Search PubMed⌕ Search

Biomedical subjects

M Wagner

Publications and source records attributed to M Wagner.

At least 487 records · Page 27Linked to original sources
PubMed1994

PCBs have a predominantly neurotoxic effect on dissociated cultures of the nervous system.

Although their manufacture and use have been restricted or banned in Europe and the United States since the 1970s, polychlorinated biphenyls (PCBs) are still an ubiquitous environmental contaminant whose low-term effects are as yet not completely clear. Clinical case studies of patients with occupational exposure report cognitive impairment and peripheral neuropathy. In our defined nerve cell culture models in which we use pure neurons, pure glia and mixed cultures prepared from dorsal root ganglia of chick embryos we observed a neurotoxic effect after the application of a PCB compound (Clophen). It was only at higher concentrations that an additional gliatoxic effect could be observed.

Animals↗
PubMed1994

Various stapling techniques in laparoscopic appendectomy: 40 consecutive cases.

The applicability and safety of a new operative technique for laparoscopic appendectomy using an automatic stapling device, the Multifire Endo-GIA 30, was evaluated. This instrument, which can be passed through a 12-mm trocar sleeve, compresses the appendix as well as the resting stump, occluding its lumen with three lines of titanium staples and cutting between them. Data from 40 laparoscopic appendectomy patients collected between August 1991 and March 1992 were analyzed prospectively. Using this stapler, the mean operation time was 58.33 min (range, 35-95 min), with no complications or mortality. In 35 cases, an acute, and in one case, a chronic, appendicitis was histologically confirmed; in four cases no inflammation was detected. Our preliminary results suggest that this new stapling device offers a simple and safe method for use in laparoscopic appendectomy.

Acute Disease↗
PubMed1994

Gene expression during tellurium-induced primary demyelination.

A compound may be "developmentally neurotoxic" because it interferes with a metabolic step exclusively or preferentially expressed during development in a particular class of neural cells. The initial metabolic specificity is often complicated by: (1) secondary responses in the affected cells, (2) involvement of other functionally-related cell types, and (3) the presence of compensatory and/or regenerative responses. In this context we study tellurium, which systemically blocks cholesterol biosynthesis at the squalene epoxidase step. Because of the high demand in developing peripheral nerves for newly synthesized cholesterol required for myelin assembly, this metabolic block leads to demyelination of the sciatic nerve. This insult is confounded by the fact that the myelin-forming Schwann cells do not upregulate their cholesterol biosynthetic pathway. This is contrary to expectations; liver (the main source of cholesterol for many tissues outside the nervous system) upregulates synthesis of cholesterol and overcomes the metabolic block. The shortage of cholesterol in Schwann cells results in an immediate secondary response down-regulation of steady-state mRNA levels for specific myelin proteins. Remyelination occurs after cessation of tellurium exposure. This model of primary demyelination allows study of Schwann-cell specific responses during the processes of myelin breakdown and subsequent steps leading to remyelination, without the complications of axonal degeneration and regeneration. Because tellurium specifically blocks the synthesis of a major required membrane component, it is also well suited for examining the coordinate control of membrane synthesis and assembly at the genomic level.

Animals↗
PubMed1994

[An empirical report on fissure sealing in private practice with a duration of up to 10 years].

This study reports a follow-up on 2415 occlusal sealings performed in a dental office. After nine to ten years service time, the survival rate of all sealed surfaces dropped to 69.5% because of either occlusal or interproximal carious activities. Retention of the sealings was intact in 91.5% after one year, but dropped to 58.2% after nine years. In the control group 49.3% of the grooves showed either caries or fillings during the last check-up whereas this occurred in only 7.3% of the sealed teeth (ratio 7:1). The difference among those two groups was even bigger (45.7% vs. 5%, ratio 9:1) when excluding all two-sided fillings. The costs of restoring one tooth surface in the control group was on average two to three times higher than for the sealings group. There is no doubt about the beneficial prophylactic effect of the use of sealants, even in the context of the private dental office, and no inconvenient side-effects have been found. The results concerning the retention rate of sealing in this study from a private dental office are comparable with the average of those reported in many papers from U.S. Dental Schools, they are even slightly better for the caries incidence.

Adolescent↗
PubMed1994

Confirmation of the SCA-2 locus as an alternative locus for dominantly inherited spinocerebellar ataxias and refinement of the candidate region.

The autosomal dominant spinocerebellar ataxias (SCAs) are a clinically heterogeneous group of neurodegenerative diseases. To date, two SCA loci have been identified-one locus (SCA-1) on the short arm of chromosome 6 and the second locus (SCA-2) on the long arm of chromosome 12. We have studied two large kindreds from different ethnic backgrounds, segregating an autosomal dominant form of SCA. A total of 207 living individuals, including 50 affected, were examined, and blood was collected. We performed linkage analysis using anonymous DNA markers which flank the two previously described loci. Our results demonstrate that the two kindreds, one Austrian-Canadian and one French-Canadian, are linked to SCA-2 (chromosome 12q). Multipoint linkage analysis places the SCA-2 locus within a region of approximately 16 cM between the microsatellites D12S58 and D12S84/D12S105 (odds ratio 2,371:1 in favor of this position). We show that the SCA-2 locus is not a private gene and represents an alternative SCA locus.

