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Biomedical subjects

H Zimmermann

Publications and source records attributed to H Zimmermann.

At least 109 records · Page 6Linked to original sources
PubMed1999

The human papillomavirus type 16 E6 oncoprotein can down-regulate p53 activity by targeting the transcriptional coactivator CBP/p300.

The transforming proteins of the small DNA tumor viruses, simian virus 40 (SV40), adenovirus, and human papillomavirus (HPV) target a number of identical cellular regulators whose functional abrogation is required for transformation. However, while both adenovirus E1A and SV40 large T transforming properties also depend on the targeting of the transcriptional coactivator CBP/p300, no such interaction has been described for the HPV oncoprotein E6 or E7. Here, we demonstrate that the HPV-16 E6 protein, previously shown to facilitate the degradation of p53 in a complex with E6-associated protein (E6AP), also targets CBP/p300 in an interaction involving the C-terminal zinc finger of E6 and CBP residues 1808 to 1826. Furthermore, this interaction is limited to E6 proteins of high-risk HPVs associated with cervical cancer that have the capacity to repress p53-dependent transcription. An HPV-16 E6 mutant (L50G) that binds CBP/p300, but not E6AP, is still capable of down-regulating p53 transcriptional activity. Thus, HPV E6 proteins possess two distinct mechanisms by which to abrogate p53 function: the repression of p53 transcriptional activity by targeting the p53 coactivator CBP/p300, and the removal of cellular p53 protein through the proteosome degradation pathway.

Amino Acid Sequence↗
PubMed1999

Cells with morphological and immunohistochemical features of hepatic stellate cells (Ito cells) form an extralittoral (extrasinusoidal) compartment in the cirrhotic rat liver.

Systematic studies on hepatic stellate cells and myofibroblasts have so far mainly focused on cells located in the perisinusoidal space of Disse, the so-called littoral compartment. Here, these cells play a key role for intralobular fibrogenesis and sinusoidal capillarization. However, advanced hepatic fibrosis and cirrhosis are characterized by portal tract fibrosis and septal fibrosis, thus involving cells outside the perisinusoidal space. To study the question as to whether hepatic stellate cells occur and are expanded in an extralittoral (extrasinusoidal) compartment in cirrhogenesis, we systematically analyzed the distribution and density of desminreactive stellate cells in a rat model of hepatic fibrosis. Fibrosis and remodeling of the liver were induced by bile duct ligation, and stellate cells were identified by single and double immunohistochemistry. We can show that desmin-reactive cells are reproducibly detectable in extralittoral compartments of the normal and fibrotic rat liver. Periductular extralittoral stellate cells are significantly more frequent in cirrhosis, indicating that extralittoral stellate cells expand in concert with proliferating ductules. The findings suggest that ductular proliferation thought to represent a pacemaker of hepatic remodeling is accompanied by a population of cells exhibiting the same phenotype as perisinusoidal stellate cells.

Animals↗
PubMed1998

Upregulation of ecto-5'-nucleotidase in human neuroblastoma SH-SY5Y cells on differentiation by retinoic acid or phorbolester.

Ecto-5'-nucleotidase has been suggested to play an important role in neural development and differentiation in situ and in vitro. In order to investigate whether neural differentiation is associated with an upregulation of ecto-5'-nucleotidase, we used all trans-retinoic acid or phorbol-12-myristate-13-acetate to induce a neural phenotype in the human neuroblastoma cell line SH-SY5Y. Both agents initiated a reduction in proliferation and an increase in polarity of SH-SY5Y cells as well as a time dependent increase in ecto-5'-nucleotidase activity. Non-specific ecto-phosphatase activity remained unaltered. Northern hybridization experiments suggest that the increase in ecto-5'-nucleotidase activity is due to increased enzyme synthesis rather than due to enzyme activation. The upregulation of ecto-5'-nucleotidase in differentiating neuroblastoma cells would be consisted with a functional role of ecto-5'-nucleotidase in neural development.

