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Biomedical subjects

M Engelhardt

Publications and source records attributed to M Engelhardt.

102 records · Page 6Linked to original sources
PubMed1983

Quantitative analysis of mRNA synthesis during early cortisol action on rat thymocytes: restricted size of a possible hormone response.

Complete inhibition of cortisol-induced pycnosis was seen by actinomycin D and cycloheximide only when added during the initial period of hormone action. This phenomenon, being a characteristic of steroid hormone effects in general, is often taken as indirect evidence for early steroid-induced mRNA synthesis. The lack of direct evidence for this theory has been tested for significance. Approximately 133 newly synthesized mRNA molecules were found to accumulate in the cytoplasm/min/cell, suggesting an average synthesis rate for individual mRNA species of about 1 copy/h/cell. Electrophoretic fractionation of double labelled RNA failed to reveal any changes of the isotope ratio of single fractions during the first 15-45 min of cortisol action, within an experimental error corresponding to +/- 2- +/- 20 molecules/cell. Possible effects of cortisol are thus restricted to changes in the range of constitutive mRNA synthesis rates. In contrast, the RNA labelling pattern was differentially changed after 45 min treatment with 10(-5) M cycloheximide.

Animals↗
PubMed1977

Dissociation between cortisol-induced pycnosis and inhibition of [3H]uridine incorporation in rat thymocytes.

Treatment of rat thymocytes with cortisol induced an inhibition of [3H]uridine incorporation after 30-90 min, an accumulation of pycnotic cells after 90 min, and a decrease in cell viability after several hours. No cortisol-resistant cells could be distinguished, and dose-response curves for a number of glucocorticoids showed a correlation to the saturation of the glucocorticoid receptors. The pycnotic effect of cortisol increased between pH 5.2--7.0 in parallel with a stimulation of the spontaneous development of pycnotic cells. The cortisol-induced accumulation of pycnotic cells and inhibition of [3H]uridine incorporation varied independently as a function of the cell density, and in a glucose-salt medium only the pycnotic effect of cortisol became inhibited. The inhibition of [3H] uridine incorporation is therefore not an integral part of the pycnotic change of the cells. The glucocorticoid sensitivity was found to increase with the age of the animals, before the onset of thymus involution.

Animals↗
PubMed1965

Odorous secretion of normal and mutant Tribolium confusum.

An autosomal recessive mutant characterized by "melanotic stink glands" has been found in the tene-brionid flour beetle, Tribolium confusum. The contents of the reservoirs of both pairs of odoriferous glands become modified in two ways as the beetles age. (i) The quinones (2-ethyl- and 2-methyl-1,4-benzoquinone) present in the secretion are reduced to 1/20 of that normally found in the wild type. (ii) The contents may be modified into a high-molecular-weight polymeric substance, which becomes visible through the exoskeleton and, upon dissection, appears as a black solid lump. The medium in densely populated cultures of the mutant becomes moldy while that containing normal beetles remains particulate. This difference suggests that one of the functions of the secretions of the odoriferous glands is to prevent the growth of fungi or bacteria in the nutrient flour.

Aging↗
PubMedDate not supplied

[Foreign body reaction in carbon fiber prosthesis implantation in the knee joint--case report and review of the literature].

We present the clinical radiological and pathological data of a patient who underwent carbon fiber implantation of the right knee. Within half a year a total knee replacement had to be performed due to persistent pain. Apart from the intraoperative, macroscopically visible, massive sclerosis around the drill holes and an obvious synovial reaction, we histopathologically found a severe granulomatous foreign body reaction around the carbon fibers. Experimental data point toward a negative influence of a foreign body reaction on attempted cartilage repair. The implantation of carbon fibers can be recommended neither for biomechanical nor for pathophysiological reasons. Before this treatment can be recommended, prospective randomized trials are mandatory.

Aged↗
PubMedDate not supplied

[Tissue engineering and gene therapy of the musculoskeletal system with muscle cells].

AIM: Muscle-based somatic gene therapy is a novel way to alleviate a biochemical deficiency. METHOD: Muscle-derived cells are very promising in the field of gene therapy and tissue engineering. First, most muscle tissue is accessible by injection. Second, muscle tissue consists of multinucleated, postmitotic myofibers, which enable a long-term expression of the transduced gene. Third, muscle tissue can be biopsied easily. It is available in abundance and the biopsy does not compromise the health and function of the patient. Finally, muscle tissue is highly vascularized, which makes systemic delivery feasible. RESULTS: Muscle-derived cells can promote muscle healing and bone healing. Implanted cells maintain a long-term transgene expression of therapeutic proteins. Isolated, muscle-derived stem cells can differentiate in osteoblasts. CONCLUSION: Based on these characteristics, we present four possible applications: inherited muscular diseases, muscle injury, bone healing, and intraarticular disorders.

