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Biomedical subjects

S Hummel

Publications and source records attributed to S Hummel.

At least 19 recordsLinked to original sources
PubMed2006

Development of autoimmunity to transglutaminase C in children of patients with type 1 diabetes: relationship to islet autoantibodies and infant feeding.

AIMS/HYPOTHESIS: Coeliac disease and transglutaminase antibodies are common in patients with type 1 diabetes and their relatives. We investigated the development of transglutaminase antibodies and analysed potential risk factors for coeliac disease autoimmunity in first-degree relatives of patients with type 1 diabetes. METHODS: The study was conducted by prospective observational follow-up from birth of 1,511 children at increased risk of type 1 diabetes or coeliac disease born in Germany between 1989 and 2000. Mean follow-up was to age 7.6 years. Children were tested for transglutaminase and islet autoantibodies. Children were classified as transglutaminase antibody-positive if antibodies were detected by both ELISA and radiobinding assays. RESULTS: The risk of developing transglutaminase antibodies was 4.9% by age 8 years (n=63; 95% CI, 3.7-6.1%). Transglutaminase antibodies developed at an older age than islet autoantibodies (median age, 4.9 vs 2.3 years; p<0.005), and only three children developed both transglutaminase antibodies and islet autoantibodies. Multivariate analysis indicated an increased risk of transglutaminase antibodies in children with the HLA-DRB1*03 allele (hazard ratio for heterozygous DR3, 5.5; 95% CI, 2.9-10.2; hazard ratio for homozygous DR3, 16.2; 95% CI, 6.7-39; p<0.0001) and in children with impaired uterine growth (birth weight < or = 1st percentile, hazard ratio, 3.1; 95% CI, 1.1-7.8, p=0.03). Neither breast-feeding or its duration nor the age of first exposure to gluten was associated with the risk of developing transglutaminase antibodies. CONCLUSIONS/INTERPRETATION: Coeliac disease autoimmunity is initiated later than islet autoimmunity in children who are at risk. An influence of infant nutrition on the development of coeliac disease autoimmunity could not be confirmed in this prospective study.

Autoantibodies↗
PubMed2005

Detection of the CCR5-Delta32 HIV resistance gene in Bronze Age skeletons.

A mutant allele of the chemokine receptor CCR5 gene (CCR5-Delta32), which confers resistance to HIV-1 infection, is believed to have originated from a single mutation event in historic times, and rapidly expanded in Caucasian populations, owing to an unknown selective advantage. Among other candidates, the plague bacillus Yersinia pestis was implicated as a potential source of strong selective pressure on European populations during medieval times. Here, we report amplifications of the CCR5-Delta32 DNA sequence from up to 2900-year-old skeletal remains from different burial sites in central Germany and southern Italy. Furthermore, the allele frequency of CCR5-Delta32 in victims of the 14th century plague pandemic in Lubeck/northern Germany was not different from a historic control group. Our findings indicate that this mutation was prevalent already among prehistoric Europeans. The results also argue against the possibility of plague representing a major selective force that caused rapid increase in CCR5-Delta32 gene frequencies within these populations.

Gene Frequency↗
PubMed2004

Chronic delayed-type hypersensitivity reaction as a means to treat alopecia areata.

The acute phase of alopecia areata (AA) is characterized by an increase in CD44v3+ and CD44v10+ skin-infiltrating leucocytes (SkIL). Induction of a contact eczema, one of the therapeutic options in AA, can be mitigated strongly by a blockade of CD44v10. The observation that induction of a delayed type hypersensitivity (DTH) reaction abrogates an autoimmune reaction, where both responses apparently use similar effector mechanisms, is surprising and prompted us to search for the underlying mechanisms. AA-affected C3H/HeJ mice were treated with the contact sensitizer SADBE (squaric acid dibutylester) and leucocyte subpopulations and their activation state was evaluated in SkIL and draining lymph nodes. AA-affected mice exhibited an increased number of SkIL with a predominance of T lymphocytes. After treatment with the contact sensitizer SADBE recovery of SkIL was reduced and monocytes predominated. However, a significantly increased number of leucocytes was recovered from draining lymph nodes. Draining lymph node cells from untreated and treated AA mice exhibited all signs of recent activation with high-level expression of co-stimulatory and accessory molecules and an increased percentage of CD44v3+ and CD44v10+ leucocytes. In contrast, SkIL of SADBE-treated AA mice contained relatively few activated T cells and reduced numbers of CD44v3+ and CD44v10+ cells. Thus, the activation state and the distribution of leucocyte subsets in SADBE-treated AA mice are consistent with a blockade of leucocyte extravasation. Accordingly, the therapeutic effect of long-term SADBE treatment may rely on impaired leucocyte traffic.

