PubMed Health⌕ Search

Biomedical subjects

Shinichi Sato

Publications and source records attributed to Shinichi Sato.

At least 19 recordsLinked to original sources
PubMed2007

B cell signaling and autoimmune diseases: CD19/CD22 loop as a B cell signaling device to regulate the balance of autoimmunity.

Autoimmune diseases, including connective tissue diseases and bullous diseases, may be life-threatening. Recent clinical and experimental approaches have demonstrated that B cells play critical roles in the manifestation of autoimmune disease not only by well-established autoantibody-mediated mechanisms but also by a variety of other functions. These B cell functions are under the regulation of B cell antigen receptor (BCR)-induced signals and by specialized cell surface coreceptors, or "response regulators", which inform B cells of their microenvironment. These response regulators include CD19 and CD22. CD19 and CD22 do not merely regulate BCR signals independently, but they have their own regulatory network. CD19 regulates CD22 phosphorylation by augmenting Lyn kinase activity, while CD22 inhibits CD19 phosphorylation via SHP-1. Importantly, this "CD19/CD22 loop" is significantly related to an autoimmune phenotype in mice. Thus, the CD19/CD22 loop may be a potential therapeutic target in autoimmune disease for modulating B cell signaling.

Animals↗
PubMed2007

Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseases.

Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma.

Adolescent↗
PubMed2006

Decreased expression levels of CD22 and L-selectin on peripheral blood B lymphocytes from patients with bullous pemphigoid.

Bullous pemphigoid (BP), an autoimmune subepidermal-blistering disease of the elderly, is caused by antibodies against BP antigens at the epidermal basement membrane zone (BMZ). CD22 is a B lymphocyte specific response regulator, which is down-regulated after B-cell activation. Old CD22-deficient mice produce class-switched autoantibodies. To assess the role of CD22 in the pathogenesis of BP, we examined CD22 expression on B cells from BP patients and correlated its expression with clinical parameters. B cell expression of CD22 was 20% lower in BP patients when compared to healthy control subjects. In addition, B cells from BP patients showed decreased expression of L-selectin, which is an indicator of leukocyte activation, and CD22 expression levels were correlated with L-selectin expression. These results suggest that the decreased CD22 expression may be associated with the activation of B cells in BP. CD22 expression levels in BP patients did not correlate with the levels of anti-epidermal BMZ antibodies, and old CD22-deficient mice did not develop the anti-epidermal BMZ antibody. These results suggest that a decrease in CD22 expression may not be associated with BP-specific antibody production.

Adult↗
PubMed2006

Leukocyte count is an independent predictor for risk of acute myocardial infarction in middle-aged Japanese men.

BACKGROUND: Leukocyte count is recognized as an inflammatory marker and a predictor of cardiovascular events. However, it is uncertain whether the contribution of leukocyte count to the risk of cardiovascular disease is independent of smoking. METHODS: The subjects were 4492 male employees aged 40-59 years who worked for nine companies in Osaka. RESULTS: After 9-year follow-up, 40 acute myocardial infarction and 26 ischemic stroke events occurred. Age-adjusted relative risk of acute myocardial infarction in the highest versus lowest quartiles of leukocyte count was 6.0 (95% CI, 1.8-20.5, P for trend <0.001) and the multivariable relative risk adjusted for smoking and other conventional cardiovascular risk factors was 3.7 (1.0-13.4, P for trend=0.01). The association between leukocyte count and the risk of acute myocardial infarction was also observed among both current smokers and nonsmokers. The positive association between leukocyte count and the risk of ischemic stroke was weak and did not reach statistical significance. CONCLUSIONS: Leukocyte count is a predictor of acute myocardial infarction among Japanese middle-aged men, both in smokers and nonsmokers.

Acute Disease↗
PubMed2006

A low level of C-reactive protein in Japanese adults and its association with cardiovascular risk factors: the Japan NCVC-Collaborative Inflammation Cohort (JNIC) study.

