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Biomedical subjects

K H Büschenfelde

Publications and source records attributed to K H Büschenfelde.

6 recordsLinked to original sources
PubMed1998

Cytokine gene transcription by NF-kappa B family members in patients with inflammatory bowel disease.

We examined the expression of the transcription factor NF-kappa B, a nuclear trans-acting factor known to play a key role in cytokine gene regulation, in patients with inflammatory bowel disease (IBD). It was found that LP macrophages in Crohn's disease (CD) and ulcerative colitis (UC) display high levels of NF-kappa B DNA-binding activity accompanied by an increased production of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) alpha. Western blot studies showed an increased expression of the p50 and c-rel subunits of NF-kappa B; however, the most striking finding was an increased expression level of NF-kappa B p65 in patients with CD and UC. Selective downregulation of p65 in IBD macrophages by a specific antisense phosphorothioate oligonucleotide was sufficient to considerably reduce production of proinflammatory cytokines. These results demonstrate a characteristic increase of NF-kappa B binding levels in patients with IBD. The data suggest that antisense DNA targeting NF-kappa B p65 can be used as a novel molecular approach for the treatment of patients with IBD.

Adolescent↗
PubMed1996

Yeast expression of the cytokine receptor domain of the soluble interleukin-6 receptor.

The complex of the soluble interleukin-6 receptor (sIL-6R) and IL-6 (IL-6) is a potent agonist on cells expressing the signal transducing protein gp 130. In contrast, IL-6 alone only stimulates cells which express a membrane bound form of the IL-6R and gp 130. The natural occurring sIL-6R is generated by shedding of the membrane receptor and to a lesser extend by alternative splicing. We have inserted the coding sequence of the 323 amino acid residues of the human sIL-6R into an expression/secretion vector suitable for the methylotrophic yeast Pichia pastoris. We obtained, however, no detectable expression and secretion of the recombinant protein. When we used only the coding sequence of the cytokine receptor domain of the sIL-6R for the construction of an expression plasmid, this truncated version of the sIL-6R accumulated in the supernatant to 1-5 mg/l. The protein was purified by a single affinity chromatography step using a monoclonal antibody directed against the human IL-6R. Following the same approach, we expressed a truncated splice variant of the sIL-6R. Both, the secreted truncated sIL-6R and the splice variant showed full agonistic biological activity on human hepatoma cells. The described expression strategy will be useful for large scale production of biologically active sIL-6R and might be adapted for the expression of other members of the hematopoietic cytokine receptor family.

Antigens, CD↗
PubMed1977

HLA in different forms of chronic active hepatitis. A comparison between adult patients and children.

108 adult patients and 34 children with chronic active hepatitis (CAH) are divided in four groups on the basis of presence and absence of hepatitis B surface antigen (HBsAg) and autoantibodies (AutoAb). There are significant differences in the numeric distribution among the four groups and the sex distribution between adult patients and children, but no differences in the frequencies of the HLA antigens tested. An increased frequency of HLA-B8 (and HLA-A1) compared with normal controls and the other groups is only found in autoimmune types of CAH, characterized as HBsAg-negative, AutoAb-positive CAH. HBsAg-negative, AutoAb-negative forms of CAH are called cyptogenic CAH and these are most likely non-hepatitis B virus induced types of CAH. In these and hepatitis B virus induced forms of CAH no significant deviation of any HLA antigen tested could be found.

Adolescent↗
PubMed1977

e System and intrahepatocelullar HBcAG and HBsAG in HBsAG positive patients with liver diseases and healthy carriers.

Patients with hepatitis-B surface antigen positive liver diseases and healthy carriers were studied for the presence of e-antigen and anti-e as well as for intrahepatocellular HBsAG and hepatitis-B core antigen. The e-antigen was demonstrated in 9 out of 12 patients with chronic perisitent hepatitis, in 15 out of 39 patients with chronic active hepatitis, in 3 out of 40 patients with acute type B hepatitis, and in 2 out of 9 patients with a protracted course of type B hepatitis. No e-antigen was found in healthy HBsAG carriers nor in patients with complete recovery from type B hepatitis one year after onset of the disease. Anti-e was detected in 24 out of 61 healthy HBsAG carriers with a normal liver histology and in one patient with a mild form of a chronic persistent hepatitis. The presence of e-antigen in serum was highly associated with the presence of HBcAG in the nuclei of the liver cells. Twenty-seven out of 29 e-positive patients had HBcAG in the liver cell nuclei. In contrast, none of 20 patients with anti-e in serum had HBcAG in the liver cells.

Acute Disease↗