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Biomedical subjects

W Hofmann

Publications and source records attributed to W Hofmann.

At least 91 records · Page 5Linked to original sources
PubMed1999

Adaptive response and dose-response plateaus for initiation in a state-vector model of carcinogenesis.

PURPOSE: To investigate whether it is possible to explain dose-response plateaus for in-vitro X-ray irradiation of different cell lines with radioprotective mechanisms such as radiologically induced expression of scavengers and repair enzymes. MATERIALS AND METHODS: A biomathematical model was developed based on a previous state-vector model. New features of the model are a mathematical description of enhanced repair and radical scavenging as a result of irradiation. RESULTS: The model produces a plateau in the dose-response for in-vitro tranformations between 0.5 and 1 Gy and for chromosome aberrations and it predicts an inverse-fractionation effect within a selected range of doses. CONCLUSIONS: Adaptive response mechanisms within a state-vector model provide a coherent explanation of the dose-response characteristics for in-vitro transformations and chromosomal aberrations. These results suggest the need for new experimental studies described in the paper.

Adaptation, Biological↗
PubMed1999

Intrinsic human immunodeficiency virus type 1 resistance of hematopoietic stem cells despite coreceptor expression.

Interactions of human immunodeficiency virus type 1 (HIV-1) with hematopoietic stem cells may define restrictions on immune reconstitution following effective antiretroviral therapy and affect stem cell gene therapy strategies for AIDS. In the present study, we demonstrated mRNA and cell surface expression of HIV-1 receptors CD4 and the chemokine receptors CCR-5 and CXCR-4 in fractionated cells representing multiple stages of hematopoietic development. Chemokine receptor function was documented in subsets of cells by calcium flux in response to a cognate ligand. Productive infection by HIV-1 via these receptors was observed with the notable exception of stem cells, in which case the presence of CD4, CXCR-4, and CCR-5, as documented by single-cell analysis for expression and function, was insufficient for infection. Neither productive infection, transgene expression, nor virus entry was detectable following exposure of stem cells to either wild-type HIV-1 or lentivirus constructs pseudotyped in HIV-1 envelopes of macrophage-tropic, T-cell-tropic, or dualtropic specificity. Successful entry into stem cells of a vesicular stomatitis virus G protein-pseudotyped HIV-1 construct demonstrated that the resistance to HIV-1 was mediated at the level of virus-cell membrane fusion and entry. These data define the hematopoietic stem cell as a sanctuary cell which is resistant to HIV-1 infection by a mechanism independent of receptor and coreceptor expression that suggests a novel means of cellular protection from HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Species-specific, postentry barriers to primate immunodeficiency virus infection.

By using replication-defective vectors derived from human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV(mac)), and murine leukemia virus (MuLV), all of which were pseudotyped with the vesicular stomatitis virus (VSV) G glycoprotein, the efficiency of postentry, early infection events was examined in target cells of several mammalian species. Titers of HIV-1 vectors were significantly lower than those of SIV(mac) and MuLV vectors in most cell lines and primary cells from Old World monkeys. By contrast, most New World monkey cells exhibited much lower titers for the SIV(mac) vector compared with those of the HIV-1 vector. Prosimian cells were resistant to both HIV-1 and SIV(mac) vectors, although the MuLV vector was able to infect these cells. Cells from other mammalian species were roughly equivalent in susceptibility to the three vectors, with the exception of rabbit cells, which were specifically resistant to the HIV-1 vector. The level of HIV-1 vector expression was very low in transduced cells of rodent, rabbit, cow, and pig origin. Early postentry restriction of primate immunodeficiency virus infection exhibits patterns largely coincident with species borders and applies to diverse cell types within an individual host, suggesting the involvement of species-specific, widely expressed cellular factors.

Animals↗
PubMed1999

Changes in human immunodeficiency virus type 1 envelope glycoproteins responsible for the pathogenicity of a multiply passaged simian-human immunodeficiency virus (SHIV-HXBc2).

