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Biomedical subjects

A Nagel

Publications and source records attributed to A Nagel.

At least 19 recordsLinked to original sources
PubMed2001

Towards environmental toxicogenomics -- development of a flow-through, high-density DNA hybridization array and its application to ecotoxicity assessment.

Assessment of the environmental hazard posed by soils/sediments containing low to moderate levels of contaminants using standard analytical chemical methods is uncertain due (in part) to a lack of information on contaminant bioavailability, the unknown interactive effects of contaminant mixtures, our inability to determine the species of a metal in an environmental matrix, and the relative sensitivity of bioassay species. Regulatory agencies compensate for this uncertainty by lowering cleanup goals, but in this process they effectively exclude otherwise attractive cleanup options (i.e. bioremediation). Direct evaluations of soil and sediment toxicity preclude uncertainty from most of these sources. However, the time and cost of chronic toxicity tests limits their general application to higher levels of tiered toxicity assessments. Transcriptional level (mRNA) toxicity assessments offer great advantages in terms of speed, cost and sample throughput. These advantages are currently offset by questions about the environmental relevance of molecular level responses. To this end a flow-through, high-density DNA hybridization array (genosensor) system specifically designed for environmental risk assessment was developed. The genosensor is based on highly regular microchannel glass wafers to which gene probes are covalently bound at discrete (200-microm diameter spot) and addressable (250-microm spot pitch) locations. The flow-through design enables hybridization and washing times to be reduced from approximately 18 h to 20 min. The genosensor was configured so that DNA from 28 environmental samples can be simultaneously hybridized with up to 64 different gene probes. The standard microscopic slide format facilitates data capture with most automated array readers and, thus high sample throughput (> 350 sample/h). In conclusion, hardware development for molecular analysis is enabling very tractable means for analyzing RNA and DNA. These developments have underscored the need for further developmental work in probe design software, and the need to relate transcriptional level data to whole-organism toxicity indicators.

Animals↗
PubMed2001

[Hemithyroidectomy on principle in cases of unclear fine needle biopsy and frozen section findings].

SUMMARY: Fine needle aspiration biopsy (FNB) and frozen section (FS) may help to validate pre- and intraoperatively dignity of thyroid nodules. Credibility and clinical valuation of both methods have to be taken into consideration of surgical treatment. Between 7/96 and 6/00 82 patients were operated for thyroid lesions using both diagnostic methods to verify thyroid lesions. The sensitivity of both methods is low. With FNB only 5/11 malignancies (45.5 %) were recognized. Within the group of "suspicious" FNB findings (22/82; 26.8 %) definitive histology demonstrated another 6 carcinomas. Only 1 of these initially not recognized carcinomas was verified by FS intraoperatively whereas 5 carcinomas were judged to be benign lesions. Follicular carcinomas and follicular variants of papillary carcinomas could not be assessed by FNB in 6/8 and by FS in 8/9 cases. Only very few malignancies, which are not found by FNB, can be verified by FS. A routine use of intraoperative FS to verify FNB results is not justified, but can give additional information about tumor size, lymph node status and extra-/intrathyroid nodules, which are not examined by FNB preoperatively. Hemithyroidectomy with lymph node dissection represents the operation of choice in cases with unclear FNB results to avoid a second operation with increased risk of recurrent nerve palsy and hypoparathyroidism.

Adenocarcinoma, Follicular↗
PubMed2000

The MITE family heartbreaker (Hbr): molecular markers in maize.

Transposable elements are ubiquitous in plant genomes, where they frequently comprise the majority of genomic DNA. The maize genome, which is believed to be structurally representative of large plant genomes, contains single genes or small gene islands interspersed with much longer blocks of retrotransposons. Given this organization, it would be desirable to identify molecular markers preferentially located in genic regions. In this report, the features of a newly described family of miniature inverted repeat transposable elements (MITEs) (called Heartbreaker), including high copy number and polymorphism, stability, and preference for genic regions, have been exploited in the development of a class of molecular markers for maize. To this end, a modification of the AFLP procedure called transposon display was used to generate and display hundreds of genomic fragments anchored in Hbr elements. An average of 52 markers were amplified for each primer combination tested. In all, 213 polymorphic fragments were reliably scored and mapped in 100 recombinant inbred lines derived from a cross between the maize inbreds B73 x Mo17. In this mapping population, Hbr markers are distributed evenly across the 10 maize chromosomes. This procedure should be of general use in the development of markers for other MITE families in maize and in other plant and animal species where MITEs have been identified.

