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Biomedical subjects

M Fujimoto

Publications and source records attributed to M Fujimoto.

At least 217 records · Page 12Linked to original sources

Elevated soluble CD23 levels in the sera from patients with localized scleroderma.

Soluble CD23 (sCD23) is closely related to B-cell activation and elevated serum levels of sCD23 have been reported in several autoimmune disorders. This study investigated the serum levels of sCD23 and determined the correlation of sCD23 with other immunologic abnormalities and clinical features in localized scleroderma. We examined 49 serum samples by an enzyme-linked immunosorbent assay in the following three subgroups: 15 patients with generalized morphoea, 22 with linear scleroderma, and 12 with morphoea. The serum levels of sCD23 were significantly elevated in patients with localized scleroderma, compared with those in healthy individuals. Of the three subgroups of localized scleroderma, patients with generalized morphoea had the highest levels of serum sCD23. The frequency of IgM antihistone antibody (AHA) and IgM rheumatoid factor (RF), the number of linear lesions, and the frequency of muscle involvement were significantly higher in patients with elevated sCD23 levels than in those with normal levels of sCD23. A significant correlation between the serum sCD23 level and the number of involved areas of the body was observed. Our data suggest that the activation of virgin B cells, which is reflected by elevated sCD23 levels, is closely associated with the production of IgM autoantibodies in localized scleroderma and furthermore that the serum levels of sCD23 are a new serological indicator of the severity of localized scleroderma.

Adolescent↗

Soluble CD4 and CD8 in serum from patients with localized scleroderma.

Localized scleroderma has been shown to be accompanied by various immunologic abnormalities. To obtain functional information on activated CD4+ or CD8+ T cells, we studied the levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) in serum from patients with localized scleroderma. Serum samples were examined by enzyme-linked immunosorbent assay. The samples were obtained from 49 patients in the following three subgroups: 15 patients with generalized morphea, 22 with linear scleroderma, and 12 with morphea. The levels of sCD4 and sCD8 were significantly elevated in patients with generalized morphea. Furthermore, these patients showed significantly higher levels of sCD4 than those with systemic sclerosis (SSc). The frequency of positivity for IgG anti-single-stranded DNA (ssDNA) antibody was significantly higher in localized scleroderma patients with elevated sCD4 levels than in patients with normal sCD4 levels. The frequency of positivity for antinuclear antibodies, IgM antihistone antibodies, IgG anti-ssDNA antibody and rheumatoid factor, and elevated sCD23 levels were significantly higher in localized scleroderma patients with elevated sCD8 levels than in patients with normal sCD8 levels. Our findings suggest that both CD4+ and CD8+ T cells are activated in vivo in generalized morphea and that the immunologic events in generalized morphea are different from those in SSc.

Adult↗

Experiences of 120 microsurgical reconstructions of hepatic artery in living related liver transplantation.

BACKGROUND: We reviewed 120 microsurgical reconstructions of a hepatic artery in living related liver transplantation and discussed the problems encountered. METHODS: From January 1991 to July 1994 we performed a series of 105 living related liver transplantations on children with end-stage liver disease. Arterial reconstruction was performed under the optical field of a continuous zoom magnification of approximately 10 times with an operating microscope. RESULTS: Twenty-six percent of the graft arteries were less than 2 mm in diameter. The time required for an arterial reconstruction was 49.5 +/- 1.8 minutes. In 15 of the 31 cases in which there were two graft arteries, two arterial reconstructions were required. The caliber differences between the graft artery and the recipient artery in 30 instances was dealt with by cutting an undersized artery obliquely (17 instances), by fish-mouth method (10 instances), by end-to-side anastomosis (1 instance), or by funnelization method (2 instances). In one case we performed an intimal dissection of a recipient hepatic artery and substituted a splenic artery. Consequently, hepatic arterial thrombosis occurred in only two cases (1.7%). CONCLUSIONS: Microsurgical technique has overcome the high risk of hepatic arterial thrombosis in cases of fine graft arteries, enabled the reconstruction of arteries with caliber difference, and decreased arterial complications with its delicate manipulation.

