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T Werner

Publications and source records attributed to T Werner.

At least 127 records · Page 7Linked to original sources

Endogenous retroviral elements in human DNA.

Endogenous retroviruses and retroviral elements represent a substantial component of vertebrate genomes. They are inherited as stable Mendelian genes and may be activated spontaneously or by physical or chemical agents. In the human genome various retroviral elements have been detected by their relationship with mammalian endogenous and exogenous retroviruses. The structure of these elements resembles either full-length or truncated proviruses. The biological function of human retrovirus-related sequences is still unknown, but like other transposable elements, they may have contributed in shaping the eukaryotic genome. Furthermore, they exhibit a number of features giving them a potential for involvement in carcinogenesis. Expression of endogenous retroviral elements has been detected in various human tissues and cell lines and in some cases appears to be associated with human neoplasias.

DNA, Viral↗

Histological and biochemical characterization of the murine cataract mutant Nop.

Nop, a spontaneous murine dominant cataract mutation, was detected by slit lamp investigations and preliminary characterized as a nuclear opacity. Histological investigations confirmed these findings and revealed additionally polar cataracts with vacuolization. In contrast to wild-type lenses, the nuclei of the cortical cells could also be detected in the area of the lens nucleus in Nop lenses. No other pathological alterations were found in the eyes. Lens wet and dry weights, as well as the content of water-soluble lens proteins, were reduced in heterozygous and homozygous mutants. The body weight was only slightly altered, indicating a rather lens-specific growth retardation. Some parameters concerning the osmotic state of the lens were changed, however, only in the homozygous mutants. Electrophoresis of the water-soluble lens proteins of the mutants revealed either additional bands, not present in the wild types, or bands of overrepresented proteins only slightly present in wild-type lenses. The changes might be related to the reduced amount of gamma-crystallins, which alters the composition of lenticular proteins in the mutants. Northern blots probed with cDNA specific for alpha-, beta- or gamma-crystallin genes suggested a reduced transcription of the gamma-crystallin genes. In contrast, the transcription of alpha- and beta-crystallins appeared to be similar in wild type and the mutants. The selective reduced amount of gamma-crystallin specific RNA can be discussed as a biochemical indicator for the histologically observed changes of differentiation in the cataractous Nop lenses.

Animals↗

S71 is a phylogenetically distinct human endogenous retroviral element with structural and sequence homology to simian sarcoma virus (SSV).

Human endogenous retroviral element S71 had previously been shown to contain gag- and pol-related regions and a 3' LTR-like sequence. The nucleotide sequence of S71 was determined and compared with the corresponding regions of SSV and its helper virus SSAV. The 1.48-kb S71 gag region consists of matrix protein p15 (MA)-, capsid protein p30 (CA)-, and nucleocapsid protein p10 (NC)-related sections and the 1.82-kb pol region of tether, RNase H (RH), and endonuclease/integrase (IN) sections. The S71 nucleotide sequence contains a 167 amino acid open reading frame encompassing MA. The boundaries of the S71 element are delimited by direct repeats and the entire element is 5.4 kb long. Similarity between S71 and the v-sis-bearing, defective SSV provirus also covers overall structural organization, including the presence of presumably nonretroviral sequences. Both the gag and the pol regions of S71 contain sequences highly conserved in numerous retroviruses. Phylogenetic analysis with conserved CA, RH, and IN sequences showed that of all other (C-type) human retroviral elements available for comparison, S71 is most closely related to infectious primate and murine retroviruses. This suggests that S71 represents a phylogenetic subgroup of its own. In addition we identified short ranges of conserved amino acid sequences within C-type retroviral gag and pol genes sufficient for phylogenetic analysis. Use of these may facilitate large-scale phylogenetic evaluation of C-type retroviral elements and allow rapid classification of new elements.

Amino Acid Sequence↗

Human SSAV-related endogenous retroviral element: LTR-like sequence and chromosomal localization to 18q21.

A new family of human endogenous retroviral sequences was recently discovered by way of its relationship to the simian sarcoma-associated virus (SSAV). One molecular clone, termed S71, contains sequences related to the genes coding for the group-specific antigens (gag) and polymerase (pol) proteins of SSAV. At the 3' end of this human retroviral element we have now found a 535-bp region which shows features characteristics of a retroviral long terminal repeat, including potential signal sequences essential for transcriptional control. By means of Southern blotting and in situ hybridization, the sequence was mapped to chromosome 18 band q21.

Animals↗

Isolation of an SSAV-related endogenous sequence from human DNA.

We have found human DNA to contain a number of sequences related to simian sarcoma associated virus (SSAV). One of these sequences was isolated from a human genomic library. The molecular clone, termed S71, contains regions homologous to SSAV gag and pol fragments and SSAV LTR. Furthermore, hybridization experiments and DNA sequencing revealed distinct homologies to the reverse transcriptase coding region of several other retroviruses including baboon endogenous virus (BaEV) and murine leukemia viruses (MuLV) as well as retrovirus-like elements. Some sequence homology was also found with the C-type retrovirus-related multicopy human clone 4-1. S71 is present in only one copy per human genome equivalent and exhibits an EcoRI restriction fragment length polymorphism.

