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Biomedical subjects

S Scholz

Publications and source records attributed to S Scholz.

At least 19 recordsLinked to original sources
PubMed2006

Physical interaction of apoptosis-inducing factor with DNA and RNA.

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein, which upon apoptosis induction translocates to the nucleus where it interacts with DNA by virtue of positive charges clustered on the AIF surface. Here we show that the AIF interactome, as determined by mass spectroscopy, contains a large panel of ribonucleoproteins, which apparently bind to AIF through the RNA moiety. However, AIF is devoid of any detectable RNAse activity both in vitro and in vivo. Recombinant AIF can directly bind to DNA as well as to RNA. This binding can be visualized by electron microscopy, revealing that AIF can condense DNA, showing a preferential binding to single-stranded over double-stranded DNA. AIF also binds and aggregates single-stranded and structured RNA in vitro. Single-stranded poly A, poly G and poly C, as well double-stranded A/T and G/C RNA competed with DNA for AIF binding with a similar efficiency, thus corroborating a computer-calculated molecular model in which the binding site within AIF is the same for distinct nucleic acid species, without a clear sequence specificity. Among the preferred electron donors and acceptors of AIF, nicotine adenine dinucleotide phosphate (NADP) was particularly efficient in enhancing the generation of higher-order AIF/DNA and AIF/RNA complexes. Altogether, these data support a model in which a direct interaction of AIF contributes to the compaction of nucleic acids within apoptotic cells.

Amino Acid Sequence↗
PubMed2006

Routine HLA sequence-specific-oligonucleotide typing and confirming sequence-based typing of a prospective bone marrow donor identified a novel B*27 allele, HLA-B*2734.

In this study, we report the identification of a new human leukocyte antigen-B allele in a sample that was tested in our routine typing for volunteer bone marrow donors. This novel allele officially named B*2734 was found in a female donor of Caucasoid origin (laboratory code 158567). The search for unrelated bone marrow donors was initiated by the Aktion Knochenmarkspende Bayern. In comparison with the closest related allele B*2707, B*2734 differs at two nucleotide positions, all located in exon 3, at position 412, 'A' in B*2707 is replaced by 'G' and at position 486, 'G' is replaced by 'A' in the novel allele. The single nucleotide polymorphism at position 412 results in an amino acid substitution at codon 138. The amino acid asparagine is changed to aspartic acid in B*2734 allele. The second nucleotide exchange is a silent mutation and codon 163 remains unaffected as ACG-->ACA, still codes for alanine.

Alleles↗
PubMed2006

LRRK2 mutations in a clinic-based cohort of Parkinson's disease.

In the last decade, major breakthroughs in the understanding of genetic contributions to Parkinson's disease (PD) have been achieved. Recently, mutations in LRRK2, encoding dardarin, have been found to be responsible for an autosomal dominant parkinsonism (OMIM 607060). We screened 311 subjects (cases: n = 202, controls: n = 109) for the three previously reported LRRK2 mutations. Our investigation revealed a sporadic case of PD with a heterozygous mutation G2019S (c.6055G>A). Here, we present the clinical phenotype of this patient and discuss the implications of genetic testing for the G2019S mutation in patients with sporadic PD.

Adolescent↗
PubMed2005

[Anaesthetic-related complications of caesarean section].

In spite of an increase in the number of caesarean sections, the incidence of anaesthetic-related complications remains low. This is due primarily to the increasing use of regional anaesthesia (spinal and or epidural anaesthesia) as general anaesthesia is associated with a 17-fold increase in complications, in particular failed endotracheal intubation, aspiration of gastric contents and hypoxia. It is most important that all obstetric patients deemed at risk for general anaesthesia (e. g. morbidly obese, hypertension, placenta praevia) should be identified as such by the obstetricians and referred to the anaesthetic department at an early stage. Furthermore there should be common procedural guidelines to define the degree of urgency of caesarean section as most anaesthetic complications occur during "emergency" cases under general anaesthesia. Many of these so-called emergency cases are not real emergencies and could be equally well performed under regional anaesthesia. A continuing audit of maternal deaths in Germany should be established along similar lines to the Confidential Enquiries into Maternal Deaths in the United Kingdom. Most importantly, the increasing use of regional anaesthesia should be propagated as its use in Germany still lies well behind other countries such as Switzerland, the USA and the United Kingdom.

Anesthesia, Conduction↗
PubMed2005

Bone marrow donor routine HLA typing identified a novel B*07 allele, B*0734, confirmed by allele-specific DNA cycle sequencing.

