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Biomedical subjects

J Suzuki

Publications and source records attributed to J Suzuki.

At least 199 records · Page 11Linked to original sources
PubMed1998

Effects of intracellular cyclic AMP modulators on human eosinophil survival, degranulation and CD11b expression.

BACKGROUND: Brochial asthma is characterized by infiltration of inflammatory cells such as lymphocytes and eosinophils. Theophylline is one of the most widely used drugs in the therapy of bronchial asthma, and phosphodiesterase (PDE) inhibition is thought to be an important mechanism of its anti-inflammatory actions. However, the detailed effects of PDE inhibition on eosinophils still remain unclear. METHODS: Eosinophils in peripheral blood obtained from normal subjects and patients with mild off-season allergic rhinitis were purified using CD16 negative selection. The following effects of theophylline (nonselective PDE inhibitor), KF19514 (selective PDE IV inhibitor), mirlinone (selective PDE III inhibitor), procaterol (beta2-adrenoceptor agonist) and N6, 2'-O-dibutyryladenosine 3'5'-cyclic monophosphate (dB-cAMP; AMP analogue) on eosinophils were examined: (1) survival in the presence of interleukin-5, (2) degranulation by granulocyte/macrophage colony-stimulating factor (GM-CSF) or platelet-activating factor (PAF), (3) CD11b expression under GM-CSF or PAF stimulation and (4) intracellular cAMP level. RESULTS: Eosinophil survival was inhibited by theophilline, KF19514 or procaterol. GM-CSF- or PAF-induced degranulation was inhibited by theophylline, KF19514, procaterol or dB-cAMP. CD11b up-regulation by PAF was inhibited by theophylline, KF19514 or dB-cAMP, while GM-CSF-stimulated CD11b up-regulation was not significantly inhibited by any of the drugs tested. The levels of intracellular cAMP were increased by theophylline, KF19514 and procaterol. CONCLUSIONS: Intracellular cAMP is an important factor in the regulation of eosinophil biological functions. PDE IV inhibitors and beta2-agonists are suggested to be useful for the treatment of bronchial asthma through inhibition of eosinophil effector function.

Bucladesine↗
PubMed1998

A case of a combination of Oguchi's disease and congenital retinoschisis.

We report here a rare case of a combination of Oguchi's disease and congenital retinoschisis. A 36-year-old male patient presented with a decrease in vision in both eyes and night blindness. Indirect ophthalmoscopy revealed bilateral macular stellate striations and golden-gray discoloration of the retina outside the vascular arcades. This discoloration turned to a normal retina after complete adaptation to darkness (Mizuo-Nakamura phenomenon).

Adult↗
PubMed1998

Bopindolol: a slowly dissociating antagonist from the beta-adrenoceptors in guinea pig atria.

The dissociating and/or residual inhibitory effects of bopindolol from beta-adrenoceptors of atria strips pretreated with this drug which was then washed out with buffers on the responses to isoprenaline were determined and compared with those of propranolol, pindolol, atenolol, and the two active metabolites of bopindolol: 18-502 and 20-785. Low concentrations of bopindolol (10(-9) to 10(-8) mol/l) and the active metabolite 18-502 (10(-9) mol/l) produced rightward shifts of the concentration-response curves. On the other hand, high concentrations of bopindolol (10(-7) mol/l) and metabolite 18-502 (10(-8) and 10(-7) mol/l) produced a reduced maximum response by isoprenaline, suggesting that these nonparallel rightward shifts have pD2 values of 7.57 (bopindolol) and 7.67 (18-502), respectively, at 0 min after washout with buffers. Pindolol (10(-7) mol/l) and propranolol (10(-7) and 10(-8) mol/l) also produced a rightward shift of isoprenaline response curves, and these concentration-response curves in guinea pig atria strips pretreated with pindolol (10(-7) mol/l) and propranolol (10(-6) mol/l) recovered to control levels. Neither of these drugs, however, reduced the maximum response by isoprenaline. A high concentration (10(-5) mol/l) of atenolol was required for a rightward shift of the isoprenaline concentration-response curve, and this drug also did not reduce the maximum response. Thus, we conclude that bopindolol and metabolite 18-502 slowly dissociate and act as noncompetitive beta-antagonists rather than easily reversible beta-adrenoceptor antagonists.

Adrenergic beta-Agonists↗
PubMed1998

Automatic system for the assay of guanidino compounds to assess uremic status and effect of hemodialysis.

