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X Mi

Publications and source records attributed to X Mi.

10 recordsLinked to original sources
PubMed2000

Polymorphisms in IgG Fc receptor IIB regulatory regions associated with autoimmune susceptibility.

Autoimmune diseases involve multiple genes. While functions of these genes are largely unknown, some may be related to an intrinsic hyperresponsiveness of B cells. B-cell responses are controlled by signaling thresholds through the B-cell antigen receptor (BCR) complex. The B1 isoform of type II IgG Fc receptors (FcgammaRIIB1) is exclusively expressed on B cells and serves as a negative regulator for inhibiting BCR-elicited activation. Thus, its allelic variants associated with functional deficits could be examined for possible associations with susceptibility to autoimmune diseases. We found that there are three types of polymorphisms in the reported FcgammaRIIB transcription regulatory regions in mouse strains. Compared to normal healthy mouse strains (group III), autoimmune disease-prone strains (group I) share three deletion sites: two in the promoter region and one in the third intron. Strains (group II) that per se are not autoimmune-prone, but have potentials to accelerate autoimmune diseases share two deletion sites in the third intron: one identical to that in group I and the other unique to group II. These polymorphisms correlated well with extents of down-regulation of FcgammaRIIB1 expression in germinal-center B cells upon stimulation with antigens and up-regulation of IgG antibody responses. Our data imply that these FcgammaRIIB polymorphisms are selected evolutionarily for natural defense against pathogens, and that such polymorphisms may, in turn, form the basis of one aspect of autoimmune susceptibility.

Animals↗
PubMed1999

Genetically determined aberrant down-regulation of FcgammaRIIB1 in germinal center B cells associated with hyper-IgG and IgG autoantibodies in murine systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multigenic disease associated with IgG hypergammaglobulinemia, IgG anti-nuclear antibodies and immune complex (IC)-type glomerulonephritis. In both human and murine SLE, one susceptibility allele has been mapped to the interval linked to the IgG Fc receptor II (FcgammaRII) gene on chromosome 1. In spontaneous SLE models of NZB and (NZB x NZW) F(1) mice, expression of FcgammaRIIB1, which acts as a negative regulator for B cells, was abnormally down-regulated in follicular germinal center B cells from aged mice, compared to findings in non-SLE NZW, while levels in non-germinal center B cells were practically identical. Such strain differences were also evident in young mice upon in vivo stimulation with foreign antigens. In the FcgammaRIIB promoter region, the NZB allele has two deletion sites, including transcription factor-binding sites. Analyses using (NZB x NZW) F(1) x NZW backcross mice showed that this NZB allele was significantly linked to hyper-IgG, irrespective of the MHC haplotype, while high levels of IgG antibodies specific for DNA were regulated by a combinatorial effect of the F(1)-unique MHC haplotype and the NZB FcgammaRIIB allele. Therefore, the FcgammaRIIB promoter polymorphism may possibly predispose to SLE through germinal center B cells abnormally down-regulating FcgammaRIIB1 expression upon autoantigen stimulations and thus escaping negative signals for IgG production.

Age Factors↗
PubMed1996

Mutations in the ligand-binding domain of the kit receptor: an uncommon site in human piebaldism.

Heterozygous mutations in the gene for the Kit transmembrane receptor have been identified recently in human piebaldism and mouse "dominant spotting." Interestingly, all of the 14 known missense mutations that cause depigmentation in these species map to the tyrosine kinase domain of the receptor, whereas none have involved the extracellular ligand-binding domain. In an attempt to detect these uncommon mutations, we screened the nine exons encoding the extracellular portion of Kit for single-strand conformation polymorphisms (SSCP) in eight piebald subjects previously reported to be negative for kinase mutations. Four of these eight kindreds proved to carry novel mutations. The first mutation, found in two apparently unrelated probands with mild piebaldism and English ancestry, substitutes an arginine for a highly conserved cysteine at codon 136. This substitution disrupts a putative disulfide bond required for formation of the second Ig-like (D2) loop of the Kit ligand-binding domain. The second mutation, detected in a piebald kindred characterized by unusually limited depigmentation, substitutes a threonine for an alanine at codon 178, a site just proximal to conserved cysteines at codons 183 and 186. The third mutation, occurring in a kindred with more extensive depigmentation, is a novel four-base insertion in exon 2 that results in a proximal frameshift and premature termination. The data strongly suggest that piebaldism can result from missense mutations in the Kit ligand-binding domain, although the resulting phenotype may be milder than that observed for null or kinase mutations. The apparent clustering of these uncommon mutations at or near the conserved cysteines for the D2 Ig-like loop further suggests a critical role for this region in Kit receptor function.

Binding Sites↗
PubMed1995

[Effects of injury to endothelial cells on the binding of t-PA to cultured human umbilical vein endothelial cells].

Tissue plasminogen activator (t-PA) plays an important role in fibrinolysis. When t-PA is bound to endothelial cells (EC), its catalytic efficiency is increased and is prevented from being inhibited by its inhibitor PAI. In this paper, diamine was used to cause injury to cultured human umbilical vein endothelial cells by lipoperoxidation, and selenium was used as an anti-oxidant. Radioassay and autoradiography were used to detect the effects of injury on the binding ability of t-PA to EC. The results showed that the binding ability of t-PA to EC was reduced significantly after injury to EC by lipid peroxidation. Selenium could inhibit this reduction to a certain extent. It suggests that the decrease of fibrinolysis was related with the decrease of the binding ability of t-PA to EC after EC was injured.

Cells, Cultured↗
PubMed1994

Ultrastructural observations on cercaria of Schistosoma japonicum.

The present paper describes the ultrastructure of the surface topography, head organ, tegument, musculature, glandular system, primary alimentary tract and flame cells of the Chinese mainland strain of Schistosoma japonicum cercaria, as visualized with both scanning and transmission electron microscopes. The results not only illustrate the morphological features of the cercarial surface and its internal structure reflecting an adaptation to the aqueous habitat but also reveal the correlation between the morphological structure and physiological function.

Animals↗
PubMed1993

Decline in US stroke mortality in the era before antihypertensive therapy.

BACKGROUND AND PURPOSE: This study was done to determine if reported declines in stroke mortality in the era before antihypertensive therapy are artifactual. METHODS: This study involved analyses of national and state vital statistics data using adjusted and specific rates. RESULTS: Adoption of the third revision of the International List of Causes of Death in 1921 produced an abrupt 6.6% decrease in stroke mortality rates, but otherwise, changes in disease classification systems had little effect on stroke mortality rates. Adoption of the second revision of the joint-cause manual produced a 9.2% drop in stroke death rates, but other revisions of the joint-cause selection rules had little effect. While rates for the expanding group of states in the death registration area progressively declined, rates for fixed component areas remained constant until around 1925 and then declined. Reselection of the underlying cause from aggregate multiple cause data for 1917, 1925, and 1940 using uniform selection rules confirmed a decline after 1925. Correlation analyses of rates of change for stroke and heart disease rates did not support a shift in diagnosis to explain the divergent trends. CONCLUSIONS: The apparent decline in stroke mortality rates before 1925 is an artifact of changes in disease classification systems, joint-cause selection rules, and nonrandom incorporation of states with different mortality rates into the expanding registration area. The decline after 1925 could not be explained by changes in coding systems or joint-cause selection rules or by a shift in diagnosis from stroke to heart disease.

Age Factors↗