M Yamamoto

Aichi Medical University, Okazaki, Aichi, Japan

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Publications (122)353.66 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The authors retrospectively examined whether long-term administration of tranilast improves semen parameters in severe oligoasthenozoospermia. Fifty-two patients presenting with sperm concentration of less than 10 x 10(6) sperm/mL were enrolled. Subjects were partitioned into 3 groups as follows: patients displaying an atrophic testis with elevated (FSH) (group 1), patients exhibiting normal testicular volume with elevated FSH (group 2), and patients with normal testicular volume and normal FSH levels (group 3). Tranilast (300mg/day) was administered until pregnancy was achieved or for a period of up to 12 months. Sperm concentration was significantly increased at 3 months in 16 subjects (44%) in groups 1 and 3. In group 2, sperm concentration was increased at 12 months (5 of 16 subjects; 31%). Total sperm count was obviously elevated at 3 months in groups 1 and 2, and at 6 months in group 3. Six pregnancies were achieved via natural intercourse. Tranilast, a mast cell blocker, demonstrates a certain clinical benefit in terms of improvement of semen parameters involving severe oligoasthenozoospermia, but it does not appear to afford clinical benefit in long-term administration.
    Archives of Andrology 07/2009; 48(6):451-9. · 0.89 Impact Factor
  • M Yamamoto, Y Tsuji, M Ohmura, H Hibi, K Miyake
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    ABSTRACT: To evaluate the effects of ligature of the internal spermatic artery at varicocelectomy on fertility, we conducted a prospective randomized study for comparison of two surgical methods (artery-ligated and artery-preserved). A total of 66 infertile patients with palpable varicocele was randomly assigned to an artery-ligated or artery-preserved group at varicocelectomy and the change in seminal characteristics and testis volume was prospectively investigated. Sperm density and motility improved significantly in the artery-ligated group. There was significant improvement in sperm density in the artery-preserved group, but motility did not reach the level of statistical significance in this group. The significant change in testis volume was not observed in both groups. Seven (23.3%) of 30 patients in the artery-ligated group and 5 (13.9%) of 36 men in the artery-preserved group managed to impregnate their partners. The difference was not statistically significant. In spite of the advocative advantage of artery preservation, our present study did not show any significant difference between artery-ligating and artery-preserving varicocelectomy when improvements in semen quality and pregnancy rate were assessed. Thus, artery-ligated varicocelectomy is warranted with regard to post-operative fertility in the patients with clinical varicocele.
    Andrologia 01/2009; 27(1):37-40. · 1.75 Impact Factor
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    ABSTRACT: Aortic valve sclerosis (AVS) may predispose to a prothrombotic state, as AVS is predictor of cardiovascular events in hypertensive populations. Thrombin exerts non-thrombotic effects such as vessel tone regulation, progression of atherosclerosis and stimulation of atrial natriuretic peptide (ANP) secretion. We hypothesized that hypertensive patients with AVS may have a persistently activated thrombin generation. We studied 234 asymptomatic never-treated hypertensive patients (73 of them with AVS). Prothrombin F1+2 (F1+2), as a marker of thrombin generation and fibrin D-dimer, as a marker of thrombus formation, ANP and brain natriuretic peptide (BNP) were measured. Presence of AVS, aortic jet velocity and left ventricular diameter at diastole were determined by echocardiography. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula. F1+2 (median and interquartile range (IQR) = 1.05, 0.87-1.38 nM vs. 0.93, 0.72-1.16) and ANP (22, 14-37 pg ml(-1) vs. 17, 11-25) levels were greater, and glomerular filtration rate values (65+/-9 ml min(-1)/1.73 m2 vs. 68+/-11) were lower in hypertensive patients with AVS than in those without AVS. F1+2 (odds ratio, 95% CI = 2.94, 1.07-8.6) was independently associated with AVS after being adjusted for age, gender and the variables of cardiorenal functions measured. After 6 months of treatment using valsartan, F1+2 levels remained elevated in hypertensive patients with AVS (1.14, 0.83-1.42 nM vs. 1.07, 0.84-1.5, n=19), but decreased in those without AVS (1.01, 0.85-1.31 vs. 0.8, 0.84-1.78, n=27). Thrombin generation was associated with AVS in untreated hypertensive patients, and this association was persistent after blood-pressure-lowering treatment using valsartan.
