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Biomedical subjects

Y Kono

Publications and source records attributed to Y Kono.

At least 127 records · Page 7Linked to original sources
PubMed1993

Pseudoautosomal region in schizophrenia: sex concordance of the affected sibpairs and the association study with DNA markers.

To test a hypothesis that the pseudoautosomal region of the sex chromosomes contributes to the pathogenesis of schizophrenia, we carried out the following studies: First, the sex concordant rates of 77 schizophrenic sibpairs were examined. Secondly, 46 schizophrenic patients and 150 healthy controls were tested for association with DXYS17, DXYS20, DXYS28, and MIC2 in the pseudoautosomal region. Sex concordant rates in sibpairs with schizophrenia were not higher than would be expected by chance. No significant associations were found between four DNA markers we tested and schizophrenia. These results did not support the hypothesis; however, linkage disequilibrium can only be detected if the marker and trait loci are located close enough. Linkage analyses in multiplex families need to be carried out before ruling out this region as a location for a gene for schizophrenia.

Chromosome Aberrations↗
PubMed1993

Hydrophobicity as the signal for selective degradation of hydroxyl radical-modified hemoglobin by the multicatalytic proteinase complex, proteasome.

Red blood cells (RBC) and many other cell types exhibit increased rates of proteolysis during exposure to oxygen radicals and other activated oxygen species (oxidative stress). One of the major RBC proteins modified and proteolytically degraded during oxidative stress is hemoglobin (Hb). We now show that Hb undergoes a partial unfolding (or denaturation) during exposure to hydroxyl radicals (.OH), with an increase in hydrophobicity (hydrophobic interaction chromatography). At low .OH/Hb molar ratios, oxidatively modified Hb exhibits increased proteolytic susceptibility during incubation with RBC lysates, cell-free extracts, Fraction II, a 40-80% (NH4)2SO4 fraction, and purified proteasome (the 670-kDa RBC multicatalytic proteinase complex that we have previously called macroxyproteinase. At higher .OH/Hb molar ratios covalent cross-linking between Hb tetramers, and decreased proteolytic susceptibility are observed. The selective degradation of .OH-modified Hb is an ATP- and ubiquitin-independent process (in fact ATP is slightly inhibitory), and antibody precipitation studies, as well as inhibitor studies, indicate that proteasome is responsible for at least 60-70% of the activity in RBC. We propose that the mechanism of oxidation-induced proteolysis involves exposure of hydrophobic amino acid R groups during the partial Hb unfolding (or partial denaturation) that occurs at relatively low .OH/Hb molar ratios. Peptide bonds flanked by hydrophobic residues are preferred substrates for the proteasome complex, which degrades .OH-modified Hb in a processive process involving apparent serine-protease, sulfhydryl-protease, and metallo-peptidase activities. Highly denatured and covalently cross-linked Hb molecules, produced at high .OH/Hb molar ratios, are poorly degraded in RBC lysates and at all stages of proteasome purification. These cross-linked Hb tetramers have molecular sizes of 120-180 kDa and are presumably too large to fit in the proteasome active site(s). Recognition of exposed hydrophobic amino acid R groups provides a simple, energy-independent, and universal explanation for the proteasome-dependent proteolysis that accompanies oxidative stress.

Animals↗
PubMed1993

Lack of association between bipolar affective disorder and tyrosine hydroxylase DNA marker.

Sixty-eight patients with bipolar affective disorder and 88 controls were investigated for genetic association of tyrosine hydroxylase (TH) restriction fragment length polymorphisms (RFLPs). No significant association between bipolar affective disorder and TH was found. Thus the hypothesis that TH is involved in the pathogenesis of bipolar affective disorder was not supported.

Adult↗
PubMed1993

Hemadsorptive activity of transfected COS-7 cells expressing BHV-1 glycoprotein gIII.

Bovine herpesvirus 1 (BHV-1) glycoprotein gIII plays an important role in virus adsorption. The SR alpha promoter expression vector containing BHV-1 gIII gene was transfected into COS-7 cells. Fluorescent antibody staining using a panel of monoclonal antibodies demonstrated antigenic authenticity with regard to at least three nonoverlapping neutralization sites as well as surface expression of the glycoprotein. C57BL mouse erythrocytes were found to absorb onto the gIII-expressing cells. The hemadsorbing activity was specifically inhibited by the monoclonal antibody blocking virus adsorption. Heparin, analog of cellular receptor for BHV-1, also prevented the erythrocytes from adsorbing to the cells and heparinase-treated erythrocytes showed no adsorption. These findings indicate that the gIII binds to the erythrocytes and probably to the host cells independently of other viral components.

Animals↗
PubMed1993

Estimation of myocardial damage in Kawasaki disease using antimyosin antibody.