Gene Expression↗
PubMedDate not supplied

[Pain reduction after cervical spine surgery. Outcome after implantation of a cervical wing cage in degenerative diseases of the cervical spine--a prospective study].

AIM: Surgery in cervical spine disease using titanium cages is a common procedure to reduce the pain and neurological deficits. This study was aimed to evaluate the results in pain reduction using the wing cage intraoperatively. METHOD: In this prospective study demographic data were noted, whereas special emphasis was placed on pain, which was noted using a visual pain scale and the prolo score, neurological deficits and the causing pathology. Furthermore, questions about the use of analgesics and the duration of pain were asked. After operation with insertion of a wing cage instead of the disk, a neurological investigation 6, 12 and 24 months later was done to evaluate the postoperative status. RESULTS: 54 patients underwent a cervical discectomy in 64 segments as therapy for neck pain or a radiculopathy caused by osteochondrosis or disc disorder. Patients with brachialgia profited most from the operation. Less improvement was seen in cases of osteochondrosis or combined pathology. CONCLUSION: Patients with pain caused by discs in the cervical spine, have better improvement than patients with other pathologies. This should be taken into account when choosing the mode of therapy.

Adult↗
PubMedDate not supplied

The implication of telomerase activity and telomere stability for replicative aging and cellular immortality (Review).

Telomerase and telomeres have been shown to be involved in the control of cell proliferation, the regulation of cell senescence and the unlimited proliferation capacity of malignant cells. Human telomeres are specialized chromosomal end structures composed of TTAGGG repeats. They function to protect chromosomes from degradation, fusion and recombination. Since the termini of linear molecules are replicated only in the 5'-3' direction by conventional DNA polymerases and require an RNA primer to initiate DNA synthesis, the removal of the RNA primer results in DNA loss with each cell division. To date, telomere shortening has been observed in most dividing somatic cells, eventually leading to cell senescence when critically short telomeres are reached. Telomerase has been identified as a ribonucleoprotein enzyme that can synthesize telomeric repeats onto chromosomes. Borderline telomerase activity has been detected in human primitive hematopoietic cells and in stimulated lymphocytes which increased with cytokine induced ex vivo expansion. However, in most other normal somatic cells, telomerase has not been detected, and consequently telomere shortening can be anticipated after a limited number of population doublings. In contrast, spontaneously immortalized tumor cell lines and the majority of malignant tumors demonstrate high telomerase activity, stable telomere length and unlimited proliferative potential. Mechanisms for telomerase and telomere length regulation are under extensive investigation. These have included the cloning of the RNA component and telomerase associated proteins, antisense experiments that have demonstrated progressive telomere length shortening in the absence of telomerase, and the identification of telomere binding proteins which may regulate telomerase by creating a negative feedback signal. This review aims to summarize important results in the rapidly moving field of telomeres and telomerase.

Base Sequence↗
PubMedDate not supplied

Bridging to transplant: allogeneic heart transplantation after xenografting.

Xenografting seems to be a solution to use to bridge time intervals when desperately needed allograft cannot be obtained. A following allograft was never ventured. Nine dogs (weight, 20 to 25 kg; age, 2 years) underwent right cervical heart transplantation. Donors were silver foxes (3 to 4 kg). The animals were treated by triple-drug therapy consisting of cyclosporine, methylprednisolone, and azathioprine in clinical dosages. For control, six recipients received only allogeneic hearts and the identical immunosuppression. After rejection of the xenograft, a second allogeneic heart was anastomosed subsequently to the same right cervical vessels. Routine histologic and immunohistologic examinations were performed. Thromboxane B2 and 6-keto-prostaglandin F1 alpha were determined daily in peripheral blood. After final rejection the sensitization of the recipient was controlled by hemagglutination test. Survival time of the xenografts was 9.6 +/- 1.2 days; the subsequent allogeneic hearts under the same therapy beat for 4.5 +/- 5.0 days. The average survival time of control hearts was 18 +/- 1.9 days. The five hyperacute second allografts showed signs of humoral rejection by absence of inflammation. The release of thromboxane B2 was different in hyperacute, accelerated, or cellular rejection. In contrast to the long-functioning grafts, thromboxane B2 persisted during hyperacute rejection at a high level. However, 6-keto-prostaglandin F1 alpha showed no significant differences between longtime survivors and hyperacute rejecting hearts. After xenogeneic transplantation, all recipients showed hemagglutinating titers between 1:4 and 1:16. Allogeneic grafts have a different kinetics of rejection after xenogeneic heart transplantation compared with control hearts. Thromboxane B2 seems to be an important mediator in hyperacute rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Noninvasive methods of rejection diagnosis after heart transplantation.

