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S Hummel

Publications and source records attributed to S Hummel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Ancient DNA profiling by megaplex amplications.

Simultaneous amplification of nine human short tandem repeat (STR) DNA sequences and the amelogenin locus allows reducing to an absolute minimum the amount of sample material that is necessary for genetic identification or kinship analysis. Valuable remains can be studied this way without any visible damage, as is demonstrated by typing the DNA of a tooth root from the Saxon warrior Widukind, who died about 1200 years ago. The broad applicability of the megaplex approach is shown by typing bone and teeth specimens ranging from a few months to 3000 years of age employing AmpFISTR Profiler Plus. Additionally, megaplex STR typing is the method of choice for proving the authenticity of molecular results derived from ancient degraded DNA.

Amelogenin↗
PubMed1999

DNA preservation: a microsatellite-DNA study on ancient skeletal remains.

To determine the effect of environmental factors on the preservation of DNA, archeological teeth of approximately similar age but greatly differing site milieu were examined for DNA content. The complex relational system of locational milieu of the samples was reduced to its essential and, at the same time, easily measurable factors. These are temperature, humidity, pH value, the geochemical properties of the soil, the amount of postmortal organic substances and the general degree of microbial infestation in the respective soil. The relative DNA content in the samples was established by determining the rate of successful polymerase chain reaction (PCR) amplifications. Differences in quantity and quality of the results are attributed to the respective prevailing environmental factor or to the respective storage conditions. Dryness, low temperature and absence of microorganisms favors the preservation of DNA. The bioapatite of bones and teeth, like the DNA, are preserved under neutral or slightly alkaline conditions. Brief storage at room temperature does not affect the amount of amplifiable DNA but does affect the reproducibility of the results. Long storage outside a lab freezer reduces the amount and the reproducibility of DNA amplifications in ancient specimens.

Bone and Bones↗
PubMed1999

DNA profiling of orangutan (Pongo pygmaeus) feces to prove descent and identity in wildlife animals.

In this study, orangutan (Pongo pygmaeus ssp.) DNA was extracted from excrements, obtained from individual zoo populations. 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 in man and the amelogenin system, were amplified in a multiplex polymerase chain reaction (PCR) approach. Five of the nine human autosomal STRs in question amplified successfully in orangutans. Furthermore, the experiments revealed that orangutans possess allele distributions comparable to humans in these systems. Fragment length determination allowed kinship structures to be reconstructed.

Animals↗
PubMed1999

Proving the authenticity of ancient DNA by comparative genomic hybridization.

In PCR-supported amplification of ancient, degraded DNA, contamination with contemporary DNA can lead to false-positive results, which frequently give rise to discussions in which the mere existence of ancient DNA is doubted. Our confirmation of ancient DNA using comparative genome hybridization (CGH) eliminates these doubts. Unlike PCR methods, CGH requires no amplification of the DNA to be analyzed if adequate amounts of specimen DNA is used. Thus, false results traceable to contaminations are practically ruled out. The examples provided here prove the authenticity of ancient DNA for a 250-year-old and a 3,000-year-old sample. At the same time, the CGH of ancient DNA offers the chance to gain insight into the pattern of DNA degradation and to monitor the preservation of certain chromosomal segments.

Chromosomes, Human↗
PubMed1999

Amplification of Y-chromosomal STRs from ancient skeletal material.

The adaptation to ancient DNA analysis of a Y-chromosomal STR (short tandem repeat) multiplex comprising the four STR systems DYS19, DYS390, and DYS389I/II shows the suitability of Y-chromosomal STR typing on ancient human remains. A new primer site for the system, DYS389I/II, resulting in products shortened by 94 bp, was chosen to serve the special needs of amplification of ancient DNA. For the first time, it was possible to amplify STR loci of the Y chromosome from historical and prehistorical bones of up to 3000 years old.

Bone and Bones↗
PubMed1998

Tree-pollen allergy is efficiently treated by short-term immunotherapy (STI) with seven preseasonal injections of molecular standardized allergens.

