Biomedical subjects

G Steiner

Publications and source records attributed to G Steiner.

At least 127 records · Page 7Linked to original sources

PubMed1996

What can 18S rDNA do for bivalve phylogeny?

Molecular characteristics, especially 18S rDNA sequences, may be of great value for the study of bivalve evolution and its numerous morphological convergencies once the reliability of these data can be evaluated. The analysis of 11 published complete molluscan sequences and two new ones, Arca noae and Atrina pectinata, reveals considerable differences in relative substitution rates. The gastropod and eulamellibranch species have the fastest and Atrina species have the slowest rates. Two methods are used to assess the information contents of the dataset in addition to bootstrap analysis, spectral analysis, and the "pattern of resolved nodes" technique. Tree reconstructions by parsimony, neighbor-joining, and maximum-likelihood differ in regard to the position of the eulamellibranch family Mactridae and of Crassostrea. Although there is a signal for the monophyly of Bivalvia, Mactridae cluster with Gastropoda in most runs, rendering Bivalvia diphyletic. The position of Crassostrea was extremely variable, probably due to the high substitution rate of this species. Atrina roots deeper than Arca in all trees, although a corresponding signal in spectral analysis is absent. Phylogenetic signals among the three pectinid species are low but sufficient to resolve the branching pattern. The tree inferred from the 18S rDNA and from morphological data has Bivalvia monophyletic with a basal polytomy of Mactridae, Crassostrea, and the remaining Pteriomorphia, where Arca branches off before Atrina and the Pectinidae. Argopecten is sister group to the other two pectinids; 18S sequence data will have great impact on our understanding of bivalve phylogeny, but only when more sequences of similar substitution rates are available.

Animals↗

PubMed1996

The Diabetes Atherosclerosis Intervention Study (DAIS): a study conducted in cooperation with the World Health Organization. The DAIS Project Group.

The incidence of coronary artery disease is greatly increased in those with diabetes mellitus. The largest number of those who have coronary artery disease have non-insulin-dependent diabetes (NIDDM). Lipoprotein abnormalities have been identified among the several risk factors that could account for this increase in atherosclerosis. There have been many studies demonstrating that correction of dyslipoproteinaemias will reduce the risk of coronary disease in non-diabetic populations. Current advice to those with diabetes is based on extrapolations from such studies. However, the justification for this, and the treatment targets are unclear as there has been no direct test of the lipid hypothesis in diabetes. This paper describes the protocol of the first intervention trial designed to examine directly whether correcting dyslipoproteinaemia in men and women with NIDDM will reduce their coronary artery disease. The Diabetes Atherosclerosis Intervention Study (DAIS), is a multinational angiographic study using the 200 mg micronized form of fenofibrate in a double-blind, placebo-controlled protocol.

Adult↗

PubMed1996

Apolipoprotein B-48.

Explore the source record for details and available documents.

Apolipoprotein B-100↗

PubMed1996

Are T cells from healthy heart really only passengers? Characterization of cardiac tissue T cells.

Numerous studies have dealt with occurrence of dendritic cells in various nonlymphoid organs such as kidney, liver or heart, whereas lymphocyte patterns in these organs have not been analyzed in detail. In the present study, leukocytes were quantified as cells/mm2 in the perivascular, interstitial and parenchymal tissue sections of normal heart. We measured an overall mean leukocyte count in normal heart tissue of 17.0 +/- 2.7 CD45+ leukocytes/mm2, 9.1 +/- 1.8 thereof being CD4+ T-helper cells (Th). By comparison, CD8+ T-cytotoxic/suppressor cells (Ts) and CD14+ macrophages each accounted for only approximately 2.5 cells/mm2, and CD20+ B cells for only 1.3 cells/mm2. These T cells were further characterized as either CD45RA+ naive T cells or as CD45RO+ memory T cells. Segmentation of the tissue as defined in Section 2 yielded an ascending number of CD45RO+ memory T cells from perivascular (0.4 +/- 0.2 cells/mm2) through parenchymal (12.8 +/- 3.0 cells/mm2) to interstitial (21.0 +/- 5.3/mm2). By contrast, the number of CD45RA+ and Leu-8+ cells decreased from perivascular to parenchymal. Peripheral T cells showed a reverse pattern of CD45RA/CD45RO antigen expression. Only approximately 3% of T cells expressed activation markers IL-2R and IL7R. Our data demonstrate that the majority of T cells in normal heart tissue are resting memory tissue T cells and are not contaminating T cells from the peripheral blood. The increase in CD45RO+ cells from perivascular to parenchymal with a corresponding decrease in CD45RO+ and Leu-8+ heart-tissue T cells argues in favor of T-cell traffic in normal heart tissue.

