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Biomedical subjects

A Tsutsumi

Publications and source records attributed to A Tsutsumi.

At least 19 recordsLinked to original sources
PubMed2005

TCR Valpha14 natural killer T cells function as effector T cells in mice with collagen-induced arthritis.

Natural killer (NK) T cells are a unique, recently identified cell population and are suggested to act as regulatory cells in autoimmune disorders. In the present study, designed to investigate the role of NKT cells in arthritis development, we attempted to induce arthritis by immunization of type II collagen (CIA) in Jalpha281 knock out (NKT-KO) and CD1d knock out (CD1d-KO) mice, which are depleted of NKT cells. From the results, the incidence of arthritis (40%) and the arthritis score (1.5 +/- 2.2 and 2.0 +/- 2.7) were reduced in NKT-KO and CD1d-KO mice compared to those in respective wild type mice (90%, 5.4 +/- 3.2 and 2.0 +/- 2.7, P < 0.01). Anti-CII antibody levels in the sera of NKT-KO and CD1d-KO mice were significantly decreased compared to the controls (OD values; 0.32 +/- 0.16 and 0.29 +/- 0.06 versus 0.58 +/- 0.08 and 0.38 +/- 0.08, P < 0.01). These results suggest that NKT cells play a role as effector T cells in CIA. Although the cell proliferative response and cytokine production in NKT-KO mice after the primary immunization were comparable to those in wild type mice, the ratios of both activated T or B cells were lower in NKT-KO mice than wild type mice after secondary immunization (T cells: 9.9 +/- 1.8% versus 16.0 +/- 3.4%, P < 0.01, B cells: 4.1 +/- 0.5% versus 5.1 +/- 0.7%, P < 0.05), suggesting that inv-NKT cells contribute to the pathogenicity in the development phase of arthritis. In addition, IL-4 and IL-1beta mRNA expression levels in the spleen during the arthritis development phase were lower in NKT-KO mice, while the IFN-gamma mRNA expression level was temporarily higher. These results suggest that inv-NKT cells influence cytokine production in arthritis development. In conclusion, inv-NKT cells may promote the generation of arthritis, especially during the development rather than the initiation phase.

Animals↗
PubMed2005

Association of mannose binding lectin (MBL) gene polymorphism and serum MBL concentration with characteristics and progression of systemic lupus erythematosus.

OBJECTIVE: To determine whether occurrence, characteristics, and progression of systemic lupus erythematosus (SLE) are associated with polymorphism of the mannose binding lectin (MBL) gene and with serum MBL concentration. METHODS: Codon 54 MBL gene polymorphism of 147 patients with SLE and 160 healthy controls was determined by polymerase chain reaction-restriction fragment length polymorphism. Serum concentration of MBL was measured by enzyme immunoassay. Fluctuations of serum MBL were analysed with respect to disease characteristics and activity. RESULTS: Frequency of homozygosity for codon 54 minority allele was 6% (9/147) in patients with SLE, and significantly higher than in controls (p = 0.0294, Fisher's exact test). MBL polymorphism in patients with SLE was not significantly associated with disease characteristics or immunological phenotypes. Patients homozygous for the B allele tended to have a higher risk of infection during treatment. Levels of C3 and CH(50) were slightly, but significantly, associated with serum MBL concentration in patients with SLE homozygous for the majority allele. During the course of SLE, serum MBL concentration increased in 6/14 patients, and decreased in 7 after initiation of immunosuppressive treatment. CONCLUSIONS: MBL gene polymorphism influences susceptibility to SLE, but has no direct effect on disease characteristics. Serum MBL levels fluctuate during the course of SLE in individual patients. MBL genotyping may be useful in assessing the risk of infection during treatment of SLE.

Adolescent↗
PubMed2005

Nutritional and mental health status of Afghan refugee children in Peshawar, Pakistan: a descriptive study.

