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Biomedical subjects

H Feldmann

Publications and source records attributed to H Feldmann.

At least 109 records · Page 6Linked to original sources
PubMed1994

Genome structure and variability of a virus causing hantavirus pulmonary syndrome.

A previously unrecognized hantavirus (family Bunyaviridae) has recently been detected and shown to be associated with a severe respiratory illness with high mortality, termed hantavirus pulmonary syndrome (HPS). This disease has now been identified throughout the western United States. We present nucleotide sequence characterization of the three RNA segments composing the HPS virus genome and address the question of the apparent emergence of this highly lethal virus. No evidence of genetic reassortment with previously recognized hantaviruses was found, each RNA segment being unique and approximately 30% different at the nucleotide level to the segments of the closest relative, Prospect Hill virus. These findings, together with the observed extensive genetic diversity of HPS viruses and examples of geographic clustering of distinct virus genotypes, suggest that HPS and associated virus have likely existed undetected for many years. The virus genome M segment was determined to be 3696 nucleotides in length and encode G1 and G2 proteins, 652 and 488 amino acids in length. The S segment was found to be 2059 nucleotides in length and to encode a nucleocapsid protein, 428 amino acids in length. S segment analysis also revealed an unusually long noncoding region with numerous repeats and evidence for a potential NSS protein encoded in an overlapping frame.

Amino Acid Sequence↗
PubMed1994

Intervertebral space nerve root entrapment after lumbar disc surgery. Two cases.

Iatrogenic pseudomeningocele formation after lumbar or cervical spine surgery is a well-described complication. Two unusual cases of transdural nerve root herniation with subsequent entrapment in the intervertebral space after lumbar disc surgery are presented. The reasons for this rare complication and its treatment are discussed.

Female↗
PubMed1994

Identification of a set of yeast genes coding for a novel family of putative ATPases with high similarity to constituents of the 26S protease complex.

There is accumulating evidence for a large, highly conserved gene family of putative ATPases. We have identified 12 different members of this novel gene family (the YTA family) in yeast and determined the nucleotide sequences of nine of these genes. All of the putative gene products are characterized by the presence of a highly conserved domain of 300 amino acids containing specialized forms of the A and B boxes of ATPases. YTA1, YTA2, YTA3 and YTA5 exhibit significant similarity to proteins involved in human immunodeficiency virus Tat-mediated gene expression but more significantly to subunits of the human 26S proteasome. YTA1 and YTA2 are essential genes in yeast. Remarkably, the cDNA of human TBP-1 can compensate for the loss of YTA1. Preliminary experiments indicate that YTA1 is a component of the 26S protease complex from yeast. Our findings lead us to propose that YTA1, YTA2, YTA3 and YTA5 function as regulatory subunits of the yeast 26S proteasome. YTA10, YTA11 and YTA12 share significant homology with the Escherichia coli FtsH protein, and together with YTA4 and YTA6 may constitute a separate subclass within this family of putative ATPases.

Adenosine Triphosphatases↗
PubMed1994

Analysis of a 70 kb region on the right arm of yeast chromosome II.

In the framework of the EC programme for sequencing yeast chromosome II, we have determined the nucleotide sequence of a 70 kb region. Subsequent analysis revealed 35 open reading frames, 14 of which correspond to known yeast genes. From structural parameters and/or similarity searches with entries in the current data libraries, a preliminary functional assessment of several of the putative novel gene products can be made. The gene density in this region amounts to one gene in 1.98 kb. Coding regions occupy 75% of the total DNA sequence. Within the intergenic regions, potential regulatory elements can be predicted. The data obtained here may serve as a basis for a more detailed biochemical analysis of the novel genes.

Amino Acid Sequence↗
PubMed1994

Characterization of filoviruses based on differences in structure and antigenicity of the virion glycoprotein.

Eight different filovirus isolates, representing major episodes of filovirus hemorrhagic disease, were propagated for structural and antigenetic analyses of their glycoprotein (GP). Carbohydrate analysis revealed that N- and O-glycosylation are features of filovirus GPs. Oligosaccharide side chains differed in their sialylation pattern and seemed to be cell line-dependent. Marburg virus (MBG) isolates are clearly distinguished from Ebola (EBO) and Reston viruses by a lack of terminal sialic acids when propagated in E6 and MA-104 cells. It was also determined that GP-specific antisera failed to show any cross-reactivity between MBG isolates and other filoviruses. These data, together with prior findings, indicate that the genus Filovirus can be divided into a MBG group and EBO group.