The efficacy and tolerance of short-term immunotherapy (STI) by seven preseasonal injections of tree-pollen allergens (ALK7 Frühblühermischung) was investigated in a double-blind, placebo-controlled, multicenter study with 111 rhinoconjunctivitis patients. Nasal and bronchial symptoms simultaneously analyzed, and nasal symptoms as a single end point, but not the overall score of nasal, bronchial, and conjunctival symptoms, showed a significantly lower increase with STI during birch-pollen exposure (both P=0.033, n=105, Mann-Whitney U-test). However, a selective analysis with patients from centers with high recruitment figures (n> or =10 patients, n=29 STI, n=32 placebo) showed a significantly lower increase of nasal, bronchial, and overall symptom score (STI 11.0 vs placebo 18.0, P=0.001, U-test). STI had equidirected effects on conjunctival, nasal, and bronchial symptoms analyzed as multiple end points, although conjunctival symptoms were not significantly different as a single end point. The seasonal increase in drug use was reduced by 62% in the STI group compared with placebo (P=0.032, t-test). Specific IgG4 increased only after STI (P<0.001); IgE was not significantly different. Eosinophil cationic protein remained unchanged with STI, but significantly increased with placebo in the pollen season (P=0.003). STI was well tolerated. In conclusion, STI was shown to be efficacious and safe for the treatment of patients with tree-pollen rhinoconjunctivitis.

Adolescent↗
PubMed1997

Automated planning target volume generation: an evaluation pitting a computer-based tool against human experts.

PURPOSE: Software tools are seeing increased use in three-dimensional treatment planning. However, the development of these tools frequently omits careful evaluation before placing them in clinical use. This study demonstrates the application of a rigorous evaluation methodology using blinded peer review to an automated software tool that produces ICRU-50 planning target volumes (PTVs). METHODS AND MATERIALS: Seven physicians from three different institutions involved in three-dimensional treatment planning participated in the evaluation. Four physicians drew partial PTVs on nine test cases, consisting of four nasopharynx and five lung primaries. Using the same information provided to the human experts, the computer tool generated PTVs for comparison. The remaining three physicians, designated evaluators, individually reviewed the PTVs for acceptability. To exclude bias, the evaluators were blinded to the source (human or computer) of the PTVs they reviewed. Their scorings of the PTVs were statistically examined to determine if the computer tool performed as well as the human experts. RESULTS: The computer tool was as successful as the human experts in generating PTVs. Failures were primarily attributable to insufficient margins around the clinical target volume and to encroachment upon critical structures. In a qualitative analysis, the human and computer experts displayed similar types and distributions of errors. CONCLUSIONS: Rigorous evaluation of computer-based radiotherapy tools requires comparison to current practice and can reveal areas for improvement before the tool enters clinical practice.

Expert Systems↗
PubMed1997

Consistency of three-dimensional planning target volumes across physicians and institutions.

PURPOSE: Three-dimensional treatment planning depends upon exact and consistent delineation of target volumes. This study tested whether different physicians from different institutions vary significantly in their creation of planning target volumes (PTVs). METHODS AND MATERIALS: Eight physicians from three different institutions created partial planning target volumes for nine clinical test cases. Their target volumes were evaluated qualitatively and quantitatively. Quantitative results were tested for significant differences. RESULTS: Qualitative analysis showed the physicians to vary in (a) the margin placed around the clinical target volume, (b) the margin used near critical structures, and (c) handling of concavities in the clinical target volume. Quantitative analysis showed these variations to result in statistically significant differences in the measured volume of the physicians' planning target volumes. CONCLUSIONS: Individual physicians and institutions differ significantly in their creation of planning target volumes, suggesting individual and institutional differences in the working definition for the PTV. Implications of this fact are discussed, along with areas where standardization can be improved.

Analysis of Variance↗
PubMed1997

Modelling and costing the consequences of using an ACE inhibitor to slow the progression of renal failure in type I diabetic patients.

