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Biomedical subjects

H Feldmann

Publications and source records attributed to H Feldmann.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Tympanic membrane massage, origin and decline of a promising therapeutic concept].

BACKGROUND, APPLICATION OF STATIC PRESSURE AT THE TYMPANIC MEMBRANE: Cleland in London (1741) presumed that the pressure of a strong sound wave would push the tympanic membrane inward, thereby causing deafness. He recommended correcting this situation by applying suction to the auditory canal, and he demonstrated a small tube suitable for this purpose. Toynbee in London (about 1860) realized that, following a malfunction of the Eustachian tube, a negative pressure would develop in the middle ear and draw the tympanic membrane inward, thus causing hearing loss. This concept resulted in efforts to actively support the aeration of the middle ear via the Eustachian tube. In addition to these measures, Politzer in Vienna (1867) suggested blocking the external auditory canal tightly so that resorption of the air would produce negative pressure, counteracting the low pressure in the middle ear. Lucae in Berlin (1874) proposed the theory that the two small muscles in the drum would act as antagonists on the tympanic membrane and accommodate the ear for high and low-pitched sounds respectively. He tried to correct malpositions of the tympanic membrane due to a misbalance of the two muscles by applying static positive or negative pressure in the auditory canal. APPLICATION OF ALTERNATING PRESSURE AT THE TYMPANIC MEMBRANE: Siegle in Stuttgart (1864) put forward the idea that repeated strong movements driven by the pneumatic ear speculum that he had invented would be able to loosen adhesions in the middle ear. Lucae (1884) later devised an elastic probe to be placed on the short process of the malleus for massage of the ossicular chain. Delstanche in Brussels (1885) presented two instruments called "rarefacteur" and "masseur du tympan et des osselets" which in the auditory canal would produce negative pressure or alternating pressure respectively. The next step were suggestions and devices enabling the patient to treat himself for reduced mobility of the tympanic membrane or the ossicular chain, such as alternating pressure on the tragus, or tubes to conduct pressure from the mouth or a rubber bag to the ear. With the aim of speeding up the frequency of the pressure impulses, mechanic pumps were constructed, which were first driven by hand, later on by electric power. CRITICAL EVALUATION: At the turn of the century numerous attempts were made to evaluate the effectiveness of the pneumatic massage of the middle ear and to specify the indication for this kind of treatment. Although no convincing and predictable results could be demonstrated and even harmful effects had been observed in animal experiments, the massage of the tympanic membrane continued its triumphant march for half a century. The reason for this seems to be the suggestive and plausible therapeutic approach to a well known pathology of the middle ear. Since the middle of this century it has been regarded as obsolete and is no longer mentioned in text books. The history of this episode is presented in detail.

Deafness↗
PubMed1996

[The Eustachian tube and its role in the history of otology. Images from the history of otorhinolaryngology, presented by instruments from the collection of the Ingolstadt German History Museum].

Even in ancient times the existence of an open pathway between the ear and the respiratory tract was assumed. Up to the middle ages, however, Aristotle's idea that the air in the ear is an innate part of the body prevailed. The first anatomical description of the tube was given by Eustachius (1563). He still adhered to the concept of "innate air" and regarded the tube only as a pathway for draining pathological matter from the tympanic cavity. Duverney (1683) realized that an important function of the tube was replacing and adjusting the pressure of the air in the tympanic cavity. He thought that the tube is permanently open, thus offering a vent to the air, when the tympanic membrane is moving inwards and outwards. Valsalva (1704) discovered a muscle for opening the tube, and he presumed that in hearing this muscle would come into action. He described the maneuver that is named after him as a method to expel pus from the tympanic cavity into the external auditory canal. E.G. Guyot, a postmaster in Versailles, was the first to try catheterization of his own Eustachian tube via the mouth. Cleland (1741) inserted the catheter via the nose, and Wathen (1756) after studies on corpses described in detail the technique how to carry out this procedure. The therapeutic application of Eustachian catheterization as practiced by physicians such as Itard (1821) centered around irrigation with water and medications as well as inflation of various fumes. Deleau (1836) later advocated a douche of pure air and, in analogy to the auscultation of the lung, described the different noises that could be perceived during this procedure. Numerous models of pumps were constructed for this air douche, which became one of the most widely used therapeutical means in otology. There were also lethal incidents caused by cutaneous emphysemata. Toynbee realized that at rest the tube is closed and that there is a constant absorption of air in the tympanic cavity. The tube would be opened only by the act of swallowing and air would then be allowed to enter to equalize pressure. He believed that the maneuver he described, namely swallowing while the nostrils are closed, would produce a positive pressure in the tympanic cavity. He died when he applied these maneuvers in order to press fumes of chloroform or cyanic acid into his ears to treat his tinnitus. Politzer could demonstrate that after Toynbee's maneuver the middle ear is left with a negative pressure, and consequently, in 1861-63, he devised his own method for actively inflating the middle ear. The history of these events is described in detail and illustrated by a number of figures and anecdotal episodes.