Animals↗
PubMed1994

Ventriculoatrial shunting via the superficial temporal vein. A new technique.

A new approach for access to the right atrium via the superficial-temporal vein is proposed. We prefer this route whenever anterior neck veins cannot be used to place the catheter into the right atrium, e.g., in patients with tracheostomy. The results seem to be as good as those obtained with conventional techniques.

Cerebrospinal Fluid Shunts↗
PubMed1994

[The Brünings 1913 polylaryngoscope, named the "nine eye", and other early attempts at demonstrating laryngoscopic findings. Pictures from the history of otorhinolaryngology, presented by instruments of the collection of the Ingolstadt German History of Medicine Museum].

Since the invention of otoscopy and laryngoscopy in the middle of the 19th century attempts have been made at demonstrating the findings live to a number of co-observers. Efforts to project the image onto a ground glass screen failed because of the faint light available at the time and the small scale of magnification which could not be increased at will due to lack of depth of focus. Such attempts by Killian in 1893 and others are quoted. W. Brünings in Jena in 1913 devised an instrument that enabled the observer and eight co-observers to see a direct uninverted image of the larynx or the tympanic membrane simultaneously in identical brightness and size. A movable mark on one of the lenses served as a pointer. Various optical equipment permitted a twofold or threefold magnification, stereoscopic and stroboscopic examination. Apart from the technical details an anecdotal report is given of Brünings' presentation and practical demonstration of his apparatus at the 20th meeting of the German Laryngological Society in 1913. The instrument was quite popular in training hospitals between the two world wars. It was only in 1937 that an adapted version of it was introduced in ophthalmology.

Germany↗
PubMed1994

[True and artificial leeches and their use in otology. Images from the history of otorhinolaryngology, presented with instruments from the Ingolstadt German Medical History Museum collection].

Based on the concepts of humoral pathology in former centuries bloodletting was used as remedy to great extent, systematically by puncturing a vein or locally by scarification and cupping glasses. In the 18th and 19th century leeches were introduced and applied in huge numbers to cure all conceivable affections including diseases of the ear. J. M. G. Itard in Paris in 1821 for treating various types of hearing disorders recommended to place leeches at the anus or in the nose to imitate bleeding of haemorrhoids or nose-bleeds, which were considered natural resources of the body to cope with disorders of the humours. H. Schwartze in Halle in 1885 still followed this suggestion. W. R. Wilde in Dublin in 1842 and A. F. von Tröltsch in Würzburg 1867 advocated local blood-letting by leeches around the external ear. The surgeon Ch. L. St. Heurteloup in Paris 1840 invented an artificial leech, which was soon widely used in otology and ophthalmology. After the first World War the application of leeches became obsolete. The humoral pathology had found new approaches: immunology including stimulation of the inherent bodily means of defence, and rheology, particularly haemodilution. The historical development and the technique of applying live and artificial leeches in otology are described in detail.

Animals↗
PubMed1994

Genetic identification of a new Puumala virus strain causing severe hemorrhagic fever with renal syndrome in Germany.

A severe case of suspected hemorrhagic fever with renal syndrome (HFRS) was recently identified in northwestern Germany. A genetic detection assay was designed that identified hantavirus-specific RNA in the patient's clinical specimens by reverse transcriptase-polymerase chain reaction amplification of virus S and M genome segments. Phylogenetic analysis of the nucleotide sequences demonstrated that this virus belonged to the Puumala (PUU) group, with the closest relationship to a PUU isolate from Finland. Within the group, this virus formed a separate lineage. This finding represents the first genetic characterization of a hantavirus causing severe HFRS in Germany. The data suggest that PUU viruses circulating in western European countries are genetically distinct from their northeastern counterparts. Comparison of deduced amino acid sequences demonstrated a loss of a potential N-glycosylation site in the G2 protein compared with other PUU viruses.

Amino Acid Sequence↗
PubMed1994

The nucleoprotein of Marburg virus is phosphorylated.

