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M Seishima

Publications and source records attributed to M Seishima.

At least 19 recordsLinked to original sources
PubMed2006

Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy.

OBJECTIVE: Myositis-specific autoantibodies (MSAs) are a useful tool in diagnosis, defining clinical subsets and predicting prognosis of dermatomyositis (DM) and polymyositis (PM). In this study, we identified a novel MSA reactive with 155 and 140 kDa nuclear proteins [anti-155/140 antibody (Ab)] and determined the clinical feature of DM patients positive for this autoantibody (autoAb). METHODS: Sera from 52 Japanese patients with DM, 9 with PM, 48 with systemic lupus erythematosus (SLE), 126 with systemic sclerosis and 18 with idiopathic interstitial pneumonia were examined by immunoprecipitation assays. Positive sera were further characterized by immunodepletion and immunofluorescence staining. RESULTS: Seven of the 52 (13%) Japanese patients with DM immunoprecipitated 155 and 140 kDa proteins from 35S-labelled K562 leukaemia cell extract. No patients with SLE, systemic sclerosis or idiopathic interstitial pneumonia as well as healthy controls were positive for this autoAb. Patients with anti-155/140 Ab developed heliotrope rash, Gottron's papules or sign and flagellate erythema significantly more frequently than those negative. Notably, internal malignancy was found at significantly higher frequency in those positive than those negative (71 vs 11%; P < 0.005). In contrast, none of these patients positive for this autoAb had interstitial lung disease. CONCLUSIONS: This novel MSA is associated with cancer-associated DM and may serve as a diagnostic serological marker for this specific subset.

Adult↗
PubMed2006

Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome.

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is characterized by a severe multiorgan hypersensitivity reaction that usually appears after a 3-6-week exposure to certain drugs, including anticonvulsants. There are some reports showing that serum IgG levels often decrease at the early stage of DIHS. Reactivation of human herpesvirus (HHV)-6 has been reported in patients with DIHS, and some other DIHS patients showed reactivation of cytomegalovirus (CMV) or Epstein-Barr virus (EBV). OBJECTIVES: To determine whether reactivation of HHV-6, HHV-7, CMV and/or EBV occurs in patients with DIHS. METHODS: Titres of IgG and IgM antibodies to HHV-6 and HHV-7 were determined using an indirect immunofluorescence antibody assay on admission and at various times after admission. Anti-CMV IgG and IgM antibody titres and anti-EBV capsid antigen IgG, IgA, IgM, and EBV nuclear antigen and EBV early antigen IgG titres were determined by enzyme immunoassay. Polymerase chain reaction (PCR) procedures for HHV-6, HHV-7, CMV and EBV DNAs were performed using serum samples. IgG antibody titres to HHV-6, HHV-7, CMV and EBV were increased after the onset in seven, six, seven and two of seven patients, respectively. IgG antibody titres to HHV-6 and HHV-7 were elevated simultaneously 21-38 days after the onset. RESULTS: IgG antibody titres to CMV and EBV were elevated 10-21 days after the elevation of HHV-6 and HHV-7 antibody titres. PCR showed that HHV-6, HHV-7, CMV and EBV DNAs became positive in six, five, seven and two of seven patients, respectively. HHV-6 and HHV-7 DNAs were detected 21-35 days after the onset, and CMV DNA was detected 10-21 days after detection of HHV-6 and HHV-7 DNAs. CONCLUSION: The present study suggests that in addition to HHV-6 reactivation, reactivation of HHV-7, CMV and/or EBV may also occur following drug eruption in some patients with DIHS.

Adult↗
PubMed2005

Identification of differentially expressed genes in psoriasis using expression profiling approaches.

