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Biomedical subjects

H Feldmann

Publications and source records attributed to H Feldmann.

At least 145 records · Page 8Linked to original sources

The use of a synthetic tRNA gene as a novel approach to study in vivo transcription and chromatin structure in yeast.

To monitor in vivo transcription and chromatin structure of yeast tRNA genes, we constructed a synthetic tRNA gene that can be used as a reporter. Constructs in which this synthetic tRNA gene is combined with different flanking regions can be integrated into the genome as single copies. The artificial tRNA gene is tagged by the insertion of an intron-like sequence that cannot be spliced out from the precursor and transcripts can thus be identified and quantitated. By several criteria, the artificial tRNA gene behaves like a resident tRNA gene. By measuring the accessibility towards DNaseI in chromatin, we found that the artificial tRNA gene exhibits the same characteristic pattern as resident tRNA genes. Three DNaseI-sensitive sites across the transcribed part of the gene and the immediate flanking regions reflect the formation of the stable transcription complex; positioned nucleosomes are observed in the upstream flanking region. We are confident that the system we have established will prove useful for studying regulatory aspects of tRNA gene expression as well as aspects of pre-tRNA processing and splicing.

Animals↗

Kluger's "fixateur interne" for spinal instability.

Kluger's "Fixateur Interne" proved to be an excellent tool not only in spinal trauma for repositioning of impacted fractures and transpedicular stabilization of the dorsal column but also in other forms of thoracic or lumbar instability. After spinal tumor excision from a dorsal approach and vertebral replacement with methylmethacrylate additional stability through dorsal fixation was achieved with this device. Spondylodiscitis, symptomatic spondylolisthesis, spinal instability from degenerative disc disease as well as "non-union" following previous surgery could be cured using Kluger's internal fixation. Rare complications, i.e. from broken screws or rods (5%) caused no problems, but some patients required a second operation for readjustment of malpositioned screws which were causing pain or neurological deficit.

Aged↗

Glycosylation and oligomerization of the spike protein of Marburg virus.

The oligosaccharide side chains of the glycoprotein of Marburg virus (MW 170,000) have been analyzed by determining their sensitivity to enzymatic degradation and their reactivity with lectins. It was found that they consist of N- and O-glycans. Studies employing chemical cross-linking showed that the glycoprotein is present as a homotrimer in the viral envelope.

Cross-Linking Reagents↗

[Heat radiation--an essential factor of heat transport in caloric vestibular tests? Current experimental findings].

According to the accepted theory, in vestibular testing the caloric stimulus is transported from the auditory canal to the lateral semicircular canal by heat conduction via the bone. Some findings, however, are not consistent with this concept, e.g. the short latency of the vestibular response, and the fact that removing of the osseous bridge does not stop the transport of heat to the semicircular canal. Physically there are three modes of heat transport: conduction, convection, and radiation. So far, only the first two have been discussed with regard to vestibular calorization, however, they fail to explain the findings mentioned above. We carried out experiments on 10 cadaveric temporal bone specimens in order to evaluate the possible effect of heat radiation. With experimental conditions strictly regulated (specimens kept in climate box, 37 degrees C, saturated humidity, standardized irrigation of the auditory canal with 50 ml of water of 50 degrees C in 15 sec., temperature measured by thermistors at selected points of the specimen), the deviation in repeated experiments was within 0.1 degree C. In normal temporal bones a spreading of heat along the osseous structures was found in accordance with heat conduction via the bone. Then the bony bridge between posterior frame of the tympanic membrane and the lateral canal was removed along with the tegmen tympani, leaving the auditory canal and labyrinth connected only by a small anterior-inferior strut. The rise of temperature in the lateral canal, however, was not delayed and reduced, as expected, but faster and greater than in the original situation. If, now, a reflecting shield was inserted in the cleft between tympanic membrane and labyrinth the heat transfer was dramatically reduced. A similar effect could be achieved in the intact middle ear by a shield or by filling the cavity with gel. Convection as means of heat transport could be excluded. The experiments show that heat transport in the vestibular calorization is a complex process, which besides heat conduction involves radiation as an essential factor. This explains a number of experimental and clinical findings that, so far, had been unclear.

Bone Conduction↗

Transport of heat in caloric vestibular stimulation. Conduction, convection or radiation?

Experiments in temporal bone specimens were carried out under strictly controlled conditions: temperature (37 degrees C) and humidity kept constant; standardized irrigation of the external ear canal by an automated system (in 15 s, 50 ml of water, 11 degrees C above temperature of specimen), thermistor probes of 0.2 mm diameter placed in different parts of the specimens. In the intact temporal bone such an irrigation causes a rise in temperature with a gradient from the external ear canal across the bony bridge to the lateral semicircular canal as expected with heat conduction. After removal of the bony bridge, which is the main route for heat conduction, the rise in temperature in the lateral semicircular canal is greater and faster than in the intact specimen. This effect again is drastically reduced by placing a reflecting shield between tympanic membrane and labyrinth. In the intact middle ear inserting a reflecting shield or filling the cavity with gel also reduces the heat transfer to the labyrinth, although the bony routes for heat conduction are left untouched. The experiments prove that radiation plays an important part in heat transfer in caloric stimulation.

