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Shinichi Sato

Publications and source records attributed to Shinichi Sato.

At least 55 records · Page 3Linked to original sources
PubMed2005

Successful treatment with sildenafil in systemic sclerosis patients with isolated pulmonary arterial hypertension: two case reports.

We describe two systemic sclerosis (SSc) patients with isolated pulmonary arterial hypertension (PAH) who were given treatment with 50 mg oral sildenafil per day. We evaluated the efficacy of oral sildenafil for isolated PAH in SSc patients by direct assessment with cardiac catheterization before and 6 months after the initiation of sildenafil. Right-heart catheterization demonstrated decreased mean pulmonary artery pressure, decreased pulmonary vascular resistance, and increased cardiac output after treatment with sildenafil. Brain natriuretic peptide levels were gradually decreased. The 6-min walking distance was greatly extended. Moreover, the physical conditions of both patients were much improved. We recognized no adverse events. We propose that oral sildenafil may be beneficial as a selective pulmonary vasodilator and as long-term treatment in SSc patients with isolated PAH.

Female↗
PubMed2005

Serum pulmonary and activation-regulated chemokine/CCL18 levels in patients with systemic sclerosis: a sensitive indicator of active pulmonary fibrosis.

OBJECTIVE: To clarify the clinical significance of serum levels of pulmonary and activation-regulated chemokine (PARC) in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc) and to compare PARC levels with KL-6 antigen or surfactant protein D (SP-D) levels. METHODS: Serum PARC levels were determined by enzyme-linked immunosorbent assay in 123 SSc patients. In a retrospective longitudinal study, correlation of serum PARC levels with the activity of PF was assessed in 21 SSc patients with active PF. RESULTS: PARC levels at the first visit were higher in patients with SSc than in patients with systemic lupus erythematosus (SLE) or healthy controls. Increased serum PARC levels were associated with involvement of PF, decreased diffusing capacity for carbon monoxide, and decreased vital capacity in SSc patients. In the longitudinal study, serum PARC levels were significantly decreased in SSc patients with inactive PF compared with those with active PF. CONCLUSION: Elevated serum PARC levels correlated with PF and more sensitively reflected the PF activity than did serum KL-6 or SP-D levels in SSc. Serum PARC levels may be a useful new serum marker for active PF in SSc.

Antigens↗
PubMed2005

Humoral autoimmunity in mice overexpressing B cell surface CD19: vital role for MHC class II.

B6 mice bearing a transgene (Tg) for human CD19 (hCD19) harbor increased numbers of splenic Ig-secreting cells (IgSC), increased serum levels of total Ig and autoantibodies, but decreased numbers of splenic B cells. To assess the influence of MHC class II (MHCII) to this phenotype, MHCII-deficient CD19-Tg mice were generated. Compared to MHCII-sufficient CD19-Tg mice, splenic IgSC numbers and serum Ig and autoantibody levels were markedly diminished, and the decrease in splenic B cell numbers was aggravated. Remarkably, genetic reconstitution of these MHCII-deficient mice with a human DQ8 Tg resulted in a hierarchical restorative pattern. Restoration of splenic B cell numbers was complete; restoration of numbers of splenic IgSC and of serum Ig levels was partial; and restoration of circulating autoantibody levels was virtually non-existent. Thus, MHCII expression has a profound effect on B cells which can be uncoupled from global Ig and autoantibody production in the hCD19-Tg model. This raises the possibility that MHCII affects B cells in a manner that, at least in part, is independent of helper T cell function.

Animals↗
PubMed2005

Pathogenesis of systemic sclerosis: altered B cell function is the key linking systemic autoimmunity and tissue fibrosis.

Systemic sclerosis (SSc) is characterized by autoimmunity and tissue fibrosis. There is a close association between specific autoantibodies and clinical features in patients with SSc. A number of studies have demonstrated that various cytokines, such as transforming growth factor-beta, modulate the synthesis of extracellular matrix by fibroblasts. However, it is not clear as to how autoimmunity and tissue fibrosis interact with each other. Recent studies have revealed that B cells play a critical role in various systemic autoimmune disorders. CD19 is a central regulator of B cell signaling threshold, and B cells from SSc patients exhibit an increased expression of CD19 that induces SSc-specific autoantibody production in transgenic mice. Furthermore, SSc patients have intrinsic B cell abnormalities characterized by decreased but activated memory B cells, which is possibly due to CD19 overexpression. Similarly, B cells from a tight-skin mouse, a model of SSc, show augmented CD19 signaling and chronic B cell activation. Remarkably, CD19 loss results in inhibition of chronic B cell hyper-reactivity and elimination of autoantibody production, which is associated with improvement in skin fibrosis and a parallel decrease in IL-6 production by B cells. Therefore, augmented cytokine production by B cells is a potential candidate for the induction of skin sclerosis. Alternatively, B cells may influence tissue fibrosis by regulating T cell activation and cytokine production through their antigen-presenting and co-stimulatory abilities. Thus, altered B cell function may result in tissue fibrosis, as well as autoimmunity, in SSc.