Antihypertensive drugs slow the progressive decline in renal function seen in patients with insulin-dependent diabetes and nephropathy. In a recent study, the ACE inhibitor captopril protected against this deterioration in renal function. We developed an economic model to analyse the cost impact of ACE inhibitor treatment on progression to endstage renal failure (ESRF) in diabetic patients over 4 years. Two scenarios were compared: one describing the progression of a cohort of 1000 patients receiving 25 mg captopril three times daily, and the other for an equivalent cohort without such prophylactic treatment. Previously published data were used to estimate the transition rates for each stage from the onset of renal failure until death. All direct costs were discounted by an annual rate of 6%, and were subjected to sensitivity analysis. The discounted cost saving of ACE inhibitor treatment for a cohort of 1000 patients was estimated as 0.95 million pounds over 4 years. Under sensitivity analysis, these results were very robust to variations in the costs of ESRF treatment. Prophylactic treatment with ACE inhibitors was predicted to provide substantial increases in life expectancy and reduction in the incidence of ESRF, while also providing significant economic savings.

Adolescent↗
PubMed1997

An economic analysis of the Survival and Ventricular Enlargement (SAVE) Study. Application to the United Kingdom.

Recent studies have shown that ACE inhibitors reduce morbidity and mortality after myocardial infarction (MI). While these trials have obvious clinical implications, the widespread introduction of a new treatment for a condition as common as MI also has clear cost implications. The results of the post-MI studies with ACE inhibitors suggest that restricted use of treatment-in high-risk patients-is likely to be most cost effective, whereas treatment of all MI survivors, many of whom are at low risk, will be least cost effective. An approach somewhere in between may maximise clinical benefit at an acceptable cost. Economic analysis may help in deciding how these drugs might be best used after MI. We have conducted a cost-effectiveness and cost-utility analysis of the Survival and Ventricular Enlargement (SAVE) study, which reported the benefit of ACE inhibitors in intermediate-risk patients. Assuming all MI survivors require measurement of left ventricular function before selection for treatment (the approach used in the SAVE study), the incremental cost per life-year gained (LYG), over 4 years, using prophylactic captopril is approximately 10000 pounds sterling (Pounds) [1994 to 1995 values]. The cost per quality-adjusted life-year (QALY) is similar. These incremental cost per LYG and cost per QALY ratios compare favourably with other commonly used symptomatic and prophylactic treatments, and argue for extending post-MI use of ACE inhibitors to intermediate-as well as high-risk patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

[Molecular sex determination in skeletal remains of premature and newborn infants of the Aegerten, Switzerland, burial field].

The morphological and morphometrical analyses of skeletal remains usually give reliable access to the gender of mature individuals while the analyses of skeletal remains of immature individuals allocate only 70-90% of the individuals. However, the use of modern techniques like the Polymerase Chain Reaction (PCR) enables a sex identification also if fragmentary material or skeletal remains of children are investigated. The present study reconstructs the sex ratio of about 120 stillborn and neonate individuals of the burial place Aegerten, Switzerland. The morphometrical sex determination of the children suggests a large excess (about 60%) of female individuals. This finding was compared to the molecular sex identification. In order to perform a molecular sex identification aDNA was extracted from bone samples of the stillborn and neonate individuals. A standard phenol/chloroform extraction and a purification with a silica powder were carried out. Finally, the aDNA samples were amplified with a primer system for the amelogenin gene, that is located on the human sex chromosomes.

Bone and Bones↗
PubMed1997

[Detection of DNA single-copy sequences of prehistoric teeth. Site milieu as a factor for preservation of DNA].

DNA-extracts from prehistoric roots of teeth were analyzed by PCR to investigate microsatellite-systems. At the same time the x/y-chromosome specific system Amel A/B was investigated. The samples were collected from different burial conditions of similar age. Factors leading to limited DNA-degradation are given. For the first time reproducible Quadruplex-amplification on single-copy loci of prehistoric tissue was obtained in samples from the Lichtenstein-Cave, Kr. Osterode/Harz. Positive results are explained by low temperature in the burial site. In addition the results show that desiccation allows DNA-preservation but cannot protect the DNA from damage due to microbial origin. Microorganisms can destroy DNA-structures completely.