Adolescent↗

Serum concentrations of basic fibroblast growth factor in collagen diseases.

BACKGROUND: Basic fibroblast growth factor (bFGF), a cytoplasmic polypeptide growth regulator that induces endothelial cell and fibroblast proliferation, is produced by endothelial cells and skeletal muscle. OBJECTIVE: We hypothesized that this factor is involved in fibrotic changes in muscle and skin in collagen diseases. METHODS: The serum level of bFGF was measured in 74 patients with systemic sclerosis, 12 with systemic lupus erythematosus, 33 with dermatomyositis, 13 with Raynaud's disease, and 20 control subjects. RESULTS: bFGF was undetectable in the serum of normal persons, but detectable levels were found in 31 of 74 patients with systemic sclerosis and 7 of 33 patients with dermatomyositis. Elevated serum bFGF level was correlated with an elevated plasma endothelin level and anticentromere antibody in patients with systemic sclerosis. An elevated serum bFGF level correlated with lung fibrosis and an elevated creatine kinase level in the patients with dermatomyositis. CONCLUSION: Measurement of the serum bFGF level may be useful to detect vascular damage in patients with systemic sclerosis and muscule fibrosis in patients with dermatomyositis.

Adolescent↗

Autoantibodies to mitochondrial 2-oxo-acid dehydrogenase complexes in localized scleroderma.

Sera from patients with localized scleroderma frequently produce cytoplasmic staining by indirect immunofluorescence, although the antigen remains to be determined. We studied the prevalence, antigen specificity and associated clinical characteristics of anti-cytoplasmic antibodies in localized scleroderma. Serum samples from 60 patients with localized scleroderma were examined by indirect immunofluorescence analysis and immunoblotting. By immunofluorescence analysis on HEp-2 cell substrate, seven of 60 (12%) patients were shown to be positive for anti-cytoplasmic antibodies. Among these, six patients with generalized morphea had anti-mitochondrial antibodies as shown by immunoblotting: they showed reactivity with the E2 component of pyruvate dehydrogenase complex (PDC), with protein X, and with the E2 component of alpha-oxo-glutarate dehydrogenase complex, while two of them showed reactivity with PDC-E1 alpha. One of these patients who was positive for anti-PDC-E1 alpha antibody showed laboratory abnormalities, suggesting the presence of primary biliary cirrhosis. The age of disease onset was significantly higher in these six patients than in those without anti-mitochondrial antibodies. Furthermore, five of them were classified into generalized morphea with multiple plaque lesions but without linear lesions (multiple plaque type). These observations suggest that major antigens for anti-cytoplasmic antibodies in patients with localized scleroderma are mitochondrial enzymes, 2-oxo-acid dehydrogenase complexes. Patients with anti-mitochondrial antibodies may comprise a unique subset of localized scleroderma designated multiple plaque type of generalized morphea of older onset.

Adolescent↗

Measurement of anticardiolipin antibodies by ELISA using beta 2-glycoprotein I (beta 2-GPI) in systemic sclerosis.

In order to determine the prevalence and clinical significance of beta 2-GPI-dependent anticardiolipin antibodies (beta 2-GPI/aCL) in patients with systemic sclerosis (SSc), serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 120 healthy control subjects were examined by ELISA using purified beta 2-GPI. IgG isotype beta 2-GPI/aCL was present in eight of 80 patients with SSc (10%), and the presence of beta 2-GPI/aCL IgG was significantly correlated with the presence of isolated pulmonary hypertension (PH). Furthermore, levels of beta 2-GPI/aCL IgG were significantly correlated with levels of mean pulmonary arterial pressure. These data suggest that IgG isotype beta 2-GPI/aCL might be a serological indicator of the severity of PH in patients with SSc.

