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H P Zimmermann

Publications and source records attributed to H P Zimmermann.

At least 19 recordsLinked to original sources

Invasive meningococcal and pneumococcal disease in Switzerland: cost-utility analysis of different vaccine strategies.

We performed a cost-utility analysis for various vaccination strategies against meningococcal and pneumococcal diseases (MenC or MenC/PCV-9) in Switzerland. The analysis compared the current recommendations of vaccinating only children with medical risks to the introduction of the vaccination with either the MenC or the MenC/PCV-9 vaccine, administered at 12 or 2, 4 and 6 months of age, into the existing immunisation programme. For a birth cohort of 80,000 children and assuming a vaccine coverage of 80%, the introduction of a generalised vaccination would be cost-effective. The strategy using three doses of MenC/PCV-9 would achieve the highest health benefit, with 440 quality-adjusted life years (QALYs) gained at costs of 34,000 per QALY.

Child↗

[Vaccine complications].

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Adverse Drug Reaction Reporting Systems↗

Surveillance of sexually transmitted diseases in Switzerland, 1973-1994: evidence of declining trends in gonorrhoea and syphilis.

The HIV/AIDS epidemic has led to growing interest in the epidemiology of sexually transmitted diseases (STDs) in Switzerland. STD surveillance data from three sources are presented: reports from six policlinics of dermatovenereology since 1973, laboratory reports of Neisseria gonorrhoeae, Treponema pallidum and Chlamydia trachomatis since 1988, and reports by the Swiss Sentinel Network between June 1991 and December 1993. The data indicate that there has been a decline in the number of cases of syphilis and, in particular, gonorrhoea since the early 1980s in Switzerland. Since many factors could explain the declines (e.g. more effective treatments, more widespread use of antibiotics, marked changes in behaviour such as increased levels of condom use) it is difficult to identify their exact causes. Evidence for two of the before-mentioned factors exists and these probably played important roles in the declines. Firstly, as a result of the emergence of penicillinase producing strains of N. gonorrhoeae, the introduction of new treatments for gonorrhoea in the early 1980s which were simpler to administer and more effective (in particular the use of spectinomycin). Secondly, the national AIDS prevention campaign which began in 1987 and has been associated with major increases in condom use in the Swiss population.

Adolescent↗

Ran-binding protein 5 (RanBP5) is related to the nuclear transport factor importin-beta but interacts differently with RanBP1.

We report the identification and characterization of a novel 124-kDa Ran binding protein, RanBP5. This protein is related to importin-beta, the key mediator of nuclear localization signal (NLS)-dependent nuclear transport. RanBP5 was identified by two independent methods: it was isolated from HeLa cells by using its interaction with RanGTP in an overlay assay to monitor enrichment, and it was also found by the yeast two-hybrid selection method with RanBP1 as bait. RanBP5 binds to RanBP1 as part of a trimeric RanBP1-Ran-RanBP5 complex. Like importin-beta, RanBP5 strongly binds the GTP-bound form of Ran, stabilizing it against both intrinsic and RanGAP1-induced GTP hydrolysis and also against nucleotide exchange. The GAP resistance of the RanBP5-RanGTP complex can be relieved by RanBP1, which might reflect an in vivo role for RanBP1. RanBP5 is a predominantly cytoplasmic protein that can bind to nuclear pore complexes. We propose that RanBP5 is a mediator of a nucleocytoplasmic transport pathway that is distinct from the importin-alpha-dependent import of proteins with a classical NLS.

Amino Acid Sequence↗

[Effect of conjugated PRP vaccines on the incidence of invasive diseases caused by Haemophilus influenzae Type B in childhood].

Prior to the introduction of conjugate vaccines, Haemophilus influenzae type b (Hib) was the leading cause of severe invasive infections in young children, in Switzerland as in other countries. From 1976 to 1990, 150 children were treated for Hib meningitis at the Children's Hospital of Lucerne, corresponding to an annual incidence of 9.2 cases per 100,000 children aged under 15 years. In the same time period, the case fatality rate for meningitis was 4%. 87.3% of the meningitis cases occurred among children aged under 5 years. For this age group an annual incidence of 26.4 cases per 100,000 children was calculated. From 1979 to 1990, 141 children were hospitalized for epiglottitis, corresponding to an annual incidence of 10.9 cases per 100,000 children aged under 15. The introduction of conjugated vaccines resulted in a significant reduction in the frequency of invasive Hib disease. From 1991 to 1992, 9 cases each of meningitis and epiglottitis were observed. In 1993, only one case of meningitis and 2 cases of epiglottitis were seen. For children under 15 years these 21 cases represent annual incidences of 3.2 cases of meningitis and 3.6 cases of epiglottitis per 100,000 children. 2 of 10 meningitis cases occurred in twice vaccinated children under 2 years of age with no signs of immunodeficiency, and another case was seen in a 5-month-old infant vaccinated with only one dose. Assuming a vaccination coverage of 70% among children under 5 during the years 1991 and 1992, the calculated efficacy is 80 to 85% for the vaccine PRP-D in this predominantly affected age group during the period when only this vaccine was available.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparison of the epidemiology and cost of Haemophilus influenzae type b disease in five western countries.

