Search PubMed⌕ Search

Biomedical subjects

H Feldmann

Publications and source records attributed to H Feldmann.

At least 55 records · Page 3Linked to original sources
PubMed1998

Processing of the Ebola virus glycoprotein by the proprotein convertase furin.

In the present study, we have investigated processing and maturation of the envelope glycoprotein (GP) of Ebola virus. When GP expressed from vaccinia virus vectors was analyzed by pulse-chase experiments, the mature form and two different precursors were identified. First, the endoplasmic reticulum form preGPer, full-length GP with oligomannosidic N-glycans, was detected. preGPer (110 kDa) was replaced by the Golgi-specific form preGP (160 kDa), full-length GP containing mature carbohydrates. preGP was finally converted by proteolysis into mature GP1,2, which consisted of two disulfide-linked cleavage products, the amino-terminal 140-kDa fragment GP1, and the carboxyl-terminal 26-kDa fragment GP2. GP1,2 was also identified in Ebola virions. Studies employing site-directed mutagenesis revealed that GP was cleaved at a multibasic amino acid motif located at positions 497 to 501 of the ORF. Cleavage was blocked by a peptidyl chloromethylketone containing such a motif. GP is cleaved by the proprotein convertase furin. This was indicated by the observation that cleavage did not occur when GP was expressed in furin-defective LoVo cells but that it was restored in these cells by vector-expressed furin. The Reston subtype, which differs from all other Ebola viruses by its low human pathogenicity, has a reduced cleavability due to a mutation at the cleavage site. As a result of these observations, it should now be considered that proteolytic processing of GP may be an important determinant for the pathogenicity of Ebola virus.

Animals↗
PubMed1998

tRNA genes and retroelements in the yeast genome.

A survey of tRNA genes and retroelements (Ty) in the genome of the yeast Saccharomyces cerevisiae is presented. Aspects of genomic organization and evolution of these genetic entities and their interplay are discussed. Attention is also given to the relationship between tRNA gene multiplicity and codon selection in yeast and the role of Ty elements.

Chromosome Mapping↗
PubMed1998

Variation in the glycoprotein and VP35 genes of Marburg virus strains.

Marburg virus, the prototype of the family Filoviridae, differs genetically, serologically, and morphologically from Ebola viruses. To better define the genetic variation within the species, VP35 and glycoprotein (GP) genes of representative human isolates from four known episodes of Marburg virus hemorrhagic fever were analyzed. The percentage nucleotide differences in the GP gene coding regions of Marburg viruses (0.1-21%) was nearly equal to the percentage amino acid changes (0-23%), while the percentage nucleotide differences in VP35 coding regions (0.3-20.9%) were higher than the percentage amino acid changes (0.9-6.1%), indicating a greater number of nonsynonymous changes occurring in the GP gene. The higher variation in the GP gene and the corresponding protein, especially those changes in the variable middle region of the GP, suggests that the variability may be the result of responses to natural host pressures. Analysis of the GP gene open reading frame shows a nonrandom distribution of nonsynonymous mutations that may indicate positive Darwinian selection is operating within the variable region. A heptad repeat region and an adjoining predicted fusion peptide are found in the C-terminal third of Marburg virus GPs, as has been previously shown for Ebola virus, and are similar to those found in transmembrane glycoproteins of retroviruses, paramyxoviruses, coronaviruses, and influenza viruses. Comparative analyses showed that there are two lineages within the Marburg virus species of filoviruses. The most recent isolate from Kenya (1987) represents a separate genetic lineage within the Marburg virus species (21-23% amino acid difference). However, this lineage likely does not represent a separate Marburg subtype, as the extent of divergence is less than that separating Ebola virus subtypes.

Amino Acid Sequence↗
PubMed1998

[History of diaphanoscopy. Pictures from the history of otorhinolaryngology, illustrated by instruments from the collection of the Ingolstadt German Medical History Museum].

