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Biomedical subjects

S Muller

Publications and source records attributed to S Muller.

At least 307 records · Page 17Linked to original sources

Presence of antibodies to ubiquitin during the autoimmune response associated with systemic lupus erythematosus.

Sera from patients with systemic lupus erythematosus (SLE) were shown to react with both ubiquitin and a synthetic fragment of it (residues 22-45) in an ELISA and with ubiquitin in immunoblotting experiments. Close to 80% of lupus patients possessed ubiquitin antibodies, whereas only 55% of them possessed native DNA antibodies, a marker of SLE. Less than 16% of patients with other rheumatic autoimmune diseases possessed antibodies to ubiquitin. Our results indicate that the combined measurement of antibodies to native DNA and to ubiquitin could appreciably increase the detection of SLE cases (up to 85% in our study). It is suggested that ubiquitin, a heat shock protein, could be involved in antibody formation against ubiquitin-protein conjugates present during cellular injury and that this represents a major characteristic of the autoimmune response in SLE.

Antibodies, Antinuclear↗

Lack of influence of cyclosporine on antigen presentation to lysozyme-specific T cell hybridomas.

Cyclosporine (CsA) was tested for its ability to inhibit antigen presentation by spleen cells or the B lymphoma line A20 to T cell hybridomas specific for hen egg-white lysozyme (HEL). Antigen-presenting cells (APC) were treated with CsA or nonimmunosuppressive derivatives thereof during or prior to encounter with antigen. The APC were then washed extensively and incubated in CsA-free medium for 6 hr before the T hybridoma cells were added. Under these conditions, CsA had no effect on antigen presentation up to the cytostatic regimen (1 microgram/ml). Omission of the 6-hr interval between CsA treatment of APC and the addition of T hybridoma resulted in inhibition of interleukin 2 production, although the CsA concentrations required were 10-75-fold higher than the ones inhibiting T cells directly (IC50: 100-150 ng/ml vs. 2-10 ng/ml). The responses to both HEL and a synthetic peptide of HEL sequence 105-120 were inhibited, indicating that the step influenced by the drug was not antigen-processing. The nonimmunosuppressive derivatives remained ineffective under these conditions. The results illustrate that the carryover of CsA from APC to T cells can mimic a drug effect on antigen presentation. Therefore, the demonstration of a CsA effect on antigen presentation can only be considered as conclusive when the readout of APC function is not a T cell response.

Animals↗

Gastric adenocarcinoma associated with adenomyoma of the stomach.

We report a case of gastric adenomyoma contiguous with adenocarcinoma of the stomach. Although a similar association is well recognized in the duodenum, we believe this to be the first documented case in the stomach. We review the literature on adenomyomata and discuss the implications of this finding. It would appear that glandular and cystic intramural lesions of the stomach are a heterogeneous group, and while there is a well established association between gastric carcinoma and gastritis cystica profunda, the same does not apply to gastric adenomyoma.

Adenocarcinoma↗

Glucose metabolism in isolated adipocytes from ad Libitum- and restricted-fed lean and obese Zucker rats at two different ages.

Chronic food restriction in Sprague-Dawley rats has been shown to alter adipose glucose metabolism. In the present study, lean and obese male Zucker rats were food restricted from 5 weeks until either 10 or 26 weeks of age and adipocyte glucose metabolism was measured. Adipocytes from restricted-fed lean and obese Zucker rats converted more glucose to CO2 and fatty acids than those from their ad libitum-fed counterparts in both the absence and the presence of increasing doses of insulin at 10 weeks of age. At the highest insulin dose, adipocytes from restricted-fed obese rats converted significantly more glucose to CO2 and fatty acids than did those from restricted-fed lean rats. Basal glyceride-glycerol values were similar in all groups at this age. At the 0.4 and 2.0 ng/ml insulin levels, glyceride-glycerol production was highest in restricted-fed lean rats; restricted-fed obese and ad libitum-fed lean rats had similar values; and ad libitum-fed obese rats had the lowest. At the 20 ng/ml dose, glyceride-glycerol values of restricted-fed rats were higher than those of ad libitum-fed rats. Basal and insulin-stimulated values were compared within each group. Most basal versus insulin-stimulated values were significantly different for the two lean groups. For ad libitum-fed obese rats, only 0 versus 20 ng/ml insulin values were significant. Restricted-fed obese rats had significant increases in 0 versus both 2 and 20 ng/ml insulin values. Restricted-fed obese rats had significantly lower serum insulin levels relative to ad libitum-fed obese rats at 10 weeks of age. Adipocytes from all rats at 26 weeks of age had similar basal rates of conversion of glucose metabolism to all three metabolites. In the presence of insulin, adipocytes from restricted-fed lean rats metabolized significantly more glucose to CO2 and glyceride-glycerol than adipocytes prepared from the three other groups. Fatty acid production was similar in all groups at each insulin level. Only restricted-fed lean rats showed consistent significant responses to insulin stimulation for the three metabolites. Whether these results are due to age, length of food restriction, or serum insulin levels remains to be determined.