To identify differentially expressed genes which play causal roles in pathogenesis and maintenance for psoriasis, we used BodyMapping and introduced amplified fragment length polymorphism approaches. From the BodyMap database, we selected 2007 genes which specifically expressed in epithelial tissues. Among 2007 genes, we surveyed genes which differentially expressed in involved or uninvolved psoriatic lesional skin samples compared with atopic dermatitis, mycosis fungoides, and normal skin samples. As a result of surveying 2007 genes, 241 genes were differentially expressed only in involved psoriatic skin but not in the other samples. Hierarchical cluster analysis of gene expression profiles showed that 13 independent psoriatic-involved skin samples clustered tightly together, reflecting highly similar expression profiles. Using the same 2007 gene set, we examined gene expression levels in five serial lesions from distal uninvolved psoriatic skin to involved psoriatic plaque. We identified seven genes such as alpha-1-microglobulin/bikunin precursor, calnexin, claudin 1, leucine zipper down-regulated in cancer 1, tyrosinase-related protein 1, Yes-associated protein 1, and unc-13-like protein (Coleonyx elegans) which show high-expression levels only in uninvolved psoriatic lesions. These seven genes, which were reported to be related to apoptosis or antiproliferation, might have causal roles in pathophysiology in psoriasis.

Apoptosis↗
PubMed2001

Tumor necrosis factor-alpha (TNF-alpha) plays a protective role in acute viralmyocarditis in mice: A study using mice lacking TNF-alpha.

BACKGROUND: It has been reported that tumor necrosis factor-alpha (TNF-alpha) is expressed in the heart with viral myocarditis and that its expression aggravates the condition. The pathophysiological effects of TNF-alpha on viral myocarditis, however, have not been fully elucidated. METHODS AND RESULTS: To investigate the role of TNF-alpha in the progression of viral myocarditis, we used TNF-alpha gene-deficient mice (TNF-alpha(-/-)) and induced acute myocarditis by infection with encephalomyocarditis virus (EMCV). The survival rate of TNF-alpha(-/-) mice after EMCV infection was significantly lower than that of TNF-alpha(+/+) mice (0% versus 67% on day 14). Injection of recombinant human TNF-alpha (0.2 to 4.0 microg/mouse IV) improved the survival of TNF-alpha(-/-) mice in a dose-dependent manner, indicating that TNF-alpha is essential for protection against viral myocarditis. The levels of viral titer and viral genomic RNA of EMCV in the myocardium were significantly higher in TNF-alpha(-/-) than in TNF-alpha(+/+) mice. Histopathological examination showed that the inflammatory changes of the myocardium were less marked in TNF-alpha(-/-) than in TNF-alpha(+/+) mice. Immunohistochemical analysis revealed that the levels of immunoreactivity of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the myocardium were decreased in TNF-alpha(-/-) mice compared with TNF-alpha(+/+) mice. CONCLUSIONS: These observations suggested that TNF-alpha is necessary for adhesion molecule expression and to recruit leukocytes to inflammatory sites, and thus, the lack of this cytokine resulted in failure of elimination of infectious agents. We concluded that TNF-alpha plays a protective role in the acute stage of viral myocarditis.

Acute Disease↗
PubMed2001

Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-gamma-independent mechanism.

Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the L-tryptophan-kynurenine pathway, which converts an essential amino acid, L-tryptophan, to N-formylkynurenine. It has been speculated that IFN-gamma is a dominant IDO inducer in vivo. The present study used IFN-gamma or TNF-alpha gene-disrupted mice and IFN-gamma antibody-treated mice to demonstrate that lipopolysaccharide (LPS)-induced systemic IDO is largely dependent on TNF-alpha rather than IFN-gamma. IFN-gamma-independent IDO induction was also demonstrated in vitro with LPS-stimulated monocytic THP-1 cells. These findings clearly indicate that there is an IFN-gamma-independent mechanism of IDO induction in addition to the IFN-gamma-dependent mechanism.

Animals↗
PubMed2001

Transient translocation of hemidesmosomal bullous pemphigoid antigen 1 from cytosol to membrane fractions by 12-O-tetradecanoylphorbol-13-acetate treatment and Ca2+-switch in a human carcinoma cell line.

