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Biomedical subjects

W Voigt

Publications and source records attributed to W Voigt.

At least 55 records · Page 3Linked to original sources

Molecular pharmacological aspects of antiarrhythmic activity, II: Interaction of class I compounds with calmodulin.

We have tested the calmodulin (CaM) inhibitory potency of class I antiarrhythmics in the phosphodiesterase (PDE) assay. The lipophilicity of the test compounds has been quantified by two experimental (log P, RM) and two calculative (sigma f, C log P) procedures. Five antiarrhythmics (asocainol, aprindine, lorcainide, propafenone, and ethmozine) exhibit IC50 values less than 250 microM for the inhibition of the CaM-stimulated PDE activity. Lipophilicity seems to be a prime, but not the sole descriptor of CaM inhibitory potency. The functional means of CaM inhibition by the test compounds for their antiarrhythmic properties remains to be clarified in further investigations.

Anti-Arrhythmia Agents↗

Mononuclear cell phenotypes and immunoglobulin gene rearrangements in lacrimal gland biopsies from patients with Sjögren's syndrome.

Immunocytochemical studies of lacrimal gland biopsies obtained from eight patients with Sjögren's syndrome revealed the major component of the mononuclear cell infiltrates to be comprised of B cells and Leu-3+ T-helper cells, which were present well in excess of control glands. Three of seven cases that were tested harbored cells that stained with monoclonal antibodies against different components of Epstein-Barr virus (EBV); one of the biopsies also contained cells that bore cytomegalovirus antigens. Immunoglobulin-gene rearrangements, but not T-cell receptor rearrangements, were demonstrated in one of two Sjögren's lacrimal gland biopsies tested. The authors conclude that the destruction of the tubuloacinar architecture of lacrimal gland tissue in Sjögren's syndrome appears secondary to lymphoproliferation of B cells and T-helper cells, probably derived from primary lymphoid follicles. Productive infection of lacrimal gland tissue with EBV may play a role in the pathogenesis of the syndrome in selective cases.

Adult↗

[Postoperative monitoring of pain under ibuprofen lysinate].

The post-operative pain therapy today places high demands on the quality of the drug applied as well as the necessary supplementary treatment. The results at hand show the pain time lapse and the effect of the applied methods when frequent interventions of oral surgery occur, for example wisdom tooth extraction. Characteristics of Ibuprofen-Lysinat have shown a quick pain relief within 20 minutes, after a dose of 1 to 2 tablets of 500 mg. The usage of a peripheral effective analgesic with high body compatibility has become the modern principle answer for post-operative treatment.

Adult↗

Characterization, localization and pharmacological profile of a high-affinity [3H]lidocaine binding site.

Electrophysiological findings support the existence of voltage-dependent, sodium channel-associated receptors for class I antiarrhythmics. We have tried to identify such receptors with tritiated lidocaine. High-affinity binding sites were discovered in heart and brain membranes, but liver and kidney particulate fractions had the highest density of sites. The dissociation constants were 75 nM in bovine heart and 29 nM in guinea-pig liver membranes. Binding was reversible (t 1/2: 102 s at 2 degrees C), optimal at pH 9-10 and was only partly destroyed by heat treatment. Subcellular fractionation experiments excluded a plasmalemmal association of the lidocaine site in heart. The competition profile of 16 antiarrhythmics indicated chemical comparability of the sites in heart and liver. These data greatly challenge the applicability of labeled lidocaine as sodium channel probe. The pharmacological significance of the site described here remains to be clarified.

Animals↗

Characterization of new resistance plasmids belonging to incompatibility group IncQ.

New IncQ R plasmids, pIE639 and pIE723, are characterized and compared to the prototype IncQ plasmid RSF1010. Additional resistance determinants not common on other R plasmids are located on small stretches of DNA interspacing essential regions at different positions in an otherwise unchanged core of IncQ plasmid DNA. The contribution of IncQ plasmids to resistance evolution in bacteria is discussed.

Anti-Bacterial Agents↗

Studies of immunoglobulin and T cell receptor gene rearrangement in cutaneous B and T cell lymphomas.

We report two patients with cutaneous B and T cell lymphomas, respectively, in which DNA rearrangement studies were instrumental in establishing a diagnosis. In each case clinical, histopathologic, and immunologic criteria were not sufficient to establish a definitive tissue classification. The use of DNA gene rearrangement studies in the analysis of cutaneous lymphomas is discussed.

Aged↗

Cloning and preliminary characterization of the streptothricin resistance determinants of the transposons Tn1825 and Tn1826.

Streptothricin resistance determinants have been cloned from the transposons Tn1825 and Tn1826 to the vector plasmid pUC8. The recombinant plasmids were characterized with respect to their physical structure. The resistance properties of their hosts were characterized with respect to the minimal inhibitory concentration of streptothricin and the activity of the streptothricin acetyltransferase. The proteins encoded by the cloned resistance determinants were analysed in a maxicell system. The results of our investigations suggest that the resistance to streptothricin is mediated by the activity of a streptothricin acetyltransferase with both, Tn1825 and Tn1826. However, the resistance determinant of Tn1825 is more complex than Tn1826 and additional functions involved in realizing the resistance phenotype must be recognized.

Acetyltransferases↗

Interactions of antiarrhythmics with artificial phospholipid membranes.

