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Biomedical subjects

M Okubo

Publications and source records attributed to M Okubo.

At least 91 records · Page 5Linked to original sources
PubMed1998

Clinical significance of serum P53 antibody in patients with gastric cancer.

The presence of serum p53 antibody has been reported to have prognostic significance in patients with breast and ovarian cancers. In order to clarify clinical and prognostic significance of p53 antibody in serum, we measured p53 antibody in patients with gastric cancer. Twenty-five patients with gastric cancer were examined as well as 9 patients with gastric polyp as controls. Eight of 25 patients (32%) with gastric cancer were positive for p53 antibody, while no patients with gastric polyp were positive in gastric polyp group (p < 0.05). The presence of p53 antibody was significantly associated with histology, liver metastasis and stage classification in gastric cancer (p < 0.05, respectively). Presence of liver metastasis, type of histology and presence of p53 antibody are independent prognostic factors (p < 0.05, respectively). The overall survival in patients with p53 antibody was significantly shorter survival than for those without antibody (p < 0.05%). These data suggest that p53 antibody serves as one of the prognostic factors in gastric cancer.

Adenoma↗
PubMed1998

Difference of (Ca2+)i movements in platelets stimulated by thrombin and TRAP: the involvement of alpha(IIb)beta3-mediated TXA2 synthesis.

This study investigated the difference of [Ca2+]i movement in platelets in response to thrombin and TRAP. The involvement of alpha(IIb)beta3 in this signaling was also studied. Stimulation of platelets with thrombin at 0.03 U/ml caused platelet aggregation and a two-peak increase in [Ca2+]i. The second peak of [Ca2+]i, but not the first peak was abolished by the inhibition of platelet aggregation with alpha(IIb)beta3 antagonists or by scavenging endogenous ADP with apyrase. A cyclooxygenase inhibitor, aspirin, and a TXA2 receptor antagonist, BM 13505, also abolished the second peak of [Ca2+]i but not the first peak, although these regents did not inhibit aggregation. Under the same assay conditions, measurement of TXB2 demonstrated that alpha(IIb)beta3 antagonists and aspirin almost completely inhibited the production of TXB2. In contrast to thrombin-stimulation, TRAP caused only a single peak of [Ca2+]i even in the presence of platelet aggregation, and a high level of [Ca2+]i increase was needed for the induction of platelet aggregation. The inhibition of aggregation with alpha(IIb)beta3 antagonists had no effect on [Ca2+]i change and TXB2 production induced by TRAP. Inhibition studies using anti-GPIb antibodies suggested that GPIb may be involved in the thrombin response, but not in the TRAP. Our findings suggest that low dose thrombin causes a different [Ca2+]i response and TXA2 producing signal from TRAP. Endogenous ADP release and fibrinogen binding to alpha(IIb)beta3 are responsible for the synthesis of TXA2 which results in the induction of the second peak of [Ca2+]i in low thrombin- but not TRAP-stimulated platelets.

Adenosine Diphosphate↗
PubMed1997

Apoptosis as a possible cause of wall thinning in end-stage hypertrophic cardiomyopathy.

A 15-year-old boy with hypertrophic cardiomyopathy died of congestive heart failure with progressive left ventricular wall thinning with poor systolic function. Microscopic examination revealed patchy fibrosis in the ventricular myocardium with wall thinning, and immunohistochemical evaluation of apoptosis showed apoptotic cells and bodies in the destroyed myocytes along the border between the fibrotic area and myofibril.

Adolescent↗
PubMed1997

Late persistent expressions of ICAM-1 and VCAM-1 on myocardial tissue in children with lymphocytic myocarditis.

BACKGROUND: Both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been implicated in cardiac allograft rejection. However, there is little information about the relationship between the expression of these adhesion molecules and myocarditis in children. METHODS AND RESULTS: Immunoreactivities of ICAM-1 and VCAM-1 were examined by enzyme immunoassay in 31 biopsy specimens obtained from 11 pediatric patients with biopsy-proven myocarditis or cardiomyopathy. Five of the 11 patients had clear evidence of acute myocarditis. The other 6 had ECG abnormalities identified by mass screening for heart disease, and subsequently had been histologically diagnosed as having non-specific cardiomyopathy. The period between onset of myocarditis or identification of ECG abnormality and immunohistochemical studies was 23 to 60 days and 8 months to 3 years, respectively. Expression of ICAM-1 and VCAM-1 was assessed by counting ICAM-1 and VCAM-1 positive vessels and dividing by the total number of vessels. ICAM-1 was significantly present on 81% (P < 0.01) of myocardial tissue samples in the 5 patients with healing-stage acute myocarditis, and on 45% (P < 0.05) in the remaining 6 patients with non-specific cardiomyopathy, compared with 24% in control specimens obtained from right ventricular muscle resected at surgery for tetralogy of Fallot. VCAM-1 was also present on 50% (P < 0.05) of the samples from the 5 patients with acute myocarditis, but was not present in those with non-specific cardiomyopathy. CONCLUSION: This persistent expression of ICAM-1 suggests that myocardial cell damage may persist immunologically for a long period in myocarditis. In addition, immunostaining for these adhesion molecules may be diagnostic value in clinically silent lymphocytic myocarditis and chronic cardiomyopathy.