We previously showed that 12-O-tetradecanoylphorbol-13-acetate (TPA) and Ca2+-switch from low (0.07 mM) to normal (1.87 mM) concentration in culture medium, which were also linked to activation of protein kinase C (PKC), lead to phosphorylation of 180 kDa-bullous pemphigoid antigen (BPAG) 2, but not of 230 kDa-BPAG1, and possibly to its disassembly from hemidesmosomes in a human squamous cell carcinoma cell line (DJM-1). In this study, we examined the effects of TPA and Ca2+-switch on intracellular localization of BPAG1 by immuno-blotting and immuno-fluorescence microscopy with monoclonal antibodies to the antigen after sub-cellular fractionation. In DJM-1 cells cultured in low Ca2+ medium, BPAG1 was detected as phosphate buffered saline-soluble (cytosolic), Triton X-100 soluble (roughly membrane-associated) and Triton X-100 insoluble (cytoskeleton-bound) forms, whereas in normal Ca2+-grown cells only as cytosolic and cytoskeleton-bound forms. In normal Ca2+-cultured cells, TPA (50 nM) caused a complete translocation of BPAG1 from cytosol to membrane fractions within 10 min, that was inhibited by pretreatment with H7 (a selective PKC inhibitor) at 40 microM. After 30 min and 4 h of TPA-treatment, BPAG1 was exclusively detected in cytoskeleton fractions. Morphologically, immuno-fluorescence microscopy showed that treatment caused a marked reduction of BPAG1 from the cytoplasm and generated a linear pattern at cell-cell contacts, suggesting translocation of BPAG1 from the cytosol to the plasma membrane. In contrast, the Ca2+-switch from low to normal caused a prominent increase of BPAG1, both in cytosolic and membrane-associated forms after 4 h, that was inhibited both with H7 and cycloheximide (an inhibitor of protein synthesis) at 70 microM, suggesting a role for PKC and BPAG1 synthesis in these Ca2+-induced effects. These results suggest that TPA and Ca2+-switch induced BPAG1 translocation to membrane fractions possibly mediated by PKC-activation. Furthermore, whereas TPA affects the redistribution of BPAG1 among their pools without inducing their synthesis, Ca2+-switch induces both membrane translocation and synthesis of BPAG1, suggesting involvement of signaling other than PKC pathways in control of BPAG1 synthesis.

Autoantigens↗
PubMed2001

Phosphatidylinositol-specific-phospholipase C cleaves urokinase plasminogen activator receptor from the cell surface and leads to inhibition of pemphigus-IgG-induced acantholysis in DJM-1 cells, a squamous cell carcinoma line.

We showed previously that pemphigus IgG enhanced both the activity of urokinase plasminogen activator (uPA) in cultured cells and the expression of its receptor (uPAR) on uPA-binding keratinocytes. In the present study, to clarify whether uPAR and uPA-activated plasmin are actually involved in the blistering process after pemphigus IgG binding to the cell surface, we examined the effects of the following on uPAR expression and on cell-cell detachment in DJM-1 cells, a squamous cell carcinoma line: (i) phosphatidylinositol-specific phospholipase C (PI-PLC) - which releases uPAR from the membrane surface into the culture medium by cleaving the glycosylphosphatidylinositol anchor thus inhibiting uPAR activity, and (ii) uPA inhibitors (tranexamic acid, aprotinin, p-aminobenzonic acid and dexamethasone). Preincubation with PI-PLC decreased dramatically the pemphigus IgG-induced uPAR expression in a dose-dependent manner, and inhibited pemphigus IgG-induced cell-cell detachment at 10 microg/mL. On the other hand, tranexamic acid (15 mM) inhibited pemphigus IgG-induced cell-cell detachment without reduction of uPAR expression, although aprotinin, p-aminobenzonic acid and dexamethasone failed to alter either of these parameters. Although uPAR expression on the pemphigus IgG-bound cell surface and uPA activation may contribute significantly to the pathogenesis of acantholysis in pemphigus, the mechanisms are complicated and should be defined further.

