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Biomedical subjects

M Okuda

Publications and source records attributed to M Okuda.

At least 145 records · Page 8Linked to original sources
PubMed1996

Angiotensin II type 1 receptor-mediated activation of Ras in cultured rat vascular smooth muscle cells.

Angiotensin II (ANG II), a potent growth-promoting factor of vascular smooth muscle cells (VSMC), induces activation of mitogen-activated protein (MAP) kinases and subsequent expression of the c-fos protooncogene in VSMC. However, it remains obscure whether ANG II induces activation of the ras protooncogene product (Ras), and if it does, whether Ras is involved in signaling from the ANG II receptor to the MAP kinase pathway in VSMC. In cultured VSMC, ANG II activated Ras comparably to epidermal growth factor. ANG II-induced Ras activation was detectable within 1 min and maximal at 2-5 min. The ANG II type 1 (AT1) receptor antagonist, CV-11974, completely inhibited this reaction. Pertussis toxin treatment of VSMC inhibited ANG II-induced Ras activation by approximately 70% but had no effect on ANG II-induced MAP kinase activation and c-fos expression. These results indicate that ANG II activates Ras via AT1 receptors, which are predominantly linked to a G protein of the Gi subfamily in VSMC1 and suggest that Ras activation may not be a prerequisite for ANG II-induced MAP kinase activation and c-fos expression in this cell type.

Angiotensin II↗
PubMed1996

Phenotypic and molecular characteristics of nasal mucosal gamma delta T cells in allergic and infectious rhinitis.

T cells expressing the T-cell receptor (TCR) gamma delta home in on various epithelia and may play an important role in local immunity to foreign antigens. The nasal mucosa is a potential site for chronic inflammatory diseases, yet little is known about the characteristics of nasal mucosal gamma delta T cells. Using flow cytometry, immunohistochemistry, and RT-PCR, we elucidated the characteristics of nasal mucosal gamma delta T cells in patients with perennial allergic rhinitis (PAR), chronic infective rhinitis (CIR), and seasonal allergic rhinitis (SAR) and in normal subjects. The gamma delta T cells were significantly increased in the nasal mucosa of patients with PAR (PAR, 24.3 +/- 4.5%; CIR, 12.9+/- 2.7%, p < 0.01), unrelated to those in autologous peripheral blood (PAR, 5.6 +/- 0.8%; CIR, 9.6 +/- 2.8%), and they were preferentially distributed in the epithelial compartment (26.7 +/- 2.3%) rather than in the lamina propria (5.4 +/- 2.5%). Of the expanded population of nasal mucosal gamma delta T cells in patients with PAR, CD4+ and CD4-8- gamma delta T cells were selectively increased (p < 0.01). Although nasal intraepithelial gamma delta T cells from all groups of patients and normal subjects dominantly expressed the V gamma 1/V delta 1 genes, and a bias for V gamma 3 gene expression was noted in those of patients with PAR, a significantly larger fraction of nasal mucosal gamma delta T cells in patients with PAR expressed the V gamma 1/V delta 1 TCR (p, 0.01), whereas those of the peripheral blood expressed the V gamma 2/V delta 2 TCR. More than 60% of V gamma 1/V delta 1 TCR+ cells in patients with PAR, were CD45RO+ ("memory cells"), independent of those in their peripheral blood (p < 0.01). Furthermore, a substantial proportion of nasal mucosal gamma delta T cells in patients with PAR synthesized IL-4 and IL-5 but negligible amounts of IFN-gamma. These observations of an increase in the proportions and activation of distinct subsets of nasal mucosal gamma delta T cells and their Th2-type cytokine profile in patients with PAR, unrelated to those in autologous peripheral blood suggest an important role for the oligoclonally expanded expanded nasal mucosal gamma delta T cells in the pathogenesis of PAR.

Adult↗
PubMed1996

[Quality of life among aged people the lower limit of the age of elderly people in an epidemiological study in Shirahama-machi, Chiba Prefecture].

To define the lower limit at which old age sets in the author examined life factors of such as religion, school career, family structure, working conditions, health conditions, income and life satisfaction as well as the quality of well-being (activity in daily life and health impairment in the modified Kaplan's Well-being scale) during the month of May 1995. A total of 273 subjects were randomly sampled from the inhabitants aged 50 years and over, in Shirahama-machi, Chiba Prefecture in uniform number of gender and cohort, and then cohort differences in the life factors and the quality of well-being and health impairment were statistically analyzed. The cohort differences were found in the majority of items examined below and over 80 years in males and below and over 70 years in females. This result indicated that the lower limit of old age is 80 years in males and 70 years in females.

Age Factors↗
PubMed1996

Hepatitis B virus carrier status linked to autoimmune hepatitis.

