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T Kawamura

Publications and source records attributed to T Kawamura.

At least 181 records · Page 10Linked to original sources

Significance of mesangial expression of alpha-smooth muscle actin in the progression of IgA nephropathy.

To determine whether phenotypic modulation of mesangial and interstitial cells correlated with the long-term prognosis of IgA nephropathy (IgAN), we analyzed retrospectively 27 patients with IgAN whose creatinine clearance at the time of renal biopsy was normal. The patients were subdivided into two groups according to the course of renal function during follow-up. Thirteen patients maintained normal renal function for more than 15 years (stable group), and 14 progressed to end-stage renal disease (ESRD group). The score of mesangial cell cellularity in the ESRD group was significantly higher than in the stable group. Immunohistochemistry localized alpha-smooth muscle actin (alpha-SMA) in renal mesangial cells of approximately half these patients. Macrophages localized predominantly in the mesangial area in patients with mesangial expression of alpha-SMA, which was associated with the expression of macrophage-colony-stimulating factor. Noteworthily, the score of mesangial alpha-SMA expression and the incidence of patients with mesangial expression of alpha-SMA at the time of renal biopsy were markedly higher in the ESRD group than in the stable group. However, there was no significant difference in both the score of interstitial alpha-SMA expression and the incidence of patients with interstitial expression of alpha-SMA between these two groups. These results suggest that macrophages recruited into the mesangium may induce phenotypic modulation of mesangial cells and that mesangial alpha-SMA expression predicts a progressive decline in renal function in patients with IgAN.

Actins↗

Risk factors for IgA nephropathy: a case-control study in Japan.

To disclose the risk factors for immunoglobulin A nephropathy (IgAN), we conducted a case-control study in the Tokai area of central Japan. The subjects were 94 patients, aged 20 years or older at diagnosis, who had histologically confirmed IgAN. Two sex-, age-, and residence-matched controls were randomly selected for each case from the general population. Information on medical history and lifestyle was collected using a self-administered questionnaire. The strength of association between IgAN and a potential risk factor was assessed by calculating an odds ratio. A family history of chronic nephritis, susceptibility to the common cold, preference for salty foods, frequent consumption of raw eggs, and a high intake of carbohydrates, including rice, were significantly associated with an increased risk for IgAN. Alcohol consumption, use of antioxidant vitamin supplements, and a high intake of protein, fat, monounsaturated fatty acids, and all/n-3 polyunsaturated fatty acids were somewhat protective against IgAN. Episodes of tonsillitis and exposure to organic solvents were found not to be associated with the risk in the present study. Our findings may provide some clues to the cause of IgAN.

Adult↗

Thyrsiferyl 23-acetate and its derivatives induce apoptosis in various T- and B-leukemia cells.

Thyrsiferyl 23-acetate (TF-23A), a cytotoxic compound from marine red alga, induced a rapid cell death in various leukemic T- and B-cell lines. During incubation of Jurkat cells with TF-23A, condensation and fragmentation of nuclei occurred and clusters composed of uneven small cellular particles were formed. Concentration- and time-dependent DNA fragmentation was also induced by the incubation of the cells with TF-23A. These results demonstrate that the TF-23A-induced cell death follows a typical apoptotic process. The TF-23A-induced apoptosis was prevented by fetal calf serum and insulin, but not by EGF or PDGF. TF-23A and its several analogous compounds showed apoptosis-inducing activity. However, only TF-23A out of these compounds showed an inhibitory activity for protein phosphatase 2A, PP2A. These results strongly suggest that a structure of TF-23A involved in induction of apoptosis is different from that involved in the PP2A inhibition.

Animals↗

Trends in site-specific mortality from oral and pharyngeal cancer among Japanese males, 1950-94.