An automated HPLC system coupled with fluorometry was established for the sensitive, rapid, and accurate assay of serum guanidines. Naturally fluorescent materials characteristic of the sera of uremic patients (uremic fluorescences) which interfere with the assay were removed simultaneously with deproteinization. Application of this method revealed that the uremic patients who are capable of excreting urine under hemodialysis therapy show low serum guanidinosuccinic acid levels. The interval between hemodialysis sessions in one of these patients was prolonged while monitoring guanidinosuccinic acid level using the present method without any hazardous effect.

Autoanalysis↗
PubMed1998

New approaches to the management of acute and chronic cardiac allograft rejection.

There are still many problems to be faced in the field of heart transplantation. Acute and chronic rejection are still the major medical obstacles. In this review, we describe recent research in this field undertaken in our laboratory. The induced intercellular adhesion molecule-1 (ICAM-1) and MHC class II antigen resulting from rejection can be visualized in vivo by radioimmunoscintigraphy. This non-invasive method is sensitive for detecting early rejection and allows quantitative assessment of rejection. Short-term administration of monoclonal antibodies to ICAM-1 and leukocyte function-associated antigen-1 (LFA-1) results in an indefinite acceptance of cardiac allografts by induction of antigen-specific tolerance, as evidenced by acceptance of the secondary skin allografts. The characteristics and possible mechanisms of this tolerance induction are discussed. Immunohistopathologic features of graft coronary arteriopathy are shown. Adhesion molecules, cytokines, and growth factors are associated with intimal hyperplasia and phenotypic transformation of smooth muscle cells in the allograft coronary arteries. Dramatic reduction in this intimal hyperplasia was demonstrated by antisense gene therapy targeting cyclin-dependent kinase 2 kinase. We hope that these investigations will contribute to the improvement of the management of patients who undergo heart transplantation.

Acute Disease↗
PubMed1998

Adaptive changes in the capillary network in the left ventricle of rat heart.

Capillaries are nonuniform thin tubes: The arteriolar and venular capillary portions express alkaline phosphatase (AP) and dipeptidyl peptidase IV (DPPIV), respectively. Differences in enzyme activities between arteriolar and venular capillary portions could be shown by staining sections of cardiac tissues for AP and DPPIV after coronary infusion of microspheres and by staining cultured endothelial cells that had been collected from coronary microvessels. Through use of a double staining method for AP and DPPIV, adaptive changes in the capillary network were studied in rat hearts exposed to cold, exercise, hypertension, chronic coronary occlusion, and transient coronary occlusion followed by reperfusion. Two patterns could be seen in the adaptations of the ventricular capillary network. The increase in the venular capillary portions is accompanied by remarkable increases in capillary density and capillary-to-myocyte ratio. The increase in the arteriolar capillary portion seemed to be accompanied by a decrease or only a limited increase in capillary density in stressed hearts. The increase in the total capillary density improves the capacity for oxygen transport to tissues with a high tissue perfusion and a short diffusion distance for oxygen. The increase in the arteriolar capillaries may also improve oxygen transport by increasing the arterial blood perfusing the tissue. This seems, however, a compensation for the limited angiogenesis: The alleviation of stresses, such as pharmacological treatment of the hypertrophied heart and reperfusion after transient ischemia, increases venular capillary portions and capillary density. These changes are discussed with immunohistochemical observations of rapid and prolonged expressions of angiogenic growth factors.

Adaptation, Physiological↗
PubMed1998

Measuring the diameter of coronary arteries on MR angiograms using spatial profile curves.

OBJECTIVE: The spatial profile curve of the nuclear MR intensity across the short axis of a coronary artery in an MR angiogram results in a gradual up-and-down slope lacking sharp definition, which indicates that display parameters may influence edge recognition. Therefore, our study was designed to determine the appropriate window setting and to devise a method of accurately measuring the diameter or width of the artery independent of window parameters. CONCLUSION: The diameter of a coronary artery measured on MR coronary arteriography significantly varied with experimentally selected display parameters. When compared with the diameter on contrast-enhanced coronary arteriograms, the window center on MR angiograms at the midpoint between the peak intensity of the intravascular lumen and the background intensity and the window width of a quarter or a half of the intensity difference between the two were proven to be appropriate. The angiographic diameter corresponded to the diameter obtained at 65% +/- 9% of the peak intensity on the spatial profile curve across the short-axis MR coronary angiogram. Accordingly, 65% of the peak intensity indicates the diameter of the coronary artery. Thus, the intensity profile curve independent of the window setting provided a new method for measurement of the diameter of the coronary artery.

