Biomedical subjects

Ulrike Schmidt

Publications and source records attributed to Ulrike Schmidt.

At least 19 recordsLinked to original sources

PubMed2003

The heat shock protein 90-targeting drug cisplatin selectively inhibits steroid receptor activation.

Cisplatin is an antineoplastic drug that binds to DNA, thereby inhibiting cell division and tumor growth. Cisplatin may also disrupt the function of some proteins, including heat shock protein 90 (Hsp90). We report that cisplatin dose-dependently inhibited transcriptional activity of the androgen receptor and the glucocorticoid receptor (GR) in transient reporter assays. A truncated, hormone-independent GR was only partially inhibited at significantly higher doses of cisplatin. Cisplatin treatment of neuroblastoma cells led to an immediate inhibition of hormone binding by GR, followed by proteasome-dependent degradation of the receptor. Other Hsp90-regulated proteins, i.e. the phosphokinases raf-1, lck, and c-src, were not affected, indicating a specific functional interference of cisplatin with the steroid receptors GR and androgen receptor. Cisplatin did not elicit a stress response, in contrast to geldanamycin. Immunoprecipitation revealed that cisplatin disrupts binding of GR to Hsp90. Moreover, cisplatin-treated Hsp90 was unable to associate with untreated ligand binding domain of GR. Reticulocyte lysate was able to restore hormone binding of GR in vitro, but not when the lysate was pretreated with geldanamycin. Our data reveal that cisplatin influences steroid receptors also independently of its DNA-mediated effects and, thus, suggest a novel modes of action for this cytostatic drug.

Androgen Receptor Antagonists↗

PubMed2003

Y-chromosomal STR haplotypes in a population sample from southwest Germany (Freiburg area).

In the present study Y-chromosomal short tandem repeat (Y-STR) haplotypes of 433 unrelated male individuals from southwest Germany (Freiburg area) were analyzed. Population data for the loci DYS19, 389I, 389II, 390, 391, 392, 393, 385 and YCA II are given. Analysis of these loci provides the data that is defined as the "extended haplotype" and is available in the on-line Y-STR haplotpye reference database (YHRD) at http://ystr.org. Special emphasis is placed on the sequence and nomenclature of YCA II.

Base Sequence↗

PubMed2003

Sequence polymorphisms within the human mitochondrial genes MTATP6, MTATP8 and MTND4.

By sequencing the control region of mitochondrial DNA, the majority of human DNA samples can be differentiated. A further increase in differentiation probability may be possible, e.g. by extending the sequenced region to coding regions of the mitochondrial genome. Restriction to those positions that do not result in a change of the amino acids guarantees that the information thus obtained does not refer to phenotypically relevant information. In the present study the sequence data of the mitochondrial genes MTATP6, MTATP8 and MTND4 were collected from 109 subjects and analyzed in order to define variable positions suitable for identification purposes. There were 32 variable base positions among 850 bases studied from MTATPase genes and 1,200 bases of the MTND4 gene showed 28 variable positions. "Hot spots" for base exchanges were found in both regions and one position (position 11,719 in the MTND4 gene) seems to be suitable for SNP investigation for forensic purposes.

DNA, Mitochondrial↗

PubMed2003

Aetiology of eating disorders in the 21(st) century: new answers to old questions.

This paper reviews the aetiology of the eating disorders, anorexia nervosa and bulimia nervosa, which is generally thought of as multi-factorial in nature. In recent years with the advent of new bio-technologies interest in the exploration of the contribution of biological, in particular genetic factors to the origins of these disorders has been revived. The challenge for the future is to understand better the relative importance of biological and psychosocial risk-factors and how these factors interact. Moreover, there is a need for a greater appreciation of the developmental perspective in the origins of eating disorders.

Adolescent↗

PubMed2003

Are top journals biased against eating disorders topics?

OBJECTIVE: This study investigated whether there is a bias against eating disorders research among the leading psychiatric, psychological, and medical journals. METHOD: The authors performed a comparison between the number of empirical articles published about anorexia nervosa and/or bulimia nervosa and the number of articles published about panic disorder and/or agoraphobia (i.e., disorders of comparable disease burden) in 29 high-impact journals over a 5-year period (1996-2001). RESULTS: There were almost twice as many published empirical articles about panic disorder and/or agoraphobia (N=365) as there were about anorexia nervosa and/or bulimia nervosa (N=169). CONCLUSIONS: The findings indicate a possible bias against eating disorders research among some leading psychiatric journals. Alternative explanations and implications are discussed.