    Journal of Human Hypertension 11/2008; 22(11):781-7. · 2.82 Impact Factor
  • Journal of Molecular and Cellular Cardiology - J MOL CELL CARDIOL. 01/2006; 40(6):982-983.
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    ABSTRACT: We used multiple techniques to generate a three-dimensional anatomical model of the rabbit right atrium with the sinoatrial node (SAN) and atrioventricular node (AVN). The model includes the right atrium, SAN, AVN, part of right ventricle, aorta with aortic valve, superior vena cava, inferior vena cava, coronary sinus, tricuspid valve, part of mitral valve, fossa ovalis and central fibrous body. The tendon of Todaro and right and left sinoatrial ring bundles were highlighted as landmarks
    Computers in Cardiology, 2005; 10/2005
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    ABSTRACT: There is an effort to build an anatomically and biophysically detailed virtual heart, and, although there are models for the atria and ventricles, there is no model for the sinoatrial node (SAN). For the SAN to show pacemaking and drive atrial muscle, theoretically, there should be a gradient in electrical coupling from the center to the periphery of the SAN and an interdigitation of SAN and atrial cells at the periphery. Any model should include such features. Staining of rabbit SAN preparations for histology, middle neurofilament, atrial natriuretic peptide, and connexin (Cx) 43 revealed multiple cell types within and around the SAN (SAN and atrial cells, fibroblasts, and adipocytes). In contrast to atrial cells, all SAN cells expressed middle neurofilament (but not atrial natriuretic peptide) mRNA and protein. However, 2 distinct SAN cell types were observed: cells in the center (leading pacemaker site) were small, were organized in a mesh, and did not express Cx43. In contrast, cells in the periphery (exit pathway from the SAN) were large, were arranged predominantly in parallel, often expressed Cx43, and were mixed with atrial cells. An approximately 2.5-million-element array model of the SAN and surrounding atrium, incorporating all cell types, was constructed. For the first time, a 3D anatomically detailed mathematical model of the SAN has been constructed, and this shows the presence of a specialized interface between the SAN and atrial muscle.
    Circulation 03/2005; 111(7):846-54. · 15.20 Impact Factor
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    ABSTRACT: We used multiple techniques to construct 3D anatomical models of the rabbit sinoatrial node (SAN) and atrioventricular node (AVN). The 3D SAN model includes atrial muscle (only atrial cells), central SAN (only central SAN cells), peripheral SAN (a mixture of peripheral SAN cells, 'central' SAN cells and atrial cells), connective tissue and the sinus node artery. The 3D AVN model includes atrial muscle, ventricular muscle, AVN, a possible transitional zone (loosely packed atrial cells) and connective tissue (including the tendon of Todaro).
    Computers in Cardiology, 2004; 10/2004
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    ABSTRACT: Recent work on isolated sinoatrial node cells from rabbit has suggested that sarcoplasmic reticulum Ca2+ release plays a dominant role in the pacemaker potential, and ryanodine at a high concentration (30 micromol/L blocks sarcoplasmic reticulum Ca2+ release) abolishes pacemaking and at a lower concentration abolishes the chronotropic effect of beta-adrenergic stimulation. The aim of the present study was to test this hypothesis in the intact sinoatrial node of the rabbit. Spontaneous activity and the pattern of activation were recorded using a grid of 120 pairs of extracellular electrodes. Ryanodine 30 micromol/L did not abolish spontaneous activity or shift the position of the leading pacemaker site, although it slowed the spontaneous rate by 18.9+/-2.5% (n=6). After ryanodine treatment, beta-adrenergic stimulation still resulted in a substantial chronotropic effect (0.3 micromol/L isoproterenol increased spontaneous rate by 52.6+/-10.5%, n=5). In isolated sinoatrial node cells from rabbit, 30 micromol/L ryanodine slowed spontaneous rate by 21.5+/-2.6% (n=13). It is concluded that sarcoplasmic reticulum Ca2+ release does not play a dominating role in pacemaking in the sinoatrial node. The full text of this article is available at http://www.circresaha.org.