Adult↗
PubMed1998

Vector analysis of the hemodynamics of atherogenesis in the human thoracic aorta using MR velocity mapping.

OBJECTIVE: Our study was designed to assess the applicability of MR velocity mapping for vector analysis of the hemodynamics of atherogenesis. SUBJECTS AND METHODS: MR velocity mapping was used to measure axial and nonaxial elements and the length of the wall shear rate (a spatial gradient of near-wall flow velocity parallel to the vessel wall) vector at 16 time points per cardiac cycle at eight anatomic locations of the thoracic aorta in six healthy subjects. An oscillatory shear index (a ratio of blood flow volume in the recessive direction divided by the sum of blood flow volume in both dominant and recessive directions) was introduced for analysis of the degree of oscillation. RESULTS: The time-averaged length, axial element, and nonaxial element of the wall shear rate vector were 118+/-53 sec(-1), 106+/-55 sec(-1), and 33+/-23 sec(-1), respectively. The oscillatory shear index in the axial direction was 0.06+/-0.10 and that in the nonaxial direction was 0.07+/-0.13. At the inner wall of the distal portion of the aortic arch, the length of the wall shear rate was smallest (74+/-32 sec(-1)) and oscillation in the axial direction was largest (0.16+/-0.19). CONCLUSION: Vector analysis of the wall shear rate in the thoracic aorta was successfully done with MR velocity mapping in humans. MR velocity mapping can noninvasively evaluate the hemodynamics of atherogenesis induced by the complicated blood flow.

Adult↗
PubMed1998

Three-dimensional conformation of the epitopes of human superoxide dismutase-2 recognized by antibody against HIV-1p17.

We have previously reported that antibodies against HIV-1p17 protein cross-react with human superoxide dismutase-2 (SOD-2). To identify and characterize the epitopes of human SOD-2 recognized by anti-HIV-1p17 antibody, we synthesized several peptide fragments of human SOD-2 and found that the antibody did not bind to the LQPALK hexapeptide which is contained in both HIV-1p17 and human SOD-2. Instead, this antibody bound to four peptides which contain amino acid sequences similar, but not identical, to the known epitopes of HIV-1p17. These peptides have two features in three-dimensional (3-D) conformation: two protruded carbohydrate side chains on the peptide chain or a concave structure in the molecule. It is suggested that the antibody does not strictly recognize the amino acid sequence itself, but may recognize these 3-D conformations.

Animals↗
PubMed1998

Preliminary report on the short stature of Southeast Asian forest dwellers, the Manni, in southern Thailand: lack of an adolescent spurt in plasma IGF-I concentration.

Plasma concentration of insulin-like growth factor type-I (IGF-I) was studied among the Mannis in Thailand to find a possible cause of their short stature. The Mannis are hunting and gathering indigenous tribal peoples living in Asian tropical rain forests. A total of 50 plasma specimens from three different Manni groups in southern Thailand were used in this study. The concentrations of acid-ethanol extract of plasma IGF-I were measured by radio-immunoassay. We found that (1) plasma concentration of IGF-I in the Mannis was low, (2) there was no adolescent spurt in IGF-I levels, and (3) the post adolescent plasma IGF-I level of the Manni was significantly lower than that of age-matched Japanese. Low IGF-I levels among the Mannis may account for their short stature.

Adolescent↗
PubMed1998

Role of selectin-dependent adhesion in cardiac allograft rejection.

BACKGROUND: Selectins play important roles in the inflammatory responses by eliciting leukocyte rolling. The roles of E- and P-selectins in the acute rejection of cardiac allografts remain unclear. This study was designed to evaluate whether E- and P-selectins participate in the pathophysiology of heart rejection. METHODS: Heterotopic heart transplantation was performed in both mice and rats in full histoincompatibility combinations. Immunohistochemistry, flow-cytometry, and reverse transcriptase- polymerase chain reaction were performed to evaluate E-, P-selectin and sialyl Lewis X (SLeX) expression in rejecting cardiac allografts. The effects of short-term administration of monoclonal antibodies (mAbs) to E- and P-selectins on cardiac allograft survival were also evaluated. RESULTS: Significant prolongation of graft survival was observed in mice treated with either anti-E- or P-selectin mAbs, or both. The enhanced endothelial and mRNA expression of E- and P-selectins was observed in the rejecting cardiac allografts. Some graft- infiltrating mononuclear cells were double-stained with both anti-SLeX and anti-alphabetaT cell receptor mAbs. Flow-cytometric analysis of graft-infiltrating cells also showed enhanced SLeX expression. CONCLUSION: These results suggest that both P- and E-selectins are critically involved in the early development of acute heart rejection.

