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Biomedical subjects

W Paulus

Publications and source records attributed to W Paulus.

300 records · Page 17Linked to original sources

[Antibody response to hemagglutinin and neuraminidase induced by an influenza subunit vaccine (author's transl)].

To study antigenicity, persistence of antibody (efficacy) and reactogenicity of a new bivalent influenza subunit vaccine, Sandovac, it was given in two different concentrations (1000 and 2000 IU) to 156 subjects from two epidemiologically destinct areas (119 students from Essen, average age 22 years, 37 residents from Kassel average age 56 years). Serum antibody response was measured by hemagglutination inhibition (HI) and neuraminidase inhibition (NI) tests before, one, two and six months after vaccination. The following results were obtained: 1. Four weeks post vaccination an excellent strain specific and crossreactive (H3 N2 variant-specific) antibody response was observed. Subtype specific (H0, H1 or H2) activity could not be detected. 2. Six months post vaccination a still notably higher antibody level as compared to the preimmunization status could be demonstrated. 3. A difference, however, existed between the immune responses of the Essen student population with an average age of 22 years, and of the Kassel resident population with an average age of 56 years. The immune response being significantly better in younger vaccinees. 4. High and low concentrated vaccines revealed neither objective nor subjective differences in reactogenicity and were very well tolerated. 5. In all immunological parameters tested the double concentrated vaccine (S 2000) proved to be slightly superior to the lower concentrated vaccine (S 1000) that is officially licensed in the German Federal Republic.

Adolescent↗

HSV-1 infected cell proteins influence tetracycline-regulated transgene expression.

BACKGROUND: This study investigates elements of herpes simplex virus type 1 (HSV-1) which influence transgene expression in tetracycline-regulated expression systems. METHODS: Different HSV-1 mutants were used to infect Vero cells that had been transfected with plasmids containing the luciferase gene under the control of tet-off or tet-on tetracycline-regulation systems. RESULTS: The baseline level of luciferase expression was elevated after infection with HSV-1 mutants lacking one or more immediate early genes encoding transactivating factors: ICP27, ICP4 and ICP0. With the tet-off system, not only was baseline expression elevated, but there was a complete loss of induction upon removal of tet when this regulatory system was brought into the cell by infection with helper virus-free amplicon vectors. Elevation of luciferase expression was also observed upon infection with the same HSV-1 mutants following transfection with a plasmid containing only a CMV minimal promoter driving luciferase (pUHC13-3). Only one HSV mutant (14Hdelta3), which bears a disruption in the transactivation domain of VP16 and is deleted for both ICP4 genes, did not increase baseline luciferase expression after transfection of pUHC13-3. The disregulating effects were dependent on virus dose and were not influenced by treatment with interferon (IFN)-alpha, which suppresses viral gene expression. Additional assays involving cotransfection of pUHC13-3 with a plasmid encoding of the HSV-1 transactivating factor ICP4 revealed that ICP4 was the most potent inducer of gene expression from the tetO/CMV minimal promoter. CONCLUSION: These results indicate that proteins encoded in the HSV-1 genome, especially the transactivating immediate early gene products (ICP4, ICP27 and ICP0) and the VP16 tegument protein can activate the tetO/ minimal CMV promoter and thereby interfere with the integrity of tetracycline-regulated transgene expression.

Animals↗

[Hypermethylation as a potential prognostic factor and a clue to a better understanding of the molecular pathogenesis of medulloblastoma--results of a genomewide methylation scan].

BACKGROUND: The molecular mechanisms controlling initiation and progression of medulloblastomas are largely unclear. Changes in DNA methylation of promoter regions have been shown to disturb the expression of growth regulatory genes. PATIENTS AND METHODS: We evaluated DNA methylation patterns in 17 medulloblastomas, 5 stPNETs and 5 medulloblastoma cell lines using Restriction Landmark Genomic Scanning (RLGS), a method displaying up to 2.000 potential gene loci in a single gene. To test whether previously characterized tumor suppressor genes are affected by hypermethylation we performed MS-PCR for p15INK4B, p16INK4A, VHL, TP53 and E-cadherin. RESULTS: The analysis of RLGS profiles from tumors revealed an abundance of hypermethylation in primary tumors and cell lines. Extrapolated to the human genome with its approximately 36,000 genes a total of 420 loci become hypermethylated in the tumor genomes. The previously characterized medulloblastoma breakpoint cluster in 17p11.2 appears to be a hotspot for aberrant methylation. Cox regression analysis of survival data identified seven CpG islands for which hypermethylation is suggestive of a poor prognosis. MS-PCR analysis of known genes demonstrated hypermethylation of p16INK4A in a limited number of tumors. The pattern of DNA hypermethylation was similar in medulloblastomas and stPNETs. However, some CpG islands were shown to be specific for a tumor type, while others were shared targets. CONCLUSIONS: Hypermethylation is a common abnormality in primary medulloblastomas and supratentorial PNETs. Several hundreds of CpG islands are potential targets for methylation in medulloblastomas including the breakpoint cluster in 17p11.2. The methylation status of certain gene sequences appears to be associated with the clinical outcome. Promoter hypermethylation has an outstanding potential as a marker for the identification of novel tumor suppressors as well as diagnostic and therapeutic targets in medulloblastomas.

