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Biomedical subjects

H Feldmann

Publications and source records attributed to H Feldmann.

At least 19 recordsLinked to original sources

Proteolytic processing of Marburg virus glycoprotein.

Processing of the transmembrane glycoprotein (GP) of Marburg virus involved the conversion of an endo H-sensitive, ER-specific form into an endo H-resistant, Golgi-specific precursor that was cleaved into GP(1) and GP(2). Cleavage was mediated by furin or another subtilisin-like endoprotease with similar substrate specificity as indicated by mutational analysis of the cleavage site and inhibition using peptidyl chloromethylketones. Mature GP consisted of disulfide-linked GP(1) and GP(2) subunits.

Animals↗

[Self-certitude and self-being in schizophrenic delusional patients].

When asking how a schizophrenic delusional patient can achieve a new, psychotically determined entity of his existence, we can differentiate the following aspects: 1. A quasi-transcendental organization of the delusional experience establishing the patient's singular self-certitude and the absoluteness of the delusion. 2. A reflexive self-confrontation and self-disclosure within his psychotic experience as the basis of the patient's new, psychotically different self-being. 3. The directly intrusive experience of becoming psychotic as a fundamental transformation of oneself may trigger the awareness of a specific new-beginning and therefore of a radical change in personal self-being. This means as well an existential self-seclusion.

Delusions↗

[History of injections. Pictures from the history of otorhinolaryngology highlighted by exhibits of the German History of Medicine Museum in Ingolstadt].

BACKGROUND: Injections are part of the arsenal of all medical disciplines. In addition to this common ground, each specialty has its own particular aspects; the historical development of these are presented here with respect to otorhinolaryngology. INTRAVENOUS INJECTIONS: The first experiments with intravenous injections were carried out in 1642 by a gentleman's hunting servant in eastern Germany. Similar experiments were done in 1656 by Christopher Wren, the astronomer, mathematician, and architect in Oxford, England, and a group of scientists around the physicist Robert Boyle. These experiments were prompted by new knowledge about blood circulation provided by William Harvey in 1628. The first books on the applications of intravenous infusions in humans were published in Germany by Major 1664 (Chirurgia Infusoria) and Elsholtz 1667 (Clysmatica Nova). Bladders of animals or enema syringes were used as instruments. Because of lethal accidents the infusions soon fell from favour. Köhler in Germany in 1776 eliminated a large bolus impacted in a patient's esophagus by an intravenous infusion of tartar emetic thus inducing violent vomiting. After this crucial experiment, foreign bodies in the esophagus were the most important indication for applying intravenous injections until Killian introduced extraction by esophagoscopy in 1990. CALIBRATED SYRINGES AFTER PRAVAZ: The French surgeon C. Pravaz in Lyon in 1853 invented a small syringe, the piston of which could be driven by a screw thus allowing exact dosage. A sharp needle with a pointed trocar could be introduced into the vessel making a dissection unnessessary. Pravaz used his syringe for obliteration of arterial aneurysms by injection of ferric sesquichlorate. Pravaz's syringe initiated the invention of a great number of various calibrated syringes made of glass or metal combined with glass. SUBCUTANEOUS INJECTION AND LOCAL ANAESTHESIA: The calibrated syringes were commonly used in the treatment of syphilis by mercurialization. In otorhinolaryngology, they had and still have their primary application in local anaesthesia, which was introduced by Carl Ludwig Schleich in Berlin in 1892. PARAFFIN-INJECTIONS: Around 1900 the injection of liquid paraffin for closing defects in subcutaneous tissues came into use (Gersuny in Vienna, Delangre in Tournai). This technique was immediately applied to rhinological indications such as a saddle nose (Stein 1901). This gave rise to the invention of special syringes and modifications of paraffin with different hardness and melting points. Around the middle of this century, paraffin was abandoned for this application because of serious complications, and new substances were introduced such like teflon, silicone and collagen. The historical development of these techniques of injections is described in details with many literature citations and figures.

Anesthesia, Local↗

Rpn4p acts as a transcription factor by binding to PACE, a nonamer box found upstream of 26S proteasomal and other genes in yeast.