In vivo passage of a poorly replicating, nonpathogenic simian-human immunodeficiency virus (SHIV-HXBc2) generated an efficiently replicating virus, KU-1, that caused rapid CD4(+) T-lymphocyte depletion and AIDS-like illness in monkeys (S. V. Joag, Z. Li, L. Foresman, E. B. Stephens, L.-J. Zhao, I. Adany, D. M. Pinson, H. M. McClure, and O. Narayan, J. Virol. 70:3189-3197, 1996). The env gene of the KU-1 virus was used to create a molecularly cloned virus, SHIV-HXBc2P 3.2, that differed from a nonpathogenic SHIV-HXBc2 virus in only 12 envelope glycoprotein residues. SHIV-HXBc2P 3.2 replicated efficiently and caused rapid and persistent CD4(+) T-lymphocyte depletion in inoculated rhesus macaques. Compared with the envelope glycoproteins of the parental SHIV-HXBc2, the SHIV-HXBc2P 3.2 envelope glycoproteins supported more efficient infection of rhesus monkey peripheral blood mononuclear cells. Both the parental SHIV-HXBc2 and the pathogenic SHIV-HXBc2P 3.2 used CXCR4 but none of the other seven transmembrane segment receptors tested as a second receptor. Compared with the parental virus, viruses with the SHIV-HXBc2P 3.2 envelope glycoproteins were more resistant to neutralization by soluble CD4 and antibodies. Thus, changes in the envelope glycoproteins account for the ability of the passaged virus to deplete CD4(+) T lymphocytes rapidly and specify increased replicative capacity and resistance to neutralization.

Amino Acid Sequence↗
PubMed1999

[Effect of antibody-containing egg powder on development of active immunity in calves].

Investigations on the influence of an egg powder containing antibodies was conducted on 15 young calves to measure the development of an active immune response. The product investigated, Globigen 88 (Lohmann Animal Health GmbH & Co. KG), was mixed with a milk replacer and administered to a group of 5 calves over 8 days twice a day. In addition, two control groups were established each consisting of 5 calves. The first group received the corresponding amount of egg powder without antibodies and the second group received exclusively milk replacer. In all groups serum antibody content was measured over 22 days. The average antibody content was decreased in the serum of the test groups. Avian immunoglobulins were not detectable. The development of active immunity in calves was not hindered. Furthermore a significant daily increase in weight was observed in test groups.

Animal Feed↗
PubMed1999

Lung dosimetry for thorotrast patients: implications for inhalation of radon progeny.

A peculiar feature of radiation-induced carcinogenesis in German Thorotrast patients is that no excess lung cancers have been observed so far in the epidemiological follow-up study. Two possibilities have been explored here to explain the apparent discrepancy between predicted and observed bronchial tumors: (1) Bronchial doses are smaller than presently predicted; and/or (2) lung cancer risk per unit exposure in Thorotrast patients is smaller than that derived from inhalation of (222)Rn progeny. First, the mean bronchial doses computed with an updated dosimetric model for the different radiation sources are indeed substantially smaller than previous dose estimates; however, the epidemiological findings still cannot be explained in terms of bronchial doses. Second, lung cancer risk estimates based on the revised dose estimates and relative risk coefficients specifically derived from chronic indoor exposures still yield a relative risk of 1.66 for the German Thorotrast patients. This suggests that either the lung cancer risk coefficient for inhalation of radon progeny cannot be applied to Thorotrast patients because of differences in dose distributions or exposure conditions, or the current tissue weighting factor should be applied primarily to the bronchial region of the lung in the case of exposure to radon progeny.

Administration, Inhalation↗
PubMed1999

[Continuing medical education (CME) in neurology. Concept of the German Society of Neurology (DGN) and the Neurology Section of the Professional League of German Neurologic Medicine (BVDN)].

Continuous medical education in Neurology (CME-Neurology) has been promoted in a concept organized by both the German society of neurology, German association for occupational interests of neurologists and psychiatrists). CME-Neurology has been started in January 1999 and is closely adapted to the CME guidelines of neurology section of UEMS and EFNS. The program shall serve to the maintenance and upgrading of knowledge skills and competence of postgraduate training in neurology.

Education, Medical, Continuing↗
PubMed1999

[Structures and possibilities of herd management on the example of respiratory enzootic infection of calves].

