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C Henze

Publications and source records attributed to C Henze.

9 recordsLinked to original sources

BCL3 is induced by IL-6 via Stat3 binding to intronic enhancer HS4 and represses its own transcription.

BCL3 is a proto-oncogene affected by chromosomal translocations in some patients with chronic lymphocytic leukemia. It is an IkappaB family protein that is involved in transcriptional regulation of a number of NF-kappaB target genes. In this study, interleukin (IL)-6-induced BCL3 expression and its effect on survival of multiple myeloma (MM) cells were examined. We demonstrate the upregulation of BCL3 by IL-6 in INA-6 and other MM cell lines. Sequence analysis of the BCL3 gene locus revealed four potential signal transducer and activator of transcription (Stat) binding sites within two conserved intronic enhancers regions: one located within enhancer HS3 and three within HS4. Chromatin immunoprecipitation experiments showed increased Stat3 binding to both enhancers upon IL-6 stimulation. Silencing Stat3 expression by small interfering RNA (siRNA) abrogated BCL3 expression by IL-6. Using reporter gene assays, we demonstrate that BCL3 transcription depends on HS4. Mutation of the Stat motifs within HS4 abolished IL-6-dependent BCL3 induction. Furthermore, BCL3 transcription was inhibited by its own gene product. This repressive feedback is mediated by NF-kappaB sites within the promoter and HS3. Finally, we show that overexpression of BCL3 increases apoptosis, whereas BCL3-specific siRNA does not affect the viability of INA-6 cells suggesting that BCL3 is not essential for the survival of these cells.

B-Cell Lymphoma 3 Protein↗

Slow N-acetyltransferase 2 status leads to enhanced intrastriatal dopamine depletion in 6-hydroxydopamine-lesioned rats.

We previously reported an association between the N-acetyltransferase 2 (NAT2) slow acetylator status and Parkinson's disease (PD). We have now investigated the possible functional relevance of this association by treating Fischer 344 (F344) rapid and Wistar-Kyoto (WKY) slow NAT2 acetylator rat strains with the neurotoxin 6-hydroxydopamine (6-OHDA). Intrastriatal treatment with either 10 or 20 microg of 6-OHDA lead to a significantly greater reduction of striatal dopamine concentrations in the WKY slow acetylator rat strain than in the F344 rapid acetylator rat strain (P < 0.004), reflecting a more marked degree of dopaminergic denervation. Nigral dopaminergic cell counts were also lower in the WKY rats, but this difference failed to reach statistical significance, suggesting that slow acetylation is especially deleterious at the level of striatal nerve endings.

Animals↗

Interleukin-6 signal transduction and lymphocyte function.

Interleukin-6 (IL-6) is a pleiotropic cytokine that acts on a wide variety of cell types. It has important regulatory functions in the immune system, is a mediator of the acute-phase response, and is involved in the regulation of differentiation, proliferation, and survival of target cells. A major signal transduction pathway for IL-6 involves activation of JAK kinases and the transcription factor Stat3. In addition, a great many of other signalling pathways are induced. Stat3 has been shown to be a central player of IL-6 signalling in many systems whereas the functions of most other IL-6-activated pathways are not yet understood. In this review, we discuss the current knowledge on IL-6 functions in the immune system, IL-6 signal transduction, and its significance for lymphocyte function.

Animals↗

The corpus luteum insufficiency: a multifactorial disease.