The study sought to ascertain and describe the physical and mental health states of Afghan refugee children after the terrorist attack on September 11, 2001 in the US and the aerial bombing of Afghanistan that followed. A cross-sectional survey was carried out in four refugee camps in Peshawar, Pakistan from February to March 2002, and comparisons among camps were made. A total of 70 males (mean age SD = 9.81 +/- 1.98 years old) and 30 females (7.94 +/- 2.07) answered a self-developed questionnaire on demographic data, traumatic events experience, living environment in the camps, and physical and mental health, through interviews. Anthropometric measures were measured and physical symptoms including anaemia and edema were assessed. Severe malnutrition was not shown and there were no significant differences in most nutritional and physical states among the camps. Nevertheless, in the newer camps more children experienced war related traumatic events. Mental symptoms were prevalent in all camps, though the characteristics of the symptoms differed among the camps.

Afghanistan↗
PubMed2004

Fhit expression in human gastric adenomas and intramucosal carcinomas: correlation with Mlh1 expression and gastric phenotype.

The fragile histidine triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in a variety of tumours, including gastric carcinomas. Recently, it has been reported that the FHIT gene may be a target of damage in some of mismatch-deficient tumours. To clarify further the role of the Fhit protein in gastric carcinogenesis, we investigated whether Fhit expression in early gastric neoplasia is associated with mismatch repair protein expression and cellular phenotype. Fhit, Mlh1 and phenotypic expression were evaluated immunohistochemically in 87 early gastric neoplasias, comprising 32 adenomas and 55 intramucosal carcinomas, resected by endoscopic mucosal resection therapy. Significant loss or reduction of Fhit expression was noted in four (12.5%) of the 32 adenomas and 21 (38.2%) of the 55 intramucosal carcinomas. The rate of abnormal Fhit expression was significantly higher in intramucosal carcinomas than in adenomas (P=0.021). Moreover, reduced Fhit expression was found to be significantly associated with loss of Mlh1 expression in early gastric neoplasia (P=0.0011). Furthermore, we also detected a significant association between reduced Fhit expression and gastric phenotype (P=0.0018). These results suggested that reduced Fhit expression occurs in the early stage of gastric carcinogenesis and could be correlated with a lack of Mlh1 expression and gastric phenotype.

Acid Anhydride Hydrolases↗
PubMed2004

Anti-mannose binding lectin antibodies in sera of Japanese patients with systemic lupus erythematosus.

Mannose-binding lectin (MBL) is a key element in innate immunity with functions and structure similar to that of complement C1q. It has been reported that MBL deficiency is associated with occurrence of systemic lupus erythematosus (SLE). We hypothesized that anti-MBL antibodies, if present, would affect the occurrence or disease course of SLE, by reduction of serum MBL levels, interference of MBL functions, or binding to MBL deposited on various tissues. To address this hypothesis, we measured the concentration of anti-MBL antibodies in sera of 111 Japanese SLE patients and 113 healthy volunteers by enzyme immunoassay. The titres of anti-MBL antibodies in SLE patients were significantly higher than those in healthy controls. When the mean + 2 standard deviations of controls was set as the cut off point, individuals with titres of anti-MBL antibodies above this level were significantly more frequent in SLE patients (9 patients) than in controls (2 persons). One SLE patient had an extremely high titre of this antibody. No associations of titres of anti-MBL antibodies and (i) genotypes of MBL gene, (ii) concentrations of serum MBL, or (iii) disease characteristics of SLE, were apparent. Thus, we have confirmed that anti-MBL antibodies are indeed present in sera of some patients with SLE, but the significance of these autoantibodies in the pathogenesis of SLE remains unclear.

Autoantibodies↗
PubMed2002

Significance of magnetic resonance imaging in the diagnosis of nodular regenerative hyperplasia of the liver complicated with systemic lupus erythematosus: a case report and review of the literature.