We describe a hepatitis B virus carrier who satisfied the criteria of autoimmune hepatitis proposed by the International Autoimmune Hepatitis Group. A 43-year-old Japanese female showed human leukocyte antigen typing including DR4 in addition to hypergammaglobulinemia, presence of autoantibodies, and liver histology suggestive of autoimmune hepatitis. Moreover, the predominant presence of hepatitis B core antigen in nuclei rather than in cytoplasm of hepatocytes suggested less of a possibility of liver cell damage related to hepatitis B virus infection. She completely responded to immunosuppressive therapy and no clinical or biochemical relapse has been recognized to date.

Adult↗
PubMed1996

[Clinical reliability of a new IgE detection system using chemiluminescent enzyme immunoassay named LUMIWARD immunoassay system].

The measurement of allergen-specific IgE antibodies and total IgE was performed with LUMIWARD immunoassay system (chemiluminescent enzyme immunoassay) using 406 serum samples obtained from patients with various allergic diseases and 81 serum samples from normal donors. These were collected by departments of internal medicine, pediatrics, dermatology and otorynolaryngology at eleven institutes in Japan. In addition to a comparative study with CAP RAST, skin tests were also performed to establish a clinical diagnosis. Simultaneous measurements were performed and an excellent correlation with CAP RAST was observed with a concordance rate of 92.6% and correlation coefficient of 0.922. The specificity determined by the normal serum samples was 96.4% for CAP RAST and 96.2% for LUMIWARD. The sensitivity determined by the samples, of which etiological allergens were identified clinically, was 84.8% for CAP RAST and 85.5% for LUMIWARD. Among them, the sensitivity of skin test was 91.8%. The concordance rate with clinical diagnosis was as high as 90.6% and 90.8% for CAP RAST and LUMIWARD. The normal upper limit of total IgE by cumulative 95% value was calculated to be 170 IU/ml for adult subjects. These results indicate the clinical usefulness of the LUMIWARD immunoassay system in evaluating IgE antibodies and total IgE.

Adult↗
PubMed1996

[Optimal dosage of UFT + MMC combination chemotherapy for advanced colorectal cancer--phase I/II study of combination chemotherapy of MMC with 2-week intervals and intermittent UFT administration--Study Group of UFTM Therapy for Advanced Colorectal Cancer].

A combined phase I/II study (UFTM) of tegafururacil (UFT) and mitomycin C (MMC) was performed to find the optimal dosage for advanced colorectal cancer. The study consisted of two parts. The first part confirmed the safety of UFTM and determined the administered doses. The second part evaluated the clinical response of UFTM. Based on the first part, the dosage regimen in the second part was established as follows; the treatment course consisted of 4 weeks and a bolus dose of MMC 6 mg/m2 was given every 2 weeks with daily oral UFT 400 mg/m2 for 5 consecutive days followed by 2 drug-free days; MMC was not given in the third course, and the treatment cycle of the above-mentioned 3 courses was repeated thereafter. In the second part, 26 of 28 patients could be evaluated for toxicity. Grade 3 or 4 toxicities were: anorexia 2, nausea and vomiting 1, leukopenia 1, and 2 cases of thrombocytopenia. The clinical responses of UFTM showed 1 CR and 4 PR in the 21 patients who could be evaluated for response (23.8%). The response rate was 38.5% (5/13) in patients naive to chemotherapy. UFTM can be performed effectively at outpatient clinics as long-term chemotherapy.

Adolescent↗
PubMed1996

[The effect of prostaglandin E1 on body temperature, catecholamines and stress hormones during prolonged surgery].

The effects of prostaglandin E1 (PGE1) on body temperature, catecholamines and stress hormones were evaluated in 10 patients undergoing elective prolonged surgery over 12 hours. PGE1 (0.03 microgram.kg-1.min-1) was administered in 5 patients and was not administered in 5 patients. Deep skin-surface temperature gradients were 5.1 +/- 2.3 degrees C in PGE1 non-administered group and 0.8 +/- 0.9 degree C in PGE1 administered group (P < 0.05). Pharyngeal-skin surface temperature gradients were 8.8 +/- 2.1 degrees C in PGE1 non-administered group and 1.5 +/- 1.5 degrees C in PGE1 administered group (P < 0.05). There were no significant differences between the two groups in respects to catecholamines, stress hormones, lactate level and blood sugar. PGE1 0.03 microgram.kg-1.min-1 is effective in maintaining peripheral circulation without causing body temperature changes during prolonged surgery.

Adrenocorticotropic Hormone↗
PubMed1996

Helicobacter pylori infection in childhood: H. pylori isolation rate in gastric juice in relation to positive serum antibody rates.