Antigens, CD↗

PubMed1996

Tumour necrosis factor alpha and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus.

Cytokines are believed to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, for tumour necrosis factor alpha (TNF-alpha) both beneficial and deleterious effects have been reported. To obtain information about the involvement of this cytokine in the pathophysiology of SLE, serum levels of TNF-alpha, the soluble forms of the 55 and 75 kDa tumour necrosis factor receptors (TNF-R55 and TNF-R75), and interleukin-6 (IL-6) were measured by ELISA in nine female patients over a period of 2 yr. Compared to healthy controls, levels of TNF-alpha (median 47 pg/ml, range < 15-222 pg/ml), TNF-R55 (median 1.9 ng/ml, range 0.8-10.8 ng/ml), TNF-R75 (median 4.7 ng/ml, range 1.5-15 ng/ml) and IL-6 (median 3.5 pg/ml, range < 3.5-52 pg/ml) were significantly elevated in SLE patients (P < 0.0001 vs controls in all cases). There were strong correlations between TNF-alpha and its soluble receptors (P < 0.0001). Moreover, TNF-alpha and both TNF-Rs strongly correlated with clinical and serological parameters of disease activity, such as the European Consensus Lupus Activity Measurement (ECLAM) score, anti-dsDNA antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anaemia (P < 0.0001 for all comparisons). TNF-alpha and TNF-R75 also correlated with IL-6 (P < 0.0001). However, no correlation between IL-6 and ECLAM was found, and the correlation of IL-6 with anti-dsDNA was relatively weak; in contrast, IL-6 correlated strongly with CRP and ESR (P < 0.0001). Although these data do not allow us ultimately to discriminate between beneficial and deleterious effects of TNF-alpha, they nevertheless suggest a central role for the TNF system in the pathophysiology of SLE.

Adult↗

PubMed1996

Autoantibodies to the A/B proteins of the heterogeneous nuclear ribonucleoprotein complex: novel tools for the diagnosis of rheumatic diseases.

Heterogeneous nuclear ribonucleoprotein (hnRNP) complexes are major constituents of the spliceosome. They are composed of approximately 30 different proteins which can bind to nascent pre-mRNA. Among these, the hnRNP-A/B proteins form a subgroup of highly related proteins: their N-terminal halves consist of two adjacent RNA-binding domains, whereas the C-terminal halves contain almost 50% glycine residues. These proteins represent a group of novel autoantigens which are targeted by autoantibodies from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD): thus, anti-A2/RA33 autoantibodies target the hnRNP proteins A2, B1, B2 (the 'RA33 complex'), and anti-A1 autoantibodies are directed to the hnRNP proteins A1 and A1b. In SLE, anti-hnRNP-A/B antibodies frequently occur together with antibodies to two other spliceosome-associated antigens, U1 small nuclear RNP (U1-snRNP) and Sm. Epitope-mapping studies have revealed that the major antibody binding sites are located in the RNA-binding regions. Furthermore, there is some indication of disease-specific epitope recognition. Studies in animal models have demonstrated the presence of anti-hnRNP-A/B antibodies in several lupus-prone mouse strains. Thus, autoantibodies to the spliceosomal hnRNP-A/B proteins are a common feature of RA, SLE, and MCTD. However, these diseases differ in their reactivities to other spliceosomal components, such as U1-snRNP and Sm antigens. Therefore, anti-hnRNP-A/B autoantibodies are not only valuable diagnostic markers but may also allow additional insights into the pathogenetic mechanisms of rheumatic autoimmune diseases.

Animals↗

PubMed1996

Tissue polypeptide-specific antigen in renal cell carcinoma.

