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Biomedical subjects

S Feder

Publications and source records attributed to S Feder.

10 recordsLinked to original sources

In vivo kinetics of intestinal absorption of riboflavin in rats.

To investigate absorption kinetics of riboflavin under in vivo conditions, with blood and lymph circulation intact, the small intestine of anesthetized rats was perfused with [14C]riboflavin in a concentration range between 0.31 and 10.00 mumol/L. Apart from the uptake of riboflavin from the perfusate, passage of the vitamin into the portal (vena portae) and peripheral (vena femoralis) blood was determined. The absorption proved to be a dual process: at low substrate concentrations (less than 2 mumol/L) a saturable component predominated; at higher concentrations simple diffusion was found to be the prevailing uptake mechanism. The apparent transport constant of the saturable component was calculated to be 0.38 mumol/L. [14C]flavin concentrations in the portal and peripheral blood were estimated as a function of the riboflavin concentration of the perfusion media. The dual character of the absorption was reflected by the portal blood flavin levels. Due to the high retaining and equalizing capacity of the liver, the [14C]flavin level of the peripheral blood was relatively low and obeyed saturation kinetics. Constants of elimination, determined by pharmacokinetic calculations, were different for the two blood compartments but independent of the concentration of riboflavin in the perfusion media.

Animals↗

Isolation and characterization of a urokinase-type plasminogen activator (Mr = 54,000) from cultured human endothelial cells indistinguishable from urinary urokinase.

A urokinase-type plasminogen activator secreted by subcultured normal human umbilical vein endothelial cells was purified and compared to urinary urokinase (Mr = 54,000). The enzyme was isolated from serum-free conditioned medium in the presence of 0.1% (v/v) Triton X-100 by p-aminobenzamidine-agarose affinity chromatography, followed by Sephacryl S-200 gel filtration, followed by immunoadsorption chromatography on affinity purified specific anti-urokinase IgG-Sepharose CL-4B. This plasminogen activator form was obtained from the culture medium with a yield of about 47% and specific activity of about 93,000 IU/mg of protein, and represented approximately 18% of the total multiple molecular plasminogen activator activity forms present in endothelial cell conditioned medium. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed a single band of plasminogen activator activity with an estimated molecular weight of about 54,000 that was completely inhibited by diisopropyl fluorophosphate (DFP) as well as a single band of radioactivity with similar molecular weight for both the isolated L-[4,5-3H]leucine and [3H]DFP-labeled enzyme. The radiolabeled protein focused as a single major band with a pI value of pH 8.5. The endothelial cell activator and urokinase appeared to be identical in terms of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, location of the [3H]DFP-labeled active site in the Mr = 33,000 heavy chain and [3H]DFP-labeled active site tryptic peptide, and two-dimensional 125I-labeled tryptic peptide maps. In quenching experiments of the fibrinolytic activities using affinity purified specific anti-urokinase IgG the endothelial cell-derived activator and urokinase appeared to be immunochemically identical, but unrelated to tissue plasminogen activator. These results indicate that the Mr = 54,000 urokinase-type plasminogen activator from cultured normal human endothelial cells is similar to, or identical with, Mr = 54,000 urinary urokinase.

Cells, Cultured↗

Culture-produced subendothelium. II. Effect of plasma, F.VIIIR:WF and fibronectin on interaction of normal platelets with normal and von Willebrand porcine aortic subendothelium.