With the keeping of cattle in bigger herds problems arise, which require a modified veterinary approach. In stead of and in addition to the treatment of individual animals improvement of hygiene, intensification of prophylaxis, fast recognition (herd diagnostics) and interregional comparability have to be established. Beside the conventional field veterinarian, who is consulted on request primarily for the treatment of single animals, specialists in team practices as an alternative, permanently employed veterinarians or firm contracts with a health service up to integrated herd control are thinkable. The clarification and control of infectious diseases of the respiratory tract in cattle operations require an exact analysis of the environmental conditions and the identification of etiologic agents. Special attention has to be drawn to the evaluation of the barn climate and the respective taking of samples concerning the actual disease situation.

Animal Husbandry↗
PubMed1998

Hyperglycemia regulates the glucose-transport system of clonal choriocarcinoma cells in vitro. A potential molecular mechanism contributing to the adjunct effect of glucose in tumor therapy.

Glucose is taken up by tumor cells via sodium-independent facilitated diffusion along a concentration gradient. To examine the regulation of this process by substrate concentration, we investigated the effect of hyperglycemia on the glucose-transport system of choriocarcinoma-derived JAR and JEG-3 cells by culturing them for 24, 48 and 96 hr in medium containing either 5.5 (normoglycemia) or 25 (hyperglycemia) mM D-glucose, respectively. Immunocytochemically, choriocarcinoma cells expressed the high-affinity glucose transporter isoforms GLUT1 and GLUT3. Based on initial uptake measurements using 3-O-[14C]methyl-D-glucose, kinetic parameters were calculated as Km = 15 mM and Vmax = 95 fmol/sec per cell for JAR and Km = 9 mM and Vmax = 64 fmol/sec per cell for JEG-3 cells. In JAR cells cultured under hyperglycemic conditions, uptake rates were significantly increased at 15, 20 and 25 mM exogenous D-glucose concentrations as compared with normoglycemic conditions. This effect was due to an increase in Vmax, whereas Km remained unchanged. Using Northern blotting, GLUT1 mRNA levels were higher but GLUT3 transcripts were reduced upon hyperglycemia. Western blotting revealed elevated GLUT1 and GLUT3 expression under hyperglycemic conditions. Hyperglycemia did not significantly influence the glucose-transport system of JEG-3 cells. We conclude that sustained hyperglycemia stimulates the glucose-transport system of JAR, but not of JEG-3, choriocarcinoma cells in vitro due to changes in GLUT1 and GLUT3 expression levels. We speculate that this mechanism may contribute to the beneficial effects of induced hyperglycemia as an adjuvant in tumor therapy.

3-O-Methylglucose↗
PubMed1998

Intrabody-mediated knockout of the high-affinity IL-2 receptor in primary human T cells using a bicistronic lentivirus vector.

A bicistronic human immunodeficiency virus type 1 (HIV-1)-based vector is described in which the expression of a selectable marker and a second gene of interest are forcibly coupled by means of an internal ribosome entry site. The vector provides high-level expression of the coselected gene in approximately 90% of transduced cells and has been used to express an endoplasmic reticulum-targeted single-chain antibody (intrabody) directed against a subunit of the interleukin-2 receptor, IL-2R alpha. In the established T cell line Kit225 and also in primary human T cells stably transduced with the intrabody vector, the cell surface expression of IL-2R alpha could be reduced to a low or undetectable level. Responsiveness to IL-2 was reduced 10-fold in the IL-2R alpha-negative cells, consistent with a lack of high-affinity IL-2 receptors. Pseudotyping of the HIV-1 core with the vesicular stomatitis virus G protein improved particle stability by two- to three-fold and enhanced vector entry into established T cell lines up to 230-fold. Vector entry into primary human T cells was most efficient when the amphotropic murine leukemia virus envelope was used. The forced, high-expression capability of the bicistronic vector, together with the capacity of HIV-1 vectors to infect nondividing cells, make this an attractive tool for the genetic manipulation of primary cell types.

Animals↗
PubMed1998

Multifractal analysis of the 137Cs fallout pattern in Austria resulting from the Chernobyl accident.

The cumulative deposition of the 137Cs fallout in Austria resulting from the passage of the Chernobyl cloud has been investigated by applying correlation dimension and hyperbolic frequency distribution methods. For the analysis, a total of 1,881 deposition values were used, which were collected by the Federal Environmental Agency of Austria and the Federal Ministry of Health, representing all available measurements of 137Cs in soil made in Austria after the Chernobyl accident. From these data a hyperbolic exponent for the frequency distribution of 4.0 and a set of fractal correlation dimensions, which decrease from 1.426 +/- 0.022 (for the whole network) to 0.706 +/- 0.047 (for 137Cs values > or = 100 kBq m(-2)), were derived, thus confirming that the fallout pattern can be described as a multifractal.

