Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 37 records · Page 2Linked to original sources

PubMed1992

An oxidized analog of alpha-human atrial natriuretic polypeptide is a selective agonist for the atrial-natriuretic-polypeptide clearance receptor which lacks a guanylate cyclase.

The differences in biological functions between alpha-human atrial natriuretic polypeptide (alpha-hANP) and its oxidized analog, MetSO-alpha-hANP, have been investigated. Analysis of the ANP receptor subtypes by affinity labeling has shown that a bovine pulmonary aortic endothelial cell line (CPAE cells) primarily expresses ANP-R1 (R, receptor) coupled to particulate guanylate cyclase, while Hela cells from human cervical carcinoma predominantly express ANP-R2, which lacks a guanylate cyclase. alpha-hANP could bind to both ANP receptor subtypes with high affinity, while MetSO-alpha-hANP showed more selective binding to ANP-R2 than to ANP-R1. The activity of MetSO-alpha-hANP for stimulation of guanylate cyclase coupled to ANP-R1 was about 520-fold less than that of alpha-hANP (median effective dose = 2.5 nM for alpha-hANP, 1.3 microM for MetSO-alpha-hANP), indicating that MetSO-alpha-hANP was a partial agonist for this receptor. While this oxidized analog could inhibit the cAMP production through ANP-R2, with 0.15 times the activity of alpha-hANP (median concentration = 0.31 nM for alpha-hANP, 2.0 nM for MetSO-alpha-hANP). In in vivo studies, the diuretic activity of MetSO-alpha-hANP was 25-100-fold less than that of alpha-hANP. In addition, MetSO-alpha-hANP could potentiate the diuretic activity of alpha-hANP that was also caused by C-ANF4-23, a specific agonist for ANP-R2. These results demonstrate that MetSO-alpha-hANP can act as an agonist more selective for ANP-R2 than for ANP-R1, both in vivo and in vitro. The relationship between receptor selectivities and the conformation of alpha-hANP or MetSO-alpha-hANP was also discussed.

Affinity Labels↗

PubMed1992

Expression of high affinity binding sites for erythropoietin on L8057 cells, a mouse megakaryoblastic cell line, associated with cell differentiation.

In this study, specific binding sites were examined for erythropoietin (EPO) on the mouse leukemic cell line, L8057. This cell line is megakaryoblastic in origin as evidenced by an enlargement of cell size, multinuclearity, intense activity of acetylcholinesterase, more expression of glycoprotein IIb and IIIa antigen, and higher ploidy distribution after the treatment with 12-o-tetradecanoylphorbor-13-acetate (TPA). The original undifferentiated cells possessed a single class of low affinity binding sites for recombinant human (rh) EPO with a Kd of 3.5 nM. Following the treatment with TPA, high affinity binding sites (Kd; 440 pM) were expressed in addition to the low affinity sites. EPO stimulated the incorporation of 3H-leucine into TPA-treated L8057 cells, and the maximal effect of EPO was observed at the same order as the Kd value of high affinity sites. The present data demonstrates that the expression of high affinity binding sites for EPO is associated with the differentiation of L8057 cells which have megakaryocytic characteristics. Furthermore, protein synthesis stimulated by EPO may be mediated through the high affinity sites.

Acetylcholinesterase↗

PubMed1992

Regulation of B cell function by lobenzarit, a novel disease-modifying antirheumatic drug.

OBJECTIVE: Lobenzarit (disodium 4-chloro-2,2'-iminodibenzoate [CCA]) is a novel disease-modifying drug for the treatment of rheumatoid arthritis (RA). Although its clinical efficacy has been demonstrated, its mechanism of action remains unclear. We therefore examined the effects of CCA on in vitro IgM and IgM rheumatoid factor (IgM-RF) production by human B cells. METHODS: IgM and IgM-RF production was induced from highly purified B cells from 8 healthy donors by stimulation with Staphylococcus aureus Cowan 1 (SAC) plus factors generated from mitogen-activated T cells (TCF) or with immobilized anti-CD3-activated CD4+ T cells. RESULTS: CCA suppressed the production of IgM-RF as well as IgM at concentrations of 25-50 micrograms/ml (therapeutic serum concentrations of the drug), although the IgM-RF production induced by SAC plus TCF was suppressed at lower concentrations of CCA (1-3 micrograms/ml). Whereas CCA suppressed interleukin-2 (IL-2) production by anti-CD3-activated CD4+ T cells, its suppressive effects on B cells were not overcome by addition of IL-2 or TCF. CCA did not inhibit the initial stages of B cell activation in either culture system, but rather, suppressed the maturation of previously activated B cells. Cell cycle analysis by acridine orange staining indicated that CCA-mediated inhibition of B cell responsiveness induced by anti-CD3-activated CD4+ T cells was the result of a block at the G1-S interphase. CONCLUSION: These results indicate that CCA suppresses the production of IgM and IgM-RF by directly inhibiting activated B cells. Thus, one of the actions of CCA in RA may be the suppression of the function of activated B cells.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1992