Eustachian Tube↗
PubMed1996

Inhibition of bunyaviruses, phleboviruses, and hantaviruses by human MxA protein.

Viruses of the Bunyaviridae family cause a variety of diseases ranging from uncomplicated fever to potentially lethal encephalitis and hemorrhagic fever. Little is known about the factors determining pathogenicity in the vertebrate host. Interferons have been reported to be inhibitory, but their mode of action against members of the Bunyaviridae has not yet been elucidated. The interferon-induced MxA protein encoded on human chromosome 21 is a large GTPase with antiviral activity against distinct negative-strand RNA viruses, notably influenza viruses. Here we show that MxA inhibits representative members of the Bunyaviridae family by interacting with an early step of virus replication. When constitutively expressed in stably transfected Vero cells, MxA prevented the accumulation of viral transcripts and proteins of Hantaan virus (genus Hantavirus). Other members of the family such as La Crosse virus (genus Bunyavirus) and Rift Valley fever virus and sandfly fever virus (both genus Phlebovirus) were likewise inhibited, and virus titers were reduced up to 10(4)-fold. Our data indicate that humans have evolved a mechanism of controlling these viruses irrespective of differences in viral coding strategies.

3T3 Cells↗
PubMed1996

Filovirus-induced endothelial leakage triggered by infected monocytes/macrophages.

The pathogenetic mechanisms underlying hemorrhagic fevers are not fully understood, but hemorrhage, activation of coagulation, and shock suggest vascular instability. Here, we demonstrate that Marburg virus (MBG), a filovirus causing a severe form of hemorrhagic fever in humans, replicates in human monocytes/macrophages, resulting in cytolytic infection and release of infectious virus particles. Replication also led to intracellular budding and accumulation of viral particles in vacuoles, thus providing a mechanism by which the virus may escape immune surveillance. Monocytes/macrophages were activated by MBG infection as indicated by tumor necrosis factor alpha (TNF-alpha) release. Supernatants of monocyte/macrophage cultures infected with MBG increased the permeability of cultured human endothelial cell monolayers. The increase in endothelial permeability correlated with the time course of TNF-alpha release and was inhibited by a TNF-alpha specific monoclonal antibody. Furthermore, recombinant TNF-alpha added at concentrations present in supernatants of virus-infected macrophage cultures increased endothelial permeability in the presence of 10 micron H2O2. These results indicate that TNF-alpha plays a critical role in mediating increased permeability, which was identified as a paraendothelial route shown by formation of interendothelial gaps. The combination of viral replication in endothelial cells (H.-J. Schnittler, F. Mahner, D. Drenckhahn, H.-D. Klenk, and H. Feldmann, J. Clin. Invest. 19:1301-1309, 1993) and monocytes/macrophages and the permeability-increasing effect of virus-induced cytokine release provide the first experimental data for a novel concept in the pathogenesis of viral hemorrhagic fever.

Base Sequence↗
PubMed1995

[Trans-subjective practice in schizophrenic delusions].

In schizophrenic delusion, the world of other humans is not so much the scope of events and actions; the patient rather sees himself as actually related to others, while including "the other persons" in the delusion of persecution as a crucial point of reference. Delusion, therefore, has a referential structure. When analysing the referential structure of "being persecuted", it is shown to be unilaterally transitive, the patient being, however, the ontological first reference point. The relationship to others in schizophrenic delusion cannot, however, achieve intersubjectivity; its significance is merely trans-subjective.