In this article, we report the identification of a new human leukocyte antigen-B allele in a sample that was tested in our routine typing for bone marrow donors. This novel allele officially designed B*0734 was found in a female donor of Bavarian Caucasoid origin (Laboratory code 121036). The search for unrelated bone marrow donors was initiated by the Aktion Knochenmarkspende Bayern. In comparison to the common B*070201, B*0734 differs at four nucleotide positions, 412 (G-->A), 539 (G-->T), 559 (G-->A) and 560 (A-->C) causing three amino acid substitutions, at postion 138 Asp-->Asn, at position 180 Arg-->Leu and at position 187 Glu-->Thr.

Adult↗
PubMed2005

Bone marrow donor routine HLA typing identified a novel B*55 allele, B*5517, confirmed by allele-specific DNA cycle sequencing.

In this article, we report the identification of a new human leukocyte antigen-B allele in a sample that was tested in our routine typing for volunteer bone marrow donors. This novel allele officially designed B*5517 was found in a male donor of Bavarian Caucasoid origin (Laboratory code 150113). The search for unrelated bone marrow donors was initiated by the Aktion Knochenmarkspende Bayern. In comparison with the common B*5501 allele, B*5517 differs at three nucleotide positions all located in exon 3, at position 379 (C-->G), 419 (T-->A), and 420 (A-->C), resulting in two amino acid substitutions at codons 127 and 140. The amino acid 127, leucine, is changed to valine, and the amino acid 140, also a leucine, is replaced by tyrosine in B*5517.

Alleles↗
PubMed2005

Minimal T-cell-stimulatory sequences and spectrum of HLA restriction of immunodominant CD4+ T-cell epitopes within hepatitis C virus NS3 and NS4 proteins.

The hepatitis C virus (HCV)-specific CD4+ T-cell response against nonstructural proteins is strongly associated with successful viral clearance during acute hepatitis C. To further develop these observations into peptide-based vaccines and clinical immunomonitoring tools like HLA class II tetramers, a detailed characterization of immunodominant CD4+ T-cell epitopes is required. We studied peripheral blood mononuclear cells from 20 patients with acute hepatitis C using 83 overlapping 20-mer peptides covering the NS3 helicase and NS4. Eight peptides were recognized by > or = 40% of patients, and specific CD4+ T-cell clones were obtained for seven of these and three additional, subdominant epitopes. Mapping of minimal stimulatory sequences defined epitopes of 8 to 13 amino acids in length, but optimal T-cell stimulation was observed with 10- to 15-mers. While some epitopes were presented by different HLA molecules, others were presented by only a single HLA class II molecule, which has implications for patient selection in clinical trials of peptide-based immunotherapies. In conclusion, using two different approaches we identified and characterized a set of CD4+ T-cell epitopes in the HCV NS3-NS4 region which are immunodominant in patients achieving transient or persistent viral control. This information allows the construction of a valuable panel of HCV-specific HLA class II tetramers for further study of CD4+ T-cell responses in chronic hepatitis C. The finding of immunodominant epitopes with very constrained HLA restriction has implications for patient selection in clinical trials of peptide-based immunotherapies.

Adolescent↗
PubMed2005

The nasal airflow in noses with septal perforation: a model study.

BACKGROUND: Septal perforation is a common clinical problem in rhinology. Affected patients suffer from a dry nose, crusts as well as recurrent epistaxis and sometimes an inspiratory whistle. The aim of this study was to investigate the underlying flow dynamic mechanisms. METHODS: The physical flow effects of such pathologies were examined in functional nose models (box models) and anatomically exact models of the nose. Therefore, septal perforations of different sizes and localisations were studied in straight and deviated nasal septa. RESULTS AND CONCLUSIONS: It could be seen that the localisation of the perforation has no impact on the flow pattern. In large septal perforations, the air jet collides with the posterior edge of the perforation and disintegrates turbulently. Since airflow is physiologically turbulent in the posterior part of the nose, posterior perforations do not cause clinical complaints. The inspiratory whistling sound during respiration is based on the principle of a lip whistle. Large perforations do not cause a whistling sound. The necessary high flow velocity needed in large perforations is usually not achievable.

Humans↗
PubMed2004

Repair of calvarial defects in rats by prefabricated hydroxyapatite cement implants.