Austria↗
PubMed1998

Tat protein induces human immunodeficiency virus type 1 (HIV-1) coreceptors and promotes infection with both macrophage-tropic and T-lymphotropic HIV-1 strains.

Chemokine receptors CCR5 and CXCR4 are the primary fusion coreceptors utilized for CD4-mediated entry by macrophage (M)- and T-cell line (T)-tropic human immunodeficiency virus type 1 (HIV-1) strains, respectively. Here we demonstrate that HIV-1 Tat protein, a potent viral transactivator shown to be released as a soluble protein by infected cells, differentially induced CXCR4 and CCR5 expression in peripheral blood mononuclear cells. CCR3, a less frequently used coreceptor for certain M-tropic strains, was also induced. CXCR4 was induced on both lymphocytes and monocytes/macrophages, whereas CCR5 and CCR3 were induced on monocytes/macrophages but not on lymphocytes. The pattern of chemokine receptor induction by Tat was distinct from that by phytohemagglutinin. Moreover, Tat-induced CXCR4 and CCR5 expression was dose dependent. Monocytes/macrophages were more susceptible to Tat-mediated induction of CXCR4 and CCR5 than lymphocytes, and CCR5 was more readily induced than CXCR4. The concentrations of Tat effective in inducing CXCR4 and CCR5 expression were within the picomolar range and close to the range of extracellular Tat observed in sera from HIV-1-infected individuals. The induction of CCR5 and CXCR4 expression correlated with Tat-enhanced infectivity of M- and T-tropic viruses, respectively. Taken together, our results define a novel role for Tat in HIV-1 pathogenesis that promotes the infectivity of both M- and T-tropic HIV-1 strains in primary human leukocytes, notably in monocytes/macrophages.

Base Sequence↗
PubMed1998

Multicentre evaluation of KONE Optima analysis system.

Optima from KONE Instruments Corporation is a new selective laboratory analyzer for turbidimetric, colorimetric and ion selective electrode measurements. Overall analytical performance of Optima and reagents provided by KONE was evaluated according to ECCLS guidelines, in a multicentre study involving four different laboratories, including substrates (cholesterol, high-density lipoprotein-cholesterol, creatinine), specific proteins (transferrin, IgG), enzyme activities (gamma-glutamyltransferase, alanine aminotransferase) and electrolytes (sodium, potassium, chloride). The results obtained attest good precision of the system for all the analytes tested: the range of within-run CV is 0.5 %-4.3 %, and range of between-day CV % is 0.8 %-7.9 % (median of four laboratories). Except for total cholesterol (5 % overestimation compared to the reference method) accuracy of measurement is adequate. Creatinine and uric acid assays were subjects of interference (defined as deviation > 10 % from target value) by bilirubin and haemoglobin respectively.

Blood Chemical Analysis↗
PubMed1998

Physiopathology of proteinuria and laboratory diagnostic strategy based on single protein analysis.

A quantification of proteins of different molecular size has been shown to be useful in characterizing the mechanism and medical causes of proteinuria. By analyzing urine albumin, alpha1-microglobulin, immunoglobulin G and alpha2-macroglobulin together with total protein, prerenal, glomerular, tubular and postrenal causes of proteinuria can be detected and differentiated by their specific urine protein patterns. Using automated turbidimetric procedures, prerenal proteinurias are characterized by an albumin/total protein ratio below 0.4. Tubulo-interstitial diseases which are negative in the protein test strip procedure are detected and clearly differentiated from other causes of proteinuria by their high alpha1-microglobulin/albumin ratios. In post-renal proteinuria, alpha2-macroglobulin proved to be a useful marker, when albumin excretion exceeds 100 mg/l urine. This protein exhibits plasma-like ratios to albumin in postrenal causes, whereas it is much lower in renal proteinurias. The new strategy, which has been evaluated in more than 500 clinically and partly histologically proven cases of renal diseases, more sensitively detects glomerular and tubulo-interstitial diseases when applied in urine screening and allows us to distinguish all clinically important causes from analysis of a morning spot urine sample.

Clinical Laboratory Techniques↗