    Circulation Research 03/2003; 92(3):e41-4. · 11.86 Impact Factor
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    ABSTRACT: Enteric bacterial and/or food antigens may be crucial in the development of colitis but little is known of the exact mechanism of antigen specific reactions in this condition. The aim of this study was to determine whether systemically primed antigen specific CD4(+) T cells containing both CD45RB(high) and CD45RB(low) populations participate as a pathogenic subset that in turn leads to inflammatory reactions selectively in the large intestine. SCID mice were reconstituted with splenic CD4(+) CD45RB(+) T cells or CD4(+) CD45RB(low) T cells isolated from donor mice systemically primed with ovalbumin (OVA) plus CFA. The reconstituted mice were then fed OVA for several weeks. Reconstitution of SCID mice with OVA primed splenic CD4(+) T cells, containing populations of CD45RB(high) and CD45RB(low), resulted in the development of colitis by 4-5 weeks following repeated administration of oral OVA. Histopathological study revealed thickened wall, inflammatory cell infiltration, crypt elongation, and loss of goblet cells in the large intestine. The CD4(+) CD45RB(low) population of cells extracted from the affected large intestine secreted high levels of interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) at the protein and mRNA levels. Administration of neutralising antibodies to TNF-alpha, but not to IFN-gamma, prevented the development of colitis. Furthermore, adoptive transfer with OVA primed splenic CD4(+) CD45RB(low) T cells evoked severe colitis. These results demonstrate that systemically primed activated/memory CD4(+) CD45RB(low) T cells can mediate the development of specific antigen induced colitis in SCID mice, and also that TNF-alpha is critical in the induction of this type of colitis. Our results contrast with those from studies in some colitis models in which CD45RB(low) T cells appeared to prevent colitis through secretion of immunosuppressive cytokines.
    Gut 04/2002; 50(3):299-306. · 10.73 Impact Factor
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    ABSTRACT: We demonstrated that the mutant of cholera toxin (mCT) E112K which was LPS-free supported the induction of protective immunity in mucosal (e.g. lung lavage) and systemic (e.g. serum) compartments when given nasally with vaccine-grade diphtheria toxoid (DT) to mice. Significant DT-specific mucosal IgA antibody (Ab) and serum IgG, IgA and IgM Ab responses were induced when LPS-depleted mCT E112K or native CT (nCT) was co-administered nasally with DT. The analysis of DT-specific Ab-forming cell (AFC) responses supported the Ab titers and significant numbers of DT-specific IgA AFC were present in the lungs, nasal passages and submandibular glands. Furthermore, DT-specific IgG AFC in cervical lymph nodes (CLN) and the spleen were induced in mice administered with DT nasally with either mCT or nCT. The analysis of antigen-specific T cell responses revealed that increased DT-specific CD4+ T cell proliferative and Th2-type cytokine responses were induced in mice nasally-immunized with DT and the LPS-free form of mCT. The neutralization of diphtheria toxin by Abs showed that DT-specific IgG Ab responses in serum and lung lavages of mice immunized with DT and mCT were protective. Furthermore, it was shown that an IgA-enriched fraction of lung lavages possessed diphtheria toxin-specific neutralizing activity. These results are the first demonstration that nasally co-administered mCT E112K can induce DT-specific protective Ab responses in mucosal compartments (e.g. lung lavages and the lungs).
    Vaccine 01/2002; 20(5-6):756-62. · 3.49 Impact Factor
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    ABSTRACT: In this study, mice were immunized nasally with surface protein antigen of Streptococcus mutans serotype c (PAc) and a nontoxic A subunit mutant of cholera toxin (mCT) E112K, as a mucosal adjuvant. Immunization with PAc and mCT elicited significant PAc-specific secretory IgA in saliva and in nasal secretions. Antibody-forming cell (AFC) analysis confirmed the antibody (Ab) titers by revealing significant numbers of PAc-specific IgA AFCs in the submandibular gland and nasal passages. Furthermore, CD4(+) T cells from cervical lymph nodes exhibited significant proliferative responses when restimulated with PAc in vitro. Importantly, mice that were nasally immunized with PAc plus mCT E112K exhibited significantly reduced oral colonization by S. mutans. These results show that nasal administration of PAc and mCT E112K is potentially an effective mucosal vaccine against dental caries and reduces the colonization of S. mutans in the oral cavity.