In order to obtain some etiological clues for oral and pharyngeal cancer in Japanese males, we examined mortality trends from cancer of the lip, buccal cavity and pharynx by site with other descriptive epidemiological features (1950-94). The data were obtained from Vital Statistics (Ministry of Health and Welfare, Japan). The 45-year trend in mortality was evaluated by computing crude and age-adjusted mortality rates, age-specific mortality rates, with birth cohort analysis. The crude mortality rate from cancer of the lip, buccal cavity and pharynx has increased by 3.7-fold, and age adjusted mortality rate by 1.7-fold in the 45-year period, with different mortality trends by site. In general, age-specific mortality has also been increasing with advancing age. The birth cohort analysis showed that the higher the mortality rate, the younger the birth cohort, but with different effects of birth cohort by site. Mortality from cancer of the lip, buccal cavity and pharynx has consistently been increasing in Japanese males from 1950 to 1994, with similar upward mortality trends for some specific sites.

Adult↗

Associations of medical status and physical fitness with periodontal disease.

To determine the possible associations of medical status and physical fitness with periodontal disease, a cross-sectional study was conducted. The subjects were 517 males and 113 females aged 23 to 83 years who participated in a multiphasic health test at the Aichi Prefectural Center of Health Care, Japan, from 1992 to 1997. Their periodontal status was assessed by means of the CPITN scoring system. To assess the strength of associations between the examined factors and the score, odds ratios were computed using ordinal logistic models. Conventional risk factors such as old age, smoking habits, and higher fasting plasma glucose and simplified debris index increased the risk of periodontal disease. Hypertension, hematuria, leucocytosis or thrombocytosis, positive C-reactive protein and higher serum alkaline phosphatase were positively associated with the score, whereas higher serum high-density lipoprotein cholesterol was related to a lower risk. Poor physical fitness affecting aerobic capacity, foot balance and reaction was associated with a higher CPITN score. These associations were independent of the conventional risk factors. Although these new potential risk factors should be further investigated for their causal relationship, our findings suggested a close relationship of oral health to medical status and physical fitness.

Adult↗

Fas/Fas ligand-mediated elimination of antigen-bearing Langerhans cells in draining lymph nodes.

Epidermal Langerhans cells (LC) are potent antigen-presenting cells (APC) that play a crucial part in initiating cutaneous immune responses. Although functional roles of LC as APC in the draining lymph node have been well investigated, little is known about the fate of LC after the antigen presentation to T cells. In this report, we demonstrate that antigen-bearing LC that migrated into the draining lymph nodes and were identified as fluorescent cells after skin painting with fluorescein isothiocyanate also expressed the Fas antigen. Clearance of the antigen-bearing LC was significantly delayed and the ratio of dead cells was reduced in Fas-deficient lpr and Fas ligand (FasL)-deficient gld mice at 2 days after skin painting, suggesting the involvement of a Fas/FasL-mediated pathway in the elimination of antigen-bearing LC in draining lymph nodes. These results suggest that a substantial population of LC after antigen presentation may undergo Fas/FasL-mediated apoptosis and that the elimination of active APC may be important for preventing excess immune responses.

Animals↗

Mechanisms involved in graft-versus-host disease induced by the disparity of minor histocompatibility M1s antigens.

In this study we investigated which type of T cells: high T-cell receptor (TCRhigh, cells of thymic origin) or intermediate TCR (TCRint, cells of extrathymic origin), expanded in the liver and other organs, resulting in the induction of graft-versus-host disease (GVHD) with minor lymphocyte stimulating (M1s) disparity. When 6.5 Gy-irradiated BALB/c (H-2d M1s-1b2a) mice were injected with interleukin-2 receptor beta-chain(-) (IL-2Rbeta(-)) CD3high cells purified from the spleen of B10.D2 (H-2d M1s-1b2b) mice, IL-2Rbeta(+)CD3high cells expanded in the liver and other organs of recipient mice. The majority of these cells were found to be IL-2Ralpha(-)Mel-14(-)CD4(+)Vbeta3(+) in GVHD mice. The CDR3 region in their TCR-alphabeta (i.e. N-Dbeta-N) was polyclonal, although there were skewed usages of Vbeta3 and Jbeta2.4. The majority of cells were confirmed to be of donor origin by the individual discrimination method, namely, they originated from isolated IL-2Rbeta(-)CD3high cells. Interestingly, these T cells lacked cytotoxicity against both a natural killer (NK)-sensitive target and thymocytes with M1s disparity and nondisparity. Another important finding was that activated granulocytes expanded at generalized sites in GVHD mice. The present results raise the possibility that M1s disparity is mainly recognized by TCRhigh cells with unique properties but that direct effector cells that induce GVHD might not be such T cells but rather accompanied granulocytes.

