Search PubMed⌕ Search

Biomedical subjects

H Zimmermann

Publications and source records attributed to H Zimmermann.

At least 163 records · Page 9Linked to original sources

Distribution of 5'-nucleotidase in the developing mouse retina.

The distribution of 5'-nucleotidase was investigated in the developing mouse retina and also in the retina of the adult mouse and rat using a monospecific antibody directed against 5'-nucleotidase isolated from bovine brain. Already at the stage of the formation of the eye cup strong immunofluorescence was found at the ventricular surface. Throughout development the enzyme remained associated with the outer surface of the retina that corresponds to the former inner surface of the eye vesicle. During embryonic development immunoreactivity was also associated with the proliferating cellular elements which at that stage cannot yet be attributed to a defined retinal cell type. In the adult stage the surface-located retinal immunoreactivity is assigned to Müller cells with strongest fluorescence at the apical and microvilli containing cell compartment. Also the cellular processes in the outer nuclear layer, the outer plexiform layer and to a minor extent the inner nuclear layer revealed immunoreactivity. 5'-Nucleotidase immunoreactivity was found at the ventricular surface also of the adult brain. There it was associated with the apical surface of ependymal cells. Our results suggest that 5'-nucleotidase is of general functional importance for the metabolism of nucleotides at the ventricular surface of the retina as well as the ventricles of the brain, a feature that is maintained throughout development. Müller cells thus share not only functional characteristics of astrocytes and oligodendrocytes, as previously revealed, but also of ependymal cells to which they are closely related.

5'-Nucleotidase↗

[The Sentinella reporting system in Switzerland exemplified by pertussis monitoring from 1991 to 1993. Sentinel Work Group].

Since 1986, 150 to 180 general practitioners, internists and pediatricians in private practises have reported morbidity data to the Swiss Federal Office of Public Health within the Sentinella network. Data on a certain number of infectious diseases, some noninfectious diseases and other reasons for consultation are collected through this reporting system. The number of participating physicians corresponded to 2.3 to 3.1% of all family practitioners for each of the three specialties. They also covered approximately 2.7% of the total annual number of consultations in Switzerland. In 1992/93, all cantons and all half-cantons except Nidwalden and the two half-cantons of Appenzell were represented by at least one physician who reported during 75% or more of the total reporting period. When compared to other countries, the network density of the Swiss Sentinel network is high. Since 1986, several infectious diseases have been continuously monitored by the Sentinella system (measles, mumps, rubella, influenza). Surveillance of pertussis, which was started in 1991, will be continued for several years. According to these data, an annual pertussis incidence rate of 60 out of 100,000 population and 100 out of 100,000 population was estimated in 1991/92 and 1992/93, resp. More than 55% of cases were children aged between one and eight years. Of these children, 70.4% were reported to be vaccinated, and 62.6% had a well-documented vaccination status (based on a vaccination certificate). In 95.6% of these cases, at least three vaccine doses were given.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

5'-nucleotidase activates and an inhibitory antibody prevents neuritic differentiation of PC12 cells.

Ecto-5'-nucleotidase catalyses the hydrolysis of AMP at the surface of a variety of cells whereas it is absent from others. In addition to its catalytic activity, a function in neural development and also its interaction with extracellular matrix proteins has been reported. In order to further elucidate the biological function of ecto-5'-nucleotidase we have investigated the effect of 5'-nucleotidase on nerve growth factor-induced differentiation of PC12 cells. Furthermore, we compared the effect of an inhibitory versus a non-inhibitory monospecific antibody against the enzyme on neuritic differentiation and survival of PC12 cells that constitutively express the enzyme. When coverslips are coated with the soluble form of ecto-5'-nucleotidase in addition to collagen, there is a considerable increase in nerve growth factor-induced neurite length during the first 24 h of culture. Addition of an antibody to a culture medium that inhibits 5'-nucleotidase activity to 33% of control values dramatically reduces the number of neurites per cell within 3 days of culture. The cells round up, cluster and eventually die. On the contrary, another antibody that had no significant effect on enzyme activity affected neither nerve growth factor-induced neurite formation nor survival of PC12 cells. Addition of adenosine (200 nM, 10 or 20 microM) to the culture medium did not influence PC12 cell differentiation. The effects induced by the inhibitory antibody could be only partially prevented by simultaneous application of adenosine. Our results suggest that 5'-nucleotidase is essential for nerve growth factor-induced neurite outgrowth and survival of PC12 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗

Calcium-dependent endogenous proteolysis of the vesicle proteins synaptobrevin and synaptotagmin.