Communication↗
PubMed1995

[Collapse of the nasal alae and instruments for treating this condition, especially with the Feldbausch nasal dilator. Pictures from the history of otorhinolaryngology, presented by instruments from the collection of the German Museum of Medical History in Ingolstadt].

Although the anatomy of the nasal muscles and the active movement of the nasal alae brought about by them, were already known in ancient times (Galenos), it was only at the end of the 19th century that the collapse of the nasal alae was recognized as a passive mechanism obstructing the inspiratory air passages. Since surgical methods for treating this condition were not available at that time, various small gadgets to be introduced into the nasal vestibulum were invented for stabilising the alae. Among these, Feldbausch's nasal dilator was the best known. It was in use up to the middle of this century, but then became completely obsolete. The history of this chapter of rhinology is related primarily by means of literal quotations of the phrases with which the authors presented their devices and praised their virtues.

Germany↗
PubMed1995

[Treatment of acute and chronic laryngeal and tracheal stenoses in the 19th and beginning of the 20th century by tracheotomy, coniotomy, intubation and dilatation. Pictures from the history of otorhinolaryngology illustrated by instruments from the collection of the Ingolstadt Medical History Museum].

Although tracheotomy had been described in the Middle Ages and especially in the 17th century in writings (Fabricius d'Aquapendente 1620) and illustrations (Scultetus 1645), there was hardly any possibility of actually performing this operation as a life-saving intervention until the middle of the 19th century. It was only after suitable cannulae had been introduced by Trousseau in 1851 (double cannula with removeable insert) that tracheotomy became a routine procedure, and it was immediately carried out in a great many cases of diphtheria, croup, typhus, and lues, which often caused critical dispnea. Within the following 25 years, all technical modifications of cannulae were devised that are in use up to this day: the flap valve for the artificial larynx (1861), inflatable cuff (1871), and extra long flexible cannula. Beginning in 1885, O'Dwyer's method of intubation became established as an alternative to tracheotomy. Both procedures, like the underlying disease itself, frequently resulted in a permanent stenosis of the larynx or the trachea rendering decannulation impossible. Since about 1870 the treatment of these stenoses, primarily by bougienage, became an important issue in laryngology, which had just been established as a discipline in its own right. The history of this evolution and the therapeutic approaches by Schrötter in Vienna and Thost in Hamburg are described in detail, including their specially devised equipment. Apart from that, other medical aspects of historical interest around the turn of the century are mentioned, such as artificial nutrition by subcutaneous injections and tracheotomy in horses.(ABSTRACT TRUNCATED AT 250 WORDS)

Germany↗
PubMed1995

[The Galton whistle and discovery of presbycusis. Images from the history of otorhinolaryngology, exemplified by equipment from the collection of the Ingolstadt German Medical History Museum].

One of the many interests of Sir Francis Galton (1822-1911), a singularly versatile English research worker, was anthropometry, i.e. measuring and comparing physical attributes in men. Here he introduced the concept of eugenics. He thought that the upper hearing threshold for high-pitched tones might be an attribute specific to each species, and in order to prove this he devised a whistle which was later named after him. Using this instrument he found that the upper hearing threshold in animals actually differs very much with the species and that in humans it is regularly depressed with age. The relevant passages of his book Inquiries into Human Faculty of 1883 are quoted in translation. Burckhardt-Merian from Basel, Switzerland, introduced Galton's whistle into otology in 1885. Appropriate instruments were soon developed by König in Paris and Edelmann in Munich and became commercially available. Zwaardemaker in Utrecht, the Netherlands, was the first to systematically investigate hearing in the elderly using Galton's whistle, and he derived from these studies what he called the "prebyacusial law." Technical details of Galton's whistle are described with reference to Edelmann's final refined version of the instrument of 1900. During the first 30 years of this century, Galton's whistle was in wide use, but due to unavoidable inherent flaws it later gave way to the monochord and eventually to tone audiometry.