BACKGROUND: In 1854 the Spanish singing teacher Manuel Garcia succeeded in inspecting his own larynx. In 1857 the neurologist Ludwig Türck in Vienna, without knowledge of Garcia's achievement, had been experimenting on laryngoscopy with his patients using a small mirror and sunlight. When in the winter of 1857-1858 he had to suspend his experiments for lack of sunlight, he lent his mirror to physiologist Johann Czermak in Budapest. Czermak, using artificial light reflected by a perforated mirror, developed modern laryngoscopy within a few weeks and made it a clinically valuable method. He described it in March 1858 as his own invention. This was the beginning of a an embittered fight with Türck about whose development had priority. DIAPHANOSCOPY OF THE LARYNX: During his very first studies on laryngoscopy Czermak noticed that the interior of the larynx could be inspected very well when the neck was illuminated by a strong light from without and the mirror was held in the dark pharynx. The tissue would then appear transilluminated in a glowing deep red. When sufficiently bright electric lamps became available in 1889, Rudolph Voltolini in Breslau, Germany, took up the transillumination of the larynx and even carried out some minor intralaryngeal operations using this method. Although suitable diaphanoscopes were soon on the market this technique was not widely adopted. It was ony used once in 1954 (Pellnitz et al.) for diagnosing early stages of laryngeal cancer. DIAPHANOSCOPY OF THE PARANASAL SINUSES: Voltolini in Breslau and Cozzolino in Naples experimented independently of each other with small electric lamps with the aim of finding new techniques of rhinoscopy. Both of them placed their lamp in the nasopharynx and performed anterior rhinoscopy using an ordinary speculum. However, it was only Voltolini who noticed the transillumination of the maxillary sinuses when the lamp was placed in the oral cavity. On October 29, 1888, in Breslau he demonstrated diaphanoscopy of the maxillary sinus for the first time. Cozzolino claimed that he had introduced this technique prior to Voltolini. Voltolini had died in 1889 and could not comment on this. A careful study of the original publications, however, shows that Cozzolino had only inspected the nasal cavity with retronasal illumination, but had not demonstrated the maxillary sinus by transillumination. The diaphanoscopy of the paranal sinuses was very soon elaborated to perfection: Vohse in 1890 applied it to the frontal sinuses, Gerber in 1900 invented a double diaphanoscope for examining both frontal sinuses simultaneously. Although the shortcomings of diaphanoscopy soon became apparent, the method was widely used for about half a century, but in the end could not compete with modern techniques of radiography and ultrasound. The history is related in detail and illustrated with numerous figures.

Germany↗
PubMed1998

[The maxillary sinus and its illness in the history of rhinology. Images from the history of otorhinolaryngology, highlighted by instruments from the collection of the German Medical History Museum in Ingolstadt].

BACKGROUND ANATOMY: In ancient times the paranasal sinuses, without any anatomical differentiation, were thought to be a system of hollow spaces through which mucus produced by the brain was drained. Leonardo da Vinci in Milano in 1489 was the first to prepare and draw anatomical specimens of the paranasal sinuses; the drawings, however, only became accessible to scientific evaluation as late as 1901. N. Highmore in England in 1651 presented the first detailed description and drawing of the maxillary sinus, and hence it is named Highmore's antrum. C. V. Schneider in Wittenberg, Germany, in 1660 realized that the mucus is not a product of the brain but is produced by the mucous lining of the region itself. F. G. J. Henle in Berlin in 1841 differentiated between various epithelia and described the special function of the ciliated epithelium of the respiratory tract. FROM OZENA TO SINUSITIS: In ancient times the word ozena originally denoted any kind of foul breath, but in the 1st and 2nd century AD (Celsus, Galenus) the term became restricted to foul odor coming from the nose. J. Drake and W. Cowper in England in 1707 reported that in some cases ozena was due to suppuration in the maxillary sinus and could be cured by extraction of a tooth and opening the sinus via the alveolus. L. H. Runge in Rinteln, Germany in 1750 compiled a nearly complete systematic survey of all diseases localized in the maxillary sinus. EARLY STAGES OF SURGERY: A. L. B. B. Jourdain in France in 1765 tried to cure suppurations of the maxillary sinus by irrigation via the natural ostium in the middle nasal meatus, however, his method did not meet with approval. L. Lamorier in Montpellier in 1743 opened the maxillary sinus form the buccal cavity, but his paper was only published in 1768. Lamorier's method and opening the sinus via a dental alveolus remained standard procedures for a long time. K. Ziem in Danzig, Germany, in 1886 analyzed 26 cases of chronic suppurations discharging from the nose, among them his own history, and found out that they can originate from different foci and that the treatment must be centered around the relevant focus. CLASSICAL OPERATIVE PROCEDURES: J. Mikulicz-Radecki in Vienna in 1886 was the first to open the maxillary sinus from the inferior nasal meatus. G. W. Caldwell in New York in 1893 published his method: opening the canine fossa wall, removal of the mucous membrane, and opening a window in the lateral wall of the inferior nasal meatus. G. Boenninghaus in Breslau, Germany, in 1896 was the first in Europe to adopt this method, and he modified it by placing a mucosal flap in the window. Unaware of Caldwell's publication, H.-P. Luc in Paris in 1897 reported on his own operative procedure, which in fact was identical to that of Caldwell's. DEVELOPMENT DURING THE LAST 100 YEARS: The operative procedures and especially the preoperative diagnosis were continually improved so that the surgical treatment of chronic suppurations of the maxillary sinus reached a high standard. During the last decades less radical interventions using an endonasal approach by endoscopy have partly superseded the classical procedures. This development is described in great detail with literal quotations of the original papers, anecdotal details, and illustrations.

