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Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 307 records · Page 17Linked to original sources
PubMed1998

Antisense homology box-derived peptides represent a new class of endothelin receptor inhibitors.

Several peptides encoded by the sense and corresponding antisense DNA have been found to recognize and bind to each other. We developed software to search for sense-antisense regions within proteins taking into account the degeneracy of the genetic code, i.e., one amino acid can have several "antisense" counterparts. Using this approach, we searched endothelin receptor type A for intramolecular regions related in sense-antisense fashion. After locating these regions (termed "antisense homology boxes"), several corresponding peptides were synthesized. The four new ET(A) receptor fragment peptides ETR-P1 ("CALSVDRYRAVASW"), ETR-P3 ("QGIGPLITAIEI"), ETR-P4 ("IADNAERYSANLSSHV") and ETR-P6 ("LNRRNGSLRIALSEHLKNRREVA") reported here can inhibit ET-1 activity.

3T3 Cells↗
PubMed1998

Complement C5a anaphylatoxin fragment causes apoptosis in TGW neuroblastoma cells.

Human neuroblastoma TGW cells express a C5a anaphylatoxin receptor-like molecule termed neuronal C5a receptor. A C5a-receptor fragment peptide (termed PR226-multiple antigenic peptide) can induce rapid apoptosis in TGW cells via neuronal C5a receptor-associated signal transduction pathways. In order to analyse role of activated complement system in neurodegeneration, TGW cells were exposed to an oligomer form of a C5a fragment (amino acids: 37-53) peptide termed PL37-multiple antigenic peptide. Upon treatment with PL37-multiple antigenic peptide, an increased nuclear c-fos expression was shown within 30 min. DNA fragmentation, a hallmark of apoptosis, was noted within 4 h. Extracellular administration of 100 nM PL37-multiple antigenic peptide evoked inward calcium current pulses. At higher doses (0.5 microM-1 microM), PL37-multiple antigenic peptide evoked higher current pulses, followed by an irreversible, high inward current. To exert its apoptotic effect, PL37-multiple antigenic peptide utilizes a pertussis toxin-sensitive signal transduction pathway associated with the neuronal C5a receptor. Activation of the complement system and therefore release of C5a has already been reported in Alzheimer's disease. In addition, the presence of the Kunitz-type proteinase inhibitors indicates an impaired protease function and a possible abnormal fragmentation of C5a anaphylatoxin. Our data suggest that neurons expressing neuronal C5a receptor are more vulnerable to the apoptosis associated with the neuronal C5a receptor and the possibility that abnormal activation of C5a receptor and C5a anaphylatoxin fragments might be involved in the pathogenesis of Alzheimer's disease.

Anaphylatoxins↗
PubMed1998

Establishment of complement-resistant retroviral vector by homologous restriction factor 20 gene.

Homologous restriction factor 20 (HRF20, CD59) is one of the complement regulatory factors. In this study, the complement-resistant retroviral vector, which possesses the HRF20 gene as a selection gene, was constructed and examined. The virus-producing cell, transduced with complement-resistant retroviral vector, was established after complement-dependent selection. NIH3T3 and PK15 cells transduced with this virus-producing cell were successfully selected by complement-dependent selection, which showed significant expression of the HRF20 antigen. In addition, these cells, transduced with tissue plasminogen activator (tPA) cDNA using complement-resistant retroviral vector, expressed tPA antigen after complement-dependent selection. These findings suggest that complement-resistant retroviral vector can be used for the double transduction of HRF20, as well as other genes.

3T3 Cells↗
PubMed1998

Basal cell carcinoma with neuroid type nuclear palisading: a report of three cases.

Nuclear palisading is a characteristic feature which is typically seen in neural tumours such as neurilemmoma, and also in some other tumours. We report here three patients with basal cell carcinoma who showed histological patterns similar to nuclear palisading. To our knowledge, this is the first such case report in the medical literature; we apply the term 'neuroid-type nuclear palisading' to these cases. In our patients, the spindle-shaped tumour cells were tightly packed and the nuclei were arranged uniformly to form this rare feature.

Aged↗
PubMed1998

Decay-accelerating factor (DAF) in stool specimens as a marker of disease activity in patients with ulcerative colitis (UC).

Colonic epithelial cells of patients with UC express DAF in relation to the severity of mucosal inflammation. The aim of this study was to determine whether this factor in stool could be used as a marker of disease activity in UC patients. Stool DAF was measured by use of an immunoassay in 181 stool specimens obtained from 55 patients with UC of various levels of disease activity. Stool DAF concentrations in patients whose UC was active (0.0-785.6 ng/g stool; median 47.1 ng/g; n = 115) were significantly higher than concentrations in patients whose disease was inactive (0.0-48.6 ng/g; median 0.0 ng/g; n = 66) (P < 0.0001). Values in active UC patients also were higher than those in control patients with diarrhoea (0.0-30.0 ng/g; median 0.0 ng/g; n = 26) (P < 0.0001) and in control subjects without apparent colorectal disease (0-20.4 ng/g; median 0.0 ng/g; n = 44) (P < 0.0001). The elevated levels of stool DAF obtained from UC patients in relapse declined markedly in specimens collected after the disease went into remission following medical therapy. Stool DAF levels correlated with the severity of endoscopic and histological findings and the degree of DAF expression on the colonic epithelia. Our results suggest that the measurement of stool DAF is useful as a non-invasive means of monitoring intestinal disease activity in patients with UC.