For clinical follow-up and prognosis in heart transplant patients, it is important to understand accurately the presence and extent of cardiac allograft rejection. Since the introduction of endomyocardial biopsy, almost 40 different noninvasive diagnostic procedures for the recognition of myocardial rejection have been proposed. However, endomyocardial biopsy is invasive and not suitable for frequent monitoring. If the pattern of rejection shows a focal distribution, false-negative results can be expected. Discrepancies between biopsy findings and allograft function are obviously possible. State-of-the-art information will be given on the most reliable noninvasive methods for rejection diagnosis, which can be differentiated from electrophysiology (fast-Fourier-transformed electrocardiography and intramyocardial electrocardiography), echocardiography, immunologic methods (cytoimmunologic monitoring, transferrin receptors, and interleukin-2 receptors), various biochemical markers (neopterines, prolactin, urinary polyamines, and beta 2-microglobulins), radioisotopic techniques (antimyosin-monoclonal antibodies, thallium, technetium, and gallium scintigraphy and indium-labeled cells), as well as magnetic resonance imaging. Thus modified and patient-adapted antirejection therapy can be provided if the decision for or against antirejection therapy is not based on biopsy findings alone but rather is confirmed along with histologic, electrophysiologic, biochemical, immunologic, and functional parameters.

Diagnostic Imaging↗
PubMedDate not supplied

Kinetics and dynamics of acute rejection after heterotopic heart transplantation.

Right cervical, heterotopic heart transplantation was performed in 18 mongrel dogs. Study design was based on three different groups (n = 3 x 6). Standard immunosuppression consisted of triple drug therapy in all dogs. Groups II and III received high dose steroids during acute rejection. In group III the native hearts of previous recipients (groups I and II) were used as donors for heterotopic transplantation ("domino" principle). The hearts were examined by daily transmural biventricular biopsies and graded according to Billingham classification. Cytoimmunologic monitoring (n = 345; activation index from peripheral and coronary sinus blood) and fast Fourier transformation ECG (n = 80; area under the curve; surface recordings) served as daily noninvasive methods. Optionally antimyosin scintigraphy (n = 25; single photon emission computed tomography; heart-to-lung ratio) was performed and immunohistologically confirmed by peroxidase staining of the antibody (n = 61). Kinetics of rejection was not uniform in group I (onset after 5.7 days) and biphasic in group II (clear rejection-free interval: 6.8 days). Group III developed a continuously persisting rejection, despite repeated high-dose steroids, with an early onset (3.2 days). The invasive data, consisting of 587 punch biopsies, showed no significant difference between right and left ventricular rejection. Clearly focal rejection appeared in 51.5% of the cases, with subendocardial involvement in 54%. Cytoimmunologic monitoring significantly (p less than 0.001) correlated with daily biopsies in groups I and II. The activation index from coronary sinus blood was two times higher than in peripheral blood. Fast Fourier transform ECG identified the onset of rejection with great accuracy (p less than 0.01). The heart-to-lung ratio of antimyosin scintigraphy corresponded exactly to the various stages of rejection (p less than 0.001). High-dose steroids led to a clear reduction of the ratio in 26% cases. Peroxidase staining showed typical locations of the antibody, depending on the grade of rejection (p less than 0.001). Considering the results of pathology in this transplantation model, relying on endomyocardial biopsy alone in a clinical setting may not seem advisable. Although the results of this study must be confirmed clinically, the simultaneous use of cytoimmunologic monitoring and fast Fourier transformation ECG may prove to be valuable to day-to-day monitoring for acute rejection in the early postoperative course. If both methods indicate the onset of an acute rejection, antimyosin scintigraphy and endomyocardial biopsy, respectively, should be performed to confirm and grade the suspected diagnosis.

Animals↗