Hemofiltration as treatment for patients with refractory heart failure.

Hemofiltration was performed in 15 patients with refractory congestive heart failure. All of these patients had oliguria, although intensive treatment with diuretics, digitalis, vasodilators, and catecholamines was prescribed. Hemofiltration was performed under hemodynamic monitoring in 14 patients. The water removal by hemofiltration decreased pulmonary arterial pressure, pulmonary capillary wedge pressure and right atrial pressure. Despite these hemodynamic improvements, nine patients (60%) died within one month after the start of hemofiltration; the causes were fatal arrhythmia in three, renal failure in two, sepsis in one and irreversible cardiogenic shock in three. Oliguria for over 15 h or a serum creatinine concentration of more than 4.0 mg/dl at the start of hemofiltration related to poor prognosis. In view of these results, hemofiltration for refractory heart failure should be started earlier and performed carefully in order to avoid arrhythmia, cardiogenic shock, and other complications.

Adult↗

PubMed1992

Left ventricular diastolic dysfunction in coronary artery disease: effects of coronary revascularization.

Left ventricular diastolic dysfunction was studied globally and regionally in patients with coronary artery disease, and the effects of coronary revascularization were evaluated. A total of 25 patients with angina pectoris who had a stenotic lesion (greater than or equal to 90%) in only left anterior descending branch underwent coronary revascularization [percutaneous transluminal coronary angioplasty (PTCA) in 13 patients and coronary artery bypass graft (CABG) in 12]. Nine patients with normal coronary artery were studied as controls. Left ventricular volume and radial axes were measured on serial frames of one cardiac cycle by cine left ventriculography. The radial axes were drawn from the left ventricular gravity to left ventricular wall at every 20 degrees. Left ventricular filling fraction and distension rate of radial axes were calculated at the times of 25%, 50%, 75%, and 100% of diastolic period, 100% being end-diastole. Although there were no significant changes of the systolic function by revascularization, the filling fraction increased from 11.2 +/- 2.6 to 14.5 +/- 3.5% (p less than 0.001) at 25% time of diastole, from 29.9 +/- 4.9 to 32.5 +/- 5.0% (p less than 0.05) at 50% time in the PTCA group, and from 11.8 +/- 3.7 to 13.4 +/- 3.8% (p less than 0.01) at 25% time in the CABG group. The distension rate of radial axis to the anterior wall also increased significantly at 25% and 50% time of diastole after revascularization, and the change was marked in the PTCA group. However, these increases did not apply to the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

PubMed1992

Man's place in Hominoidea revealed by mitochondrial DNA genealogy.

Molecular biology has resurrected C. Darwin and T.H. Huxley's question about the origin of humans, but the precise branching pattern and dating remain controversial. To settle this issue, a large amount of sequence information is required. We determined mitochondrial (mt) DNA sequences for five hominoids; pygmy and common chimpanzees, gorilla, orangutan, and siamang. The common region compared with the known human sequence is 4759 bp long, encompassing genes for 11 transfer RNAs and 6 proteins. Because of the high substitution rates in mammalian mtDNA and an unprecedentedly large region compared, the sequence differences clearly indicate that the closest relatives to human are chimpanzees rather than gorilla. For dating the divergences of human, chimpanzee, and gorilla, we used only unsaturated parts of sequence differences in which the mtDNA genealogy is not obscured by multiple substitutions. The result suggests that gorilla branched off 7.7 +/- 0.7 million years (Myr) ago and human 4.7 +/- 0.5 Myr ago; the time difference between these divergences being as long as 3 Myr.

Animals↗

PubMed1992

Polymorphonuclear leukocyte function and serum opsonic activity in surgical patients.

