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Biomedical subjects

R Engelhardt

Publications and source records attributed to R Engelhardt.

At least 109 records · Page 6Linked to original sources
PubMed1984

Biochemical characterization of endogenous carbohydrate-binding proteins from spontaneous murine rhabdomyosarcoma, mammary adenocarcinoma, and ovarian teratoma.

Three entirely different tumor types were investigated biochemically for the presence and characteristics of endogenous carbohydrate-binding proteins in an inbred Brown Norway rat, an outbred Sprague-Dawley rat, and an outbred Han:NMRI mouse. The patterns under investigation included specificities for alpha- and beta-galactosyl, alpha-mannosyl, and alpha-fucosyl moieties, respectively, and specificities for heparin, analyzed by affinity chromatography on resins with immobilized sugars or glycoproteins and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The patterns were divided into categories according to dependence of the binding activity on the presence of Ca2+ and dependence on extraction conditions. Rhabdomyosarcoma revealed only Ca2+-independent activities, i.e., activities with specificity for beta-galactosides at a molecular weight of 12,000, with specificity for alpha-galactosides at molecular weights of 29,000, 43,000, and 45,000, with specificity for heparin at molecular weights of 13,000 and 16,000, and with specificities for mannose and fucose at molecular weights ranging from 62,000 to 70,000. For the spontaneous mammary adenocarcinoma the pattern was entirely different and more diverse, including species with the Ca2+ requirement. Extracts with the use of 0.2 M NaCl (salt) and 2% Triton X-100 (detergent) from teratoma contained at least nine different carbohydrate-binding proteins. The only similarities between the pattern of endogenous carbohydrate-binding proteins from teratoma and from mammary adenocarcinoma were beta-galactoside-binding proteins, one with a Ca2+ requirement and one without a Ca2+ requirement, and the heparin-binding proteins. These heparin-binding proteins were the only types of carbohydrate-binding proteins common to all three tumor types. The analysis indicates that certain bands represented newly identified proteins capable of binding to galactose-, mannose- or fucose-containing glycoconjugates, respectively. When assayed with rabbit erythrocytes, the different fractions showed agglutination activity. They can thus be termed "endogenous lectins." The use of endogenous lectin patterns as potential diagnostic markers in addition to the corresponding changes in the glycoconjugate composition is proposed.

Adenocarcinoma↗
PubMed1983

Evolutionary aspects of accuracy of phenylalanyl-tRNA synthetase. Accuracy of fungal and animal mitochondrial enzymes and their relationship to their cytoplasmic counterparts and a prokaryotic enzyme.

Phenylalanyl-tRNA synthetases from mitochondria of yeast and hen liver resemble their corresponding cytoplasmic counterparts. Whereas slight intraspecies differences at the amino acid binding site, reflecting variations in the structures of these distinct enzymes, are exploitable by phenylalanine analogues, no intraspecies difference can be noted for the strategies to achieve the high fidelity of protein synthesis. While the yeast mitochondrial enzyme follows the pathway of posttransfer proofreading, the hen liver mitochondrial enzyme uses a tRNA-dependent pretransfer proofreading in the case of the natural amino acids. The accuracy of mitochondrial phenylalanyl-tRNA synthetases appears to be even better than the accuracy of the corresponding cytoplasmic enzymes. Interspecies rather than intraspecies differences for the functional role of certain amino acid residues of the enzymes further indicate the close relationship of the intracellular heterotopic isoenzymes. By use of a highly sensitive immunospotting procedure, common antigenic determinants are detected only within the enzymes from the two intracellular compartments of the same organism. The results suggest the origin of the cytoplasm-mitochondrion isoenzyme pair by independent gene duplication of the ancestral nuclear gene. A similarity of mitochondrial enzymes to the phenylalanyl-tRNA synthetase from Escherichia coli is not observed.

Adenosine Monophosphate↗
PubMed1983

[Does febrile proteinuria exist?].

The significance of proteinuria during febrile infectious diseases is widely underestimated, although the more marked proteinuria probably signalizes a parainfectious nephropathy rather than a functional disorder. This study shows that mild proteinuria of less than 0.65 g/24 h (normal range less than 0.3 g/24 h using the sensitive tannine-FeCl3-technique) might be caused by the elevated body temperature alone. 9 out of 18 volunteers without renal disease undergoing experimental hyperthermia of 40-41 degrees C for 1-2 h did not develop a proteinuria according to quantitative and qualitative (SDS-PAGE) measurements. In 6/18 the amount and composition of urinary proteins changed giving a glomerular type of proteinuria, possibly caused by temperature related transient glomerular alterations. In 3/18 a mild glomerulopathy existed before hyperthermia, as deduced from a glomerular pattern despite a quantitatively physiological proteinuria, leading in all 3 to pathological proteinuria during hyperthermia. In all 18 volunteers alterations reversed to normal within 12 h. Therefore, the degree of proteinuria during febrile diseases should be considered. Proteinuria of less than 0.5-1 g/24 h in adults might be explained by an altered glomerular function alone. Proteinurias exceeding this value, with a slow regressing tendency will indicate glomerular or tubulo-interstitial diseases, caused possibly by immunologic or toxic products resulting from underlying infectious disease.