Adoptive Transfer↗

Smooth muscle tumors of the esophagus: clinicopathological findings in six patients.

Preoperatively, it is difficult to discriminate leiomyoma and leiomyosarcoma of the esophagus, which are rare smooth muscle tumors. The objective of this study was to evaluate the clinicopathological findings of this unusual lesion. A search of the surgery archives of the Toyama Prefectural Central Hospital of Pathology revealed six cases of esophageal smooth muscle tumors. Clinicopathological findings were reviewed retrospectively. Only three patients (50%) presented with dysphagia, and the remaining three patients were asymptomatic. These patients underwent surgical excision. Histologically four of the six tumors were leiomyomas, and the other two tumors were leiomyosarcomas. Two tumors were in the upper to middle esophagus, and the remaining four were in the distal esophagus. On endoscopic examination, all tumors were noted to be polypoid. The two leiomyosarcomas measured over 5 cm and the four leiomyomas less than 4 cm. Neither ulceration nor necrosis proved to be of use in discriminating leiomyoma and leiomyosarcoma. The two patients with leiomyosarcoma died of liver metastasis 10 and 22 months after the treatment. Patients with leiomyosarcoma presented with distant metastasis and/or recurrence, with hematogeneous metastasis being the predominant type of recurrence.

Adult↗

Effect of aldose reductase inhibitors on glucose-induced changes in sorbitol and myo-inositol metabolism in human neutrophils.

AIM: To investigate the influence of glucose and the efficacy of two different aldose reductase (AR) inhibitors, epalrestat and SNK-860, on the polyol pathway and myo-inositol metabolism in human neutrophils. METHODS: We incubated neutrophils with various concentrations of glucose and AR inhibitors. The neutrophils from healthy volunteers were incubated in the media containing 5-40 mmol/l glucose with or without an AR inhibitor. The sorbitol and myo-inositol contents, and myo-inositol uptake were measured by high performance liquid chromatography and radio isotope technique with 2-[3H]-myo-inositol. RESULTS: After 2 h incubation, the sorbitol content increased with rising extracellular glucose concentrations, while the myo-inositol content decreased. Both AR inhibitors reduced the sorbitol content in neutrophils exposed to 40 mmol/l glucose medium. A 70% fall in the myo-inositol content in neutrophils exposed to 40mmol/glucose medium was attenuated approximately 40% by the addition of AR inhibitors. myo-Inositol uptake into neutrophils was inhibited by high glucose. AR inhibitors significantly ameliorated the decrease in myo-inositol uptake, but did not completely normalize it. CONCLUSIONS: Our present in vitro studies showed that the glucose-induced metabolic alterations in human neutrophils were similar to those in tissues prone to diabetic complications, and that AR inhibitors effectively corrected glucose-induced imbalances of the polyol pathway and myo-inositol uptake in neutrophils. In addition, our study suggests that glucose-induced metabolic alterations may result in the neutrophil dysfunction and that an AR inhibitor may be capable ameliorating it.

Adult↗

Prostaglandin E1 transported into cells blocks the apoptotic signals induced by nerve growth factor deprivation.