Base Sequence↗

[Positive modification of hemodynamics in post cardiac surgery patients by hemofiltration. Improved method for the demonstration of myocardial depressant factor (MDF) in hemofiltrate].

The method of haemofiltration was used in 29 postoperative cardio-surgical patients with low blood pressure, high left ventricular filling pressure and low total peripheral resistance, which did not respond to the use of the intraaortic balloon pump or pharmaco-therapy. In severe low-output syndrome hemodynamic parameters are: reduced mean arterial pressure, increased left ventricular filling pressure, increased mean arterial pulmonary pressure as well as significantly reduced total peripheral resistance [4-6, 28]. Inspite of pharmaco-therapy, cardiac performance regarding peripheral perfusion is insufficient; this leads to a vicious cycle of irreversible O2-debt and severe cellular damage. After haemofiltration there was a significant improvement in the haemodynamic parameters, which in our opinion was due to the elimination of toxic peptides such as Myocardial Depressant Factor (MDF). In 27 of a total of 29 patients, haemodynamic parameters returned to normal after treatment. 19 patients were discharged, eight patients died after a number of days or weeks from causes not related to the original cardiogenic shock (cerebral embolism, reinfarction, myocardiopathy and pneumonia).

Adult↗

Influence of the immunomodulating compound BM 12.531 (azimexone) on radioresistance and granulopoietic colony forming units in mice.

BM 12.531 (azimexone) increases the survival of mice exposed to 650 rad. Levamisole, isoprenosine or aristolochia acid have no effects in this system. After administration of 25 mg/kg azimexone to C57 Bl/6-mice a statistically significant increase in CFUc was found. Maybe this increase in CFUc can explain the radioprotective effect of azimexone.

Adjuvants, Immunologic↗

Metabolic activation of haloalkanes and tests in vitro for mutagenicity.

1. During incubation of 14CCl4, 14CHCl3, [14C]halothane, or 14CCl3F with liver microsomes and NADPH, considerable radioactivity is bound irreversibly to endoplasmic protein and lipid. However, no 14C was detected in the ribosomal RNA. 2. None of the four haloalkanes studied induced mutations after incubation with liver microsomes and the bacterial tester strains S. typhimurium TA 1535 and TA 1538. 3. Very low or no activity was associated with soluble protein or RNA added to incubation mixtures of the four haloalkanes with liver microsomes.

Animals↗

A comparative study on the irreversible binding of labeled halothane trichlorofluoromethane, chloroform, and carbon tetrachloride to hepatic protein and lipids in vitro and in vivo.

1) After intraperitoneal injection of labeled CCl4, CHCl3, and halothane in mice, 14C is preferentially bound to liver endoplasmic protein and lipid. A considerable activity is also associated with mitochondrial constituents. Maximal protein binding (nmol/mg): CCl4: 2.8 (0.5 hrs); CHCl3: 11.5 (6 hrs); halothane: 5 (6 hrs). Lipid binding: CCl4: 6.4 (5 min); CHCl3: 8 (4 hrs); halothane: 13.5 (2 hrs). The form of the binding curves in microsomal and mitochondrial protein and lipid differed with the individual haloalkanes. 2) The irreversible (covalent) binding of 14C from labeled haloalkanes in anaerobic suspensions of isolated rabbit liver microsomes and NADPH after 30 min was for protein (lipid) (nmol/mg): CCl4: 15 (58); CHCl3: 3.4 (3.2); halothane: 2.3 (10); trichlorofluoromethane: 6.5 (30). Anerobic incubation favored dehalogenation, but CHCl3 metabolism and irreversible binding requires oxygen. The greatest differences in the in vitro "covalent" binding rates were observed with CHCl3 in rat, mouse, and rabbit. 3) Altered microsomal cytochrome P-450 concentrations in newborn animals, or produced by pretreatment of rats with phenobarbital, 3-methylcholanthrene (MC), or CoCl2 effected similar, but not proportional changes in the rates of irreversible protein and lipid binding. Upon addition of CCl4 the difference of light absorption of reduced liver microsomes from MC-pretreated rats containing cytochrome P-448 appeared at 452 nm. The irreversible binding rate in these microsomes was also increased. The small accleration in irreversible binding in liver microsomes from rats pretreated with isopropanol is not proportional to the high increase of CCl4 toxicity. 4) Practically no binding to added, soluble albumin or RNA was observed in microsomal incubates. However, 14C is bound to the nicotine-adenine dinucleotides of the NADPH system. All haloalkanes produced a similar increase of NADPH oxidation in incubates of rabbit liver microsomes and NADPH.

1-Propanol↗