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Biomedical subjects

G Schettler

Publications and source records attributed to G Schettler.

At least 37 records · Page 2Linked to original sources

Atherosclerosis and coronary heart disease.

The formation of the "early proliferative lesion" of arteriosclerosis is the result of a chronic interaction of endothelial cells, monocytes/macrophages, smooth muscle cells, and potentially other cells such as T-lymphocytes and platelets. The precise manner in which these cells ineract during the early stage of the disease is unclear. The initial mechanisms involved in the pathophysiological interaction of these cells in the presence of the clinically important risk factors remain to be determined and represent a major challenge for future research. As we learn more about the molecular mechanisms we will be able to develop new strategies of therapy to prevent the disease.

Arteriosclerosis↗

The role of diet and drugs in lowering serum cholesterol in the postmyocardial infarction patient.

Lipid disorders are the most important factors in the development of coronary heart disease (CHD). They need to be treated in primary as well as in secondary prevention. U.S. and European Consensus Conferences agreed that desirable serum cholesterol levels should not exceed 200 mg/dL. When baseline cholesterol averages above 250 mg/dL, the minimum requirement for characterizing the lipoprotein disorder is measurement of cholesterol, triglycerides, and high-density lipoprotein (HDL) in the fasting state. In selecting targets for serum lipid values, it may be taken into account that CHD incidence is lowest in persons with serum cholesterol below 180 mg/dL. Any kind of lipid-lowering therapy should be commenced with dietary treatment. If this is ineffective, drugs may be applied additionally. Possible causes of secondary hyperlipidemia should be excluded. There is no strict age limit for treatment but the subject's cardiovascular status should be examined carefully, especially in secondary prevention. The patient in whom extensive myocardial damage is the main arbiter of prognosis is unlikely to gain from strenuous efforts aimed at retarding progression of atheromata, the major causes of CHD. A simple classification distinguishes drugs with a predominant effect on hypercholesterolemia from those effective in endogenous hypertriglyceridemia but with a somewhat weaker cholesterol-lowering action. Using lipid-lowering drugs, their indications and side effects should be considered.

Cholesterol↗

Iliac crest needle biopsy as a method for determining estrogen receptors in bone metastases from breast cancer.

The purpose of our study was to clarify whether the amount of tissue extracted by means of iliac crest needle biopsy (ICNB) would suffice for a quantitative determination of estrogen receptors (ER) in bone metastases, and to see if the method currently used for determining ER in primary tumors could also be successfully utilized in ICNB. 22 of 31 breast cancer patients examined could be evaluated. ER was positive in 7 (31.8%). Reasonable data are to be expected when the biopsy weight exceeds 0.1 g. Our study confirms that the necessary amount of tissue for ER analysis can indeed be extracted by ICNB. Our results justify further studies on a larger group of patients, since we cannot make conclusive statements concerning the value of this method for predicting the ultimate success of an endocrine treatment.

Adult↗

The value of bone marrow examination for tumor staging in breast cancer.

The purpose of our study was to investigate the value of cytokeratin antibodies for identifying bone marrow involvement in breast cancer patients who showed no evidence of distant metastases using noninvasive tumor staging procedures. Bone marrow for histological (biopsy) and immunocytochemical (aspiration) evaluation was obtained from the anterior iliac crest from 50 unselected consecutive women during surgical treatment of the primary tumor. The histological examination was done on nondecalcified bone sections. The immunocytochemical studies were carried out on interface smears of the bone marrow aspirates. For staining, cytokeratin antibodies (PKK 1) and the immune alkaline phosphatase method was used. Cytokeratin-positive cells were found in 4 of the 50 cases (8%). Of those 4 patients, however, 2 also showed evidence of neoplastic bone marrow infiltration histologically. We thus were able to prove that immunocytochemistry on aspirates is superior to conventional histology in identifying tumor in bone marrow. Nonetheless, our results clearly fell below the rate found in previous studies where epithelial membrane antigen antibodies were used.

Bone Marrow↗

The Eberbach/Wiesloch Study: lipoprotein profiles of 35- to 49-year-old men and women.

Plasma lipid- and lipoprotein profiles of a representative sample of men and women aged 35 to 49 years in the Federal Republik of Germany were investigated. Mean plasma cholesterol levels, triglyceride levels, and phospholipid levels were significantly higher in men than in women. An extensive investigation of plasma lipoproteins, including measurement of all major apolipoproteins and lipids in each density class revealed profound sex differences in the distribution and composition of lipoproteins. In men mean plasma levels of VLDL-cholesterol (33.20 mg/dl) and of VLDL-triglycerides (155 mg/dl) were three times as high as in women (11.38 mg/dl and 50.08 mg/dl, respectively). The relative amount of triglyceride was 15% higher in VLDL of men, due to decreased relative amounts of VLDL-phospholipids. Intermediate-density lipoproteins (IDL) were significantly higher in men. Men had also higher levels of Apo B in low-density lipoproteins (LDL). Interestingly, LDL-cholesterol levels of men and women were not significantly different. Women had more high-density lipoproteins (HDL), and the absolute and relative amounts of HDL2-cholesterol were significantly higher in women. In summary, besides well-known sex differences in plasma lipid levels, sex-specific differences in the levels of certain plasma lipoproteins were observed. The most important finding was that the composition of the lipoproteins showed profound differences between men and women. With regard to risk for atherosclerotic cardiovascular disease, women have more favorable lipoprotein profiles than men. These data may provide a basis for further investigations on alterations in plasma lipid and lipoprotein profiles in respect to risk for atherosclerotic cardiovascular disease.