To determine and compare the cost of Haemophilus influenzae type b (Hib) disease in Australia, Finland, Israel, Switzerland and the United Kingdom a collaborative study was undertaken. The incidence of Hib disease varies in these 5 countries from 34 to 58.5 cases per 100,000 children less than 5 years of age. Although the incidence of meningitis in this age group is similar (between 18 and 26/100,000) in these countries, the incidence of epiglottitis varies from 0 to 22.7/100,000. The cost of hospitalization and the frequency of sequelae are similar for 4 of the 5 countries; however, the break even cost of a vaccination program to prevent 90% of Hib disease is estimated to vary from $22 to $84 per child (US$). Because of a lower incidence of Hib disease and lower cost for hospitalization, these costs are considerably less than those for the United States ($301.64 using similar calculations).

Australia↗

Monoclonal antibodies distinguishing between two rat pancreatic carcinoma cell lines with different metastatic capacities.

Two new monoclonal antibodies, E5/E10 and E10/B4, were raised which reacted with surface antigens on the metastatic rat pancreatic adenocarcinoma cell line ASML, but not with antigens localized on the cell surface of the nonmetastatic rat pancreatic adenocarcinoma line AS. These two monoclonal antibodies are of the IgG1 subclass and recognize protein bands with molecular weight 28,000 and 35,000 D. E5/E10 and E10/B4 cross-reacted only with antigens on the human colon cancer cell line HT-29, as well as with normal rat kidney.

Adenocarcinoma↗

[Mortality in influenza epidemics in Switzerland 1969-1985].

In Switzerland from 1969-1985, 9 out of 11 influenza epidemics were associated with a statistically significant increase in mortality. A total of 12,202 excess deaths from all causes was identified. Expected deaths were forecast for each epidemic period separately for 4 age groups using Fourier and Arima modeling. 75.7% of all-cause excess deaths occurred in age group 70 to 89 and 5.1% in age group 1-59. In the 70-89 years old group the excess mortality risk during influenza epidemics was 271.6 per 100,000, whereas in age group 1-59 it was only 1.7 per 100,000. Only 40% of all excess deaths had been ascribed to acute respiratory conditions. Influenza viruses A H3N2 were the most frequently identified agents. In some instances mortality increased before the morbidity reports of the Swiss practitioners indicated the occurrence of an epidemic. Also, morbidity reporting decreased over successive years. A decrease in mortality following the epidemics was not observed. A more complete vaccination of high risk patients in Switzerland is desirable.

Adolescent↗

Fusion of lipid vesicles with ascites tumor cells and their lipid-depleted variants. Studies with radioactive- and fluorescent-labeled vesicles.

Cultured ascites tumor cells and their lipid-depleted variants, which contained 35-40% less membrane phospholipid and cholesterol, were used for fusion experiments with unilamellar lipid vesicles which were between 300 and 600 nm in diameter. Vesicle-cell interaction was followed by tracer studies using vesicles double-labeled in the lipid moiety, by vesicle-encapsulated [3H] dextran, and by measurements of energy transfer between N-(10-[1-pyrene]decanoyl)sphingomyelin-labeled vesicles and alpha-parinaric acid-labeled cells in the presence of poly(ethylene glycol) (PEG) as fusogen. The reaction rates measured with the radiolabeled vesicles were found to follow patterns similar to those obtained with the resonance energy transfer assay. This latter method revealed a vesicle-cell membrane fusion reaction, which was substantiated by radiolabeling the internal cellular compartment after treatment of the cells with [3H]dextran-encapsulated vesicles as shown by electron microscopic autoradiography on semi-thin sections. Endocytosis as a reaction mechanism can be excluded, since no energy transfer was observed at 25 degrees C in the absence of PEG. Investigations of vesicle bilayer order and fluidity on vesicle-cell interaction revealed optimal reactivity, with intermediate fluidity corresponding to cholesterol/phospholipid ratios between 0.7 and 1.0 and fluorescence depolarization (P) values of 0.18 and 0.21. Lipid depletion decreased the reaction velocity between cells and vesicles by about 20%, exhibiting V values of 33.2 mumol/min, as compared to the control of 41.4 mumol/min determined for 10(7) cells. The affinity constants for vesicle lipid were affected only slightly with Km values of 0.195 mM (0.210 mM). The activation energies for the reaction were calculated to give values of EA = 22.44 kJ/mol for the control and of EA = 20.4 kJ/mol for the modified cells. These data indicate that the decrease in membrane lipid content apparently has no major influence on the extent of the interaction.

Animals↗

Identification of the phosphorylated beta-tubulin isotype in differentiated neuroblastoma cells.