Aged↗
PubMed1995

[The monochord, its path from Pythagorean musicology to testing the upper auditory tone limit. Pictures from the history of otorhinolaryngology, represented by instruments of the Ingolstadt German Medical History Museum].

The monochord consists of a frame with a string or pianowire stretched across it. The length of the wire can be varied by a movable bridge. The string or wire is plucked, hit, or bowed, producing transverse vibrations. In this mode the number of vibrations per second is dependent on the length, tension, and thickness of the string. In ancient times, the Pythagoreans used such an instrument to study the natural laws underlying musical intervals; in the 19th century it also served for various other physical experiments. F. A. Schulze, physicist in Marburg, Germany, introduced the monochord for testing the upper tone limit in 1908. He produced longitudinal vibrations by rubbing the wire with a piece of felt moistened with benzol. The vibrations of this mode are dependent only on the length of the wire and the elasticity of the material; they are independent of its tension and thickness. H. J. L. Struycken, otologist in Breda, Holland, presented an improved type of monochord in 1910 which also allowed testing bone conduction. K. L. Schaefer, physiologist in Berlin, modified Struycken's instrument in such a way that bowing the wire or hitting it with a small hammer also produced transverse vibrations. This enlarged the range of tones in the lower region. In this combined version the monochord was an indispensable piece of hearing testing equipment before the era of electronic audiometers. The technical development and clinical application of the monochord is described in detail.

Audiometry, Pure-Tone↗
PubMed1995

[From otoscope to ophthalmoscope and back. The interwoven history of their invention and introduction into medical practice. Pictures from the history of otorhinolaryngology, illustrated by instruments from the collection of the Ingolstadt German Medical History Museum].

Friedrich Hofmann, medical officer in Burgsteinfurt, Westphalia, Germany, in 1841 described a concave mirror with a central aperture in it as the ideal instrument that allowed reflecting and focussing light into the external auditory canal and simultaneously inspecting the tympanic membrane without obstructing either the light or the view. He recommended his device also for the inspection of other concealed regions of the body. His invention was referred to by Martell Frank in his textbook of otology in 1845, but otherwise attracted no attention. Hermann Helmholtz, physiologist in Königsberg, East Prussia, devised his ophthalmoscope in 1850-51 in order to study the phenomenon of glowing eyes. With this instrument he was the first to see the retina of a living human. As means of illumination he used small panes of glass similar to cover-glasses which were introduced into the common visual axis of the observer and the subject at such an angle that light from a lamp was reflected into the subject's eye while the observer inspected the subject's retina through the glass and an appropriate lens. He recommended this type of illumination also for otoscopy. His invention was at once acclaimed throughout the world and opened completely new opportunities in ophthalmology. The slanting panes of glass, however, were not the ideal solution for illumination. It was only one year later that Ruete in Göttingen replaced them with a concave mirror with a central aperture, and there is every indication that Frank's report on Hofmann's mirror had suggested this technique to him. During the following two years quite a number of other modifications of the ophthalmoscope were constructed, all of them using the concave mirror with a central aperture, which soon became synonymous with the ophthalmoscope as such. Von Tröltsch, otologist and ophthalmologist in Würzburg, presented a concave mirror with a central aperture for otoscopy in Paris in 1855-56. His instrument was obviously derived from the already well known ophthalmoscope by adapting the diameter and focal distance to this special application. His primary concern was to use daylight instead of artificial light for otoscopy. Von Tröltsch did not know Hofmann's publication, but later did not hesitate to acknowledge Hofmann's priority. It was von Tröltsch who popularized the concave reflector with a central aperture as the instrument of choice in otoscopy, and subsequently also for rhinoscopy and laryngoscopy. Further modifications were devised to have the hands free for operations. Thus the reflector was fixed to the forehead by strap and buckle or a vulcanite band, or it was provided with a handle that was to be held between the teeth, or it was attached to a spectacle frame. The details of this interwoven history are related and highlighted by numerous quotations and historical illustrations.

Ear↗
PubMed1995

A newly recognized virus associated with a fatal case of hantavirus pulmonary syndrome in Louisiana.