Adolescent↗
PubMed1997

A G+1 to C mutation in a donor splice site of intron 2 in the apolipoprotein (apo) C-II gene in a patient with apo C-II deficiency. A possible interaction between apo C-II deficiency and apo E4 in a severely hypertriglyceridemic patient.

Familial apolipoprotein C-II (apo C-II) deficiency is an autosomal recessive genetic disorder characterized by fasting hypertriglyceridemia and accumulation of chylomicrons in the plasma. To elucidate the genetic defect, the apo C-II gene of a neonatal Japanese patient (C-IITokyo) was analyzed. Nucleotide sequence analysis showed a G+1 to C transversion at the donor splice site of intron 2 (INT2 G+1 to C). Restriction fragment length polymorphism analyses of the patient's family members with Hph I showed that the patient was homozygous and the parents were heterozygous for the INT2 G+1 to C mutation. Although consanguinity could not be demonstrated, haplotype analysis of the C-II gene revealed the identity of the patient's alleles on the mutation, suggesting that the parents had a common Japanese ancestor. Sequence analysis of the patient's cDNA isolated from peripheral blood lymphocytes revealed that the INT2 G+1 to C mutation causes skipping of exon 2, which encodes the initiation codon, and results in deficiency of apo C-II proteins. The outstanding feature of our patient was that he showed severe hypertriglyceridemia beginning in the neonatal period, a feature not reported in a case of apo C-II deficiency (C-IIHamburg) with the same mutation as our patient. A previous report of another case of apo C-II deficiency (C-IIToronto) suggested that the apo E4 isoform is associated with higher levels of plasma triglycerides in subjects heterozygous for the apo C-II mutation. Determination of the apo E isoform of our patient revealed that apo E4 was coinherited with the INT2 G+1 to C mutation, whereas the apo E isoform has been reported to be E2/3 in C-IIHamburg. We speculate that apo E4/4 aggravated the hypertriglyceridemia in our patient with apo C-II deficiency.

Apolipoprotein C-II↗
PubMed1997

Prognostic significance of serum anti-p53 antibody in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Abnormalities of the p53 gene can lead to the production of anti-p53 antibody in the serum of cancer patients. We evaluated the prognostic significance of anti-p53 antibody in 86 patients with hepatocellular carcinoma (HCC) in comparison with clinicopathological factors: age, sex, etiology, smoking and drinking habits, history of blood transfusion, presence of encephalopathy and ascites, Child classification, Pugh score, bilirubin, albumin, prothrombin time, indocyanine green retention time at 15 min (ICG), underlying liver disease, alpha-fetoprotein (AFP), tumor size, number of tumors, differentiation degree of HCC, presence of extrahepatic metastasis and therapy for HCC. METHODS: The serum anti-p53 antibody in 86 patients with HCC, 20 with chronic hepatitis (CH) and 20 with liver cirrhosis (LC) was measured by an enzyme-linked immunosorbent assay (ELISA). A single-strand conformation polymorphism-polymerase chain reaction (SSCP-PCR) analysis and loss of heterozygosity (LOH) study of the p53 gene were performed using 8 tissue samples of 8 HCC from four antibody-positive and four antibody-negative patients. The survival probabilities were assessed by the Kaplan-Meier technique, and a Cox regression analysis was used to identify the independent factors for prognosis. RESULTS: Anti-p53 antibody was positive in 32% (28 of 86) of the sera from patients with HCC, but in none of the 20 with CH and 20 with LC. p53 antibody positivity was associated with bilirubin and the number of tumors (p=0.027 and p=0.018, respectively). Overall survival was shorter in the HCC patients with p53 antibody than in those without p53 antibody (p<0.02). Bilirubin, p53 antibody, AFP and ICG were found to be significant prognostic factors by univariate analysis. A Cox multivariate analysis showed that bilirubin and p53 antibody were independent prognostic variables (p<0.0001 and p=0.003, respectively). In four antibody-positive patients, mutation and LOH of the p53 gene were detected in one patient and two patients, respectively. In contrast, only one of four antibody-negative patients exhibited LOH of the p53 gene. CONCLUSIONS: Serum anti-p53 antibody could be a useful prognostic factor in patients with HCC.

Adult↗
PubMed1997

Prenatal determination of human platelet antigen type 4 by DNA amplification of amniotic fluid cells.