OBJECTIVES: The usefulness of serum tissue polypeptide-specific antigen (TPS), a cytokeratin 18-associated marker, in renal cell carcinoma (RCC) was assessed in vitro and in vivo. METHODS: Indirect immunoperoxidase staining for TPS expression was performed on frozen sections of normal renal tissue and RCC specimens. By using a monoclonal TPS immunoradiometric assay, serum TPS concentrations were analyzed in 82 healthy controls, in 20 patients with locoregional RCC before and after surgery and in 18 patients with advanced disease following surgery receiving immunotherapy with interferon-gamma. RESULTS: Using immunohistochemistry, TPS was found to be expressed by both normal and cancerous renal epithelial cells. The mean TPS concentrations in 82 healthy controls was 56 +/- 49 U/1 with a 95% percentile of 78.5 U/1. Out of 20 patients with locoregional RCC, 8 presented with elevated values (mean 168 +/- 82 U/1) above the cut-off level (78.5 U/1, sensitivity 40%) which dropped to normal within 2 weeks after surgery. During a follow-up period of 1 year, none of the patients presented with tumor recurrence and TPS concentrations remained low (mean 52 +/- 36 U/1). In 18 patients receiving interferon-gamma therapy, serum TPS concentrations were monitored over a period of 12 months. In 5/18 patients, baseline levels were within the normal range (mean 37 +/- 21 U/1); interestingly, these at the same time were the only responders to immunotherapy (n = 2) or at least showed stable disease (n = 3). Response to therapy was reflected by low serum TPS levels (mean 28 +/- 23 U/1) over the entire observation period. Thirteen patients suffered progressive disease during therapy, all of them exhibiting significantly elevated (p < 0.005) pretherapeutic TPS concentrations (mean 186 +/- 124 U/1) that remained equally elevated throughout therapy (mean 192 +/- 102 U/1), reflecting tumor progression. CONCLUSIONS: TPS might have some clinical value as prognostic marker in RCC, possibly by reflecting the proliferative tendency of the tumor.

Adult↗

PubMed1996

The reliability of analysis of intraoperative frozen sections for identifying active infection during revision hip or knee arthroplasty.

A prospective study was performed to determine the reliability of analysis of intraoperative frozen sections for the identification of infection during 175 consecutive revision total joint arthroplasties (142 hip and thirty-three knee). The mean interval between the primary and the revision arthroplasty was 7.3 years (range, three months to twenty-three years). To reduce selections bias, tissue was obtained for frozen sections during all revisions in patients who did not have active drainage from the wound or a sinus tract. Of the 175 patients, twenty-three had at least five polymorphonuclear leukocytes per high-power field on analysis of the frozen sections and were considered to have an infection. Of these twenty-three, five had five to nine polymorphonuclear leukocytes per high-power field and eighteen had at least ten polymorphonuclear leukocytes per high-power field. The frozen sections for the remaining 152 patients were considered negative. On the basis of cultures of specimens obtained at the time of the revision operation, nineteen of the 175 patients were considered to have an infection. Of the 152 patients who had negative frozen sections, three were considered to have an infection on the basis of the results of the final cultures. Of the twenty-three patients who had positive frozen sections, sixteen were considered to have an infection on the basis of the results of the final cultures; all sixteen had frozen sections that had demonstrated at least ten polymorphonuclear leukocytes per high-power field. The sensitivity and specificity of the frozen sections were similar regardless of whether an index of five or ten polymorphonuclear leukocytes per high-power field was used. Analysis of the frozen sections had a sensitivity of 84 per cent for both indices, whereas the specificity was 96 per cent when the index was five polymorphonuclear leukocytes and 99 per cent when it was ten polymorphonuclear leukocytes. However, the positive predictive value of the frozen sections increased significantly (p < 0.05), from 70 to 89 per cent, when the index increased from five to ten polymorphonuclear leukocytes per high-power field. The negative predictive value of the frozen sections was 98 per cent for both indices. The current study suggests that it is valuable to obtain tissue for intraoperative frozen sections during revision hip and knee arthroplasty. At least ten polymorphonuclear leukocytes per high-power field was predictive of infection, while five to nine polymorphonuclear leukocytes per high-power field was not necessarily consistent with infection. Less than five polymorphonuclear leukocytes per high-power field reliably indicated the absence of infection.