Genetic analysis of virus detected in autopsy tissues of a fatal hantavirus pulmonary syndrome-like case in Louisiana revealed the presence of a previously unrecognized hantavirus. Nucleotide sequence analysis of PCR fragments of the complete S and M segments of the virus amplified from RNA extracted from the tissues showed the virus to be novel, differing from the closest related hantavirus, Sin Nombre virus, by approximately 30%. Both genome segments were unique, and there was no evidence of genetic reassortment with previously characterized hantaviruses. The primary rodent reservoir of Sin Nombre virus, the deer mouse Peromyscus maniculatus, is absent from Louisiana. Thus, the virus detected in Louisiana, referred to here as Bayou virus, must possess a different rodent reservoir.

Base Sequence↗
PubMed1995

Identification of a new North American hantavirus that causes acute pulmonary insufficiency.

In May 1993, a pulmonary disease syndrome with novel clinical and epidemiologic features was identified in the southwestern United States. Healthy young adults developed a febrile prodrome followed by the rapid onset of often lethal acute respiratory distress. Although an infectious disease was suspected, intensive investigations initially failed to identify the causative agent. Multiple specialized microbiology laboratories at the National Center for Infectious Diseases (Centers for Disease Control and Prevention) applied classic serologic and culture methods as well as recently developed molecular biological techniques to samples collected from field investigations of the patients. Serologic tests detected the presence of an active immune response to a hantavirus. Reverse transcription and polymerase chain reaction amplification of RNA extracted from human tissues used primers designed from sequences of known hantaviruses to demonstrate genomic sequences of a novel hantavirus. Immunohistochemistry showed the presence of hantavirus antigens in the endothelium of lung tissues from patients and provided the final pathogenetic link to this group of viruses. These methods were concordantly positive in virtually all samples available from 18 patients with compatible clinical histories identified between January and July 1993. Test results of control subjects and searches for other agents in identified cases were negative. This newly recognized hantavirus causes a novel syndrome of acute pulmonary edema and shock; the pathogenesis is related to the presence of virus antigens in the pulmonary capillaries. The virus may be an important cause of severe and fatal disease presenting as adult respiratory distress syndrome in otherwise healthy persons.

Antibodies, Viral↗
PubMed1994

Complete DNA sequence of yeast chromosome II.

In the framework of the EU genome-sequencing programmes, the complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome II (807 188 bp) has been determined. At present, this is the largest eukaryotic chromosome entirely sequenced. A total of 410 open reading frames (ORFs) were identified, covering 72% of the sequence. Similarity searches revealed that 124 ORFs (30%) correspond to genes of known function, 51 ORFs (12.5%) appear to be homologues of genes whose functions are known, 52 others (12.5%) have homologues the functions of which are not well defined and another 33 of the novel putative genes (8%) exhibit a degree of similarity which is insufficient to confidently assign function. Of the genes on chromosome II, 37-45% are thus of unpredicted function. Among the novel putative genes, we found several that are related to genes that perform differentiated functions in multicellular organisms of are involved in malignancy. In addition to a compact arrangement of potential protein coding sequences, the analysis of this chromosome confirmed general chromosome patterns but also revealed particular novel features of chromosomal organization. Alternating regional variations in average base composition correlate with variations in local gene density along chromosome II, as observed in chromosomes XI and III. We propose that functional ARS elements are preferably located in the AT-rich regions that have a spacing of approximately 110 kb. Similarly, the 13 tRNA genes and the three Ty elements of chromosome II are found in AT-rich regions. In chromosome II, the distribution of coding sequences between the two strands is biased, with a ratio of 1.3:1. An interesting aspect regarding the evolution of the eukaryotic genome is the finding that chromosome II has a high degree of internal genetic redundancy, amounting to 16% of the coding capacity.

Base Composition↗
PubMed1994

Yta10p, a member of a novel ATPase family in yeast, is essential for mitochondrial function.

