After intravenous injection, sotalol follows a two-compartment distribution pattern. The processes of distribution and elimination are of first order; the intravenous biological half-life is 6 to 8 hours. The drug is mainly excreted by glomerular filtration via the kidney, and metabolites are not found. Of the pharmacodynamic parameters measured, the isoproterenol-induced changes in heart rate, diastolic blood pressure, and free fatty acid return to baseline values immediately during the injection of the beta blocker. Peripheral arterial circulation, lactate, glucose, and pyruvate respond to the beta blocker after a delay. Besides the compartmental distribution of sotalol, other mechanisms of sotalol such as varying responses of the receptors to sotalol or more sluggish intrinsic kinetics of the decrease of parameters measured have to be considered. The effects of various beta blockers may be qualitatively and quantitatively differentiated on the basis of experiments with our test model using steady-state isoproterenol infusion in humans.

Adult↗

PubMedDate not supplied

[Helicobacter pylori associated gastrointestinal mucosal lesions: is there an increased risk during therapy with nonsteroidal antirheumatic agents?].

ENDPOINTS: Are there connections between Helicobacter pylori-induced and NSAID-induced gastrointestinal mucosal lesions leading to an increased risk? Are there any diagnostic or therapeutic consequences? METHODS: Evaluation of H.P. infection, NSAID medication and mucosal lesions in 303 patients with rheumatic diseases. RESULTS: The prevalence of H.P. infection was 67.7%. Positive H.P. antibodies were found in 96.2% of patients with mucosal lesions, confirmed by endoscopy. There was no statistically significant increase of mucosal lesions in patients with both H.P.-infection and NSAID therapy. CONCLUSIONS: The main cause for gastrointestinal mucosal lesions is H.P. infection (> 90%). A general mucoprotective therapy in patients with H.P. infection and NSAID therapy cannot be supported. It may be supposed that a part of mucosal lesions connected to NSAID-therapy in recent decades probably was the consequence of H.P. infections. Eradication of H.P. might be of higher importance in the future.

Adult↗

PubMedDate not supplied

Kinetics of endosomal acidification in Dictyostelium discoideum amoebae. 31P-NMR evidence for a very acidic early endosomal compartment.

We have examined the pH of the various endosomal compartments in the amoebae of the cellular slime mould Dictyostelium discoideum. This was accomplished both by fluorescence and by in vivo 31P-NMR methods. The fluid-phase marker, fluorescein-labeled dextran, was fed to the amoebae to report the average pH of their endocytic vesicles. During the progressive loading of successive endosomal compartments, we observed an early acidification down to a minimum value of pH < or = 5.3 after 30 min at 20 degrees C followed by an increase to an average pH of 5.8 when all the endosomal compartments were loaded by the fluid-phase marker. The weak fluorescence intensity of FITC-dextran at acidic pH precluded a more detailed investigation and we checked various phosphonate compounds as potential 31P-NMR pH probes for the endosomal compartments. Two molecules, aminomethylphosphonate and 2-aminoethylphosphonate, were selected for this study because of the large amplitudes of their chemical shift variation with pH (2 and 2.5 ppm, respectively) and their acidic pKs of 5.5 and 6.3, respectively. They were only moderately toxic (IC50% approximately 10 mM) towards both the axenic growth and the differentiation program of Dictyostelium amoebae. Internalization of the two aminophosphonates occurred only through the fluid-phase pinocytosis pathway as revealed by the full inhibition of their entry with 1 mM vanadate or 7.5 mM caffeine, two previously characterized inhibitors of endocytosis in Dictyostelium. We found that in vivo 31P-NMR of amoebae suspensions incubated with the aminophosphonates allowed the detection of three distinct intracellular compartments at pH 4.3, 5.8-6.0 and 7.3. Kinetics of aminophosphonate entry were analyzed and the results allowed us to reconstruct the time course for the acidification sequence during endocytosis. The data are consistent with the hypothesis that in Dictyostelium amoebae phosphonates occupy a highly acidic early endosomal compartment (t1/2 = 18 min; pH 4.3) before reaching a less acidic late endosomal/prelysosomal compartment (pH 5.8-6.0) from where they are immediately transported to, and trapped in, the cytoplasm (pH 7.3).

Acids↗

PubMedDate not supplied

Induction of anti-tumor activity following autologous stem cell transplantation: immunotherapeutic implications.

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Acute Disease↗

PubMedDate not supplied

Acute glomerulonephritis preceded by passage of uric-acid calculus.

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Acute Disease↗

PubMedDate not supplied

UV light-induced immunoglobulin heavy-chain class switch in a human lymphoblastoid cell line.

During attempts to select nonsecretory variants from 0.467.3, and Epstein-Barr virus-transformed human lymphoblastoid cell line that secretes small amounts of IgM lambda, we exposed the cells to UV light. Cells that survived the irradiation were subcultured and their supernatants were screened for immunoglobulin production by an enzyme-linked immunosorbent assay (ELISA). Although stable nonsecretory variants were not isolated, we report here that an immunoglobulin class switch occurred in the UV-treated cell population. All survivors were found to produce large quantities of IgG lambda. Some cell cultures also produced the original IgM lambda. The UV-light-induced class switch was regularly reproducible with this target cell line.

Cell Differentiation↗

PubMedDate not supplied

Rat c-myc oncogene is located on chromosome 7 and rearranges in immunocytomas with t(6:7) chromosomal translocation.