Adult↗
PubMed1983

Age-related changes in different steps of protein synthesis of liver and kidney of rats.

Protein synthesis in cell-free systems of rat liver and kidney decreases markedly with age. Examination of activity changes of the different steps revealed for both types of organs that reduced binding of aminoacyl-tRNA to ribosomes and reduced peptidyl transfer might be of major importance for the decrease in overall protein synthesis whereas ageing has only little effect on translocation as well as on initiation and termination.

Aging↗
PubMed1983

Phenylalanyl-tRNA synthetases from yeast cytoplasm and mitochondria. The presence of a carbohydrate moiety in the mitochondrial enzyme and immunological evidence for structural relationship.

Homogeneous yeast cytoplasmic and mitochondrial phenylalanyl-tRNA synthetases (L-phenylalanine:tRNAPhe ligase (AMP-forming), EC 6.1.1.20) are analysed for structural differences. Only the large subunit of the mitochondrial enzyme is a glycoprotein with nearly 3% carbohydrate by weight. The carbohydrates present are: glucose, N-acetylglucosamine, mannose, galactose and N-acetylneuraminic acid. Removal of the sugar moieties yields an activity increase, but no significant change of sensitivity to proteolytic degradation. Antibodies to both homogeneous enzymes demonstrate a structural similarity for both types of subunit using the highly sensitive immunoblotting technique.

Amino Acyl-tRNA Synthetases↗
PubMed1983

Simplified method for the discrimination of acute myelogenous and non-myelogenous leukemias.

Rapid discrimination of acute myelogenous and non-myelogenous leukemias is of great importance when chemotherapy is urgently needed in severely ill patients. For decades the most reliable cytochemical method for this classification is the demonstration of myeloperoxidase in blast cells [1-4, 6, 7]. We combined the simplified myeloperoxidase stain as described by Kaplow with a brief stain similar to Pappenheim's procedure or with commercially available Hemacolor rapid blood smear: this proved to be a simple staining method that permits good morphological judgment of the cells as well as reliable demonstration of peroxidase activity. This procedure takes less than 10 min using Hemacolor and can easily be done with prepared solutions without technical assistance.

Cell Nucleus↗
PubMed1983

[Recruiting patients and results of a preliminary study on the therapy of acute lymphatic leukemia and acute undifferentiated leukemia in adults].

The aim of the study was to improve remission quality through application of an intensified induction therapy successful in childhood ALL; in a modified form for patients of 15-35 years and in a reduced form for patients of greater than 35-65 years with ALL or AUL. The 8-week induction therapy consists of two phases. In phase I, prednisone, vincristine, daunorubicin, and L-asparaginase are given and in phase II, cyclophosphamide, cytosine-arabinoside, and 6-mercaptopurinee. As CNS-prophylaxis, intrathecal methotrexate, and CNS-irradiation with 24 Gy are used. After 3 months a re-induction therapy similar to the induction therapy is given with dexamethasone and adriamycin instead of prednisone and daunorubicin and without L-asparaginase. Maintenance therapy with 6-mercaptopurin and methotrexate follows over a period of 2 years. Since the formation of the study group in 1979 up to 30.06.81, 170 patients from 25 hospitals with newly diagnosed ALL or AUL were treated according to the protocol. Up to 30.11.81, 162 patients had completed treatment and were evaluable. Of these, 77.8% achieved complete remission, 80.7% in the age group 15-35 years and 68.3% in the age group greater than 35-65 years. The median survival time for all patients was 24 months and for the 126 patients with complete remission the median has not yet been reached (last observation 31 months). The median remission duration is 20 months. Prognostic factors for remission duration are (1) the number of chemotherapy courses required to reach complete remission, (2) the immunological subtype, (3) age and (4) initial leukocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

[Phase II study of AMSA in adults with acute therapy-refractory leukemias].

The acridine derivative AMSA, Amsacrine, is a new anticancer drug which was effective in patients with advanced AML and ALL in studies performed in USA. In a multicenter phase II trial we treated 27 patients with acute resistant leukemia with AMSA. All presented progressive disease following several drug combination regimens. Out of the 25 evaluable patients 5 were resistant to primary therapies, 13 were in 2nd relapse, 6 in 3rd, and 1 in 4th relapse. Dosage was 75 mg/m2, iv, day 1-7, all 3-5 weeks. On an average, only 76% of the planned dose per cycle could be given, due to severe leucopenia. From 21 patients with ALL, 1 CR and 3 PR were observed; the 3 patients with ALL presented 1 CR and 1 PR. 1 AUL showed progressive disease. In all patients a marked cell reduction could be observed in the peripheral blood. The general tolerance was good. The most important side-effect was bone-marrow toxicity, 48% (12/25) presented leucopenia less than or equal to 600/mm3, 5 (20%) had fatal septic complications. All 5 early death presented high initial leucocyte counts of greater than or equal to 32.000 mm3 as a common risk factor. In conclusion, AMSA is an effective drug in heavily pretreated patients with AML and ALL.