Acantholysis↗
PubMed2001

Increased antibody levels to desmogleins 1 and 3 after administration of carbamazepine.

Desmoglein (Dsg) 1 and Dsg3 are recognized as the autoantigens in pemphigus foliaceus and pemphigus vulgaris. Pemphigus-like syndromes have been reported to occur in individuals after exposure to a variety of drugs, but pemphigus caused by carbamazepine is not common. We found that anti-Dsg1 and anti-Dsg3 antibody titres were increased in three individuals administered carbamazepine. Antibody titres against Dsgs 1 and 3 were measured by enzyme-linked immunosorbent assay (ELISA). Of 42 serum samples (25 patients administered carbamazepine, eight patients administered valproic acid and nine healthy volunteers) tested by ELISA, three patients administered carbamazepine showed positive reactivity against both Dsg1 and Dsg3. The patient with the highest titre against Dsg1 and Dsg3 (the index values of anti-Dsg1 and anti-Dsg3 were 79.3 and 86.4, respectively) was a 23-year-old woman (Case 1). The other two patients with positive reactivity were a 5-year-old boy (Case 2) and a 65-year-old man (Case 3). In addition, indirect immunofluorescence study showed intercellular antibodies to the cell surface of the whole epidermis with a titre of 1 : 64 in Case 1 and 1 : 2 in Cases 2 and 3. However, no skin or mucosal involvement was found in any of these cases. There was no difference in the serum concentrations of carbamazepine between the three positive cases and the 22 negative cases of carbamazepine administration. From these facts, the lack of skin diseases may be explained by relatively low values of anti-Dsg 1 and 3 antibodies in Cases 2 and 3. However, it cannot be excluded that undefined exogenous and/or endogenous factors are involved in an outbreak of pemphigus. Furthermore, these findings might be helpful for preventing susceptible individuals from exposure to the suspect drugs.

Adolescent↗
PubMed2001

Erythema multiforme associated with cytomegalovirus infection in nonimmunosuppressed patients.

BACKGROUND: It is widely known that cytomegalovirus (CMV) primarily brings about subclinical and asymptomatic infection in the early stages of life and can cause various dermatological and systemic disorders under immunosuppressed conditions. Nonimmunosuppressed individuals very rarely present with cutaneous CMV involvement. OBJECTIVE: In the present study, we described the clinical characteristics of 5 nonimmunosuppressed adult patients with positive IgM antibody to CMV. METHODS: The systemic symptoms and dermatological features of these 5 patients were described. Laboratory examinations including blood cell counts, liver and renal functions were performed. IgG and IgM antibodies to CMV were also examined at the first consultation and 2-3 months after the skin eruption. Polymerase chain reaction for CMV DNA was performed in the skin samples of the patients. RESULTS: All 5 patients had fever and complained of a sore throat. Multiple exudative erythema and target lesions with itching were observed mainly on the extremities. These symptoms and eruptions disappeared within 1 week after the onset and IgM antibody titers significantly decreased after 2-3 months. IgG antibody to CMV was already positive in 3 cases but was negative in 2 cases at the initial consultation. CONCLUSION: We propose that CMV infection may cause erythema multiforme by primary, recurrent infections or reactivation of CMV even in nonimmunosuppressed adults.

Adult↗
PubMed2001

3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-gamma.