Thirty-six patients who underwent major surgery were studied in order to clarify the perioperative changes in polymorpho - nuclear leukocyte (PMNL) function and serum opsonic activity. In patients without postoperative infection, the PMNL phagocytic-bactericidal capacity and plasma elastase levels significantly increased, while the serum opsonic index remarkably decreased just after surgery, however, all returned to the preoperative levels within 1 or 2 weeks. Conversely, in patients with postoperative infection, the PMNL bactericidal capacity and plasma elastase levels remained at high levels even after 1 or 2 weeks, while the PMNL phagocytic capacity and serum opsonic index substantially decreased after 2 weeks compared with the patients without postoperative infection. Plasma leukotriene B4, which is a potent chemo-attractant for PMNL, noticeably decreased in the patients with postoperative infection on the first postoperative day compared with that in the patients without postoperative infection. Our data suggests that the most important predisposing factors to postoperative infection may be a depressed PMNL phagocytic capacity and a lower serum opsonic activity after surgery, and that the increased PMNL bactericidal capacity and high plasma elastase levels during postoperative infection may contribute to the susceptibility to multiple organ failure.

Adult↗

PubMed1992

Cloning and mapping of the CYS4 gene of Saccharomyces cerevisiae.

A DNA fragment containing the CYS4 gene of Saccharomyces cerevisiae was isolated from a genomic library. The cloned fragment hybridized to the transverse-alternating-field-electrophoresis band corresponding to chromosomes VII and XV. According to the 2 microns DNA chromosome-loss procedure, the cys2 and cys4 mutations, which are linked together and co-operatively confer cysteine dependence, were assigned to chromosome VII. By further mapping involving tetrad analysis, the cys2-cys4 pair was localized between SUP77 (SUP166) and ade3 on the right arm of chromosome VII.

Acetyltransferases↗

PubMed1992

Identification of epitopes associated with different biological activities on the glycoprotein of vesicular stomatitis virus by use of monoclonal antibodies.

Thirteen monoclonal antibodies (MAbs) to the glycoprotein (G) of vesicular stomatitis virus (VSV) serotype Indiana were prepared and examined for their effects on various biological activities of VSV, including in vitro infection, hemagglutination, adsorption to cells, and mediation of cell fusion. Competitive binding assays with these MAbs revealed the presence of at least seven distinct antigenic determinants (epitopes) on the G protein. In some cases, overlappings among epitopes to various degrees were observed as partial inhibition or binding enhancement. The MAbs to all the epitopes but one (epitopes 1-6) reacted with the denatured G protein in a Western immunoblot analysis. Four of the epitopes (epitopes 2, 4, 5, and 7) were involved in neutralization and two (epitopes 1 and 2) in hemagglutination inhibition. None of the MAbs inhibited the adsorption of radiolabeled VSV to BHK-21 cells; the MAbs to epitope 2 slightly enhanced the virus adsorption. All neutralization epitopes except epitope 2 (epitopes 4, 5, and 7) were associated with inhibition of VSV-mediated cell fusion. These results show a direct spatial relationship between the epitopes recognized by the MAbs and functional sites on G protein and further insights into the structure and function of G protein.

Adsorption↗

PubMed1992

Restriction polymorphisms in the internal transcribed spacers and 5.8S rDNA of Saccharomyces.

Polymorphisms in enzymatically amplified ribosomal DNA (rDNA) were examined in 18 strains of Saccharomyces. Restriction patterns generated from the region spanning the internal transcribed spacers (ITS) and the 5.8S rDNA produced two clusters corresponding to S. bayanus and S. cerevisiae. The type culture of S. carlsbergensis (ATCC 76529), which could not be separated from the S. cerevisiae group by small subunit (SSU) rDNA patterns, showed a ScrfI profile that was distinct from all the other strains. The type culture of S. intermedius var. turicensis (ATCC 76519) is assigned to S. bayanus on the basis of the combined results of SSU and ITS restriction analyses. S. kluyveri occurred at a separate branch of the distance tree and is unrelated to any of the strains. Results were in general agreement with reported DNA homologies and are discussed in relation to other molecular and genetic data.

Base Sequence↗

PubMed1992

Vascular invasion of colorectal carcinoma readily visible with certain stains.