In a retrospective study, 121 children with Kawasaki disease (KD) were investigated to determine (i) the incidence of myocardial damage using the antimyosin antibody (AMA) titer; (ii) the differences in the electrocardiograms between the AMA-positive and -negative patients; and (iii) the effect of treatment with intravenous gamma globulin (IVGG) on the AMA. Comparisons were made with 117 normal children (controls). Patients with KD showed a significantly higher mean AMA titer and more patients were positive for AMA than the controls. The AMA titer in the KD group was not related to the presence of coronary artery lesions. Electrocardiograms obtained during the acute and the convalescent stage of KD revealed that patients positive for AMA had a significantly lower voltage of T wave in lead V6 at week four than at week two of illness, whereas patients negative for AMA showed no T wave change after week two. The group treated with IVGG showed a significantly lower AMA titer than that not given IVGG. These observations suggest that myocardial damage occurs in some patients with KD which is unrelated to the presence of coronary artery lesions and that the treatment with IVGG reduces the AMA titer in patients with KD.

Adult↗
PubMed1993

Exponential correction of QT interval to minimize the effect of the heart rate in children.

The exponential correction of the QT interval (eQTc) was studied using 12,543 resting electrocardiograms obtained in children (first and seventh graders) who were screened for heart disease in Kagoshima City. The values of eQTc to minimize the effect of the RR interval were estimated using following exponential model, eQTc = (QT interval)/(RR interval)--k. The parameter k = 0.31 was found to be the most useful exponent. The distribution of eQTc values showed a hiatus or break at probability points near p < 0.001 or p < 0.0005. Tentative criteria for an abnormally long eQTc were selected using these points and the following convenient data: 0.430 and 0.435 for the male and female first graders, and 0.440 and 0.445 for the male and female seventh graders, increased by 0.005, respectively. Abnormal values must ultimately be selected using data on patients with the long QT syndrome; however, our findings suggest that the exponential correction of the QT interval may be useful in large-scale screening programs for detecting a QT prolongation in young school children.

Child↗
PubMed1993

Ultrastructure and cytochemical characteristics of leukocyte infected with Hepatozoon canis.

We have observed the ultrastructure of a canine leukocyte infected with Hepatozoon canis by transmission electron microscope. The infected leukocytes contained many small vesicles and a few typical granules in the cytoplasm. They also contained a few rough surfaced endoplasmic reticula, mitochondria and a segmented nucleus with condensed chromatin. Cytochemical analysis indicated that the infected leukocytes with H. canis contained little alkaline phosphatase, peroxidase, naphthol AS-D chloroacetate esterase or alpha naphthol acetate esterase. These results suggested that the infected leukocytes were neutrophils or monocytes which lost their typical characteristics.

Alkaline Phosphatase↗
PubMed1993

Inhibition of appearance of pH-dependent virus-cell fusion by neutralizing monoclonal antibodies to transmissible gastroenteritis virus.

Five MAbs, which showed neutralizing (NT) activity and recognized S (previously designated E2) glycoprotein of TGE virus TO-163, inhibited cell fusion by TGE virus in IB-RS-2 cells. Other S-specific MAbs with no NT activity did not inhibit the cell fusion. The results indicate that a neutralization epitope is same or very close to a fusion active site. The kinetics of membrane fusion following a reduction in pH were also investigated. The cell fusion appeared between 2 and 6 hr after the binding medium was added.

Animals↗
PubMed1993

Diversity of the virulence for C57BL mice among BHV-1 strains.

Virulence of bovid herpesvirus 1 (BHV-1) for C57BL suckling mice was compared among respiratory, genital and attenuated vaccine strains. The 50% mouse lethal dose of the respiratory strain was approximately 1,000-fold lower than that of the vaccine strain. The genital strain showed intermediate virulence. The kinetic studies suggested that the respiratory strain appeared to multiply in the brain of the animals, and that the genital and vaccine strains were eradicated from the animals.

Animals↗
PubMed1993

Cytokines and periodontal disease: immunopathological role of interleukins for B cell responses in chronic inflamed gingival tissues.

Localized and chronically-inflamed gingival tissues of adult periodontitis (AP) are generally characterized as a hyper-responsiveness of B lineage cells where increased numbers of plasma cells occur. It was previously shown that high numbers of IgG subclass antibody-secreting cells (e.g., IgG1 > IgG2 > IgG3 > or = IgG4) with significant numbers of IgA subclass antibody-producing cells were seen in enzymatically dissociated gingival mononuclear cells (GMC) from inflamed periodontal tissues. An interesting finding was that the frequency of IgA2 plasma cells was elevated in the severe stage of AP when compared with the moderate stage. IgM plasma cells were essentially not found in these tissues. To understand the cytokine involvement in these increased B cell responses in inflamed gingiva, GMC isolated from inflamed tissues of AP patients were examined for cytokine production, specifically for IL-2, IL-4, IL-5, and IL-6 at both the protein and mRNA levels, since these cytokines have been shown to be essential interleukins for the regulation of the B cell response. Freshly-isolated GMC and peripheral blood mononuclear cells (PBMC) from AP patients were initially examined for IL-6 production because of its essential role for the terminal differentiation of B cells to become Ig-producing plasma cells. High levels of IL-6 were produced by GMC but not by PBMC unless cells were stimulated with T cell mitogen. A similar findings was also obtained when levels of IL-6 specific mRNA were examined in GMC and PBMC.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1993

[Comparison of high-pass resolution perimetry and differential light sensitivity perimetry in glaucoma patients].