Antibodies, Anticardiolipin↗

Chronological positron emission tomographic study of severe diffuse brain injury in the chronic stage.

Cerebral blood flow and metabolism were investigated in five patients with severe diffuse brain injury in the chronic stage, using positron emission tomography (PET). Regional cerebral blood flow, regional oxygen extraction fraction, regional cerebral blood volume, regional cerebral metabolic rate for oxygen, and regional cerebral metabolic rate for glucose were measured bilaterally in the frontal, temporal, occipital, and parietal gray matter, as well as the white matter of the centrum semiovale. In 4 of 5 patients, a follow-up PET study was also performed. In three cases, below-normal regional cerebral blood flow and regional cerebral metabolic rate for oxygen values accompanied by above-normal regional oxygen extraction fraction values, as well as low metabolism, were demonstrated in the initial PET studies. In two of three cases, clinical improvements were observed, and follow-up PET data also improved. These findings suggest that chronological PET studies may be able to assess quantitatively clinical improvements in patients with diffuse brain injury.

Adult↗

Connective tissue growth factor gene expression in tissue sections from localized scleroderma, keloid, and other fibrotic skin disorders.

Connective tissue growth factor (CTGF) is a novel peptide that exhibits platelet-derived growth factor-like activities and is produced by skin fibroblasts after activation with transforming growth factor-beta. Coordinate expression of transforming growth factor-beta followed by CTGF during wound repair suggests a cascade process for control of tissue regeneration. We recently reported a significant correlation between CTGF mRNA expression and histologic sclerosis in systemic sclerosis. To confirm the relation between CTGF and skin fibrosis, we investigated CTGF gene expression in tissue expression in tissue sections from patients with localized scleroderma, keloid, other sclerotic skin disorders using nonradioactive in situ hybridization. In localized scleroderma, the fibroblasts with positive signals for CTGF mRNA were scattered throughout the sclerotic lesions with no preferential distribution around the inflammatory cells or perivascular regions, whereas the adjacent nonaffected dermis was negative for CTGF mRNA. In keloid tissue, the fibroblasts positive for CTGF mRNA were diffusely distributed, especially in the peripheral expanding lesions. In scar tissue, however, the fibroblasts in the fibrotic lesions showed partially positive signals for CTGF mRNA. In eosinophilic fasciitis, nodular fasciitis, and Dupuytren's contracture, CTGF mRNA was also expressed partially in the fibroblasts of the fibrotic lesions. Our findings reinforce a correlation between CTGF gene expression and skin sclerosis and support the hypothesis that transforming growth factor-beta plays an important role in the pathogenesis of fibrosis, as it is the only inducer for CTGF identified to date.

Adolescent↗

Anti-ribosomal P protein antibodies in a Japanese patient with systemic sclerosis.

A 56-year-old Japanese woman developed Raynaud's phenomenon and digital ulcerations at the age of 50. She showed rapid and diffuse skin sclerosis; visceral involvement was mild. She showed no symptoms or laboratory findings suggestive of other collagen diseases, including systemic lupus erythematosus and Sjögren's syndrome. Based on the clinical and histological findings, she was diagnosed as having diffuse cutaneous systemic sclerosis (SSc). The patient's serum produced nucleolar and cytoplasmic staining by indirect immunofluorescence analyses on HEp-2 cell substrate and reacted with P0, P1 and P2 proteins in immunoblotting using purified ribosomal antigens. She was negative for anti-topoisomerase I, centromere, and U1RNP antibodies. Antiribosomal P protein antibodies are considered highly specific for systemic lupus erythematosus; this is the first case report of an SSc patient with anti-ribosomal P protein antibodies. The clinical features of SSc patients with these antibodies need to be clarified by an accumulation of cases.

Autoantibodies↗

Detection of antiendometrial antibodies in patients with endometriosis by cell ELISA.