5'-Nucleotidase↗
PubMed1998

Upregulation of the enzyme chain hydrolyzing extracellular ATP after transient forebrain ischemia in the rat.

A short ischemic period induced by the transient occlusion of major brain arteries induces neuronal damage in selectively vulnerable regions of the hippocampus. Adenosine is considered to be one of the major neuroprotective substances produced in the ischemic brain. It can be released from damaged cells, but it also could be generated extracellularly from released ATP via a surface-located enzyme chain. Using the rat model of global forebrain ischemia, we applied a short (10 min) transient interruption of blood flow and studied the distribution of ectonucleotidase activities in the hippocampus. Northern hybridization of mRNA isolated from hippocampi of sham-operated and ischemic animals revealed an upregulation of ectoapyrase (capable of hydrolyzing nucleoside 5'-tri- and diphosphates) and ecto-5'-nucleotidase (capable of hydrolyzing nucleoside 5'-monophosphates). A histochemical analysis that used ATP, UTP, ADP, or AMP as substrates revealed a strong and selective increase in enzyme activity in the injured areas of the hippocampus. Enhanced staining could be observed first at 2 d. Staining increased within the next days and persisted at 28 d after ischemia. The spatiotemporal development of catalytic activities was identical for all substrates. It was most pronounced in the CA1 subfield and also could be detected in the dentate hilus and to a marginal extent in CA3. The histochemical staining corresponded closely to the development of markers for reactive glia, in particular of microglia. The upregulation of ectonucleotidase activities implies increased nucleotide release from the damaged tissue and could play a role in the postischemic control of nucleotide-mediated cellular responses.

Actins↗
PubMed1998

Formation and sequence analysis of secretoneurin, a neuropeptide derived from secretogranin II, in mammalian, bird, reptile, amphibian and fish brains.

Secretoneurin is a recently-characterized neuropeptide derived from secretogranin II, a protein belonging to the class of chromogranins. We investigated the phylogeny of this peptide by immunoblotting and gel-filtration high performance liquid chromatography followed by radioimmunoassay of brain extracts of various species including chicken, lizard, frog and fish. In addition the amino acid sequence of secretoneurin from pig, hamster, rabbit, guinea-pig and chicken was established by reverse transcriptase polymerase chain reaction. Secretoneurin is strongly conserved during evolution, it is not only expressed in various mammalian species but found also in the brain of birds, reptiles, amphibians and fish. In all these species a significant or near complete processing of secretogranin II to secretoneurin was observed. These data provide significant evidence for the neuropeptide nature of the novel functional peptide.

Amino Acid Sequence↗
PubMed1998

Association of ecto-5'-nucleotidase with specific cell types in the adult and developing rat olfactory organ.

A unique feature of the olfactory epithelium is its ability to give rise to new sensory neurons throughout life and also following injury. Cells at the basal side of the epithelium serve as neurogenic progenitor cells. The enzyme ecto-5'-nucleotidase is expressed at the surface of developing nerve cells and is regarded as a marker of neural development. To study the expression pattern of the enzyme, we analyzed its distribution in the adult and developing rat olfactory organ. Labeling is restricted to specific cell types and varies between the epithelia investigated. At the basal side of the olfactory epithelium, activity of 5'-nucleotidase is associated specifically with the dark/horizontal basal cells. Neither the light/globose basal cells, which are the immediate precursors of the sensory receptor cells, nor subsets of potentially immature olfactory receptor cells are labeled. On the other hand, microvillar cells dispersed at the lumenal side of the epithelium contain 5'-nucleotidase activity. The enzyme is also present at the inner lining of the ducts of Bowman's glands as they traverse the epithelium. Within the respiratory epithelium, activity of 5'-nucleotidase is associated with basal cells as well as with the epithelial surface. During development, 5'-nucleotidase is initially limited to the respiratory epithelium, including its basal cells. Dark/horizontal basal cells of the olfactory epithelium, which are positive for 5'-nucleotidase, first appear at the border of the respiratory epithelium, suggesting that they might originate from immigrating basal cells of the respiratory epithelium. Within the vomeronasal organ, labeling is largely restricted to the receptor-free epithelium. Although the functional role of 5'-nucleotidase in the olfactory system needs to be further defined, the distribution of the enzyme can be used successfully as a marker for defined cell types.