Europe↗
PubMed1998

Recombinant Ebola virus nucleoprotein and glycoprotein (Gabon 94 strain) provide new tools for the detection of human infections.

After cloning and sequencing the glycoprotein (GP) gene of one of the Gabonese strains of Ebola virus isolated during the 1994-1996 outbreak, it was shown that the circulating virus was of the Zaire subtype. This was confirmed in this study by cloning and sequencing the nucleoprotein (NP) gene of this strain. These two structural proteins were also expressed as recombinant proteins and used in ELISA tests. NP was expressed as a His-tagged fusion protein in Escherichia coli and was purified on resins charged with nickel ions. GP was expressed by means of recombinant baculoviruses in Spodoptera frugiperda cells. Both recombinant proteins reacted positively in ELISAs for the detection of IgG antibodies in convalescent human sera from Gabon and Zaire. The difference in the relative titres of anti-NP and -GP antibodies was variable, depending on the sera. In addition, the recombinant NP reacted with heterologous sera from Côte d'Ivoire and was used successfully to detect IgM antibodies by mu-capture ELISA in sera from Gabonese patients.

Amino Acid Sequence↗
PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.

Chromosome XV was one of the last two chromosomes of Saccharomyces cerevisiae to be discovered. It is the third-largest yeast chromosome after chromosomes XII and IV, and is very similar in size to chromosome VII. It alone represents 9% of the yeast genome (8% if ribosomal DNA is included). When systematic sequencing of chromosome XV was started, 93 genes or markers were identified, and most of them were mapped. However, very little else was known about chromosome XV which, in contrast to shorter chromosomes, had not been the object of comprehensive genetic or molecular analysis. It was therefore decided to start sequencing chromosome XV only in the third phase of the European Yeast Genome Sequencing Programme, after experience was gained on chromosomes III, XI and II. The sequence of chromosome XV has been determined from a set of partly overlapping cosmid clones derived from a unique yeast strain, and physically mapped at 3.3-kilobase resolution before sequencing. As well as numerous new open reading frames (ORFs) and genes encoding tRNA or small RNA molecules, the sequence of 1,091,283 base pairs confirms the high proportion of orphan genes and reveals a number of ancestral and successive duplications with other yeast chromosomes.

Base Sequence↗
PubMed1997

Emergence of subtype Zaire Ebola virus in Gabon.