High-sensitivity C-reactive protein (hs-CRP) levels vary remarkably by race and ethnic group. We examined hs-CRP levels and their association with cardiovascular risk factors in the Japanese general population. The Japan National Cardiovascular Center (NCVC)-collaborative Inflammation Cohort (JNIC) Study recruited 5213 men and 7071 women aged > or = 40 years from seven communities in Japan during 2002-2004. hs-CRP was measured using nephelometry calibrated with CRM 470, the international plasma protein reference material. Traditional cardiovascular risk factors and their aggregation were studied in multivariate logistic models, stratified by overweight status. Median hs-CRP levels in men and women were 0.60 and 0.45 mg/L, respectively. The percentage of subjects with hs-CRP levels < 1.0, 1.0-3.0, and > 3.0 mg/L was 67.4%, 22.0%, and 10.6% in men, respectively, and 76.3%, 16.7%, and 7.0% in women. hs-CRP levels showed significant linear associations with traditional risk factors. Overweight, hypertension, dyslipidemia (men only), smoking (men only), and diabetes (women only) contributed significantly to elevated hs-CRP levels. Overweight individuals with hypertension, dyslipidemia, and diabetes had a high prevalence of elevated hs-CRP levels in both sexes. Japanese adults have very low hs-CRP levels. An aggregation of metabolic risk factors is associated with elevated hs-CRP levels among overweight individuals, particularly in women.

Aged↗
PubMed2006

Plasma fibrinogen concentrations and risk of stroke and its subtypes among Japanese men and women.

BACKGROUND AND PURPOSE: We aimed to examine the impact of fibrinogen concentrations on the incidence of stroke. METHODS: We examined the association between fibrinogen and risk of total stroke and stroke subtypes in an 11-year prospective study of 4608 men and 7589 women aged 40 to 79 years with no history of stroke and/or coronary heart disease. The analysis was repeated, stratified by smoking status, to examine whether the association between fibrinogen and stroke was modified by smoking. RESULTS: There were 317 incident total strokes comprising 103 hemorrhagic strokes (70 intraparenchymal hemorrhages [22.1% of strokes], 33 subarachnoid hemorrhages [10.4%]), 206 ischemic strokes (65.0%), and 8 strokes of undetermined type (2.5%). The multivariable hazard ratio (95% CI) for the highest versus lowest fibrinogen quartiles after adjustment for age, sex, area, and known cardiovascular risk factors was 2.5 (1.3 to 5.0), P<0.01, for hemorrhagic stroke and 3.2 (1.4 to 7.4), P<0.01, for intraparenchymal hemorrhage. There was no positive association of fibrinogen with risk of ischemic stroke or subarachnoid hemorrhage. Among never-smokers, the multivariable hazard ratio (95% CI) for the highest versus lowest fibrinogen quartiles was 3.5 (1.3 to 9.3), P=0.01, for hemorrhagic stroke and 4.4 (1.3 to 15.2), P=0.02, for intraparenchymal hemorrhage. CONCLUSIONS: High plasma fibrinogen concentration can be a predictor for risk of intraparenchymal hemorrhage.

Adult↗
PubMed2006

Proportions of stroke subtypes among men and women > or =40 years of age in an urban Japanese city in 1992, 1997, and 2002.

BACKGROUND AND PURPOSE: Higher proportions of hemorrhagic stroke and lacunar infarction were reported in rural Japan compared with those in Western countries. We examined the relative proportions of stroke subtypes in an urban Japanese city where westernized lifestyles are more common than in rural areas. METHODS: Stroke registration was performed in 1992, 1997, and 2002 for residents > or =40 years of age who were admitted with acute strokes to all of the 10 hospitals with > or =90 beds in Yao City, Osaka, Japan. Strokes were classified as intraparenchymal hemorrhage, subarachnoid hemorrhage, or ischemic strokes (embolic infarction, large-artery occlusive infarction, lacunar infarction, and unclassified thrombotic infarction) by criteria using computed tomography or MRI. RESULTS: A total of 650 first-ever strokes were registered. The age-adjusted proportion of each stroke subtype was not significantly different among the 3 study periods in both men and women. Throughout the 3 periods, intraparenchymal hemorrhage, subarachnoid hemorrhage, and ischemic stroke accounted for 26%, 7%, and 65% in men, respectively. In women, the respective proportions were 29%, 21%, and 44%. The proportion of each subtype for total ischemic strokes was as follows: 51% to 61% lacunar infarction, 25% to 26% large-artery occlusive infarction, and 11% to 17% embolic infarction. CONCLUSIONS: Our study showed that hemorrhagic stroke represented a large proportion of all strokes, especially among women, and lacunar infarction was the most common subtype of ischemic stroke among both men and women in Yao City, which differed from findings in Western countries.