Nodular regenerative hyperplasia of the liver (NRH), characterized by multiple hepatic nodules in the absence of fibrosis, is a rare but important complication of systemic lupus erythematosus (SLE) associated with non-cirrhotic portal hypertension. The diagnosis of NRH is based on the pathological examination, and radiological findings of NRH are poorly documented. We report a case of a 40-year-old woman with SLE complicated with NRH. Sixteen years after diagnosis of SLE, esophageal varices were incidentally found and diagnosis of portal hypertension due to NRH was made by magnetic resonance imaging (MRI) and confirmed by needle liver biopsy. Although MRI showed the lesions as significant nodules, neither computed tomography nor ultrasonography could demonstrate the nodules. However, serial MRI showed significant enlargement of the nodules for 2 years Because NRH may lead to portal hypertension with life-threatening variceral haemorrhage in patients with SLE, MRI is a useful, non-invasive examination to screen the patients for its presence and follow-up. We reviewed the literature regarding NRH in SLE and discuss the management of the affected patients.

Adult↗
PubMed2001

Ectopic arachnoid granulomatosis: a case report.

BACKGROUND: Arachnoid granulation can sometimes show hypertrophy, developing extensively apart from the venous sinus, and in that case, a differential diagnosis should be made between this granulation and tumors. In this case, we hypothesized that cerebrospinal fluid was absorbed in the region of abnormal stains revealed by angiography. CASE DESCRIPTION: A 67-year-old female with headache was admitted to our hospital. A plain radiograph revealed accumulated numerous osteolytic lesions in the right frontal bone. T1-weighted magnetic resonance (MR) images demonstrated mixed-intensity lesions. On the T2-weighted MR images, we observed that the lesions were mixed, with areas of the same intensities as gray matter and cerebrospinal fluid. An abnormal vascular stain from the frontal branch of the middle meningeal artery was confirmed. After a craniotomy, numerous white granular masses were observed. These masses had penetrated the dura mater and adhered rigidly to the arachnoid membrane. Histological examination revealed them to be normal arachnoid granulations and villi. CONCLUSION: This case was diagnosed as an ectopic arachnoid granulomatosis. No case report has previously been published describing numerous arachnoid granulations away from the venous sinuses.

Arachnoid↗
PubMed2001

Stem cell factor prevents Fas-mediated apoptosis of human erythroid precursor cells with Src-family kinase dependency.

The Fas ligand (Fas-L) expressed on mature erythroblasts may induce apoptosis of more immature erythroid cells that express Fas, whereas stem cell factor (SCF) may prevent Fas-mediated cell death in hematopoietic progenitor cells. The manner in which SCF prevents Fas-mediated cell death still is unclear. Given the essential role of SCF and the potentially important involvement of the Fas/Fas-L system in the development of erythrocytes, we studied mechanisms related to SCF prevention of Fas-mediated apoptosis. We used primary cultured human erythroid colony-forming cells (ECFC) derived from CD34+ cells and enriched glycophorin A positive (GPA+) c-kit+ cells in ECFC. Apoptosis of ECFC was induced by an Fas-L mimetic monoclonal antibody CH11. DNA fragmentation and the activation of caspase-3 and caspase-8 were measured using commercially available kits. Characterization of expanded cells was performed using multiparameter flow cytometry. Lyn kinase activity was measured by enolase kinase assays. SCF inhibited the CH11-induced DNA fragmentation of ECFC as well as enriched GPA+ c-kit+ cells in ECFC, but not those of GPA+ c-kit- cells. SCF also inhibited the activation of caspase-3 and caspase-8, without downregulation of the surface expression of Fas, suggesting that SCF prevents apoptosis through uncoupling of Fas ligation from subsequent caspase activation. PP2, a specific inhibitor of Src-family kinases, antagonized the effects of SCF in preventing Fas-mediated apoptosis. We propose that SCF prevents Fas-mediated apoptosis of erythroid progenitor cells in a manner dependent on the activity of Src-family tyrosine kinases. We also identified active Lyn in erythroid cells. These data suggest the presence of a novel Src-family-dependent function of SCF in the development of erythrocytes.

Antibodies, Monoclonal↗
PubMed2001

Anti-phosphatidylserine/prothrombin antibodies are not frequently found in patients with unexplained recurrent miscarriages.

