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Biomedical subjects

K Takehara

Publications and source records attributed to K Takehara.

At least 55 records · Page 3Linked to original sources
PubMed2001

Elevated serum levels of soluble L-selectin in patients with systemic sclerosis declined after intravenous injection of lipo-prostaglandin E1.

To determine whether serum soluble L-selectin (sL-selectin) levels are elevated in patients with systemic sclerosis (SSc) and whether serum sL-selectin levels change after treatment with lipo-prostaglandin E1 (lipo-PGE1), serum sL-selectin levels were examined by ELISA in patients with SSc (n=24), psoriasis vulgaris (n=22), and contact dermatitis (n=9), as well as normal control subjects (n=26). In five patients with SSc, serum sL-selectin levels were examined before and after intravenous injections of lipo-PGE1. Serum sL-selectin levels were significantly increased in patients with SSc (P<0.01) than those in normal control subjects. The elevated serum sL-selectin levels in patients with SSc significantly decreased 1 day (P<0.05), 7 days (P<0.05) and 14 days (P<0.05) after starting the treatment with lipo-PGE1. These results suggest that L-selectin may be involved in the disease process in SSc, and lipo-PGE1 may alter some inflammatory events in SSc.

Adolescent↗
PubMed2001

Serum levels of interleukin-6 and interleukin-10 correlate with total skin thickness score in patients with systemic sclerosis.

Various growth factors and cytokines have been suggested to play a central role in initiating and developing fibrosis in systemic sclerosis (SSc). To determine which serum levels of soluble mediators are the most relevant to the degree of skin sclerosis in SSc, serum levels of various soluble mediators were examined by ELISA and correlated with skin thickening that was measured using modified Rodnan total skin thickness scoring (TSS) system. Serum levels of IL-4, IL-12, IL-13, tumor necrosis factor-alpha, connective tissue growth factor (CTGF), vascular endothelial growth factor, monocyte chemotactic protein-1, macrophage inflammatory protein-1beta, soluble IL-6 receptor, and soluble L-selectin were higher in SSc patients than normal controls. Levels of IL-6, IL-10, and CTGF in patients with diffuse cutaneous SSc were higher than patients with limited cutaneous SSc and controls. Serum levels of IL-6 and IL-10 positively correlated with TSS in patients with SSc (r=0.625, P<0.0001 and r=0.663, P<0.0001, respectively). In addition, IL-10 levels significantly correlated with pulmonary fibrosis. Thus, serum levels of IL-6 and IL-10 most strongly reflect the extent of skin thickening in SSc, suggesting that levels of IL-6 and IL-10 are useful serological indicators for skin fibrosis in SSc.

Adult↗
PubMed2001

No evidence of deregulated patched-hedgehog signaling pathway in trichoblastomas and other tumors arising within nevus sebaceous.

Nevus sebaceous is a congenital malformation of the skin within which a number of neoplasms showing adnexal differentiation may arise. Recently, deletions in the patched gene region were reported in nevus sebaceous and constitutive activation of the patched-hedgehog signaling pathway was implicated in the development of tumors arising within nevus sebaceous. To substantiate further a role of the patched-hedgehog signaling pathway in secondary tumors arising within nevus sebaceous, we examined 11 nevus sebaceous associated with secondary tumors for loss of heterozygosity of the patched gene region by microsatellite polymerase chain reaction and patched mRNA expression by in situ hybridization. Unexpectedly, however, none of the tumors (including eight trichoblastomas) and nevus sebaceous lesions showed loss of heterozygosity at any polymorphic loci close to the patched gene. Further more, none of the nevus sebaceous lesions and secondary tumors gave detectable signals for patched mRNA. In contrast, four of 11 sporadic basal cell carcinomas, that were examined for comparison, showed loss of heterozygosity at the patched gene locus (p <0.05), and moderate to strong signals for patched mRNA was observed in all seven basal cell carcinoma tumors examined (p <0.0001). Additional investigation by reverse transcription-polymerase chain reaction in four basal cell carcinomas and two nevus sebaceous tumors also showed the expression of Gli-1, another target gene in the patched-hedgehog signaling pathway, in all the basal cell carcinomas samples but not in any of the nevus sebaceous tumors examined. The findings in this study do not support the view that the deregulation of the patched-hedgehog signaling pathway is involved in the pathogenesis of nevus sebaceous and associated tumors, and show that, although morphologically similar, trichoblastomas and basal cell carcinomas have a different molecular pathogenesis.