Animals↗
PubMed2005

B lymphocytes and systemic sclerosis.

PURPOSE OF REVIEW: Systemic sclerosis is characterized by fibrosis and autoimmunity. Systemic sclerosis displays a variety of abnormal immune activations, including the production of disease-specific autoantibodies, although the pathogenic relation between systemic autoimmunity and the clinical manifestations of systemic sclerosis remains unknown. Recent studies have rediscovered that B cells play critical roles in systemic autoimmunity and disease expression through various functions more than autoantibody production, such as antigen presentation and cytokine production. This review focuses on recent advances in understanding the B cell's role in systemic sclerosis. RECENT FINDINGS: Patients with systemic sclerosis have altered B-cell homeostasis characterized by expanded naive B cells and diminished memory B cells. Although memory B cells are decreased in number, they are chronically activated, possibly because of CD19 over-expression in B cells from patients with systemic sclerosis. CD19 over-expression can be genetically explained in part by a polymorphism of CD19 promoter region. Similarly, B cells from a tight-skin mouse, a genetic model of systemic sclerosis, show augmented CD19 signaling and chronic hyper-reactivity. CD19 hyper-phosphorylation in tight-skin B cells is caused by impaired function of CD22, a negative response regulator expressed on B cells. Classic roles of autoantibody secretion may also be important in systemic sclerosis because autoantibodies to matrix metalloproteinases can be pathogenic in vivo. SUMMARY: B cells may have more pathogenic roles in systemic sclerosis than had been appreciated. Further studies are required to clarify the precise molecular basis that links B cells and fibrosis. Collectively, B cells and B-cell-specific response regulators such as CD19/CD22 appear to be potential therapeutic targets of the disease.

Animals↗
PubMed2005

Abnormal natural killer cell function in systemic sclerosis: altered cytokine production and defective killing activity.

Natural killer (NK) cells are innate immune effectors that produce various immunoregulatory cytokines. Recent studies have shown that NK cells are involved in the initiation of autoimmunity. In this study, we determined abnormalities of NK cells in systemic sclerosis (SSc), an autoimmune connective tissue disease, by assessing the frequency and absolute number, activation marker expression, cytokine production, and killing activity. The frequency and absolute number of NK cells increased in diffuse cutaneous SSc (dcSSc), whereas they were normal in limited cutaneous SSc (lcSSc). NK cells from both dcSSc and lcSSc patients exhibited activated phenotypes characterized by up-regulated CD16 and CD69 expression and downregulated CD62L expression. Interferon (IFN)-gamma production by non-stimulated NK cells from both dcSSc and lcSSc patients was increased compared to the normal control, whereas on stimulation, a reduced amount of IFN-gamma was produced. Interleukin (IL)-5 and IL-10 production by non-stimulated NK cells and IL-6 production by stimulated NK cells were augmented in dcSSc patients, but not in lcSSc patients. Despite the augmented cytokine production by non-stimulated NK cells, natural cytotoxicity activity and granzyme B secretion was reduced in NK cells from dcSSc and lcSSc patients. These results suggested that altered NK cell function contributes to immunological abnormalities in SSc.

Adult↗
PubMed2005

Drug-induced hypersensitivity syndrome associated with human herpesvirus 6 and cytomegalovirus reactivation.

We describe a patient with drug-induced hypersensitivity syndrome (DIHS) associated with human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) infection induced by sulfasalazine. Two weeks after starting sulfasalazine to treat a rectal ulcer, the patient developed disseminated macular erythema accompanied by fever, liver injury, and lymphadenopathy. Seroconversion of antibodies to HHV-6 was observed. Systemic steroid treatment was not effective against the eruptions. Five months after the onset, he presented with an acute febrile disease. The detection of CMV antigen on peripheral blood leukocytes and positive staining for CMV on cutaneous endothelium indicated active CMV infection. Furthermore, he developed a bacteremia of methicillin resistant Staphylococcus aureus. An association the CMV reactivation with DIHS was suggested, although there remains the possibility that the systemic steroid treatment precipitated CMV reactivation. Recently, HHV-6 has been documented to have immunomodulating effects and to be associated with CMV reactivation. Therefore, we should pay attention to the possibility of CMV reactivation in patients with DIHS in whom the immunomodulating virus of HHV-6 has been reactivated.