    The Journal of Infectious Diseases 04/2001; 183(5):823-6. · 5.85 Impact Factor
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    ABSTRACT: To clarify the role of Peyer's patches in oral tolerance induction, BALB/c mice were treated in utero with lymphotoxin beta-receptor Ig fusion protein to generate mice lacking Peyer's patches. When these Peyer's patch-null mice were fed 25 mg of ovalbumin (OVA) before systemic immunization, OVA-specific IgG Ab responses in serum and spleen were seen, in marked contrast to low responses in OVA-fed normal mice. Further, high T-cell-proliferative- and delayed-type hypersensitivity responses were seen in Peyer's patch-null mice given oral OVA before systemic challenge. Higher levels of CD4(+) T-cell-derived IFN-gamma, IL-4, IL-5, and IL-10 syntheses were noted in Peyer's patch-null mice fed OVA, whereas OVA-fed normal mice had suppressed cytokine levels. In contrast, oral administration of trinitrobenzene sulfonic acid (TNBS) to Peyer's patch-null mice resulted in reduced TNBS-specific serum Abs and splenic B cell antitrinitrophenyl Ab-forming cell responses after skin painting with picryl chloride. Further, when delayed-type hypersensitivity and splenic T cell proliferative responses were examined, Peyer's patch-null mice fed TNBS were unresponsive to hapten. Peyer's patch-null mice fed trinitrophenyl-OVA failed to induce systemic unresponsiveness to hapten or protein. These findings show that organized Peyer's patches are required for oral tolerance to proteins, whereas haptens elicit systemic unresponsiveness via the intestinal epithelial cell barrier.
    Proceedings of the National Academy of Sciences 04/2001; 98(6):3310-5. · 9.81 Impact Factor
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    ABSTRACT: Cholera toxin (CT) and heat-labile toxin (LT) of Escherichia coli act as adjuvants for the enhancement of mucosal and serum antibody (Ab) responses to mucosally co-administered protein antigen (Ag). Both LT and CT induce B7-2 expression on antigen-presenting cells (APCs) for subsequent co-stimulatory signalling to CD4+ T cells. CT directly affects CD4+ T cells activated via the TCR-CD3 complex with selective inhibition of Th1 responses whereas LT maintains Th1 cytokine responses with inhibition of interleukin (IL)-4 production. Interestingly, while CT failed to induce mucosal adjuvant activity in the absence of IL-4, LT did so. Nontoxic mutant (m)CTs (S61F and E112K) retain adjuvant properties by inducing CD4+ Th2 cells, which provided effective help for the Ag-specific mucosal immunoglobulin (Ig)A, as well as serum IgG1, IgE and IgA Ab responses. The mCT E112K has been shown to exhibit two distinct mechanisms for its adjuvanticity. Firstly, mCT enhanced the B7-2 expression of APCs. Secondly, this nontoxic CT derivative directly affected CD4+ T cells and selectively inhibited Th1 cytokine responses. Thus, several lines of evidence indicate that enzyme activity can be separated from adjuvant properties of CT and this offers promise for the development of safe delivery of vaccines for mucosal IgA responses.
    Scandinavian Journal of Immunology 04/2001; 53(3):211-7. · 2.20 Impact Factor
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    ABSTRACT: Effects of brief postganglionic vagal nerve stimulation on the activation sequence of the rabbit sinoatrial (SA) node were investigated. Activation sequences in a small area (7 mm x 7 mm) on the epicardial surface were measured in a beat-to-beat manner using an extracellular potential mapping system composed of 64 modified bipolar electrodes with high-gain and low-frequency band-pass filtering. The leading pacemaker site was recognised clearly from both the activation sequence and the characteristic morphology of the potentials. Vagal stimulation resulted in a short-lasting initial slowing of spontaneous rate followed by a long-lasting secondary slowing; a brief period of relative or absolute acceleration was interposed between the two slowing phases. During these changes of spontaneous rate, the leading pacemaker site shifted in a complex beat-to-beat manner by 1-6 mm alongside the crista terminalis in the superior or inferior direction. For the first spontaneous excitation following stimulation, the greater the slowing, the larger the distance of the pacemaker shift. There was no such linear relationship between the extent of slowing and the distance of pacemaker shift for the subsequent beats. These changes in the leading pacemaker site in response to vagal stimulation may be the result of the functional and morphological heterogeneity of the mammalian SA node in terms of innervation, receptor distribution and ion channel densities. Experimental Physiology (2001) 86.2, 177-184.
