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Biomedical subjects

H Fehr

Publications and source records attributed to H Fehr.

At least 19 recordsLinked to original sources
PubMed1997

Histone-specific Th0 and Th1 clones derived from systemic lupus erythematosus patients induce double-stranded DNA antibody production.

OBJECTIVE: To investigate whether histone-specific T helper (Th) cells that are able to induce anti-double-stranded DNA (anti-dsDNA) antibodies can be isolated from patients with systemic lupus erythematosus (SLE) and to characterize the cytokine secretion pattern of such Th clones. METHODS: Peripheral blood mononuclear cells from SLE patients and healthy donors were stimulated with autologous apoptotic cell material or purified histones, expanded with interleukin-2 (IL-2), and cloned by limiting dilution. Histone reactivity of clones was examined by histone-specific proliferation and cytokine release. Cytokines were determined by enzyme-linked immunosorbent assay (ELISA) and CTLL-2 bioassay. Induction of anti-dsDNA antibodies was measured in cocultures of autologous B cells and Th clones by ELISA: RESULTS: Numerous histone-specific T cell receptor (TCR) alpha/beta+ Th clones were established from 2 of 3 patients with active SLE and from 1 of 2 healthy individuals. Most Th clones secreted IL-2, interferon-gamma (IFNgamma), and IL-4, whereas some produced predominantly IL-2 and IFNgamma. Th clones that could stimulate the production of anti-dsDNA antibodies were derived from SLE patients and from a healthy individual. CONCLUSION: Th cells specific for histones may play an important role in the pathogenesis of SLE by inducing autoantibodies to dsDNA. Both Th1 and Th2 cytokines may be involved in the pathogenesis of SLE. The presence of histone-specific Th cells in a healthy individual indicates the importance of peripheral tolerance for preventing autoimmunity to nuclear antigens.

Adult↗
PubMed1995

Preferential recognition of specific DNA motifs by anti-double-stranded DNA autoantibodies.

Although antibodies (Ab) specific for double-stranded (ds) DNA are thought to be involved in the etiopathogenesis of systemic lupus erythematosus (SLE), the fine structure of their DNA targets remains elusive. We have adapted a polymerase chain reaction (PCR)-assisted immunoprecipitation method to define the binding sites in DNA sequences recognized by high affinity anti-dsDNA Ab of SLE patients. SLE sera were used to bind templates from a pool of double-stranded oligonucleotides (ON). A central part of 20 base-pair random sequence was flanked by restriction endonuclease recognition sites and sequences complementary to predefined PCR primers. Immunoselected ON were precipitated, isolated from the immune complexes and then subjected to a further immunoprecipitation step after amplification by PCR. After five cycles of immunoprecipitation and PCR, the resulting ON were cloned. Sequence analysis revealed that sera from SLE patients and two human monoclonal anti-dsDNA Ab obtained from SLE patients preferentially select sequences expected to form non-B-DNA structures. Inhibition studies of the Farr assay confirmed the increased affinity of the selected epitopes for anti-DNA Ab as compared to random B-DNA.

Antibodies, Antinuclear↗
PubMed1993

[Endoscopic, biopsy and functional results in irradiated esophageal carcinoma].

83 patients of average age 64 (36-86) years with esophageal cancer were irradiated according to a prospectively defined treatment concept. After 60 Gy, re-endoscopy with biopsy was scheduled. If the tumor was still macro- or microscopically described, a boost to 70 Gy was given. During consistent weekly monitoring particular attention was focused on patients' ability to feed themselves. While initially only 7.2% could swallow solid food, by the end 84% of patients with a radiation dose of 60 Gy or more reported normal daily eating. Patients in whom the tumor was no longer present endoscopically or histologically survived four times longer (13.5 months) than those with persistent malignoma.

Adenocarcinoma↗
PubMed1992

Analysis of immunoglobulin variable region genes from human IgG anti-DNA hybridomas.