We investigated the prevalence of Helicobacter pylori infection by isolation of H. pylori and by antibody detection in the serum of Japanese children. The children were distributed into four groups by age: group I, under 1 year; group II, 1-5 years; group III, 6-11 years; and group IV, 12-15 years. For the isolation of H. pylori, gastric juice was obtained from 115 children from middle class families. In the 103 samples obtained from asymptomatic children, H. pylori was not isolated in any from group I. The isolation rate in groups II, III, and IV was 3% (1/32), 20% (5/25), and 75% (3/4), respectively. In symptomatic children, H. pylori was isolated only in group IV (66.7%). The antibody positive rate in group I, II, III, and IV was 13% (6/47), 10% (11/112), 18% (16/89), and 26% (11/43), respectively, in asymptomatic children. In group I, however, 4 of 25 samples (18%) were obtained from babies under 3 months of age; this result was regarded as reflecting maternal antibodies. Nineteen samples were obtained from children with hepatitis A who lived in Nanki hospital for handicapped children, where hygiere was poor. The antibody positive rate in this population was 60% (3/5) in group III and 90% (9/10) in group IV. These results suggest that H. pylori infection in Japanese children is related to age and hygiene conditions. The antibody positive rate was similar to that reported in other countries.

Adolescent↗
PubMed1995

The interaction of RepC initiator with iterons in the replication of the broad host-range plasmid RSF1010.

The replication origin of the broad host-range plasmid RSF1010 contains 3.5 copies of a 20mer iteron sequence that bind specifically to the plasmid-encoded initiator, RepC. Here we demonstrated that even a single iteron was bent upon binding of RepC. Moreover, the bending angle seems to become larger along with the increment of the number of iterons. In a mutational analysis of the iteron sequence, we isolated seven kinds of base-substitution mutants of iterons, and estimated the replication activity of these mutants in vivo. We found that each of the subsections in the 20mer iteron sequence made a distinct contribution to the initiation of RSF1010 DNA replication. With the binding assay of RepC and mutated iterons in vitro, we found that the formation of a productive RepC-iteron complex was required for the initiation of plasmid DNA replication.

Bacterial Proteins↗
PubMed1995

Structural analysis of mono- and bis-sulfated glycosphingolipids by negative liquid secondary ion mass spectrometry with high- and low-energy collision-induced dissociation.

Several underivatized mono- and bis-sulfated glycosphingolipids having gangliotriaose or gangliotetraose core structure were analyzed by negative liquid secondary ion mass spectrometry (LSIMS) with high- and low-energy collision-induced dissociation (CID). In the normal negative LSIMS spectra, each mono-sulfated glycolipid gave abundant [M - H]- ions and each bis-sulfated glycolipid gave abundant [M + Na - 2H]- ions as well as the hydrogen sulfate anion [OSO3H]-. In high-energy CID spectra of the deprotonated molecule, only ions containing a sulfate ester were clearly observed. When a sulfate was present on the non-reducing terminal saccharide residue, a series of ions corresponding to sulfated mono- to tetra-saccharides, resulting from sequential cleavage of glycosidic bonds, were observed. If the sulfate was attached to an internal hexose of the sugar chain, the product ions corresponding to the non-sulfated, non-reducing terminal residue were absent. In contrast, the low-energy CID resulted in extremely simple spectra that contained only one or two major product ions characteristic of each sulfated glycolipid. These results provided clear information on the overall sugar and ceramide compositions, and allowed saccharide structures differing in location and number of sulfate esters to be distinguished.

Animals↗
PubMed1995

Angiotensin II transduces its signal to focal adhesions via angiotensin II type 1 receptors in vascular smooth muscle cells.

In cultured vascular smooth muscle cells (VSMCs), angiotensin II (Ang II) stimulated tyrosine phosphorylation of several proteins including a cluster of 70-80-kDa proteins as assessed by anti-phosphotyrosine immunoblotting. These 70-80-kDa proteins were identified as a focal adhesion-associated protein, paxillin, by anti-paxillin immunoprecipitation. Ang II-stimulated tyrosine phosphorylation of paxillin was detectable within 1 min and maximal at around 10 min and was concentration dependent (half-maximal effect at around 1 nM). Ang II also stimulated tyrosine phosphorylation of focal adhesion kinase in a time- and concentration-dependent manner. The Ang II type 1 (AT1) receptor antagonist, CV-11974, but not the Ang II type 2 receptor antagonist, PD123319, inhibited these reactions. These results indicate that Ang II transduces its signal to focal adhesions via AT1 receptors in cultured VSMCs.

Angiotensin II↗
PubMed1995

Detection of K-ras mutations in DNAs isolated from feces of patients with colorectal tumors by mutant-allele-specific amplification (MASA).

