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Biomedical subjects

M Fujimoto

Publications and source records attributed to M Fujimoto.

At least 253 records · Page 14Linked to original sources
PubMed1995

Induction of IgA1 and IgA2 production in immature human fetal B cells and pre-B cells by vasoactive intestinal peptide.

We studied the effects of vasoactive intestinal peptide (VIP) on IgA1 and IgA2 production in human fetal B cells and pre-B cells derived from bone marrow. VIP induced IgA1, IgA2, and IgM production in sIgM+, CD19+ fetal B cells stimulated with anti-CD40 monoclonal antibody (MoAb) without inducing the production of IgG1, IgG2, IgG3, IgG4, or IgE. The anti-CD40 MoAb plus VIP also induced IgA1, IgA2, and IgM production in sIgM-, CD19+ pre-B cells, which was enhanced by the addition of interleukin-7 (IL-7). This induction by VIP was specific, as the anti-CD40 MoAb plus other neuropeptides [ie, somatostatin (SOM) or substance P (SP)] had no effect, and moreover, the induction was specifically blocked by a VIP antagonist. Furthermore, the anti-CD40 MoAb plus various cytokines, including IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, transforming growth factor beta (TGF-beta), low-molecular-weight B-cell growth factor (BCGF), and interferon-gamma (IFN-gamma), did not induce IgA1 and IgA2 production in fetal B cells or pre-B cells. These findings indicate that, in the presence of costimulators, VIP may induce IgA1 and IgA2 production by isotype switching.

Antibodies, Monoclonal↗
PubMed1995

Interleukin 8 (IL-8) inhibits the interleukin 4 (IL-4)-induced but not the spontaneous growth of human B cells via mechanisms that may involve protein kinase C.

IL-8 inhibited the IL-4-induced but not the spontaneous growth of both a human B cell line, CBL, and in vivo activated B cells. This inhibition was specific to IL-8, since anti-IL-8 mAb, but not control IgG1, blocked inhibition. Phorbol 12, 13 dibutyrate did not affect the IL-4-induced B cell growth; however, it reversed the IL-8-mediated inhibition, and this reversal was blocked by H7 (a protein kinase C inhibitor), but not by H8 (a protein kinase A inhibitor). These results indicate that IL-8 inhibits IL-4-induced B cell growth via specific mechanisms that may involve protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Autoantibodies to pyruvate dehydrogenase complex in patients with systemic sclerosis. Possible role of anti-E1 alpha antibody as a serologic indicator for development of primary biliary cirrhosis.

OBJECTIVE: To determine the prevalence and clinical significance of anti-pyruvate dehydrogenase complex (anti-PDC) antibodies in systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (n = 81) or diffuse cutaneous SSc (n = 63) were examined for anti-PDC antibodies by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: IgG- and/or IgM-isotype anti-PDC antibodies were demonstrated by ELISA in 26 of 144 patients with SSc (18%). By immunoblotting, 19 patients had IgG anti-PDC antibodies. Among these patients with IgG anti-PDC antibodies, antibody to the E1 alpha subunit was significantly associated with the presence of laboratory abnormalities typical of primary biliary cirrhosis (PBC). CONCLUSION: Antibody to the E1 alpha subunit of PDC may be a serologic indicator for the development of PBC in patients with SSc.

Adult↗
PubMed1995

Involvement of interleukin (IL)-13, but not IL-4, in spontaneous IgE and IgG4 production in nephrotic syndrome.

Nephrotic syndrome (NS) is a renal disease characterized by proteinuria and hypoalbuminemia. In NS patients without any allergic disease, serum IgE and IgG4 levels were selectively increased, and peripheral blood mononuclear cells (MNC) spontaneously produced IgE and IgG4. T cells produced interleukin (IL)-13 spontaneously, and B cells constitutively expressed IL-13 receptors (IL-13R). In addition, T cells stimulated surface IgE-negative (sIgE-) and sIgG4- B cells to produce IgE and IgG4, respectively, and IgE and IgG4 production was specifically blocked by anti-IL-13 antibody (Ab). MNC from atopic dermatitis (AD) patients also produced IgE and IgG4 spontaneously. However, in AD patients, T cells spontaneously produced IL-4, but not IL-13, and B cells constitutively expressed IL-4R, but not IL-13R. T cells stimulated sIgE- and sIgG4- B cells to produce IgE and IgG4, respectively, and the production was specifically blocked by anti-IL-4 Ab. On the other hand, sIgE+ and sIgG4+ B cells from both NS and AD patients spontaneously produced IgE and IgG4, respectively, and this production was not affected by T cells, anti-IL-4 Ab, or anti-IL-13 Ab. These results indicate that IL-13 is involved in the enhanced production of IgE and IgG4 in NS, while IL-4 is involved in these responses in AD.