    Experimental Physiology 04/2001; 86(2):177-84. · 2.79 Impact Factor
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    ABSTRACT: A new digital video imaging system was developed and its performance to analyze the spiral wave dynamics during polymorphic ventricular tachycardia (PVT) with high spatiotemporal resolution was evaluated. The epicardial surface of isolated rabbit heart stained with di-4-ANEPPS was illuminated by 120-high-power bluish-green light emitting diodes (LED). The fluorescence image (256×256 pixels) passing though a long-pass filter (lc=600 nm) was monitored by a high-speed digital video camera recorder (DVCR) at 750 fps. 2D images of excitation wave and single-pixel action potentials at target sites during S2-induced spiral reentry were displayed for 10.9 s. The waveform quality is high enough to observe phase 0 upstroke and to identify repolarization timing. The effects of Na<sup>+</sup> channel blockade was investigated by use of this system and the results suggest that Pilsicainide (3uM) caused the prolongation of the effective refractory period without affecting APD<sub>90</sub>, which was associated with the magnify of excitable gap and longer VT cycle length. Our new digital video-BGLED system has an advantage over previous ones for more accurate and longer time action potential analysis during spiral wave reentry.
    Engineering in Medicine and Biology Society, 2001. Proceedings of the 23rd Annual International Conference of the IEEE; 02/2001
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    ABSTRACT: The purpose of the present research is to analyze the behavior of the reentrant spiral wave, which is one of the main causes of sudden cardiac death using computer simulation models of cardiac excitation propagation. The simulation model is a two dimensional electric circuit network model where many electric circuit models of cardiac membrane action potential were connected with electric resistance standing for intra- and extra-cellular conductance. As cardiac membrane action potential model, we used BeeleReuter (DR) model and. LuoRudy (L-R) model. In order to investigate the effect of ionic current modification by antiarrhythmic drugs on the reentrant pattern, we controlled the sodium current, I<sub>Na</sub>, and the potassium current, I<sub>K</sub>, of the cardiac action potential models and investigated the obtained reentrant patterns. In order to validate the simulation results, we are comparing the reentry pattern under dose of anti-arrhythmic drugs observed by a high-resolution optical mapping system.
    Engineering in Medicine and Biology Society, 2001. Proceedings of the 23rd Annual International Conference of the IEEE; 02/2001
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    ABSTRACT: Although many drug treatments have been reported to theoretically improve semen parameters in male infertility, a standard method has not been established. The authors examined whether tranilast, a mast cell blocker, improves fertility and/or semen parameters in severe oligozoospermia. Seventeen patients with a sperm density of less than 10 x 10(6) sperm/mL and their fertile partners were enrolled in this study. Patients were prescribed tranilast 300 mg/day for at least 12 weeks. Semen and blood samples were collected before and after the prescription of tranilast for 12 weeks. Semen parameters, serum gonadotropins, luteinizing hormone, follicle-stimulating hormone, serum testosterone, and testicular size were evaluated. One patient complained of mild drowsiness during treatment. The sperm count was significantly increased after administration of tranilast in 7 patients (41.1%), although sperm motility was not altered. Semen volume and normal morphology were also unaltered. Three pregnancies were achieved. Endocrine profile and testicular size were unchanged. Tranilast, a mast cell blocker, is clinically useful for the treatment of severe idiopathic oligozoospermic men.
    Archives of Andrology 01/2001; 47(2):107-11. · 0.89 Impact Factor
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    ABSTRACT: Although obstructive azoospermia is treatable with microscopic seminal reconstruction, the number of patients who choose to undergo vasoepididymostomy is limited because of recent advances in assisted reproductive technology (ART). We attempted to define the outcome of surgical reconstruction in patients with suspected epididymal obstruction and no previous history of vasectomy. We described 40 eligible end-to-side vasoepididymostomy procedures performed on 24 azoospermic patients who had either bilateral or unilateral epididymal obstruction. The overall patency rate following surgery was 54% (13/24) and for four patients (17%), natural intercourse resulted in pregnancy. Two pregnancies were initiated with intracytoplasmic sperm injections using frozen sperm collected during vasoepididymostomy. In the era of modern ART, microsurgical vasoepididymostomy with cryopreservation of sperm collected during the operation is recommended for patients with epididymal obstructions.
