On the mechanism of coded binding of aminoacyl-tRNA to ribosomes: number and properties of sites.
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Amino Acids↗
Biomedical subjects
K Eckert
Publications and source records attributed to K Eckert.
Suitability of incorporated vascular stents for surgical patch-plasty: an experimental study.
PURPOSE: Evaluate the feasibility of expanding arterial and venous stents incorporated into the vessel wall by surgical patch-plasty in an experimental study. METHODS: An 8-mm Wallstent was percutaneously implanted into the carotid artery of 11 sheep and into the ipsilateral jugular vein in three of them. Three months after implantation, a patch-plasty was performed on the incorporated stents using a 0.4-mm-thick synthetic patch made of polytetrafluoroethylene (PTFE). Stent patency was monitored by color-coded duplex ultrasound and angiography for 6 months after operation. RESULTS: No suture dehiscence or aneurysm formation were observed. Nine of 11 arterial and 2 of 3 venous stents remained fully patent during follow-up. In arteries, complications encountered were a complete stent thrombosis early after surgery, as well as a floating thrombus in the stent, found at final angiography after 6 months. In veins, one partial stent thrombosis was observed. Microradiographic and histological examinations revealed marked intimal hyperplasia in both arterial and venous stents. Intimal hyperplasia was significantly more pronounced in patched than in stented arterial segments (p < 0.005). CONCLUSION: Patch-plasty surgery of previously incorporated vascular stents is technically feasible. Mid-term patency rates were acceptable.
Aneurysm↗
Preclinical studies with prothymosin alpha1 on mononuclear cells from tumor patients.
The immunomodulating potential of the thymic protein prothymosin alpha1 (Pro alpha1) on the lymphocyte and monocyte directed antitumor reactions of melanoma and colorectal tumor patients in comparison with healthy controls were studied in vitro. On average, tumor patients showed lower NK- and LAK-cell activities than healthy controls, being associated with a lower adhesion capacity to tumor target cells. The NK-cell activity of the tumor patients was inversely related to the tumor stage. Pro alpha1 stimulated the impaired patients LAK-cell activity only at an early stage of disease. The Pro alpha1 effects were associated with an increased adhesion of lymphocytes to tumor target cells and an increased secretion of deficient IFN-gamma and IL-2 secretion. By flow cytometry, Pro alpha1 in combination with IL-2 increased the NK-cell marker CD56, CD16/56 and CD25 as well as CD18/11a adhesion molecule expression. Monocytes from tumor patients showed deranged tumoristatic activities compared with healthy controls. Pro alpha1 elevated the mean of the antitumor activity, when applied alone or in combination with rIFN-gamma. In the presence of IFN-gamma, Pro alpha1 stimulated the adhesion of monocytes to cultured tumor cells, mainly by increasing CD54 expression. Pro alpha1 stimulated alone or in combination with IFN-gamma the TNF-alpha and IL-1beta secretion by monocytes and decreased the high PGE2 and TGF-beta level, especially in the patients groups. Perspectively, this may provide the basis for applying Pro alpha1 in selected antitumor immunotherapy protocols.
Adjuvants, Immunologic↗
Effects of differentiation inducers on cell phenotypes of cultured nontransformed and immortalized mammary epithelial cells: a comparative immunocytochemical analysis.
We examined the effects of the differentiation-inducing agents 1, 25-dihydroxyvitamin D(3) (calcitriol), phorbol myristate acetate (PMA), the cytokine interferon-gamma (IFN-gamma), and the tumor necrosis factor-alpha (TNF-alpha) alone and in combination with calcitriol on cell growth and differentiation parameters of cultured nontransformed human mammary epithelial cell (HMEC) lines, the chemically transformed HMEC line H184 A1N4, and the human mammary carcinoma cell line CAL51. Cell differentiation was phenotyped by semiquantitative immunocytochemistry using a panel of 15 monoclonal antibodies against marker molecules representing epithelial cell differentiation, cell-cell adhesion processes and malignancy. Cell proliferation of HMEC and H184 A1N4, but not of CAL51 cells was reduced by the agents. Cell phenotypes were analyzed by examining the expression of cytokeratins (pan CK and CK19), the epithelial mucin (MUC1), isoactin, and the blood group-related H type 2 carbohydrate antigen. HMEC and H184 A1N4 cells showed characteristics of basal cells, whereas CAL51 cells resembled a lumenal phenotype. The cell-cell adhesion molecules E-cadherin, intracellular adhesion molecule (ICAM-1), and the tumor markers carcinoembryonic antigen (CEA) and CD44v6 were expressed on all 3 mammary cell lines, with moderate differences. With respect to effects on cell phenotypes, HMEC were sensitive to PMA and IFN-gamma resulting in an increased expression of MUC1, CEA and ICAM-1 molecules. H184 A1N4 cells responded to TNF-alpha in combination with calcitriol by increased expression of pan CK, MUC1, and decreased H type 2 antigen expression, suggesting a transition towards a lumenal phenotype. Furthermore, CEA, ICAM-1 and CD44v6 were increased by TNF-alpha plus calcitriol. In contrast, CAL51 cells were overall less sensitive to differentiation induction attempts; only TNF-alpha stimulated MUC1, isoactin and epithelial cell adhesion molecule (Ep-CAM) expression.
