Expression of the growth-associated protein GAP-43 in adult rat retinal ganglion cells following axon injury.

We have studied the expression of the growth-associated protein GAP-43 after injury to the axons of adult rat retinal ganglion cells (CNS neurons that do not normally regenerate injured axons). Both the biosynthetic labeling of GAP-43 and the GAP-43 immunoreactivity of the retina increased after axotomy, but only when the injury was within 3 mm of the eye. These results suggest the following conclusions: First, axon injury is sufficient to alter GAP-43 expression in CNS neurons, even in the absence of regeneration. Second, mechanisms that regulate GAP-43 expression are sensitive to the length of uninterrupted axon remaining after injury. Finally, the conditions that favor increased GAP-43 are similar to those that favor regrowth of injured CNS axons into grafts of peripheral nerve, suggesting that GAP-43 induction is accompanied by an increased potential of injured CNS neurons to regenerate.

Generation of autologous Epstein-Barr virus-specific cytotoxic T cells for adoptive immunotherapy in solid organ transplant recipients.

BACKGROUND: Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative disorders (PTLD) affect 2%-27% of solid organ transplant (SOT) recipients. Adoptive immunotherapy may have therapeutic potential in this setting, but there is little experience in generating autologous EBV-specific cytotoxic T-cell lymphocytes (EBV-CTLs) from SOT recipients, and their efficacy and persistence in an immunosuppressed environment is unknown. METHODS: EBV-CTLs were generated from eight SOT recipients, using weekly stimulations with autologous lymphoblastoid cell lines (LCLs) and interleukin-2. CTL phenotype and function were evaluated in the presence of therapeutic concentration of cyclosporin A or FK506. RESULTS: In all cases, CTLs expanded with normal kinetics. The majority was CD3+CD8+ (mean, 76%), with less than 3% of natural killer cells. All ex vivo-generated CTLs produced significantly higher killing of autologous LCLs than of HLA-mismatched LCLs (mean, 56% vs. 14% at 20:1 ratio). No lysis of autologous or allogeneic PHA blasts was observed. The CTL expansion rate was reduced in a concentration-dependent manner in the presence of immunosuppressive drugs; however, neither lytic activity nor phenotype was affected. CONCLUSIONS: Using methods that are approved for clinical application, EBV-CTLs can be generated from SOT recipients, even those with frank lymphoma, or who are receiving immunosuppressive drugs. These CTLs retain their function in the presence of immunosuppressive agents. Although in vivo efficacy, safety, and persistence can be assessed only in clinical trials, our results suggest that CTLs can be effective for the treatment of PTLD, even when immunosuppression cannot be reduced because of the high risk of graft rejection.

Renal transplant diet recommendations: results of a survey of renal dietitians in the United States.

A survey of dietitians at renal transplant centers in the United States was conducted to identify diet modifications currently used for nondiabetic adults after kidney transplantation. The survey focused on the diet recommended for the first 21 days after successful transplantation. Questionnaires were mailed to 100 centers randomly selected from a comprehensive list obtained through the Organ Transplant Coordinating Office of the Texas Medical Center, Houston. A 66% response rate was obtained. The results of the survey showed that dietitians were most frequently recommending 1.2 to 1.5 gm protein per kg body weight, 40% to 50% of total energy as carbohydrate, a fat intake of less than 30% of total energy, and an energy level consistent with achieving or maintaining desirable body weight. Sodium intake was most commonly restricted to 2 to 4 gm, whereas potassium and phosphorus intakes were individualized according to the patient's serum values. Comments on the returned questionnaires indicated that many institutions were reviewing and updating their transplant diet to include a polyunsaturated fat to saturated fat ratio and restrictions of cholesterol and simple sugars. The findings of the survey indicated that the renal transplant diet should focus on optimal protein and energy intake as well as restriction of simple sugars, total fat, cholesterol, and saturated fat to restore nitrogen balance and minimize clinical symptoms of post-transplant diabetes and hyperlipidemia.

[Cardiac glycosides and metabolites--problems of recovery in tissue extracts. Separation of visible substance spots in the nanogram range (author's transl)]. / Herzglykoside und Metaboliten--Probleme der Wiederfindung in Gewebsextrakten. Abtrennung sichtbarer Substanzflecke im Nanogrammbereich mittels HPTLC.

The recovery measurements in rat tissues performed via i.p. injected radioactive digoxin derivates (3H-digoxin, 125J-digoxin derivative) showed that approximately 50% of the total glycoside content will be extracted. Thus, an addition of digoxin standards to drug-free tissues may lead to false negative determinations. By comparison of the radioactivity before and after extraction the following results were obtained: Recovery from tissues 3H-digoxin 50% 125J-digoxin 40% from serum 3H-digoxin 60% added to drug free tissue homogenates 3H-digoxin 85% After i.p. application of 15 mg/kg of beta-methyldigoxin to BD9 (Berlin)-rats the resulting tissue concentrations were extracted by Amberlite XAD-2. beta-Methyldigoxin and its metabolites digoxin and digoxinbisdigitoxide could be separated and distinguished from artifacts by fluorescence detection on HPTLC-plates with a detection limit of 60 ng/spot. Concentration determined by radioimmunoassay are in satisfactory agreement with HPTLC results.

The opportunity and obligation to eliminate rubella from the United States.

The licensure of rubella vaccines in the United States in 1969 offered the opportunity to prevent the devastating consequences of congenital rubella infection, including miscarriages, therapeutic abortions, and congenital rubella syndrome (CRS), with its average lifetime cost of more than $220,000 per case. With the widespread use of vaccine, rubella transmission in the United States has been reduced to record low levels. Epidemics of rubella and CRS, previously reported every six to nine years, have not occurred, and since 1980, following decreases of rubella incidence rates in the postpubertal population, the endemic incidence rates of CRS have also begun to decrease. We have both the opportunity and the obligation to hasten elimination by (1) ensuring that susceptible females of childbearing age are vaccinated, (2) initiating and/or enforcing existing legislation requiring proof of rubella immunity for all children enrolled in schools, (3) intensifying surveillance for both acquired rubella and CRS, and (4) aggressively controlling rubella outbreaks.