Gabon has recently been struck three times by Ebola hemorrhagic fever. The first isolate originating from the 1994 outbreak has been subjected to molecular characterization of its GP and VP24 genes. Sequence analysis demonstrates that the agent, Gabon-94 virus, belongs to subtype Zaire of Ebola virus. The isolate is closely related to the Kikwit-95 isolate, and both viruses seem to have evolved from a progenitor virus different from that of the Zaire-76 isolates. The relatively close relationship of all subtype Zaire viruses isolated at different geographical locations and up to 20 years apart suggests an extreme conservation in the yet unknown natural reservoir of Ebola viruses. The level of genetic variability in the human host might be different as indicated by the comparison of isolates from a single outbreak (Mayinga-76 and Eckron-76), but needs further investigation on clinical material of patients by PCR since both isolates have different levels of passages in tissue culture.

Animals↗
PubMed1997

Molecular characterization of Borna disease virus from naturally infected animals and possible links to human disorders.

In this review data are presented which indicate a high degree of genetic stability of BDV in his natural host, the horse. Despite this high degree of sequence conservation, variation in antigenicity was found, which did not influence the pathogenic properties of the virus. In addition, the correlation between BDV-seropositivity and a variety of psychiatric and neurological disorders in humans is discussed. In diagnostically unselected psychiatric patients we found a similar distribution of psychiatric disorders in BDV seropositives compared to seronegatives. Investigations of cerebrospinal fluid revealed cases of BDV encephalitis in BDV seropositive psychiatric and neurological patients. In contrast to others, we have found no evidence for the presence of BDV-RNA or BDV in human peripheral blood leucocytes.

Animals↗
PubMed1997

[Structural affinities of the incomprehensible in schizophrenic delusion].

Schizophrenic delusion constitutes a fictive reality of its own; moreover, it transforms the originally experienced psychotically incomprehensible into a structure of meaning. It is assumed that the incomprehensible is reified in the actual delusion by means of structural affinities. Reciprocally, it is through these structural affinities that we can approximate hermeneutically to the characteristics of psychotic existence.

Delusions↗
PubMed1997

[History of the tuning fork. I: Invention of the tuning fork, its course in music and natural sciences. Pictures from the history of otorhinolaryngology, presented by instruments from the collection of the Ingolstadt German Medical History Museum].

BACKGROUND: G. Cardano, physician, mathematician, and astrologer in Pavia, Italy, in 1550 described how sound may be perceived through the skull. A few years later H. Capivacci, also a physician in Padua, realized that this phenomenon might be used as a diagnostic tool for differentiating between hearing disorders located either in the middle ear or in the acoustic nerve. The German physician G. C. Schelhammer in 1684 was the first to use a common cutlery fork in further developing the experiments initiated by Cardano and Capivacci. For a long time to come, however, there was no demand for this in practical otology. THE INVENTION OF THE TUNING FORK: The tuning fork was invented in 1711 by John Shore, trumpeter and lutenist to H. Purcell and G.F. Händel in London. A picture of Händel's own tuning fork, probably the oldest tuning fork in existence, is presented here for the first time. There are a number of anecdotes connected with the inventor of the tuning fork, using plays on words involving the name Shore, and mixing up pitch-pipe and pitchfork. Some of these are related here. The tuning fork as a musical instrument soon became a success throughout Europe. THE PHYSICS OF THE TUNING FORK: The German physicist E. F. F. Chladni in Wittenberg around 1800 was the first to systematically investigate the mode of vibration of the tuning fork with its nodal points. Besides this, he and others tried to construct a complete musical instrument based on sets of tuning forks, which, however, were not widely accepted. J. H. Scheibler in Germany in 1834 presented a set of 54 tuning forks covering the range from 220 Hz to 440 Hz, at intervals of 4 Hz. J. Lissajous in Paris constructed a very elaborate tuning fork with a resonance box, which was intended to represent the international standard of the musical note A with 435 vibrations per second, but this remained controversial. K. R. Koenig, a German physicist living in Paris, invented a tuning fork which was kept in continuous vibration by a clockwork. H. Helmholtz, physiologist in Heidelberg, in 1863 used sets of electromagnetically powered tuning forks for his famous experiments on the sensations of tone. Until the invention of the electronic valve, tuning forks remained indispensible instruments for producing defined sinusoidal vibrations. The history of this development is presented in detail. The diagnostic use of the tuning fork in otology will be described in a separate article.