We identified a new, unique upstream activating sequence (5'-GGTGGCAAA-3') in the promoters of 26 out of the 32 proteasomal yeast genes characterized to date, which we propose to call proteasome-associated control element. By using the one-hybrid method, we show that the factor binding to the proteasome-associated control element is Rpn4p, a protein containing a C2H2-type finger motif and two acidic domains. Electrophoretic mobility shift assays using proteasome-associated control element sequences from two regulatory proteasomal genes confirmed specific binding of purified Rpn4p to these sequences. The role of Rpn4p to function as a transregulator in yeast is corroborated by its ability of stimulating proteasome-associated control element-driven lacZ expression and by experiments using the RPT4 and RPT6 gene promoters coupled to the bacterial cat gene as a reporter. Additionally, we found the proteasome-associated control element to occur in a number of promoters to genes which are related to the ubiquitin-proteasome pathway in yeast.

Amino Acid Sequence↗

The glycoproteins of Marburg and Ebola virus and their potential roles in pathogenesis.

Filoviruses cause systemic infections that can lead to severe hemorrhagic fever in human and non-human primates. The primary target of the virus appears to be the mononuclear phagocytic system. As the virus spreads through the organism, the spectrum of target cells increases to include endothelial cells, fibroblasts, hepatocytes, and many other cells. There is evidence that the filovirus glycoprotein plays an important role in cell tropism, spread of infection, and pathogenicity. Biosynthesis of the glycoprotein forming the spikes on the virion surface involves cleavage by the host cell protease furin into two disulfide linked subunits GP1 and GP2. GP1 is also shed in soluble form from infected cells. Different strains of Ebola virus show variations in the cleavability of the glycoprotein, that may account for differences in pathogenicity, as has been observed with influenza viruses and paramyxoviruses. Expression of the spike glycoprotein of Ebola virus, but not of Marburg virus, requires transcriptional editing. Unedited GP mRNA yields the nonstructural glycoprotein sGP, which is secreted extensively from infected cells. Whether the soluble glycoproteins GP1 and sGP interfere with the humoral immune response and other defense mechanisms remains to be determined.

Animals↗

Functional analysis of 150 deletion mutants in Saccharomyces cerevisiae by a systematic approach.

In a systematic approach to the study of Saccharomyces cerevisiae genes of unknown function, 150 deletion mutants were constructed (1 double, 149 single mutants) and phenotypically analysed. Twenty percent of all genes examined were essential. The viable deletion mutants were subjected to 20 different test systems, ranging from high throughput to highly specific test systems. Phenotypes were obtained for two-thirds of the mutants tested. During the course of this investigation, mutants for 26 of the genes were described by others. For 18 of these the reported data were in accordance with our results. Surprisingly, for seven genes, additional, unexpected phenotypes were found in our tests. This suggests that the type of analysis presented here provides a more complete description of gene function.

Cell Differentiation↗

A new Clethrionomys-derived hantavirus from Germany: evidence for distinct genetic sublineages of Puumala viruses in Western Europe.

Puumala (PUU) viruses are the predominant etiologic agents of hantavirus infections in Europe. The most important reservoir is the bank vole, Clethrionomys glareolus (Cg), belonging to the subfamily Arvicolinae of the Muridae family. Here we report on the molecular characterization of the first rodent-derived sequence (PUU/Cg-Erft) from Germany. Comparison of the S and M segment coding regions revealed 92.5 and 92.8% identity, respectively, with PUU/H-9013, a human isolate from France. However, only 83.1% identity was found with the S segment of a previously reported PUU sequence from a German HFRS case (PUU/H-Berkel) indicating the co-existence of two distinct sublineages in Germany. Phylogenetic and alignment analyses of S and M segment coding regions enabled us to assign PUU viruses/sequences to at least six distinct genetic sublineages. Membership was defined by nucleotide sequence differences of < 8%, whereas a diversity of > 14% clearly outgrouped a virus/sequence. Based on S segment sequences the sublineage represented by Clethrionomys rufocanus-derived viruses from Japan diverged at a well supported node from the clade harbouring all Clethrionomys glareolus-derived European PUU viruses. A correlation between genetic relationship and geographic origin of PUU viruses was observed which may support a co-evolution of PUU viruses with distinct subspecies of their reservoir host.

Animals↗

The self adapting washer for lag screw fixation of mandibular fractures: finite element analysis and preclinical evaluation.

