Biomedical subjects

Susanne Müller

Publications and source records attributed to Susanne Müller.

7 recordsLinked to original sources

PubMed2003

HMGB1 interacts differentially with members of the Rel family of transcription factors.

HMGB1 is an architectural factor that enhances the DNA binding affinity of several proteins. We have investigated the influence of HMGB1 on DNA binding by members of the Rel family. HMGB1 enhances DNA binding by p65/p50 and p50/p50, but reduces binding by p65/p65, c-Rel/c-Rel, p65/c-Rel, and p50/c-Rel. In pull-down assays, HMGB1 interacts directly with the p50 subunit via its HMG boxes and this interaction is weakened by the presence of the acidic tail. Functionally, HMGB1 is required for the NF-kappaB-dependent expression of the adhesion molecule VCAM-1.

Animals↗

PubMed2002

Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele.

Expression analysis of genes encoding components of the phosphotyrosine signaling system by cDNA array hybridization revealed elevated levels of FGFR4 transcripts in several mammary carcinoma cell lines. In the FGFR4 gene transcript from MDA-MB-453 mammary carcinoma cells, a G to A conversion was discovered that results in the substitution of glycine by arginine at position 388 in the transmembrane domain of the receptor. The Arg(388) allele was also found in cell lines derived from a variety of other tumor types as well as in the germ-line of cancer patients and healthy individuals. Analysis of three geographically separated groups indicated that it occurs in approximately 50% of the human population. Investigation of the clinical data of 84 breast cancer patients revealed that homo- or heterozygous carriers of the Arg(388) allele had a significantly reduced disease-free survival time (P = 0.01) within a median follow-up of 62 months. Moreover, the FGFR4 Arg(388) allele was associated with early lymph node metastasis and advanced tumor-node-metastasis (TNM) stage in 82 colon cancer patients. Consistent with this finding, MDA-MB-231 mammary tumor cells expressing FGFR4 Arg(388) exhibited increased motility relative to cells expressing the FGFR4 Gly(388) isotype. Our results support the conclusion that the FGFR4 Arg(388) allele represents a determinant that is innocuous in healthy individuals but predisposes cancer patients for significantly accelerated disease progression.

Alleles↗

PubMed2002

[High utilizing as a team effort].

The following report describes Mr. Z., who was a former long-term hospitalized psychiatric patient and who turned from a permanent inpatient into a high utilizer of a hospital in a process of several years. In addition the report describes the commitment and often unconventional ways of cooperation by different staff and institutions, that made it possible for Mr. Z. to look forward to a future outside the hospital.

Activities of Daily Living↗

PubMed2002

[Attachment representation of adolescents in residential care].

In this investigation the attachment representations of adolescents in residential care were examined for the first time. 72 adolescents were interviewed by using the Adult Attachment Interview (AAI). At the same time the degree of adolescent psychopathology was recorded. For this purpose the caregivers completed Achenbach's Child Behavior Checklist (CBCL), the adolescents themselves answered Achenbach's Youth Self Report (YSR). The adolescents in this sample proved to be severely burdened in psychopathological terms. They had access to only an insecure and, in many cases, an extremely insecure attachment representation. For a sub-group of adolescent mothers the early infant-mother attachment was examined using Ainsworth's Strange Situation. The findings show an intergenerational transmission of insecure attachment relationships. The implications of these results for the practice of residential care inspired by attachment theory are discussed.

Adolescent↗

PubMed2001

SigB, an alternative sigma factor of the myxobacterium Stigmatella aurantiaca, is synthesized during development and heat shock.

Alternative sigma factors have been detected in the myxobacterium Stigmatella aurantiaca during indole-induced sporulation, fruiting body formation and heat shock using an antiserum raised against sigma factor SigB. The time course of sigB gene expression was analysed by RT-PCR and by determining beta-galactosidase activity during development in a merodiploid strain that harboured a sigB-lacZ fusion gene. Inactivation of the sigB gene by insertion of the neo gene resulted in the loss of one sigma factor as shown by Western analysis. Neither fruiting body formation nor sporulation, nor the production of possible SigB targets, such as DnaK, GroEL or HspA, were affected.

Bacterial Proteins↗

PubMed1999

Endocrinological and genetic studies in patients with Polycystic Ovary Syndrome (PCOS).

Our studies involved 21 women of Caucasian descent with PCOS, as diagnosed by ultrasound, clinical and hormonal findings. We determined 17alpha-OHP, 21-DOF and cortisol levels both just before and one hour after intravenous ACTH administration (0.25 mg Synacthen) in addition to the basal plasma levels of DHEA-S and free testosterone. We screened the CYP21 gene for 12 common-point mutations, finding five heterozygous mutations in 4 out of 21 cases (19%): a splice-site mutation in intron 2 in three cases, and a I172N mutation in exon 4 in two cases. These patients also displayed significantly higher 21-DOF or 17alpha-OHP plasma levels after ACTH administration, suggesting a partial 21-hydroxylase deficiency. Furthermore, we found the basal plasma DHEA-S levels or DHEA-S/F ratios in 11 of 21 patients (52%) to be higher than the means + 2SD of control females, indicating partial 3beta-HSD deficiency or 17,20-LHA. According to the literature, mutations could not be found in the genes of PCO cases with hormonal activity changes in the last two enzymes. The DDT metabolite o,p'-DDD is a strong inhibitor of 3beta-HSD, and DDT can induce 17,20-LHA, implying a possible connection between cases of PCOS women born in East Germany after 1955 and their prenatal DDT uptake. The approximately fourfold higher prevalence of PCO and significantly increased frequency of 3beta-HSD-deficiency and 17,20-LHA found in women with PCOS born since 1955-the time of massive application of DDT-give weight to the thesis that DDT, rather than genetic factors, has played a part in this upsurge.

Journal Article↗

PubMed1997

Mutant studies of phosphofructo-2-kinases do not reveal an essential role of fructose-2,6-bisphosphate in the regulation of carbon fluxes in yeast cells.

The effect of the allosteric regulator fructose-2,6-bisphosphate (F2,6bP) on the regulation of carbohydrate metabolism was investigated in vivo with Saccharomyces cerevisiae mutants containing no, very high or unregulated 6-phosphofructo-2-kinase activity. Simultaneous overproduction of F2,6bP and 6-phosphofructo-1-kinase activity did not increase the glycolytic flux to ethanol. Overexpression of fructose-1,6-bisphosphatase during growth on glucose in a mutant strain devoid of F2,6bP did not cause pronounced effects on the cells. Moreover, high levels of F2,6bP during growth on ethanol in a strain with a highly active 6-phosphofructo-2-kinase enzyme did not affect either carbon flux to glycogen or growth rate. Site-directed mutagenesis of 6-phosphofructo-2-kinase (Pfk26) revealed that serine 644 is involved in the activation of Pfk26 by protein kinase A phosphorylation, but that, additionally, the enzyme can be further activated by phosphorylation of another amino acid residue. The results demonstrate that F2,6bP is not needed to sustain an adequate glycolytic flux under fermentative conditions, but rather is concerned with the homeostasis of metabolite concentrations. Moreover, they fail to indicate a physiological significance for inhibition of fructose-1,6-bisphosphatase by F2,6bP.

Allosteric Regulation↗