To predict a fetus at risk for neonatal alloimmune thrombocytopenia (NATP) caused by human platelet antigen (HPA)-4 incompatibility, we applied a sequence-specific polymerase chain reaction (PCR-SSP). We were able to determine the HPA-4 genotype of three infants at risk using amniotic fluid cells without the need for fetal blood sampling. The HPA-4 genotypes of amniotic fluid cells determined in this way were completely concordant with the genotype and phenotype of infants' venous blood samples obtained after delivery. Therefore, this technique is also convenient to a fetus at risk in the antenatal management of NATP induced by HPA-4 incompatibility.

Adult↗
PubMed1997

Interferon increases serum thrombopoietin in patients with chronic hepatitis C.

We measured serum thrombopoietin (TPO) in chronic hepatitis C treated with interferon (IFN). The platelet count before the therapy was 161.9 x 10(9) +/- 64.1 x 10(9)/l, which decreased to 116.3 x 10(9) +/- 48.4 x 10(9)/l 1 week after IFN therapy (P < 0.01). On the other hand, serum TPO increased from 1.96 +/- 0.60 fmol/ml to 2.68 +/- 0.69 fmol/ml (P < 0.02). Contrary to a recent report that serum TPO was not altered in liver cirrhosis, these data indicate that serum TPO was increased in chronic hepatitis C in response to thrombocytopenia by IFN therapy.

Adult↗
PubMed1997

Recovery of pancreatic beta-cell function in hemochromatosis: combined treatment with recombinant human erythropoietin and phlebotomy.

A patient with diabetes mellitus caused by secondary hemochromatosis was treated using recombinant human erythropoietin and phlebotomy. A total of 12 g of iron had been infused in the patient because of iron deficiency anemia. Blood glucose level was 17.3 mmol/L, and hemoglobin A1c level was 9.0% at admission. He was treated using phlebotomy (400 mL per week), along with subcutaneous injection of 3,000 U of recombinant human erythropoietin three times a week. After approximately 100 days, a total of 5,500 mL of blood (2.75 g iron) could be removed. Serum ferritin level decreased from 10,000 micrograms/L to 4,807 micrograms/L. Fasting and maximum serum C-peptide immunoreactivity values during 100-g oral glucose tolerance tests were improved from 0.14 nmol/L to 0.42 nmol/L and from 1.84 nmol/L to 2.61 nmol/L, respectively. This case suggests that pancreatic beta-cell recovers in diabetes caused by hemochromatosis by reducing iron overload during a short period.

Aged↗
PubMed1997

Synovial mononuclear cells consist with T cells which produce high levels of tumor necrosis factor alpha.

To determine whether synovial mononuclear cells include a population of tumor necrosis factor alpha-producing T cells, we measured tumor necrosis alpha levels in culture supernatants of synovial mononuclear cells by ELISA and analyzed tumor necrosis alpha mRNA-positive cell frequencies. There were no significant differences in the spontaneous levels of TNF alpha between synovial mononuclear cells and peripheral mononuclear cells. The frequency of tumor necrosis factor alpha mRNA-positive cells in synovial mononuclear cells was higher than that of peripheral mononuclear cells. When stimulated with a superantigen, mononuclear cells from the synovial fluid of rheumatoid arthritis patients showed higher levels of tumor necrosis factor alpha production (1,035 +/- 817 pg/ml) than did mononuclear cells from their peripheral blood (236 +/- 180 pg/ml). In addition, we observed that a few T cell clones were resistant to superantigenic restimulation in vitro. We conclude that when these types of T cells persist in the synovium, they play a role in the development of rheumatoid arthritis via a mechanism involving tumor necrosis factor alpha production.

Animals↗
PubMed1997

Identification of a point mutation (G727T) in the glucose-6-phosphatase gene in Japanese patients with glycogen storage disease type 1a, and carrier screening in healthy volunteers.

Glycogen storage disease type 1a (GSD 1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). We analyzed the G6Pase gene of two unrelated Japanese families with GSD 1a. DNA sequencing of all five exons and exon-intron junctions revealed a G-to-T transversion at nucleotide 727 (G727T) in exon 5, which has been previously reported to cause abnormal splicing. Family studies using mismatch PCR showed that three patients were homozygous for the G727T mutation, while the parents were heterozygous. To investigate allele frequencies, we screened 216 Japanese healthy volunteers and found one asymptomatic carrier. Our findings suggest that the G727T mutation may be prevalent in Japan.

Adult↗
PubMed1997

In situ characterization of islets in diabetes with a mitochondrial DNA mutation at nucleotide position 3243.