Agoraphobia↗

PubMed2003

Service variation in baseline variables and prediction of risk in a randomised controlled trial of psychological treatment in repeated parasuicide: the POPMACT Study.

The treatment protocol and baseline characteristics of 480 subjects with a history of repeated parasuicide recruited in five centres to a randomised therapeutic trial of manual assisted cognitive-behaviour therapy (MACT) and treatment as usual (TAU) are described. Most patients had significant anxiety and depressive disturbance with 42% having a personality disorder. Variation in service policies influenced recruitment, with earlier assessment centres seeing people with more frequent episodes of self-harm and greater parasuicide risk than later ones. Parasuicide risk was also significantly greater in those with their first parasuicide episode at an earlier age and in those with a more recent latest episode.

Adult↗

PubMed2003

Anorexia nervosa.

Explore the source record for details and available documents.

Anorexia Nervosa↗

PubMed2002

Essential role of the unusual DNA-binding motif of BAG-1 for inhibition of the glucocorticoid receptor.

The co-chaperone BAG-1 is involved in the regulation of steroid hormone receptors, including the glucocorticoid receptor (GR). More recently, BAG-1 was found in the nucleus where it decreases GR transactivation. Moreover, nonspecific DNA binding of BAG-1 has been reported. We discovered that of the N-terminal part of BAG-1M, the first 8 amino acids are sufficient for DNA binding, containing a stretch of three lysines and a stretch of three arginines. Changing the spacing between these stretches had no effect on DNA binding. Surprisingly, this small, nonsequence-specific DNA binding domain was nonetheless necessary for the inhibitory function of BAG-1 for GR-dependent transcription, whereas the following serine- and threonine-rich E(2)X(4) repeat domain was not. Mutational analysis of these two domains revealed that only mutants retaining DNA binding capability were able to down-regulate GR-mediated transactivation. Intriguingly, lack of DNA binding could not be functionally rescued by BAG-1M harboring a point mutation abolishing interaction with hsp70. Thus, DNA binding and hsp70 interaction are required in cis. We propose that the nonsequence-specific DNA-binding protein BAG-1 acts at specific chromosomal loci by interacting with other proteins.

Animals↗

PubMed2002

Diagnosis of a captive-bolt injury in a skull extremely destroyed by fire.

The authors report on a combined suicide of a 71-year-old farmer who fired a shot to his forehead with a livestock stunner before burning himself. As the fire was fueled by a pile of firewood it burnt for many hours, thus, causing subtotal incineration of the body. The remaining bones were calcined and reduced to a residual mass of only 3 kg. In spite of the extreme destruction, a circular bone defect corresponding to the site where the captive-bolt had entered the skull could be identified in the frontal squama. The example of this suicide is used to illustrate the problems of distinguishing between mechanical and thermal fractures. As expected, the attempted isolation and amplification of both nuclear and mitochondrial DNA for the purpose of identification was not successful.

Abattoirs↗

PubMed2002

Haemodialysis for the prevention of contrast-induced nephropathy: outcome of 31 patients with severely impaired renal function, comparison with patients at similar risk and review.

RATIONALE AND OBJECTIVES: To investigate whether haemodialysis prevents contrast-induced nephropathy (definition: increase of serum-creatinine of >or= 0.5 mg/dL within 7 days). MATERIALS AND METHODS: Thirty-one patients (mean serum-creatinine 4.01 +/- 1.83 mg/dL) were dialyzed for 4.36 +/- 1.0 hours within one hour after 278.4 +/- 160.5 mL of contrast medium. RESULTS: Dialysis resulted in a significant reduction of serum-creatinine (2.25 +/- 1.46 mg/dL; P< 0.0001) and stable mean serum-creatinine levels 2, 3, 4, and 7 days after contrast medium and at discharge compared with baseline values. However, 19 patients (61%) developed contrast-induced nephropathy within 7 days. Four patients had to be repeatedly dialyzed. A comparison of our patients' 48 hours-incidence of contrast-induced nephropathy (9/31; 29%) versus patients at comparable risk included in seven previous studies demonstrated a prophylactic effect of dialysis only versus a subgroup in one study. CONCLUSIONS: Data provide no hint that haemodialysis prevents contrast-induced nephropathy. Therefore, postprocedural dialysis should be restricted to patients participating in clinical studies.

Acute Kidney Injury↗

PubMed2002

Genetic engineering of brewing yeast to reduce the content of ethanol in beer.