Adult↗
PubMed2006

System for simultaneously monitoring heart and breathing rate in mice using a piezoelectric transducer.

We propose a novel system for simultaneously monitoring the heart rate (HR) and breathing rate (BR) of anesthetized mice using a piezoelectric transducer (PZT) placed under the body. It is known that a PZT, which transforms mechanical vibrations into electrical signals, can detect heart sounds and breathing movements. However, no PZT system has been reported for simultaneous and continuous monitoring of HR and BR, possibly due to difficulties in eliminating noises and errors caused by the amplitude fluctuation of heart sounds and breathing movements. These difficulties were overcome by custom-designed analogue circuitry and a microprocessor program, resulting in detection of HR and BR with a high reliability compared to the values obtained from ECG and a conventional airflow sensor. We believe that this practical and easy-to-use system can be applied to a wide variety of basic and clinical research fields.

Algorithms↗
PubMed2006

Both Th1 and Th2 chemokines are elevated in sera of patients with autoimmune blistering diseases.

Although chemokines are critical elements for the selective attraction and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning T helper (Th) 1 or Th2 chemokines in autoimmune blistering disease (ABD). To determine whether serum levels of chemokines that are preferentially chemotactic for Th1 (monokine induced by IFN-gamma (MIG/CXCL9)) and Th2 (thymus and activation regulated chemokine (TARC/CCL17) and macrophage derived chemokine (MDC/CCL22)) cells were elevated and whether they correlated with the clinical features in patients with ABD. Serum chemokine levels were examined using ELISA in patients with pemphigus vulgaris (PV, n=19), pemphigus foliaceous (PF, n=14), or bullous pemphigoid (BP, n=27) and normal controls (n=20). Serum MIG levels were significantly higher in patients with PV, PF, or BP than those in the control subjects. Serum levels of TARC and MDC were also significantly elevated in patients with PV, PF, or BP relative to the normal controls. Among the ABD subgroups, the levels of each chemokine tended to be higher in BP patients than in PV patients. Furthermore, serum TARC levels correlated positively with serum IgE levels in patients with ABD. Levels of TARC, MDC, and MIG were significantly decreased after treatment when the skin lesions disappeared in these patients. Furthermore, serum MIG levels correlated positively with serum levels of TARC and MDC in the ABD patients. These results suggest that both a Th1 chemoattractant MIG and Th2 chemoattractants, TARC and MDC, cooperatively play a role in the development of ABD.

Adult↗
PubMed2006

Averaged time evolution of rough surfaces.

We propose a method of extracting an approximated evolution equation of distribution of height fluctuations for a class of discrete growth models of rough surfaces where the behavior of local slopes can be described by a Markov process. Using the Markov property of the fluctuating field, the evolution equation is obtained as a map describing the time evolution averaged over possible growth paths. Applying the method to a -dimensional restricted solid-on-solid model, we obtain a map with finite degrees of freedom. The obtained map describes well the averaged evolution of surfaces.

Journal Article↗
PubMed2006

L-selectin and intercellular adhesion molecule-1 regulate the development of Concanavalin A-induced liver injury.