The synaptic vesicle integral protein synaptobrevin/VAMP is a target of the clostridial metalloproteases tetanus toxin and botulinum toxins. We provide evidence that synaptobrevin can also be cleaved by an endogenous protease. As revealed by Western blotting proteolysis is calcium-dependent, results in the formation of an 8 kD peptide that becomes apparent within 10 min. Proteolysis can be inhibited by the chelating agents EGTA and EDTA, whereas other protease inhibitors failed to prevent degradation. In addition, a proteolytic degradation of the synaptic vesicle specific protein synaptotagmin could be observed. Other proteins including the synaptic vesicle proteins synapsin I and synaptophysin remained unaltered. Partial calcium-dependent degradation of select synaptic vesicle proteins may play a role in the life cycle of the organelle.

Animals↗

[A look back at 2 mumps outbreaks].

Two studies are presented. The first one concerns a mumps outbreak in a kindergarten in Geneva in June 1991. Of 26 children, nine (34.6%) got mumps. Of nine children vaccinated with the Rubini vaccine strain, seven had the disease as opposed to only one of 14 children vaccinated with the Urabe strain. The vaccine efficacy of the Rubini strain was estimated at 22% with a 95% confidence interval of -10% to 45%. The second study concerns a cluster of 112 mumps patients seen by a pediatrician in the Bernese Jura region between September 1992 and May 1993. A case-control study was carried out resulting in a vaccine efficacy estimate of 50% with a 95% confidence interval of -19% to 81%. Of the cases, 51 (45.5%) had been vaccinated against mumps, 50 of them (98%) with the Rubini vaccine strain. Of the controls, 30 (61.2%) had been vaccinated, 86.7% of them with Rubini. Methodological problems of case selection and their possible effects on the estimated vaccine efficacy are discussed. The results of these two studies have been confirmed by more recent investigations. In retrospect, we therefore conclude that small studies can serve as early indicators for epidemiological evidence and that they can be finally integrated into a more complete picture.

Child↗

[Mumps epidemiology in Switzerland: results from the Sentinella surveillance system 1986-1993. Sentinella Work Group].

UNLABELLED: Since 1990, there have been reports of an increasing number of mumps cases in Switzerland, in particular among vaccinated children, and of local outbreaks of mumps. Using data from the Sentinella reporting system, a network of voluntary participating doctors (general practitioners, internists and paediatricians, yearly average: n = 141), trends and factors influencing mumps incidence in the general population were assessed during the last seven years. Following an initial decline in mumps reports, since 1990, there has been a continuous and marked increase in reports from a minimum of 0.7 cases per physician and year in 1989/90 to a near five-fold increase of 3.3 cases in the last reporting period from June-December 1993 (calculated for one year). Half of this increase, which is reflected in a doubling of the number of cases reported in 1986/87, is explained by an increase in cases among vaccinated children. The trend in mumps cases contrasts with that of measles and rubella, where there has been a clear decline in these reports since 1986 (approximately 70-80%). Complications were reported in 75 (4.0%) of the total number of mumps patients (n = 1894); in 2/5 of the cases this was a meningitis, in 1/3 an orchitis. Based on available data on vaccination coverage, the estimated efficacy of the mumps vaccines against parotitis is between 47-77%; this is clearly lower than the corresponding figure for measles (91-97%) and rubella (89-97%) vaccines. The relatively low efficacy against parotitis is mainly due to a protective level of 13-73% of the vaccines containing the Rubini strain. The estimated efficacy of the Rubini vaccines against complications is 50-81%; it is nearly 60-90% if a possible reporting bias is taken into consideration. CONCLUSIONS: 1. The Rubini strain vaccines, which are the most commonly used in Switzerland, seem to have played an important role in the clear increase in mumps cases since 1990. 2. The situation seems more favourable concerning the efficacy against complications of the vaccines used. 3. Our data support the high efficacy of all measles and rubella vaccines. 4. The surveillance of MMR by the Sentinella reporting system provides a useful and effective manner to evaluate the MMR vaccination programme.