The nucleoprotein (NP) of Marburg virus (MBG), a filovirus, is encoded by the gene closest to the 3' end of the non-segmented negative-strand RNA genome. Sequence comparison has indicated that NP is the functional equivalent to the nucleoproteins of paramyxoviruses and rhabdoviruses. Expression of recombinant NP in two eukaryotic systems using vaccinia virus and baculovirus (vectors pSC11 and pAcYMB1, respectively) and analysis of MBG-specific proteins have demonstrated that the NP of MBG is phosphorylated. The NP appeared in two forms differing in M(r) by about 2K (94K and 92K respectively). Dephosphorylation clearly demonstrated that the 94K form is phosphorylated whereas the 92K form is unphosphorylated. In virion particles NP was exclusively present in the phosphorylated form. These findings suggest that only the phosphorylated NP can form nucleocapsid complexes and interact with the genomic RNA.

Antibodies↗
PubMed1994

Trehalose-6-P synthase is dispensable for growth on glucose but not for spore germination in Schizosaccharomyces pombe.

Trehalose-6-P inhibits hexokinases in Saccharomyces cerevisiae (M. A. Blázquez, R. Lagunas, C. Gancedo, and J. M. Gancedo, FEBS Lett. 329:51-54, 1993), and disruption of the TPS1 gene (formerly named CIF1 or FDP1) encoding trehalose-6-P synthase prevents growth in glucose. We have found that the hexokinase from Schizosaccharomyces pombe is not inhibited by trehalose-6-P even at a concentration of 3 mM. The highest internal concentration of trehalose-6-P that we measured in S. pombe was 0.75 mM after heat shock. We have isolated from S. pombe the tps1+ gene, which is homologous to the Saccharomyces cerevisiae TPS1 gene. The DNA sequence from tps1+ predicts a protein of 479 amino acids with 65% identity with the protein of S. cerevisiae. The tps1+ gene expressed from its own promoter could complement the lack of trehalose-6-P synthase in S. cerevisiae tps1 mutants. The TPS1 gene from S. cerevisiae could also restore trehalose synthesis in S. pombe tps1 mutants. A chromosomal disruption of the tps1+ gene in S. pombe did not have a noticeable effect on growth in glucose, in contrast with the disruption of TPS1 in S. cerevisiae. However, the disruption prevented germination of spores carrying it. The level of an RNA hybridizing with an internal probe of the tps1+ gene reached a maximum after 20 min of heat shock treatment. The results presented support the idea that trehalose-6-P plays a role in the control of glycolysis in S. cerevisiae but not in S. pombe and show that the trehalose pathway has different roles in the two yeast species.

Amino Acid Sequence↗
PubMed1994

[Melancholia as existential condition].

Starting from the anthropological understanding and structural analysis of melancholia (Minkowski, E. Straus, von Gebsattel, L. Binswanger, Tellenbach), it is made an attempt to show historicity of man as significant for existential condition. Melancholic patients are basically lacking historical meaning of existence.

Depressive Disorder↗
PubMed1993

Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness.

A mysterious respiratory illness with high mortality was recently reported in the southwestern United States. Serologic studies implicated the hantaviruses, rodent-borne RNA viruses usually associated elsewhere in the world with hemorrhagic fever with renal syndrome. A genetic detection assay amplified hantavirus-specific DNA fragments from RNA extracted from the tissues of patients and deer mice (Peromyscus maniculatus) caught at or near patient residences. Nucleotide sequence analysis revealed the associated virus to be a new hantavirus and provided a direct genetic link between infection in patients and rodents.

Animals↗
PubMed1993

TKL2, a second transketolase gene of Saccharomyces cerevisiae. Cloning, sequence and deletion analysis of the gene.

Transketolase activity is indispensable for the generation of erythrose 4-phosphate and therefore necessary for the biosynthesis of the aromatic amino acids. Yeast mutants with a deletion of the transketolase gene, TKL1, can grow without aromatic amino acid supplement indicating an additional source of erythrose 4-phosphate in the cells. Here we describe the cloning of TKL2, a gene coding for a second transketolase enzyme in Saccharomyces cerevisiae. The deduced protein sequence of TKL2 demonstrates 71% identity with TKL1 [Sundström, M., Lindqvist, Y., Schneider, G., Hellman, U. & Ronne, H. (1993) J. Biol. Chem., in the press]. Double mutants for both genes, TKL1 and TKL2, are auxotrophic for aromatic amino acids, indicating a complete block in the transketolase activity. Deletion of TKL2 alone does not lead to a significant phenotype, and transketolase activity is not reduced in these mutants. Overexpression of TKL2 on a multi-copy plasmid in a tkl1 background showed that TKL2 is functionally expressed: transketolase enzyme activity was detectable in the transformants and the protein reacts with anti-transketolase serum in Western blot analysis. In addition, transformation of the tkl1 tkl2 double mutant with the TKL2 plasmid can compensate the growth defect on a medium without aromatic amino acids.