Animals↗
PubMed1998

[Changes of 24-h Holter monitor recordings in association with interferon alpha therapy for chronic hepatitis C].

We examined cardiovascular complication of interferon (IFN) therapy in 23 patients with chronic hepatitis C who did not have cardiac disease prospectively. Twenty four-h Holter monitor recordings were performed before and during IFN therapy. Seven of these patients (30%) showed abnormalities on their 24-h Holter monitoring recordings. Premature ventricular contraction (PVC) occurred in two patients, intermittent WPW syndrome in one, and ST-T change in four. Only one patient with PVC complained of palpitation. These complications were not severe and immediately after IFN therapy was stopped. There was no correlation between Holter ECG abnormalities and sex, age, quantity of HCV, or 2-5 oligoadenylate synthetase activity. It was suggested that cardiovascular complications caused by IFN therapy occurred more frequently than expected. However, diagnosis of these complications is difficult because most patients have no subjective symptoms and there is scarcely any change in laboratory test results. Careful observation of patients may be required during IFN therapy regardless of cardiovascular symptoms.

Adult↗
PubMed1998

[A pediatric case of myeloperoxidase-antineutrophil cytoplasmic (ANCA)-related crescentic glomerulonephritis associated with propylthiouracil treatment for Graves' disease].

We treated a 13-year-old girl who developed myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related crescentic glomerulonephritis (GN) during propylthiouracil (PTU) treatment for Graves' disease. MPO-ANCA-related crescentic GN during PTU therapy has been described previously in only one recent report of 2 children. We report this case here and describe 15 (13 adult cases) more patients with MPO-ANCA-related GN associated with PTU found in a literature review. The mean age at onset was 41.3 years, and the length of PTU administration ranged from 2 weeks to 6 years (mean 3.5 years). Clinical signs and symptoms were hematuria (100%), proteinuria (100%), arthralgia (7 of 16 cases; 43.8%), fever (4 cases; 20.0%), purpura (2 cases; 12.5%), skin ulcer (1 case; 6.3%) and dyspnea (1 case; 6.3%). These patients were treated with steroid (15 cases; 93.8%), cyclophosphamide (8 cases; 50.0%), steroid pulse therapy (4 cases; 25.0%), or plasma exchange (1 case; 6.3%), or were not treated (1 case; 6.3%). Most patients revealed crescentic GN (15 cases; 93.8%) on renal biopsy, while one exhibited mesangial proliferative GN (6.3%). For 2 of the 16 patients (12.5%) irreversible renal dysfunction persisted and hemodialysis was started. Patients with Graves' disease treated with PTU should be observed carefully by urinalysis and monitoring of the serum creatinine level.

Adolescent↗
PubMed1997

Regulation by differential development of Th1 and Th2 cells in peripheral tolerance to cardiac allograft induced by blocking ICAM-1/LFA-1 adhesion.

BACKGROUND: Specific immune tolerance to cardiac allografts is induced by anti-ICAM-1 and anti-LFA-1 MAbs. Although the expression of the Th1 cytokines IL-2 and IFN-gamma is shown to increase in association with acute rejection, the roles of cytokines in the induction of peripheral tolerance by anti-ICAM-1 and anti-LFA-1 MAbs are not yet known. METHODS AND RESULTS: BALB/c hearts were transplanted into C3H/He mice. The MAbs to ICAM-1 and LFA-1 were injected for 3 days after transplantation in some recipients, and others were treated with FK506. IL-2 concentration in the supernatant of splenocytes from MAb-treated mice that were mix-cultured with donor splenocytes was lower than in normal controls. The expression of Th1 cytokines, detected by Northern blot assay, was enhanced in grafts or spleens of nontreated mice, whereas Th2 cytokines were expressed in the spleens of MAb-treated mice. No cytokine expression was enhanced in mice treated with FK506. Also, the induction of tolerance was prevented by the administration of rIL-2 in vivo in 5 of 7 mice, which were rendered tolerant. CONCLUSIONS: These data provide evidence that impairment of IL-2 production is critically involved in this tolerance induction and suggest that predominance of Th2 over Th1 cells is essential for tolerance induction by antiadhesion therapy.