Adolescent↗
PubMed1983

[Possibilities of whole-body hyperthermia].

Significant modifications in tissues, even death of cells, are caused by hyperthermia of few degrees centigrade. The extent of these modifications depends on the temperature applied. In a whole-body treatment, only not directly cytotoxic temperatures can be tolerated. The authors compare the methods of induction of whole-body hyperthermia with respect to expenditure, temperature applied, and side effects. Total-body hyperthermia aims at a reinforcement of other tumoricide therapies (radiotherapy, chemotherapy). - A pilot study performed with patients suffering from microcellular bronchial carcinomas, extensive disease, showed that the results of ACO and total-body hyperthermia (41 degrees C) are encouraging as compared with single ACO therapy: complete remission 8/15, partial remission 5/15, no change and progressive disease 2/15, 53-week survival rate 0,5, one-year survival rate 0,53, two-year survival rate 0,18.

Carcinoma, Small Cell↗
PubMed1981

[Combined treatment of non-small cell carcinoma of the lung with radiotherapy and moderate whole-body hyperthermia (author's transl)].

Nine patients suffering from non oat cell carcinoma bronchial carcinomas were treated with extended-field irradiations. The treatment was executed under the conditions of whole-body hyperthermia. All patients had inoperable but not yet disseminated carcinomas, seven among them a squamous cell carcinoma and two an undifferentiated carcinoma. The hyperthermia was produced by a Siemens cabin (chamber of Pomp) with preheated air of 55 to 60 degrees C and a radio frequency of 27 MHz, 400 W. A temperature of body cavities of 40 to 40.5 degrees C was reached within 40 to 60 minutes. Fifteen minutes after having reached this temperature, the patient was irradiated. The nominal standard dose of 18 to 18.5 Gy was fractioned into three times three Gy per week. Three to thirteen single doses were combined with whole-body hyperthermia. The initial tumor regression seemed increased. One patient became operable; he was submitted to pneumonectomy. All patients showed partial remissions. Compared to radiotherapy alone, there is no improvement of remission period and survival time until now. Better results could possibly be reached by an additional systemic chemotherapy.

Adult↗
PubMed1979

[Influence of hyperthermia on toxic side effects of cytostatic agents (author's transl)].

14 patients with tumors in generalised stages (Hodgkin's disease, oat-cell-carcinoma, Fibrosarcoma, acute leukemia) were treated altogether 54 times with cytostatics in combination with hyperthermia. The temperature was induced by microwaves with a frequency of 27 MHz. A temperature of 40 degrees C was reached after 40 min. At this point cytostatics were applicated; afterwards the temperature was maintained for one hour at 40-40,5 degrees C. Cardia, pulmonary and circulatory complications did not occur. Controls of the laboratory parameters could exclude effects on electrolytes, muscles, blood, liver and kidney. The laboratory controls were made before, during, immediately after and 24 h after hyperthermia. There were no signs for an enhancement of toxicity typical for cytostatics. The observations are compared to the results of other investigators. To date the therapeutic effect of this treatment can not be stated.

Adult↗
PubMed1979

[A variant of the von Willebrand-Jürgens-syndrome with abnormalities of the factor VIII/von Willebrand factor protein (author's transl)].

A family is reported with a variant of von Willebrand's disease. The members of this family showed a qualitative defect of the factor VII/von Willebrand factor protein. The qualitative defect was characterized by an abnormal electrophoretical mobility of factor VIII-related antigen and an abnormal elution pattern as demonstrated by gelfiltration on Sepharose 4 B. Factor VIII-subunits in these patients were found to be normal by polyacrylamidgelelektrophoresis.

Blood Coagulation Factors↗
PubMed1978

[Changes in clinical and immunological laboratory parameters of healthy adults after exposure to a one-hour 40 degree C-whole-body hyperthermia (author's transl)].

There are no signs of organ lesions in healthy subjects exposed to an 1-hour 40 degree C whole-body hyperthermia, induced by radiofrequency or infrared light. As to the immunological in vitro parameters, only a slight decrease of the relative T-cell count is seen, T-cell functions however being normal. A leukocytosis appearing during infrared-induced hyperthermia is probably related to the erythema caused by skin heating. About possible indications and clinical values of this treatment, nothing can however be said so far.

Adult↗