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Biomedical subjects

R G Kladetzky

Publications and source records attributed to R G Kladetzky.

At least 19 recordsLinked to original sources
PubMed1986

Stimulation of the scavenger receptor on monocytes-macrophages evokes release of arachidonic acid metabolites and reduced oxygen species.

Mouse peritoneal macrophages are endowed with a scavenger receptor recognizing modified low density lipoproteins (LDL). Metabolic sequelae of receptor occupancy distinct from lipoprotein processing were examined. Adherent peritoneal macrophages were kept in short term culture. Release into culture supernatants of the arachidonic acid derived eicosanoids prostaglandin E, 6-keto-prostaglandin F1a, thromboxane B2, and leukotriene C4 was assessed, and production of reduced oxygen species superoxide anion and hydrogen peroxide, generated in the oxidative burst, was monitored after challenge of macrophages with acetylated or malondialdehyde modified LDL. Modified LDL at concentrations ranging from 50 to 250 micrograms of protein/ml was noted to augment macrophage arachidonic acid metabolism within 6 hours of addition. Cyclo-oxygenase derivatives were synthesized predominantly, but leukotriene C4 generation was also observed. Further, scavenger receptor occupation triggered the release of superoxide anion and hydrogen peroxide which was more rapid in onset and plateaued after 60 minutes of incubation. Human monocyte-derived macrophages, after 4 days in culture, also generated reduced oxygen species and eicosanoids in response to modified LDL. Along with our previous finding of scavenger receptor mediated lysosomal enzyme liberation, the present study indicates novel functions of these binding sites. Our observations may shed new light on the possible role of monocyte-macrophages in atherogenesis.

Animals↗
PubMed1986

[Significance of lipids in the diagnosis of coronary heart disease in patient groups and individuals].

Several epidemiologic studies confirmed the significance of the risk ratio cholesterol/HDL-cholesterol in predicting coronary heart disease. Therefore we examined the lipid values of 364 men and 133 females who underwent coronary arteriography because of angina pectoris and/or pathological ECG changes at rest or during exercise stress testing. Although patients with coronary heart disease showed higher cholesterol (male 238 mg/dl vs. 210 mg/dl, female 251 mg/dl vs. 219 mg/dl, p less than 0.001), higher triglycerides (male 204 mg/dl vs. 162 mg/dl, female 179 mg/dl vs. 125 mg/dl, p less than 0.001) and significantly lower HDL-cholesterol levels (male 39.9 mg/dl vs. 44 mg/dl, female 45.9 mg/dl vs. 54.9 mg/dl, p less than 0.01) than the control group, lipid values did not lead to a good discrimination between patients with or without coronary heart disease. The patients' histories and ECGs showed a higher sensitivity (male 83%/male 85%) and specificity (male 81%/female 83%) than the lipids (sensitivity male 57%/female 67%, specificity male 55%/female 74%). We conclude from our results that blood lipids, the risk ratio cholesterol/HDL-cholesterol and other risk factors are diagnostic tools which have to be handled with caution when applied to the individual patient with suspected coronary heart disease.

Angina Pectoris↗
PubMed1985

Chemically modified low density lipoproteins as inducers of enzyme release from macrophages.

Macrophages carry receptors on their surface for acetylated low density lipoprotein (ac-LDL). Receptor-mediated endocytosis of ac-LDL is followed by intracellular cholesterol accumulation. We investigated whether occupation of these binding sites evokes the release of hydrolytic enzymes from mouse peritoneal macrophages cultured for up to 48 h. ac-LDL at concentrations ranging from 25-250 micrograms protein/ml was noted to promote in a dose-dependent fashion secretion of the neutral proteinase elastase (EC 3.4.21.37) and the lysosomal acid hydrolases N-acetyl-beta-glucosaminidase (EC 3.2.1.30), beta-glucuronidase (EC 3.2.1.31), beta-galactosidase (EC 3.2.1.23), alpha-mannosidase (EC 3.2.1.24) and cathepsin D (EC 3.4.23.5). This stimulatory effect was non-cytotoxic. LDL modified by treatment with malondialdehyde was also capable of augmenting enzyme liberation into culture supernates. These findings may have implications for some aspects of the atherosclerotic process.

Acetylation↗
PubMed1985

Spontaneous progression and regression of small carotid atheroma.