Animals↗
PubMed1997

An activated mutant of R-Ras inhibits cell death caused by cytokine deprivation in BaF3 cells in the presence of IGF-I.

R-Ras belongs to a family of low molecular weight GTP-binding proteins and exhibits 55% amino acid identity to H-Ras. It has been demonstrated that H-Ras inhibits cell death caused by interleukin-3 (IL-3) withdrawal in BaF3 cells (Kinoshita et al. (1995b); Terada et al. (1995)). In the present study, we examined whether R-Ras also rescues BaF3 cells from the factor-deprived cell death. To do this, several BaF3 transfectants were established, in which expression of wild-type as well as mutant R-Ras was regulated by an inducible promoter. Using these transfectants, we found that expression of an activated R-Ras mutant, R-Ras (Q87L), suppressed the death of IL-3-deprived BaF3 cells. On the other hand, expression of the wild-type and the dominant-negative mutant of R-Ras showed no inhibitory effect on cell death, indicating that R-Ras x GTP abrogated cell death caused by deprivation of IL-3. Furthermore, it was found that IGF-I in serum was required for the anti-apoptotic activity of R-Ras. Suppression of cell death by R-Ras(Q87L) was inhibited by wortmannin, LY294002 (phosphatidylinositol 3-kinase (PI3K) inhibitors), or PD98059 (inhibitor for MEK, a specific activator of mitogen-activated protein kinase (MAPK)). In addition, we have shown that, in HEK293 cells, R-Ras and IGF-I could activate MAPK synergistically. Also, PI3K activity was co-immunoprecipitated with an activated mutant of R-Ras. These results suggest that R-Ras in collaboration with IGF-I suppressed apoptotic cell death of BaF3 caused by IL-3 deprivation, presumably by modulating the activitites of MAPK and PI3K.

Androstadienes↗
PubMed1997

Effects of various types of Triton X on the susceptibilities of methicillin-resistant staphylococci to oxacillin.

We examined the effect of six types of the nonionic detergent Triton X on the susceptibilities of methicillin-resistant staphylococci to oxacillin. We used five methicillin-resistant Staphylococcus aureus isolates and 17 methicillin-resistant coagulase-negative staphylococci isolates. All strains of S. aureus, S. epidermidis and S. sciuri had enhanced susceptibility to oxacillin following exposure to the types of Triton X having 7-13 polymerized ethylene oxides. These strains were altered from homogeneously resistant to heterogeneously resistant by Triton X-100. Those types of Triton X that affected the resistance level also promoted the release of lipoteichoic acid. These results and those of previous studies suggest that Triton X might act on factors other than the mecA or femA products.

Detergents↗
PubMed1997

Amended structure of side chains in a cell wall mannan from Candida albicans serotype A strain grown in yeast extract-Sabouraud liquid medium under acidic conditions: detection of the branched side chains corresponding to antigenic factor 4.

In a previous study, we reported the excess production of alpha-1,3-linked mannose residues with the complete disappearance of beta-1,2-linked mannose residues in cell wall mannans of Candida albicans serotype A strain cells, which were grown in yeast extract-Sabouraud liquid medium at pH 2.0. In the present study, we examined the immunochemical reactivity of the same mannan of NIH A-207 with an enzyme-linked immunosorbent assay (ELISA) using several antisera to antigenic factors of the genus Candida (FAbs) and the structure of the mannan by two-dimensional homonuclear Hartmann-Hahn analysis. The ELISA showed that the mannan reacts to FAb 4 but not to FAbs 13b and 34, which are reported to be antibody factors against linear side chains containing an alpha-1,3-linked mannose residue. In the Hartmann-Hahn analysis, we found two branched side chains, Man alpha 1-2Man alpha 1-3[Man alpha 1-6]Man alpha 1-(2Man alpha 1-)(2)2Man and Man alpha 1-3[Man alpha 1-6]Man alpha 1-(2Man alpha 1-)(2)2Man, instead of the previously reported linear side chains. The branched side chains are oversynthesized under acidic conditions.

Antibodies, Fungal↗