Adult↗
PubMed2001

Paraneoplastic pemphigus without antidesmoglein 3 or antidesmoglein 1 autoantibodies.

Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous blistering disease characterized by IgG autoantibodies that bind to various epithelia and immunoprecipitate a complex of 250, 230, 210, 190 and 170 kDa proteins. A recent study has suggested that PNP patients have antidesmoglein (Dsg) 3 autoantibody and that the antibody plays a pathogenic role in PNP. We report a 72-year-old woman with PNP associated with thymoma and adenocarcinoma of the lung. Diagnosis of PNP was made by the characteristic clinical, histological and immunopathological findings, as well as immunoprecipitation of characteristic 230, 210 and 190 kDa proteins. Using enzyme-linked immunosorbent assay with baculovirus-expressed recombinant proteins, the patient's serum was negative against both Dsg 3 and Dsg 1. This finding is unusual, and it suggests that the target antigen, which is involved in acantholysis, may be other than Dsg 3 in this case.

Aged↗
PubMed2001

Elevated serum L-selectin levels and decreased L-selectin expression on CD8(+) lymphocytes in systemic sclerosis.

L-selectin is expressed on most circulating leucocytes and mediates leucocyte rolling on endothelium at sites of inflammation. Following rolling or activation of leucocytes, cell surface L-selectin is released as soluble L-selectin (sL-selectin). In the present study, we assessed serum levels of sL-selectin by ELISA and blood leucocyte L-selectin expression by flow cytometry in patients with systemic sclerosis (SSc). Serum levels of sL-selectin in patients with SSc (n = 51) were significantly higher than in normal controls (n = 30) while sL-selectin levels were similar for systemic lupus erythematosus patients (n = 20) and normal controls. Furthermore, SSc patients with elevated sL-selectin levels had inflammatory joint involvement, pitting scar/ulcers, and diffuse pigmentation more frequently than those with normal sL-selectin levels. The frequency of L-selectin(+) population among CD8(+) T cells was significantly decreased in SSc patients (n = 30) compared with normal controls (n = 20), while that among CD4(+) T cells, B cells, monocytes, and neutrophils was similar for SSc patients and normal controls. These suggest that elevated sL-selectin levels and decreased frequency of L-selectin+ CD8(+) T cells in SSc patients may be involved in inflammation associated with SSc.

Adolescent↗
PubMed2001

CCR4 memory CD4+ T lymphocytes are increased in peripheral blood and lesional skin from patients with atopic dermatitis.