PROBLEM: To determine whether infertile patients with endometriosis have serum antiendometrial antibodies. METHODS: Sera from 40 infertile patients with or without endometriosis were tested by cell enzyme-linked immunosorbent assay (ELISA), in which endometrial cancer cells were used as endometrial antigens, and uterine cervix cancer cells as control antigens. As a negative control, eight healthy adult males were included. The level greater than the mean +/- 2 standard deviations (SD) of the male control group was judged positive. RESULTS: The mean value of antiendometrial antibody level was significantly higher in patients with endometriosis than in those without endometriosis (ANOVA, P < 0.01). The frequency of antiendometrial antibody-positive patients was also higher in the former than in the latter (chi 2 test, P < 0.05). However, when uterine cervix cancer cells were used as antigens, no difference was observed in the mean antibody levels or in the positive rates between the two groups. CONCLUSIONS: Endometriosis seems to be associated with autoantibody production against the endometrium-related antigen(s).

Adult↗

Antiubiquitin antibody in localised and systemic scleroderma.

OBJECTIVE: To determine the presence of antiubiquitin antibody (AUbA) in localised scleroderma and systemic sclerosis, as it is frequently found in the sera of patients with systemic lupus erythematosus (SLE) and has also been shown to have a close relationship with antihistone antibodies that have an important role in scleroderma. METHODS: Serum samples from patients with localised scleroderma (n = 48) and systemic sclerosis (n = 52) were examined by enzyme linked immunosorbent assay. Twenty samples from patients with SLE, 20 from patients with dermatomyositis, and 30 samples from healthy individuals were used as controls. RESULTS: AUbA was demonstrated in 44% of patients with localised scleroderma and in 42% of those with systemic sclerosis. The presence of AUbA correlated with the presence of antihistone antibodies in both localised scleroderma and systemic sclerosis. CONCLUSIONS: AUbA is frequently present in patients with localised scleroderma and systemic sclerosis. Induction of AUbA is closely associated with that of antihistone antibodies, suggesting that ubiquitinated histone may be the target in autoimmune responses of these disorders.

Adolescent↗

Juvenile temporal arteritis with eosinophilia: a distinct clinicopathological entity.

BACKGROUND: Juvenile temporal arteritis has been proposed as an entity but remains controversial. CASE REPORT: A 39-year-old male, who was otherwise asymptomatic, developed painless bilateral nodules in the temporal areas. His eosinophil blood count was 2,660/mm3 (31%), while the erythrocyte sedimentation rate was normal. Histologic examination of the lesion revealed non-giant-cell granulomatous inflammation with abundant eosinophil infiltration. The clinical and pathologic manifestations in our patient were different from those in classic temporal arteritis, which occurs almost exclusively in individuals over the age of 50 years, allergic granulomatosis and angiitis, and thromboangiitis obliterans. Eight cases of this disease have previously been reported in the literature. CONCLUSION: We consider that 'juvenile temporal arteritis with eosinophilia' is a distinct clinical and pathologic entity. The prognosis of the diseases is considered to be good.

Adult↗

Requirement for transglutaminase in progesterone-induced decidualization of human endometrial stromal cells.

Differentiation of endometrial stromal cells (decidualization) is essential for embryo implantation and maintenance of pregnancy. By sequential complementary DNA subtractive hybridization, one of the messenger RNAs (mRNA) induced by progesterone in human endometrial stromal cells decidualized in vitro was identified as that of a tissue transglutaminase type II (TGase). TGase mRNA was induced within 6 h after the addition of progesterone to the culture, and the effect was dose dependent. Both the TGase inhibitor monodansylcadaverine and oligodeoxynucleotide complementary to the TGase mRNA inhibited the decidualization, as assessed by PRL production and morphological transformation. Expression of TGase mRNA in human decidua and endometria exposed to high levels of progesterone in vivo was demonstrated by Northern blotting and in situ hybridization. These data suggest that TGase is necessary for the decidualization of human endometrial stromal cells and that clarification of the mechanism of action of TGase will facilitate further insight into the diagnosis and treatment of infertility.