Caloric Tests↗

[Unilateral paralysis of the abdominal wall musculature caused by thoracic intervertebral disk displacement].

Herniated thoracic discs are rare. Many cases present with local radicular or cord symptoms. We describe a case which became symptomatic by a unilateral paresis of the muscles of the abdominal wall. This radicular syndrome has only been described for lumbar disc herniations before. The differential diagnosis is discussed as well as the importance of myelography and the value of Myelo-CT.

Abdominal Muscles↗

Yeast homoserine kinase. Characteristics of the corresponding gene, THR1, and the purified enzyme, and evolutionary relationships with other enzymes of threonine metabolism.

THR1, the gene from Saccharomyces cerevisiae, encoding homoserine kinase, one of the threonine biosynthetic enzymes, has been cloned by complementation. The nucleotide sequence of a 3.1-kb region carrying this gene reveals an open reading frame of 356 codons, corresponding to about 40 kDa for the encoded protein. The presence of three canonical GCN4 regulatory sequences in the upstream flanking region suggests that the expression of THR1 is under the general amino acid control. In parallel, the enzyme was purified by four consecutive column chromatographies, monitoring homoserine kinase activity. In SDS gel electrophoresis, homoserine kinase migrates like a 40-kDa protein; the native enzyme appears to be a homodimer. The sequence of the first 15 NH2-terminal amino acids, as determined by automated Edman degradation, is in accordance with the amino acid sequence deduced from the nucleotide sequence. Computer-assisted comparison of the yeast enzyme with the corresponding activities from bacterial sources showed that several segments among these proteins are highly conserved. Furthermore, the observed homology patterns suggest that the ancestral sequences might have been composed from separate (functional) domains. A block of very similar amino acids is found in the homoserine kinases towards the carboxy terminus that is also present in many other proteins involved in threonine (or serine) metabolism; this motif, therefore, may represent the binding site for the hydroxyamino acids. Limited similarity was detected between a motif conserved among the homoserine kinases and consensus sequences found in other mono- or dinucleotide-binding proteins.

Amino Acid Sequence↗

An element of symmetry in yeast TATA-box binding protein transcription factor IID. Consequence of an ancestral duplication?

TATA-box binding factor TFIID is one of the key factors in transcriptional activation. Surprisingly, the yeast TFDII protein [(1989) Nature 341, 299-303; (1989) Cell 56, 1173-1181; (1989) Proc. Natl. Acad. Sci USA 86, 7785-7789] reveals only limited homology with other DNA-binding proteins. From computer-assisted searches we infer that yeast TFIID possesses a domain structure in which homologous segments are repeated. The greatest similarity is found between two segments, each 33 amino acids in length, in which the positions of four basic residues are strictly conserved. The high homology is also reflected at the gene level. Implications of this novel type of domain structure for possible interactions in transcriptional activation are discussed.

Amino Acid Sequence↗

[Forensic evaluation of physical damage in the early Middle Ages--a comparison with current occupational disability guidelines].

The legal systems of the Germanic tribes in the early Middle Ages elaborated detailed catalogs of forfeits in compensation for certain physical injuries. The perpetrator had to pay the forfeit to the injured person, or in case of manslaughter, to the tribe of the dead. By doing so he could avert the feud which otherwise faced him. These catalogs of forfeits exactly reflect the relative value that was appointed to certain parts of the body and to sensory functions. The catalog of the Lex Saxonum (c. 802), in which physical injuries are listed, ranging from loss of single phalanges, differentiated between thumb, forefinger, small finger, and the other fingers, to death, is compared with modern grades of disability. There are surprising parallels and interesting contrasts. Bilateral deafness is put on a level with bilateral blindness, the loss of both hands, both feet, both testicles, and death.

Disability Evaluation↗

[Aneuralgic root paralyses caused by lumbar intervertebral disk displacement. Follow-up of surgical therapy].

It is a controversial issue whether or not a painless paralysis caused by a lumbar disc herniation should be managed surgically because of the possible fatal destruction of the nerve root. In a retrospective study we examined 46 patients concerning the reversibility of their neurological deficits. Our results show that the so called "aneuralgic state" of the lumbar root compression syndrome and the death of the nerve root are not identical. More than half of the patients with the symptoms of nerve root death gained significant improvement above their preoperatively existing paralysis sometimes even up to several years later. The appearance of the compressed root at the time of surgery is of special importance because it allows conclusions concerning the remission of preexisting paresis. Defects of sensibility or the reflex status never improved without simultaneous improvement of paresis. The damage of the nerve root due to disc herniation is discussed with the help of literature sources with special consideration as to the time of reinnervation. Our results demonstrate that patients with an "aneuralgic state" can benefit from disc surgery and thus surgery could be recommended for these patients. Two cases are described.