Adipose Tissue↗

Antibodies to histones in rheumatoid arthritis.

Using a newly developed enzyme-linked immunosorbent assay, antibodies to histones (H1, H2A, H2B, H3 and H4) were found in 32 out of 40 rheumatoid arthritis patients with antinuclear antibodies at a titer greater than or equal to 100 as measured by indirect immunofluorescence. The anti-H2A reactivity was higher in patients with secondary Sjögren's syndrome than in those without, but the highest antihistone reactivity and the most heterogeneous patterns were observed in patients who were receiving D-penicillamine.

Adult↗

Specificity of antibodies raised against triacetylated histone H4.

Ten monoclonal antibodies (mAbs) were obtained by immunizing animals with triacetylated histone H4 from cuttle-fish. The fine specificity of these antibodies was studied using various populations of acetylated H4, (H3H4)2 tetramers and histone octamers as well as with acetylated and nonacetylated peptides of H4. None of these mAbs were found to recognize triacetylated H4. Only five of them bound to diacetylated, monoacetylated and nonacetylated H4. One antibody was specific for H4 associated in the form of histone octamers and did not bind to any nonacetylated or acetylated form of H4 monomers. Eight of the antibodies were specific for residues situated in the region 9-23 of H4. None of the mAbs was completely specific for acetylated forms of H4. In contrast, antisera raised in rabbits against triacetylated H4 reacted strongly with tri and diacetylated H4, weakly with monoacetylated H4 and barely or not at all with nonacetylated H4.

Acetylation↗

Effects of long-term moderate food restriction on growth, serum factors, lipogenic enzymes and adipocyte glucose metabolism in lean and obese Zucker rats.

The effects of long-term moderate food restriction were assessed in lean and obese male Zucker rats. A 30% reduction in food intake from 5 to 68 wk of age resulted in parallel lowering of body weight in both lean and obese rats compared to their respective ad libitum-fed control groups. In lean rats, epididymal and retroperitoneal fat pad weights and cell size were lowered by food restriction. In obese rats there was an effect of food restriction on growth of the epididymal pad but not the retroperitoneal pad. Hyperinsulinemia, hyperlipidemia and elevated serum albumin levels, as well as higher activity of lipogenic enzymes, were also not affected by food restriction in the obese rat. In a second experiment, long-term food restriction resulted in greater glucose conversion to CO2 in response to insulin in adipocytes from lean rats but not obese rats compared to their respective control groups. These results indicate that food restriction throughout the first year of life in the obese Zucker rat does not alter the development of hyperplastic obesity and insulin resistance.

Adipose Tissue↗

Virus-specific IgM and IgG antibody production by B cells during herpes simplex virus type 2-induced immunosuppression as analysed by an immunospot assay.

The mechanism of herpes simplex virus (HSV)-2-induced immunosuppression was analysed by determination of the number of IgM and IgG antibody-secreting B cells in female BALB/c mice using an immunospot assay. Primary HSV-1 or -2 as well as homologous or heterologous booster infections at different times were performed. In accordance with earlier results on humoral antibody generation, in contrast to HSV-1, HSV-2 induced only very low numbers of antibody-producing B cells in dose-response experiments. They appeared late after infection compared to HSV-1. Despite a homologous humoral booster reaction against HSV-1 at day 8 no IgM- or IgG-secreting cells in the spleen could be detected. This non-reactivity of the spleen had vanished 10 days later, when secondary reactions of B cells could be observed. Secondary infections with a high homologous dose of HSV-2 after a low primary dose produced only a low booster response of IgG-secreting B cells. Suppression of humoral antibody production induced by HSV-2 (high dose) waned after more than 50 days, indicating that the HSV-2-induced suppression did not impair antigen presentation or memory cell generation.

Animals↗

Ulcerative colitis complicated by disseminated intravascular coagulation.