BACKGROUND: Recent studies have reported that TH1 and TH2 cells express CXCR3 and CCR4, respectively. OBJECTIVE: Our goal was to assess the association of CCR4 and CXCR3 expression with TH2 and TH1 cells and association of CCR4 and CXCR3 expression with inflammation in patients with atopic dermatitis (AD). METHODS: Intracellular cytokine production and chemokine receptor expression in blood T cells were examined by flow cytometry. Immunohistochemical expression of chemokine receptors was also investigated in chronically lesional skin. RESULTS: CCR4+ and CXCR3+ CD4+ T cells predominantly produced IL-4 and IFN-gamma, respectively. Although the frequency of CXCR3+ cells among CD4+ CD45RO+ T cells was similar for patients with AD (n = 29) and healthy control subjects (n = 19), patients with severe AD (n = 14) had a reduced frequency of CXCR3+ cells. In contrast, the frequency of CCR4+ cells and the CCR4/CXCR3 ratio were higher in patients with AD (n = 22) than healthy control subjects (n = 16) and correlated with disease severity of AD. The frequency of CCR4+ cells correlated positively with eosinophil numbers and serum IgE levels, whereas the frequency of CXCR3+ cells correlated inversely with eosinophil numbers. The frequency of CCR4+ or CXCR3+ cells was similar in patients with psoriasis (n = 6) and healthy control subjects. Immunohistochemical analysis showed that the frequency of CCR4+ cells among CD4+ T cells in chronically lesional skin of patients with AD (n = 9) was higher than that of patients with psoriasis (n = 4). CONCLUSION: Our data suggest the association of CCR4 expression with TH2 cells, the predominance of CCR4+ cells in blood from patients with AD, and an important role of CCR4 in the migration of TH2 cells from blood into AD lesional skin.

CD4-Positive T-Lymphocytes↗
PubMed2001

Pemphigus foliaceus developing after metastasis of cutaneous squamous cell carcinoma to regional lymph nodes.

We describe a patient in whom pemphigus foliaceus developed after cutaneous squamous cell carcinoma (SCC) metastasized to regional lymph nodes. Immunologic analysis revealed that production of anti-desmoglein 1 autoantibodies started when SCC metastasized, and the SCC expressed desmoglein 1, suggesting a pathogenic role of metastasized SCC in developing pemphigus foliaceus.

Aged↗
PubMed2001

Clinical significance of anti-topoisomerase I antibody levels determined by ELISA in systemic sclerosis.

OBJECTIVE: To determine the clinical associations of the levels of anti-topoisomerase I (topo I) antibody in patients with systemic sclerosis (SSc). METHODS: Anti-topo I antibody levels were determined by enzyme-linked immunosorbent assay. In a longitudinal study, 125 sera from 21 patients were analysed during a follow-up period of 0.2-4.7 yr. RESULTS: Anti-topo I antibody levels were correlated positively with skin thickness score and renal vascular resistance, and inversely with percentage vital capacity. In the longitudinal study, five patients with a low anti-topo I antibody level at their first visit exhibited a stable antibody level or a small decrease in the level during the follow-up period, and their skin sclerosis was stable. Of 16 patients with a high anti-topo I antibody level at their first visit, seven showed a stable level, four had an increasing level and five had a decreasing level. The decreasing levels were accompanied mainly by atrophic skin change during the follow-up period, whereas the increasing levels were associated with new onset or worsening of organ involvement. CONCLUSIONS: These results suggest the potential clinical significance of anti-topo I antibody levels in evaluating disease severity and the prognosis in SSc.

Adolescent↗
PubMed2001

Renal vascular damage in Japanese patients with systemic sclerosis.

OBJECTIVE: To evaluate renal vascular damage in Japanese patients with systemic sclerosis (SSc) by colour-flow Doppler ultrasonography. METHODS: The pulsatility index (PI) was measured in renal interlobar and segmental arteries by colour-flow Doppler ultrasonography. RESULTS: PI values of interlobar arteries were increased in SSc patients (n=53) with normal renal function compared with healthy persons (n=16), systemic lupus erythematosus patients (n=12) and dermatomyositis patients (n=3). SSc patients with elevated PI levels had digital pitting scar, short sublingual frenulum, contracture of phalanges, pulmonary fibrosis, decreased per cent vital capacity, heart involvement, positivity for anti-topoisomerase I antibody, and elevated C-reactive protein more frequently than those with normal PI levels. CONCLUSION: Although renal crisis is rare in Japanese SSc patients, our study suggests that latent and subclinical renal damage exists in these patients.