Base Sequence↗
PubMed2000

The influence of cell adsorbent interactions on protein adsorption in expanded beds.

Expanded bed adsorption (EBA) is a primary recovery operation allowing the adsorption of proteins directly from unclarified feedstock, e.g. culture suspensions, homogenates or crude extracts. Thus solid-liquid separation is combined with adsorptive purification in a single step. The concept of integration requires that the solid components of the feed solution are regarded as a part of the process, which influences stability, reproducibility, and overall performance. This aspect is investigated here at the example of the influence of presence and concentration of intact yeast cells (S. cerevisiae) on the adsorption of model proteins (hen egg white lysozyme and bovine serum albumin) to various stationary phases (cation and anion-exchange, hydrophobic interaction, immobilised metal affinity). The interaction of the cells with the adsorbents is determined qualitatively and quantitatively by a pulse response method as well as by a finite bath technique under different operating conditions. The consequence of these interactions for the stability of expanded beds in suspensions of varying cell concentration is measured by residence time distributions (RTDs) after tracer pulse injection (NaBr, LiCl). Analysis of the measured RTD by the PDE model allows the calculation of the fraction of perfectly fluidised bed (phi), a parameter which may be regarded as a critical quantity for the estimation of the quality of fluidisation of adsorbents in cell containing suspensions. The correlation between bed stability and performance is made by analysing the breakthrough of model proteins during adsorption from unclarified yeast culture broth. A clear relationship is found between the degree of cell/adsorbent interaction, bed stability in terms of the phi parameter, and the sorption efficiency. Only beds characterised by a phi value larger than 0.8 in the presence of cells will show a conserved performance compared to adsorption from cell free solutions. A drop in phi, which is due to interactions of the fluidised adsorbent particles with cells from the feed, will directly result in a reduced breakthrough efficiency. The data presented highlight the importance of including the potential interaction of solid feedstock components and the expanded adsorbents into the design of EBA processes, as the interrelation found here is a key factor for the overall performance of EBA as a truly integrated operation.

Adsorption↗
PubMed2000

Evolutionary dynamics of the SGM transposon family in the Drosophila obscura species group.

SGM (Drosophila subobscura, Drosophila guanche, and Drosophila madeirensis) transposons are a family of transposable elements (TEs) in Drosophila with some functional and structural similarities to miniature inverted-repeat transposable elements (MITEs). These elements were recently active in D. subobscura and D. madeirensis (1-2 MYA), but in D. guanche (3-4 MYA), they gave rise to a species-specifically amplified satellite DNA making up approximately 10% of its genome. SGM elements were already active in the common ancestor of all three species, giving rise to the A-type specific promoter section of the P:-related neogene cluster. SGM sequences are similar to elements found in other obscura group species, such as the ISY elements in D. miranda and the ISamb elements in Drosophila ambigua. SGM elements are composed of different sequence modules, and some of them, i.e., LS and LS-core, are found throughout the Drosophila and Sophophora radiation with similarity to more distantly related TEs. The LS-core module is highly enriched in the noncoding sections of the Drosophila melanogaster genome, suggesting potential regulatory host gene functions. The SGM elements can be considered as a model system elucidating the evolutionary dynamics of mobile elements in their arms race with host-directed silencing mechanisms and their evolutionary impact on the structure and composition of their respective host genomes.

Animals↗
PubMed1999

Genetic basis of enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprint pattern in Sinorhizobium meliloti and identification of S. meliloti employing PCR primers derived from an ERIC-PCR fragment.

The enterobacterial repetitive intergenic consensus (ERIC)-PCR method was employed to generate genomic amplification products of Sinorhizobium meliloti strain 2011. Eleven distinctive PCR fragments obtained in PCR reactions by using the ERIC2 primer were cloned and their partial or complete nucleotide sequences established. DNA sequences that extended past the ERIC2 primer region were not conserved among the 11 PCR fragments and showed no sequence similarity to the enterobacterial ERIC consensus sequence. Thus, repetitive ERIC or ERIC-like sequences seem not to be an integral part of the S. meliloti genome. An amplification product of S. meliloti 2011 was identified which was present in S. meliloti strains but absent in other rhizobial species. Based on the nucleotide sequence information, a pair of PCR primers was designed and used for PCR amplification of sequences of S. meliloti laboratory strains 2011, L5-30, AK631 and 102F34. Nucleotide sequence analysis of the amplification products revealed a 100% DNA sequence conservation. Database searches showed that the DNA fragment putatively encodes the C-terminal part of a protein displaying similarity to 2-hydroxyacid dehydrogenases of various organisms. The newly designed PCR primers should be useful for the rapid identification of S. meliloti isolates.

