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Biomedical subjects

M Nishio

Publications and source records attributed to M Nishio.

At least 145 records · Page 8Linked to original sources
PubMed1997

Treatment of squamous cell carcinoma of the esophagus with alternating radiotherapy and chemotherapy (cisplatin, methotrexate, and peplomycin).

Between 1985 and 1990, 20 patients with stage 2 and 3 esophageal cancer without esophagopulmonary fistulas were treated with alternating radiotherapy and chemotherapy (cisplatin, methotrexate, and peplomycin). Patients given the combined therapy received courses of chemotherapy during weeks 1 and 6 and radiotherapy during weeks 2-5 and 7-9. Chemotherapy consisted of i.v. cisplatin (80 mg/ m2 of body surface area) on day 1, i.v. methotrexate (40 mg/ m2) on day 2, and s.c. peplomycin (10 mg/day) continuously from day 2 to day 5. Radiotherapy was external irradiation with or without intracavitary irradiation. In seven cases, external irradiation alone was administered at 65-70 Gy, and in 13 cases, external irradiation (50-55 Gy) was combined with intracavitary irradiation (14-20 Gy). At the end of treatment, the rate of complete response was 60% with an overall response rate of 95%. Five-year total survival was 25%; cause-specific survival was 36.8%. The most common acute toxicities were bone marrow suppression, hepatic and renal damage, pneumonitis, and esophagitis. There was no life-threatening toxicity.

Aged↗
PubMed1997

An anti-fusion regulatory protein-1 monoclonal antibody suppresses human parainfluenza virus type 2-induced cell fusion.

Fusion regulatory protein-1 (FRP-1) regulates virus-mediated cell fusion and induces poly-karyocyte formation of monocytes without any fusogen. We have recently reported that FRP-1 and the 4F2/CD98 heavy chain are identical molecules. Cell fusion in Newcastle disease virus (NDV)-infected HeLa cells was enhanced when cells were incubated with anti-FRP-1 MAb. Anti-FRP-1 MAbs also induced human immunodeficiency virus gp160-mediated cell fusion. However, HBJ127, an anti-FRP-1/4F2/CD98 MAb that enhanced cell fusion in NDV-infected cells, delayed human parainfluenza virus type 2 (HPIV-2)-induced cell fusion in HeLa cells, although these viruses belong to the same genus Rubulavirus. No anti-FRP-1 MAbs enhanced cell fusion in HPIV-2-infected HeLa cells. Anti-FRP-1 MAbs including HBJ127 showed no effect on virus growth and expression levels of virus-specific poly-peptides in HPIV-2-infected HeLa cells, indicating that the delay in cell fusion by an anti-FRP-1 MAb is not due to suppression of virus replication. When HeLa cells were transfected with an expression vector harbouring HPIV-2 HN and F genes, cell fusion was also suppressed by HBJI27, but the effect was weak in comparison with virus-infected cells. These data indicate anti-FRP-1 antibodies not only induce/enhance, but also inhibit/delay virus-induced cell fusion and therefore FRP-1 molecules are multifunctional.

Animals↗
PubMed1997

Paramyxovirus-induced syncytium cell formation is suppressed by a dominant negative fusion regulatory protein-1 (FRP-1)/CD98 mutated construct: an important role of FRP-1 in virus-induced cell fusion.

Syncytium formation and subsequent generalized cell fusion have been reported as potentially important mechanisms of virus-induced cytotoxic effects. We tried to clarify the roles of fusion regulatory factor-1 (FRP-1) in virus-induced cell fusion. Two mutated human FRP-1/CD98 proteins [FRP-1/HN, in which the cytoplasmic domain was replaced with the cytoplasmic domain of human parainfluenza virus type 2 (HPIV-2) haemagglutinin-neuraminidase (HN), and FRP-1/330 (serine), in which a cysteine at amino acid 330 was mutated to serine], when expressed stably in L929 cells, were lacking in cell-fusion-enhancing activity stimulated by anti-FRP-1 antibodies. Anti-FRP-1 antibodies enhanced Newcastle disease virus (NDV)-mediated polykaryocyte formation in parent HeLa cells, while anti-FRP-1 antibodies showed no/low effect on polykaryocyte formation in NDV-infected HeLa cells constitutively expressing FRP-1/HN (HeLa-FRP-1/HN cells), indicating that the FRP-1/HN molecule is capable of acting as a dominant negative inhibitor. Furthermore, when HeLa-FRP-1/HN cells were infected with various rubulaviruses (HPIV-2, mumps virus, simian viruses 5 and 41), virus-induced cell fusion was also suppressed, although virus replication was not inhibited in these cells, showing that FRP-1 molecules are required for virus-induced cell fusion. Therefore, FRP-1 is considered to be related to the pathogenesis of paramyxoviruses.