Adolescent↗

Inhibition by clostridial neurotoxins of calcium-independent [3H]noradrenaline outflow from freeze-thawed synaptosomes: comparison with synaptobrevin hydrolysis.

Clostridial neurotoxins are known to inhibit regulated, i.e. calcium-dependent exocytosis. In the present study we have investigated their potential role in also inhibiting calcium-independent exocytosis. Synaptosomes from rat forebrain were preloaded with [3H]noradrenaline and permeabilized reversibly by freezing in Ca(2+)-free potassium glutamate containing dimethyl sulfoxide and the toxins to be assayed. Subsequently, outflow of radioactivity was measured in isotonic calcium-free potassium glutamate. The synaptic vesicle protein synaptobrevin-2/VAMP-2 and its toxin-dependent degradation were analysed by Western blotting. The light chain of tetanus toxin reduced the synaptosomal outflow of radioactivity, whereas the activity of the heavy chain was at the detection limit. The respective activities of the dichain toxins from Clostridium tetani and C. botulinum A, B and E were enhanced by pretreatment with dithiothreitol. Reduced single-chain tetanus toxin was less potent than reduced dichain tetanus toxin. Pretreatment with ethylene diamine tetraacetic acid as an inhibitor of Zn(2+)-proteases abolished the actions of the tetanus toxin light chain and of the reduced dichain toxins. Hydrolysis of synaptobrevin-2/VAMP-2 was obtained with tetanus toxin light chain, reduced dichain tetanus toxin and C. botulinum B toxin. Its hydrolysis by single-chain tetanus toxin was less pronounced, and it was absent with botulinum toxins A and E. It is concluded that clostridial neurotoxins can not only inhibit calcium-dependent release but also affect calcium-independent outflow from synaptosomes. Since this is accompanied by selective intrasynaptosomal proteolysis of synaptobrevin, calcium-independent outflow may at least in part involve the vesicular release apparatus.

Animals↗

Complete nucleotide sequence and biological properties of an infectious clone of prototype echovirus 9.

The prototype Hill of echovirus 9, a human enterovirus, exhibits no pathogenicity for newborn mice in contrast to some other echovirus 9 strains isolated subsequently during epidemics. In this communication we report the first complete nucleotide sequence and construction of an infectious clone of echovirus 9. Aside from the 3' poly(A)-tract, the RNA genome is 7420 nucleotides (nt) in length and encodes a single polyprotein of 2193 amino acids (aa). The open reading frame extends from position 740 to position 7318 of the genome. Sequence comparisons to other enteroviruses reveal a strong overall amino acid identity to echovirus types 11 and 12 (in each case 76%). The proteolytic cleavage sites of the three major capsid proteins were determined after purification by HPLC and protein sequencing. A full-length clone coding for an infectious RNA transcript was constructed, and recombinant echovirus 9 particles could be isolated from the supernatant of transfected cell culture. It is shown that the recombinant virus, like the original prototype, is non-pathogenic for newborn mice and does not multiply in skeletal muscles.

Amino Acid Sequence↗

The overexpression of proliferating cell nuclear antigen in biliary cirrhosis in the rat and its relationship with epidermal growth factor receptor.

