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Biomedical subjects

K Tillman

Publications and source records attributed to K Tillman.

6 recordsLinked to original sources
PubMed2003

[Endoprosthetic replacement of the ankle joint].

Endoprosthetic replacement of the ankle joint is considered to be a modern alternative of the well-tried fusions of the joint. We try to explain indications and limits of alloarthroplasty in comparison to arthrodesis. The recent technical evolution will be presented: starting with the two-component-("first generation") and leading to the three-component ("second generation") designs, Suitable for cemented and cementless implantation as well. Results of three-component endoprostheses in the literature and our own experiences with implants of both generations especially regarding the time of survival will be discussed. Basing on the actual knowledge, we try to deduce a prognosis of the future way of ankle replacement.

Ankle Joint↗
PubMed2001

p53 represses androgen-induced transactivation of prostate-specific antigen by disrupting hAR amino- to carboxyl-terminal interaction.

Prostate-specific antigen (PSA) is highly overexpressed in prostate cancer. One important regulator of PSA expression is the androgen receptor (AR), the nuclear receptor that mediates the biological actions of androgens. AR is able to up-regulate PSA expression by directly binding and activating the promoter of this gene. We provide evidence here that that this AR activity is repressed by the tumor suppressor protein p53. p53 appears to exert its inhibition of human AR (hAR) by disrupting its amino- to carboxyl-terminal (N-to-C) interaction, which is thought to be responsible for the homodimerization of this receptor. Consistent with this, p53 is also able to block hAR DNA binding in vitro. Our previous data have shown that c-Jun can mediate hAR transactivation, and this appears to result from a positive effect on hAR N-to-C interaction and DNA binding. Interestingly, c-Jun is able to relieve the negative effects of p53 on hAR transactivation, N-to-C interaction, and DNA binding, demonstrating antagonistic activities of these two proteins. Importantly, a p53 mutation found in metastatic prostate cancer severely disrupts the p53 negative activity on hAR, suggesting that the inability of p53 mutants to down-regulate hAR is, in part, responsible for the metastatic phenotype.

Animals↗
PubMed1998

c-Fos dimerization with c-Jun represses c-Jun enhancement of androgen receptor transactivation.

The transcriptional activity of the human androgen receptor (hAR), like other nuclear receptors, is dependent on accessory factors. One such factor is c-Jun, which has been shown to have a selective function of mediating androgen receptor-dependent transactivation. This c-Jun activity is inhibited by c-Fos, another protooncoprotein that can dimerize with c-Jun to form the transcription factor AP-1. Here we show that c-jun mediates hAR-induced transactivation from the promoter of the androgen-regulated gene, human kallikrein-2 (hKLK2), and c-Fos blocks this activity. Using c-Fos truncation mutants and measuring hKLK2-dependent transcription, we have determined that the bZIP region of c-Fos is required and sufficient for inhibiting c-Jun enhancement of hAR transactivation. Further truncation analysis of the bZIP shows that the c-Fos dimerization function, mediated through the leucine zipper, is essential for the negative activity, whereas DNA binding, mediated through the basic region, is dispensable. These results suggest that heterodimerization by c-Fos with c-Jun blocks c-Jun's ability to enhance hAR-induced transactivation.

Animals↗
PubMed1977

[Biochemical methods in the assessment of activity in rheumatoid arthritis (author's transl)].

An investigation was carried out in 120 patients with classical rheumatoid arthritis (RA). Prolylhydroxylase activity was determined in the synovial membrane and serum and compared with the level of collagen-like protein in plasma and the hydroxyproline-creatinine quotient in urine. The data were related to the activity of RA as measured according to Voit and Gamp and also according to Lansbury. Activity was, furthermore, also assessed on the basis of newly defined criteria considering clinical, biochemical and histological findings. Prolylhydroxylase activity was significantly correlated to the activity of the RA assessed according to each of these systems. The significance of the known parameters, collagen-like protein in plasma and hydroxyproline-creatinine quotient in urine were confirmed in this larger series of patients. The positive correlation between prolylhydroxylase activities in the synovial membrane, as well as in serum, and the level of collagen metabolites in plasma and urine corroborated the value of biochemical methods in the assessment of activity of RA in order to undertake differentiated therapy.

Arthritis, Rheumatoid↗