Aged↗
PubMed2005

Change of suicidal ideation induced by suicide attempt.

Some studies have reported that a suicide attempt has a cathartic effect. We studied a change of suicidal ideation just before and after a suicide attempt to test whether a cathartic effect exists and, if a cathartic effect does exist, to identify factors that may affect it. Subjects consisted of 88 suicide attempters (29 males, 59 females, mean age=35.5 years) who attended the emergency medical center of Kobe City General Hospital, Kobe, Japan. Strength of suicidal ideation just before and after a suicide attempt was evaluated by 11 steps from 0 to 10, where 0 indicates no suicidal ideation and 10 indicates the strongest suicidal ideation. Subjects were also interviewed about any clinical backgrounds related to suicide attempts. Diagnoses were made by psychiatrists based on ICD-10. Scores of suicidal ideation decreased significantly after the suicide attempt in comparison with those just before the suicide attempt (P<0.0001). In suicide attempters of each generation under 60 years of age, there were significant decreases in scores of suicidal ideation after the suicide attempt, but not in those of over 60 years of age. Scores of suicidal ideation after the suicide attempt were significantly higher in the group of F4 classified by ICD-10 than that of F2. Our results indicate that the cathartic effect induced by suicide attempt is different among generations and psychiatric disorders.

Adolescent↗
PubMed2005

The CD19-CD21 signal transduction complex of B lymphocytes regulates the balance between health and autoimmune disease: systemic sclerosis as a model system.

Cell-surface CD19 functions as a general rheostat for defining intrinsic and antigen receptor-induced signaling thresholds critical for clonal expansion of the B cell pool and humoral immunity. CD19 also governs B cell responses initiated through the CD21 receptor, where complement C3d binding to CD21 links humoral immune responses with the innate immune system. Alterations in this signaling pathway can predispose mice and humans to autoantibody production and systemic autoimmunity. Transgenic mice that overexpress CD19 by 20-170% lose tolerance and generate autoantibodies. Likewise, B cells from CD21-deficient mice overexpress CD19 by approximately 50%, which leads to autoantibody production. Autoimmune patients with systemic sclerosis also overexpress CD19 by approximately 20%, which may contribute to their intrinsic B cell abnormalities and autoantibody production. Thus, chronic B cell activation resulting from augmented CD19 expression or signaling through the CD19 pathway may reveal a prototype autoimmune disease susceptibility pathway in mice and humans.

Animals↗
PubMed2005

[The role of BAFF in autoimmune diseases].

B cell activating factor belonging to the tumor necrosis factor family (BAFF) is a tumor necrosis factor (TNF) superfamily member best known for its role in the survival and maturation of B cells. BAFF is a ligand for three TNF receptor superfamily members: B-cell maturation antigen (BCMA), transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), and BAFF receptor (BAFF-R). Among them, BAFF-R plays the central role in the BAFF system, whereas TACI plays the inhibitory role. BAFF/BAFF receptors appear to span nearly all stages of B-lineage differentiation, ranging from the development, selection, and homeostasis of naive primary B cells to the maintenance of long-lived bone marrow plasma cells. Furthermore, excessive BAFF rescues self-reactive B cells from anergy, which may play a crucial role in the induction and development of autoimmunity. Mice overexpressing BAFF exhibit increased B cell numbers in spleen and lymph node and autoimmune phenotype similar to patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome. Furthermore, inhibition of BAFF by TACI-Ig and BAFFR-Ig has been successful in treating murine models of SLE and rheumatoid arthritis. In humans, previous reports have shown elevated serum BAFF levels in SLE, rheumatoid arthritis, Sjögren's syndrome, and systemic sclerosis patients. Thus, the dysregulation of BAFF/BAFF receptor system may contribute to induction and development of autoimmune diseases and become one of important therapeutic targets.

Animals↗
PubMed2005

Evaluation of coronary artery calcification by multi-detector row computed tomography for the detection of coronary artery stenosis in Japanese patients.