Allergens↗
PubMed2003

Clinical and cost-effectiveness of new and emerging technologies for early localised prostate cancer: a systematic review.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of new and emerging technologies for early, localised prostate cancer. DATA SOURCES: Electronic databases, reference lists of relevant articles and various health services research-related resources. REVIEW METHODS: A list of new and emerging technologies was identified and agreed. A systematic review was undertaken and selected studies were reviewed against a set of criteria. An economic model was developed and used to compare the specified newer treatments with the traditional approaches. RESULTS: For neoadjuvant hormonal therapy, no evidence of benefit was seen in terms of biochemical disease-free survival. For adjuvant hormonal therapy, there was no evidence of benefit in terms of survival, but some conflicting evidence that higher risk patients may benefit. The largest number of studies reported results for brachytherapy, where some evidence suggested that it may be more effective than standard treatments for lower risk patients, although less effective for intermediate- and high-risk patients, in terms of biochemical disease-free survival. Lower quality evidence reported fewer complications than for standard treatments. Higher quality evidence suggested that disease-specific quality of life (QoL) for brachytherapy patients was lower than for patients receiving standard treatments. The review of three-dimensional conformal radiotherapy (3D-CRT) considered treatment-related morbidity, where significantly fewer gastrointestinal complications occurred than with standard radiotherapy. It was suggested that higher radiation doses achieved better disease control, although patient characteristics were often reported as independent indicators of control. The review of intensity-modulated conformal radiotherapy suggested that late gastrointestinal toxicity may be reduced compared with 3D-CRT. For cryotherapy, high rates of impotence were reported. Owing to the paucity and poor quality of evidence identified for other interventions, conclusions regarding their clinical effectiveness cannot be drawn. Cost-effectiveness estimates were based on the impact of adverse events on quality-adjusted life-years and the assessment was restricted to brachytherapy, 3D-CRT and cryotherapy compared with standard treatments. Of the new treatments included, only cryotherapy appeared not to be potentially cost-effective compared with traditional treatments, owing to the associated high incidence of impotence. CONCLUSIONS: The results of the clinical effectiveness review should be viewed in the context of the quality of the available evidence. Very few randomised controlled trials (RCTs) were identified, with the majority of included studies being descriptive case series, open to patient selection bias and measuring surrogate end-points with short-term follow-up. It is difficult therefore to draw conclusions on the relative benefits or otherwise of the newer technologies owing to the lack of substantive evidence of any quality and the lack of comparisons between the newer technologies and with standard treatments. Given the lack of high-quality clinical evidence with long-term follow-up and the uncertainty surrounding the assumptions in the economic analysis, the following areas are recommended for further research: RCTs with sufficient follow-up to measure benefits in terms of overall survival to include QoL measurement to establish trade-offs between potential adverse events and benefits of treatment; the identification of prognostic risk factors among men diagnosed with early prostate cancer; QoL studies to compare the utility of health states among patients on active monitoring, patients receiving treatment and the comparable healthy population; the relationship between surrogate end-points and survival; and the adoption of standard definitions for adverse events.

Cost-Benefit Analysis↗
PubMed2001

Refinement of the chromosome 5p locus for craniometaphyseal dysplasia.

Craniometaphyseal dysplasia--Jackson type (CMDJ) is an autosomal dominant bone dysplasia with hyperostosis and sclerosis of the skull and abnormal modelling of the metaphyses. In a large German pedigree, a locus for CMDJ has been mapped previously to the short arm of chromosome 5 (5p15.2-p14.1), defining a 19-cM disease interval between markers D5S2004 and D5S502. Analysis of a large Australian pedigree together with a second German family confirms linkage to the same region. Obligate recombinations in the new families and confirmation of a supposed recombination in the previously reported German kindred have enabled us to narrow the critical region down to approximately 4 cM between markers D5S1987 and D5S1991.

Australia↗
PubMed2000

[Determining the severity of venous insufficiency with duplex sonography].

OBJECTIVE: The volume flow in the common femoral vein (SV) as a representative parameter of the venous hemodynamics of the leg can be measured using duplex-sonography. A direct correlation between the SV-data and the clinical grade of the venous disease was postulated. PATIENTS/METHODS: SV was measured in 36 patients (62 limbs) with complete varicosis of the long saphenous vein, 18 patients (24 limbs) with an incomplete form of varicosis and 40 healthy persons (78 limbs). The assessments were done under standardized conditions. We found a significant difference of the SV-data between the three groups. RESULTS: The values of SV were significantly elevated in varicosis compared with the healthy limbs. The data determined in legs with complete varicosis were significantly raised compared to incomplete varicosis. The means were 0.38 l/min in complete varicosis, 0.26 l/min in incomplete varicosis and 0.13 l/min in healthy limbs. During a time course of 30 minutes the values were stable. CONCLUSIONS: The results demonstrate a significant correlation between the measured SV data and the grade of venous disease.

