Actions of phencyclidine on the action potential and membrane currents of single guinea-pig myocytes

The direct actions of phencyclidine (PCP) on mammalian sarcolemma were examined by determination of the drug's effects on the action potentials of isolated guinea-pig ventricular cells, and on the underlying ionic currents. PCP (10(-6) to 10(-4) M) did not alter the resting membrane potential but produced a dose-dependent prolongation of the duration of the action potential, and a reduction of the rate of depolarization of phase 0 (Vmax) of the action potential. Voltage clamp experiments revealed that PCP blocks both myocardial Ca++ channels and myocardial time-dependent K+ channels. The K+ channel blockade was shown to exhibit an apparent voltage-dependence. The effects of PCP on these ionic channels could explain previous reports of it prolonging myocardial action potentials and conflicting reports of positive and negative inotropism.     

Role of Integrin CD103 in Promoting Destruction of Renal Allografts by CD8+ T Cells

Infiltration of CD8(+)TCRalphabeta(+) T-effector populations (CD8 effectors) into graft epithelial compartments has long been recognized as a key lesion in progression of clinical renal allograft rejection. While the afferent phase of allograft immunity is increasingly well-defined, the efferent pathways by which donor-reactive CD8-effector populations access and ultimately destroy the graft renal tubules (rejection per se) have received remarkably little attention. This is an important gap in our knowledge of transplantation immunology, because epithelial compartments comprise the functional elements of most commonly transplanted organs including not only kidney, but also liver, lung, pancreas, and intestine. Furthermore, there is increasing evidence that attack of graft epithelial elements by CD8-effector populations not only causes short-term graft dysfunction but is also a major contributor to development of chronic allograft nephropathy and late graft loss, which now represent the salient clinical problems. Recent studies of the T-cell integrin, alpha(E)beta(7) (CD103), have provided insight into the mechanisms that promote interaction of CD8 effectors with graft epithelial compartments. The purpose of this communication is to review the known properties of the CD103 molecule and its postulated role in the efferent phase of renal allograft rejection.     

Anti-platelet opsonic activity in alloimmune and autoimmune thrombocytopenia

A chemiluminescence technique (CLT) has been developed which measures the interaction between human monocytes and antibody-coated (opsonized) platelets. This technique has an objective end-point, is simple to perform and is of comparable sensitivity to the platelet suspension immunofluorescence test (PSIFT) when used to detect anti-platelet allo-antibodies. In contrast, only 4/20 sera from patients with clinically diagnosed autoimmune thrombocytopenia were opsonic in the CLT, while 8/20 of these same sera bound IgG to platelets in the PSIFT. Only one serum gave positive results in both tests.     

Bacteriology of the marine environment: implications for clinical therapy

Ocean water and tissue samples were obtained from a variety of sources with phylogenetic and geographic diversity. Purified bacterial colonies were isolated and identification procedures were performed. A total of 67 isolates were recovered. Thirty-eight isolates belonged to the genus Vibrio and included six species. Twenty-four non-fermentative bacteria and four Gram-positive isolates were recovered. Antibiotic susceptibility testing showed that while the non-fermentative marine bacteria generally were susceptible to the antibiotics tested, marine Vibrio species were relatively resistant to a wide variety of antimicrobials. Antibiotics effective against all species included imipenem, trimethoprim/sulfamethoxazole, and chloramphenicol. Further recommendations for treatment are based on sensitivity in culture. Some isolates failed to grow in the medium used for susceptibility testing. Because commercial test kits may not yield accurate identifications of bacteria, the acquisition of antimicrobial susceptibility data gains added importance.     

A protocol for the successful long-term enzyme replacement therapy of scurvy in guinea pigs

Summary Gulonolactone oxidase, a key enzyme in the biosynthesis of ascorbic acid, is missing from guinea pigs and certain other scurvy-prone species. Weekly intraperitoneal injections of glutaraldehyde cross-linked immunoprecipitates of this enzyme have been shown to provide guinea pigs with the capability of synthesizing their own ascorbic acid and of surviving without an exogenous source of this vitamin. This protocol, however, was successful in only a small percentage of the animals tested. The reasons for the limited therapeutic success were investigated. Apparently, the gulonolactone oxidase-treated guinea pigs fed without ascorbic acid were receiving insufficient nutrition. By supplementing these enzyme-treated animals with vitamins A, B, D and E and selenium, we successfully maintained a high proportion of guinea pigs fed without vitamin C.