Animals↗
PubMed1997

Human parainfluenza virus type 2 phosphoprotein: mapping of monoclonal antibody epitopes and location of the multimerization domain.

The epitopes recognized by 42 monoclonal antibodies directed against the human parainfluenza virus type 2 (hPIV-2) phosphoprotein (P) were mapped on the primary structure of the P protein by testing their reactivities with deletion mutants. By Western Immunoblotting with these monoclonal antibodies and P protein deletion mutants the region essential for P-P interactions was determined. The P protein region encompassing amino acids 211-248 was required for proper folding and oligomerization which is mediated by predicted coiled-coils in this region. The oligomer was shown to be a homotrimer by chemical cross-linking experiments.

Animals↗
PubMed1997

Interferon-gamma-inducing factor gene transfection into Lewis lung carcinoma cells reduces tumorigenicity in vivo.

To investigate the immunoregulatory effect of murine interferon-gamma-inducing factor (mIGIF), we transfected Lewis lung carcinoma (LLC) cells with a mammalian expression vector containing the mIGIF complementary DNA. The culture medium of the transfectant cells stimulated interferon-gamma (IFN-gamma) production by spleen cells in vitro in the presence of anti-CD3 antibody and markedly potentiated the effect of interleukin-12 (IL-12) on IFN-gamma production by spleen cells. mIGIF transfectant cells showed reduction of tumorigenicity and induction of an in vivo immuno-protective effect against the parental LLC cells. To examine the combined effect of systemic administration of recombinant IL-12 (rIL-12) and local mIGIF on the tumorigenicity, mice were challenged with LLC or transfectant cells on day 0, and the tumor-bearing mice were injected with 50 ng of rIL-12 intraperitoneally from day 7 to 11. Systemic rIL-12 showed an anti-tumor effect. However, mIGIF gene expression did not potentiate this effect of systemic rIL-12 in vivo.

Animals↗
PubMed1997

Traumatic tricuspid regurgitation associated with congenital partial pericardial defect.

Traumatic tricuspid regurgitation (TR) and congenital pericardial defects are rare conditions, there being fewer than 200 recorded cases of each. Here we describe the interesting case of a patient with traumatic TR due to rupture of chordae tendineae in association with a congenital pericardial defect. We suggest that the association of traumatic TR and congenital pericardial defect has a high probability of occurrence. We hypothesize that traumatic rupture of valvular structures occurs readily in patients with congenital pericardial defects.

Aged↗
PubMed1997

TMC-2A, -2B and -2C, novel dipeptidyl peptidase IV inhibitors produced by Aspergillus oryzae A374. I. Taxonomy of producing strain, fermentation, and biochemical properties.

TMC-2A(1), -2B (2) and -2C (3), novel dipeptidyl peptidase IV (DPIV) inhibitors, were isolated from the fermentation broth of Aspergillus oryzae A374. TMC-2A, -2B and -2C inhibited rat kidney DPIV with IC50 value of 8.1 microM, 17 microM, and 20 microM, respectively, as well as human DPIV prepared from mononuclear cells and adenocarcinoma cells. TMC-2 compounds inhibited only DPIV among the proteases tested, indicating their high selectivity for DPIV. The kinetic analyses revealed that TMC-2A was an uncompetitive inhibitor. Taxonomy and fermentation of the producing strain are also described.

Animals↗
PubMed1997

TMC-2A, -2B and -2C, new dipeptidyl peptidase IV inhibitors produced by Aspergillus oryzae A374. II. Isolation and structure determination.

New dipeptidyl peptidase IV inhibitors, TMC-2A, -2B, and -2C, were isolated from the fermentation broth of Aspergillus oryzae A374. On the basis of chemical, spectroscopic and X-ray crystallographic analyses, their structures were established to be peptide-like compounds composed of three moieties, L-tryptophan, mono- or dihydroxy-L-leucine and highly substituted isoquinoline.

Amino Acids↗
PubMed1997

Structure-activity relationships of spontaneous nitric oxide releasers, FK409 and its derivatives.