Changes in the pancreas of diabetic patients with the A-to-G mitochondrial DNA (mtDNA) mutation at nucleotide position 3243 base pair (bp) have not previously been described. The clinical phenotypes of diabetes associated with the mtDNA 3243 mutation range from NIDDM to IDDM. We sought the presence of the mutation and studied volume of beta-, alpha-, and delta-cells, mitochondrial enzyme activity, and presence of apoptosis in diabetic pancreases obtained at autopsy. Pancreases were obtained from 16 patients with IDDM, from 18 patients with NIDDM, and from 11 nondiabetic patients. Mitochondrial enzyme activity was determined for cytochrome c oxidase (COX), the subunits of which are partially encoded by mtDNA, and for succinate dehydrogenase (SDH), the subunits of which are solely encoded by nuclear DNA. The volumes of islet beta-, alpha-, and delta-cells were estimated by computerized morphometry. Pancreatic cells were examined for apoptosis by an in situ end-labeling procedure. The mtDNA 3243 mutation was detected in 1 of 16 (6%) pancreases from the IDDM patients; none of the pancreases from 18 NIDDM patients and 11 nondiabetic patients had the mutation. The single patient with the mtDNA 3243 mutation was a 56-year-old woman with IDDM, aged 39 years at diabetes onset, whose mother was diagnosed with NIDDM. The patient had a history of secondary failure of oral hypoglycemic agents and had a marked decrease in the number of beta-cells. The islet beta-cells and non-beta-cells of the patient showed extremely decreased COX enzyme activity. The islet cells in the patient showed a high activity when examined for SDH. Some pancreatic exocrine cells also showed decreased COX activity with high SDH activity. In IDDM, NIDDM, and nondiabetic patients without the mtDNA 3243 mutation, only weak staining for SDH of the islet cells showed. The percentage of heteroplasmy of the mtDNA 3243 mutation in pancreatic micropunched islet specimens was 63 +/- 5% (mean +/- SD) in the islets, 32 +/- 3% in the exocrine pancreas, and 8 +/- 1% in peripheral polymorphonuclear cells. Apoptotic cells were not observed in the IDDM pancreas in the patient with the mtDNA 3243 mutation. The fact that higher levels of mutated mtDNA at 3243 bp were found in affected islets rather than in other tissue suggests that the distribution of the mutant may determine the effect on islet function. A characteristic decrease in the mitochondrial enzyme with COX activity and accelerated SDH activity of the affected islets may provide new insights into the pathogenesis of mitochondrial diabetes.

Adult↗
PubMed1997

Synoviocyte proliferation in joints of SCID mice induced by toxic shock syndrome toxin-1 stimulated T cells from patient with rheumatoid arthritis.

OBJECTIVE: To investigate the histopathological arthropathy in severe combined immunodeficient (SCID) mice given intraarticular injection of toxic shock syndrome toxin-1 (TSST-1) stimulated T cells from patients with rheumatoid arthritis (RA). METHODS: Unstimulated or TSST-1 stimulated T cell blasts (TB-TSST) of synovial fluid mononuclear cells from patients with RA (RASFMC) were intraarticularly injected into the knee joint of SCID mice. Four weeks later, the knee joints were histopathologically examined and the numbers of fibroblasts in the synovial tissues were compared with those of controls. Total RNA of the SCID mouse knee joints was isolated and Southern analysis for human T cell receptor (TCR) V beta 2 and human tumor necrosis factor-alpha (TNF-alpha) was carried out. RESULTS: Hyperplasia and increased numbers of the fibroblasts as well as neovascularization of the synovial tissues were observed in the SCID mouse knee joint tissues injected with TB-TSST of RASFMC compared with those injected with unstimulated T cells from RASFMC or with TB-TSST from peripheral blood of healthy controls. Messenger RNA for human TCR V beta 2 and TNF-alpha were detected in the SCID mouse knee joint tissues injected with TB-TSST from RASFMC. CONCLUSION: Superantigen TSST-1 stimulated T cells from RASFMC have the ability to induce chronic arthropathy with fibroblast proliferation and neovascularization in the SCID mouse.

Animals↗
PubMed1996

A novel donor splice site mutation in the glycogen debranching enzyme gene is associated with glycogen storage disease type III.

Analysis of glycogen debranching enzyme (debrancher) cDNA from a patient with glycogen storage disease type III revealed a deletion of 124 base pairs. A donor splice site mutation (IVS G+1 to T) was identified in the patient's debrancher gene, which caused exon skipping of the upstream exon and resulted in a truncated enzyme due to premature termination. Mutational analysis of the patient's family showed that this point mutation was inherited from the father. Southern blot analysis of the patient's genomic DNA showed an additional, unique EcoRI fragment of 5.8 kb, which was inherited from the mother. These results suggested that the patient was a compound heterozygote for the donor splice site mutation, which is the first identified in the debrancher gene, and had a genetic defect relating to an aberrant 5.8-kb EcoRI fragment.

Adult↗