Actins↗
Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients.
The protease bromelain from pineapple was suggested for adjuvant therapy of malignant diseases. We studied immunological effects of an orally applied bromelain drug on 16 breast cancer patients in comparison with healthy donors. Bromelain was applied for 10 days with a daily dose of 3000 F.I.P. units and the immunocytotoxicity of blood monocytes and lymphocytes against the leukemic K562 and MDA-MB-231 mammary carcinoma target cells was determined in vitro. In addition, the expression of the cell surface markers CD44, CD16, CD11a and CD62L on lymphocytes and the secretion of IL-2 and IL-1beta from monocytes was measured. Patients leukocytes expressed lower bMAK-, MAK-, NK- and LAK-cell activities, compared with those from healthy donors. Orally applied bromelain increased the reduced bMAK- and MAK-cell activity of patients monocytes about 2-fold. When the patients were classified on the basis of bromelain effects on the monocytic cytotoxicity into bromelain responders and nonresponders, about 40% of the patients responded to bromelain with an increase of cytotoxicity from 7.8% to 54% (bMAK-cell activity) and from 16% to 47% (MAK-cell activity). Bromelain was less effective on the higher cytotoxicity of monocytes from healthy donors, but stimulated the secretion of IL-1beta from monocytes. In contrast, patient monocytes secreted no detectable IL-1beta, before, during and after bromelain treatment. Bromelain had no effects on the impaired patients NK- and LAK-cell activity, but reduced the LAK-cell activity of healthy donors. No IL-2 was found in the supernatants of untreated and treated lymphocytes from healthy donors. Bromelain reduced the expression of CD44, but weakly increased CD11a and CD62L expression on patient lymphocytes, whereas CD16 remained unchanged. In vitro bromelain application to lymphocytes had similar effects, with greater reduction rates of CD44 and CD16 expression. As to coagulation parameters in plasma of healthy donors, the activated partial thromboplastin time was increased from 38 to 46 sec, leaving prothrombin time and plasminogen unchanged. These data suggest, that orally applied bromelain stimulates the deficient monocytic cytotoxicity of mammary tumor patients, which may partially explain its proposed antitumor activity.
Administration, Oral↗
Bromelain proteases reduce human platelet aggregation in vitro, adhesion to bovine endothelial cells and thrombus formation in rat vessels in vivo.
The thiol protease, bromelain, an extract from pineapple stem, was suggested to have antithrombotic and anticoagulant activities in vivo. We studied the effects of bromelain on cell size distribution of isolated human platelets in vitro by Coulter Counter measurements. Preincubation of platelets with bromelain (10 micrograms/mL) completely prevented the thrombin (0.2 U/mL) induced platelet aggregation. Papain was less active in preventing platelet aggregation. In vitro, bromelain (0.1 microgram/mL) reduced the adhesion of bound, thrombin stimulated, fluorescent labeled platelets to bovine aorta endothelial cells. In addition, preincubation of platelets with bromelain, prior to thrombin, activation, reduced the platelet adhesion to the endothelial cells to the low binding value of unstimulated platelets. On the basis of mass concentrations, the proteases papain and trypsin were as effective as bromelain. Using a laser thrombosis model, the in vivo effects of orally and intraveneously applied bromelain on thrombus formation in rat mesenteric vessels were studied. Bromelain, orally applied at 60 mg/kg body weight, inhibited the thrombus formation in a time dependent manner, the maximum being after 2 hours in 11% of arterioles and 6% of venoles. Intravenous application at 30 mg/kg was slightly more active in reducing thrombus formation in arterioles (13%) and venoles (5%), suggesting that orally applied bromelain is biologically active. These results may help to explain some of the clinical effects observed after bromelain treatment in patients with thrombosis and related diseases.
Adult↗
Cytostatic effects of various alkyl phospholipid analogues on different cells in vitro.
Phospholipid analogues were studied with regard to their cytostatic activity on different tumour cell lines and on murine bone marrow cells. Compounds compared for their activity were alkylglycero- and alkyl-phosphocholines with the corresponding serines and the alkylphosphocholines and -serines with the corresponding phosphono derivatives. Moreover, compounds containing cytidine 5'-diphosphate instead of the phospho (or phosphono-) choline or serine moiety were studied. rac-2-Chloro-2-deoxy-2-deoxy-1-0-hexadecyl-glycero-3-phosphocholine (cpd. Id), hexadecylphosphocholine (cpd. Ia) as well as hexadecylphosphonocholine (cpd. Ib) inhibited growth of tumour cells in suspension and monolayer culture and their colony and cluster formation in agar culture but not that of bone marrow cells. The exchange of choline for serine in these compounds results in the loss of this type of antitumour specificity. However, dodecylphospho-L-serine (cpd. IIc) is as specific as the choline derivatives Ia, b, d mentioned. Thus, for serine compounds the specificity for tumour cells might depend in a critical way on the length of the alkyl chain. The phosphono compounds Ib, IIb show almost the same activity as the corresponding compounds hexadecylphosphocholine (cpd. Ia) or hexadecylphosphoserine (cpd. IIa). The CDP-derivatives (IIIa, d, e, f) inhibited growth of tumour cells in suspension or monolayer cultures but not the colony and cluster formation in agar (i.e. they do not decrease the plating efficiency) from either tumour or bone marrow cells.