Burial↗
PubMed1997

[Reproducibility of aDNA typing].

The reproducibility of short tandem repeat (STR) amplification of aDNA extracts is limited by means of formation of artifacts during PCR. One of these artifacts, the so called allelic-dropout (failure of the amplification of alleles), may result in false-homozygote typing of a sample, if genotyping is based on the analysis of a single amplification product. 30 tooth- and bone samples collected from 17 individuals of three burial sites were investigated in a blind test. Using the polymerase chain reaction (PCR) the two independent segregating STR-loci HUMVWA and HUMTH01 were amplified. Corresponding to a mathematical estimation, multiple amplifications of each sample and genelocus were carried out. The results of this genotyping were compared intraindividually.

Bone and Bones↗
PubMed1997

[Classification of isolated skeletal elements using aDNA typing].

Analysis of ancient DNA of material found in the Lichtensteinhöhle, a burial site of the Younger Bronze Age has been used for the first time to assign isolated skeletal elements to corresponding individuals. The method involved DNA typing through amplification of five Short Tandem Repeat loci which are also used in forensic genetics for the determination of kinship and identification. From all of the examined bone samples DNA was successfully extracted and amplification by means of Polymerase Chain Reaction could be carried out. For the skeletal elements allelic profiles which are specific for an individual were set up. These profiles made it possible to recognize bones belonging to one individual. Elements which were not from this individual could be excluded with certainty by aDNA analysis.

Bone and Bones↗
PubMed1997

[Determination of kinship by aDNA analysis].

Molecular sex determination and aDNA typings were carried out on a group of five prehistoric individuals. Due to the burial situation and the individual ages the group was assumed to be a family consisting of the parents and three children. DNA was extracted from teeth and bone samples of all skeletons. The aDNA typings based on the PCR amplification of four different microsatellite DNA loci, so-called human short tandem repeats (STR). Results of the molecular sex determinations and allele determinations are presented and compared with morphological determinations. Up to now, the individual biological kinship could be verified for three of the individuals. This is the first proof of individual biological kinship on the molecular level for prehistoric individuals.

Adult↗
PubMed1996

Amplification of human short tandem repeats from medieval teeth and bone samples.

The suitability of typing hypervariable DNA loci for the genetic analysis of prehistoric populations is demonstrated for the first time. Alleles of the human short tandem repeat locus VWA31/A have been amplified from ancient teeth and bone samples derived from an early medieval burial site at Weingarten, Germany, using the polymerase chain reaction. The DNA results for 76 individuals reveal remarkable similarity of the allelic frequencies between the past and modern populations. A surplus of apparent homozygotes in the ancient population is most likely due to a stochastic problem of amplification of degraded DNA. Therefore technical obstacles for the application to ancient DNA were evaluated. The substantial perspectives of using microsatellite typing for the analysis of heritable diseases, determination of relatedness, and establishment of genealogies in prehistoric populations are outlined.

Alleles↗
PubMed1995

Seed and vascular expression of a high-affinity transporter for cationic amino acids in Arabidopsis.

In most plants amino acids represent the major transport form for organic nitrogen. A sensitive selection system in yeast mutants has allowed identification of a previously unidentified amino acid transporter in Arabidopsis. AAT1 encodes a hydrophobic membrane protein with 14 membrane-spanning regions and shares homologies with the ecotropic murine leukemia virus receptor, a bifunctional protein serving also as a cationic amino acid transporter in mammals. When expressed in yeast, AAT1 mediates high-affinity transport of basic amino acids, but to a lower extent also recognizes acidic and neutral amino acids. AAT1-mediated histidine transport is sensitive to protonophores and occurs against a concentration gradient, indicating that AAT1 may function as a proton symporter. AAT1 is specifically expressed in major veins of leaves and roots and in various floral tissues--i.e., and developing seeds.

Amino Acid Sequence↗