A specially designed high-resolution (10 MHz) ultrasound duplex-system was used to study prospectively the appearance of 43 extracranial non-stenotic carotid plaques (less than 30% lumen narrowing) in 31 patients over 18 months. 13 presented with ipsilateral and 9 with contralateral cerebrovascular events; 9 were asymptomatic. Most carotid atheromas remained unchanged (51%) or progressed (30%), but spontaneous regression was seen in 19% at regular 3 monthly re-examination. Regression was restricted to volume reduction of soft plaques and healing of ulcerative lesions; fibrous and hard plaques remained unchanged or progressed. Intraplaque haemorrhage was only observed in 3 instances and was always associated with later progressive encroachment. Comparison of bilateral plaques in the same individual suggested a uniform advance with duration of the atherosclerotic process. None of the patients had cerebrovascular events during follow-up.

Adult↗
PubMed1985

[Development of nonstenotic extracranial carotid plaques--a prospective study of its course with the Duplex system].

The natural history of a prospectively investigated group of patients with small non-stenotic extracranial carotid lesions (less than 30% lumen narrowing) was studied during 18 months. Using a specially designed high resolution (10 MHz) ultrasound Duplex system, 43 lesions were followed in 31 patients. Whereas the majority of the carotid atheromas remained unchanged (51%) or deteriorated (30%), spontaneous regression could be observed in 19%. Regression was limited to volume reduction of "soft plaques" and healing of "ulcerative" lesions, while "fibrous" and "hard plaques" remained unchanged or deteriorated. None of the patients developed cerebrovascular events during follow-up.

Adult↗
PubMed1984

Frequency of apolipoprotein A-I mutants in the German population.

A randomly chosen population in the area of Westphalia (West Germany) was screened for apolipoprotein A-I mutants. About 5000 individuals were investigated and compared with a group of 1300 patients who had undergone coronary angiography. Four electrophoretically different apolipoprotein A-I-mutants (named Münster-1 to 4) were discovered. Five non-related probands were observed in the group of the unselected patients and three non-related probands in the group of coronary angiography patients. In most cases the familial nature of the abnormality was confirmed by pedigree analysis.

Adult↗
PubMed1982

[Mitral valve prolapse and platelet activity in young patients with cerebral ischaemia (author's transl)].

In 47 patients under 45 years of age (average age 35.4 years) with more or less localised cerebral ischaemia without evidence of arteriosclerosis echocardiography showed mitral valve prolapse in 13 cases. This was slightly more frequent than in an age and sex-matched control group. The difference was not statistically significant. In three quarters of the patients (n = 35) a significantly raised beta-thromboglobulin level was found indicating increased platelet activity. No definite conclusions can be drawn as to the cause of cerebral ischaemia which is probably due to embolism. However, treatment with platelet aggregation inhibitors should be considered.

Adult↗
PubMed1982

One-step screening method for the polymorphism of apolipoproteins A-I, A-II, and A-IV.

Apolipoprotein A-I exhibits a polymorphism that can be easily investigated in native serum by a simple method involving incubation of serum in the presence of decylsulfate and beta-mercaptoethanol and subsequent isoelectric focusing. From six to eight proteins can be separated in a pH gradient from 4 to 6 and thus patients with apolipoprotein A-I variants can be distinguished from normal persons. This method also permits monitoring for polymorphic forms of apoA-II and apoA-IV as well as detection of C apolipoproteins. To verify the identity of the different apolipoproteins, a two-dimensional electrophoresis technique was applied, with an SDS system for the second dimension. In addition, monospecific antibodies for apolipoproteins A-I, A-II, and A-IV were used for the immunological identification. The method described here led to the discovery of three different familial apolipoprotein A-I variants.

Apolipoprotein A-I↗
PubMed1981

[Serum lipid levels under chronical treatment with beta-receptor blocking agents in patients with coronary artery disease (author's transl)].

Concerning the effects of beta-receptor blocking agents (beta-RB) on serum lipids levels of total cholesterol, HDL cholesterol and triglycerides were determined in 237 consecutive male patients with coronarographically proven coronary artery disease. 43% (n = 101) of all patients were taking beta-RB. The percentage of factors apt to influence serum lipid levels and the extent of coronary artery disease were similar in the subsets with (group 1) and without (group 2) chronical beta-RB therapy.-The mean values of total cholesterol (group 1: 242 mg%, group 2: 239 mg%) and HDL cholesterol (group 1: 42 mg%, group 2: 41 mg%) were nearly identical; there were, however, significantly enhanced triglyceride concentration under beta-RB therapy (group 1: 222 mg%, group 2: 184 mg%, p less than 0.0125). This difference was most pronounced in patients with one-vessel disease. Patients treated with beta-1-selective RB had lower triglyceride levels than those treated with nonselective RB (208 mg% vs. 222 mg%, n.s.). In accordance with findings of other authors, these data might indicate that serum triglycerides are elevated by chronical administration of beta-RB. It should be a topic of further investigations if the present results can be interpreted the way that chronical application of beta-RB might favour development and/or deterioration of coronary artery disease.