Adolescent↗
PubMed1995

Microheterogeneity of mouse antidextran monoclonal antibodies.

Mouse antidextran monoclonal antibodies showed microheterogeneity which was analyzed by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Not only the heavy (H) chains but also the light (L) chains were heterogeneous in terms of isoelectric point (pI). The higher the pI, the more prominent the H chain spots. To demonstrate the cause of the microheterogeneity an IgG1 monoclonal antibody (mAb 35.8.2H) was examined especially for involvement of the sugar moiety in the microheterogeneity. The glycosylated region was determined in the Fc portion from serine 239 to methionine 309 by a glycan detection method using mild periodate oxidation, which confirms that the sugar chain is attached to the conserved glycosylation site of asparagine 297. However, charge heterogeneity of the H chain was not entirely attributed to the Fc because the papain digest of the antibody was separated into two Fc spots, a few Fd spots and two L chain spots by 2-D PAGE. This indicates that factors other than the sugar moiety are responsible for charge heterogeneity of IgG monoclonal antibody. On the other hand, the H chain isoforms of lower pI were shown to be more susceptible to V8 protease by peptide mapping. This result strongly suggests the occurrence of deamidation at glutamine or asparagine residues.

Amino Acid Sequence↗
PubMed1995

Differential expression of nucleophosmin and stathmin in human T lymphoblastic cell lines, CCRF-CEM and JURKAT analyzed by two-dimensional gel electrophoresis.

Two-dimensional gel electrophoresis was used to study the expression of intracellular proteins in adherent cells of human T lymphoblastic cell line, CCRF-CEM. The adherent cells grown in monolayer on a culture plate decreased the amount of proteins of M(r) 37,000 and pI 4.7-4.9, and of 17,000 and pI 5.7. The proteins were identified to be nucleophosmin for the 37,000 protein and stathmin for the 17,000 protein by microsequencing their CNBr fragments. The amount of proteins was increased in CCRF-CEM cells grown in floating mass to a comparable level of JURKAT cells which grew in floating mass throughout the culture. The adherent cells decreased their growth rate as compared with the cells in the floating mass. These results suggest that the adhesion of human T lymphoblastic cells modulates their morphology and proliferation via a concomitant decrease in the amount of nucleophosmin and stathmin.

Amino Acid Sequence↗
PubMed1995

Evaluation of protective effects of prostaglandin E1 on ischemic liver damage with in vivo 31P-MR spectroscopy.

The cytoprotective effect of prostaglandins (PG) was evaluated by in vivo 31P MR spectroscopy. Twenty rabbits were divided into two groups; the control group given physiological saline, and the PG group given prostaglandin E1 (0.5 microgram/kg/min). Each solution was infused for 8 min, after which complete hepatic ischemia was induced for 20 min, followed by reperfusion for 40 min. During ischemia, beta-ATP decreased to 23.6% and 42.3%, phosphomonoester increased to 260% and 200% of their initial values in the control and the PG groups, respectively. Inorganic phosphate also increased. After reperfusion, beta-ATP recovered to 65.2% and 96.5%, phosphomonoester to 130% and 110%, inorganic phosphate to 140% and 120% in the control and PG groups, respectively. The changes during ischemia were significantly smaller and the recoveries during reperfusion were more complete in the PG group. These results may confirm the cytoprotective effect of prostaglandins by in vivo 31P-MR spectroscopy.

Adenosine Triphosphate↗
PubMed1995

Recovery of graft circulation following percutaneous transluminal angioplasty for stenotic venous complications in pediatric liver transplantation: assessment with Doppler ultrasound.

