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B E Wenzel

Publications and source records attributed to B E Wenzel.

33 records · Page 2Linked to original sources
PubMed1991

Detection, cellular localization, and modulation of heat shock proteins in cultured fibroblasts from patients with extrathyroidal manifestations of Graves' disease.

We hypothesize that fibroblasts obtained from the retroocular space and the pretibial skin, sites affected by the peripheral manifestations of Graves' disease, share unique characteristics that may in part explain the site specificity of Graves' ophthalmopathy (GO) and pretibial myxedema (PTM). Heat shock proteins (HSPs), synthesized by cells undergoing stress, function to maintain cellular homeostasis and are probably involved in the intracellular processing and cell surface presentation of antigens. We investigated possible differences in the expression of 70-kDa HSPs between cultured fibroblasts obtained from patients with severe GO and normal individuals. In addition, we compared HSP expression in fibroblasts derived from tissues involved in the extrathyroidal manifestation of Graves' disease (GO and PTM) with that in fibroblasts from uninvolved tissues. HSPs were detected by both immunoblotting and indirect immunofluorescence, using monoclonal antibodies that are directed against HSP72, HSP72/73 (termed HSP70), and HSP90. HSP expression at baseline and after treatment with various cytokines and heat stress was examined. At baseline, HSP72 reactivity was exclusively detected in retroocular and pretibial fibroblasts from patients with severe GO and PTM, but was not observed in abdominal fibroblasts from these patients and was not detectable in fibroblasts from any anatomical site of normal individuals. The abundance of HSP70 expression at baseline and after treatment with certain cytokines was significantly greater in retroocular and pretibial fibroblasts from patients with GO than in normal individuals. In addition, characteristic changes in the cellular localization of HSPs before and after exposure to heat stress and cytokines were observed; cell surface expression of HSP70 was detected at baseline in fibroblasts from patients, but not in normal fibroblasts. These data provide the first evidence that HSPs are differentially expressed by fibroblasts derived from tissues affected by the extrathyroidal manifestations of GD. These proteins may have a role in localized immune processes, leading to the development of GO and PTM.

Biopsy↗
PubMed1991

Increased cellular growth of FRTL-5 thyroid cells mediated by discontinuous stimulation with bTSH.

Previous reports showed pulsatile secretion of TSH in man. Therefore, we investigated the effect of discontinuous versus continuous TSH stimulation on the cellular level of FRTL-5 thyroid cells, namely the expression of a nuclear proliferation antigen (NPAg). The expression of this antigen correlates linearly with the 3H-thymidine incorporation and is a marker for cellular growth. The FRTL-5 cells were stimulated for 4 hours with bTSH (0.01-1.0 U/l). Compared to continuously stimulated cell cultures the discontinuous stimulation of FRTL-5 cells with bTSH showed a significant higher rate of NPAg expression, i.e. cellular growth.

Animals↗
PubMed1990

Antibody activity against lipopolysaccharides, lipid A and proteins from Enterobacteriaceae in patients with chronic inflammatory liver diseases.

These studies are concerned with detection of circulating antibodies against various defined enterobacterial antigens in patients with chronic inflammatory liver diseases such as chronic hepatitis type B (n = 46), chronic active hepatitis (CAH) of autoimmune type (n = 10), alcoholic cirrhosis (n = 24) and primary biliary cirrhosis (PBC) (n = 24) as well as in healthy individuals (n = 39). Anti-LPS and anti-lipid A were determined by hemolytic and hemagglutination assay. Immunoblot technique was used to investigate the antibody activity against plasmid encoded proteins from Yersinia enterocolitica. Persistent titers of anti-LPS up to serum dilution 1:32.768 were found with hemolytic and hemagglutination assay in patients with alcoholic cirrhosis or PBC and in healthy control. In contrast nearly 50% of patients with chronic hepatitis B had no hemolytic antibodies against the two LPS E. coli serotypes at the time of liver biopsy. Anti-lipid A was detectable in 58% of patients with alcoholic cirrhosis but in low titers in less than 10% in the other groups (p less than 0.001). Alcoholic cirrhosis was also associated with a high frequency of IgG and IgA antibodies against plasmid encoded proteins from Yersinia enterocolitica. The data indicate that the O-polysaccharides as strong antigens are physiologically exposed to the immune system while lipid A and enterobacterial proteins are solely immunogenic under abnormal conditions.

Adult↗
PubMed1989

Thyroid growth stimulating activity in highly purified IgG-fractions of patients with nonimmune thyroid diseases.