We made use of hematoxylin and eosin (H&E) stain, Verhoeff van-Gieson stain for elastic tissue (EVG), and factor VIII-related antigen (FVIII-RA) to stain tissues excised from 94 patients with colorectal carcinoma. Of these 94, 49 died of disease within two years (Group I), and 45 survived for five years or longer (Group II) after surgery. In the tissues from both groups, the use of EVG stain revealed a higher incidence of vascular invasion than was seen with H&E stain. In Group I, the rates were 28.6 percent and 61.2 percent with H&E and EVG, respectively, and those in Group II were 4.4 percent and 31.1 percent, respectively. Conversely, the FVIII-RA stain showed a decrease in the incidence of vascular invasion in both groups. In Group I, when vascular invasion was examined in EVG-stained tissues, the incidence was 81.3 percent in cases of hematogenous metastases and 23.5 percent in those without hematogenous metastases (P less than 0.01). These differences were not evident with H&E. When observing the site of vascular invasion in tissues of the colorectal wall stained with EVG, intramural and extramural types of vascular invasion were seen in 20 percent and 80 percent of cases in Group I and in 93 percent and 7 percent of those in Group II, respectively. Thus, not only the frequency, but also the site, of vascular invasion into the colorectal wall evidenced with EVG stain provides a more precise prediction of the recurrence of hematogenous metastases.

Colorectal Neoplasms↗

PubMed1992

Effects of interferon-alpha on human B cell responsiveness: biphasic effects in cultures stimulated with Staphylococcus aureus.

Although interferon-alpha (IFN-alpha) has been found to be involved in the immune regulation in vivo, the effects of IFN-alpha on human B cells have not yet been clarified because of conflicting results in the literature. The present study therefore examined the effects of several subtypes of IFN-alpha (natural, alpha 1, alpha 2a, alpha 2b) on B cell responsiveness in detail by comparing different experimental conditions. Highly purified B cells from normal human individuals were cultured with Staphylococcus aureus (SA) + IL-2 or with immobilized anti-CD3-activated T4 cells in the presence or absence of IFN-alpha. IFN-alpha enhanced the immunoglobulin (Ig) production induced by immobilized anti-CD3-activated T4 cells. By contrast, IFN-alpha (5-50,000 IU/ml) suppressed the Ig production induced by SA + IL-2. The suppression by IFN-alpha was dependent on the concentration of SA. The inhibitory effects of IFN-alpha in SA-stimulated cultures were exerted in the first 72 hr of cultures and required the presence of IL-2, whereas IFN-alpha enhanced the maturation of B cells when it was added after 72 hr of cultures. The suppressive effects of IFN-alpha were overcome by addition of immobilized anti-CD3-preactivated T cells that had been treated with mitomycin C, but not by the addition of fresh T cells or soluble factors produced by activated T cells. Of interest, IFN-alpha did not inhibit the expression of IL-2R, but inhibited that of intercellular adhesion molecule-1 (ICAM-1) on B cells after stimulation with SA + IL-2, suggesting that the suppressive effects of IFN-alpha might be related to the regulation of B cell-B cell contacts through ICAM-1. There was no significant difference in effects on B cells among various subtypes of IFN-alpha. These results suggest that the effects of IFN-alpha on human B cell responsiveness may be different depending on the nature of stimulation. Moreover, the data indicate that IFN-alpha enhances the differentiation of activated B cells irrespective of the activation signals.

Antibodies, Monoclonal↗

PubMed1992

Induction of IL-2 receptor expression and proliferation of T cell clones by a novel cytokine(s).

We found a unique T cell IL-2 receptor (IL-2R)3-inducing activity in the supernatant (SN) of the TH1 clone stimulated with antigen on spleen cells as antigen-presenting cells (APC). We have tentatively named this activity the IL-2R-inducing factor (IL-2RIF) and have characterized the activity. The SN induced IL-2R and proliferation of TH1 clones stimulated with B cell APC, which could not induce IL-2R in the absence of the SN. Other known cytokines were examined for a IL-2RIF activity; however, none of cytokines examined exerted a similar activity. Moreover, the neutralizing antibodies against the known cytokines tested did not block the IL-2RIF activity in the SN. When TH1 clones were stimulated with immobilized anti-CD3 or with fixed B cell APC in the presence of partially purified IL-2RIF, these clones expressed IL-2R and showed IL-2-dependent proliferation, whereas they induced neither IL-2R expression nor proliferation in the absence of IL-2RIF activity. These observations suggest that IL-2RIF activity is mediated by a novel cytokine(s) and the cytokine plays an important role as a second signal in the activation of the TH1 clone.

Animals↗

PubMed1992

Accumulation of crystallin in developing chicken lens.

