Michael H. Ross

Ultrastructural Alterations in the Adluminal Testicular Compartment in Men with Varicocele

Testicular biopsies from 21 otherwise healthy men with diagnosed varicocele were processed for light and electron microscopy. Whereas germ cell morphology and tissue architecture of the basal testicular compartment appeared normal, cellular mophology and intercellular associations of the adluminal testicular compartment were variably altered. In affected tubules, spermatid nuclear and acrosomal morphology was abnormal and sloughing was evident. Spermatids were maloriented relative to Sertoli cells, and Sertoli-germ cell junctional complexes appeared to be structurally abnormal. Contradistinctly, Sertoli-Sertoli cell junctional complexes appeared unaffected. Results from this study indicate that testicular disruption in varicocele is a phenomenon of the adluminal compartment, that the Sertoli cell is, in fact, more sensitive to perturbation of the testicular environment than are germ cells, and that the Sertoli cell is the primary intratubular site of alteration leading secondarily to spermatogenic disruption.

Sustained reflow in dogs with coronary thrombosis with K2P, a novel mutant of tissue-plasminogen activator.

Coronary artery reocclusion after thrombolysis with human recombinant tissue-type plasminogen activator (rt-PA) is related to the short half-life of this agent in plasma. K2P, a mutant of rt-PA lacking the fibronectin fingerlike, epidermal growth factor-like and first kringle domains (amino acids 6 to 173) and having the glycosylation site Asn184 mutagenized to Gln, has been produced in Chinese hamster ovary cells. In this study we compared the thrombolytic effect of K2P and rt-PA in dogs with electrically induced coronary artery thrombosis. Both agents were given intravenously in equimolar amounts over 20 min after the occlusive thrombus was stable for 30 min; dogs were monitored for 1 h after reperfusion if flow occurred. Coronary blood flow was restored by rt-PA in 6 (60%) of 10 dogs. The restored flow lasted for 49 +/- 12 min and mean flow at 60 min from the start of reperfusion was 7 +/- 3 ml/min. The reocclusion rate was 50% (three of six dogs). Flow was restored in five (100%) of five dogs by K2P. The restored blood flow lasted during the entire 1-h observation period in all but one dog and mean flow at 60 min was 49 +/- 16 ml/min (p less than 0.02 vs. flow in rt-PA-treated dogs). Restored coronary blood flow showed marked cyclic flow variations in rt-PA-treated but not in K2P-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic acid and isolated human umbilical vein: Concentration-limited prostacyclin generation and absence of direct toxic effects on endothelial integrity

Previous studies show that administration of high doses of arachidonic acid to rabbits causes disruption of vascular integrity. To examine if similar changes would occur in isolated human vascular tissue, we treated human umbilical veins with arachidonic acid (0, 0.01, 0.1, 1.0 mM). Prostacyclin biosynthesis was quantitated in the supernatants and the endothelial integrity was evaluated by scanning electron microscopy. Prostacyclin synthesis was maximum at low concentrations (0.01-0.1 mM) with no additional increase with higher concentrations of arachidonic acid (1mM) confirming previous observations. There was no evidence for endothelial disruption with any concentration of arachidonic acid. This study shows that arachidonic acid has no direct effects on the vascular lining of isolated human umbilical vein, arachidonic acid-induced sudden death in experimental animals is not due to limitation of prostacyclin synthesis.