OBJECTIVE: To determine whether the presence of anti-phosphatidylserine/ prothrombin antibodies (anti-PS/PT) can be a major factor in otherwise unexplained recurrent miscarriages. PATIENTS AND METHODS: Eighty-one consecutive patients with history of 2 or more recurrent miscarriages were studied. Patients with history of overt thrombotic events were not included. Patients were examined for plausible causes of miscarriages, and titer of IgG, IgM and IgA anti-PS/PT were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Thirty-five patients had one or more plausible causes of recurrent miscarriages, including 12 positive for well-established anti-phospholipid antibodies, such as anti-beta2-glycoprotein I. None of the patients included in this study was found to be positive for anti-PS/PT. CONCLUSION: Detection of anti-PS/PT in addition to other anti-phospholipid antibodies does not seem to aid in the evaluation of patients with unexplained recurrent miscarriages.

Abortion, Habitual↗
PubMed2001

Mannose-binding lectin gene: polymorphisms in Japanese patients with systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome.

Mannose-binding lectin (MBL) is a key element of the innate immunity, with a structure similar to complement C1q. Serum MBL levels are greatly affected by the polymorphisms of the MBL gene. In particular, codon 54 mutation of the MBL gene results in a significant reduction of serum MBL. To determine whether polymorphism of the MBL gene is associated with occurrence of systemic lupus erythematosus (SLE), rheumatoid arthritis and Sjögren's syndrome in the Japanese population, we analyzed the MBL gene polymophisms of these patients and controls, by polymerase chain reaction-restriction fragment length polymorphism methods. We found that patients studied had a significantly higher frequency of having homozygous codon 54 mutation compared to controls. In particular, patients with SLE or Sjögren's syndrome showed higher probabilities of being homozygous for this mutation. Among subjects with the same genotype, SLE patients tended to have higher serum MBL concentration than controls. Analysis of the promotor region suggested that SLE patients heterozygous for the codon 54 mutation have a higher probability of having a low producing haplotype for the gene without the codon 54 mutation. We conclude that persons homozygous for codon 54 mutation of the MBL gene may be prone to occurrence of autoimmune disorders including SLE, in the Japanese. MBL may have protective effects on occurrence and progression of SLE.

Arthritis, Rheumatoid↗
PubMed2001

Association between job strain and prevalence of hypertension: a cross sectional analysis in a Japanese working population with a wide range of occupations: the Jichi Medical School cohort study.

OBJECTIVES: To explore the association between the prevalence of hypertension in a Japanese working population and job strain (a combination of low control over work and high psychological demands), and to estimate this association in different sociodemographic strata. METHODS: From a multicentre community based cohort study of Japanese people, sex specific cross sectional analyses were performed on 3187 men and 3400 women under 65 years of age, all of whom were actively engaged in various occupations throughout Japan. The baseline period was 1992-95 [corrected]. The association between job characteristics--measured with a Japanese version of the Karasek demand-control questionnaire--and the prevalence of hypertension defined by blood pressure and from clinical diagnoses were examined. Adjustments were made for possible confounders. The analyses were repeated for stratified categories of occupational class, educational attainment, and age group. RESULTS: In men, the level of job strain (the ratio of psychological job demands to job control) correlated with the prevalence of hypertension. In a multiple logistic regression model, job strain was significantly related to hypertension (odds ratio 1.18; 95% confidence interval 1.05 to 1.32), after adjustment for age, employment (white collar v blue collar), marital status, family history of hypertension, cigarette smoking, alcohol intake, physical activity, and body mass index. The stratified analyses showed significant excess risks in the subordinate groups compared with managers, blue collar workers, less educated workers, and the older age groups. This association was not significant in women. Multiple linear regression analyses, with systolic and diastolic blood pressures as dependent variables, did not show any significant association. CONCLUSIONS: The findings provided limited proof that job strain is related to hypertension in Japanese working men. Older men in a lower social class may be more vulnerable to the hypertensive effects of job strain.

Adult↗
PubMed2001

The liquid-state 31P-nuclear magnetic resonance study on microfiltrated milk.