Adult↗
PubMed2000

Molecular sex identification of stillborn and neonate individuals ("Traufkinder") from the burial site Aegerten.

The study reconstructs the sex ratio of 121 stillborn and neonate individuals from the early modern burial site Aegerten, Switzerland. The immature individuals, who were not baptised before death, were buried along the walls of the church. To perform a molecular sex identification, bone samples from the infants were collected from different skeletal elements. Ancient DNA (aDNA) was isolated by a combination of automated phenol/chloroform extraction and precipitation with silica powder. A combination of manuell Chelex extraction and purification kit was also used to perform an extraction. Finally, the aDNA extracts were amplified with a primer system that amplifies a part of the amelogenin gene located on the human sex chromosomes. The morphometrical sex determination of the children suggests a large disproportion of female individuals (about 60%). This finding was compared to PCR-based amplification results. In contrast, the results of the molecular sex identification were a high proportion of male individuals. Looking at these results, it should be noted that the high mortality of male individuals during the last months of pregnancy and during the first month after birth is in accordance with the natural sequence of death also found in recent populations.

Female↗
PubMed2000

Evaluation of morphological sex determinations by molecular analyses.

The study presents an evaluation of morphological sex determinations of adult skeletal individuals based on traits of the ossa coxae and the cranium. The evaluation criterion was genetic analysis of the amelogenine gene, which represents parts of the X- and the Y-chromosome (Mannucci et al. 1994). The study was carried out on 33 human skeletons from an early modern burial site in Lower Saxony. In this skeletal series, 88% of the morphological sex determinations matched the genetic sex. The percentage of matches was further improved, if only those morphological determinations were taken into account that were classified as unambiguous by a self-evaluation. In the reverse case, a significant number of non-matching determinations (33%) resulted from those cases in which a sex determination still seemed possible but was classified as "ambiguous" in the self-evaluation. At least within this skeletal series, no clear connection could be detected between the number of matching results and the presence or absence of the ossa coxae. This might be due to a strong cranial dimorphism within this particular skeletal series.

Adult↗
PubMed2000

Megaplex DNA typing can provide a strong indication of the authenticity of ancient DNA amplifications by clearly recognizing any possible type of modern contamination.

Recent experiments revealed the perfect applicability of megaplex typing by autosomal short tandem repeats (STRs) to degraded DNA. The advantages of megaplex approaches lie in reduced amounts of sample material that are necessary and in remarkable time saving. Furthermore, megaplex typing clearly recognizes possible contaminations and thus has a large potential for indicating authenticity in ancient DNA analysis. This is demonstrated by three examples in which various types of contaminations could clearly be identified as such and even traced back to their origin. This would have been impossible using control samples, due to the sporadic nature of these types of contaminations.

Artifacts↗
PubMed2000

STR-genotyping of archaeological human bone: experimental design to improve reproducibility by optimisation of DNA extraction.

The analysis of degraded DNA with the help of short tandem repeat loci (STRs) is an important source of information both in forensic casework and in the anthropological context. The reproducibility of STR-genotyping of highly degraded or "ancient" DNA can be reduced by the generation of artifacts during PCR amplification. The frequency and amount of these artifacts--allelic dropout and the generation of shadow bands--are related to the quality and quantity of the extracted DNA amplified in a PCR reaction. Therefore, one important strategy to increase the reproducibility of STR-genotyping of samples containing degraded DNA is the optimisation of the DNA extraction.

Archaeology↗
PubMed2000

Ancient DNA-typing approaches for the determination of kinship in a disturbed collective burial site.

Several DNA-typing approaches are applied for identification and kinship analysis. Autosomal Short Tandem Repeat (STR) typing produces the genetic fingerprint that is unique to an individual. Y-chromosomal STR typing identifies individuals of the same paternal lineage, and sequence analysis of the hypervariable region of the mitochondrion can identify maternally related individuals. The combined approach of these DNA-typing methods allows the determination of kinship even in complex collective burial situations. In a bronze age collective site, the typing methods were tested for applicability to ancient DNA. For each approach, results were obtained, leading to the conclusion that the determination of kinship is achievable.