We report a case of chronic ulcerative colitis complicated by clinical evidence of disseminated intravascular coagulation and pathological evidence of intestinal ischaemia secondary to venular and capillary fibrin thrombi. This may well represent an example of univisceral Shwartzman reaction occurring in a sensitized target organ.

Colitis, Ulcerative↗

Human antinuclear autoantibodies crossreacting with the plasma membrane and the N-terminal region of histone H2B.

A subset of human antinuclear autoantibodies (denoted X-ANA) with affinity for mononucleosomes crossreacts with an antigen in the plasma membrane of viable leukocytes. The nature of the nuclear antigen recognized by these antibodies was studied in detail. In immunoblot experiments, it was shown that X-ANA recognizes the core histone H2B, but not the other histones. By using synthetic peptides corresponding to different parts of the core histones as antigens in ELISA, it was shown that X-ANA reacts with the N-terminal residues 6-18 of H2B. The binding of X-ANA to the synthetic 6-18 H2B peptide used as solid-phase antigen in ELISA was inhibited by nucleosomes and by the 6-18 H2B peptide but not by free H2B. These observations agree with earlier suggestions that the N-terminal tail of H2B is located at the surface of the nucleosome and indicate that the native structure of monomeric H2B is different from its structure when complexed within the nucleosomes.

Antibodies, Antinuclear↗

High prevalence of antibodies to histones among patients with primary biliary cirrhosis.

Histones are small, basic proteins involved in the packing of DNA into the eucaryotic nucleus. Using an immunodot assay and an enzyme-linked immunosorbent assay (ELISA), sera from patients with liver disease were tested for antibodies to the five individual histones H1, H2A, H2B, H3 and H4. Histones extracted from calf thymus and separated into individual fractions by gel exclusion chromatography were either immobilized on nitrocellulose or adsorbed to microtitre plates and the resulting immune complexes examined via a streptavidin-biotin bridge. Of the liver disease sera tested, only specimens obtained from primary biliary cirrhosis patients contained antibodies reactive with histones. The predominant reactivity was to histone H1 and H2B, and amounted to 74% for IgM antibodies, and 60% for IgG antibodies. Our data indicate that antibodies specific for histones might represent a novel serological marker for primary biliary cirrhosis.

Adult↗

Detection of papillomavirus DNA in human semen.

Human papillomavirus DNA has been detected in the semen of three patients, two of whom have severe chronic wart disease. These data support the contention that sexual transmission of human papillomavirus DNA could occur via semen, a possibility suggested by epidemiological data on the sexual transmission of human papillomavirus.

DNA, Viral↗

Comparison of different methods for localizing antigenic regions in histone H2A.

Four different variations of enzyme-linked immunosorbent assays (ELISA) were used to analyze the antigenic structure of histone H2A. Eleven natural and 10 synthetic peptides of H2A were tested for their capacity to bind antibodies raised against the complete molecule in a direct binding assay. Results were compared to those obtained in a direct test using several peptide-BSA conjugates. The capacity of peptides to inhibit the reaction between H2A antibodies and the complete H2A molecule or large fragments of it was also measured. Inhibition assays detected antigenic activity in a large number of peptides than did direct binding assays. Antisera raised against eight synthetic, unconjugated peptides all reacted with histone H2A in ELISA. Using as probes peptides of 14-21 residues, at least 11 antigenic regions could be recognized, indicating that virtually the entire H2A polypeptide chain possessed antigenic activity.

Animals↗

Crohn's disease involving the penis.

Perianal complications of Crohn's disease occur in 25-70% of patients but perineal and genital lesions are rare. Treatment is controversial and there is a risk of recurrent or persistent disease. We report two cases of Crohn's disease involving the penis, one with multiple scrotal urinary fistulae, partial destruction of the proximal urethra, and ulceration of the penile shaft; the other with metastatic cutaneous ulceration of the penile shaft. The second case is particularly unusual in that the patient presented at the VD clinic as a case of syphilis.

Adolescent↗

Ulcerative colitis complicated by Budd-Chiari syndrome.

We present two cases of ulcerative colitis associated with a chronic pattern of hepatic vein thrombosis (Budd-Chiari syndrome). Progression of the hepatic disorder appeared to be unrelated to the activity of the colitis. Liver function tests were normal until a late stage in the disease except for a high serum alkaline phosphate and a low serum albumin. This combination of abnormalities together with ascites merit further investigation and should raise the suspicion of hepatic vein thrombosis complicating ulcerative colitis.

Adult↗