Adult↗

PubMed1996

Hyperinsulinemia and triglyceride-rich lipoproteins.

Hypertriglyceridemia is the most frequent form of hyperlipidemia seen in diabetes. Because hypertriglyceridemia and hyperinsulinemia often coexist in the general population and because patients with NIDDM generally are hyperinsulinemic, we have undertaken a series of in vivo studies to examine the effects of hyperinsulinemia on VLDL production. These studies showed that chronic hyperinsulinemia is accompanied by increased VLDL production and that this occurs even when plasma free fatty acid (FFA) levels have fallen. By contrast, acute hyperinsulinemia is accompanied by a reduction in VLDL production, and this reduction is, at least in part, mediated by an associated reduction in the availability of plasma FFAs as a substrate for VLDL-triglyceride (TG). The studies also raise the possibility that the difference in the dependence of VLDL production on plasma FFAs in acute versus chronic hyperinsulinemia results from an increase in hepatic lipogenic enzymes and from the availability of an alternate substrate such as fructose. The overall effect of hyperinsulinemia on VLDL production is postulated to reflect both the effect of insulin on apolipoprotein B production and the hepatic synthesis of TG from either plasma FFAs or newly made fatty acids.

Animals↗

PubMed1996

Acute effects of insulin in the control of VLDL production in humans. Implications for the insulin-resistant state.

The role of hyperinsulinemia in the pathogenesis of triglyceride (TG) and VLDL over-production in insulin-resistant states remains controversial. While studies in humans and animals have generally suggested that chronic hyperinsulinemia facilitates VLDL production, particularly in the presence of an abundant supply of substrate for VLDL synthesis, the majority of in vitro studies using cultured hepatocytes and hepatoma cell lines have demonstrated an acute inhibitory effect of insulin. Using radiolabeled VLDL tracers we have examined the acute effect of hyperinsulinemia on VLDL production in humans. We found a rapid suppression of plasma free fatty acid (FFA) levels in response to insulin and a consistent 50-60% insulin-induced suppression of both VLDL TG and VLDL apolipoprotein (apo) B in lean insulin-sensitive individuals. Elevation of plasma FFA levels by infusing heparin and Intralipid without hyperinsulinemia resulted in a marked increase in VLDL TG and VLDL apoB production. When the insulin-induced suppression of plasma FFA levels was prevented during hyperinsulinemia, VLDL TG production was still inhibited, although to a lesser extent than with insulin alone. We concluded from these findings that insulin suppresses VLDL production in insulin-sensitive humans partly by suppressing plasma FFA levels and partly by a non-FFA-mediated (perhaps direct hepatic) mechanism. In addition, we found that chronically insulin-resistant hyperinsulinemic obese individuals were resistant to this suppressive effect of insulin on VLDL apoB production, in keeping with similar findings by others performing in vitro experiments using cultured hepatocytes isolated from insulin-resistant or hyperinsulinemic rats. The relevance of these findings to the mechanism of hypertriglyceridemia associated with chronic insulin-resistant states in humans remains a matter of speculation. One hypothesis is that resistance to the normal suppressive effect of insulin, in association with other metabolic abnormalities associated with insulin resistance, may contribute to postprandial and postabsorptive hypertriglyceridemia.

Animals↗

PubMed1996

The role of T-lymphocytes and cytokines in rheumatoid arthritis.

In this review the involvement of T cells, in addition to that of the monocyte/macrophage lineage, in the pathogenesis of rheumatoid arthritis is discussed. The evidence for the pathogenetic importance of T cells is based upon their state of activation in the synovial membrane and the cytokines produced. These cytokines can be detected in synovial fluids as well as in the synovial membrane by both immunohistochemistry and in situ hybridization. However, cytokine production can be detected only in a minor fraction of the T cells which contrasts the number of non-T cells observed to synthesize cytokines. Nevertheless, it can be assumed that the small amount of lymphokines is sufficient to activate a cytokine cascade derived from other cells. The cytokine profile secreted is indicative for a T cell response that primarily involves Th1-like cells.