Neuronal apoptosis in rat pheochromocytoma PC12 cells, which was confirmed by TUNEL (terminal transferase-mediated dUTP-biotin nick end-labeling) staining and detection of chromatin condensation, appeared within 8 h after nerve growth factor (NGF) deprivation. Prostaglandin (PG) E1 (10(-7)-10(6) M) reduced the incidence of apoptotic cell death in PC12 cells. The genes encoding PG transporter specific to prostaglandins such as PGE2 or PGF2alpha were expressed in the cell lines as shown by RT-PCR. Bromcresol green, an inhibitor of PG transporter, reversed the antiapoptotic effect of PGE1. Moreover, treatment of PC12 cells with an antisense oligonucleotide corresponding to PG transporter cDNA also blocked the inhibitory effects of PGE1 on apoptotic cell death. In addition, PGE1 counteracted the increased activities of stress-activated protein kinase/cJun N-terminal kinase within 1-2 h after NGF deprivation in PC12 cells. These results indicated that the antiapoptotic effect of PGE1 in NGF-deprived PC12 cells was achieved by inhibitory signals following uptake into neurons through the PG transporter.

Alprostadil↗

Bone marrow transplantation attenuates murine IgA nephropathy: role of a stem cell disorder.

BACKGROUND: The pathogenesis of IgA nephropathy is still obscure. The aim of this study was to investigate whether the fundamental pathogenesis of IgA nephropathy lies in bone marrow stem cells (BMCs). METHODS: We used donors of two different strains for bone marrow transplantation (BMT) into mice with a high content of serum IgA (ddY strain, HIGA mice), a murine model of IgA nephropathy. One group (B6-->HIGA, N = 5) received BMCs of C57BL/6j (B6) mice, and the other (HIGA-->HIGA, N = 8) were reconstituted with BMCs of HIGA mice. RESULTS: Twenty-six weeks after BMT, in B6-->HIGA mice, mesangial deposits of IgA and C3 were statistically milder than those in HIGA-->HIGA mice. Light microscopic observations disclosed that glomerular sclerosis and mesangial matrix expansion in B6-->HIGA mice were decreased compared with those in HIGA-->HIGA mice. These B6-->HIGA mice also excreted less urinary albumin than HIGA-->HIGA mice. Furthermore, serum levels of IgA in B6-->HIGA mice were markedly lower than those in HIGA-->HIGA mice. Size analysis of serum IgA revealed that macromolecular IgA were notably lower in B6-->HIGA mice than in HIGA-->HIGA mice. CONCLUSIONS: Our results suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells, and that BMT from normal donors can attenuate glomerular lesions in HIGA mice. This approach may offer a new avenue to study the pathogenesis of IgA nephropathy.

Age Factors↗

Up-regulation of glomerular extracellular matrix and transforming growth factor-beta expression in RF/J mice.

BACKGROUND: RF/J mice were first reported as a murine model of spontaneous glomerulosclerosis by Gude and Lupton in 1960, but the precise histologic characteristics and immunopathological background of this mouse have not been investigated further. METHODS: Measurements of serum levels of immunoglobulins, anti-single strand DNA (anti-ss-DNA) antibody, complement (C3), and circulating immune complex (IC) were performed. Analyses of glomerular histological and immunopathological lesions in association with the detection of mRNA expression of collagen IV, TGF-beta, matrix protein turnover related enzymes, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) and platelet-derived growth factor (PDGF) were also performed in young (10-week-old) and elderly (60-week-old) RF/J mice with age-matched BALB/C mice as the controls. RESULTS: High levels of serum IgA and IgG from as early as 20 weeks of age were noted in the RF/J mice. Serum anti-ss-DNA antibody of aged RF/J mice increased up to 23% of that of aged MRL-lpr/lpr mice, and serum C3 concentration significantly decreased with age, reaching lower levels than that of BALB/c mice. IgA-IC levels were significantly high compared to BALB/C mice both in the early and late stages of life, whereas IgG-IC levels were high only in mice younger than 20 weeks. Semiquantitative and quantitative analyzes of renal histopathological findings revealed significantly marked and age-related mesangial matrix expansion in RF/J mice, with increasing frequency of global glomerular sclerosis and tubulointerstitial damage. On the other hand, although precise measurements of glomerular cell numbers also showed an apparent augmentation in both young and old RF/J mice compared to BALB/C mice, glomerular cellularity decreased with age in RF/J mice. Immunohistochemical study revealed massive immunoglobulin deposition from a young age in association with significantly higher accumulation of matrix proteins, such as types I and IV collagen and laminin from the early stage of life. In addition, in these glomeruli, transforming growth factor-beta1 (TGF-beta1) was highly expressed both in young and old mice. The mRNA expression of MMP-2 was up-regulated only in the early stage of life. Although PDGF mRNA of RF/J mice was significantly up-regulated in the early stage of life, the differences between the mice disappeared in the late stage of life. CONCLUSIONS: These findings suggest that in RF/J mice, an immunopathological background inducing high serum immunoglobulin and IC levels from the early stage of life is closely related to mesangioproliferative glomerular lesions mediated by PDGF, and that development of massive extracellular matrix accumulation in glomeruli was induced by up-regulated expression of TGF-beta with inappropriate regulation of protein turnover-related enzyme production.