Acoustics↗
PubMed1997

[History of the tuning fork. II: Evolution of the classical experiments by Weber, Rinne and Schwabach].

BACKGROUND: Since the 17th centrury it was known that sounds could be perceived via air conduction and bone conduction and that this provided a means of differentiating between hearing disorders located in the middle ear and those located in the acoustic nerve. For a long time to come, however, there was no need for such a differential diagnosis. After the invention of the tuning fork in 1711 this instrument had soon become widely used in music, but it took well over 100 years until it was introduced into physiology and otology. FROM DIRECTIONAL HEARING TO WEBER'S TEST: J. B. Venturi, a physicist in Modena, Italy, in 1802 had shown that the perception of the direction from which a sound is coming is governed by the fact that one ear is hit by the sound more intensely than the other ear. C. T. Tourtual, a physician in Münster, Germany, demonstrated in 1827 that this also holds true for sound conducted via the skull bones. He used a watch as sound source. He found that occlusion of both ear canals would increase the sensation in both ears equally, but that occlusion of only one ear would increase the sensation only in the occluded ear, thus giving the impression that the sound were coming from that side. He was interested in a comparison between vision and audition, and he concluded that with regard to recognizing the direction of a sensory signal vision was superior to audition. In the same year 1827 C. Wheatstone, a physicist in London, investigating the mode of vibration of the tympanic membrane and using a tuning fork found the same phenomena as Tourtual and some more effects. E. H. Weber, an anatomist and physiologist in Leipzig, Germany, described the very same phenomena as Tourtual and Wheatstone once more in 1834. He wanted to prove that airborne sound is perceived by the vestibulum and the semicircular canals, bone conducted sound by the cochlea. None of these investigators was thinking of a clinical use of their findings and made no such suggestion. E. Schmalz, an otologist in Dresden, Germany, in 1845 introduced the tuning fork and the test later named after Weber into otology and explained in great detail all possibilities of a diagnostic evaluation of the test. His grand achievement, however, passed unnoticed at his time. THE RINNE TEST: A. Rinne, a physician in Göttingen, Germany. In 1855 described the test which later was named after him, in an elaborate treatise on the physiology of the ear. He wanted to demonstrate that in man and animals living in the air, as opposed to those living in water, the conduction of sound via the bones of the skull is just an unavoidable side effect of sound perception. He mentioned a clinical application of his test only in a footnote and obviously never used it himself in a systematic way. His test was made generally known by Lucae in Berlin only after 1880. The value of Weber's and Rinne's tuning fork tests was much disputed even at the turn of the century and only gradually became generally accepted.

Bone Conduction↗
PubMed1997

[History of the tuning fork. III: On the way to quantitative pure-tone measurement. Pictures from the history of otorhinolaryngology, represented by instruments from the collection of the Ingolstadt German Medical History Museum].

BACKGROUND: Weber's and Rinne's tuning-fork tests were for a long time considered unreliable, as they often seemed to yield inconsistent results. The sources of error were manifold and lay in the fields of physics, physiology, pathophysiology, and psychology. When the problems came to be understood, more sophisticated instruments and techniques were developed. TECHNICAL IMPROVEMENTS IN TUNING FORKS: The prongs of the tuning fork were fitted with clamps to deaden overtones when it was put into vibration (Politzer 1870). By shifting the clamps along the prongs the tone of the tuning fork could be varied in a range up to one octave (Könlg 1878). A knob of hom or metal was fixed to the end of the shaft to ensure a good coupling to the skull when testing bone conduction (Lucae 1886). A small hammer fixed to the shaft and driven by a spring would activate the tuning fork with reproducible strength (Lucae 1899). A wedge-shaped figure drawn on the lateral surface of the clamps would allow one to optically control the amplitude of vibration (Gradenigo 1899). METHODS FOR QUANTIFICATION OF MEASURING HEARING ACUITY: The time during which a patient hears the tuning fork after it has been struck as compared to that of a normal hearing subject was measured as parameter of hearing acutiy (v. Conta 1864). A number of tuning forks at intervals of one octave each were assembled in sets to cover the whole frequency range of hearing. The most sophisticated example of these sets was the Bezold-Edelmann continuous tone series (1894). It comprised ten tuning forks with sliding clamps, two pipes of the organ type, and a Galton whistle. With this instrumentation it was possible to test the whole range of hearing. GRAPHIC PRESENTATION OF QUANTITATIVE RESULTS OF HEARING TESTING: The results of testing the hearing via air conduction and bone conduction measured in duration and calculated as percentage of normal hearing were presented in charts (Hartmann 1885, Gradenigo 1893) which can be considered precursors of modern audiograms. The evolution of these instruments and methods is described in detail and illustrated by exhibits from the museum.

