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Biomedical subjects

S J Friedman

Publications and source records attributed to S J Friedman.

84 records · Page 5Linked to original sources

The inhibition of thymidine kinase in glial tumor cells by an amino sugar, D-glucosamine.

Thymidine kinase activity in rat C6 glioma cells is inhibited by 50 to 70% after 4 hr incubation with 20 mM D-glucosamine. The inhibition is uncompetitive with respect to thymidine, reducing both the apparent Km and Vmax of the enzyme. The inhibition does not appear to be caused by the reversible combination of the enzyme with a cytoplasmic inhibitor, including D-glucosamine and its metabolites. The addition of D-glucosamine or its metabolites to cell-free thymidine kinase produced an inhibition which differed quantitatively and qualitatively from that which resulted from treatment of intact cells with D-glucosamine. The presence of a reversible cytoplasmic inhibitor of the enzyme was also excluded by mixing experiments. D-Glucosamine inhibited the incorporation of labeled uridine and amino acids into acid-precipitable material. The magnitude of inhibition of thymidine kinase activity and amino acid incorporation by D-glucosamine was comparable to that produced by cycloheximide, suggesting that the inhibition might arise from interference with enzyme synthesis. However, whereas the kinetics of recovery of amino acid incorporation from inhibition was rapid, thymidine kinase activity was depressed for at least 6 hr after drug washout. The results presented are best explained by assuming either that two forms of thymidine kinase are present in rat C6 cells and are differently affected by D-glucosamine or that D-glucosamine acts by two separate mechanisms to inhibit a single form of the enzyme.

Amino Acids↗

The inhibition of thymidine metabolism in tumor cells treated with D-glucosamine.

The amino sugar, D-glucosamine, inhibits the preformed route of thymidine metabolism in rat C6 glioma cells. This inhibition results from a concatenation of several distinct effects, including the inhibition of thymidine uptake, the reduction of thymidine phosphorylation, and an increased leakage of thymidine to the extracellular space. Each of these effects, while ostensibly small in magnitude, is significant and contributes to the observed inhibition of acid-precipitable thymidine incorporation by D-glucosamine. These effects of D-glucosamine, together with its known ability to reduce uridine nucleotide pools, may contribute to its toxicity toward certain experimental animal tumors.

Cell Line↗

Catecholamine levels in the injured spinal cord of monkeys.

The authors report a study of catecholamine levels in the spinal cords of monkeys following a 300 gm-cm blow to the midthoracic spinal cord. There was a progressive decrease in norepinephrine (NE) activity as a first-order process with a half-life of 6.4 hours. The NE activity in injured tissue never exceeded control levels, which remained unchanged both above and below the injured segment. Dopamine activity remained unchanged in the injured tissue as well as in control segments above and below the area of trauma for the first hour.

Animals↗

Blood flow in normal and injured monkey spinal cord.

The authors used indicator fractionation techniques to determine blood flow in normal and bluntly traumatized spinal cords of Macaca rhesus monkeys. Normal flow rates were determined for several levels of spinal cord as well as differential values for white and gray matter from representative areas. Flow rates in traumatized tissue, obtained at several different time intervals up to 4 hours after injury, demonstrated marked differences in regional perfusion of the white matter and gray matter after trauma. Gray matter perfusion was nearly obliterated while white matter blood flow persisted and in fact was higher than uninjured controls. The findings do not support the concept of ischemia as a factor in white matter failure. If toxic pathobiochemical alterations are induced by trauma, it may be possible to reverse these changes by exploiting the preserved white matter blood flow for chemotherapeutic intervention.

Animals↗

Intracellular enzyme liberation in primate spinal cord injury.

Intracellular lysosomal and nonlysosomal enzymes, as well as tissue edema, were measured in spinal cords of monkeys up to 20 days following a 300 gm-cm open injury. Although edema was maximal between six hours and 11 days, enzyme elevation was delayed. Lysosomal enzyme acid cathepsin increased beginning at five days and the beta-glucuronidase and beta-glycerophosphatase increase began at 11 days. Nonlysosomal enzymes were either not elevated or showed a slight rise. These data suggest that edema, one of the secondary damaging factors in spinal injury, is not a result of release of these intracellular enzymes. Also it appears that intracellular enzymes do not participate in early secondary damaging processes in severe spinal injury.

Acid Phosphatase↗

Increased serum iodide concentration from iodine absorption through wounds treated topically with povidone-iodine.

Increased serum iodide concentrations secondary to iodine absorption through wounds treated with povidone-iodine dressings is described. Hyperchloremic acidosis and a disparity between serum chloride concentrations determined by two different methods suggested the presence of an unidentified halide. Cardiovascular instability and renal failure occurred concurrent with systemic iodide accumulation. Measurement of serum iodide concentration should be performed when povidone-iodine is used topically in patients with impaired renal function.

Aged↗

Arthroscopically treated tears of the glenoid labrum. Factors influencing outcome.

Labral tears and associated glenohumeral ligament injuries were classified and treated arthroscopically in 83 patients. Transverse labral tears were the most common. Subtle increased glenohumeral translation was noted in 24% of patients. Glenohumeral ligament injury was present in 58% of the shoulders, with the middle and superior ligaments or middle ligaments alone most commonly involved. These ligament injuries were classified into different groups based on severity. Partial excision of the torn labrum was the primary treatment in all patients and was combined with glenohumeral ligament repair in 9 patients. Seventy-eight patients were available for subjective follow-up evaluation (average, 3.2 years), while 53 patients were objectively evaluated (average followup, 2.8 years). There were 14% excellent, 71% satisfactory, and 15% poor results. The main factor associated with poor results was a grade III glenohumeral ligament injury in which only partial excision of the torn labrum was performed. There was a positive correlation between injury to both the superior and middle glenohumeral ligaments and increased anterior translation demonstrated by preoperative stability testing at 60 degrees of humeral abduction in neutral rotation. We believe glenohumeral ligament injury is often associated with labral tears and arthroscopic partial labral excision is only effective in those patients who have grade I or II (less severe) glenohumeral ligament injuries.

Adolescent↗