Besides rigid fixation, lag screws have distinct advantages compared with plates in appropriate indications in mandibular fractures. However, in current lag screw systems, the relatively small area of the screw head has to transfer the tensile force which can exceed 1000 N in the symphysis, to the thin cortical bone plate. Countersinking, which is obligatory in most systems, will weaken the cortical plate. Finite element analysis (FEA) revealed that load in this situation can exceed the normal tensile strength of metal and bone. Consequently, a new washer was constructed which both increased the supporting surface and did not require countersinking. The washer is self adapting (SAW) to the cortical plate in a defined position, forming a ball and socket joint with the screw head. Using the FEA model, a ten-fold reduction in load on bone and metal was observed with the new washer. In a miniature pig mandibular symphysis fracture model, the clinical applicability and a favourable histological reaction were demonstrated, compared with conventional lag screw designs.

Alloys↗

Polymerase chain reaction detection of Puumala virus RNA in formaldehyde-fixed biopsy material.

BACKGROUND: Infections with hantaviruses, mainly Clethrionomys-derived Puumala viruses, are known causes of acute renal failure [hemorrhagic fever with renal syndrome (HFRS)] in western Europe. Laboratory diagnosis is primarily based on serology. At the time of clinical symptoms, viral RNA can hardly be detected in the blood or urine, indicating that polymerase chain reaction (PCR) is of little diagnostic value for these infections. Biopsy material is usually formaldehyde-fixed and, thus, regarded as poor quality for PCR applications. The aim of this study was to establish a technique to retrieve such material for laboratory diagnostic. METHODS: Formaldehyde-fixed, paraffin-embedded kidney biopsies of 14 patients with renal failure either clinically suspected for HFRS (7 cases) or caused by unknown (2 cases) or known other causes (drugs, sarcoidosis; 5 cases) were histologically investigated. An established S segment-specific PCR assay was applied to RNA isolated from the biopsies, and amplification products were verified by direct sequence determination. RESULTS: Investigations revealed a typical histopathological appearance for hantavirus infections in all seven suspected HFRS cases and one case of unknown cause. With five of the suspected HFRS cases, hantavirus-specific RNA was detected. Sequence comparison revealed a close relationship to corresponding nucleoproteins of known Puumala viruses. CONCLUSION: The established technique provides a simple and powerful tool that expands the diagnostic possibilities, especially for otherwise unidentified or retrospective cases. It further allows insight into the molecular epidemiology of HFRS-causing agents.

Amino Acid Sequence↗

[The nasopharynx and pharyngeal tonsil in the history of otology and rhinology. Pictures from the history of otorhinolaryngology, presented by instruments from the collection of the Ingolstadt Medical History Museum].

Anatomy, nomenclature, first clinical observations: In ancient Greece and Rome and in the Middle Ages the posterior opening of the nasal passage was known (Greek "choane" = funnel) as an atomical structure, and it was also known that chronic nasal catarrh is common in children, but it was not realized that this was associated with special pathological alterations. The anatomist H. von Luschka in Tübingen, Germany, was the first to describe the nasopharynx in detail, and he coined the term "pharyngeal tonsil." The otologists of the 19th century like Kramer and Toynbee had placed the Eustachian tube in the center of their investigations and carried out numerous dissections with demonstration of the tubal orifice. They also knew that middle ear infections usually originated in the nasopharynx, but they did not realize that the hypertrophic pharyngeal tonsil was the cause. Posterior rhinoscopy and the diagnosis of the hypertrophy of the pharyngeal tonsil: Czermak in Budapest in 1860 had invented posterior rhinoscopy, and he was the first to diagnose hypertrophic alterations around the tubal orifice and the first to realize that they were the cause of tubal malfunction. Wilhelm Meyer in Kopenhagen in 1868 and 1873-1874 described hypertrophy of the pharyngeal tonsil ("adenoid vegetations") in detail and associated this finding with a syndrome characterized by mouth-breathing, snoring, a typical facial expression, deafness, recurring middle-ear affections, and characteristic alterations of speech. He based his conclusions on 5 years' experience with 175 observations in his office and on examination of 2700 children in Denmark and England. Surgical therapy of adenoid vegetations: Voltolini in Breslau in 1865 had observed a few cases of hypertrophy of the pharyngeal tonsil, and he was the first to treat them by galvanic cauterization. Meyer developed various instruments for reducing the pharyngeal tonsil. They were introduced through the nose while the application of the instrument was assisted digitally via the mouth and pharynx. The operation of the pharyngeal tonsil was adopted very eagerly by a great number of nasal surgeons. Among the numerous special instruments that subsequently were invented the most promising was the ring knife invented by Gottstein in 1886. Anesthesia and positioning: The pioneers of this intervention, Voltolini, Meyer, Semon and others, all operated without any anesthesia, but they usually would need up to 12 sessions (Semon) until the pharyngeal tonsil had been sufficiently reduced. Beckmann in Berlin, who had invented a modification of Gottstein's ring knife, reported in 1897 on more than 5000 cases in which he had removed the adenoids in just one session, in each case without anesthesia. Besides these surgeons, others used cocaine for local anesthesia or chlorethyl or bromethyl for general anesthesia. The German surgeon Edmund Rose (Berlin and Zürich) in 1874 introduced the position with the head suspended for larger interventions like resection ot the maxilla. Rudloff in Wiesbaden, Germany, in 1900 adopted this position for adenoidectomy, but this was generally accepted only after the mouth gags developed by Davis-Boyle and Negus had been introduced. The diagnostic and surgical interventions in the nasopharynx were a powerful link in the process of fusion between otology and rhinolaryngology around the turn of the century. This historical development is described in great detail with many figures and quotations from the literature.