Percutaneous transluminal angioplasty was performed for venous stenosis after living related liver transplantation in three children. Two of them had hepatic vein stenosis and one had stenosis of both the hepatic and portal veins. Progressive development of ascites and deterioration of liver function were found in all cases. Serial Doppler ultrasound studies showed that the flow velocity in the hepatic vein gradually decreased with a flattened velocity waveform, followed by a decrease in portal blood flow. After a successful hepatic vein angioplasty, the velocity in the hepatic and portal veins increased and the Doppler waveform in the hepatic vein became pulsatile in two cases. In the remaining case, a remarkable recovery of both graft perfusion and clinical findings was achieved via combined hepatic vein and portal vein angioplasty. We conclude that balloon angioplasty is an effective alternative to surgery for post-transplant vascular stenosis and that Doppler ultrasound is useful in monitoring graft circulation.

Angioplasty, Balloon↗
PubMed1995

Autoantibodies to the heat-shock protein hsp73 in localized scleroderma.

We determined the presence of antibodies to the heat-shock protein hsp73 (anti-hsp73) in 57 serum samples from patients with localized scleroderma using an enzyme-linked immunosorbent assay (ELISA). In addition, 30 samples from healthy individuals, 30 from patients with systemic lupus erythematosus (SLE) and 32 from patients with systemic sclerosis were assessed. IgG and/or IgM anti-hsp73 antibodies were detected in 33% (19/57) of the patients with localized scleroderma. Among the three subtypes of localized scleroderma, generalized morphoea showed the highest incidence of anti-hsp73 antibodies (40%, 6/15). IgG and/or IgM anti-hsp73 antibodies were also detected in 9/30 samples (30%) from patients with SLE and in 13/32 samples (41%) from patients with systemic sclerosis, while the samples from the healthy controls were all negative for anti-hsp73. By immunoblotting, specific binding of antibodies to hsp73 was confirmed with representative serum samples that were positive for anti-hsp73 in the ELISA. Our findings indicate that the presence of anti-hsp73 is an additional immunological abnormality in localized scleroderma.

Adolescent↗
PubMed1995

Demonstration of interleukin-2, interleukin-4 and interleukin-6 in sera from patients with localized scleroderma.

Localized scleroderma has been reported to be accompanied by immunological abnormalities related to B cells, but little is known about T-cell activation in this disease. In this study, serum levels of interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6), which are known to be released by activated T cells, were determined using a sensitive enzyme-linked immunosorbent assay in 48 patients with localized scleroderma and 20 with systemic sclerosis, and in 20 healthy control subjects. IL-2, IL-4 and IL-6 were detected in serum from patients with localized scleroderma but not in that from healthy controls. The presence of antihistone antibodies correlated significantly with elevated IL-4 and IL-6 levels. Decreased serum levels of IL-2, IL-4 and IL-6 paralleled improvement in cutaneous sclerosis. Frequent detection of these lymphokines in serum from patients with localized scleroderma reflects T-cell activation in this disorder.

Autoantibodies↗
PubMed1995

Kissing aneurysms of distal anterior cerebral arteries demonstrated by magnetic resonance angiography.

BACKGROUND Multiple aneurysms, associated with distal anterior cerebral artery (ACA) aneurysm, are not rare; therefore, it is important to examine multiplicity of the aneurysms preoperatively. CASE REPORT A case of ruptured distal ACA aneurysm, associated with another one in a mirror position, is reported. A 43-year-old woman suffered subarachnoid hemorrhage. Conventional angiography demonstrated a saccular aneurysm on the bifurcation of the right or left distal ACA; however, magnetic resonance angiography (MRA) revealed two mirror-image aneurysms on both bifurcations. CONCLUSION MRA was useful for preoperative diagnosis of kissing aneurysms on distal ACAs.

Adult↗
PubMed1995

Vascular complications in living related liver transplantation detected with intraoperative and postoperative Doppler US.