Alkylation↗
Relationship between 43 kDa epidermal growth factor-related clonogenic activity and clinical parameters for breast cancer.
The clonogenic activity of a previously purified 43 kDa EGF-related protein (16) was estimated in the urine of breast cancer patients. Increase of activity was statistically significant in lymph node-positive patients, in a group of patients with larger carcinomas, with accelerated tumor growth, in premenopausal patients and younger age and in estrogen receptor negative patients. In 31 patients the activity was estimated during polychemotherapy before surgery. Differences between the values at the begin and the end of treatment were compared between all groups by the Kruskal-Wallis test (p = 0.02). Patients with progressive disease showed increasing activities (mean values from 315 to 811) while in those with complete remission activity decreased (from 449 to 213). Partial- and non responders showed no change. In a long-term follow-up study with 25 patients the pre- and postoperative activities were estimated. In 17 of 18 patients who had no local recurrence or metastasis the activity declined after surgery, whereas in 6 of 7 patients who died, activity increased 2-5 fold prior to death. A life table analysis with a total of 101 patients revealed a trend to shorter survival in the group with higher activity (p = 0.042). These observations suggest a role for the EGF-like growth factor activity in the expression of the malignant phenotype and may have significance for breast cancer diagnosis and prognosis.
Aged↗
Prothymosin alpha augments deficient antitumor activity of monocytes from melanoma patients in vitro.
Human peripheral blood monocytes derived from normal donors, melanoma patients (MP) before and after chemotherapy (MPa) were assayed for their capacity to inhibit SK-MEL-28 melanoma cell growth in vitro; in addition, growth modulating effects by prothymosin alpha 1 (ProTa) were studied. After preincubation with or without ProTa for 1 day, monocytes were cultured in the absence or presence of interferon-gamma (rIFN-gamma) for a further day, and after cocultivation with SK-MEL-28 melanoma cells for 3 days monocyte/macrophage-mediated tumoristatic activity was determined employing the microculture tetrazolium (MTT) assay. The level of baseline growth inhibitory activity of unstimulated MP and MPa monocytes was 22% and 15%, respectively, and was significantly lower (p < 0.001) than that of normal monocytes (35%). The stimulation of monocytes/macrophages by rIFN-gamma greatly elevated the mean of their antitumor activity up to 44%, 49% and 58% in the group of MP, MPa and normal donors, respectively. ProTa significantly increased the level of monocyte-mediated growth inhibition of MP and normal donors, when it was applied alone or in combination with rIFN-gamma. Monocytes of MP at early stages (I and II) of their disease, when incubated with rIFN-gamma, showed a higher increase in tumoristatic activity than at stage III and tended to be the most susceptible to preincubation with ProTa followed by rIFN-gamma activation. However, on average tumoristatic activity of MP/MPa monocytes was significantly lower compared with that of normal monocytes, when activated with rIFN-gamma or ProTa alone or combined. Moreover, no effects on TNF-alpha secretion of MP/MPa monocytes were found by ProTa and/or rIFN-gamma, whereas TNF-alpha levels from normal monocytes were significantly increased by the two stimuli. These results indicate that monocyte disorders in melanoma patients may be partially normalized by ProTa.
Adult↗
Docetaxel enhances the expression of E-cadherin and carcinoembryonic antigen (CEA) on human colon cancer cell lines in vitro.
The in vitro effects of docetaxel on the human colon carcinoma cell lines-HT-29 and SW620 were studied by measuring the expression of the differentiation markers E-cadherin and CEA with a recently developed immunohistochemical assay. Docetaxel was shown to increase the expression of E-cadherin and CEA in the low concentration range of 3 x 10(-10) M - 3 x 10(-9) M for HT-29 cells and 0.6 - 3 x 10(-9) M for SW620 cells. Docetaxel strongly increased CEA (270%) and E-cadherin (160%) expression in HT-29 cells, compared with both marker expression in SW620 cells (60%). E-cadherin and CEA expression were found to be inversely correlated to the antiproliferating potential of docetaxel, which inhibits the cell proliferation of HT-29 cells at an IC50 of 6 x 10(-10) M and of SW620 cells at 8 x 10(-10) M. The data suggest, that in addition to its antiproliferative activity docetaxel also exhibits a strong differentiation inducing capacity at concentrations < 10(-9) M in vitro. These docetaxel effects were more pronounced on the differentiated HT-29 cells than on the poorly differentiated SW620 cells.
Antineoplastic Agents, Phytogenic↗