Adolescent↗
PubMed1998

Cytokine-stimulated release of decay-accelerating factor (DAF;CD55) from HT-29 human intestinal epithelial cells.

Expression of DAF (CD55) is enhanced on colonic epithelial cells of patients with ulcerative colitis (UC), and stool DAF concentrations are increased in patients with active disease. Cytokines are known to modulate DAF expression in various human cells, and lesions of UC reveal altered profiles of cytokine production. In this study, we evaluate the effects of various cytokines, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, and interferon-gamma (IFN-gamma), on the synthesis and kinetics of DAF protein in HT-29 human intestinal epithelial cells. Using flow cytometry and an ELISA, we found that HT-29 cells constitutively express DAF on the cell surface and spontaneously release DAF into the culture supernatant under standard culture conditions. When the culture supernatant was centrifuged at 100000g, nearly a half of DAF was precipitated, indicating that one half of the released DAF was present as a membrane-bound form and the other half as a soluble form. Analysis of the culture supernatant of biotin surface-labelled HT-29 cells suggested that the soluble form DAF was derived by secretion from within the cell or by cleavage from the cell surface. Among the cytokines, IL-4 markedly, and IL-1beta moderately, enhanced the expression and the release of DAF. Actinomycin D, cycloheximide, and brefeldin A inhibited the increase in DAF release induced by IL-4 and IL-1beta stimulation. These results suggest that DAF is released from intestinal epithelial cells in response to cytokine stimulation and that IL-4 and IL-1beta are possible cytokines involved in DAF release into the colonic lumen of patients with UC.

Anti-Bacterial Agents↗
PubMed1998

Tissue distribution of the guinea-pig decay-accelerating factor.

MCA44 is a monoclonal antibody (mAb) to guinea-pig decay-accelerating factor (DAF) and, using this mAb, tissue distribution of guinea-pig DAF was studied by immunofluorescence. Guinea-pig DAF was found to be expressed not only on the vascular endothelium but also on different types of cells, such as the tubular epithelium of the kidney, epidermal cells of the skin and synovial lining cells. As there was no significant reduction in staining intensity with MCA44 following treatment with phosphatidylinositol-specific phospholipase C, many guinea-pig DAF molecules expressed in these tissues may be of the transmembrane form.

Animals↗
PubMed1998

Interleukin (IL)-1 and IL-4 synergistically stimulate NF-IL6 activity and IL-6 production in human mesangial cells.

BACKGROUND: While interleukin (IL)-4 inhibits pro-inflammatory cytokine expression by human monocytes, we have observed that it potentiates IL-6 production by IL-1-activated human mesangial cells (MC). To study the mechanism of this cell-type specific interaction between IL-1 and IL-4 in MC, we examined the effect of both cytokines on the activities of nuclear factor kappa B (NF-kappa B) and nuclear IL-6 NL-IL 6), transcription factors that are essential for IL-6 gene expression. METHODS: We evaluated IL-6 synthesis, mRNA expression, and mRNA stability by ELISA, Northern analysis, and the actinomycin D method, respectively. Activities of NF-kappa B and NF-IL 6 were analyzed by gel shift assay. RESULTS: IL-4 augmented the IL-1 stimulated IL-6 mRNA levels by about threefold without altering mRNA stability. IL-1 treatment rapidly induced the binding activity of NF-kappa B. In contrast, IL-4 did not affect basal and IL-1-induced NF-kappa B activities. Both IL-1 and IL-4 stimulated NF-IL6 activity as early as 30 minutes after treatment. When MC were treated with both cytokines together, marked activation of NF-IL6 was observed at five hours. CONCLUSIONS: These results suggest that simultaneous activation of NF-kappa B and NF-IL6 is essential for IL-6 gene expression and that IL-1 and IL-4 cooperatively stimulate MC IL-6 production through their synergistic activation of NF-IL6.

CCAAT-Enhancer-Binding Proteins↗
PubMed1998

Plasma lactic acid and pyruvic acid levels in migraine and tension-type headache.

We examined the lactic and pyruvic acid levels in the plasma of 14 patients with migraine, 17 patients with tension-type headache, and 12 normal controls. The lactic and pyruvic acid levels in the plasma of the migraine patients were significantly higher than those of the normal controls (9.6 +/- 5.0 mg/dL and 0.51 +/- 0.30 mg/dL versus 3.3 +/- 1.9 mg/dL and 0.26 +/- 0.20 mg/dL, respectively). There were no significant differences in the levels between the patients with tension-type headache and normal controls. Our results suggest that migraine patients may have functional abnormalities in mitochondrial energy metabolism.

Adult↗
PubMed1998

Leiomyoma of the urinary bladder causing tamponade.

