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Biomedical subjects

G Beck

Publications and source records attributed to G Beck.

At least 199 records · Page 11Linked to original sources

Rat hematopoietic cell receptors for very low density lipoprotein (VLDL) growth inhibitor.

Physiologic concentrations of rat plasma very low density lipoproteins (VLDL) have profound inhibitory effects in tissue culture on the proliferation of hormonally stimulated bone marrow granulocytic and erythrocytic cells and mitogen-stimulated spleen cells. In this study we have evaluated the in vitro uptake and binding of 125I-VLDL by rat marrow cells and spleen lymphocytes. To this end, VLDL were isolated from rat plasma by sequential ultracentrifugation flotation and radioiodinated using iodine monochloride. Biological activity of 125I-VLDL was ascertained by demonstrating that 125I-VLDL and native VLDL had comparable proliferative inhibitory effects when added to erythropoietin-stimulated marrow cells and PHA-stimulated lymphocytes. After 1 h exposure of marrow to VLDL, exhaustive cell washing did not reverse the lipoprotein growth inhibitory effect. The cell uptake of VLDL was evaluated by adding 125I-VLDL to marrow or spleen cells. Uptake of 125I-VLDL by rat cells showed a preference for binding of VLDL as compared to chylomicrons, LDL, or HDL. Based on Scatchard plot analysis of 125I-VLDL binding at 37 degrees C, the approximate number of saturable VLDL receptors available per marrow or spleen cell during a 3 h incubation was 34,000 and 63,000, respectively. We conclude that rat marrow cells and lymphocytes have specific receptors for plasma VLDL and that receptor binding of VLDL is an initial step in its growth inhibitory effect. The physiologic role of plasma lipoprotein cell growth inhibitors will remain speculative, however, until the in vivo distribution of the biologically active lipoprotein moiety to extravascular sites of hematopoiesis has been determined.

Animals↗

Age-related changes of liver tyrosine aminotransferase in senescent rats.

Tyrosine aminotransferase was induced in adult and senescent rat liver and its properties studied. We show the appearance of a 'cross-reacting material' for induced tyrosine aminotransferase of old rats compared to basal enzyme; this cross-reacting material can be provoked in adult rats after injection of cycloheximide, and suppressed in adult and old rats after injection of a serine protease inhibitor (tosylphenylalanine chloromethylketone). Other properties of induced tyrosine aminotransferase (thermostability, Km for tyrosine, isoelectrofocusing) are identical except for the proportion of the three forms and their sensitivity to trypsin in the absence of pyridoxal phosphate, which is increased in senescent animals. The suppression of cross-reacting material clearly indicates that it is not due to errors on old rat liver DNA but rather to post-translational modifications. This demonstrates also the role of serine proteases in tyrosine aminotransferase degradation. We suggest that induced enzyme of senescent rats would undergo a conformational change, possibly due to a release of pyridoxal phosphate from the enzymic molecules, which would thus become more susceptible to proteolytic attack than those of adult rats.

Aging↗

Identification of the major metabolite of prostacyclin and 6-ketoprostaglandin F1 alpha in man.

Human volunteers were infused with 3H- and 2H-labeled prostacyclin or 3H-labeled 6-ketoprostaglandin F1 alpha and, in separate experiments, with the unlabeled prostanoids. The urine was purified by different chromatographic steps and finally separated into several fractions by high-performance liquid chromatography. The major fractions contained 20.5 and 23.0% of the eluted readioactivity for the metabolites of prostacyclin and 6-ketoprostaglandin F1 alpha, respectively. The structure of both metabolites was identified by gas-liquid chromatography-mass spectrometry as dinor-6-ketoprostaglandin F1 alpha. It is concluded that the major metabolite of prostacyclin and 6-ketoprostaglandin F1 alpha in man is dinor-6-ketoprostaglandin F1 alpha.

6-Ketoprostaglandin F1 alpha↗

Action on ricin and its polypeptide chains on cultured hepatoma cells.

The effect of ricin, the glycoproteic toxin from castor beans, as well as of its two polypeptide chains A and B, was studied on hepatoma tissue cell suspension cultures (HCT). The isolated A and B chains have no action. Ricin at a 0.3 microgram/ml concentration, for 3 x 10(5) cells/ml, has a cytostatic effect which becomes cytotoxic after 72 h. This effect exists even if the cells are preincubated for 4 with ricin and washed afterwards. The protein content of the ricin-treated cells decreases. Protein synthesis measured by the incorporation of [3H]-leucine in the cell proteins begins to be inhibited after 30 min and is completely blocked after 2 h for a ricin concentration of 0.3 microgram/ml. DNA synthesis is inhibited from 1 h on. Finally the level of the DNA slows down from 3 h on, whereas the level of RNA abruptly falls between 4 and 5 h. The inhibitory effects are likely to be a consequence of protein synthesis inhibition, but a direct effect on the nucleic acids is not excluded.

Animals↗

Antihypertensive activity of 16, 16-dimethyl-oxa-alkyl-prostaglandins of the PGA2, PGE2 and trans-delta 2-11-deoxy-PGE1 series: structure-activity relationships.

Utilizing Corey's synthesis, a variety of prostaglandins (PGs) with a modified omega-side chain were prepared. The 16, 16-dimethyl-oxa-alkyl analogues of PGA2 had potent antihypertensive activity. HR 466 (16, 16-dimethyl-18-oxa-PGA2), the best compound out of this series was active for 5-6 hours after oral administration of 0, 1 mg/kg to conscious renal hypertensive dogs. The corresponding analogues of PGE2 were also potent anti-hypertensive compounds, but were much more spasmogenic. Structural variations within the trans-delta 2-11-deoxy-PGE1-series, in both side chains, gave HR 601 (trans-delta2-15alpha-acetoxy-16, 16-dimethyl-18-oxa-11-deoxy-PGE1-methylester) which was orally active in the hypertensive dog with similar activity to HR 466.