BACKGROUND/AIMS: The purpose of this study was to clarify changes in the graft hemodynamics induced by vascular complications in living related liver transplantation. METHODS: This study included 46 pediatric recipients who underwent partial liver transplantation from living related donors. The blood flow was evaluated in the portal system, the hepatic artery and the hepatic vein with serial intra- and post-operative Doppler ultrasound (US). RESULTS: In 12 patients, intraoperative Doppler US showed a decrease in portal venous inflow (< 9 ml.min-1.kg-1) toward the liver graft and could act as a guide for ligation of collaterals in seven patients, portal re-construction in two, thrombectomy in one and relief of hepatic venous outflow obstruction in two for increasing the portal venous inflow. In five patients, intraoperative Doppler US showed poor arterial inflow, i.e. dampened arterial waveforms which involved both low pulsatility index (< 0.90) and low peak-systolic velocity (< 31 cm/s). In three of them, the waveform was more pulsatile after re-anastomosis or relief from stretching of the hepatic artery. The remaining two patients developed hepatic artery thrombosis. Most of the hepatic venous outflow obstruction (four of five patients) had flat waveforms, low flow velocity (< 10 cm/s) of the hepatic vein, and poor portal inflow (flow velocity < 14 cm/s). Postoperative Doppler US showed hepatic venous outflow obstruction in three patients, hepatic artery thrombosis in three (twice in one patient), portal vein stenosis in two and portal vein thrombosis in one. These complications were successfully managed with surgical procedures in three patients, transhepatic angioplasty in three and conservative treatments in four. Six patients died of non-vascular complications. CONCLUSIONS: Serial intra- and post-operative Doppler US was a useful technique for making an early diagnosis of abnormal hemodynamics of the graft circulation. Furthermore, intraoperative Doppler US could assess reconstructed vessels objectively and would reduce the incidence of vascular complications following transplantation.

Adolescent↗
PubMed1995

Serum tissue inhibitor of metalloproteinases in patients with systemic sclerosis.

BACKGROUND: One of the suggested contributory factors to the development of dermal fibrosis is a decrease in collagenase activity, which may be related to levels of serum tissue inhibitors of metalloproteinase-1 (TIMP-1). OBJECTIVE: The aim of this study was to determine the clinical significance of serum TIMP-1 levels in systemic sclerosis (SSc). METHODS: We measured serum TIMP-1 concentration in 62 patients with SSc, 11 patients with systemic lupus erythematosus, 14 patients with rheumatoid arthritis, and 22 members of a normal control group. The clinical features of the patients with SSc and elevated TIMP levels were examined. RESULTS: The mean TIMP-1 level in the patients with SSc was significantly higher than that in the members of the control group or the patients with systemic lupus erythematosus or rheumatoid arthritis. In 44% of the patients with SSc the serum TIMP-1 level was elevated. The mean serum TIMP-1 level in patients with diffuse cutaneous SSc (dSSc) was significantly higher than that in those with limited cutaneous SSc. The patients with dSSc and elevated serum TIMP-1 levels showed a significantly greater incidence of lung fibrosis and anti-topoisomerase I antibody than those with normal serum TIMP-1 levels. The TIMP-1 level and diffusing capacity for carbon monoxide in the patients with SSc were negatively correlated. Increased mitogenic activity on dermal fibroblasts caused by serum from patients with dSSc was partially blocked by anti-TIMP-1 IgG. CONCLUSIONS: These findings suggest that serum TIMP-1 level is a useful indicator of disease activity in patients with SSc and that TIMP is involved in the pathogenesis of SSc.

Adolescent↗
PubMed1995

Expression of leukaemia inhibitory factor (LIF) receptor in human placenta: a possible role for LIF in the growth and differentiation of trophoblasts.

Leukaemia inhibitory factor (LIF) is a cytokine that displays multiple activities in various tissues and is essential for blastocyst implantation in mice. In the human uterus, LIF is expressed in endometrial tissue and the decidua. To elucidate the role it plays, the mRNA levels for two LIF receptor (R) subunits, LIF-R and gp130, were examined in human endometrium, placenta and decidua by Northern blot hybridization. The expression of LIF-R gene was detected in the chorionic villus during the first trimester, in term placenta, and at lower levels in the decidua. The expression of LIF-R gene was not detectable in non-pregnant endometrium. The expression of the gp130 gene was detected in all tissues examined. During pregnancy, there was no significant change in the mRNA concentration of LIF-R in the placenta, while that of gp130 increased after the second trimester. The human choriocarcinoma cell line, BeWo, was found to express LIF-R and gp130. LIF inhibited forskolin-induced human chorionic gonadotrophin (HCG)-beta production by BeWo in a dose-dependent manner, and it ameliorated forskolin-induced growth suppression. These findings suggest that LIF plays a regulatory role in trophoblast growth and differentiation during pregnancy in human placenta.