The tubulin molecule consists of an alpha- and a beta-subunit, each of which exists in several isotypic forms. It has been previously shown that one of the isotypes of neuroblastoma beta-tubulin is phosphorylated at a serine residue in vivo [(1985) J. Cell Biol. 100, 764-774]. Here we identify the phosphorylated isotype as beta 2 (type III). Moreover, the large size of the phosphorylated tryptic peptide and sequence comparisons of vertebrate beta-tubulins suggest that one of the two serines in positions 444 and 446 is the phosphorylated residue. Our results raise the possibility that beta 2-tubulin differs functionally from the other beta-tubulin isotypes.

Cell Differentiation↗

Microtubule rearrangements during mitosis in multinucleate cells.

The peroxidase-antiperoxidase (PAP) method for the detection of polymerized tubulin has been used to study the microtubule rearrangements during mitosis in PtK1 and HeLa multinucleate cells obtained by polyethyleneglycol (PEG)-mediated fusion. We demonstrate here that the transition of the microtubular cytoskeleton from interphase to mitosis is an inducible event and independent of the factor(s) responsible for chromatin condensation and nuclear envelope breakdown. However, for the induction of the microtubule rearrangements nuclear envelope breakdown is required. At midprophase, cytoskeletal microtubule rearrangements start for multinucleate PtK1 cells, whereas in HeLa cells such changes are delayed, and a more abrupt transition is observed here. After complete nuclear envelope breakdown (prometaphase) mitotic asters and spindles but no cytoplasmic (interphase) microtubuli can be observed in both systems. Metaphase is characterized by an interaction between the different mitotic poles which show the form of bipolar spindles, but individual separated mitotic poles far removed from the chromatin can also be seen.

Animals↗

The interaction of triethyl lead with tubulin and microtubules.

The impact of triethyl lead chloride was studied on: (i) the in vitro assembly and disassembly of microtubules from porcine brain by turbidometry and electron microscopy, (ii) the microtubule system of living mammalian cells using immunofluorescence microscopy, (iii) cell motility and chemotaxis employing the methods of phagokinetic track formation and the Boyden chamber assay, respectively, and (iv) thiol groups of the protein tubulin by their titration in the presence and absence of the organic lead compound. Triethyl lead chloride inhibited microtubule assembly and depolymerized preformed microtubules in vitro and in living cells. Random motility of cells was not markedly inhibited by triethyl lead chloride, whereas chemotaxis (directed cellular movement) was strongly inhibited. Triethyl lead chloride was found to interact with 2 thiol groups of the tubulin dimer. The interaction of triethyl lead chloride with the tubulin/microtubule system in vivo likely causes aneuploidy and is at least partly responsible for the cytotoxicity of the drug.

Animals↗

Influence of triethyl lead on neurofilaments in vivo and in vitro.

The influence of triethyl lead chloride (TriEL) on the organization of neurofilaments in vivo was studied by indirect immunofluorescence microscopy employing mouse neuroblastoma cells (Neuro-2a). TriEL induces perinuclear coil formation of neurofilaments in those cells. The rearrangements observed are not correlated with significant changes of the microtubular system. Cells in which the microtubular network was stabilized by Taxol treatment prior to incubation with TriEL even show the rearrangement of the neurofilaments. The effect of TriEL is reversible. In vitro, the effect of TriEL on isolated neurofilaments and on filament formation as well as on the structure of preformed filaments was investigated by electron microscopy. If isolated neurofilaments from porcine spinal cord are incubated in the presence of TriEL, they show constrictions and bulges. Additionally, many fragments are seen. If preformed filaments are treated with TriEL, unraveling of fibers into protofilamentous strands is observed. The assembly of neurofilaments in vitro is disturbed in the presence of TriEL. The interaction of TriEL with neurofilaments in vivo is likely to be at least partly responsible for the neurotoxicity of TriEL.

Animals↗

Radiation induced formation of giant cells in Saccharomyces uvarum. III: Effect of X-rays on nuclear division.

Spindle formation and nuclear division of budding and irradiated yeast cells (Saccharomyces uvarum) was investigated by fluorescence microscopy of protoplasted cells. Protoplasts were treated with antitubulin antibodies and DAPI, a fluorescent dye staining DNA. In budding yeast cells, duplication of spindle pole bodies as well as formation of complete 1-micron spindles and elongated 8-micron spindles were documented. In X-irradiated cells, spindle pole bodies were duplicated as well, forming the complete 1-micron spindle. Nuclei of giant cells have lost the elongation ability and remain in a "normal" G2-phase state, thus preventing nuclear as well as cellular division.

Cell Cycle↗

[Morbidity detection in general practice].

A system of morbidity registration in the domain of primary health care is presented on the basis of experiences made abroad. A pilot project (Sentinella) functions in the environments of Berne since November 1984. Its extension to the whole of Switzerland is scheduled for the middle of 1986.

Air Pollution↗