BACKGROUND: The development of an efficient noninvasive examination to detect coronary atherosclerosis is needed as a strategy to prevent coronary heart disease. To evaluate the usefulness of calcium score measured by multi-detector row computed tomography (MDCT), we compared calcium score derived from MDCT with findings of coronary artery stenosis assessed by coronary angiography (CAG). METHODS: In 108 patients (94 men, 14 women; average age, 65.7 years), we performed unenhanced CT scans and calculated coronary artery calcium score in 259 vessels without previous intervention and severe motion artifact to determine the correlation with the degree of coronary stenosis by CAG. RESULTS: The sensitivity and the specificity of calcification (calcium score 0.1+) for severe stenosis (75+%) were 89% and 43%, respectively. All four vessels with calcium score 1000+ had a severe stenosis. The areas under the receiver operating characteristics curve of calcium score for severe stenosis were 0.80 +/- 0.04, indicating the efficacy of this technique. CONCLUSIONS: Coronary artery calcification and calcium score determined by MDCT were associated with coronary arteries with severe stenosis. This technique appears to be useful for the evaluation of coronary atherosclerosis.

Aged↗
PubMed2005

Trends in dietary intake of folate, vitamins B6, and B12 among Japanese adults in two rural communities from 1974 through 2001.

BACKGROUND: The 5th edition of the Japanese food composition table enables us to evaluate intakes of folate and vitamins B6 and B12, which are associated with risk of chronic diseases. METHODS: We investigated long-term trends in dietary intake of those nutrients in two rural communities; Ikawa from1974 through 2000, and Kyowa from 1982 through 2001. The 24-hour recall method was adopted. Intake of green tea interviewed from 1994 was used to examine food sources for these nutrients in the latest period, but not to evaluate long-term trends. Reduced intakes of nutrients due to cooking were not taken into account. RESULTS: Age-adjusted mean folate intake increased by 30% in Ikawa between the 1970's and 1980's, and then leveled off to the latest survey, while that in Kyowa did not change throughout the survey periods. The increased folate intake was primarily due to green/yellow vegetables. Mean vitamin B6 intake did not change except that it increased for Ikawa women in the 1980's and decreased for Kyowa men in the latest period. No secular trend was found for mean vitamin B12 intake. The largest source for folate intake was total vegetables (38-58% of total intake) and the second largest source was alcohol/beverages including green tea (11-24%). Fish/shellfish was the largest source for vitamins B6 (16-23%) and B12 (77-84%). CONCLUSIONS: Dietary intakes of folate, vitamins B6 and B12 showed no notable long-term trend, except for an increased folate intake between the 1970's and 1980's due to an increased intake of green/yellow vegetables.

Adult↗
PubMed2005

Anti-lipoprotein lipase antibody in systemic sclerosis: association with elevated serum triglyceride concentrations.

OBJECTIVE: The vascular damage systemic sclerosis (SSc) consists mainly of microvascular changes, but recently macrovascular changes with dyslipidemia were recognized. In systemic lupus erythematosus (SLE), autoantibody to lipoprotein lipase (LPL), a key enzyme that hydrolyzes triglycerides, suggested a role of autoimmunity for elevated serum triglyceride levels and atherosclerosis. We investigated the prevalence and levels of anti-LPL antibodies, their clinical correlation, and their functional significance in patients with SSc. METHODS: Serum samples from patients with diffuse cutaneous SSc (dSSc; n = 55), limited cutaneous SSc (lSSc; n = 75), SLE (n = 21), and dermatomyositis (DM; n = 21) and healthy controls (n = 41) were examined by ELISA. The presence of anti-LPL antibody was evaluated by immunoblotting analysis using purified LPL. To determine the functional relevance of anti-LPL antibody in vivo, we assessed whether anti-LPL autoantibody was able to inhibit LPL activity using the LPL activity kit. RESULTS: ELISA revealed that IgG or IgM anti-LPL antibodies were detected in 35% of SSc patients, while they were also positive in 67% of SLE patients and 43% of DM patients. The presence of IgG anti-LPL antibody was associated with elevated serum triglyceride levels, greater extent of skin fibrosis, and more frequent presence of lung fibrosis, heart involvement, and anti-topoisomerase I antibodies. The presence of anti-LPL autoantibody was confirmed by immunoblotting analysis. LPL activity was inhibited by IgG anti-LPL antibodies in sera from SSc patients with elevated serum triglyceride levels. CONCLUSION: Our results suggest that anti-LPL autoantibody contributes to elevated serum triglyceride levels by inhibiting LPL enzyme activity in patients with SSc.

Autoantibodies↗
PubMed2005

[Scleroderma].

Explore the source record for details and available documents.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

[Examination of urine acrolein in Yusho victims].

