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Biomedical subjects

H Feldmann

Publications and source records attributed to H Feldmann.

At least 37 records · Page 2Linked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

Release of viral glycoproteins during Ebola virus infection.

Maturation and release of the Ebola virus glycoprotein GP were studied in cells infected with either Ebola or recombinant vaccinia viruses. Significant amounts of GP were found in the culture medium in nonvirion forms. The major form represented the large subunit GP1 that was shed after release of its disulfide linkage to the smaller transmembrane subunit GP2. The minor form were intact GP1,2 complexes incorporated into virosomes. Vector-expressed GP formed spikes morphologically indistinguishable from spikes on virus particles, indicating that spike assembly is independent of other viral proteins. Analysis of a truncation mutant revealed an early and almost complete release of GP1,2 molecules, showing that membrane anchoring is mediated by the carboxy-terminal hydrophobic domain of GP2. We have also compared wild-type virus which requires transcriptional editing for synthesis of full-length GP with a variant that does not depend on editing. Both viruses released comparable amounts of GP1, but the variant expressed only minute amounts of the small, soluble GP which is the expression product of nonedited mRNA species of the GP gene. The abundant shedding of soluble GP1 may play an important role in the immunopathology of Ebola hemorrhagic fever in experimentally and naturally infected hosts.

Cell Line↗
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↗