Bone and Bones↗
PubMed2000

STR allelic frequencies in a German skeleton collection.

Chromosomal DNA was isolated from bones from a German skeleton collection (Goslar, 18th century) and detected by PCR. Nine microsatellite regions were amplified by multiplex reactions using the AmpFlSTR Profiler Plus kit and analysed to obtain their allelic distribution. A statistical evaluation of the results revealed no allelic differentiation between the historic sample and a modern German one at each locus.

Alleles↗
PubMed2000

Ancient DNA fragments longer than 300 bp.

It is widely assumed that ancient DNA (aDNA) extracts contain no authentic templates longer than 300 bp. Here we present results which show that fragments of up to 800 bp in length can be reproducibly amplified from aDNA extracts. The amplification involves the short tandem repeat (STR) locus HUMVWA31A. Authentication of the amplified fragments is carried out by measures of expectancy.

DNA↗
PubMed2000

Reconstruction of kinship by fecal DNA analysis of orangutans.

Genetic analysis is a useful tool for assigning biological relationships. Thus, it will improve genetic management of wild animal populations and breeding colonies. Kinship analysis will give new insights into the behavior, sociobiology and genetic management of orangutans. In this study, chromosomal DNA from orangutan (Pongo pygmaeus ssp.) was extracted from excrements. Feces samples were screened for up to nine microsatellite markers from related zoo populations of orangutans (Pongo pygmaeus ssp.) kept at the Zoological Garden Berlin and the Zoological Garden Heidelberg, Germany. Family structures are documented in the "International Studybook of the Orangutan" (Perkins 1995) and the "Europäisches Erhaltungszucht Programm 1998" (Becker 1998). To examine whether human short tandem repeat loci (STR) are suitable for the reconstruction of kinship in orangutans, nine STRs, commonly used in forensic studies and the amelogenin system, were amplified in a multiplex-PCR approach (AmpFlSTR Profiler Plus). We were able to show that five of the nine human autosomal STRs in question amplified successfully in orangutans. Thus, we could reconstruct kinship structures of the Berlin and Heidelberg populations.

Amelogenin↗
PubMed2000

Palaeogenetic analysis of (pre)historic artifacts and its significance for anthropology.

The possibility of isolating ancient DNA (aDNA) from all kinds of (pre)historic anthropogenetic artifacts opens new perspectives. This study applies palaeogenetic techniques to three anthropological issues: 1. Palaeodiet. DNA sequences from organic residues in vessels identify Precolumbian Aztec diet. 2. (Pre)historic husbandry and economic structures. aDNA data can reveal the species and the genetic evolutionary stage of animals and plants and show the manner and the extent of their growth, cultivation, or domestication. 3. Production techniques, use, and functionality. Identification of the plant or animal source of an archaeological find can reveal the use or the function of the find. Examples from a Celtic "sausage-end" and an Aztec "eye salve" are given.

Archaeology↗
PubMed2000

Trace analysis of endogenous and exogenous biomolecules from archaeological skeleton materials.

An analytical procedure was developed for the determination of pharmacologically active substances in archaeological skeleton materials. In comparative model studies, added ("spiked") test biomolecules of varying chemical behaviours were extracted from sample matrices and percentage of the analytes recovered were estimated using gas chromatography/mass spectrometry (GC/MS) or high performance liquid chromatography (HPLC). For the sterols and steroids studied, several organic solvents were appropriate. Extraction yields for the alkaloid nicotine, representing non-endogenous basic agents, were increased by alkalizing with triethylamine or by extracting with a two-phase system consisting of an alkaline aqueous and an organic layer (toluene). The flavonol quercetin was extractable only in an acidic environment. In a screening for native biomolecules using GC/MS, nicotine was identified in individual samples, in addition to lipophilic substances such as the endogenous cholesterol and its degradation products and two phytosterols which may have migrated into the bones from the surrounding soil.

Alkaloids↗
PubMed1999

Optimized DNA extraction to improve reproducibility of short tandem repeat genotyping with highly degraded DNA as target.

The reproducibility of short tandem repeat (STR) genotyping of highly degraded DNA is often reduced due to artifacts generated during polymerase chain reaction (PCR) amplification. The frequency and amount of these artifacts are related to the quality and quantity of the DNA amplified. Consequently, the aim of this investigation was the optimization of DNA extraction to increase the reproducibility of STR genotyping of samples containing highly degraded DNA. Starting from a standard extraction protocol, systematic variation of individual parameters resulted in optimized protocols for three categories of ancient human bone material (different degrees of DNA degradation) and a consensus protocol for the extraction of a broad range of ancient DNA preservation states.

DNA↗