The yeast gene, YTA10, encodes a member of a novel family of putative ATPases. Yta10p, as deduced from the nucleotide sequence, is 761 amino acids in length (predicted molecular mass 84.5 kDa). The amino acid sequence of Yta10p exhibits high similarity to two other yeast proteins, Yta11 and Yta12, and to E. coli FtsH. Several features of Yta10p are compatible with its localization in mitochondria. We report here that Yta10p is a yeast mitochondrial protein and that import is dependent on a membrane potential and accompanied by processing to a protein of approximately 73 kDa. Disruption of YTA10 leads to a nuclear petite phenotype and to a loss of respiratory competence, as shown by spectrophotometric measurement of the activities of respiratory complexes I-III and IV, respectively. These findings together with the high similarity of Yta10p to several ATP-dependent proteases suggest that Yta10p is a mitochondrial component involved, directly or indirectly, in the correct assembly and/or maintenance of active respiratory complexes.

Adenosine Triphosphatases↗
PubMed1994

Yta10p is required for the ATP-dependent degradation of polypeptides in the inner membrane of mitochondria.

Incompletely synthesized polypeptides in the mitochondrial inner membrane are subject to rapid proteolysis. We demonstrate that Yta10p, a mitochondrial homologue of a conserved family of putative ATPases in Saccharomyces cerevisiae, is essential for this proteolytic process. Yta10p-dependent degradation requires divalent metal ions and the hydrolysis of ATP. Yta10p is an integral protein of the inner mitochondrial membrane exposing the carboxy terminus to the mitochondrial matrix space. Based on the presence of consensus binding sites for ATP, and for divalent metal ions found in a number of metal dependent endopeptidases, a direct role of Yta10p in the proteolytic breakdown of membrane-associated polypeptides in mitochondria is suggested.

Adenosine Triphosphatases↗
PubMed1994

Suppressors of nmtl-181, a conditional lethal allele of the Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase gene, reveal proteins involved in regulating protein N-myristoylation.

Several essential Saccharomyces cerevisiae proteins require myristate to be covalently bound to their amino-terminal glycine for biological activity. Protein N-myristoylation is catalyzed by myristoyl-CoA:protein N-myristoyl-transferase, Nmt1p. nmt1-181 encodes a mutant enzyme with a Gly451-->Asp substitution. nmt181p has a reduced affinity for myristoyl-CoA and produces global defects in protein N-myristoylation at > or = 30 degrees C. nmt1-181 results in growth arrest at various stages of the cell cycle within 1 hr after cells are shifted to > or = 30 degrees C and lethality within 8 hr. The growth-arrest phenotype and loss of viability do not require components of the mating pathway and are associated with lysis sensitivity that may be related to undermyristoylation of two protein phosphatases, Ppz1p and Ppz2p. Growth can be rescued at 30 degrees C by adding myristate or sorbitol to the medium or by removing inosine. Cells can be rescued at 37 degrees C by overexpressing nmt1-181p or Nmt1p or by adding myristate to the medium. Selection of high-copy suppressors of the myristate auxotrophy and lethality observed at 37 degrees C yielded only NMT1, whereas six unlinked suppressors of the myristoylation defect (SMD1-6) were obtained when the screen was conducted at 30 degrees C. The protein products of three SMD loci were identified: (i) cdc39-delta 1.7p, which transactivates NMT1; (ii) Fas1p, the beta subunit of the fatty acid synthetase complex, activates FAS2's promoter and increases myristoylation of Gpa1p; and (iii) Pho5p, the major secreted acid phosphatase produced by this yeast. PHO5 is normally induced when yeast are grown in phosphate-depleted medium. Removal of inorganic phosphate from the medium also rescues nmt1-181 cells at 30 degrees C. PHO5's mechanism of suppression of nmt1-181 appears to involve, at least in part, activation of FAS2 transcription and a resulting effect on FAS1 expression. There is an inverse relationship between cellular N-myristoyltransferase and secreted acid phosphatase activities. These observations provide a potential mechanism for coupling phosphate metabolism with the regulation of myristoyl-CoA synthesis and protein N-myristoylation.

Acid Phosphatase↗
PubMed1994

Complete DNA sequence of yeast chromosome XI.

The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome XI has been determined. In addition to a compact arrangement of potential protein coding sequences, the 666,448-base-pair sequence has revealed general chromosome patterns; in particular, alternating regional variations in average base composition correlate with variations in local gene density along the chromosome. Significant discrepancies with the previously published genetic map demonstrate the need for using independent physical mapping criteria.

Base Sequence↗