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Biomedical subjects

J Sindermann

Publications and source records attributed to J Sindermann.

8 recordsLinked to original sources

Radiofrequency energy modification of the atrioventricular junction in patients with atrial fibrillation: modes of ventricular response under autonomic blockade and long-term effect.

The short- and long-term effect of radiofrequency (RF) modification of the AV junction on ventricular rate and left ventricular function and the different types of ventricular response during energy application under autonomic nervous blockade were assessed in 28 patients with medically refractory atrial fibrillation. During the successful RF application, ventricular rate slowed progressively (type I response, ten patients) or accelerated at first and then slowed (type II response, 11 patients). Type II response was associated with a more anterior ablation site compared to Type I response. A primary successful outcome was achieved in 21 patients. Inadvertent complete AV block developed in three patients, while in four patients AV nodal ablation was performed after an unsuccessful modification attempt. During 6-month follow-up, the ventricular rate was adequately controlled in only four patients. Among the 16 patients with a recurrence of uncontrolled AF were all 10 patients with type I response and 6 of 11 patients with type II response. One patient died suddenly 10 weeks after the procedure.

Aged↗

Sequence-specific antiproliferative effects of antisense and end-capping-modified antisense oligodeoxynucleotides targeted against the 5'-terminus of basic-fibroblast-growth-factor mRNA in coronary smooth muscle cells.

Basic fibroblast growth factor (bFGF), a potent mitogen for arterial smooth muscle cells, has been shown to play a fundamental role in the pathogenesis of arteriosclerosis and restenosis by stimulating the proliferation of vascular smooth muscle cells. We found that partially phosphorothioate-modified 15-residue antisense oligodeoxynucleotides complementary to bFGF mRNA at 0.1-2.0 microM block growth and division of cultured human and bovine coronary smooth muscle cells in a dose-dependent manner. The effect is sequence specific at low (0.1-0.5 microM) nontoxic concentrations. It is associated with inhibition of expression of pericellular and intracellular bFGF, with a decreased de novo synthesis of bFGF and is partly reversible by the addition of exogenous (recombinant) bFGF. The antisense effect lasts 48-72 h and diminishes thereafter. If the antisense oligodeoxynucleotide medium is replaced by an oligonucleotide-free medium after 24 h, the [3H]thymidine incorporation rate returns to control levels. Under the same conditions, the corresponding sense oligodeoxynucleotide exerts negligible nonspecific inhibitory actions. The antiproliferative potency of the 15-residue antisense oligodeoxynucleotide is markedly enhanced by adding 3-4 nonbase-pairing guanosine residues at the 5'- and 3'-termini of the 15-residue antisense oligonucleotide. The data implicate bFGF in the process of smooth muscle cell proliferation and an effective and specific antiproliferative potency of bFGF-specific antisense oligonucleotides. The results point to possible new therapeutic strategies for the use of antisense methodology in the suppression of post-angioplasty restenosis.

Animals↗

A simple method for the flow cytometric analysis of intracellular antigens in whole smooth muscle cells: quantification of cyclin-dependent kinase 2.

Flow cytometry has become a widely used technique for the quantitative analysis of antigens at the single cell level. In the past, several protocols have been published for the detection of cytoplasmic and nuclear antigens in various cell lines, especially blood cells or cells growing in fluid culture. The applicability of these protocols to cells growing in a monolayer, such as smooth muscle cells (SMC) is often restricted, although flow cytometry is of great interest in the fields of arteriosclerosis and cancer research. We here describe a simple and reproducible method for the flow cytometric analysis of intracellular antigens such as cyclin-dependent kinase 2 (Cdk2) in rat aortic SMC. The sensitivity of the method was analyzed under growth and growth-inhibitory conditions using lovastatin, a cholesterol-lowering compound with antiproliferative capacity. Various antigens (Ras-protein, protein kinase C-alpha (PKC-alpha), Ki-67/MIB-1) in rat and bovine SMC were detectable using this methodology which should have a wide range of applications.

Animals↗

Investigations of the lymphokine system in elderly individuals.

Elderly people are at risk from an increased incidence of infections. Therefore we have studied the correlation between the production of several immunological parameters such as interferon-gamma (IFN-gamma), interferon-alpha-2 (IFN-alpha-2), interleukin-2 (IL-2), soluble interleukin-2 receptors (sIL-2R) and interleukin-6 (IL-6) in young controls of 25-34 years old and old individuals with a minimum age of 65 years. All persons were selected according to the basic concept of the 'Senieur protocol'. Heparinized blood was taken and cultured in the whole-blood assay. The determination of all cytokines in the supernatants of stimulated cultures was done by the ELISA technique. We found significantly decreased levels of sIL-2R and IFN-alpha-2 after stimulation, whereas the values of IFN-gamma and IL-2 showed no significant difference between elderly and young persons. The values of IL-6 showed a distinct trend towards an increased synthesis for the elderly. We also studied the lymphocyte subpopulations T4 and T8 by flow cytometry. Elderly individuals showed a significantly increased T4/T8 ratio, caused by a slightly but not significantly decreased level of T8 cells. These results show that the elderly have decreased values of some immunological parameters such as IFN-alpha-2 and sIL-2R, which might explain an increased susceptibility of elderly individuals to bacterial and viral infections.

Adult↗

Macrophage colony-stimulating factor (CSF-1) is expressed by spontaneously outgrown EBV-B cell lines and activated normal B lymphocytes.

Human B lymphocytes activated by mitogens or infected by Epstein Barr virus (EBV) have previously been shown to release colony-stimulating activity (CSA) supporting the growth of normal human bone marrow progenitors. We established five different human EBV-B cell lines spontaneously outgrown from nonmalignant peripheral blood cells and long-term bone marrow cultures. CSA derived from all of these lines induces the growth of murine macrophage colonies, whereas virtually no human bone marrow cell progenitors were stimulated. As observed in the tumor cell line MIA PaCa-2, a 4.3-kilobase (kb) transcript was detected in all cases using a human colony-stimulating factor (CSF)-1 probe. Expression of this transcript can be further stimulated within three hours upon addition of phorbol myristate acetate (PMA). The highly purified native protein exerting macrophage colony-stimulating activity (M-CSA) exhibits a molecular size of approximately 75 to 97 Kd in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The identity of EBV-B cell derived M-CSA with human urinary CSF-1 was confirmed by a complete neutralization of macrophage CSA by an antihuman urinary CSF-1 antiserum. Normal human B lymphocytes purified from tonsils or from mononuclear blood cells also express CSF-1 upon stimulation with Staphylococcus aureus Cowan I. No CSF-1 expression, however, could be detected in normal resting B lymphocytes or in the Burkitt lymphoma cell line RAJI.

Animals↗