Adenoidectomy↗

[2000-year history of the ear syringe and its relationship to the enema. Images from the history of otorhinolaryngology, represented by instruments from the collection of the Ingolstadt Medical History Museum].

SYRINGES WITH A PISTON AND THEIR USE AS "CLYSTER ORICULARIUS" IN THE ANCIENT ROME: Syringes with a piston were already known in ancient times and have been mentioned as a device for spraying rose water (Philon of Byzantium, about 230 BC), and for fighting fires (Heron of Alexandria about 110 AD). Celsus mentions it several times in his grand opus "De Medicina" (1st century AD) in the treatment of purulent discharge from the ear and for removing foreign bodies from the external ear canal. He always calls it "clyster oricularius", i.e. ear syringe, even when he describes its use in applications other than otological, such as in urology. Later the ear syringe fell from favor for a very long time and was reinvented only at the beginning of the 19th century. IRRIGATION OF THE BOWELS, FROM THE BAG SYRINGE TO THE PISTON SYRINGE: Irrigations of the bowels, clysters, were performed from ancient times to the 18th century with a baglike syringe using the bladder of animals as a pouch. Syringes with a piston were used by barbers and surgeons only for cleansing wounds or irrigating natural cavities of the body. Irrigation of the external ear canal had completely fallen from favor. In France in the 18th century large syringes with a piston made of tin oder brass came into use for enemas and replaced the old baglike devices. THE REINVENTION OF THE EAR SYRINGE AFTER THE PROTOTYPE OF THE ENEMA SYRINGE: Itard, an otologist in France in 1821, was the first to describe irrigating the ear with a syringe to remove hard wax. He recommended using an enema syringe ("seringue à lavement") for the procedure. Soon after his publication special ear syringes of appropriate size were developed and described by Beck in Freiburg, Germany, in 1827; by Fabrizi in Modena, Italy, 1839; and Schmalz in Dresden, Germany, 1846, who also introduced the kidney-shaped bowel for catching the water. Apart from that, small baglike syringes made of rubber were devised especially for use by the patient himself (Kramer, Berlin, 1860). This historical development is described in detail and illustrated by numerous figures.

Enema↗

Serologic survey among hospital and health center workers during the Ebola hemorrhagic fever outbreak in Kikwit, Democratic Republic of the Congo, 1995.

From May to July 1995, a serologic and interview survey was conducted to describe Ebola hemorrhagic fever (EHF) among personnel working in 5 hospitals and 26 health care centers in and around Kikwit, Democratic Republic of the Congo. Job-specific attack rates estimated for Kikwit General Hospital, the epicenter of the EHF epidemic, were 31% for physicians, 11% for technicians/room attendants, 10% for nurses, and 4% for other workers. Among 402 workers who did not meet the EHF case definition, 12 had borderline positive antibody test results; subsequent specimens from 4 of these tested negative. Although an old infection with persistent Ebola antibody production or a recent atypical or asymptomatic infection cannot be ruled out, if they occur at all, they appear to be rare. This survey demonstrated that opportunities for transmission of Ebola virus to personnel in health facilities existed in Kikwit because blood and body fluid precautions were not being universally followed.