Chronic bile duct obstruction in the rat leads to biliary cirrhosis but maintained hepatocellular mass. We have previously demonstrated translocation of epidermal growth factor receptor to nuclei. It remained unclear, however, whether this was due to hepatocyte proliferation and/or altered handling of epidermal growth factor receptor. Therefore, in the present investigation we stereologically estimated expression of proliferating cell nuclear antigen, a marker of the S phase of teh cell cycle at 1, 2, 3, 7, 14, 21 and 28 days after bile duct ligation. Proliferating cell nuclear antigen positive hepatocytes averaged 2.1 +/- 3.6% in sham-operated control animals. This increased to 20.7 +/- 6.4, 26.8 +/- 18.7, 31.3 +/- 23.9, 42.3 +/- 16.6 and 24.7 +/- 28.0% 3, 7, 14, 21 and 28 days after bile duct ligation, respectively (p<0.005 by ANOVA). This was correlated with the number of epidermal growth factor receptor positive nuclei (rs = 0.737) and inversely with the maximal binding capacity of epidermal growth factor to a crude plasma membrane fraction (rs = 0.697) reported previously. We conclude that bile duct ligation in the rat induces a significant hepatocellular proliferation as assessed by proliferating cell nuclear antigen expression and that this process could, at least in part, be related to increased nuclear expression of the epidermal growth factor receptor.

Analysis of Variance↗

[Risk factors, prevention and therapy of fibrin reactions after IOL implantation].

BACKGROUND: Postoperative fibrinous reactions following the small-incision technique seem to be very rare. Problem cases can be treated with tissue Plasmin Activator. METHOD: To investigate the new prophylactic and therapeutic possibilities the last 2,056 cataract procedures with PMMA lens implantation were statistically analyzed. RESULTS: In 152 (7.4%) fibrin cases we observed after ECCE (n = 586) 12.8%, after phacoemulsification (PE) with sutured 6.5-mm corneoscleral incision (n = 546) 7.0% and after PE with clear corneal selfsealing 4.1-mm incision (n = 924) only 3.9% fibrinous reactions (p < 0.01). In case of ECCE the rate of fibrinous reactions amounted to 22.4% following prolonged procedures (< 50 min), while it was low as 9.5% with a short period of time (< 30 min) (p < 0.01). In 8 steroid-resistant cases we applied 25 micrograms Plasmin Activator intraocularly. The injections led to complete dissolution of the fibrinous membranes without complications. CONCLUSION: Postoperative fibrinous reactions can be reduced statistically significantly by application of the corneal small-incision technique. The most efficient therapy is intraocular Plasmin Activator fibrinolysis.

Aged↗

[Histomorphometric and histological investigations of the morphometric effects of furazolidone on spermatogenesis in mature rats].

The antispermatongenic effects of furazolidone on the testes of mature Wistar rats were investigated using histological and morphometric methods. The sections showed a varying degree of depopulation of the germinal epithelium, a shrinking and a deformation of the Tubuli contorti, and an enlargement of the intertubular lymphatic sinuses. The strain led to a standstill in the spermatogenesis at the primary-spermatocyte stage. After administering furazolidone, the following results could be seen: a weight loss of up to 42.1% and a decrease in testes volume by up to 30.2%; a decrease in the volume of the nuclei of the Leydig-cells by up to 51.6%; a reduction in the diameter, perimeter and area covered by Tubuli seminiferi contorti of up to 33.5%, 30.8%, and 53.4%, respectively; an increase in the number of Tubuli seminiferi contorti per mm2 by up to 44.8%; a decrease in the percentage of Tubuli seminiferi contorti of the total testes tissue by up to 39.1%.

Animals↗

Measles, mumps, and rubella: monitoring in Switzerland through a sentinel network, 1986-94. Sentinella Arbeitsgemeinschaft.