Polychlorinated biphenyls (PCB) causes the release of superoxide during the metabolic process. Therefore, Yusho victims are thought to be exposed to oxidative stress caused by PCB, because high concentrations of PCB are still detected in the serum of Yusho victims. Recently, acrolein (ACR) has been reported to be one of excellent markers of oxidative stresses. In order to estimate the influence of oxidative stress by PCB, we measured urine ACR in Yusho victims and age-matched controls. The mean concentration of urine ACR was 355.4 +/- 37.2 in Yusho victims and 314.5 +/- 54.6 nmol/ml in controls, respectively. Unfortunately, there was no difference in urine concentrations of ACR between Yusho victims and controls. ACR is reported to be one of ubiquitous pollutants in the environment. It was supposed that PCB can give rise to ACR as an oxidative stress, but the influence seemed to be common even in the control subjects who had never been exposed to PCB. The exact mechanism is still unclear, and further examinations should be conducted in the near future.

Acrolein↗
PubMed2005

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2003). I. Susceptibility distribution].

The bacterial strains isolated from 565 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2003 and July 2004. The susceptibilities of them to many kinds of antimicrobial agents were investigated. Of them, 701 strains were estimated as prophlogistic bacteria and used for the investigation. The strains consisted of 258 Gram-positive bacterial strains (36.8%) and 443 Gram-negative bacterial strains (63.2%). Against Staphylococcus aureus, vancomycin (VCM) showed the strongest activity and prevented the growth of all strains with 2 microg/mL. Against Streptococcus agalactiae, ampicillin (ABPC), cefozopran (CZOP), imipenem (IPM), and clarithromycin (CAM) showed a strong activity and the MIC90 was 0.125 microg/mL or less. Against Enterococcus faecalis, VCM, ABPC, and IPM showed a strong antibacterial activity. The antibacterial activity of cephems to Escherichia coli was generally good, and especially CZOP and cefpirome (CPR) showed the strongest activity (MIC90: < or = 0.125 microg/mL). Quinolone resistant E. coli [MIC of ciprofloxacin (CPFX): > or =4 microg/mL] was detected at frequency of 15.7%, which was higher than that in the last year. Against Klebsiella pneumoniae, meropenem (MEPM) showed the strongest activity and next, the antibacterial activity of CRMN and CZOP was good. The antibacterial activity of the other cephems, however, significantly decreased, compared with that evaluated in last year. Against Serratia marcescens, MEPM had the strongest antibacterial activity. Against Proteus mirabilis, MEPM and CRMN showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. Nest, cefmenoxime (CMX), ceftazidime (CAZ), cefixime (CFIX), cefpodoxime (CPDX), CPR, CZOP, and cefditoren (CDTR) showed a strong activity. The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC90 of all the drugs was ranged from 32 to < or = 256 microg/mL except IPM and amikacin (AMK) having 16 microg/mL. The antibacterial activity of CZOP was relatively good (MIC50: 2 microg/mL).

Drug Resistance, Microbial↗
PubMed2005

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2003). II. Background of patients].

Seven hundred and nineteen bacterial strains isolated from 565 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2002 and July 2003. The frequency of bacteria isolation divided with patient clinical background was compared. The clinical background investigated included sex, age, type of infections, timing of antibiotics administration, and presence or absence of surgery affecting a decrease in defense against infection. The bacterial strains were divided with the age and sex of the patients and the types of infections. In males, the number of patients aged less than 50 years was few and the complicated UTIs without indwelling catheter was observed most frequently. Number of patients aged 20-39 years was greater in female than male. In all of ages except 0-9 and 70-79 years, the ratio of the uncomplicated UTIs was high, accounting for 44.4-91.7% of all types of infections. In the present time, the bacteria most frequently isolated were Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis also were relatively frequently isolated. E. coli was most frequently isolated from the uncomplicated UTIs, and P. aeruginosa and E. faecalis were frequently isolated from the complicated UTIs with indwelling catheter. With respect to the relation of these results to the age of the patients, in the uncomplicated UTIs, the isolation frequency of E. coli was the highest in all age groups, accounting for 40% or higher. In the complicated UTIs without indwelling catheter, the isolation frequency of E. coli decreased with aging of the patients but still was the highest in all age groups. In the complicated UTIs with indwelling catheter, the isolation frequency of E. coli was lower than in the uncomplicated UTIs in all age groups and P. aeruginosa and E. faecalis were more frequently isolated. In comparison of causative bacteria in UTIs between before and after the administration of antibiotics, P. aeruginosa increased after the administration in any types of UTIs. In comparison of causative bacteria in UTIs with or without surgery, E. coli was more frequently isolated in the patients without surgery, while P. aeruginosa and E. faecalis were more frequently isolated in the patients with surgery in any UTIs.

Adolescent↗