Adult↗

Prevalence of IgG antibodies to Ebola virus in individuals during an Ebola outbreak, Democratic Republic of the Congo, 1995.

During the 1995 outbreak of Ebola (EBO) hemorrhagic fever in Kikwit, Democratic Republic of Congo, two surveys using a new ELISA for EBO (subtype Zaire) virus antigen were conducted to assess the prevalence of EBO IgG antibodies among residents of Kikwit and the surrounding area. The first study determined the proportion of antibody-positive individuals who were self-identified forest and city workers from the Kikwit area. Serum samples from 9 (2.2%) of 414 workers had IgG EBO antibodies. The second study determined the proportion of EBO antibody-positive individuals who lived in villages surrounding Kikwit. The prevalence of IgG EBO antibodies in this population was 9.3% (151161). The difference in the overall prevalence of EBO antibodies may indicate that villagers have a greater chance of exposure to EBO virus compared with those living in and in close proximity to cities.

Adolescent↗

Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit.

A cohort of convalescent Ebola hemorrhagic fever (EHF) patients and their household contacts (HHCs) were studied prospectively to determine if convalescent body fluids contain Ebola virus and if secondary transmission occurs during convalescence. Twenty-nine EHF convalescents and 152 HHCs were monitored for up to 21 months. Blood specimens were obtained and symptom information was collected from convalescents and their HHCs; other body fluid specimens were also obtained from convalescents. Arthralgias and myalgia were reported significantly more often by convalescents than HHCs. Evidence of Ebola virus was detected by reverse transcription-polymerase chain reaction in semen specimens up to 91 days after disease onset; however, these and all other non-blood body fluids tested negative by virus isolation. Among 81 initially antibody negative HHCs, none became antibody positive. Blood specimens of 5 HHCs not identified as EHF patients were initially antibody positive. No direct evidence of convalescent-to-HHC transmission of EHF was found, although the semen of convalescents may be infectious. The existence of initially antibody-positive HHCs suggests that mild cases of Ebola virus infection occurred and that the full extent of the EHF epidemic was probably underestimated.

Adolescent↗

Characterization of the L gene and 5' trailer region of Ebola virus.

The nucleotide sequences of the L gene and 5' trailer region of Ebola virus strain Mayinga (subtype Zaire) have been determined, thus completing the sequence of the Ebola virus genome. The putative transcription start signal of the L gene was identical to the determined 5' terminus of the L mRNA (5' GAGGAAGAUUAA) and showed a high degree of similarity to the corresponding regions of other Ebola virus genes. The 3' end of the L mRNA terminated with 5' AUUAUAAAAAA, a sequence which is distinct from the proposed transcription termination signals of other genes. The 5' trailer sequence of the Ebola virus genomic RNA consisted of 676 nt and revealed a self-complementary sequence at the extreme end which may play an important role in virus replication. The L gene contained a single ORF encoding a polypeptide of 2212 aa. The deduced amino acid sequence showed identities of about 73 and 44% to the L proteins of Ebola virus strain Maleo (subtype Sudan) and Marburg virus, respectively. Sequence comparison studies of the Ebola virus L proteins with several corresponding proteins of other non-segmented, negative-strand RNA viruses, including Marburg viruses, confirmed a close relationship between filoviruses and members of the Paramyxovirinae. The presence of several conserved linear domains commonly found within L proteins of other members of the order Mononegavirales identified this protein as the RNA-dependent RNA polymerase of Ebola virus.

Amino Acid Sequence↗

The nonstructural small glycoprotein sGP of Ebola virus is secreted as an antiparallel-orientated homodimer.

The nonstructural small glycoprotein sGP, which unlike the transmembrane GP is synthesized from primary nonedited mRNA species, is secreted from infected cells as a disulfide-linked homodimer. Site-directed mutagenesis of all cysteine residues revealed that dimerization is due to an intermolecular disulfide linkage between cysteine residues at positions 53 and 306. Formic acid hydrolysis of sGP demonstrated that sGP dimers consist of monomers in antiparallel orientation. Another editing product of the GP gene of Ebola virus (ssGP), which shares 295 amino-terminal amino acid residues with sGP, is secreted from cells in a monomeric form due to the lack of the carboxyl-terminal part (present in sGP), including cysteine at position 306.

Animals↗