High-pass resolution perimetry (HRP) enables one to estimate the number of functioning retinal ganglion-cells. We investigated the correlation between HRP and Humphrey Field Analyzer 630 in 35 eyes of 23 primary open-angle glaucoma and 75 eyes of 46 normal-tension glaucoma patients. In a total of 110 eyes, both functional channels and global deviation of HRP were significantly correlated with MD (r = 0.74, p < 0.01: r = -0.71, p < 0.01, respectively). Local deviation of HRP was also significantly correlated with corrected pattern standard deviation (r = 0.77, p < 0.01). These correlations tended to be higher in eyes with more advanced field changes than in those with fewer changes. These results indicate that HRP may be useful for evaluation of glaucomatous visual field abnormalities. The observed discrepancies between the two different methods in early stage glaucoma may be attributable to differences in physiological factors tested in these methods.

Adult↗
PubMed1993

Gingival mononuclear cells from chronic inflammatory periodontal tissues produce interleukin (IL)-5 and IL-6 but not IL-2 and IL-4.

A unique characteristic of the localized inflammatory tissue in the periodontium (e.g., adult periodontitis [AP]) is the accumulation of IgG (IgG1 > IgG2 > IgG3 > or = IgG4) followed by IgA plasma cells (IgA1 > IgA2). However, the exact molecular mechanisms contributing to these elevated B-cell responses at the local disease site are still unknown. Thus, this study has examined the production of cytokines of importance in B-cell responses, e.g., interleukin (IL)-2, IL-4, IL-5, and IL-6 by gingival mononuclear cells (GMC) isolated from patients in severe stages of AP. These cytokines were assessed at the protein and messenger (m)RNA levels to understand their importance for the observed increased B-cell responses present in these tissues. Among the four cytokines tested by respective cytokine-specific, polymerase chain reaction and dot-blot hybridization, high levels of IL-5- and IL-6-specific mRNA were noted in GMC freshly isolated from AP patients. On the other hand, specific message for IL-2 and IL-4 were not present. Further, the analysis of culture supernatants of GMC also revealed that cells from AP patients spontaneously produced IL-5 and IL-6 but not IL-2 and IL-4. In contrast, when peripheral blood mononuclear cells isolated from the same patients were examined for these cytokines, no detectable levels of mRNA or secreted cytokines were noted. These results showed that GMC from localized inflammatory tissues in severe stages of AP possess a distinct cytokine profile represented by high levels of IL-5 and IL-6 mRNA expression and protein synthesis, whereas IL-2 and IL-4 were not detected. Further, this study supports the concept that AP is a localized inflammatory disease, because GMC from the inflamed tissue actively produce IL-5 and IL-6, whereas peripheral blood mononuclear cells from the same patients do not.

B-Lymphocytes↗
PubMed1992

Effects of IL6 on B cells in mucosal immune response and inflammation.

Freshly isolated surface IgA+ (sIgA+) B cells from human gut-associated lymphoreticular tissues (GALT), e.g. the appendix, express high levels of IL6 receptor (IL6R) and respond to IL6 with significant increases in the number of IgA-secreting cells. On the other hand, neither sIgM+ nor sIgG+ B cells from appendix express IL6R. When the effect of IL6 on IgA subclass antibody synthesis was examined, the numbers of both IgA1- and IgA2-producing cells were increased upon incubation of GALT B cells with IL6; however, 60-70% of IgA-secreting cells were IgA2 subclass. Aberrant local production of IL6 can contribute to increased B-cell responses that occur in mucosal inflammation such as gingiva of patients with adult periodontitis (AP). When gingival mononuclear cells (GMC) isolated from AP patients were cultured without any stimulus, GMC spontaneously produced biologically active IL6 which induced peripheral blood mononuclear cells (PBMC) from the same patients to become IgG- and IgA-producing cells. Further, mRNA extracted from GMC possessed high message for IL6. When the expression of IL6R was compared between GMC and PBMC isolated from AP patients, IL6R-bearing cells were only seen in the former population. Thus, a high production of IL6, which have the ability to regulate later stages of IL6R+ B-cell development and to induce them to become Ig-secreting plasma cells and to support plasmacytoma growth, are important immunopathological elements for the induction of the increased B-cell response region in inflamed mucosal tissues.