Adult↗
PubMed2001

Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily, which regulate the differentiation of osteoprogenitor cells. Here we show that among members of the BMP family, BMP-4 and growth/differentiation factor 5 (GDF-5) induce osteoblast differentiation through the activation of three receptor-regulated Smads (i.e. Smad1, Smad5 and Smad8). By contrast, BMP-6 and BMP-7 induce alkaline phosphatase activity through Smad1 and Smad5, but not through Smad8. Consistent with these findings, BMP-4 induced phosphorylation and nuclear translocation of Smad1, Smad5 and Smad8, but BMP-6 activated only Smad1 and Smad5. BMP-4 and GDF-5 are known to bind to activin receptor-like kinase 3 (ALK-3) and/or ALK-6 (also termed BMP type IA and type IB receptors, respectively), whereas BMP-6 and BMP-7 preferentially bind to ALK-2. Compared with the effects induced by only one of the type I receptors, the combination of constitutively active forms of ALK-2 and ALK-3 (or ALK-6) more strongly induced alkaline phosphatase activity in C2C12 cells. Moreover, addition of BMP-4 and BMP-6 to C2C12 cells resulted in higher alkaline phosphatase activity than that of only one of these BMPs. The combination of ALK-2 and ALK-3 also induced higher transcriptional activity than either receptor alone. Thus, ALK-2 and ALK-3 (or ALK-6) might synergistically induce osteoblast differentiation of C2C12 cells, possibly through efficient activation of downstream signaling pathways.

Activin Receptors↗
PubMed2001

Diastolic dysfunction in patients with systemic sclerosis detected by gated myocardial perfusion SPECT: an early sign of cardiac involvement.

UNLABELLED: Diagnosis of cardiac involvement is important for the management of patients with systemic sclerosis (SSc). This study was undertaken to determine the significance of gated myocardial perfusion SPECT in patients with SSc and whether diastolic function measured by gated SPECT is an early sign of cardiac complications. METHODS: Thirty-four patients with SSc and 16 control patients were studied using exercise nongated and resting gated myocardial perfusion SPECT. The SSc was classified by the modified Rodnan total skin score (TSS) into high-TSS (score > or = 10; n = 18) and low-TSS (score < 10; n = 16) groups. Gated SPECT was performed using 99mTc-methoxyisobutylisonitrile with 16 frames per cardiac cycle and quantitatively analyzed by QGS software and Fourier filtering of the volume curve. The parameters of ejection fraction (EF), peak filling rate (PFR), one-third mean filling rate, and time to PFR (TPFR) were calculated. RESULTS: A slight perfusion abnormality was observed in four and five patients in the low-TSS and high-TSS groups, respectively (not statistically significant). A decreased resting EF less than 55% was found in no and two patients in the low-TSS and high-TSS groups, respectively. TPFR was 166 +/- 22, 168 +/- 38, and 216 +/- 82 ms (P = 0.05, high-TSS group versus low-TSS group; P = 0.04, control group versus high-TSS group) and TPFR/R-R interval was 0.18 +/- 0.02, 0.19 +/- 0.04, and 0.26 +/- 0.09 (P = 0.01, high-TSS group versus low-TSS group; P = 0.005, control group versus high-TSS group) for the control, low-TSS, and high-TSS groups, respectively. CONCLUSION: Diastolic function can be evaluated by gated myocardial perfusion SPECT. Significant diastolic abnormalities were shown even in patients with normal perfusion and systolic function and were related to the severity of SSc.

Coronary Circulation↗
PubMed2001

[A case of malignant pheochromocytoma associated with von Recklinghausen's disease].

A 48-year-old woman suffering from chest and lumbar pain was referred to our clinic for treatment. She had a history of von Recklinghausen's disease with multiple café-au-lait spots and neurofibromatosis. Computed tomography demonstrated a large tumor in the left adrenal gland and a small lesion in the liver, with the levels of plasma and urinary catecholamines being elevated. 131I-metaiodobenzylguanidine (MIBG) scintigraphy showed abnormal accumulations in the left adrenal tumor and multiple-bone lesions. A diagnosis of malignant pheochromocytoma with liver and bone metastases was made, and the patient received chemotherapy. Seven months after the diagnosis of malignant pheochromocytoma, she died of pulmonary edema due to disease progression. Autopsy revealed malignant pheochromocytoma with liver, lung, bone and lymph nodes metastases. We reviewed the literature on pheochromocytoma associated with von Recklinghausen's disease. To our knowledge, only 7 cases of malignant pheochromocytoma associated with von Recklinghausen's disease have been reported in Japan.