STUDY OBJECTIVES: Since 1986, the national sentinel network in Switzerland (Sentinella) has collected reports of measles, mumps, and rubella cases in order to evaluate the impact of the Swiss MMR vaccination campaign (started in 1987) on disease frequency. DESIGN: Passive surveillance of clinical measles, mumps, and rubella cases through a voluntary physician based sentinel network in Switzerland. SETTING: Each year between June 1986 and May 1994, 150 to 200 general practitioners, specialists in internal medicine, and paediatricians in private practice covering the whole country have reported weekly numbers of consultations. PATIENTS: Every patient who fulfilled the case definition and consulted a physician participating in the Sentinella network was reported. MAIN RESULTS: Since 1986, the annual number of reported measles cases per physician has fallen--from 1.3 (95% confidence interval (CI) 1.11, 1.50) in 1986-87 to 0.4 (95% CI 0.30, 0.50) in 1993-94. A decreasing trend, although less pronounced, was also observed for rubella. An initial decrease in mumps cases was reported--from 1.8 (95% CI 1.57, 2.03) annually reported cases per physician in 1986-87 to 0.7 (95% CI 0.55, 0.83) in 1989-90. This was followed, however, by a net and sustained increase. In 1993-94, the mean annual number of reported mumps cases per practitioner reached 4.7 (95% CI 4.34, 5.01) which was the highest level since surveillance had started. Over the whole eight year period, reported mumps cases, in terms of the percentage of consultations, were four times more frequent in the French speaking part of Switzerland than in the rest of the country. The proportion of mumps cases in people reported to have been vaccinated also increased--from 10% in 1986-87 to 60% in 1993-94. CONCLUSIONS: Reductions in cases of measles and rubella but an appreciable increase in mumps cases have been observed in the past three years in Switzerland. This findings, combined with increasing vaccination coverage and the fact that 60% of mumps cases are reported in vaccinated people, suggests that the overall efficacy of the mumps vaccines used in Switzerland is probably below 80%. Under these conditions the goal of eliminating mumps will probably not be reached. Further studies are needed to evaluate the efficacy of the different mumps vaccines used.

Adolescent↗

Immunocytochemical characterization of the synaptic innervation of a single spinal neuron, the electric catfish electromotoneuron.

The electric catfish, Malapterurus electricus, possesses electric organs that are innervated by a pair of identifiable electromotoneurons located within the cervical spinal cord. The pattern of synaptic innervation of the electromotoneurons can be revealed by an antibody against the synaptic vesicle protein SV2. Both somata and proximal dendrites are densely innervated. Several transmitters contribute to this innervation. Glutamate, the neurotransmitter of the dorsal root sensory fibers, reveals a weak punctuate immunoreactivity. The previously described electrical synapses of the electromotoneurons were visualized by an antibody against a gap-junctional protein. In contrast to the electromotoneurons of other electric fish, the electric catfish electromotoneurons possess many inhibitory synapses. With antibodies against glycine and against the glycine receptor, a dense immunoreactivity of the surface of the somata and proximal dendrites can be revealed. The glycine receptor-like immunoreactivity exhibits a patch-like distribution similar to that revealed by the anti-SV2 antibody. gamma-Aminobutyric acid (GABA)-immunopositive terminals contribute to the inhibitory electromotoneuron innervations to a lesser degree. The chemical characteristics of the electromotoneuron innervations of Malapterurus resemble those of other spinal motoneurons rather than spinal electromotoneurons of other electric fish. Thus our immunocytochemical study supports the view that the pattern of electromotoneuron innervations in Malapterurus reveals little specialization. The capacity for information processing required for the control of the electric organ discharge appears to be achieved by the increased integrational capacity of the newly evolved multiple dendrites and not by an additional parallel channel specific for the electromotor system.

Animals↗

Selectivity of sterically fixed tryptamine and 5-methoxytryptamine derivatives for serotonin receptor subtypes, I: Synthesis of N-alkyl- and N,N-dialkyl-3-indolylbicyclo[2.2.1]heptane-2-amines.

Twenty-six title compounds with the ethylamine part of tryptamine or 5-methoxytryptamine fixed in an anticlinal ecliptic conformation were synthesized for assaying them at the different known serotonin receptors. Several alkylation methods have been improved and adapted for the space consuming norbornane system. The structures were fully elucidated by high-field NMR spectroscopy. All 1H- and 13C-signals could be assigned by means of 1H-1H- and 13C-1H-correlation spectroscopy (COSY).

Bridged Bicyclo Compounds↗