    International Journal of Urology 01/2001; 7(12):435-9. · 1.73 Impact Factor
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    ABSTRACT: Systemically primed BALB/c mice developed severe diarrhea after repeated oral administration of ovalbumin (OVA). Histological analysis demonstrated that dramatic infiltration of eosinophils and mast cells occurred in the large intestine but not in the small intestine of mice with diarrhea. Interestingly, CD4(+) alphabeta T cells of the large intestine secreted IL-4 and IL-13 at high levels. Identically treated STAT6 gene-disrupted mice failed to develop OVA-induced diarrhea. Further, treatment of BALB/c mice with monoclonal anti-IL-4 antibody prevented the development of allergic diarrhea. An adoptive transfer study showed that systemically primed splenic CD4(+) T cells were preferentially recruited into the large intestine upon exposure to oral OVA. These results strongly suggest that systemically derived CD4(+) alphabeta T cells of the large intestine play a critical role in the onset of Th2-mediated intestinal allergic disorders via STAT6 signal transduction.
    Journal of Clinical Investigation 08/2000; 106(2):199-206. · 12.81 Impact Factor
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    ABSTRACT: In an in vitro study, Escherichia coli heat-labile toxin (LT) was shown to directly affect activated CD4(+) T cells and support interleukin (IL)-5 production in IL-4-deficient (IL-4(-/-)) mice, whereas cholera toxin (CT) did not. Both LT and CT enhanced B7-2 expression on B cells and macrophages. These effects were not influenced by CD40-CD40 ligand cosignaling. Addition of LT- or CT-treated antigen-presenting cells to anti-CD3-triggered CD4(+) T cells resulted in the induction of T cell proliferative responses. Further, these responses were inhibited by anti-B7-2 monoclonal antibody. Cocultivation of CD4(+) T cells with LT- or CT-treated antigen-presenting cells and anti-CD3 enhanced Th1- and IL-4-mediated Th2-type cytokine production. The results from in vitro studies were supported by in vivo studies in IL-4(-/-) mice, in which LT induced mucosal IgA responses but CT did not. Thus, although both LT and CT induce mucosal adjuvant responses via IL-4-dependent Th2-type responses, LT also elicits Th1- and IL-4-independent Th2-type responses.
    The Journal of Infectious Diseases 08/2000; 182(1):180-90. · 5.85 Impact Factor

Publication Stats

3k Citations
353.66 Total Impact Points


  • 2001–2009
    • Aichi Medical University
      • Department of Urology
      Okazaki, Aichi, Japan
    • International University of Health and Welfare
      Otahara, Tochigi, Japan
    • Tokyo Women's Medical University
      • Department of Cardiology
      Tokyo, Tokyo-to, Japan
  • 2005
    • The University of Manchester
      Manchester, England, United Kingdom
  • 1998–2005
    • University of Leeds
      • School of Biomedical Sciences
      Leeds, England, United Kingdom
  • 1993–2003
    • Nagoya University
      • • Research Institute of Environmental Medicine
      • • Division of Urology
      • • Division of Obstetrics and Gynecology
      Nagoya-shi, Aichi-ken, Japan
  • 2002
    • Niigata University
      • Division of Bacteriology
      Niahi-niigata, Niigata, Japan
  • 1999–2002
    • Osaka University
      • Mucosal Immunology Group
      Ibaraki, Osaka-fu, Japan
    • Kagoshima University
      • Department of Otolaryngology
      Kagosima, Kagoshima, Japan
  • 2000–2001
    • The University of Tokyo
      • • Faculty & Graduate School of Engineering
      • • Department of Precision Engineering
      Tokyo, Tokyo-to, Japan
    • Montana State University
      Bozeman, Montana, United States
    • Nihon University
      • Department of Clinical Pathology
      Edo, Tōkyō, Japan
  • 1996–2001
    • University of Alabama
      Tuscaloosa, Alabama, United States
  • 1992–1999
    • University of Alabama at Birmingham
      • • Department of Microbiology
      • • Department of Biomedical Engineering
      Birmingham, AL, United States