3-Hydroxyanthranilic acid (3-HAA), a metabolite of L-tryptophan, accumulates in monocyte-derived cells (THP-1), but not in other cell lines tested (MRC-9, H4, U373MG, Wil-NS), following immune stimulation that induces indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme in the L-tryptophan kynurenine pathway. We examined whether metabolites of the L-tryptophan-kynurenine pathway act to induce apoptosis in monocytes/macrophages. Of the L-tryptophan metabolites tested, only 3-HAA at a concentration of 200 micromol/L was found to induce apoptosis in THP-1 and U937 cells. The addition of ferrous or manganese ions further enhanced apoptosis and free radical formation by 3-HAA in these two types of cells. The apoptotic response induced by 3-HAA was significantly attenuated by the addition of antioxidant, alpha-tocopherol or Trolox (a water-soluble analogue of vitamin E), and the xanthine oxidase inhibitor, allopurinol. In addition, the 3-HAA-induced apoptotic response was slightly attenuated by catalase, but not by superoxide dismutase (SOD), indicating that generation of hydrogen peroxide is involved in this response. Interferon-gamma (IFN-gamma), an inducer of IDO, potently induced apoptosis in THP-1 cells, but not in U937 cells, in the presence of ferrous or manganese ions. This different susceptibility to apoptosis inducer between THP-1 and U937 cells may depend on the capacity of the cells for 3-HAA synthesis following IDO induction by IFN-gamma. Furthermore, apoptosis was suppressed by cycloheximide in THP-1 cells, suggesting that newly synthesized proteins may be essential for apoptotic events. These results suggest that 3-HAA induces apoptosis in monocytes/macrophages under inflammatory or other pathophysiological conditions.

3-Hydroxyanthranilic Acid↗
PubMed2001

[Lipoprotein X].

Explore the source record for details and available documents.

Animals↗
PubMed2001

Inhibitory action of gemfibrozil on cholesterol absorption in rat intestine.

This study was designed to determine whether gemfibrozil inhibits intestinal lipid absorption. Male Sprague-Dawley rats received an oral dose of 30 mg gemfibrozil/kg body weight for 14 days. Mesenteric lymph cannulation was performed, and a lipid infusion containing 40 micromol/h (35.4 mg/h) of radiolabeled triolein and 2.74 micromol/h (1.06 mg/h) of radiolabeled cholesterol with the addition of 1 mg/h of gemfibrozil was infused intraduodenally at a rate of 3 ml/h for 8 h. The lymph was collected, and the radioactivity levels of the lumen and gut mucosa were measured after the infusion. Lymph cholesterol transport was depressed in gemfibrozil-treated rats, in terms of mass measurements as well as radioactivity in a lesser degree. More radioactive cholesterol remained in the proximal portion of the intestinal lumen and mucosa in the treated rats than in the control rats. More radioactive triglycerides also remained in the proximal intestinal lumen of treated rats, although no difference in lymphatic triglyceride transport was observed between the groups. A significant portion of the radioactive cholesterol remained in the lumen in the gemfibrozil-treated rats. Gemfibrozil increased biliary cholesterol excretion. Thus, this study shows that gemfibrozil inhibits cholesterol absorption in rat intestine.

Animals↗
PubMed2001

[Reference values of serum lipid].

The guideline for the reference value of serum lipid(total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride) was proposed by the Japan Atherosclerosis Society in 1997. These values are utilized for the diagnosis and treatment of hyperlipidemia to protect patients from ischemic heart disease. The upper limit of reference value was not determined by the 95 percentile range from healthy subjects, but on the basis of clinical data on serum lipid in the Japanese. This way to determine the reference value will be suitable in case of lipid, because there is a tendency to increase cholesterol level in the Japanese for these thirty years. The standardization for each lipid assay is crucial. The CDC-established Reference Methods for measuring total cholesterol(TC), HDL-C. LDL-C, and triglyceride(TG) are used to set reference values for the serum pools used for LSP(Lipid Standardization Panel) standardization. In Japan, the routine methods for cholesterol and triglyceride have been proposed by the special committee in the Japan Society of Clinical Chemistry. In contrast, homogeneous assay for HDL- and LDL-C, which are used routinely at present, have still some problems in the point of accuracy. A new ELISA for Lp(a) has been developed using antibody not reacting to kringle IV type 2. Its standardized assay, thus, will be available sooner or later. With respect to other lipid-related test such as RLP(remnant-like particles) and oxidized LDL, it is necessary to accumulate more clinical data for the determination of reference value.