Adrenal Gland Neoplasms↗
PubMed2001

Anti-agalactosyl IgG antibodies in sera from patients with systemic sclerosis.

OBJECTIVE: To determine the prevalence and clinical correlations of anti-agalactosyl IgG antibodies (anti-AG IgG) in patients with systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (lSSc; n = 49), diffuse cutaneous SSc (dSSc; n = 21), rheumatoid arthritis (RA; n = 10), systemic lupus erythematosus (SLE; n = 20), and healthy individuals (n = 20) were examined by lectin-enzyme immunoassay using human agalactosyl IgG as antigen. RESULTS: Anti-AG IgG were detected in 52 (74%) of 70 patients with SSc, which was much higher than the frequency of rheumatoid factor positivity in SSc (16%). Levels of anti-agalactosyl IgG antibodies were significantly higher than in healthy controls or patients with SLE, but lower than patients with RA. Levels of anti-AG IgG in patients with dSSc were significantly higher than in lSSc. SSc patients with anti-topoisomerase I antibodies had significantly higher levels of anti-AG IgG than SSc patients with anticentromere antibodies. Concerning clinical correlation, patients with pulmonary fibrosis showed elevated levels of anti-AG IgG compared to those without pulmonary fibrosis. Patients with decreased %VC or %DLCO showed increased levels of anti-AG IgG. Elevated levels of anti-AG IgG were associated with the presence of contracture of phalanges or cutaneous calcinosis, but not the presence of arthritis/arthralgia. CONCLUSION: The results suggest that anti-agalactosyl IgG antibody is frequently detected in SSc and is a serological indicator for more severe SSc.

Adolescent↗
PubMed2001

Clinical significance of soluble CD31 in patients with systemic sclerosis (SSc): association with limited cutaneous SSc.

OBJECTIVE: To determine serum levels of soluble CD31 (sCD31) and its clinical associations in patients with systemic sclerosis (SSc). METHODS: Serum sCD31 levels from 70 patients with SSc were examined by ELISA. For a longitudinal study, 64 sera from 17 SSc patients were analyzed (followup: 0.4-3.9 yrs). RESULTS: Serum sCD31 levels were elevated in patients with SSc (n = 70) compared with healthy controls (n = 20) and patients with systemic lupus erythematosus (n = 15). Serum sCD31 levels were higher in patients with limited cutaneous SSc (lSSc; n = 37) than those with diffuse cutaneous SSc (n = 33). Patients with elevated sCD31 levels had pulmonary fibrosis and decreased percentage vital capacity (%VC) less frequently than those with normal sCD31 levels. sCD31 levels correlated positively with %VC in patients with SSc. This association of elevated sCD31 levels with the lower frequency of pulmonary involvement and better %VC was still observed when analyzed among ISSc patients alone. The elevation of sCD31 was associated with shorter disease duration in patients with lSSc. In a longitudinal study, 75% of patients with SSc showed increased sCD31 levels only transiently in the early phase of the disease. Serum sCD31 levels remained normal during followup in all patients with normal sCD31 levels at the first visit. CONCLUSION: Elevated sCD31 levels were associated with ISSc with relatively early onset and lower frequency and severity of pulmonary fibrosis. These results suggest that sCD31 would be a protective factor for the development of skin sclerosis and pulmonary fibrosis in SSc, since sCD31 has an antiinflammatory effect by inhibiting CD31 mediated transendothelial migration of leukocytes.