16,16-Dimethylprostaglandin E2↗

Combined action of citrinin and ochratoxin A on hepatoma tissue culture cells.

Citrinin (CTN) and ochratoxin A (OT-A) may occur simultaneously in mould-contaminated commodities. Both are cytotoxic to hepatoma tissue culture (HTC) cells. The effect of both mycotoxins, eiter alone or in association on cellular protein, RNA and DNA synthesis was tested. In the presence of ochratoxin A protein synthesis is first inhibited 30 min after the addition of the toxin and RNA synthesis after 150 min. No inhibition of DNA synthesis occurs for at least 5 h, whereas citrinin inhibits first the RNA synthesis after 10 min, second protein synthesis after 20 min and third DNA synthesis after 120 min. When both mycotoxins are added simultaneously to HTC cells the inhibition of RNA and protein synthesis occurs immediately, that of DNA synthesis after a short lag time. This suggests a cooperative effect of both mycotoxins.

Animals↗

Studies on the different molecular forms of tyrosine aminotransferase from rat liver and hepatoma cells.

In an attempt to clarify the significance of the separable forms of tyrosine aminotransferase, the enzyme from rat liver and from cultured hepatoma cells was studied by carboxymethyl-Sephadex chromatography. Our studies of the form conversion during the purification procedure of the enzyme, where all cellular components were quickly discarded, do not allow us to invoke a specific "converting factor", the existence of which in the particulate fraction has been suggested. Moreover the addition of serine protease inhibitors is not sufficient to prevent the classical conversion. More probably, several factors depending on the environmental conditions might influence different reactions which lead to a preferential conformation of the enzyme in vitro. The difference in the PO4- content of the various enzyme forms and the consecutive differences in negative charge may be the determining factor in the elution pattern of the three forms of the isolated soluble enzyme. This observation raises the possibility that phosphorylation might play a specific role in the regulation of tyrosine aminotransferase synthesis.

Animals↗

Tyrosine aminotransferase in senescent rat liver.

We have studied tyrosine aminotransferase in the liver of adult and old rats. Thermostability and trypsin action were not modified, and no charge differences have been found by isoelectric focusing between 'adult' and 'old' enzymes. Inducibility by glucocorticoids was increased in vivo in these 27- to 31-month-old rats, but not in vitro, in cultured hepatocytes. Moreover, we have shown the absence of 'cross-reacting material' for tyrosine aminotransferase in senescent rat livers. The rapid turnover of this enzyme may explain the apparent absence of alterations during aging.

Aging↗

Metabolism of prostacyclin and 6-keto-prostaglandin F1 alpha in man.

The major metabolites of prostacyclin and 6-keto-prostaglandin F1 alpha in man were investigated. Healthy male volunteers were infused with the labeled and unlabeled prostanoids. The urine was chromatographed on different systems including high-pressure liquid chromatography (HPLC). The material under the major peak was derivatized to the methyl ester methoxime trimethyl silyl ether and analyzed by gas chromatography-mass spectrometry (GC-MS). Open bed reversed-phase chromatography of the urine obtained from PGI2 infusion resulted in two peaks. On further separation by two different HPLC systems one major peak containing 20.5 % of the radioactivity was obtained and was shown by GC-MS to be identical with dinor-6-keto-prostaglandin F1 alpha. Urine obtained from 6-keto-prostaglandin F1 alpha infusion was chromatographed similarly. Its major peak on HPLC appeared with a retention volume and mass spectrum identical with the major metabolite of PGI2. It is concluded that the major metabolite of PGI2 and 6-keto-prostaglandin F1 alpha in human urine is dinor-6-keto-prostaglandin F1 alpha.

6-Ketoprostaglandin F1 alpha↗

[Quantitative cytobacteriological study of sputum in chronic bronchitics (author's transl)].

A quantitative cytobacteriological study of sputum was carried out in 259 chronic bronchitics. In non-purulent sputum (leukocyte count lower than 2,000/mm3), flora identified was salivary in 73% of the cases. In purulent sputum (leukocyte count higher than 5 000/mm3), the most frequently identified predominant bacterial species were Haemophilus influenzae (20%), Pseudomonas aeruginosa (13%) and Streptococcus pneumoniae (10.5%). In the most severely ill patients, admitted to the intensive care unit, Haemophilus influenzae was rarely identified as a predominant bacteria (9.8%), whereas in 26.3% of the cases, Pseudomonas aeruginosa was identified as the only bacteria present. In the less severely ill chronic bronchitis admitted to the medical department, the most common bacteria was Haemophilus influenzae (34.4%), Streptococci (19%) and Streptococcus pneumoniae (8.8%). The leukocyte count in sputum was systematically higher in the patients admitted to the intensive care unit even when the mean bacterial concentration was identical to that observed in the patients in the medical department.

Bacteria↗

What's next?

Although maximum exposure limits are not listed for radiologic examinations, a study conducted by the United States Government has determined the average values for ten selected radiologic examinations. This study entitled Nationwide Evaluation of X-ray Trends (NEXT) can be used as a guide to determine if your x-ray department meets these criteria. Recommendations are made for the reduction of patient exposure in the event that the Entrance Skin Exposure Guides (ESEG) are exceeded. The ESEG's are a direct result of the NEXT study.

Humans↗