5'-Nucleotidase↗
PubMed1998

Mortality from respiratory tuberculosis in Switzerland.

Since 1901, the Swiss Federal Office of Statistics has published at least each decade detailed mortality statistics from tuberculosis. These cross-sectional data on deaths from respiratory tuberculosis from 1901 to 1991 were utilized to analyse retrospectively tuberculosis death experience within each birth cohort. The cross-sectional data indicate that tuberculosis mortality increases with age in each successive decade. Nevertheless, the cohort-contour approach indicates that this phenomenon is the result of a much higher mortality that each cohort experienced in their early adulthood, and that mortality form respiratory tuberculosis in Switzerland always preferentially affected the young. The data also indicate that tuberculosis mortality in Switzerland has been decreasing for at least 160 years, and perhaps peaked as early as in the eighteenth century.

Adolescent↗
PubMed1998

[Epidemiology of hepatitis B in Switzerland].

Between 1988 and 1996, the Swiss Federal Office of Public Health received 200 to 500 reports of acute hepatitis B each year, mostly affecting adults aged 15 to 40 (80% of all reports). Considering the problem of underreporting and the fact that most infections are asymptomatic or remain undiagnosed because of atypical symptoms, the yearly incidence of new infections is estimated to be between 2000 and 3000. About 20,000 persons are chronically infected (0.3% of the population) and acute and chronic complications of hepatitis B (fulminant hepatitis, cirrhosis, hepatocarcinoma) lead to an estimated 40 to 80 deaths each year.

Adolescent↗
PubMed1998

[Transmission of hepatitis B].

Hepatitis B is transmitted by three main routes: contact with blood and body fluids, sexual contacts, and perinatally from the infected mother to her newborn baby. Horizontal transmission within the household of an infected person is common, especially in families with infants. In such situations, unnoticed contacts with blood probably account for most of the transmissions.

Blood-Borne Pathogens↗
PubMed1998

[Prevention of hepatitis B (excluding vaccination)].

The immunisation programme against hepatitis B should not neglect other preventive measures. The main measures are: Always use condoms with casual sexual partners, do not exchange syringes or injection material, always apply universal precautions with blood and other biological liquids as these must always be considered potentially infectious.

Female↗
PubMed1998

[Hepatitis B vaccination strategies].

With the introduction of a vaccine against hepatitis B in the early 1980s, a vaccination strategy targeted at high risk groups was implemented in most developed countries. Although such a strategy is efficient on an individual basis, it has been shown that it only has a limited impact on the overall rate of infections in the population. Public health authorities were therefore prompted to additionally recommend a universal vaccination strategy to reduce and ultimately eliminate hepatitis B infections. The option to primarily vaccinate infants, adolescents or both age groups depends on the epidemiological situation of a country, the availability of organisational facilities, financial resources and acceptability. Combining a targeted and a universal vaccination strategy provides the optimal protection against hepatitis B, both at an individual and population level.

Adolescent↗
PubMed1998

[Introduction of general hepatitis B vaccination in Switzerland].

The Swiss Federal Office of Public Health and the Advisory Board on Immunisation recommended that all adolescents aged 11 to 15 should be vaccinated against hepatitis B in December 1997. The introduction of universal immunisation is justified for epidemiological and economical reasons. Universal immunisation in no way excludes the immunisation of all persons exposed to a specific risk and the prenatal screening and immunisation of exposed newborns. Hepatitis B vaccines are safe and highly effective. The main reasons for this recommendation are summarised in the article.

Adolescent↗
PubMed1998

[Information strategy for physicians and public health regarding introduction of general hepatitis B vaccination in Switzerland].