Benign mesenchymal tumours of the bladder are rare, accounting for only 1-5% of bladder neoplasms. We describe what appears to be the first reported case of massive bleeding from a leiomyoma of the urinary bladder causing tamponade requiring emergency surgery.

Constriction, Pathologic↗
PubMed1998

Telomerase activity in the testis of infertile patients with selected causes.

In human testes, stem cells such as spermatogonia need to produce progeny cells continually. Telomere length is maintained throughout spermatogenesis, i.e. from spermatogonia to spermatozoon, and telomerase is reported to be present in the testes. In this study, we measured the activity of telomerase in the human testes of 16 cases of idiopathic azoospermia, 10 of obstructive azoospermia, and 17 of oligozoospermia in order to understand the role of telomerase in spermatogenesis. Telomerase activity in the testes with Sertoli cell-only and in testes with maturation arrest were 0.08 +/- 0.05 optical density (OD) (mean +/- SD) and 1.96 +/- 0.98 OD, respectively (P < 0.05). Classifying those testes with maturation arrest into two groups, the telomerase activity of those with early maturation arrest (arrest at spermatocyte) and of those with late maturation arrest (arrest at round spermatid) was 1.82 +/- 0.82 OD and 2.10 +/- 1.14 OD respectively. There was no significant difference between the two groups. The telomerase activity in the testes showing hypospermatogenesis in obstructive azoospermia and in those of oligozoospermia with hypospermatogenesis was 1.89 +/- 1.06 OD and 1.92 +/- 1.02 OD respectively. No difference in telomerase activity existed between the testes with maturation arrest and those with hypospermatogenesis in obstructive azoospermia or oligozoospermia. Sertoli cell-only testes without germ cells showed no telomerase activity. The source of the telomerase activity was likely to be germ cells. The telomerase activity in the testes (n = 63) was related to the histology of the testes. The activity of telomerase showed no significant correlation with the sperm concentration in each patient. Only serum oestradiol level significantly correlated with telomerase activity (P < 0.05). The concentrations of follicle stimulating hormone, luteinizing hormone, or testosterone had no significant relationship with the telomerase activity. Therefore similar levels of telomerase activity were detected in the testes of infertile men with azoospermia and oligozoospermia and in testes showing maturation arrest.

Adult↗
PubMed1998

Complement-mediated cytolysis and azidothymidine are synergistic in HIV-1 suppression.

Some normal human sera contain a natural IgM antibody against gangliotetraose and GM2 which is capable of initiating complement-mediated cytolysis of HIV-1-infected cells. A potent cytolytic serum (lytic serum) harboring this antibody also caused lysis of HIV-1 virions. When lytic serum was added to a mixed culture of HIV-infected cells and naive cells at a ratio of 1:100, expansion of HIV-1 infection was postponed by 1 week. Furthermore, the co-presence of both the lytic serum and azidothymidine continued to significantly suppress infection, even after 4 weeks of cultivation.

Anti-HIV Agents↗
PubMed1998

Endothelin (ET)-1 induced mucosal damage in the rat small intestine: role of ET(A) receptors.

The role of endothelin (ET)-1 as a mediator of small intestinal mucosal perfusion failure and tissue damage was investigated in the rat using intravital fluorescence videomicroscopy. The effects of intravenous infusion of ET-1 (3 nmol/kg) on functional capillary density, mucosal thickness, and the degree of mucosal damage were evaluated. Administration of ET-1 caused pronounced mucosal injury with a significant reduction of mucosal thickness compared with vehicle-treated control animals. Concomitantly, villous functional capillary density was markedly reduced 30 and 90 min after the infusion of ET-1. ET(A) receptor blockade by pretreatment with BQ 610 or with the novel ET(A) receptor antagonist ETR-P1/FL peptide prevented ET-1 induced capillary perfusion failure and mucosal damage. In contrast, the ET(B) receptor antagonist IRL 1038 was not effective. These results indicate that, acting via the ET(A) receptor, elevated levels of circulating ET-1 under various pathophysiological conditions, such as septic or hemorrhagic shock, might impair nutritive perfusion of the intestinal mucosa and contribute to tissue injury.

Animals↗
PubMed1998

Measurement of arginine carboxypeptidase-generating activity of adult plasma.

Arginine carboxypeptidase (CPR) is a novel carboxypeptidase which was first described by Campbell and Okada. CPR is generated from a stable precursor of CPR (proCPR) during coagulation or under other circumstances and is promptly inactivated at 37 C. Therefore, it is not easy to determine CPR in blood samples. Since proCPR can be separated from the other basic carboxypeptidase (carboxypeptidase N; CPN) by passing plasma through DEAE gel, we have established a method to determine the amount of proCPR after converting it to active CPR by trypsin treatment. We first separated the proCPR from CPN using a filter cup tube (FC tube) packed with DEAE Sephadex, and measured activity after conversion of the enzyme to its active form using trypsin. With this method, no significant decrease in proCPR was noted in the plasma of patients including those with rheumatoid arthritis (RA), although CPR activity in fresh sera has been reported to be decreased. This discrepancy suggests that proCPR is not depleted in most patient sera, but that the level of activity of the enzyme which converts proCPR into active CPR may be compromised in RA patients.

Adult↗