and the inhibition rates were in proportion to the amount of contrast agent. The detection of serum concentrations of CEA, CA-130 and TPA was significantly inhibited in the mixtures with more than 5.0 microl of contrast agent in all cases. Apart from Iomeprol 400, there was no significant inhibition of detection at the lowest concentrations of contrast agents. Iomeprol 400 was the strongest inhibitor and Gadopenteic acid the weakest inhibitor for each IRMA of the contrast agents employed. In conclusion, our results demonstrate that contrast agents may reduce the immunoreaction of antibody and antigen and lead to in vitro inhibition during immunoassays. It would be unwise to perform any plasma/serum immunoassay on a sample collected within 24 h of the administration of contrast agent considering the pharmacokinetics.

Aged↗
PubMed1998

Identification of two novel mutations in the OCRL1 gene in Japanese families with Lowe syndrome.

The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked disorder with features of congenital cataracts, Fanconi syndrome of the renal tubule, and mental retardation. The OCRL1 gene has been positionally cloned and shown to encode a phosphatidylinositol 4,5-biphosphate-5-phosphatase. OCRL is thus thought to be an inborn error of inositol polyphosphate metabolism. We analyzed the gene in two Japanese OCRL patients and their families by DNA sequencing and mismatch polymerase chain reaction (PCR) followed by restriction digestion. A novel nonsense mutation (C1399T) replacing the glutamine of codon 391 (Gln 391 Stop) was identified in exon 12 in 1 patient and also in his mother. A novel missense mutation (C1743G) was identified in exon 15 in the second patient. his mother and maternal grandmother. The missense mutation predicts a substitution of serine for arginine (Ser 505 Arg) in a domain highly conserved among the inositol-5-phosphatase family. Our observations expand the range of OCRL1 mutations that cause Lowe syndrome, and will be useful for genetic counseling in these two families.

Amino Acid Sequence↗
PubMed1998

Altered expression levels and impaired steps in the pathway to phosphatidylinositol 3-kinase activation via insulin receptor substrates 1 and 2 in Zucker fatty rats.

To elucidate the mechanism of obesity-related insulin resistance, we investigated the impaired steps in the processes of phosphatidylinositol (PI) 3-kinase activation through binding with insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in liver and muscle of Zucker fatty rats. The expressions of IRS-1 and IRS-2 were shown to be downregulated in both liver and muscle in fatty rats (hepatic IRS-1, 83%; hepatic IRS-2, 45%; muscle IRS-1, 60%; muscle IRS-2, 78%), resulting in decreased tyrosine phosphorylation in response to insulin stimulation. Despite the decrease in the tyrosine phosphorylation levels of hepatic IRS-1 and IRS-2 being mild to moderate, associated PI 3-kinase activities were dramatically decreased in fatty rats (IRS-1, 14%; IRS-2, 10%), which may suggest alteration in the sites of phosphorylated tyrosine residues of hepatic IRS-1 and IRS-2. In addition, we demonstrated that the expressions of p85alpha and p55alpha regulatory subunits of PI 3-kinase were reduced (p85alpha, 67%; p55alpha, 54%), and that the p50alpha regulatory subunit was markedly upregulated (176%) in the livers of fatty rats without apparent alterations in expressions of the catalytic subunits p110alpha and p110beta. These alterations may reflect the obesity-related insulin resistance commonly observed in human NIDDM.

Albumins↗
PubMed1998

Effect of whey hydrolysate formula on the transfer of beta-lactoglobulin into serum and milk in mice.

This study was performed to elucidate the effect of whey hydrolysate formula on the transfer of an antigen into serum and milk. The concentrations of beta-lactoglobulin in serum and milk were positively correlated (p < 0.01). The concentration of beta-lactoglobulin in serum tended to become low in the mouse and to be accompanied with a high level of fecal anti-beta-lactoglobulin IgA concentration. The fecal anti-beta-lactoglobulin IgA of mice fed hydrolysate formula for 12 weeks was significantly higher than that of the control formula-fed mice (p < 0.05). These results suggest that a high level of intestinal IgA elicited by the feeding of hydrolysate formula may reduce the transfer of beta-lactoglobulin into serum and milk.

Animals↗
PubMed1998

Increased expression of human histocompatibility leukocyte antigen-G in colorectal cancer cells.

Human histocompatibility leukocyte antigen (HLA)-G is a nonclassical major histocompatibility complex class I molecule. HLA-G is known to provide tolerance from recognition by natural killer cells. We studied HLA-G expression in 39 human colorectal cancers and 23 extra-neoplastic colon tissue samples by RT-PCR. The expression of HLA-G mRNA was significantly more frequent in colorectal cancer (34 of 39 cases) than in the extraneoplastic tissue (10 of 23 specimens; chi2 test, p = 0.0003). HLA-G expression was also confirmed on the cancer cells immunohistochemically. These results suggested that HLA-G on colorectal cancer cells may be correlated with escape from immunological surveillance during colon cancer development.

Colon↗