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Biomedical subjects

M Sumiya

Publications and source records attributed to M Sumiya.

At least 19 recordsLinked to original sources
PubMed2001

Recurrent miscarriage and variant alleles of mannose binding lectin, tumour necrosis factor and lymphotoxin alpha genes.

Variant alleles of the mannose binding lectin (MBL) gene are associated with increased susceptibility to infection and polymorphisms of tumour necrosis factor and lymphotoxin alpha genes (TNF, LTA) are associated with increased severity of infection. Studies have associated recurrent miscarriage with low serum mannose binding lectin concentrations and premature membrane rupture and preterm delivery with elevated maternal and fetal levels of TNF and the TNF (- 308) polymorphism. In this study the frequencies of variant MBL, TNF and LTA alleles in 76 Caucasian couples with idiopathic recurrent miscarriage were compared with those in 69 Caucasian control couples with no history of miscarriage and at least one previous live birth. A new assay based on hybridization to immobilized sequence-specific oligonucleotides (SSO) was used to rapidly detect nine MBL, two TNF and two LTA sequence variants. The assay genotyped all the structural and promoter MBL variants known to influence serum MBL concentrations. This assay was more reliable than restriction digestion or nested allele-specific PCR for the structural variants at codon 54 or 52, respectively. Reliability for codon 57 alleles was not assessed because of the low frequency in this population. The MBL haplotype frequencies in antenatal controls were similar to those reported in other control populations. The frequencies of structural variant MBL genes and of low, medium and high MBL level haplotypes were similar in the recurrent miscarriage and control couples. The TNF and LTA haplotype frequencies were similar in the recurrent miscarriage and control couples. In this carefully defined population no association has been found between recurrent miscarriage and variant alleles of the MBL, TNF or LTA genes.

Abortion, Habitual↗
PubMed2001

Endothelial cell-binding activity of anti-U1-ribonucleoprotein antibodies in patients with connective tissue diseases.

In order to elucidate the immunological properties of anti-U1-ribonucleoprotein (RNP) antibody, one of the autoantibodies detected in patients with connective tissue diseases (CTDs), we tested the endothelial cell-binding by anti-U1-RNP antibodies and epitopes on human pulmonary artery endothelial cells (HPAECs) to which the autoantibody bound. IgG fractions positive for anti-U1-RNP from patients with CTDs bound to the HPAECs. Furthermore, intact and F(ab')2 IgG anti-U1-RNP purified by affinity chromatography also bound to endothelial cells. The binding activity of IgG fractions positive for anti-U1-RNP to the endothelial cells could be effectively absorbed by U1-RNP-Sepharose. An immunoblotting assay of purified IgG anti-U1-RNP antibodies showed that these antibodies could bind to various membrane proteins of NP40-treated HPAECs such as 68, 48, 43, 38, 33, 29, 28 and 24 kDa. Some bands, 68, 33, 28 and 24 kDa, seemed to correspond to components of U1-RNP, i.e. 68 kDa, A, B' and C peptides, respectively. We confirmed that the anti-U1-RNP antibody from patients with CTDs can directly recognize a variety of antigens on the endothelial surface of the pulmonary artery, including the components of U1-RNP or other unknown polypeptides. These results suggest that binding to pulmonary artery endothelial cells of this autoantibody may be one of the triggers of endothelial cell inflammation in CTDs.

Animals↗
PubMed2000

Synthesis and antitumor activities of novel 5-deazaflavin-sialic acid conjugate molecules.

6-Nitro-5-deazaflavin derivatives bearing O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha- and beta-D-galacto-non-2-ulopyranosylonate)alkyl group (sialosylalkyl group) at N(3) or N(10) and 8-amino-5-deazaflavin substituted with the sialosylalkyl group at the amino group were synthesized and their physicochemical properties as well as antitumor effects on KB and L1210 cells have been investigated. The configurations of the glycosides were determined by 1H NMR and rate of hydrolysis of the glycosidic bond. It has been found that these conjugate molecules show significant antitumor activities. Combination of an 8-amino-5-deazaflavin with the sialosylalkyl group have been found to give rise to significant increase in antitumor activities of the compound. Antitumor effects of 6-nitro-5-deazaflavin-sialic acid conjugate molecules were similar or rather weak in comparison with those of the 6-nitro-5-deazaflavin derivatives without sialosylalkyl group.

Animals↗
PubMed1999

Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. Meningococcal Research Group.

BACKGROUND: The reasons why meningococcal disease develops in only a small proportion of individuals carrying the causative bacteria are unknown. Differences in host responses to bacterial colonisation are thought to be involved, since people with deficiencies in the terminal components of the complement pathway, or of properdin, are susceptible to meningococcal disease. We postulate that genetic variants of mannose-binding lectin (MBL), a plasma opsonin that initiates another pathway of complement activation, might similarly cause susceptibility to meningococcal disease. METHODS: The frequency of variants of the MBL gene was ascertained in children with meningococcal disease and controls from two independent studies; one hospital-based (194 patients and 272 controls [patients with non-infectious disorders]), and one community-based (72 patients and 110 controls [healthy individuals]), by means of PCR and restriction-enzyme digestion, with confirmation by DNA sequencing. FINDINGS: The proportion of people homozygous for MBL-variant alleles was higher in patients with meningococcal disease than in controls in the hospital study (15 [7.7%] vs four [1.5%]; odds ratio 6.5 [95% CI 2.0-27.2]) and in the community study (six [8.3%] vs three [2.7%]; 4.5 [0.9-29.1]). The population attributable fraction of cases attributable to MBL variants (homozygous and heterozygous) was 32%. INTERPRETATION: The MBL pathway is a critical determinant of meningococcal-disease susceptibility, and genetic variants of MBL might account for a third of all disease cases.