Culture-produced normal and von Willebrand (vWd) porcine aortic subendothelium (SE) was prepared on glass and fibronectin (FN)-coated surfaces. Washed porcine platelets reacted extensively with normal SE (on glass) as single adherent non-spread and spread (5%) platelets, whereas vWd SE (on glass)-platelet interaction was decreased with no spreading. Normal porcine plasma increased normal SE-platelet interaction 3 to 5-fold and spreading 5-fold (20-30%); vWd SE-platelet interaction was increased 2 to 4-fold with no spreading. vWd porcine plasma did not affect normal or vWd SE-platelet interaction or spreading. Purified porcine F.VIIIR:WF (0.5-2 U/ml) increased both normal and vWd SE-platelet interaction 2 to 4-fold without increasing spreading. Purified human FN (50-200 micrograms/ml) did not increase normal of vWd SE-platelet interaction but increased spreading 5 to 7-fold (25-35%) with normal SE. F.VIIIR:WF (2 U/ml) plus FN (200 micrograms/ml) increased normal SE-platelet interaction 4 to 5-fold and spreading 8 to 9-fold (41%) with extensive SE-associated microaggregate formation; vWd SE-platelet interaction was increased about 6-fold with no spreading. Platelets reacted more extensively with normal and vWd SE prepared on FN-coated surfaces than SE on glass. Normal SE (on FN)-platelet interaction increased 6 to 7-fold and spreading 12-fold (60%); vWd SE (on FN)-platelet interaction increased about 110-fold with about 10% spreading. Plasma (normal and vWd), and F.VIIIR:WF did not significantly increase normal or Vwd SE (on FN)-platelet interaction or spreading. Results suggest a possible role for FN as a spreading factor in SE-platelet interactions.

Animals↗

Culture-produced subendothelium. I. Platelet interaction and properties.

Culture-produced subendothelium (SE) has been prepared from cultured porcine aortic endothelial cells (ECs) by a rapid freeze-thaw, ice-shearing method. En face preparations of this in situ SE material are essentially free of intact or damaged cells and cell debris and consisted of an extensive meshwork of microfibrillar and amorphous material. Washed porcine platelets reacted extensively with this SE material and were associated with the SE as single adherent platelets, single spread platelets, and varying-sized platelet aggregates or 'microthrombi'. Platelet aggregates were associated only with the damaged or frayed edges of the SE, and the platelets had undergone extensive SE-induced contraction and degranulation, as indicated by transmission electron microscopy. Platelet-SE interaction was affected by pH, calcium, platelet concentration, rapid shaking and exposure time. Platelet-SE interaction was significantly enhanced by the addition of 0.1-1% citrated plasma or purified porcine F.VIIIR:WF. Pretreatment of the SE with thrombin, elastase, neuraminidase or hyaluronidase had no effect on platelet-SE interaction, whereas pretreatment with pepsin, plasmin, trypsin, alpha-chymotrypsin or collagenase decreased or completely abolished all platelet-SE interaction. Extraction of the SE with various solutions (high salt, detergents, etc.) had no effect on platelet-SE interaction, only solutions containing sodium dodecyl sulfate completely abolished all platelet-SE interaction.

Animals↗

Tardive dyskinesia--reversible and persistent.

Twenty-one hospitalized patients over 50 years of age who had tardive dyskinesia were studied for 13 months. After withdrawal of neuroleptics and antidepressants for three months, dyskinetic symptoms abated in 12 patients and persisted in nine. Discriminant function analysis showed that the persistent and reversible dyskinesia groups could be clearly separated and that the best discriminator was the number of drug-free intervals. The persistent dyskinesia group had had significantly longer neuroleptic treatment (mean, 10.8 yr) and a greater number (mean, 5.6) of drug interruptions of at least two months' duration each than did the reversible dyskinesia group. Our finding, as well as the literature reviewed, does not support the commonly held notion that frequent lengthy interruptions of long-term drug treatment reduce the incidence of persistent dyskinesia, at least in patients who are otherwise predisposed to the development of tardive dyskinesia.

Aged↗

Radioimmunoassay for human alpha 1 -fetoprotein.

A method of radioimmunoassay has been developed for the quantitation of alpha(1)-fetoprotein in human serum. The assay requires 20 mul of serum, can be completed in 8 hr, and can reproducibly detect concentrations of 20 ng of alpha(1)-fetoprotein per ml of serum. Hence, the method is about 500-fold more sensitive for the detection of alpha(1)-fetoprotein than the Ouchterlony teohnique currently in general use. The procedure is of potential clinical value as an aid in the diagnosis of cancer and a number of noncancerous hepatic diseases.

Adult↗