Concanavalin A (Con A)-induced hepatitis is a model for human T cell-mediated hepatitis. We evaluated the role of L-selectin and intercellular adhesion molecule-1 (ICAM-1) in this model by injecting Con A intravenously in mice lacking L-selectin (L-selectin-/-), ICAM-1 (ICAM-1-/-), or both (L-selectin/ICAM-1-/-). Blood and liver samples were collected 0, 8, 24, and 48 h after Con A treatment. Increases in plasma transaminase levels, which peaked 8 h after injection, were reduced significantly in L-selectin-/-, ICAM-1-/-, and L-selectin/ICAM-1-/- mice compared with wild-type mice. Liver necrosis was more strongly inhibited in ICAM-1-/- mice than in L-selectin-/- mice but was most prominently reduced in L-selectin/ICAM-1-/- mice, in parallel with decreased plasma transaminase levels. The reduced severity of hepatitis in the mutant mice correlated with decreases in numbers of liver CD4+ T cells but not numbers of CD8+ T cells or neutrophils. Following Con A treatment, L-selectin deficiency reduced liver mRNA expression of tumor necrosis factor-alpha, and ICAM-1 deficiency reduced expression of interleukin-4. By contrast, reductions in liver macrophage inhibitor protein-1alpha mRNA occurred in all mutant mice. These results indicate that L-selectin and ICAM-1 contribute cooperatively to the development of Con A-induced hepatitis by regulating leukocyte infiltration and subsequent cytokine production.

Animals↗
PubMed2006

B cell antigen receptor and CD40 differentially regulate CD22 tyrosine phosphorylation.

Cell surface molecules on lymphocytes positively or negatively modulate the Ag receptor signaling, and thus regulate the fate of the cell. CD22 is a B cell-specific cell surface protein that contains multiple ITIMs in the cytoplasmic tail, and critically regulates B cell activation and survival. CD22 regulation on B cell signaling is complex because CD22 can have both positive and negative roles in various contexts. We generated phosphospecific polyclonal Abs reacting four major CD22 tyrosine motifs (Y762, Y807, Y822, and Y842) and analyzed the pattern and intensity of phosphorylation of these tyrosine residues. The tyrosine motifs, Y762, Y822, and Y842, are considered as ITIM, whereas the other, Y807, is suggested to be important for Grb2 recruitment. Approximately 10% of the four tyrosine residues were constitutively phosphorylated. Upon anti-IgM ligation, CD22 Y762 underwent most rapid phosphorylation, whereas all four tyrosine residues were eventually phosphorylated equally at approximately 35% of all CD22 molecules in the cell. By contrast, anti-CD40 stimulation specifically up-regulated anti-IgM-induced phosphorylation of tyrosines within two ITIM motifs, Y762 and Y842, which was consistent with in vivo finding of the negative role of CD22 in CD40 signaling. Thus, CD22 phosphorylation is not only quantitatively but also qualitatively regulated by different stimulations, which may determine the outcome of B cell signaling.

Amino Acid Sequence↗
PubMed2006

Elevated serum BAFF levels in patients with systemic sclerosis: enhanced BAFF signaling in systemic sclerosis B lymphocytes.

OBJECTIVE: To determine serum levels of BAFF, a potent B cell survival factor, in patients with systemic sclerosis (SSc) and relate the results to the clinical features of SSc. METHODS: Serum BAFF levels in 83 patients with SSc were examined by enzyme-linked immunosorbent assay (ELISA). In a longitudinal study, 131 serum samples obtained from 21 patients with SSc were analyzed. The expression of BAFF messenger RNA (mRNA) in the skin was quantified by real-time reverse transcription-polymerase chain reaction. The expression of BAFF receptor (BAFFR) on CD19+ B cells was assessed by flow cytometry. The production of IgG and interleukin-6 (IL-6) by isolated B cells was examined by ELISA. RESULTS: Serum BAFF levels were elevated in SSc patients compared with healthy controls and correlated positively with the extent of skin fibrosis. Among the 21 patients with SSc in the longitudinal study, 7 had decreased BAFF levels, 11 had levels that remained unchanged, and 3 patients had increased levels. Decreasing BAFF levels were accompanied by regression of skin sclerosis, whereas increasing levels of BAFF were associated with the new onset or worsening of organ involvement. BAFF mRNA expression was up-regulated in the affected skin of patients with early diffuse cutaneous SSc. BAFFR expression on B cells was increased in SSc patients relative to healthy controls. Furthermore, SSc B cells that were stimulated by BAFF exhibited an enhanced ability to produce IgG and IL-6. CONCLUSION: These results suggest that BAFF and its signaling in B cells contribute to B cell abnormalities and disease development in patients with SSc.