Female↗

Characterization of the prephenate dehydrogenase-encoding gene, TYR1, from Saccharomyces cerevisiae.

TYR1, the gene from Saccharomyces cerevisiae, which encodes prephenate dehydrogenase, one of the tyrosine biosynthetic enzymes, has been cloned by complementing a yeast tyr1 mutant strain. The DNA fragment containing the gene is part of a 45-kb cosmid clone which represents a region of chromosome II covering the genetically mapped tyr1 locus. The nucleotide sequence of a 3.1-kb region carrying the TYR1 gene and adjacent regions has been determined. The open reading frame contains 441 codons, corresponding to about 52.2 kDa for the encoded protein. The canonical NAD-binding domain is located within the first 45 amino acids of the protein. By primer extension, we show that there is one transcription start point. Presumably, the expression of TYR1 is not under the general GCN4 control. Instead, we find a dependence on the presence or absence of phenylalanine. These data were obtained by analysing CAT activity in constructs containing promoter fragments of TYR1 and the cat reporter gene.

Amino Acid Sequence↗

Ty4, a novel low-copy number element in Saccharomyces cerevisiae: one copy is located in a cluster of Ty elements and tRNA genes.

We have identified a composite element, Ty4, in S. cerevisiae that is ca 6.3 kb in length and contains two tau sequences as long terminal repeats. According to hybridization analyses, Ty4 occurs in low but varying copy number (one to four copies) in different yeast strains. By several criteria, Ty4 is a novel type of retroelement which is similar but not related to the other Ty elements in yeast. Two cosmid clones from strain C836 (c90 and c476) carrying individual copies of Ty4 were isolated. By restriction analysis and nucleotide sequence we show that c476 derives from the 'transposition right arm hot spot' of chromosome III [1]. The analysis of c476 revealed that an initiator tRNA(Met) gene is present at this locus and that an unusual concentration of different Ty elements has occurred: in addition to the Ty4, a Ty1 and a Ty2 element were detected in this region, confirming its highly polymorphic character.

Base Sequence↗

A hot-spot for transposition of various Ty elements on chromosome V in Saccharomyces cerevisiae.

Ty4 is a novel transposable element in the yeast, Saccharomyces cerevisiae, which is present in only a few copies in the genome (Stucka et al. 1989). In strain C836 one of the three copies (Ty4-90) is contained in cosmid clone c90, where it resides on chromosome V. Analysis of this region reveals a "hot-spot" of transposition: in addition to Ty4-90, the locus contains a complete Ty3 element and seven singular delta, sigma and tau elements. Three tRNA genes (for His, Lys, and Ile) are located in this region, and these are closely associated with one or the other of the elements, a phenomenon commonly observed in yeast. A comparison of c90 with corresponding regions from other strains shows that the locus is highly polymorphic and that this polymorphism is explicitly associated with Ty transposition and recombination events.

Base Sequence↗

Objective evidence of tinnitus in auditory evoked magnetic fields.

The waveforms of the auditory evoked magnetic field in normal-hearing individuals and patients suffering from tinnitus are distinctly different. In tinnitus patients, the magnetic wave M200 (corresponding to the electric wave P200, or P2) is delayed and only poorly developed or even completely missing, while the amplitude of the magnetic wave M100 (corresponding to the electric wave N100, or N1) is significally augmented. A very characteristic feature turned out to be the amplitude ratio of the two waves M200 and M100. Below the age of 50, the amplitude ratio M200/M100 represents a clear-cut criterion to distinguish between tinnitus patients and individuals without tinnitus. In tinnitus patients, the ratio is less than 0.5, independent of age, whereas, in young and middle-aged normal-hearing individuals, it is greater than 0.5. Since in normal-hearing individuals the average amplitude ratio decreases linearly with age, the clusters of amplitude ratios of the two groups begin to overlap beyond the age of 50. The hypothesis is put forward that the decrease of the average amplitude ratio in normal-hearing individuals reflects a degenerative process, probably initiated by multiple exogenous and endogenous factors, which leads to sustained neural activity in the generators of wave M200 and eventually gives rise to the sensation of tinnitus. The absence or poor development of wave M200 is a concomitant phenomenon, resulting from the involved generators being less responsive to external stimuli.

Acoustic Stimulation↗

[Aspects of the dynamics of delusions].

Delusion ist the outcome of psychotic experience, but can also be seen as a structure of meaning with patterns of mental and anthropological significance of its own. In schizophrenic delusion, there is some 'effort after meaning' manifest, compensating for psychotic disintegration. In the light of generative linguistics, there seems creating of delusional ideas to be performed in separated steps, but contextually linked to integrate them into a holistic delusional view of reality. Subjective evidence of delusional thinking is analyzed on the basis of semantic logics.

Delusions↗