The molecular mechanisms leading to anti-double-stranded (ds) DNA antibody production in systemic lupus erythematosus (SLE) are poorly understood. We describe here the immunoglobulin variable region genes of six human hybridomas secreting IgG anti-dsDNA antibodies derived from three SLE patients. The monoclonal IgG anti-dsDNA antibodies have been shown to be of high affinity and no multireactivity was observed (Winkler et al., Clin. Exp. Immunol., 1991. 85: 379). The comparison of the variable region genes expressed in the hybridomas with known germ-line genes as well as with the germ-line counterparts from one patient shows that the VH and VL sequences are somatically mutated. The pattern and extent of the observed somatic mutations are suggestive for an antigen-driven selection of at least four of these B cell clones. Several VH and VL genes used by the hybridomas were found to be expressed in the natural antibody repertoire, in the restricted fetal repertoire and in B cell malignancies expressing the CD5 antigen.

Amino Acid Sequence↗
PubMed1987

[Radiotherapy of esophageal carcinoma. Results checked clinically by radiology, endoscopy, biopsy and autopsy].

Forty-four patients with histologically confirmed esophageal cancer were irradiated with 60 Gy, checked endoscopically and by biopsy, and then followed clinically or radiologically until their death. The findings confirm the local destructibility of esophageal cancer with loosely ionized radiation and a favorable effect on quality of life. Three quarters of the patients were able to take normal food at the end of the radiotherapy, while the remainder were at least able to swallow soft foods. Radiotherapy can be offered as an effective alternative to patients, especially when operation is associated with a high risk. This is also demonstrated by the fact that 23 of 32 patients who had endoscopy and biopsy again at the end of the radiotherapy had no histologically demonstrable tumor.

Adenocarcinoma↗
PubMed1987

[Microangiopathic hemolytic anemia, erythrophagocytosis and consumption coagulopathy in vinyl chloride-induced hemangiosarcoma of the spleen and liver].

A case of angiosarcoma of the liver and the spleen following vinyl chloride exposure is described. The main symptoms in clinical diagnosis were microangiopathic hemolysis, disseminated intravascular coagulation, hepatosplenomegaly and exposure to vinyl chloride thirty years ago. It is the first case in which liver and spleen are involved in angiosarcoma due to vinyl chloride exposure. The tumor cells showed angioformative and solid histiocytoid growth with erythrophagocytosis.

Aged↗
PubMed1980

[Lysolecithin and stress ulcers in rats].

The effect of lysolecithin on gastric mucosa in rats has been investigated using a new operative model. Ten rats underwent sham-laparotomy. In 4 other groups, each of 10 animals, the rats underwent pyloro-jejunostomy and Roux-en-Y anastomosis. 9 of 10 rats operated upon in this way, and given a solution of lysolecithin to drink before administration of restraint stress, produced stress ulcers. However, only 3 of 10 animals given Ringer-solution produced minor mucosal defects. Lysolecithin not combined with stress had no noteworthy deleterious effect on gastric mucosa either in sham-operated rats or in those with our operation model. Thus, lysolecithin combined with stress in our model performed an important function in the pathogenesis of stress lesions. Lysolecithin is produced in considerable quantities during fat metabolism in the intestine, and may be regurgitated together with duodenal contents into the stomach.

Animals↗
PubMed1980

Experimental microsurgical model in rats preventing duodenogastric reflux. A preliminary report.

For the purpose of studying the significance of the bile and duodenal reflux into the stomach in rats we present an experimental animal model which--in contrast to the procedures reported until now--can exactly be reproduced due to the advantage of microsurgical techniques, thus reducing the operative trauma and accidental results during experimentation. The surgical procedure consists of a pylorojejunostomy with a Roux-en-y loop. This experimental model offers the possibility to discern a great deal of the problems and conditions which may be responsible in the adverse effect of bile and/or duodenal juice on the gastric mucosa.

Animals↗