Base Sequence↗
PubMed1999

Membrane-based cell culture systems--an alternative to in vivo production of monoclonal antibodies.

A new generation of membrane-based cell culture devices especially designed for small scale production of monoclonal antibodies (mabs) has entered the market in the last few years. In contrast to conventional perfusion hollow fibre bioreactors, these devices contain two functionally different membranes--one ultrafiltration membrane for nutrient supply and one gas-permeable membrane for direct oxygenation of cells. The latest systems of this generation are static culture systems which are of moderate cost and either better than, or equal to, the ascites mice in terms of quality and quantity of produced monoclonal antibodies. We have investigated the advantages of the perfused Tecnomouse bioreactor and the static CELLine culture flasks in comparison to ascites production and conventional roller bottle cultures.

Animal Welfare↗
PubMed1996

Proximal tibial osteotomy. A subjective outcome study.

We performed a retrospective study of the results of proximal tibial osteotomy in thirty-four men (thirty-seven knees) who had had unicompartmental osteoarthrosis of the knee. The average age of the patients at the time of the procedure was forty-nine years (range, twenty-eight to sixty years). The functional results were evaluated according to the system of Tegner and Lysholm, in which the level of participation in work and sports activities is graded on a scale from 0 points (complete disability) to 10 points (the ability to participate in competitive sports at the elite professional level). The average functional score was 5.4 points (range, 2 to 8 points) preoperatively and 4.8 points (range, 1 to 8 points) postoperatively. Postoperatively, many of the patients were able to participate in activities, such as running and jumping, that can lead to damage of the components of a total knee arthroplasty. Twenty-eight (82 per cent) of the thirty-four patients stated that the results had met their expectations and that they would have the operation again given the same situation.

Adult↗
PubMed1995

The energetics of the common mole rat Cryptomys, a subterranean eusocial rodent from Zambia.

Body temperature, oxygen consumption, respiratory and cardiac activity and body mass loss were measured in six females and four males of the subterranean Zambian mole rat Cryptomys sp. (karyotype 2 n = 68), at ambient temperatures between 10 and 35 degrees C. Mean body temperature ranged between 36.1 and 33.2 degrees C at ambient temperatures of 32.5-10 degrees C and was lower in females (32.7 degrees C) than in males (33.9 degrees C) at ambient temperatures of 10 degrees C but did not differ at thermoneutrality (32.5 degrees C). Except for body temperature, mean values of all other parameters were lowest at thermoneutrality. Mean basal oxygen consumption of 0.76 ml O2.g-1.h-1 was significantly lower than expected according to allometric equations and was different in the two sexes (females: 0.82 ml O2.g-1.h-1, males: 0.68 ml O2.g1.h-1) but was not correlated with body mass within the sexes. Basal respiratory rate of 74.min-1 (females: 66.min1, males: 87.min-1) and basal heart rate of 200.min-1 (females: 190.min-1, males: 216.min-1) were almost 30% lower than predicted, and the calculated thermal conductance of 0.144 ml O2.g-1.h1.degrees C-1 (females: 0.153 ml O2.g-1.h-1.degrees C-1, males: 0.131 ml O2.g-1.h-1.degrees C-1) was significantly higher than expected. The body mass loss in resting mole rats of 8.6-14.1%.day-1 was high and in percentages higher in females than in males. Oxygen consumption and body mass loss as well as respiratory and cardiac activity increased at higher and lower than thermoneutral temperatures. The regulatory increase in O2 demand below thermoneutrality was mainly saturated by increasing tidal volume but at ambient temperatures < or = 15 degrees C, the additional oxygen consumption was regulated by increasing frequency with slightly decreasing tidal volume. Likewise, the additional blood transport capacity was mainly effected by an increasing stroke volume while there was only a slight increase of heart frequency. In an additional field study, temperatures and humidity in different burrow systems have been determined and compared to environmental conditions above ground. Constant temperatures in the nest area 70 cm below ground between 26 and 28 degrees C facilitate low resting metabolic rates, and high relative humidity minimizes evaporative water loss but both cause thermoregulatory problems such as overheating while digging. In 13-16 cm deep foraging tunnels, temperature fluctuations were higher following the above ground fluctuations with a time lag.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Foot drop in a long-distance runner. An unusual presentation of neurofibromatosis.