Adult↗

Binding of acetylated low density lipoprotein and maleylated bovine serum albumin to the rat liver: one or two receptors?

The liver is the major organ involved in clearance of acetylated low density lipoprotein (acetyl-LDL) and maleylated serum albumin (Mal-BSA). Quantitative analysis of the hepatic uptake by sequential scintigraphy in rats shows that the hepatic uptake capacity for Mal-BSA is at least 15 times larger than for acetyl-LDL particles. A membrane-associated M approximately 250,000 daltons hepatic receptor for acetyl-LDL and Mal-BSA was 1450-fold purified from total membrane by Triton X-114 solubilization, chromatography on polyethylenimine cellulose and gel filtration. This receptor incorporated into liposomes displayed a saturable binding of [131I]Mal-BSA with a dissociation constant Kd = 15 nM and to [131I]acetyl-LDL with a dissociation constant Kd = 0.9 nM. The binding of both ligands was sensitive to poly(vinyl sulfate). The purified scavenger receptor system has a binding capacity for [131I]Mal-BSA 20 times larger than for [131I]acetyl-LDL. This is similar to the maximal removal capacity of the rat liver for both ligands in vivo. Binding studies with Mal-BSA, acetyl-LDL and anti-idiotypic receptor antibodies as competitors for [131I]Mal-BSA and [131I]acetyl-LDL binding demonstrate that [131I]Mal-BSA and [131I]acetyl-LDL compete for a common binding site. However, not all of the Mal-BSA binding sites are capable of interacting with acetyl-LDL.

Albumins↗

[Neutralization of low molecular weight heparin Kabi 2165 by protamine chloride].

Low molecular weight (LMW) heparin Kabi 2165 possesses improved pharmacodynamic properties compared with conventional heparin. It is currently investigated in the prophylaxis of thromboembolism. The neutralization of Kabi 2165 by protamine chloride was analysed after i.v. injection of both the agent and the antidot in healthy persons. The anticoagulant effects of the LMW heparin on the activated partial thromboplastin time, thrombin, and thromboelastography are completely and immediately suppressed by protamine chloride. The inhibition of factor Xa is antagonized up to 50%-60%. The bleeding time remained unaffected. The data indicate that protamine chloride may be used in clinical situations as an antidot to the LMW heparin Kabi 2165. A rebound phenomenon of the anticoagulant effect does not occur.

Blood Coagulation↗

Low density lipoprotein receptor-dependent prostaglandin synthesis in Swiss 3T3 cells stimulated by platelet-derived growth factor.

We studied the effects of human plasma lipoproteins on the synthesis of prostaglandin (PG) E2 in Swiss 3T3 mouse fibroblasts. Quiescent cells, maintained in medium deficient in both platelet-derived growth factor (PDGF) and lipoproteins, synthesized less than 8 ng of PGE2 per 10(6) cells per 22 hr, and this rate did not change in response to the addition of lipoproteins. In contrast, PDGF-stimulated cells, incubated in medium deficient in lipoproteins, synthesized 45-110 ng of PGE2 per 10(6) cells during the same period of time, and this rate increased 2- to 5-fold in the presence of added low density lipoproteins (LDL). This stimulatory effect of LDL seemed to depend on LDL receptor-mediated binding, uptake, and degradation of the lipoproteins because: both LDL and very low density lipoproteins were active, whereas high density lipoproteins were not; low concentrations of LDL were effective; the effect of native LDL was blocked by acetylation of the LDL; PDGF increased both the expression of LDL receptors and the cellular uptake of LDL; chloroquine blocked the effect of LDL but not that of exogenous arachidonic acid. These results provide evidence that the LDL pathway is critically linked to PG synthesis in PDGF-stimulated cells.

Acetylation↗

Review and current status of thrombolytic therapy with streptokinase.

In 1933 Streptokinase (SK) was isolated from bacterial strains of haemolytic Streptococci. Since then it has become the widest spread drug for fibrinolysis. SK, a protein, consists of 415 aminoacids and has a molecular weight of 47,000u. Together with the plasminogen (PLG) of the blood it forms activator complexes, which then convert other PLG molecules of the blood to plasmin. Plasmin attacks and dissolves fibrin deposits. As a substance produced by bacteria SK stimulates antibody formation in the body, the titer will increase during therapy, and SK lysis should be terminated after 6 days of treatment. Usually SK is administered intravascularly to treat a wide range of diseases, associated with pathological activation of hemostasis, like deep vein thrombosis, pulmonary embolism, myocardial infarction etc.. Contraindications can be traced back to the effects of SK on coagulation and the immune system. Bleeding is the most common side effect, but also a few anaphylactic reactions, caused by massive antigen-antibody precipitation have been observed. The rate of lethality of the treatment was established at 0.7% of the cases. To reduce the incidence of side effects modifications of the drug have been proposed, such as activator complex, light B chain SK, and acylated activator therapy. Compared with Urokinase, SK shows a higher rate of side effects, especially in the field of the immune system. Therapy with Urokinase can be controlled more easily. Nevertheless because of considerable price differences and logistics, SK is preferred in Europe and the USA. If strict guidelines in therapeutic use are followed, the rate of side effects of the drug can be curtailed and will be comparable to those of Urokinase.

Humans↗