Austria↗
PubMed1993

Most gamma delta T cells develop normally in the absence of MHC class II molecules.

MHC class I and class II molecules are essential for intrathymic maturation of a normal repertoire of alpha beta T cells. The development of gamma delta T cells may similarly require exposure to conventional MHC or MHC-like molecules for appropriate negative and positive selection. The availability of mice that are devoid of cell surface expression of MHC class II molecules allowed us to test directly the hypothesis that conventional class II molecules play a role in the development of gamma delta T cells. The proportions of gamma delta cells in thymus, lymph nodes, and spleens were indistinguishable between class II-deficient mice and littermate controls by FACS analysis. gamma delta T cells from class II-deficient mice proliferated normally in response to anti-TCR mAb. Examination of epidermal sheets from ear, torso, and tail skin demonstrated that class II-deficient mice had the same population density and distribution of gamma delta+ dendritic epidermal T cells as that of control littermates. gamma delta Cells in the epidermis of class II-deficient mice expressed Thy-1 and CD3 and were predominantly V gamma 3+. There were no significant differences in the immunophenotype of class II-deficient mice and their normal littermates in two-color immunofluorescence analysis of intestinal intraepithelial lymphocytes. Class II-deficient mice and control mice had 29 to 39% gamma delta bearing intestinal intraepithelial lymphocytes, of which 16 to 21% expressed V delta 4. Dendritic cells that stained positively for Thy-1, CD3, and gamma delta were identified in the vaginal epithelium of class II-deficient mice and their normal littermates. Our results indicate that MHC class II expression is not essential for the development of most gamma delta T cells.

Animals↗
PubMed1993

Effect of macromolecules on the regulation of the mitochondrial outer membrane pore and the activity of adenylate kinase in the inter-membrane space.

Macromolecules as components of the physiological mitochondrial environment were substituted by dextrans of different molecular weight. The addition of 10% dextran (molecular weights varying between 20 and 500 kDa) affected neither basic mitochondrial parameters (state 4 and state 3 respiration) nor kinetic properties of soluble kinases. A significant increase by 10% dextran was however observed of the voltage sensitivity of isolated porin when reconstituted in planar bilayers. The pores adapted the low conducting state already at a voltage of 10 mV. This effect of the macromolecules may explain the higher diffusion resistance of adenine nucleotides across the outer membrane as observed in different experiments: (i) the Michaelis constant of adenylate kinase in the inter-membrane space increased, in contrast to the soluble enzyme, from 118 +/- 10 microM to 193 +/- 20 microM ADP, (ii) in the presence of competing external pyruvate kinase, the mitochondrial utilization of ADP, produced by adenylate kinase in the inter-membrane space, was improved 3-fold suggesting a reduced ADP diffusion out of the outer mitochondrial compartment. The influence of the various dextrans correlated with the increase in molecular weight of the dextrans. The effect on the kinetic constants was dependent on the dextran concentration in terms of weight and not of molarity. The oncotic pressure and viscosity of dextran solutions with different molecular weight showed a comparable dependence. In general, the data indicate that the outer membrane pore responds to an increased oncotic pressure by reducing adenine nucleotide permeability. This suggests the physiological existence of a third adenine nucleotide compartment between the two envelope membranes which may be important especially at high metabolic fluxes.

Adenosine Diphosphate↗
PubMed1993

Effect of macromolecules on the structure of the mitochondrial inter-membrane space and the regulation of hexokinase.

Macromolecules as components of the physiological mitochondrial environment were substituted by addition of 10% dextran 70. This led to a significant reduction of the space between the two envelope and the crista membranes and to an increase of contact sites as observed by freeze-fracture analysis. The preferential binding of hexokinase in these sites was employed to further analyze the dextran effect: (i) desorption of the enzyme by digitonin treatment was found to be significantly reduced in the presence of dextran although liberation of adenylate kinase and monoamine oxidase were not affected, (ii) the affinity of isolated hexokinase isozyme I to liver mitochondria was increased by dextran. Generally the binding of hexokinase to intact mitochondria (also control mitochondria) followed a co-operative mechanism and led to an activation. Cooperativity and activation were not observed when the contact formation was suppressed by dinitrophenol or glycerol. The binding of hexokinase to the isolated outer membrane resembled that of mitochondria in the absence of contacts (i.e., no cooperativity and activation). Conversely to the observation in intact mitochondria, dextran rather reduced the affinity of hexokinase to the isolated outer membrane. Kinetic analyses of the dextran effect served to explain the function of contact site specific hexokinase binding. We observed that dextran improved the hexokinase dependent stimulation of the oxidative phosphorylation (state 3 respiration), while the activity of the enzyme with internal or external ATP remained unaffected. The results suggest three things: (i) that contact sites are probably more frequent in the intact cell than in vitro in the absence of macromolecules, (ii) that the contact preference of hexokinase serves rather the ADP supply of the translocator than the ATP transfer to the enzyme and (iii) that the total cellular hexokinase activity may be regulated by specific binding of the enzyme to the contact sites, either because of a different pore structure or because of additional components exclusively exposed in these sites.

Animals↗