Animals↗

PubMed1996

Will correction of dyslipoproteinaemia reduce coronary heart disease risk in patients with non-insulin-dependent diabetes? Need for trial evidence.

The incidence of atherosclerotic vascular disease is greatly increased in patients with non-insulin-dependent diabetes (NIDDM). The most frequent lipoprotein abnormalities in this type of diabetes are an increase in triglyceride-rich lipoproteins and a decrease in high-density lipoproteins. Hypertriglyceridaemia appears to be a stronger coronary heart disease risk factor in patients with NIDDM than in nondiabetic subjects. Plasma total and low-density lipoprotein cholesterol levels in NIDDM patients and nondiabetic subjects do not differ. Hypercholesterolaemia is, however, as powerful a predictor of coronary heart disease risk in diabetic patients as in nondiabetic subjects. In spite of this knowledge, there is to date no solid evidence to indicate whether correction of dyslipoproteinaemia in order to reduce coronary heart disease risk in patients with NIDDM is more, equally, or less beneficial than it is in nondiabetic subjects. The only available data come from post-hoc subgroup analyses of the Helsinki Heart Study and the Scandinavian Simvastatin Survival Study (4S). Other trials including patients with diabetes are in progress. Only one intervention trial (currently in its treatment phase), the Diabetes Atherosclerosis Intervention Study (DAIS), is specifically designed to examine the lipid hypothesis in patients with NIDDM.

Clinical Trials as Topic↗

PubMed1996

Fine specificity of anti-Ro(SSA) autoantibodies and clinical manifestations in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the fine specificity of the anti-Ro(SSA) autoimmune response in patients with systemic lupus erythematosus (SLE), and to correlate it with clinical and serological manifestations. METHODS: The frequency of anti-Ro and anti-La autoantibodies was determined by double immunodiffusion (DID), ELISA, and immunoblotting (IB) in 69 patients with SLE and 39 controls. Protein and RNA immunoprecipitation were used to further characterize anti-Ro positive sera. RESULTS: Anti-Ro antibodies were detected in 37 (54%) patients: 33 (48%) were positive by DID, 35 (51%) by ELISA, and 25 (35%) by IB; 32 sera were reactive in at least 2 of these 3 assay systems. By IB, 12 patients had antibodies to both the 60 kDa Ro (Ro60) and the 52 kDa Ro (Ro52), 11 patients were anti-Ro60 positive, 2 patients were anti-Ro52 positive, and 12 patients were not reactive with blotted Ro antigens. However, in immunoprecipitation assays all but one anti-Ro positive sera precipitated both Ro proteins. Anti-La reactivities were found in 15 anti-Ro positive patients: 13 sera were positive by IB, 11 by ELISA, and 9 by DID. Significant associations of anti-Ro antibodies with clinical symptoms were found for sicca syndrome, which was increased in anti-Ro positive patients (p < 0.05 vs anti-Ro negative patients), and for nephritis, for which an inverse correlation was found, since it was less frequently diagnosed in anti-Ro positive patients (p < 0.01). However, this association was seen only for those anti-Ro positive patients who were not reactive with Ro52 by IB. No difference was observed between anti-Ro/La and anti-Ro positive patients. CONCLUSION: DID and ELISA were of comparable sensitivity for detection of anti-Ro, IB was the most sensitive method for detection of anti-La. Moreover, our data indicate that IB may help to characterize clinically distinct subgroups of anti-Ro positive patients with SLE. Thus, determination of anti-Ro by IB may increase the prognostic value of this autoantibody.

Adolescent↗

PubMed1996

Molecular differential diagnosis of renal carcinoma: from microscopes to microsatellites.