The aim of the present study was to test the hypothesis that calvarial defects can be repaired by using preformed implants of calcium phosphate bone cement (CPBC) in rats. Sixty adult female Sprague-Dawley rats received full-thickness calvarial nonhealing defects with a diameter of 8 mm. Three different CPBCs were used: group 1: tetracalcium phosphate-based powder; group 2: a blend of amorphous and crystalline calcium phosphate precursors; and group 3: an alpha-tricalcium phosphate (alpha-TCP)-based powder. Implants were left to cure for 25-40 min at room temperature in a silicon mold of 7.9 mm and inserted press fit into the defects. Fifteen animals served as unfilled controls. After 13, 26, and 52 weeks, the material was analyzed qualitatively by using surface-stained undecalcified thick-section specimens and quantitatively by using semiautomated histometry. Kruskal-Wallis tests were applied to compare mean values of periimplant bone formation at a significance level of p < 0.05. Three implants of group 1 fractured during insertion. Resorption of CPBC without complementary bone formation was noticed in these implants. Unfractured implants were resorbed with simultaneous apposition of bone on the implant surface. After 52 weeks, the resorption rate varied between 23.1 and 39.3%. Periimplant bone formation increased continuously on average around all implant types, but it reached statistical significance only in group 2. The results showed that repair of calvarial defects can be achieved by preformed CPBC implants. The rate of resorption of preformed implants is, however, much lower than that reported for in vivo cured CPBC.

Animals↗
PubMed2004

[DRGs in dermatology. A critical assessment].

The obligatory implementation of the DRG system in 2004 represents a fundamental change in German hospital financing. Since the first version of G-DRG catalogue was published, the final adaptation of the system to German clinical reality has consumed much time and energy. This adjustment has been very challenging for dermatology for a variety of reasons. A DRG evaluation project conducted by the German Society of Dermatology made possible improvements in the G-DRG catalogue 2004 from the perspective of dermatology. The hospitals now have to adjust to the new situation and to find their position in this system. A high coding quality is of greatest importance. When developing their clinical priorities, hospitals should not make the mistake of pursuing the temptations presented by the latest version of the DRG catalogue. Strategies of the practical use of the DRG system in hospitals are reviewed.

Cost-Benefit Analysis↗
PubMed2004

[Psychological distress associated with acute tinnitus].

BACKGROUND: We question whether patients with acute tinnitus can be differentiated in their perceived handicap and emotional distress. Dysfunctional mechanisms for coping with stress and illness in patients with acute tinnitus were investigated. METHODS: Twenty patients (symptoms for less than 1 week) were examined for distress due to tinnitus (TF), degree of depression (BDI), global distress (SCL- 90-R) and coping with stress (SVF). RESULTS: Patients could be differentiated in terms of their psychological distress and annoyance caused by the symptoms. There is a high correlation between the degree of depression, dysfunctional way of coping with stress and emotional distress caused by tinnitus. Dysfunctional stress coping strategies are found more frequently in highly affected patients. CONCLUSION: Patients with acute tinnitus can be differentiated in terms of their distress and the psychological impairment caused by their symptoms. These results suggest that the immediate reaction to the manifestation of tinnitus might be of prognostic value for the level of emotional distress experienced in chronic tinnitus. The question arises of whether psychological intervention in the acute stage of tinnitus might be beneficial.

Acute Disease↗
PubMed2004

Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism?

BACKGROUND: Patients with inflammatory bowel disease (IBD) are thought to be at increased risk of venous thromboembolism (TE). However, the extent of this risk is not known. Furthermore, it is not known if this risk is specific for IBD or if it is shared by other chronic inflammatory diseases or other chronic bowel diseases. AIMS: To compare the risk of TE in patients with IBD, rheumatoid arthritis, and coeliac disease with matched control subjects. PATIENTS AND METHODS: Study subjects answered a questionnaire assessing the history of TE, any cases of which had to be confirmed radiologically. A total of 618 patients with IBD, 243 with rheumatoid arthritis, 207 with coeliac disease, and 707 control subjects were consecutively included. All three patient groups were compared with control subjects matched to the respective group by age and sex. RESULTS: Thirty eight IBD patients (6.2%) had suffered TE. This was significantly higher compared with the matched control population with only 10 cases reported (1.6%) (p<0.001; odds ratio (OR) 3.6 (95% confidence interval (CI) 1.7-7.8)). Five patients with rheumatoid arthritis (2.1%) had suffered TE compared with six subjects (2.5%) in the control population matched to patients with rheumatoid arthritis (NS; OR 0.7 (95% CI 0.2-2.9)). TE had occurred in two patients with coeliac disease (1%) compared with four subjects (1.9%) in the control population matched to the coeliac disease group (NS; OR 0.4 (95% CI 0.1-2.5)). In 60% of TE cases in the IBD group, at least one IBD specific factor (active disease, stenosis, fistula, abscess) was present at the time TE occurred. CONCLUSIONS: IBD is a risk factor for TE. It seems that TE is a specific feature of IBD as neither rheumatoid arthritis, another chronic inflammatory disease, nor coeliac disease, another chronic bowel disease, had an increased risk of TE.

Adult↗
PubMed2002

Results after laparoscopic lysis of adhesions and placement of seprafilm for intractable abdominal pain.