Adolescent↗

New phenotype of adult alpha-L-iduronidase deficiency (mucopolysaccharidosis I) masquerading as Friedreich's ataxia with cardiopathy.

Clinical, ultrastructural and biochemical studies are reported in a 42-year-old woman presenting with congenital pes cavus who, at the age of 23 years, developed slowly progressive distal amyotrophies, hypesthesia, bilateral hearing loss and severe cardiopathy leading to death. There were skeletal anomalies, mild reduction of motor NCVs, but no corneal opacity, retinitis pigmentosa, organomegaly or vacuolated lymphocytes. Autopsy disclosed severe thickening of fibrous tissues (endocardium, cerebrospinal dura) with accumulation of vacuolated cells containing glycosaminoglycans in numerous membrane-bound cytoplasmic vacuoles, and/or compound multilamellar or zebra-body-like structures. The CNS, in addition to enlarged perivascular lacunes in cerebral white matter with lipid-containing macrophages, showed neuronal lipid storage in thalamus, hypothalamus, hippocampus, brain stem nuclei, spinal motor neurons and Purkinje cell dendrites. Ultrastructurally, lamellated inclusions containing gangliosides were seen in mesenchymal cells, oligodendrocytes, pericytes and Schwann cells. Neurons contained abundant ceroid but no lamellated inclusions. Neurochemistry revealed decrease of alpha-L-iduronidase activity in brain tissue to 4% of normal, normal activities of other lysosomal enzymes, and normal lipid and ganglioside patterns. While the morphology and neurochemistry data are characteristic of mucopolysaccharidosis I, the phenotype of adult alpha-L-iduronidase deficiency mimicking Friedreich's disease has not been described so far.

Adult↗

[Diabetes screening in pregnant patients with different risk factors. Benefits, therapeutic success, consequences].

600 ethnically heterogeneous patients with various risk factors from outpatient obstetric clinic of the UFK Ulm were screened for gestational diabetes. Incidence with the 100 g oGTT was 21%, with fasting levels having the lowest prognostic value, and one hour levels having the best. After the diagnosis of gestational diabetes was established patients were counselled and put on diet, 7% received insulin additionally. Weight gain was far more acceptable in those patients compared to the group of patients with normal metabolism. We observed no significant differences concerning fetal macrosomia, caesarean section-rates, newborn apgar and ph-values compared to normal pregnant women. We confirmed the known risk factors, personal history, familial disposition and maternal age. A screening based only on these criteria, however, would fail to detect 20% of patients with gestational diabetes. A general screening must be postulated.

Adolescent↗

Progesterone receptors are detectable in tumor fragment spheroids of meningiomas in vitro.

Progesterone receptors (PgR) are hardly to be found in monolayer tissue culture of meningiomas although 60-70% of native tissue specimens are PgR positive. Thus we examined whether RgR might be detectable in fragment spheroids of meningiomas in vitro. 25 meningiomas of 17 women and 8 men were investigated as native tissue, monolayer cell culture (primary passage and passage 3) and as fragment spheroid culture after 1 and 3 weeks. 18/25 native tissue samples revealed the PgR. There was no prevalence of sex or histological subtypes discernible. PgR was preserved in cell clumps of the primary passage but was completely lost when cells grew as monolayers (primary passage and passage 3). 21 meningiomas formed spheroids in vitro. In 8 out of 15 native PgR positive tumors the fragment spheroids showed PgR on cryosections after 1 and 3 weeks of culture. We conclude that PgR are preserved in a considerable amount of tumor fragment spheroids of meningiomas in contrast to monolayer culture. Thus spheroids seem to be a suitable tool to investigate progesterone/anti-progesterone effects in meningiomas in vitro.

Culture Techniques↗