Base Sequence↗

Vasoactive intestinal peptide enhances immunoglobulin production and growth in human plasma cells via mechanisms that may involve protein kinase C.

The effects of various neuropeptides on human plasma cells were studied. Of the various neuropeptides tested, vasoactive intestinal peptide (VIP) enhanced Ig production and growth in human plasma cell lines, IM-9 and AF-10, and in plasma cells generated in vivo (four out of four patients with plasma cell leukemia) and in vitro. In contrast, other neuropeptides (neuropeptide Y, somatostatin, substance P, peptide YY, neurokinin A, calcitonin gene-related peptide, chole-cystokinin octapeptide, and beta-endorphin) were ineffective. Moreover, VIP-induced enhancement was specifically blocked by VIP receptor antagonist. Among the various cytokines, IL-6, GH, and insulin-like growth factor I (IGF-I) also enhanced Ig production and thymidine uptake in plasma cells. However, VIP-induced enhancement was not mediated by IL-6, GH, or IGF-I because antibodies to these cytokines failed to block VIP-induced enhancement. Phorbol 12,13 dibutyrate enhanced Ig production and thymidine uptake in plasma cells, and the Phorbol 12,13 dibutyrate-induced enhancement was blocked by H7 (a protein kinase C inhibitor) but not by H8 (a protein kinase A inhibitor). Similarly, VIP-induced enhancement was blocked by H7 but not by H8. Collectively, VIP enhances plasma cell responses via mechanisms that may involve protein kinase C.

Cell Division↗

Endothelin receptor antagonist triterpenoid, myriceric acid A, isolated from Myrica cerifera, and structure activity relationships of its derivatives.

As the first non-peptide endothelin receptor antagonist from a higher plant, a new triterpenoid, myriceric acid A (50-235) (1) was isolated from the bayberry, Myrica cerifera. Myriceric acid A (1) inhibited not only an endothelin-1-induced increase in cytosolic free Ca2+ concentration (IC50 = 11 +/- 2 nM) but [125I]endothelin-1 binding in rat aortic smooth muscle cells (Ki = 66 +/- 15 nM). Two new related triterpenoids, myriceric acid C (6), and myriceric acid D (8), were also isolated. Furthermore, the chemical modification of these natural products led to the synthesis of sulfated derivatives (13, 14, 15) which showed 1.5 to 20 times higher affinity for endothelin receptors. The structure activity relationships of myriceric acids and their derivatives are discussed.

Animals↗

Expression of two different cholecystokinin receptors in Xenopus oocytes injected with mRNA from rabbit pancreas and rat hippocampus.

Electrophysiological responses to cholecystokinin (CCK) were studied in Xenopus oocytes injected with mRNA from rabbit pancreas or rat hippocampus. CCK-octapeptide(26-33) (sulfated form) (CCK-8) elicited inward currents in both groups. In oocytes injected with pancreatic mRNA, CCK-8-induced currents were composed of two components, fast and slow. However, in oocytes injected with hippocampal mRNA, fast currents disappeared. The potency ranking of the agonists and the antagonist indicated that the receptors expressed by pancreatic and hippocampal mRNA were CCKA- and CCKB-subtypes, respectively. Extracellular application of EGTA had little effect on the CCKB-mediated response, but attenuated the CCKA-mediated one. Intracellular injection of EGTA abolished the CCKB-mediated response, whereas small smooth currents remained in oocytes expressing the CCKA-receptor. The reversal potentials of the CCKA- and CCKB-receptor-mediated responses were consistent with that for CI- currents. However, the reversal potential of the small smooth currents in EGTA-loaded oocytes expressing the CCKA-receptors was close to that for a non-selective cation channel. These results suggest that CCK-8 activates at least two different channels, a Ca(2+)-dependent Cl- channel and a non-selective cation channel in oocytes expressing the CCKA-receptor, while the CCKB-receptor elicits only a Ca(2+)-dependent Cl- channel.

Animals↗