Adult↗
PubMed2006

Reactive hemophagocytic syndrome in a patient with polyarteritis nodosa associated with Epstein-Barr virus reactivation.

A 73-year-old woman with erythematous nodules was admitted to our hospital in December 2003. She was diagnosed with polyarteritis nodosa (PAN) from skin biopsy and laboratory data. Following the treatment with oral prednisolone (40 mg/day), her condition improved. Four days after the reduction of prednisolone, she became febrile. Bone marrow aspiration revealed an increase in the number of marrow macrophages, and phagocytosis of blood cells. The Epstein-Barr virus genome was detected in her peripheral blood. A diagnosis of hemophagocytic syndrome was made. Moreover, intestinal bleeding developed and the patient was given medical treatment consisting of methylprednisolone pulse therapy, intravenous immunoglobulin, weekly intravenous VP-16, and several blood transfusions. In addition, embolization of a branch of the ileal artery was performed. Despite the above treatments, the patient died. Autopsy revealed hemophagocytosis in bone marrow and perforation of ileocecal region. This case suggests that risks for hemophagocytic syndrome in PAN patients should be recognized.

Aged↗
PubMed2006

Redo total aortic arch replacement using an extended homograft for graft infection.

A 65-year-old man developed graft infection 3 years after total aortic arch replacement for a chronic dissecting aneurysm. Redo total aortic arch replacement was performed using an extended homograft following 2 days of open drainage of the mediastinum. The patient has been free from a recurrent mediastinitis over the last 3 years.

Aged↗
PubMed2006

Relationship of smoking and smoking cessation with ankle-to-arm blood pressure index in elderly Japanese men.

BACKGROUND: Cigarette smoking is associated with an increased risk of peripheral arterial disease, but the relationship between smoking cessation and preclinical peripheral atherosclerosis is uncertain. DESIGN AND METHODS: A cross-sectional, population-based study to examine the effect of smoking and smoking cessation on the prevalence of peripheral arterial disease among 1215 men aged 60-79 years in two Japanese communities in 1999-2000. The ankle-to-arm systolic blood pressure index (AAI) was used as an estimate of the presence of peripheral atherosclerosis. RESULTS: The mean AAI correlated inversely and linearly with smoking status and pack-years of smoking. The multivariate prevalence odds ratio [95% confidence interval (CI)] of low AAI (< 0.90) compared with never-smokers was 3.7 (95% CI 1.1-12.7) for current smokers and 4.2 (95% CI 1.2-14.6) for men with 45 or more pack-years of smoking. In men who have quit smoking for 20 years or more, the mean AAI was higher and the prevalence of low AAI (< 0.90) was lower than those of current smokers, but similar to those of never-smokers. CONCLUSIONS: Our results confirm that current smoking and pack-years of smoking correlate with the presence of peripheral artery disease. The results suggest that smoking cessation for 20 years or more is associated with the regression of atherosclerosis in peripheral arteries. This finding needs to be confirmed by a prospective study.

Aged↗
PubMed2006

[Roles of oxidative stress in photoaging and the pathogenesis of systemic sclerosis].

Human skin is exposed to high amount of solar ultraviolet (UV) radiation, as well as to other environmental oxidants. Photoaging refers to the effect of long-term UV exposure and sun damage superimposed on intrinsically aged skin. The clinical photoaging features are dyspigmentation, laxity, wrinkles, and cutaneous malignancies. Most conspicuous photoaging change in dermis, which is caused by elastin materials accumulation, is termed "solar elastosis". Reactive oxygen species are known to be generated by UV radiation, and play an important role of photoaging. Although the pathogenesis of systemic sclerosis (SSc) remains unknown, oxidative stress has been suggested to contribute to clinical manifestations associated with SSc, such as vascular damage including Raynaud's phenomenon. This review focuses on recent data including our data which have demonstrated the critical role of oxidative stress in photoaging and the pathogenesis of SSc.

Animals↗