(+/-)-(E)-4-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409) shows both potent in vitro vasorelaxant and antiplatelet activities via nitric oxide (NO) generated spontaneously from the compound. In this study, we measured spontaneous NO-releasing rates of a series of FK409 derivatives, of which chain lengths or substituents were systematically modified, in sodium-phosphate buffer solution at pH 7.4. Furthermore, we studied their in vitro antiplatelet and vasorelaxant effects to evaluate relationships between spontaneous NO-releasing activities of FK409 analogs and their biological activities. FK409 derivatives were found to possess different spontaneous NO-releasing rates and biological activities according to their structural modification. In addition, these studies revealed a close correlation between NO-releasing rates of FK409 derivatives and their in vitro antiplatelet activities in human platelet-rich plasma, whereas the in vitro vasorelaxant activities of these compounds in isolated rat aorta did not correlate with the rates of NO liberation. The vasorelaxant effects were supposed to be affected by the structural properties of FK409 derivatives as well as their NO-releasing abilities.

Animals↗
PubMed1997

Muscarinic inhibition of basal L-type calcium current in pacemaker cells from the rabbit atrioventricular node.

Effects of acetylcholine (ACh) on the L-type calcium current were examined in isolated atrioventricular nodal cells that exhibited spontaneous contractions. ACh (0.1 to 10 microM) inhibited basal calcium current dose-dependently. This inhibition was eliminated by dialysis with 8Br cAMP or cAMP-dependent kinase inhibitory peptide. Both extracellular N-ethylmaleimide 50 microM and intracellular GDPssS 0.2 mM abolished the ACh effect. Dialysis with cGMP or NG-monomethyl-L-arginine did not significantly affect ACh inhibition of basal calcium current. Similarly, cGMP-dependent protein kinase inhibitor KT5823 (1 microM) and the type II phosphodiesterase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (30 microM) did not attenuate the ACh effect. Therefore, ACh inhibits the basal calcium current in the atrioventricular node mainly by suppressing cAMP synthesis through the inhibitory GTP-binding protein.

Acetylcholine↗
PubMed1997

Prognostic significance of cyclin D1 and retinoblastoma expression in combination with p53 abnormalities in primary, resected non-small cell lung cancers.

This study was conducted to evaluate the prognostic significance of cyclin D1 and retinoblastoma (Rb) expression in combination with abnormal p53 accumulation in primary, resected non-small cell lung cancers (NSCLCs). We evaluated immunohistochemically the expression of cyclin D1 and Rb in 208 NSCLC patients whose resections were consecutively performed between January 1984 and December 1988 and determined their prognostic significance by comparison with follow-up data. Expression of cyclin D1 and Rb was detected immunohistochemically in 39 and 80% of the 208 NSCLCs, respectively. The Kaplan-Meier survival curve demonstrated that absence of cyclin D1 expression was significantly associated with shortened survival (P = 0.01 by the log-rank test), particularly in adenocarcinomas (n = 100; P = 0.004). Expression status of the Rb protein was not significantly associated with clinical outcome in any of the cohorts. The predictive power of these prognosticators was also assessed in combination with findings for abnormal p53 accumulation by multivariate analysis using the Cox proportional hazards modeling. Patients with cyclin D1-negative tumors had a significantly greater risk of earlier death than those with cyclin D1-positive tumors (risk ratio, 1.61; P = 0.03), particularly in adenocarcinomas (risk ratio, 2.49; P = 0.002). Cases showing abnormal p53 accumulation tended to have a shortened survival only when the tumors were adenocarcinomas (risk ratio, 1.75; P = 0.06). Absence of cyclin D1 expression may be a useful prognosticator for shortened survival in primary, resected NSCLCs with particular significance for adenocarcinomas. In contrast, Rb expression status is not a useful prognostic factor for any type of NSCLC.

Adenocarcinoma↗
PubMed1996

CD80 (B7.1) and CD54 (intracellular adhesion molecule-1) induce target cell susceptibility to promiscuous cytotoxic T cell lysis.

Overexpression of B7 and intracellular adhesion molecule-1 (ICAM-1) on syngeneic cells triggered MHC-unrestricted lysis by MHC-restricted CD8+ CTL without TCR/CD3 engagement. Both CD28/B7 and LFA-1/ICAM-1 interactions were required for MHC-nonrestricted cytotoxicity. Cytotoxicity was measured in 4-h and 16- to 18-h cytotoxicity assays. B7-ICAM-1 overexpression triggered perforin- and Fas ligand-mediated lysis, while TNF-alpha was not elicited in MHC-unrestricted cytotoxicity. These results suggest that target cells may elicit MHC-unrestricted lysis from CTL through up-regulation of membrane adherence and costimulatory receptors.