Adolescent↗
PubMed1999

Up-regulation of intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and class II MHC molecules on pulmonary artery endothelial cells by antibodies against U1-ribonucleoprotein.

In order to elucidate the pathogenic role(s) of autoantibodies in connective tissue disease (CTD), we examined whether autoantibodies against U1-ribonucleoprotein (RNP) and double-stranded (ds) DNA can up-regulate ICAM-1, ELAM-1 and class I and II MHC molecule expression on pulmonary artery endothelial cells (HPAEC). ICAM-1, ELAM-1 and class II MHC molecule expression on HPAEC cultured in the presence of anti-U1-RNP-containing and anti-dsDNA-containing IgG from CTD patients was up-regulated significantly in comparison with that on HPAEC cultured with IgG from normal healthy volunteers. Affinity chromatographic enrichment and depletion of the anti-U1-RNP antibody content of anti-U1-RNP-containing IgG confirmed that the anti-U1-RNP antibody did up-regulate ICAM-1, ELAM-1 and class II MHC molecule expression. The finding that an IgG F(ab')2-purified anti-U1-RNP antibody also up-regulated expression of these molecules may indicate that mechanisms other than Fc receptor-mediated stimulation are involved. These in vitro findings suggest that autoantibodies against U1-RNP and dsDNA play important roles in the immunopathological processes leading to the proliferative pulmonary arterial vasculopathy observed in CTD patients with pulmonary hypertension by up-regulating adhesion and class II MHC molecule expression on endothelial cells.

Adult↗
PubMed1999

Immunological analysis of pulmonary hypertension in connective tissue diseases.

OBJECTIVE: To analyze the immunological characteristics of the sera of patients with inflammatory connective tissue diseases complicated by pulmonary hypertension (PH). METHODS: Sera of 24 patients with mixed connective tissue disease complicated by PH (MCTD-PH), sera of 11 patients with other connective tissue diseases complicated by PH (Other-PH; 6 systemic sclerosis, 3 systemic lupus erythematosus, 2 rheumatoid arthritis), and sera of 15 patients with MCTD not complicated by PH (MCTD-non-PH) were tested for IgG antibodies against U1RNP proteins, U1RNP-70K protein, U1RNP-A protein, and U1RNP-C protein, and for IgG and IgM antibodies to beta2-glycoprotein I dependent cardiolipin (CL) and human umbilical vein endothelial cells. We also measured the serum levels of von Willebrand factor related antigens and interleukin 6 (IL-6). RESULTS: (1) The titers of the anti-U1RNP, anti-U1RNP-70K, anti-U1RNP-A, and anti-U1RNP-C antibodies were significantly higher in the MCTD-PH and MCTD-non-PH groups than in the Other-PH group. However, there were no statistically significant differences in the titers of these 4 antibodies between the MCTD-PH and MCTD-non-PH groups. (2) The titers of the IgG aCL and the serum IL-6 levels were significantly higher in the MCTD-PH group than in the MCTD-non-PH group. (3) Statistically significant correlations between the anti-U1RNP and IgG anti-CL antibody titers, and between the IgG anti-endothelial cell and IgG anti-CL antibody titers were observed within the MCTD-PH and Other-PH groups, but not within the MCTD-non-PH group. CONCLUSION: The occurrence of anti-U1RNP, anti-endothelial cell, and anti-CL antibodies is associated with PH in certain patients with connective tissue disease.

Autoantibodies↗
PubMed1998

Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans.

We retrospectively studied MBP genotypes in patients with malaria, tuberculosis (TB), and persistent hepatitis B virus (HBV) carriage, in clinics and hospitals in The Gambia. Children under 10 years with cerebral malaria and/or severe malarial anaemia, were compared with children with symptomatic, mild malaria, and controls of the same age and ethnicity. Adult TB cases with smear-positive pulmonary TB were compared with healthy blood donors from the same ethnic groups. Malaria cases and controls were tested for hepatitis B core antibody (anti-HBc) and surface antigen (HBsAg). TB patients were tested for HIV antibodies. Genotyping used sequence-specific oligonucleotide analysis to identify MBP variant alleles. Overall, 46% (944/2041) of patients and controls were homozygous for the wild-type MBP allele, 45% (922/2041) were carriers of a single variant allele and 8.6% (175/2041) had two variant alleles. Neither homozygotes nor heterozygotes for MBP variants were at increased risk of clinical malaria, persistent HBV carriage or TB. The most common mutation in Africans, the codon 57 variant allele, was weakly associated with resistance to TB (221/794 in TB cases and 276/844 in controls, p = 0.037). MBP deficiency is not a significant risk factor for persistent HBV, severe malaria nor pulmonary TB in West Africa.

Adult↗
PubMed1998

Mannose-binding protein in HIV-seropositive patients does not contribute to disease progression or bacterial infections.

This study set out to investigate whether plasma mannose-binding protein (MBP) deficiency caused by mutations in the MBP gene associates with pyogenic or opportunistic infections in HIV-infected patients. Plasma samples were selected randomly from 131 HIV-infected patients followed prospectively for a period not exceeding 12 months or until death. Plasma MBP concentrations were measured by an ELISA and genotyping was determined by amplification of exon 1 of the MBP gene by polymerase chain reaction (PCR) technology, followed by restriction enzyme analysis and Southern blotting using sequence-specific oligonucleotide probes. Neither MBP concentration nor genotype was found to associate with disease progression or opportunistic infection rate. There was an unexpected increased bacterial infection rate in patients with MBP levels greater than 100 ng/ml and wild type genotype. Thus, MBP does not appear to play a role in HIV infection. MBP is an acute phase reactant and this may explain the higher levels in those with more frequent pyogenic infections.

AIDS-Related Opportunistic Infections↗