The pulsatile release pattern of LH during the entire menstrual cycle is well defined; however, the response of corpora lutea to these LH pulses in patients suffering from corpus luteum insufficiencies (CLI) is largely unknown. Patients suffering from CLI were selected from infertile patients on the basis of low progesterone (P < 25 nmol/L) in a blood sample withdrawn during a monitoring cycle. During the next cycle, nine blood samples were collected during the follicular and luteal phase and follicular development was assessed by vaginal sonography. Of 109 patients who had a CLI in the monitoring cycle, 55 had a CLI again, and 38 women agreed to undergo assessment of pulsatile hormone secretion. These women again had P < 25 nmol/L at days 6 and 7 of the luteal phase and blood samples were withdrawn through antecubital vein catheters from 0900-1700 h at 10-min intervals on days 7, 8, or 9 following ovulation. From 38 patients with such defined CLI, 16 (42%) had no LH episode and significantly lower basal LH levels in comparison with 14 control subjects. Thirteen (34%) of the patients had normal appearing LH episodes despite too low P and E2 concentrations, but their CL did not react to the LH episodes. The remaining 9 patients (24%) had normal LH episodes; their CL reacted to these episodes, but their basal P levels were too low. In all blood samples LH was not only determined using an immunoassay but also by the mouse Leydig cell testosterone production bioassay. It could be established that no CLI exists, which is due to the release of bioinactive LH. It is anticipated that the differentiation of three different types of CLI, one of hypothalamic and two of ovarian origin, may allow the development of differential diagnostic and therapeutic tools in the future.

Adult↗

Regulation of luteal function by luteinizing hormone and prolactin at different times of the luteal phase.

In 54 healthy women luteal function was assessed by sequential withdrawals of blood samples at 10-min intervals for 8-10 h. Subgroups of the women were studied during the early and late ovulatory period and during the early, mid- and late luteal phase. Bio- and immunoreactive luteinizing hormone (LH), prolactin, testosterone, estradiol and progesterone levels were determined in each sample. While the bio- and immunoreactivity of LH pulses correlated fairly well, a number of bio- or immunoreactive LH pulses were observed that were not detected by the respective other method. Responsivity of the corpus luteum to LH episodes developed during the second half of the luteal phase and was most marked in cases where LH episodes were accompanied by prolactin episodes. In the absence of prolactin episodes. LH episodes did not stimulate progesterone or estradiol secretion. The highest incidence of coincident LH and prolactin pulses was observed during the mid- and late luteal phase. Serum testosterone levels showed also some fluctuations but these were independent of immuno- or bioactive LH episodes and therefore most likely not of luteal origin. Prior to menstruation LH episodes were not any more stimulatory to progesterone secretion, indicating that it is not the withdrawal of LH but, rather, another possibly intraovarian mechanism that results in luteolysis. In a number of women, increased estradiol and progesterone secretion was strictly related to the prior occurrence of LH and prolactin pulses. In other subjects, both gonadal steroids fluctuated largely with no discernible correlation to LH fluctuations. This may indicate that in these subjects the corpora lutea have some degree of autonomous regulation.

Adolescent↗

[CA-125 serum level in early pregnancy follow hMG/hCG stimulated and unstimulated cycles].

The CA-125-antigen could not only be identified in the epithelium of serous ovarian carcinoma, but also in the regular surface epithelium of the endometrium, the decidua and the peritoneum. The aim of this study was, to examine the pattern of CA-125 in the serum of women at early stages of pregnancy, after hMG/hCG-stimulation and subsequent insemination, IVF or GIFT. In particular, it was differentiated between simple or twin pregnancies, ovarian hyperstimulation syndrome and mole pregnancies. 16 patients, who spontaneously became pregnant after cyclus-monitoring, served as a control group. Among the total of 77 patients, 16 women with single pregnancies without stimulation showed an increase of CA-125 values to maximum amounts of 42.9 +/- 18.8 U/ml in the 8th week. 21 patients with single pregnancies after hMG/hCG-treatment and IVF, exhibited maximums of 97.5 +/- 66.8 U/ml in the 6th week, in cases of twins (n = 10) of 216.8 +/- 85.1 U/ml in the 7th week. Considering the group with the hMG/hCG-stimulation and following insemination (n = 20), maximum values of 91.4 +/- 57.3 U/ml were found in the 6th week, just as in the IVF-group. In cases of ovarian hyperstimulation syndrome (n = 5) as well as in such of a mole pregnancy (n = 5), drastically elevated values of 9519 and 1496 U/ml respectively, have been demonstrated. The decidua is regarded as a presumable source of high antigen levels in normal pregnancy, while the peritoneum is assumed to be such as for the ovarian hyperstimulation syndrome. Concerning mole pregnancy, the antigen levels could possibly emerge from the amniotic fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