An athletic patient presented with a nontraumatic peroneal neuropathy that failed to resolve after a period of rest. A magnetic resonance image (MRI) showed a multilobulated mass in the course of the common peroneal nerve consistent with a plexiform neurofibroma. Surgical exploration revealed a mass, which coursed from the midthigh to the fibular neck, that was intimately involved with the fibers of the nerve bundle and had cystic degeneration with vesicles along its length. The authors recommend MRI as highly accurate in diagnosing unusual causes of peroneal neuropathy.

Adult↗
PubMed1993

Newly recognized congenital myasthenic syndrome associated with high conductance and fast closure of the acetylcholine receptor channel.

We describe here a new congenital myasthenic syndrome associated with a kinetic abnormality of the acetylcholine receptor (AChR) channel. The propositus had poor suck and cry after birth. Subsequently, she had intermittent ocular symptoms and fatigued abnormally on exertion. At age 9 years, significant weakness was detected only in the frontalis, levator palpebrae, and neck flexor muscles. Electromyography showed no decrement in limb muscles but single-fiber examination of the facial muscles was consistent with a neuromuscular transmission defect. The ocular symptoms responded partially to pyridostigmine, but the abnormal fatigability did not. Tests for anti-AChR antibodies were negative. A younger sister had elements of the same disease. An intercostal muscle specimen was obtained from the propositus at age 9 years for endplate studies. The quantal content of the endplate potential was normal. Miniature endplate currents were abnormally large and their decay time constant was abnormally short. AChR channel properties were studied by analysis of acetylcholine-induced current noise. The mean single-channel conductance was increased 1.7-fold and the mean channel open time was 30% shorter than normal. The number of AChR per endplate was normal. Electron microscopy of most endplates showed no abnormality, but a few were degenerating or simplified. The channel abnormality may stem from a point mutation in an AChR subunit affecting a single amino acid residue lining the pore of the AChR channel. The mechanism by which the physiological abnormality produces clinical symptoms is not known, but possible explanations are considered.

Adult↗
PubMed1993

Congenital myasthenic syndromes: I. Deficiency and short open-time of the acetylcholine receptor.

A 5.5-year-old girl had myasthenic symptoms since birth. Tests for antiacetylcholine receptor (AChR) antibodies were negative. To investigate the character of the neuromuscular transmission defect, an intercostal muscle specimen was obtained at age 27 months. Immune deposits were absent from the endplates. On electron microscopy, most postsynaptic regions appeared normal, but the density of AChR on the junctional folds was diffusely reduced. In vitro microelectrode studies revealed that the number of transmitter quanta released by nerve impulse was normal. The amplitude of miniature of endplate potentials and currents was abnormally low. A study of the kinetic properties of AChR by analysis of acetylcholine-induced current noise demonstrated a significant decrease in mean channel open-time; the mean channel conductance was normal. The safety margin of neuromuscular transmission in this disorder is likely to be compromised by the deficiency and abnormal kinetic properties of AChR. The findings are unique among those patients with congenital AChR deficiency described to date.

Acetylcholinesterase↗
PubMed1993

Congenital myasthenic syndromes: II. Syndrome attributed to abnormal interaction of acetylcholine with its receptor.

A 21-year-old woman had myasthenic symptoms since birth that responded poorly to anticholinesterase therapy. Tests for acetylcholine receptor (AChR) antibodies were negative. An intercostal muscle specimen was obtained to investigate the character of the neuromuscular transmission defect. There were no immune deposits at the endplates. The quantal content of the endplate potential was normal. Miniature endplate potentials and currents were very small, but the number of AChR per endplate was normal. On electron microscopy, the synaptic vesicles were of normal size, the junctional folds were intact, and the density and distribution of AChR on the folds was normal. The kinetic properties of AChR were studied by analysis of acetylcholine (ACh)-induced current noise. The mean single channel conductance was normal. The noise power spectrum was abnormal, containing two components of different time course. This could result from an abnormal interaction of ACh with AChR, or from two populations of AChR at the endplate. The second possibility is unlikely because if two populations of AChR were present at the endplate, then both would have to have low conductance to explain the small miniature endplate current, but the average conductance of the channels that did open was normal.

Acetylcholine↗
PubMed1993

Application of a hollow fiber membrane cell culture system in medicine.

The Tecnomouse system is useful for cultivating transformed cell lines producing MAbs or recombinant proteins, but human tumor cells can also be propagated for autologous immunization protocols or research properties. Lymphokine-activated killer cell production and stem cell proliferation seem to be possible. Moreover, primary human cells of lymphoid organs can be successfully kept viable over long periods of time in a three-dimensional, tissue-like culture. Therefore, the bioreactor is a tool for the in vitro modulation of a variety of human organs.

Animals↗