Binding of antiarrhythmics to phospholipids has been quantified by measuring the drug-induced fluorescence increase in 8-anilino-1-napthalenesulfonate (ANS)-treated phosphatidylcholine membranes. The ability of test compounds to increase fluorescence intensity to 50% varies between 1.3 and 88 X 10(-6) M, exhibiting a potency ratio of 1.8 log units. The antiarrythmics tested in this study exhibited a wide spectrum of lipophilicity ranging between sigma f = 6.66 for the most lipophilic compound asocainol, to sigma f = 1.21 for the most hydrophilic compound procainamide. The pKa values ranged from 10.80 for quinacainol to 6.26 for ethmozine. Consequently, the test compounds are 99.9 to 6.8% protonated at physiological pH. Binding of antiarrythmics to phosphatidylcholine membranes appears to be determined mainly by their lipophilicity (r = 0.91), irrespective of the pKa, as demonstrated for ethmozine and lidocaine which showed an excellent fit to the regression line. Binding of a variety of antiarrhythmics (n = 8) to phosphatidylcholine appeared to correlate significantly with the mean daily dosage for these drugs (r = 0.97).

Anti-Arrhythmia Agents↗

Malignant angioendotheliomatosis--a true lymphoma: a case of intravascular malignant lymphomatosis studied by southern blot hybridization analysis.

Malignant angioendotheliomatosis is a rare, systemic, usually fatal disease characterized by a massive proliferation of large, bizarre-looking mononuclear cells within small and medium-sized blood vessels. The histogenesis of the neoplastic cells has been the subject of long-standing controversy since the disease's initial description. Early investigators concluded that the entity represented a neoplasm of endothelial cells, but recently others have suggested that it is of lymphoid origin. We studied a case of malignant angioendotheliomatosis by Southern blot hybridization analysis which showed clonal rearrangements of the immunoglobulin heavy-chain gene strongly suggesting a B-lymphocyte origin. Our results provide additional evidence that malignant angioendotheliomatosis is an intravascular malignant lymphomatosis.

Aged↗

Response to tamoxifen in estrogen receptor-poor metastatic breast cancer.

While hormone receptor values are extremely valuable in breast cancer management, many variables leading to falsely negative receptor results should be considered before clinical decision making in the setting of metastatic disease. At the Papanicolaou Comprehensive Cancer Center in Miami, Florida 271 patients with metastatic breast cancer received tamoxifen over a 4-year period. Only 40 of the 204 patients (19.6%) with available estrogen receptor assay information had pretreatment receptor values classically considered receptor-poor. While four patients had inevaluable tamoxifen trials and 12 patients had "compassionate" use in end-stage situations, 24 patients received tamoxifen therapy in the face of receptor-poor values because of clinical or histopathological correlates suggesting the possibility of false negative assay results. Six of 36 evaluable patients (16.6%), including those treated on "compassionate grounds," responded to tamoxifen, while 6 of 24 more highly selected patients (25%) responded. Response durations in these six patients were 11, 12, 28, 28+, 49, and 51 months, respectively; two of these six also had significant, objective tamoxifen withdrawal responses of 9 and 14 months. Based on these results, it is urged that receptor values are studied and integrated with classical clinical and histopathologic variables before making a clinical decision so that patients with receptor-poor assay results are not prematurely labeled hormonally unresponsive.

Adult↗

Cross-reactivity of a monoclonal antibody directed against an estrogen-induced protein in MCF-7 human breast cancer cells with murine Leydig cell tumor proteins.

An estrogen-responsive murine Leydig cell tumor (M5480A) was examined for the presence of cross-reactive proteins to a monoclonal antibody directed against a Mr 24,000 estrogen-regulated protein in human breast cancer cells. Human breast tumor biopsies were used as controls for the cytosol preparations, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blot conditions used in these experiments. The estrogen-regulated Mr 24,000 protein was detected in sodium dodecyl sulfate-polyacrylamide gels of cytosols from four human breast tumor biopsies examined. Larger amounts of the Mr 24,000 protein were present in the two estrogen-progesterone receptor-positive tumor biopsies in comparison to the two estrogen-progesterone receptor-negative samples. In addition, the two receptor-positive samples demonstrated an additional, less intense immunoreactive band at Mr 21,000. Under identical conditions, the same monoclonal antibody bound to two major protein bands from sodium dodecyl sulfate-polyacrylamide gels of Leydig cell tumor cytosols at Mr 56,000 and Mr 86,000. Antibodies prepared from BALB/c mouse ascites fluid of animals bearing the parent myeloma cell line (P3X63NS1) exhibited no immunoreactivity against the human breast or Leydig cell tumor proteins. In light of the high degree of specificity which this monoclonal antibody exhibits, our results suggest that similar antigenic determinants may exist in these proteins from two distinct tumors.

Animals↗

[Cell wall proteins of Escherichia coli: a substance resembling the thermolabile enterotoxin (LT)].

In ultrasonic extracts of all 19 investigated non-enterotoxigenic E. coli strains a substance (LTLS) could be detected reacting positively in all tests which are commonly used to detect specifically E. coli thermolabile enterotoxin (LT). Culture supernatants of these strains in general did not contain LTLS in detectable amounts. LTLS can be found in the whole cell, however, the membrane fraction contains the highest quantities. Released LTLS appears mainly aggregated with components of the cell wall, especially with lipopolysaccharides. This fact in combination with the very low quantities produced by the bacteria renders very difficult purification of LTLS.

Animals↗