Audiometry, Pure-Tone↗
PubMed1997

[2000 year history of tonsillectomy. Images from the history of otorhinolaryngology, highlighted by instruments from the collection of the German Medical History Museum in Ingolstadt].

BACKGROUND: The etymology of the anatomical terms and their use in history are elucidated: "Tonsil" (from Latin tonsa = the oar) in use since Celsus (about 40 AD). The Greek terms of that time, "antiádes", "paristhmia", were not adopted in later medical terminology. "Amygdala" (Greek/Latin = the almond) was introduced by Vesalius in 1543. Vesalius was also the first to depict the tonsils in a specimen of the whole human body; Duverney (1761) gives the first exact depiction of the pharyngeal region. Special anatomical and histological studies of the tonsils were carried out in the 19 century. DIGITAL EXTRACTION OF THE TONSILS: Cornelius Celsus in Rome (about 40 AD) described the blunt removal of the tonsils by use of the finger. This method was favoured anew by numerous laryngologists at the beginning of the 20th century when it had been realised that a gentle enucleation of the entire tonsil including its capsule was advisable against cutting off a slice, but before long this procedure was discarded again for hygienic reasons. OPERATION WITH SNARES AND CUTTING INSTRUMENTS: Precursors of special instruments for tonsillectomy were instruments designed for shortening the uvula: uvulotomy. Paré (1564) and Scultetus (1655) devised instruments that permitted placing a thread shaped like a snare around the uvula and cutting it off by strangulation. Hildanus (1646), Scultetus (1655) and Heister (1763) presented an instrument of the guillotine-type for uvulotomy. This instrument was modified by P. S. Physick (USA 1828) and used for tonsillotomy. It became the prototype for a number of similar instruments which were to follow: W. M. F. Fahnestock (USA 1832). M. Mackenzie (London 1880), G. Sluder (USA 1911). Besides these guillotines snares were also perfected and used for tonsillotomy, e.g. by W. Brünings (1908). The concentration on tonsillotomy aimed at performing the operation as quickly as possible, especially in children, as it was not yet possible to sustain general anaesthesia for a longer period of time while doing surgery in the pharynx. The operation of the tonsils, that had been started by general surgeons, at the end of the 19th century became the domain of the otolaryngologists because they had the superior technique of illumination. Important steps of progress were later on mouth-gags combined with tongue-depressors, and placing the head in a suspended and reclined position. This position had already been advocated by Killian in 1920, but it could only be introduced after improved techniques of general anaesthesia were available. These stages of historical development are described and illustrated with many details.

Germany↗
PubMed1997

Failure to detect Borna disease virus infection in peripheral blood leukocytes from humans with psychiatric disorders.

The presence of antibodies reactive with Borna disease virus (BDV) in the sera of some patients with certain psychiatric illnesses has been taken as evidence that this veterinary neurotrophic virus may occasionally infect and cause psychiatric disorders in humans. In this paper, we report the results of our studies concerning the detection of BDV-specific RNA in blood cells from patients with psychiatric diseases. Contrary to the results obtained by others, we have found no evidence for the presence of BDV-RNA in such cells. Prior work with BDV sequences in the assay environment, together with the exquisite sensitivity of RT-PCR, may account for the sporadic appearance of false positive evidence that BDV-specific RNA is present in human blood cells.

Adult↗