Amino Acid Sequence↗
PubMed1993

A putative homologue of the human autoantigen Ku from Saccharomyces cerevisiae.

We have identified and purified a new DNA binding protein, designated HDF (high affinity DNA-binding factor) from Saccharomyces cerevisiae. HDF binds in a sequence-independent manner to the ends of double-stranded DNA. The protein appears as a stable heterodimer of two polypeptides with molecular masses of 70 and 85 kDa. We have cloned and sequenced the 70-kDa subunit of the HDF protein. The amino acid sequence shows a weak but significant homology with the p70 subunit of the human Ku autoantigen, a protein that also binds to the ends of double-stranded DNA. Hdf- strains generated by one-step gene disruption show a temperature-sensitive phenotype for growth at 37 degrees C. Cells arrest growth at 37 degrees C and after several hours appear as enlarged single-budded cells with abnormally high DNA content indicating a defect in the regulation of DNA replication coupled with or causing a cell cycle arrest in G2 or mitosis.

Amino Acid Sequence↗
PubMed1993

Molecular biology and evolution of filoviruses.

The family Filoviridae contains extremely pathogenic human viruses causing a fulminating, febrile hemorrhagic disease. Filoviruses are enveloped, filamentous particles with a nonsegmented negative-strand RNA genome showing the gene arrangement 3'-NP-VP35-VP40-GP-VP30-VP24-L-5'. Genes are flanked by highly conserved transcriptional signals and are generally separated by variable intergenic regions. They are transcribed into monocistronic polyadenylated messenger RNAs which contain relatively long 5' and 3' untranslated regions. Seven structural proteins are encoded by the genome of which four form the helical nucleocapsid (NP-VP35-VP30-L), two are membrane-associated (VP40-VP24), and one is a transmembrane glycoprotein (GP). Comparison of filovirus genomes with those of other nonsegmented negative-strand RNA viruses suggest comparable mechanisms of transcription and replication and a common evolutionary lineage for all these viruses. Sequence analyses of single genes, however, showed that filoviruses are more closely related to paramyxoviruses, particularly human respiratory syncytial virus. These data support the concept of the taxonomic order Mononegavirales for all nonsegmented negative-strand RNA viruses and the classification of Marburg virus, Ebola virus, and Reston virus in the family Filoviridae, separate from the families Paramyxoviridae and Rhabdoviridae.

Animals↗
PubMed1993

Utilization of autopsy RNA for the synthesis of the nucleocapsid antigen of a newly recognized virus associated with hantavirus pulmonary syndrome.

A newly recognized hantavirus was recently found to be associated with an outbreak of acute respiratory illness in the southwestern United States. The disease, which has become known as hantavirus pulmonary syndrome, has an unusually high mortality (64%). Virus isolation attempts have been unsuccessful thus far, resulting in a lack of homologous antigen for use in diagnostic assays. For this reason, a molecular approach was initiated to produce recombinant homologous antigen. The virus nucleocapsid (N) protein was selected, since N has been shown to be a sensitive antigenic target in other hantavirus systems. The N protein open reading frame of the virus S genome segment was synthesized from frozen autopsy tissue by polymerase chain reaction amplification, followed by cloning and expression in Hela cells (vaccinia-T7 RNA polymerase system) and Escherichia coli. N protein-expressing Hela cells served as excellent antigens for an improved indirect immunofluorescence assay. Use of the E. coli-expressed N protein in an enzyme-linked immunosorbent assay improved the sensitivity and specificity when compared with heterologous antigens used previously. Preliminary analysis also indicates that the higher sensitivity could result in earlier detection of infected persons. These data demonstrate that even in the absence of a virus isolate, the necessary homologous antigen can be produced and can serve to improve the detection and diagnostic capabilities needed to combat this newly recognized fatal respiratory illness in the United States.

Amino Acid Sequence↗