In the last decade, specific chromosomal alterations have been associated with different tumor types. These aberrations were originally detected by karyotyping and then by more sophisticated cytogenetic analysis. A few karyotypic alterations can be directly linked to distinct malignancies, such as the Philadelphia chromosome in acute lymphoblastic leukemia, loss of distal chromosome 3p 14 in small-cell lung cancer, the loss of distal chromosome 11p13 in Wilms' tumor, and loss or rearrangement of the short arm of chromosome 3 in clear and chromophobe RCC. The relative specificity of the latter findings enabled investigators to diagnose an occult renal clear-cell carcinoma from a supraclavicular lymph node metastasis by analysis of G-banded metaphase chromosomes obtained from this mass. A similar report based also on cytogenetic findings was published earlier. Karyotypic changes, however, detect only gross alterations visible to an observer. With more refined diagnostic tools, such as microsatellite analysis, other, even smaller, well defined lesions can be analyzed. A summary of the known frequencies of chromosomal losses is given in Table 1. The combination of certain LOH patterns has shown great promise in the differential diagnosis of renal tumors. The transfer of molecular genetics from the laboratory to surgical pathology and other clinical departments is a meaningful event and a challenging task. Molecular pathology is certain to become important in the diagnosis of tumors with unclear histology. Diagnosis based widely upon staining techniques and determination of a patient's prognosis by staging and grading alone will be increasingly accompanied by molecular genetic methods. Pathology may be on the verge of the greatest change since the introduction of the microscope.

Carcinoma, Renal Cell↗

PubMed1996

Contribution of de novo fatty acid synthesis to very low density lipoprotein triacylglycerols: evidence from mass isotopomer distribution analysis of fatty acids synthesized from [2H6]ethanol.

A detailed comparison of the structures of plasma very low density lipoprotein (VLDL) and liver triacylglycerols (TG) (Yang et al. 1995. J. Lipid Res. 36: 125-136) has demonstrated that a minimum of 60% of the secreted TG could have been derived from partial lipolysis and reesterification of stored TG and a maximum of 40% could have been derived from direct secretion of newly made TG. To investigate the processes involved in the transfer of TG to VLDL in vivo, we have determined the distribution of deuterium among the molecular species of the liver-TG and VLDL-TG during the infusion of perdeuterated ethanol along with fructose or glucose and during the provision of either glucose or fructose in the drinking water for 2 weeks. The deuterium labeling (percent excess and percent replacement) of the total fatty acids was determined by GC/MS of the methyl esters while the labeling of the glycerol and the glycerol plus fatty acids of the enantiomeric diacylglycerol moieties of TG was determined by LC/MS with on-line mass spectrometry. Supplementation of the diet for 2 weeks with either glucose and fructose stimulated the synthesis of TG containing new fatty acids and glycerol. The proportion of the newly made to preexisting TG differed in VLDL from that in the liver. The 2H % replacement in glycerol and in total fatty acids was greater in VLDL-TG than in the liver-TG. On the basis of the mass isotopomer distribution analysis it was estimated that a maximum of 30% of the VLDL-TG could have been derived directly from TG that was made de novo and did not equilibrate with the liver-TG stores. The transfer of the stored TG to VLDL was best accounted for by a degradation to 2-monoacylglycerols and resynthesis via the 2-monoacylglycerol pathway with addition of an excess of newly synthesized fatty acids to the resynthesized TG.

Animals↗

PubMed1995

Phenotypic patterns of mononuclear cells in dilated cardiomyopathy.

BACKGROUND: Immunological factors in the pathogenesis of idiopathic dilated cardiomyopathy (IDC) were suggested previously on the basis of the demonstration of mononuclear cell infiltrates and autoantibodies against the myocardium. The present study investigated whether tissue leukocyte subpopulations isolated from hearts with IDC (n = 6) differ in phenotype from those of tissues without IDC (n = 7). METHODS AND RESULTS: Leukocytes were quantified as reactive cells per square millimeter in perivascular, interstitial, and parenchymal tissue sections. Freshly isolated heart-tissue T cells and peripheral-blood T cells from the same patients were analyzed by triple staining and flow cytometry to identify T-cell subpopulations as well as their states of differentiation (expression of CD45RA and Leu-8 versus CD45RO) and activation (IL-2R, IL-7R, very late antigen-1, HLA-DR). All types of infiltrating cells (T cells, B cells, macrophages, granulocytes) are increased in hearts with IDC compared with normal hearts, but only CD8+ T cells and macrophages are increased relative to the other leukocyte subpopulations. CD45RO+/CD45RA-/Leu-8- cells constitute the majority of heart-tissue T cells in both normal hearts and hearts with IDC. Strikingly, hearts with IDC are infiltrated by eightfold greater numbers of perivascularly located IL-2R(+)- (26% of all T cells) and CD45RO(+)-activated memory T cells; moreover, in contrast to normal heart, approximately 40% of both CD4+ and CD8+ heart-tissue T cells express activation markers. CONCLUSIONS: Both normal hearts and hearts with IDC are populated by leukocytes. The quantitative increase in IDC, associated with a dramatically altered activation status of heart-tissue T cells, suggests a direct role of infiltrating leukocytes in the pathogenesis of IDC.