Appendix↗
PubMed1992

Sporadic congenital transmission of avian leukosis virus in hens discharging the virus into the oviducts.

The efficacy of the albumen test for infectious avian leukosis virus (ALV) was examined in detecting congenitally transmitting hens. Seventy-three White Leghorn non-viremic hens with antibody to ALV were used. Eleven of the hens shed infectious ALV into their egg albumen, whereas only 7 of the 11 ALV-positive hens shed ALV antigens. The egg albumen test for infectious ALV was shown to be more effective in detecting the congenitally transmitting hens than that for ALV antigens. Then, twenty of the 62 hens which shed no infectious ALV into the albumen were studied for transmission of ALV to their embryos and for discharging ALV into the oviduct and vagina. Six of the 50 embryos from 4 hens were found to be infected with ALV but all of the 227 embryos from remaining 16 hens were free from the infection. Discharge of the virus into the oviduct and vagina was found both in the 4 transmitting hens and in 6 of the 16 non-transmitting hens. These results suggest that the hens discharging ALV into the oviduct, even though they do not shed ALV into egg albumen, may transmit the virus sporadically to their embryos.

Animals↗
PubMed1992

[Diffuse subendocardial ischemia in a patient with aortic valve stenosis without coronary artery disease by exercise 201Tl SPECT].

A case of aortic valve stenosis without coronary artery disease was confirmed to have diffuse subendocardial ischemia by exercise Thallium-201 myocardial single photon emission computed tomography. A 72-year-old woman, who had been diagnosed as aortic valve stenosis, was admitted because of chest pain during exercise. In cardiac catheterization findings, the patient angiographically had normal coronary arteries and no asynergy of left ventricular wall motion. The peak flow velocity in continuous wave Doppler echocardiography was about 5.0 m/sec at aortic valve level, providing a pressure drop of 100 mmHg across a stenotic valve with calculating on a modified Bernoulli equation (PG = 4V2). Thallium-201 myocardial SPECT images during exercise showed a transient "dilation and a widespread wall thinning" of left ventricle with apical perfusion defect. Simultaneous electrocardiogram showed further ST depression and the patient had chest pain. In 6 months after aortic valve replacement the patient no longer demonstrated both apical perfusion defect and "wall thinning" in postoperative thallium-201 myocardial SPECT images and also had neither ST depression nor chest pain. Thus; a transient "dilation and wall thinning" of left ventricle in this patient is suspected to be a sign of diffuse subendocardial ischemia.

Aged↗
PubMed1991

Cytokine regulation of localized inflammation. Induction of activated B cells and IL-6-mediated polyclonal IgG and IgA synthesis in inflamed human gingiva.

It is well established that increased numbers of plasma cells occur in the localized tissues of chronic inflammatory diseases such as adult periodontitis, and enzymatic isolation has shown that most B lineage cells produce IgG-subclass with some IgA-subclass responses. It would be of importance to determine if excess production of cytokines in the localized lesion account for these responses and in the present study we have assessed gingival mononuclear cell (GMC) supernatants for cytokines that activate B cells including IL-6R expression and for levels of IL-6 present. Inasmuch as limited numbers (approximately 1 to 3 x 10(6) cells) of GMC were obtained from surgically removed tissues (approximately 400 mg), we have focused on the analysis of IL-6 production by GMC in this study. Further, initial evidence of additional cytokines that are produced by GMC and induce expression of IL-6R on resting B cells has been obtained. The GMC and PBMC from individual patients were cultured in the presence (or absence) of Con A. Higher levels of IL-6 were produced spontaneously by GMC when compared with Con A-stimulated PBMC. When PBMC cultures were supplemented with GMC supernatants obtained from the same patient, high numbers of spot-forming cells (SFC), mainly of IgG followed by IgA isotype, were seen. The induction of SFC by GMC supernatants was inhibited by incubation with a goat anti-human IL-6 antibody. When the effect of GMC supernatants on subclasses of PBMC SFC was determined, the response was IgG1 greater than IgG2 greater than IgG3 = IgG4 and IgA1 greater than IgA2, a pattern remarkably similar to the distribution of plasma cells in the GMC itself. To assess for cytokines in GMC supernatants that mediated B cell activation, supernatants containing anti-IL-6 were cultured with PBMC or purified B cells for 72 h. This treatment induced small proliferative B cell responses and elevated expression of IL-6R on B cells, but did not induce SFC responses. Further, incubation of B cells with GMC supernatants induced resting B cells (G0/G1) to enter the cell cycle (S and G2/M). Addition of human rIL-6 to these cultures on day 3 restored IgG- and IgA-subclass SFC responses by day 7. Cytokine-induced IL-6R expression also occurred in vivo because freshly isolated GMC expressed high levels of this receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

B-Lymphocytes↗