Age Factors↗

Sudden death in the working population: a collaborative study in central Japan.

AIM: Few epidemiological data are available describing the sudden death of persons in their prime. This study aims to elucidate when and how sudden death occurs among employees. METHODS: A total of 196775 employees from 10 workplaces in Central Japan were surveyed for non-traumatic sudden death during 1989-1995. Demographic data and information regarding onset were collected by their workplace healthcare professionals. RESULTS: We identified 251 male and 13 female cases of sudden death. The annual incidence was 21.9 (for men) and 5.7 (for women) per 100000 population. Sudden death occurred more frequently in April when the new business year starts (risk ratio [95% confidence interval], 1.62 [0.94-2.79]) than in other months, without seasonality. Sudden death peaked on Sundays (risk ratio, 1.90 [1.20-2.99]) and Saturdays (risk ratio, 1.36 [0.83-2.21]) as compared with weekdays, and was likely to occur in the small hours (risk ratio, 1.71 [0.94-3.10] at 00-0300 h and 1.47 [0.79-2.72] at 0300-0600 h vs at 0900-1200 h. Only 17% of employees died at work, which was significantly less than expected (P<0.001). CONCLUSION: These findings differed from those of elderly people and suggest that sudden death of persons in their prime is related to occupational stress and its relief.

Adult↗

Resolved splenic accumulation of Tc-99m HMDP after recovery of disseminated intravascular coagulation in a patient with rhabdomyosarcoma.

Unusual, intense splenic radioactivity was seen on bone scintigraphy with Tc-99m HMDP in a 14-year-old boy with alveolar rhabdomyosarcoma complicated by disseminated intravascular coagulation. Abnormal splenic radioactivity was resolved after recovery from the disseminated intravascular coagulation. During treatment of disseminated intravascular coagulation and tumors, the patient received repeated blood transfusions, resulting in iron overload, but this did not prevent the abnormal splenic uptake from resolving. This case indicates that disseminated intravascular coagulation may be a cause of splenic accumulation of bone-seeking agents, and that abnormal splenic uptake can be resolved.

Adolescent↗

Influence of methylprednisolone on cytokine balance during cardiac surgery.