Information is extremely important for immunisation programmes. The information should be clear, transparent, easily accessible and adapted to the different target populations. Parents consider the information presently available to be insufficient. This constitutes an obstacle to the introduction of universal vaccination against Hepatitis B in Switzerland. The population groups targeted by the information have to be the public health authorities, physicians, adolescents, parents and teachers. Various documents are now available or in preparation and should allow an effective discussion between these different partners.

Adolescent↗
PubMed1998

Approaches to the replacement of ethinylestradiol by natural 17beta-estradiol in combined oral contraceptives.

The strong hepatic estrogenic actions of ethinylestradiol (EE) are very likely to be the cause of the cardiovascular morbidity related to the use of combined oral contraceptives (COCs). This survey presents results of EE replacement in COCs with natural 17beta-estradiol (E2) in the following stages: reduction of EE to daily doses of 0.01 mg and concomitant replacement with E2 (as valerate, EV), complete replacement of EE with E2 using a novel multiphasic combination containing EV and the progestin dienogest (DNG), and the use of natural E2 to develop estrogen sulfamates (J 995) showing sufficient dissociation of uterine from liver estrogenicity. Recent data from preclinical and clinical studies show that these approaches seem to be promising.

Animals↗
PubMed1998

A novel YY1-independent silencer represses the activity of the human papillomavirus type 16 enhancer.

Regulation of the human papillomavirus type 16 (HPV-16) E6 promoter is a complex process in which transcriptional repression as well as activation plays an important role. Here, we identify a negative regulatory element that in the context of a continuous long control region fragment overcomes the activation of the HPV-16 enhancer. This silencing element, which we have termed a PSM (papillomavirus silencing motif), consists of two copies of the sequence 5'-TAYAATAAT-3' that overlap the origin of replication. Each copy of this 9-bp sequence binds the same unknown cellular factor, which we refer to as PSM-BP (PSM binding protein). Both copies of the binding sequence are required for transcriptional repression, and we provide evidence that suggests that this particular organization results in the stabilization of a PSM-BP dimer. The silencing motif, while functioning in either orientation, showed a positional requirement between the enhancer and the promoter. Experiments with both a heterologous enhancer and a promoter also demonstrated a general ability of this element to function as a transcriptional silencer in non-HPV systems. Our findings provide an important addition to our understanding of HPV-16 gene regulation and an interesting model for the study of transcriptional repression.

Base Sequence↗
PubMed1998

False positive staining in the TUNEL assay to detect apoptosis in liver and intestine is caused by endogenous nucleases and inhibited by diethyl pyrocarbonate.

BACKGROUND: The terminal transferase uridyl nick end labelling (TUNEL) assay allows the easy demonstration of cell death as a result of apoptosis. However, when this assay is applied to liver tissue, the number of TUNEL positive cells is dependent on the time of incubation with proteinase K. AIM: To test whether false positive results are the result of the release of endogenous endonucleases by proteinase K and can be abolished by pretreatment with diethyl pyrocarbonate (DEPC). METHODS: Involution of hyperplastic ductules in bile duct ligated rats after biliary decompression by Roux-en-Y anastomosis and acute CCl4 intoxication were studied as models of apoptosis and necrosis, respectively. A standard TUNEL assay was applied to formalin fixed tissue sections mounted with cement. To inhibit putative endogenous endonucleases, tissue slides were pre-incubated with DEPC. RESULTS: In the standard TUNEL assay, the number of positive nuclei was highly dependent upon the length of time that sections were incubated with proteinase K. After pretreatment with DEPC, only cells that also exhibited morphological features of apoptosis stained positive. DEPC pretreatment abolished false positive staining in CCl4 induced hepatocyte necrosis and blocked interference by endogenous alkaline phosphatase in intestine. The method of gluing the tissue section to the glass slide was found to be of utmost importance because the effect of DEPC was abolished on silanised slides. CONCLUSIONS: False positive staining in the TUNEL assay in the liver is caused by the release of endogenous endonucleases as a result of proteinase treatment. This can be abolished by pretreatment of tissue slides with DEPC.

Animals↗