Apoproteins↗
PubMed2000

Neurobehavioral alterations in mice with a targeted deletion of the tumor necrosis factor-alpha gene: implications for emotional behavior.

Tumor necrosis factor-alpha (TNF-alpha) is emerging as an important modulator of the function of the central nervous system. In the present study, we investigated a role of endogenous TNF-alpha in cognitive and emotional function using mice with targeted deletions of the TNF-alpha gene. TNF-alpha-(-/-) mice showed normal diurnal rhythms of spontaneous locomotor activity and cognitive functions. Emotional behavior in the mutant mice, however, was significantly altered, which manifested in the performance in the open-field, elevated plus maze, and forced swimming tests. The altered performance in the elevated plus maze test was significantly alleviated by treatment with diazepam. Postmortem brain analysis of TNF-alpha-(-/-) mice revealed a significant increase in serotonin metabolism in the brain. These findings suggest a role for endogenous TNF-alpha in emotional behavior, which may possibly be related to alterations of serotonine metabolism.

Animals↗
PubMed2000

Autonomic regulation after exercise evidenced by spectral analysis of heart rate variability in asthmatic children.

BACKGROUND: Bronchial asthma is associated with abnormal autonomic nervous function in childhood. Exercise is one of the most common precipitating factors of acute asthmatic crises although the exact mechanism of autonomic regulation in asthmatic children after exercise is unclear. OBJECTIVE: The aim of this study was to investigate the features of autonomic regulation after exercise in asthmatic and control children. METHODS: Pulmonary function tests and heart rate variability spectral analysis were performed in 15 asthmatic children and 7 control children (age 6 to 15 years) during and after an exercise challenge. RESULTS: The maximum % fall of forced expiratory volume in 1 second (FEV1) was significantly greater (P < .01) in asthmatic subjects (9.1 +/- 5.1%) than in normal control subjects (1.0 +/- 2.5%). The high frequency band (HF) amplitude, an index of cardiac vagal tone, 5 minutes after exercise was significantly higher (P < .05) in the asthmatic subjects (14.4 +/- 7.9 msec) than in control subjects (5.9 +/- 2.6 msec). Furthermore, the difference in the HF amplitude between the control group and the exercise-induced asthma group was significant both 5 minutes (P < .01) and 10 minutes (P < .05) after challenge. There was a significant correlation (P = .565, P = .0165) between HF amplitude 5 minutes after exercise and the magnitude of the decrease in FEV1. On the other hand, no significant difference was observed in the low frequency band amplitude between the controls and the asthmatic subjects. The ratio of low frequency to high frequency power, which is suggested to correlate with cardiac sympathetic activity, did not differ between the two groups. CONCLUSION: These findings suggest that autonomic nervous activities, particularly vagal response after exercise, in asthmatic children is different from that in control children.

Adolescent↗
PubMed2000

A refractory case of secondary erythermalgia successfully treated with lumbar sympathetic ganglion block.

A 59-year-old Japanese man with myasthenia gravis, who had a 10-year history of temperature-sensitive pain in the lower extremities, i.e. improved by cooling and worsened by warming, consulted us because the pain had become intolerable during the previous 4 months. Bilateral erythema, swelling and large ulcers were noted on the calves, dorsal aspects of the feet, and soles. Laboratory data showed thrombocythaemia and a positive antibody to the acetylcholine receptor, but were negative for antinuclear and antiphospholipid antibodies. A diagnosis of secondary erythermalgia was made because of the clinical features, the laboratory data, and the lack of family history of this disease. Although steroid pulse therapy, oral aspirin and antiserotonin drugs were ineffective, bilateral lumbar sympathetic ganglion block succeeded in relieving the severe pain and curing the ulcers. The clinical course in our patient suggests that sympathetic ganglion block may be one of the most effective treatments for secondary erythermalgia. Although the mechanism of this effect is uncertain, microcirculation disturbance in secondary erythermalgia, if any, may be improved by this block.

Erythromelalgia↗