The GPD1 gene encoding the glycerol-3-phosphate dehydrogenase was overexpressed in an industrial lager brewing yeast (Saccharomyces cerevisiae ssp. carlsbergensis) to reduce the content of ethanol in beer. The amount of glycerol produced by the GPD1-overexpressing yeast in fermentation experiments simulating brewing conditions was increased 5.6 times and ethanol was decreased by 18% when compared to the wild-type. Overexpression of GPD1 does not affect the consumption of wort sugars. Only minor changes in the concentration of higher alcohols, esters and fatty acids could be observed in beer produced by the GPD1-overexpressing brewing yeast. However, the concentrations of several other by-products, particularly acetoin, diacetyl and acetaldehyde, were considerably increased.

Beer↗

PubMed2002

Mucosal immunization with live recombinant bovine respiratory syncytial virus (BRSV) and recombinant BRSV lacking the envelope glycoprotein G protects against challenge with wild-type BRSV.

Recombinant bovine respiratory syncytial virus (rBRSV) and an rBRSV deletion mutant lacking the G gene (rBRSVDeltaG) were characterized in calves with respect to replication competence, attenuation, and protective efficacy as live-attenuated BRSV vaccines. Both recombinant viruses were safe and induced protection against a BRSV challenge infection. rBRSV replicated efficiently in the upper respiratory tract. Intranasal immunization with rBRSVDeltaG led to infection but not to mucosal virus replication. Neutralizing antibodies were induced by rBRSV and rBRSVDeltaG. Thus, the BRSV attachment glycoprotein G seems to be dispensable in vaccinating calves against BRSV.

Administration, Intranasal↗

PubMed2002

Anorexia nervosa.

Explore the source record for details and available documents.

Adolescent↗

PubMed2002

Anorexia nervosa.

Explore the source record for details and available documents.

Adolescent↗

PubMed2001

Recombinant bovine respiratory syncytial virus with deletions of the G or SH genes: G and F proteins bind heparin.

Bovine respiratory syncytial virus (BRSV) encodes three transmembrane envelope glycoproteins, namely the small hydrophobic (SH) protein, the attachment glycoprotein (G) and the fusion glycoprotein (F). The BRSV reverse genetics system has been used to generate viable recombinant BRSV lacking either the G gene or the SH gene or both genes. The deletion mutants were fully competent for multicycle growth in cell culture, proving that, of the BRSV glycoprotein genes, the SH and G genes are non-essential. Virus morphogenesis was not impaired by either of the deletions. The deletion mutants were used to study the role of the F glycoprotein and the contributions of SH and G with respect to virus attachment. Attachment mediated by the F protein alone could be blocked by soluble heparin, but not by chondroitin sulphate. Heparin affinity chromatography revealed that both the BRSV G and F glycoproteins have heparin-binding activity, with the affinity of the F glycoprotein being significantly lower than that of G. Therefore, the roles of the BRSV glycoproteins in virus attachment and receptor binding have to be reconsidered.

Animals↗

PubMedDate not supplied

[Fatal thoracic compression after being partially run over by an automobile].

The authors report on a fatal pedestrian accident in which the victim lay on the street and got under a car being run over by one of the front wheels. Both the car driver and the killed pedestrian were strongly alcohol-intoxicated at the time of the accident (2.45 a.m.). After the car had come to a standstill, the pedestrian remained trapped under the car until she was rescued by the fire brigade. On the basis of the autopsy findings and the technical expert opinion it could be reconstructed that the pedestrian's death was not caused by the consequences of being run over by the car, but by the subsequent compression of her thorax in the final accident position.

Accidents, Traffic↗

PubMedDate not supplied

[Fatal accident with a special automobile].

The authors report on a traffic accident in which the passenger of a Light Four-wheeled Vehicle (Microcar) approved for use by a disabled person was killed after a rear collision with a compact car. The severity of the accident trauma was critically determined by the vehicle's light construction. Consideration is also given to the legal situation regarding registration and driver's license issues.

Accidents, Traffic↗

PubMedDate not supplied

[Possible applications of Y chromosome STRs in examination of abortion tissue].

By application of Y-chromosomal STRs, DNA analysis of abortion material can be considerably facilitated since great excess of maternal DNA is tolerated without disturbing the Y-STR amplification. If paternity can't be excluded on the basis of the Y-STR haplotype, further examinations must follow, e.g. autosomal STR analysis. For this purpose, histological preparation of the abortion tissue might still be necessary. Different Y-chromosomal haplotypes of embryo and putative father usually lead to an exclusion from paternity. Based on four case examples, the feasibility of this method is discussed.

Abortion, Legal↗