To gain further insight into diversiform phosphorus in bovine milk, we separated skim milk into casein micelle and serum fractions by microfiltration and subjected them to liquid-state 31P-nuclear magnetic resonance (NMR) spectroscopy. As previously reported, the skim milk spectrum showed a broad and indistinct peak from phosphoserine residue (SerP) of casein. In the casein micelle spectrum, however, the SerP peak was more clearly observed with a phosphate peak that may be from micellar calcium phosphate (MCP). The serum spectrum was the same as skim milk spectrum, except for SerP peak. Furthermore, two types of casein micelle fractions, with 0.90 and 1.04 of [beta-casein + kappa-casein]/[alpha(s1)-casein + alpha(s2)-casein] ratios were generated by different temperature microfiltrations, occurring because beta-casein is released from the micelle at a low temperature. The shape of SerP peaks changed dramatically in both the casein micelle spectra, when the temperature dropped from 35 to 5 degrees C. Deconvolution analysis indicated that each SerP peak comprised the same set of four peaks. Half-width and composition discriminated between the two types of casein micelle fractions. As a consequence, there was significant interaction between casein micelle and milk serum, causing cloudiness of SerP in the liquid-state 31P-NMR spectrum of milk. Casein composition influenced the SerP-MCP interaction in micellar structure. Shape changing of the SerP peak was discussed in connection with beta-casein-release phenomenon.

Animals↗
PubMed2001

Association between job stress and depression among Japanese employees threatened by job loss in a comparison between two complementary job-stress models.

OBJECTIVES: This study compared the separate effects produced by two complementary stress models--the job demand-control model and the effort-reward imbalance model--on depression among employees threatened by job loss. METHODS: A cross-sectional analysis was conducted to examine these associations among 190 male and female employees who responded to a self-administered questionnaire in a small Japanese plant with economic hardship. The employees were engaged in 2 job types--direct assembly line and indirect supportive tasks--and the latter was threatened by job loss because of downsizing. Independent variables were measured by the Japanese versions of Karasek's demand-control questionnaire and Siegrist's effort-reward imbalance questionnaire. Depression was assessed by the Center for Epidemiologic Studies Depression Scale. RESULTS: The employees with indirect supportive tasks (target for downsizing) were more likely to have depressive symptoms than direct assembly-line workers. Job strain, a combination of high demand and low control at work, was more frequent among the latter, while the combination of high effort and low reward was more frequent among the former. After adjustment for work environment factors, low control [odds ratio (OR) 4.7], effort reward imbalance (OR 4.1), and overcommitment (the person characteristic included in the effort-reward imbalance model) (OR 2.6) were independently related to depression. There is some indication that these effects were particularly strong in the subgroup suffering from potential job loss. CONCLUSIONS: This study confirms that the 2 job stress models identify different aspects of stressful job conditions. Moreover, effort-reward imbalance and low control at work are both associated with symptoms of depression.

Adult↗
PubMed2000

Alternative splicing forms of the human CD1D gene in mononuclear cells.

CD1d is a critical molecule for the presentation of lipid antigens to natural killer (NK) T cells. To investigate the molecular complexity of CD1d, alternatively spliced transcripts in peripheral blood mononuclear cells from three healthy subjects were analyzed by PCR and sequencing methods. We found eight alternatively spliced variants of the CD1D gene (V1-V8), seven of which are newly established variants (V2-V8). V1 and V4 are in-frame; however, the other six variants (V2, V3, V5-V8) are out-of-frame. V1, V2, V4, and V5 lack a beta(2)-microglobulin binding site (alpha3 domain), indicating the unstable presentation of the CD1d molecule on the surface. In V2 and V5, the transmembrane region is absent, supporting a soluble CD1d. In the V3-V8 variants, the antigen binding region (alpha1 and alpha2 domains) is partially defective, suggesting incomplete functional products. In contrast, the V1 and V2 transcripts bear the complete antigen binding site, resulting in functional proteins. Especially, the V2 splicing variant might function as an inhibitory soluble CD1d molecule and regulate the presentation of antigens on APC to NKT cells.

Alternative Splicing↗