Cardiomyopathy, Dilated↗

PubMed1995

Autoimmune response to the spliceosome. An immunologic link between rheumatoid arthritis, mixed connective tissue disease, and systemic lupus erythematosus.

OBJECTIVE: To assess the significance of autoantibodies to RA33, the A2 protein of the heterogeneous nuclear ribonucleoproteins (hnRNP), and to the related hnRNP proteins A1, B1, and B2 in rheumatic diseases. METHODS: Using a partially purified preparation of hnRNP-A and hnRNP-B proteins, sera from 303 patients with various rheumatic diseases were investigated by immunoblotting. For the analysis of cross-reactivities, autoantibodies were affinity purified by blot elution. RESULTS: Anti-A2/RA33 was found in 35% of rheumatoid arthritis (RA) patients, 38% of mixed connective tissue disease (MCTD) patients, 23% of systemic lupus erythematosus (SLE) patients, and, apart from single exceptions, not in patients with other rheumatic diseases. All anti-A2/RA33-positive sera were also reactive with B1 and B2, and anti-A2/RA33 antibodies cross-reacted with both proteins. Antibodies to hnRNP-A1 were found less frequently; moreover, the majority of anti-A1-positive sera also contained anti-A2/RA33 antibodies. In anti-A1, anti-A2/RA33 double-positive sera, cross-reactivity between the 2 antibodies was generally observed. In SLE patients, the presence of anti-A2/RA33 was correlated with the presence of anti-(U1) small nuclear RNP (snRNP) and anti-Sm (P < 0.0001 and P < 0.005, respectively), but there was no evidence for cross-reactivity between antibodies to hnRNP and antibodies to snRNP antigens. CONCLUSION: Since both hnRNPs and snRNPs are essential components of the spliceosome, the data show that the immune systems of patients with RA, SLE, and MCTD react to this functional complex. However, compared with MCTD and SLE patients, RA patients have a more restricted immune response to the spliceosome: they react to hnRNP proteins, particularly to hnRNP-A2/RA33, but not to snRNPs.

Arthritis, Rheumatoid↗

PubMed1995

Activated naive CD4+ peripheral blood T cells in autoimmune thyroid disease.

To better understand the clinical significance of changes in lymphocytes in thyroid disease this study analyzed the proportion of CD19+, CD3+, CD4+ and CD8+ cells among circulating lymphocytes in Graves' disease (GD, n = 34) and autoimmune hypothyroidism (AH, n = 28) vs healthy subjects (n = 15). In addition, the expression of CD25 and CD45 isoforms on CD4+ T cells as well as their modulation by methimazole in patients with GD was measured using three color flow cytometry. It was observed that, irrespective of age, both patients with GD (17.6 +/- 7.0% +/- SD) and those with AH (19.0 +/- 9.5%) had an increased percentage of the CD25+CD45RA+ (naive) subpopulation of helper cells vs healthy subjects (7.9 +/- 2.3%, p < 0.0001). In patients with AH peripheral memory cells and hence overall CD25+ cells were more frequent among helper cells (56.7 +/- 12.2%) than in healthy subjects (40.8 +/- 14.0%, p < 0.001). Patients with GD (46.2 +/- 13.4%) did not differ from normal subjects in this respect. Treatment of GD with MMI reduced the percentage of CD25+CD45RA+ cells among CD4+ cells toward values seen in healthy subjects. In addition, we confirm previous reports that CD8+ cells toward values seen in healthy subjects. In addition, we confirm previous reports that CD8+ cells are significantly reduced in AH (23.9 +/- 4.9%) and untreated Graves' disease (23.2 +/- 6.6%) vs healthy subjects (32.2 +/- 5.9%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