Two B-cell-derived tumours, human Burkitt's lymphoma (BL) and murine plasmacytoma (MPC), are regularly associated with a distinctive form of chromosomal translocation (for reviews see refs 1, 2). In BL, the distal portion of chromosome 8 breaks off and is transposed, in most cases, to chromosome 14, known to carry the immunoglobulin heavy-chain locus. In about 5% of the cases the same distal part of the chromosome 8 has moved to either chromosome 2 or 22, to the neighbourhood of the kappa or the lambda locus, respectively. In MPC the distal region of chromosome 15 is transposed to the chromosome 12, known to carry the immunoglobulin heavy-chain locus, or enters into reciprocal exchange with the kappa locus-carrying chromosome 6 (ref. 7). Several laboratories have located c-myc, the cellular homologue of the MC29 retroviral oncogene v-myc, to human chromosome 8 (refs 8-10) and mouse chromosome 15 (refs 11-13). It has also been shown that the BL- and MPC-associated translocations remove the c-myc gene from its original site and transpose it into or close to one of the immunoglobulin gene clusters. In view of the above findings we also looked for possible involvement of the c-myc gene in a B-cell-derived tumour of a third species, the rat. Rat immunocytomas of spontaneous origin carry a reciprocal translocation between chromosomes 6 and 7 (ref. 17). Here we have localized the c-myc locus to chromosome 7 of the rat. Moreover, we have found that the c-myc gene was rearranged in four of five immunocytomas carrying the characteristic chromosomal translocation.

Animals↗

PubMedDate not supplied

Evolution of tumours and the impact of molecular oncology.

It is generally accepted that tumours arise through the accumulation of several changes affecting the control of cell growth. Recent advances in molecular biology have made it possible to define some of these changes in molecular terms and to trace the steps by which certain tumours evolve.

Animals↗

PubMedDate not supplied

Elevated c-myc expression facilitates the replication of SV40 DNA in human lymphoma cells.

The v-myc oncogene can induce tumours in haematopoietic, mesenchymal and epithelial tissues. The corresponding c-myc proto-oncogene can contribute to the genesis and/or the progression of an equally wide variety of tumours when activated by retroviral insertions, chromosomal translocations or gene amplification. The c-myc gene product is a DNA-binding, nuclear phosphoprotein that is involved in the control of cell proliferation and possibly in DNA synthesis. The replication of Simian virus 40 (SV40) is a useful model system to study eukaryotic DNA replication as the virus relies almost entirely on cellular DNA replication apparatus. The SV40-based vector, pSVEpR4, replicates poorly in the human BJAB lymphoma line and in most human cells, but replicates well in Burkitt lymphoma lines, which have fused immunoglobulin and c-myc genes, resulting in high c-myc expression. Cotransfection of the BJAB cells with a c-myc-expressing construct (pI4-P6) increased the replication of pSVEpR4 tenfold. Our findings indicate that overexpression of the c-myc gene product allows the replication of SV40 in human lymphoma cells, suggesting that c-myc is involved in the control of replication.

Antigens, Viral, Tumor↗

PubMedDate not supplied

[Inhalation bronchial provocation tests in children: comparative measurements of oscillation, occlusion pressure and plethysmographic resistance].

Examination of the lung function and bronchial provocation tests are useful for confirmation of an airway obstruction. There is a need for measurements independent of child cooperation. The standard method is body plethysmography. Forced oscillation method and interrupted occlusion method were recently introduced. Measurements of airway resistance by body plethysmography (Raw), by forced oscillation (Ros) and by interrupted occlusion method (Rvd) were compared during 78 inhalative bronchial provocation tests. The correlation index between Raw and Ros total was 0,84 and between Raw and Rvd 0,89. There is a good sensitivity and specifity in allergen bronchial provocation testing in all three methods. A bronchial sensitivity is confirmed in body plethysmography by 100% increase of Raw. In the interrupted method a 50% increase of Rvd in children smaller than 165 cm and in forced oscillation method a relative increase of 25% (0,15 kPa/l/s) is sufficient to assess a bronchial sensitivity to tested allergen.

Adolescent↗

PubMedDate not supplied

[Possibilities for interpreting digital migration analysis of cement-free PM total hip endoprostheses].

PURPOSE: Aim of this study was the validation of a digital measurement device for hip implants. METHODS: From 43 patients with a minimum of four subsequent roentgenograms 246 roentgenograms of PM-shafts (an average 5.72/shaft) and 142 roentgenograms of PM-cups (an average 6.45/cup) were digitized on a DiagnostiX 2048 basis station (Pace Systems, Germany). Modified Sutherland/Nunn methods were chosen for measuring purposes. Regression analysis was done and the results were correlated to implant loosening. RESULTS: Concerning the total vertical migration of the cup there is a significant (p < 0.04) difference between the loosened components (6.02 +/- 2.59 mm) and the fixed cups (2.26 +/- 2.89 mm). The average annual vertical migration rate of the stem shows a highly significant difference (p < 0.007) when comparing loosened stems (0.82 +/- 0.43 mm, total migration 4.78 +/- 2.89 mm) and fixed ones (0.20 +/- 0.54 mm, total migration 1.72 +/- 3.02 mm) CONCLUSIONS: Using the regression analysis and a sufficient number of pictures the system allows us to give migration values that make loosening likely. However for the single implant an individual prognosis of loosening is not possible.

Follow-Up Studies↗