Base Sequence↗
PubMed1995

Neuropeptide YY1 receptors-mediated increase in intracellular Ca2+ concentration via phospholipase C-dependent pathway in porcine aortic smooth muscle cells.

In porcine aortic smooth muscle cells, neuropeptide Y (NPY) stimulates mobilization of CA(2+) from intracellular store sites via Y1 receptors. However, it has been debated whether or not Ca(2+) mobilization by Y1 receptors depends on the generation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] following activation of phospholipase C. To examine this question, we studied the effect of U73122, an inhibitor of phospholipase C-mediated inositol phosphate accumulation on the NPY-induced rise in cytosolic free Ca(2+) concentration ([Ca(2+)]i) in comparison with that on angiotensin II (AII)-induced [Ca(2+)]i increase, which is dependent on Ins(1,4,5)P3 generation. Digital-imaging microscopy study using the Ca(2+)-sensitive dye fura-2 revealed that application of AII induced a rapid but transient [Ca(2+)]i increase in a single cell, arising from intracellular calcium stores. Application of NPY to the same cell induced a [Ca(2+)]i rise with a pattern similar to that induced by AII. AII increased the formation of Ins(1,4,5)P3 by about 3.0 fold, while the NPY-induced [Ca(2+) formation was very small. U73122 completely inhibited not only Ins(1,4,5)P3 synthesis, but also Ca(2+) mobilization induced by either agonist. The effect of U73122 on the NPY-induced Ca(2+)i increase was about 10-fold more potent that on the AII-induced one. U73343, an inactive analog of U733343, had no influence on any of the AII- and NPY-mediated effects. Herbimycin A completely inhibited the platelet-derived growth factor-induced [Ca(2+]i increase but had no effect on the NPY-induced [Ca(2+)]i increase, indicating that phospholipase C-gamma is not involved in the NPY effect. These results suggest that NPY-induced Ca2+ mobilization from intracellular stores in porcine smooth muscle cells is secondary to the very small generation of Ins(1,4,5)P3 following stimulation of phospholipase C-beta, which may account for the hypersensitivity of the NPY effect to U73122.

Angiotensin II↗
PubMed1995

Detection of antiribosomal P protein antibodies in patients with systemic sclerosis.

This study investigated the prevalence and clinical significance of anti-ribosomal P protein (anti-P) antibodies in patients with systemic sclerosis (SSc). Serum samples from 150 patients with SSc were examined by indirect immunofluorescence. ELISA and immunoblotting. Anti-P antibodies were detected in four (3%) patients with SSc. Three of the four patients showed SSc/SLE (systemic lupus erythematosus) overlap syndrome, but psychiatric disorders were not observed in these patients. By longitudinal immunoblotting analysis one patient, who was initially diagnosed with SSc, later developed anti-P antibodies along clinical manifestations of SLE. Our data suggest that anti-P antibodies are uncommon in SSc and that the presence of anti-P antibodies in patients with SSc indicates an overlap with SLE.

Adult↗
PubMed1995

Ultrasound measurement of skin thickness in systemic sclerosis.

Sclerotic skin change in systemic sclerosis (SSc) usually accompanies increased skin thickness. In order to quantify the cutaneous changes and to clarify the changes in the 'uninvolved' skin in systemic sclerosis (SSc), we measured the skin thickness on the chest, the forearms and the hands of 79 patients with SSc and 81 healthy controls with a B-mode ultrasound (30 MHz) apparatus. The thickness of the 'uninvolved', as well as the 'involved' skin in patients with SSc was significantly greater than that of healthy controls. Increased skin thickness on the forearms and/or the hands showed a 64.6% sensitivity and a 100% specificity for SSc. These results indicated that the skin which appears to be 'uninvolved' in patients with SSc is already pathologic, as shown by increased thickness. Moreover, measurement of skin thickness may be beneficial in the diagnosis of this disease at an early stage.

Adolescent↗