Adolescent↗
PubMed2001

[Clinical evaluation of renal angiomyolipoma].

Between April 1980 and December 1999, 23 kidneys in 20 patients were diagnosed as having renal angiomyolipoma at our institution. The patients were 6 males and 14 females aged 24 to 79 years, with a mean age of 55.4 years. Two patients had associated tuberous sclerosis and 3 had bilateral disease. Of all patients the main clinical symptoms were pain (45%) and palpable mass (40%); 5 patients (25%) had asymptomatic lesions. The size of the tumor ranged from 1.3 to 24 cm (mean 7.7 cm). Treatment consisted of nephrectomy in 9 patients, partial nephrectomy in 6 and selective embolization in one. Pre-operative diagnosis was renal cell carcinoma in 5 of the 9 patients who underwent nephrectomy. Six patients with 7 diseased kidneys were followed radiologically. One patient underwent percutaneous biopsy to confirm the diagnosis. We suggest that nephron-sparing surgery for patients with renal angiomyolipoma should be the first step if tumor size is 4 cm < or = or increasing rapidly. Selective embolization is also a useful method. However, we need long-term follow-up to evaluate the effectiveness of embolization.

Adult↗
PubMed2001

[Quantitative evaluation of esophageal scintigraphy in systemic sclerosis].

BACKGROUND: Esophageal involvement by systemic sclerosis (SSc) is frequent. The purpose of this study was to evaluate esophageal motility disorders quantitatively. METHODS: We investigate esophageal scintigraphy in 22 patients with SSc. Esophageal scintigraphy was obtained with swallowing physiological saline in supine position, and swallowing soup in supine and sitting positions. Data was acquired with 0.5 sec per frame for 192 frames in the anterior view. We employed a condensed image as a visual evaluation, half-life and retention rate as a quantitative evaluation, which were obtained from time-activity curves generated from regions of interest on the whole esophagus. The half-life and retention rate were compared with classification of Barnett, stages of SSc, and modified Rodnan total skin score (TSS). RESULTS: No significant differences were seen in classification of Barnett and the stages of SSc. No significant difference was seen between swallowing water and soup in the supine position. The retention rate was significantly prolonged in the supine position than in the sitting position. The retention rate of soup study in the sitting position correlated with TSS (r = 0.61). CONCLUSION: Esophageal scintigraphy in the sitting position is useful in evaluation of esophageal motility in SSc.

Adult↗
PubMed2000

Quantitative genetic variation in CD19 expression correlates with autoimmunity.

Signaling thresholds influence the balance between humoral immunity and autoimmunity. Cell surface CD19 regulates intrinsic and Ag receptor-induced B lymphocyte signaling thresholds, and transgenic mice that overexpress CD19 by 3-fold generate spontaneous autoantibodies in a genetic background not associated with autoimmunity. To quantify the extent that genetically determined differences in expression of a single cell surface molecule can influence autoantibody production, we have assessed autoimmunity in a C57BL/6-transgenic mouse line with subtle 15-29% increases in CD19 cell surface expression (CD19 transgenic). Antinuclear Abs, especially anti-spindle pole Abs, rheumatoid factor, and autoantibodies for ssDNA, dsDNA, and histone were produced in these transgenic mice, but not littermate controls. This demonstrates that small changes in CD19 expression can induce autoantibody production. Remarkably, similar changes in CD19 expression were found on B cells from patients with systemic sclerosis, a multisystem disorder of connective tissue with autoantibody production. CD19 density on blood B cells from systemic sclerosis patients was significantly ( approximately 20%) higher compared with normal individuals, whereas CD20, CD22, and CD40 expression were normal. These results suggest that modest changes in the expression or function of regulatory molecules such as CD19 may shift the balance between tolerance and immunity to autoimmunity. Thereby autoimmune disease may result from a collection of subtle multigenic alterations that could include incremental density changes in cell surface signaling molecules.

Adult↗