Animals↗
PubMed1996

Aberrant hypermethylation at the bcl-2 locus at 18q21 in human lung cancers.

Accumulating evidence suggests that altered DNA methylation may play a role in the oncogenesis of human neoplasms, including lung cancer. The presence of aberrant hypermthylations at 3p, 9p, 11p, ad 17p, which are known to be hot spots for allele loss in lung cancers, is suggested to be a reflection of the existence of tumor suppressor genes in these chromosomal regions. In the present study, we investigated the methylation status of the Rb locus at 13q14 as well as that of the bcl-2 locus at 18q21 in 134 lung cancer specimens, representing all major histological subtypes. As a result, 18q21 was identified to be the fifth chromosomal region affected by frequent tumor-specific aberrant hypermethylation in lung cancers. The occurrence of aberrant hypermethylation at the bcl-2 locus at 18q21 was restricted to non-small cell lung cancers, and among non-small cell lung cancers, such epigenetic aberrations were observed most frequently in adenocarcinomas without any association with bcl-2 expression. Interestingly, allelic loss at the bcl-2 locus was also seen in 40% (7 of 17 informative cases) of adenocarcinomas; this frequency was also the highest among values for the various histological subtypes of lung cancers. These results suggest that aberrant hypermethylation at the bcl-2 locus may be a reflection of a putative tumor suppressor gene residing at 18q21, and aberrant hypermethylation might play a role in its inactivation. In contrast, altered methylation status of the Rb locus appears to be quite rare in lung cancers, if present at all.

Adenocarcinoma↗
PubMed1996

Allelic-expression imbalance of the insulin-like growth factor 2 gene in hepatocellular carcinoma and underlying disease.

It has been well documented that the liver is an exceptional organ in which the monoallelic expression of insulin-like growth factor 2 (IGF2) due to genomic imprinting is relaxed during the postnatal period, resulting in biallelic expression thereafter. In the present study, changes in the status of genomic imprinting were examined in 15 hepatocellular carcinomas (HCCs) as well as in 29 liver biopsies of chronic hepatitis or liver cirrhosis without clinical evidence of HCC, following screening for heterozygotes with an ApaI polymorphism in IGF2 in 34 HCCs and 80 such non-HCC cases. Extreme allelic-expression imbalance, leading to restoration of monoallelic IGF2 expression, was observed in 15 (100%) of 15 informative HCCs for the polymorphism with this monoallelic IGF2 expression appearing to be non-random from the paternal allele. Interestingly, the same allelic-expression imbalance was also present in a significant fraction of noncancerous liver specimens of patients with underlying disease known to be associated with HCC development. In contrast, the status of genomic imprinting of H19, another gene closely mapped at 11p15 under opposite imprinting, was strictly maintained in seven (100%) of seven cases informative for an RsaI polymorphism of H19. Together with the previous reports on altered genomic imprinting of IGF2 and H19 in embryonal lesions such as Wilms tumors as well as in lung cancers, the results suggest that perturbations of imprinting status occur as locus and tumor-type specific events in the development of human cancers.

Alleles↗
PubMed1996

Na(+)-permeable channels induced by maitotoxin in guinea-pig single ventricular cells.

The characteristics of maitotoxin-induced single channel currents were studied in guinea-pig single ventricular cells using the cell-attached or inside-out configuration of the patch clamp. When the patch electrode was filled with normal Tyrode solution containing 10 nM maitotoxin, elementary currents flowing through the single channel were observed in the cell-attached patch. The amplitude of the single channel current at the resting potential was 1.6 +/- 0.1 pA. The current-voltage relation of the current was linear and the single channel conductance was 16.0 +/- 0.9 pS. The distribution of open times was fitted by a single exponential function (decay time constant: 27 ms), while that of closed times was fitted by the sum of two exponential functions (decay time constants: 1.6 and 34 ms). When the electrode solution was filled with the Ca(2+)-free Tyrode solution, maitotoxin also induced single channel currents with parameters similar to those in the normal Tyrode solution. Under inside-out patch clamp conditions and in 150 mM Na+ solution on both sides of the patch membrane, maitotoxin also induced single channel currents. Choline+ could not substitute for Na+. These results indicate that maitotoxin induces single ionic channels irrespective of the presence or absence of Ca2+ and that the charge carrier of the single channel current is Na+ rather than Ca2+. The increase in Na+ permeability through maitotoxin-induced channels may be possibly responsible for its biological actions.

Animals↗