Adrenergic beta-Antagonists↗
PubMed1980

Coagulation parameters and heparin levels in open-heart surgery.

Coagulation parameters were studied during open-heart surgery. Severe reduction of the platelet count and of several other clotting factors was observed. The half-rate of heparin varied threefold in the patients. This may indicate that the dosage of protamine chloride prior to the end of the surgical procedure has to be adjusted to the individual heparin levels.

Antithrombin III↗
PubMed1980

Lipoprotein and apoprotein values in coronary angiography patients.

In this study the lipoprotein and apoprotein patterns of patients with coronary artery disease were evaluated. The patient population consisted of 179 men who underwent coronary arteriography. On the basis of the results of coronary arteriography these patients were subdivided into a control group (score 0) with normal arteriograms and three groups each having coronary artery disease (CAD) of increasing severity (scores 1 to 3). The patients with coronary artery disease had significantly higher plasma concentrations of total cholesterol, LDL cholesterol, triglycerides and apolipoprotein B (apo B) than the controls. HDL cholesterol as well as apolipoprotein A-I (apo A-I) were significantly lower in patients with coronary artery disease. However, no difference was found in apolipoprotein A-II (apo A-II) values. Apo B and LDL cholesterol increased with the degree of coronary atherosclerosis. In the discriminant function analysis, apo B was the best separating parameter between control patients and CAD patients (scores 1-3).

Apoproteins↗
PubMed1978

Isolation and purification of Lea blood-group active and related glycolipids from human plasma of blood-group A Lea individuals.

From 81 of human plasma of blood-group A Lea nonsecretors three different Lea blood-group active ceramide pentasaccharides (a total of 4.65 mg) have been isolated, all revealing glucose, galactose, N-acetylglucosamine and fucose in molar ratios of 1 : 2 : 1 : 1 as determined by gas liquid chromatography. A fourth blood-group active fraction (0.72 mg) represents a mixture of a Lea active ceramide pentasaccharide and an A active ceramide hexasaccharide (molar ration 7.7 : 2.3 as calculated from the content of different aminosugars). Additionally, two different globosides, two different hematosides and a new N-acetylglucosamine containing ceramide tetrasaccharide were obtained. All 9 glycolipid fractions demonstrated homogeneity in analytical high performance thin layer chromatography (HPTLC) using 4 different solvent systems. 0.2 microgram of each Lea active glycolipid completely inhibited the agglutination of O Le(a+b-) erythrocytes by 50 microliter of 4 hemagglutinating units of caprine anti Lea serum. At least 0.04 microgram of each Lea antigen are sufficient for incubation to convert 9 x 10(7) O Le(a-b-) erythrocytes into Lea-positive cells. Mainly due to the relatively low content of the blood-group A glycolipid in plasma (0.17 mg/81), previously negative erythrocytes readily become agglutinable by anti Lea sera and not by anti A sera after incubation with appropriate plasma.

ABO Blood-Group System↗
PubMed1977

[Effects of premedication, narcosis and surgery on the coagulation and fibrinolysis systems and the platelets. The influence of dextran and hydroxyethyl starch (hes) during and after operation (author's transl)].

Patients who had undergone orthopaedic surgery were investigated. The changes attributable to premedication and narcosis were characterized by a primary fibrinolysis which was accompanied by a slight hypercoagulability. This increased fibrinolytic activity was more pronounced immediately after the beginning of the operation. The post operative changes are characterized by increased ADP-induced aggregation, increased release of platelet factors 3 and 4 and hypercoagulability with reduced fibrinolysis. The reduction in platelets during the operation could be prevented due to the influence of dextran and hydroxyethyl starch (HES). It came further to a slight increase in the activity of factor VII, to an increased fibrinogen polymerization and also to an increased release of platelet factor 4.

Adenosine Diphosphate↗