Two different proliferation assays have been used to measure the proliferative potential of IgG-fractions from 57 patients with nontoxic goiter of an iodine-deficient area: primary human thyroid epithelial cells (TEC) and the thouroughly investigated FRTL-5 cell line. IgG-fractions from patients with nontoxic goiter (n = 30), nontoxic recurrent goiter (n = 8), toxic-nodular goiter (n = 15) and carcinoma of the thyroid (n = 4) were highly purified on DEAE-Sepharose and additionally Protein A-Sepharose in some cases. The two proliferation assays gave contradictory results: primary cultures of human thyroid epithelial cells (TEC) could not be stimulated by any of the patient's IgG-fractions nor by bTSH. The FRTL-5 cells, however, were stimulated with 10 microU/ml bTSH by 326% +/- 96% (range: 222% - 497%, p less than 0.001). In one experimental series, 72% of all patients exceeded mean + 2 SD of normal controls, when the stimulation index was referred to the effect of bTSH (NTG: 77%, Rec. G.: 88%, Tox. G.: 53%, Ca. thyroid: 75%). With a different method of calculation - stimulation index referred to the basal value - the number of patients above mean + 2 SD of normal controls decreased to 30% (NTG: 33%, Rec. G.: 12.5%, Tox. G.: 33%, Ca. thyroid: 25%). Statistical analysis, however, of results of different patient groups compared to the normal control group failed to show any significance.

Adolescent↗
PubMed1987

Modulation of class-II antigen expression in human thyroid epithelial cell cultures.

The modulation of HLA-D expression of thyroid epithelial cells (TEC) was studied in vitro by means of immunofluorescence. Under serum-free culture conditions, TSH and TSH-receptor antibodies induce HLA-D on TECs derived from GD-patients. Serum-free culture conditions provide a higher availability of TSH-receptors by a 'right side right' polarity of the cellular morphology. There was no evidence for IFN-gamma producing cell contaminations on GD-TECs. TSH in contrast to IFN-gamma does not induce HLA-DQ on TECs. HLA-DQ is not displayed by spontaneously class-II antigen expressing GD-TECs. Methimazole as well as perchlorate do not suppress HLA-D expression of TECs.

Cells, Cultured↗
PubMed1984

Biological activity of lymphocytotoxic antibodies in Graves' disease and Hashimoto's thyroiditis.

Sera of 48 patients with Graves' disease (GD) and 23 with Hashimoto's thyroiditis (HT) were tested for lymphocytotoxic (LCT), granulocytotoxic (GCT) and monocytotoxic (MCT) activity. In GD, 12 patients (25%) had cold-reacting LCT and 13 patients (27%) had warm-reacting LCT. LCT were cytotoxic to both B and T cells but the majority of sera with cold-reacting LCT and eluates from lymphocytes were more cytotoxic to B lymphocytes. Warm-reacting LCT were directed exclusively against B cells. LCT did not correlate with peripheral lymphocyte counts, antithyroglobulin or antimicrosomal antibodies, sex, age, pregnancies, thyroid status or medication. However the mean duration of the disease was 15 months in LCT positive group and 55 months in LCT negative group (p less than 0.01). Weak GCT were found in 8 of 35 sera (23%). Six of 33 sera (18%) contained cold-reacting MCT and 9 (27%) had warm-reacting MCT. Some cytotoxins were directed against several types of cells as evidenced by cytotoxicity of eluates from lymphocytes against PMN and/or monocytes. Of 23 patients with HT, 11 (48%) had cold-reacting LCT. None had warm-reacting LCT. Sera and eluates from lymphocytes showed predominant cytotoxicity toward B cells. No correlation to the presence of antibodies, sex, age, pregnancies, thyroid status or medication was detected. Four of 23 sera had weak cold-reacting GCT, 5 had cold-reacting MCT which killed on average 31% of monocytes and 4 had weak warm-reacting MCT. Twelve of 22 sera from GD and HT had cytotoxic activity against thyroid cells (TCT). TCT correlated with LCT at p less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Spontaneous secretion of thyroid autoantibodies by cultured peripheral blood lymphocytes from patients with Hashimoto's thyroiditis detected by micro-ELISA techniques.

The spontaneous in vitro production of anti-thyroglobulin (aTg) and anti-microsomal (aM) antibodies by mononuclear cells (MNC) from patients with Hashimoto's thyroiditis (HT) was analysed by an ELISA detection system. MNC from 35 HT patients spontaneously produced detectable levels of both autoantibodies in vitro (i.e., without mitogenic or antigenic stimulation). aTg was quantified using a reference aTg IgG standard and ranged from 55 to 9,000 ng aTg. Specificity of aTg by ELISA was assessed using heterologous Tg antigen (Ag). Microsomal Ag obtained by gel filtration was far less contaminated with Tg than the ultracentrifugation pellet. Specificity of aM ELISA was assessed using insulinoma membrane as unrelated Ag and by blocking aM detection only with microsomal Ag. aM levels in the 35 supernatants ranged from 0.1 to 1.12 OD. A direct correlation was found between aM serum titres detected by haemagglutination and in vitro aM spontaneous production, but not for aTg. This lack of correlation for aTg might have biological relevance. Tg restimulation in vitro enhanced aTg production in only four out of 18 cases, of which only one was significant. This system provides a tool for studies of the immunoregulation of thyroid autoantibody formation in vitro.

Antibody Specificity↗