BACKGROUND: The surgical treatment of patients with chronic abdominal pain resulting from intraabdominal adhesions is controversial. We report our experience with treatment of this challenging patient population using laparoscopic lysis of adhesions (LOA) and placement of Seprafilm (Genzyme, Cambridge, MA, USA). METHODS: The participants in this study were 19 consecutive patients (2 men and 17 women) who underwent laparoscopic LOA and placement of Seprafilm between July 1998 and July 2001. Patients with abdominal pain resulting from irritable bowel syndrome, hernias, or endometriosis were excluded. The patients had undergone a mean of 6.4 previous abdominal procedures (range, 1-14) and 2.3 previous LOAs (range, 0-10). They had experienced chronic, intractable abdominal pain for at least 4 months (range, 4-180). Eight patients had preoperative obstructive symptoms. RESULTS: A completely laparoscopic procedure was used to treat 16 patients, whereas the procedure for 3 patients was converted to open surgery because of dense adhesions. Perioperative complications included two patients in whom enterocutaneous fistulae developed and one patient with intraabdominal hematoma. At follow-up (mean, 9.6 months; range, 1-32 months), 14 patients (73.7%) had completely discontinued all pain medications. At this writing, 12 of these patients are completely symptom free. Two patients are taking nonsteroidal antiinflammatory drugs (NSAIDs) as needed, and three patients require round-the-clock narcotics. Three patients were readmitted with small bowel obstruction, which was managed nonoperatively. One patient had diagnostic laparoscopy for recurrent pain 6 months postoperatively, but had no adhesions. CONCLUSION: Chronic intractable abdominal pain is relieved in most patients via this approach. Repeat laparoscopy in two patients showed no intraabdominal adhesions. Laparoscopic LOA and placement of Seprafilm is an excellent approach to this challenging patient population with symptoms caused by intraabdominal adhesions.

Abdominal Wall↗
PubMed2002

[Partial CO(2) rebreathing technique versus thermodilution: measurement of cardiac output before and after operations with extracorporeal circulation].

BACKGROUND: The NICO(2) monitor determines "pulmonary capillary blood flow" (Qpc) and cardiac output (Qt) using the "partial CO(2) rebreathing technique". The agreement between NICO(2) and thermodilution (TD) cardiac output was compared before and after cardiac surgery with cardiopulmonary bypass (CBP). In addition, the possibility of calculating the intrapulmonary shunt fraction (Qs/Qt) by combining data from the NICO(2) monitor and the TD was investigated. METHODS: In 32 patients measurements were made following induction of anesthesia ("pre-CBP"), 30 min after weaning from CBP ("post-CBP"), and 6-8 h after surgery ("post-OP"). Qt was determined by the NICO(2) monitor and TD, Qpc by the NICO(2) monitor, and Qs/Qt(O(2)) from the standard formula. An intrapulmonary shunt was calculated using Qpc(NICO(2)) and Qt(TD) according to the equation Qs/Qt=1-Qpc/Qt. Bland-Altman and regression analysis techniques were used for statistical evaluation. RESULTS: "Pre-CBP" there was a good agreement between Qt(NICO(2)) and Qt(TD) with both a bias and precision of -0.13+/-0.46 l/min and a correlation of r=0.88+/-0.47 ( p<0.001). In contrast, "post-CBP" and "post-OP" there was a lack of agreement for Qt (bias and precision: 0.97+/-1.05 l/min and -0.33+/-0.8 l/min, respectively). Regarding the shunt calculations no significant correlations between methods could be found. CONCLUSION: Cardiac output measurement by the NICO(2) monitor agree well with TD under steady-state conditions but after CBP the agreement was too small. Combining Qpc(NICO(2)) and Qt(TD) does not offer a reliable possibility for calculating intrapulmonary shunt.

Algorithms↗
PubMed2001

Transposition of the maize transposable element Ac in barley (Hordeum vulgare L.).

Transposition of the maize autonomous element Ac (Activator) was investigated in barley (Hordeum vulgare L.) with the aim of developing a transposon tagging system for the latter. The Ac element was introduced into meristematic tissue of barley by microprojectile bombardment. Transposon activity was then examined in the resulting transgenic plants. Multiple excision events were detected in leaf tissue of all plant lines. The mobile elements generated empty donor sites with small DNA sequence alterations, similar to those found in maize. Reintegration of Ac at independent genomic loci in somatic tissue was demonstrated by isolation of new element-flanking regions by AIMS-PCR (amplification of insertion-mutagenized sites). In addition, transmission of transposed Ac elements to progeny plants was confirmed. The results indicate that the introduced Ac element is able to transpose in barley. This is a first step towards the establishment of a transposon tagging system in this economically important crop.

Base Sequence↗