K-ras mutations are found in approximately half of all colorectal tumors examined. To explore the possibility of detecting mutated K-ras rapidly and efficiently in DNAs isolated from fecal material, we applied the mutant allele specific amplification (MASA)-PCR method to DNA from feces of patients with colorectal tumors. Among 55 colorectal adenocarcinomas or adenomas examined, 19 were found to carry K-ras mutations in codons 12 or 13. We were able to PCR-amplify DNAs isolated from feces of 15 of these 19 patients, but in only three of the fecal samples, we were able to detect the K-ras mutations corresponding to tumor DNA by MASA and ethidiumbromide staining of the gel. The carcinomas in these three cases were more than 40 mm x 40 mm in size and located in the sigmoid colon or rectum. However, we identified the K-ras mutations in fecal DNAs of additional seven patients by MASA when the gels were blotted and probed with a radio-labeled oligonucleotide; the tumors in those patients had arisen in the distal half of the colon and the smallest of these tumors was only 7 mm x 5 mm. No K-ras mutations were detectable in feces of the remaining five cases, whose tumors were relatively small and/or located in the proximal region. The results suggested that the MASA-PCR system has potential for development as a simple, rapid and noninvasive method for diagnosing the presence of colorectal tumors that carry mutant K-ras alleles, particularly tumors located in the distal colon.

Adenocarcinoma↗
PubMed1995

Serial assay of hepatitis C virus RNA in serum for predicting response to interferon-alpha therapy.

To determine whether the loss of serum hepatitis C virus RNA (HCV-RNA) early in interferon therapy would indicate a sustained response to this agent, we detected serum HCV-RNA successively during and after therapy. Serum samples for detection of HCV-RNA were obtained serially from 36 patients with chronic hepatitis C treated with interferon-alpha. In 28 of these patients, results of the assay were compared with genotypes and quantitative levels of HCV-RNA in serum before therapy. HCV-RNA was detected by a reverse transcription polymerase chain reaction using the 5'-noncoding region as a primer. Genotypes were determined by using type-specific primers, and serum levels of HCV-RNA were determined by a competitive reverse transcription polymerase chain reaction (RT-PCR). HCV-RNA disappeared from serum in eight of 10 responders (80%), but in only one of the 26 nonresponders (3.8%) at the second week of therapy (P < 0.0005). The time until the disappearance of HCV-RNA was correlated with the serum level of HCV-RNA present before therapy (P < 0.05). The early disappearance of HCV-RNA from serum during interferon therapy was useful in predicting a sustained response in patients with chronic hepatitis C.

Adult↗
PubMed1995

Glycine-to-arginine substitution at codon 145 of HBsAg in two infants born to hepatitis B e antigen-positive carrier.

Two daughters born to an HBeAg-positive carrier became hepatitis B virus carriers despite immunoprophylaxis with hepatitis B immune globulin or hepatitis B vaccine. The elder daughter received hepatitis B immune globulin alone and the younger daughter received both hepatitis B immune globulin and hepatitis B vaccine. They acquired anti-HBs passively immediately after birth, and the younger daughter did not respond to active immunization. The nucleotide sequence of the S gene of hepatitis B virus DNA from the four carriers in the family was determined. A 531-bp fragment within the S gene, which includes a region encoding both the common a and type-specific d/y or r/w determinants, was amplified by polymerase chain reaction and sequenced. Antigenic subtypes of HBV were identified as adr in the father and adw in both the mother and two daughters. Amino acid residues 122-160 of HBsAg were identical between the daughters and their mother except for a glycine-to-arginine substitution at codon 145. A possibility that this escape mutant had selective advantage over wild-type hepatitis B virus under immune pressure is discussed.

Amino Acid Sequence↗
PubMed1995

Hot water extracts of Chlorella vulgaris reduce opportunistic infection with Listeria monocytogenes in C57BL/6 mice infected with LP-BM5 murine leukemia viruses.

The bacterial elimination after infection with Listeria monocytogenes was impaired in mice with murine acquired immunodeficiency syndrome (MAIDS) by infection with LP-BM5 murine leukemia virus. Oral administration of hot water extracts of Chlorella vulgaris (CVE) restored the capacity of MAIDS mice to eliminate L. monocytogenes in association with improvement of the deteriorated immune response to L. monocytogenes. DTH response to Listeria in CVE-treated MAIDS mice was significantly higher than that of MAIDS mice after Listeria infection in association with increases in number of CD4+CD8- and CD4-CD8+ alpha beta T-cells in the infected sites. CVE might be effective in the treatment of opportunistic infection in retrovirus-induced immunodeficient patients.

Animals↗