OBJECTIVE: To determine the influence of methylprednisolone on the cytokine balance during cardiac surgery. DESIGN: Prospective, randomized, nonblinded study. SETTING: University hospital. PATIENTS: Twenty-one patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery. INTERVENTIONS: According to a randomized sequence, the patients either received methylprednisolone (30 mg/kg) [corrected] before cardiopulmonary bypass and before declamping of the aorta (MPS group, n = 11) or received nothing (control group, n = 10). MEASUREMENTS AND MAIN RESULTS: Serum proinflammatory cytokines (interleukin [IL]-8, IL-6) and anti-inflammatory cytokines (IL-10, IL-1ra) were measured by enzyme-linked immunosorbent assays. Serum IL-6 and IL-8 concentrations in the control group (15.2 +/- 4.1 and 14.1 +/- 1.9 pg/mL, preoperatively) increased to 242 +/- 70.1 and 97.3 +/- 18.3 pg/mL at 60 mins after declamping of the aorta (p < .01, p < .01, respectively). The increases were greater than those from 2.5 +/- 0.6 and 2.5 +/- 0.5 pg/mL to 109.5 +/- 29.0 and 33 +/- 4.1 pg/mL in the MPS group for IL-6 and IL-8, respectively. Serum IL-10 concentrations increased significantly 60 mins after declamping of the aorta compared with its preoperative value in the two groups (the control group, from 1.0 +/- 0 to 537.9 +/- 61.7 pg/mL; the MPS group, from 0.3 +/- 0.2 to 654.9 +/- 24 pg/mL [p < .01, p < .01, respectively]). No difference was found between the two groups. Similarly, serum IL-1ra concentrations in the two groups increased the preoperative value in the control group from 304 +/- 120 to 44,374 +/- 14,631 pg/mL and in the MPS group from 616.5 +/- 109.6 to 35,598 +/- 9,074 pg/mL at 60 mins after declamping of the aorta (p < .01, p < .01, respectively). There was no difference between the two groups. CONCLUSIONS: Methylprednisolone reduces the production of IL-6 and IL-8 but not that of IL-10 and IL-1ra. These results suggest that one of the mechanisms of the cytoprotective effect of methylprednisolone may be to make changes in the proinflammatory and anti-inflammatory cytokine balance.

Aged↗

Identification and rapid quantification of early- and late-lytic human herpesvirus 8 infection in single cells by flow cytometric analysis: characterization of antiherpesvirus agents.

Human herpesvirus 8 (HHV-8) infection is associated with Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. In this study, we used monoclonal antibodies (MAbs) directed against HHV-8 lytic cycle-associated proteins encoded by open reading frame (ORF) 59 (nuclear PF-8 protein) and ORF K8.1 (viral envelope glycoprotein K8.1 [gpK8.1]) to investigate HHV-8 lytic infection in single cells. Lytically infected cells were labeled with MAbs, stained with fluorescently conjugated secondary Abs, and analyzed by flow cytometry. A 3-day stimulation of HHV-8-positive PEL cell lines (BCBL-1 and BC-3) with 12-O-tetradecanoylphorbol-13-acetate (30 nM) or n-butyric acid (0.3 mM) maximized the expression of lytic-phase viral proteins and minimized cell toxicity. The absolute number of expressing cells was inducer and cell line dependent. Expression of PF-8 occurred earlier and more frequently (in up to 20% of cells) than did expression of gpK8.1. A subset of PF-8 positive cells (25%) co-expressed gpK8.1, representing the majority of gpK8.1 expressing cells. Acyclovir, foscarnet, cidofovir, and PMEA reduced the number of cells expressing gpK8.1, but not the number expressing the nonstructural early lytic gene product PF-8. By contrast, alpha interferon (IFN-alpha) and IFN-beta reduced expression of both PF-8 and gpK8.1, implying an overall inhibitory effect on viral gene transcription or translation. In summary, we have characterized and quantified HHV-8 lytic infection in single cells by dual measurement of early- and late-lytic-cycle HHV-8 protein expression. This technique should prove useful for screening of possible antiherpesvirus agents and for detailed phenotypic characterization of HHV-8-infected cells in vitro and in patients with HHV-8-associated diseases.

Acyclovir↗

Esophageal sarcomas: report of three cases.

BACKGROUND/AIMS: Sarcomas of the esophagus, including carcinosarcoma, are rare neoplasms. METHODS: The clinical and pathologic characteristics of 3 patients with esophageal sarcomas are presented, including the only recorded esophageal carcinosarcoma and 2 patients with leiomyosarcoma. RESULTS: All 3 patients were males who presented with dysphagia or an abnormal shadow of the mediastinum on a plain chest X-ray. Two tumors were in the middle esophagus, and the remaining one was in the distal esophagus. On endoscopic examination, all three tumors were noted to be polypoid. These patients underwent surgical excision. One patient died 7 days following the operation, and the remaining 2 patients died of liver metastasis 10 and 22 months following the treatment. CONCLUSION: Esophagectomy or esophagogastrectomy is a surgical choice. Even if metastases are present, a palliative resection can still be performed.

Aged↗