Separation and quantitation of crystallin subunits in embryonic and post-hatched chicken lens were carried out by two-dimensional gel electrophoresis and an image analysing system in order to elucidate detail in the accumulation process of each crystallin subunit in lens differentiation. Complete separation of the subunits was possible when 7 M urea was included in the second dimension gel of the electrophoresis. In particular, beta-crystallin could be separated into more than 24 spots on the gel. These experiments showed that delta-crystallin accumulated rapidly during early development up to more than 80% of total crystallins, while beta-crystallin accumulated quickly only after hatching. In contrast with the contents of beta- and delta-crystallins, alpha-crystallin content in total crystallins was kept at approximately 18% throughout lens development. Therefore, it was concluded that crystallins accumulated in several different ways. This suggests that different regulation mechanisms work on the accumulation of each crystallin subunit and that the subunit composition of lens proteins is specific to each state of lens development.

Animals↗

PubMed1992

Development of hepatocellular carcinoma associated with increases in DNA synthesis in the surrounding cirrhosis.

The relationship between DNA synthesis activity in hepatocytes from cirrhotic tissue and development of hepatocellular carcinoma was studied in 33 posthepatitic patients with Child's grade A cirrhosis. DNA synthesis activity was measured by a bromodeoxyuridine (a thymidine analogue) labeling index, using the bromodeoxyuridine-antibromodeoxyuridine in vitro method, and the patients were followed up prospectively with frequent liver ultrasonography for 2 years. During the 2-year follow-up, 11 of the 33 cirrhotic patients developed hepatocellular carcinoma; they included 8 of the 15 patients (53%) in the high labeling index (greater than 1.5%) group compared with only 3 of the 18 patients (17%) in the low labeling index (less than 1.5) group (P less than 0.05). Five of the latter 18 subsequently had increased synthesis activity. Of these 20 patients who showed high synthesis activities either initially or subsequently, 10 (50%) developed hepatocellular carcinoma, in contrast to 1 of 13 (8%) with persistently low activities (P less than 0.05). Thus, hepatocellular carcinoma seems to develop or may become detectable when DNA synthesis in the background cirrhosis is increasing or remains high.

Adult↗

PubMed1992

Hepatic resection for metastatic squamous cell carcinoma from the uterine cervix.

A solitary hepatic tumor was diagnosed 3.5 years after a 67-year-old woman had undergone radical hysterectomy and postoperative irradiation for stage Ib squamous cell carcinoma of the cervix. Hepatic resection confirmed squamous cell carcinoma that had metastasized from the uterine cervix. One year and 10 months following hepatic resection, this patient is doing well with no evidence of any recurrence. This is a report of successful hepatic resection for metastatic carcinoma from the uterine cervix.

Aged↗

PubMed1992

Structural requirements for the effects of neuropeptide Y on the hypothalamic-pituitary-adrenal axis in the dog.

Neuropeptide Y (NPY), administered into the third cerebral ventricle of the dog stimulates plasma ACTH and cortisol secretion. To further investigate the structure-activity relationships of this action, we examined the effect of COOH-terminal fragment, NPY 19-36 and its analogues, NPY-(1-36)-OH (deamidated NPY) and avian pancreatic polypeptide (APP) on ACTH-cortisol secretion following intracerebroventricular (i.c.v.) injection in the dog. NPY (1.19 nmol) evoked a significant increase in the secretion of both plasma ACTH and cortisol. However, NPY 19-36 and NPY-(1-36)-OH each failed to increase plasma ACTH and cortisol secretion at doses of 1.19-11.9 nmol injected i.c.v. APP was less active than NPY. These data demonstrate that the entire NPY molecule is required for the full expression of the stimulatory effect of NPY on the secretion of ACTH and cortisol.

Adrenocorticotropic Hormone↗

PubMed1992

Trisomy 4 in a case of acute lymphocytic leukemia (L1).

Trisomy 4 has been identified previously as a chromosome abnormality associated with acute nonlymphocytic leukemia (ANLL) with myelomonocytic lineage and in myelodysplastic syndromes (MDS). We report a case of acute lymphocytic leukemia (ALL) (French-American-British, FAB L1) in a 42-year-old Japanese man, with trisomy 4 as the sole chromosomal anomaly. Immunophenotypically, the leukemic blasts demonstrated reactivity with CD2, CD5, and CD7 and indicated on early stage of T cell.

Adult↗