Permanent rat cardiac allograft survival induced by ultraviolet B-irradiated donor lymphocytes and peritransplant cyclosporine

This study examines the effect of pretreatment with 10(8) ultraviolet B-irradiated donor leukocytes (UV-DL) with or without peritransplant cyclosporine (CyA) treatment (20 mg/kg on days 0, +1, and +2 relative to transplantation) on rat cardiac allograft survival across major histocompatibility loci. A single UV-DL pretreatment on day -3 or -7 (before transplantation) significantly prolonged survival of heart allografts from Wistar-Furth rats (W/F) in Lewis recipients from 6.8 +/- 0.8 days to 18.4 +/- 2.1 and 17.6 +/- 1.5 days (p less than 0.001), respectively. Multiple UV-DL infusions on days -14 and -7 increased the mean survival time to 20.0 +/- 0.9 days (p less than 0.001). Similarly, UV-DL infusion on day -3 or -7 significantly prolonged the mean survival time of heart allografts from ACI rats in Lewis rats. A single or multiple UV-DL infusions combined with peritransplant CyA led specifically to permanent W/F cardiac allograft survival (more than 200 days) in all recipients. Similarly, UV-DL infusion combined with peritransplant CyA led to indefinite survival of ACI cardiac allografts in two thirds of Lewis recipients. Adoptive transfer of splenocytes from long-term recipients of cardiac allografts, which specifically prolonged donor test grafts in syngeneic hosts, suggests that unresponsiveness to cardiac allografts is, in part, dependent on suppressor cells. This study emphasizes the importance of UV irradiation of DLs in the modulation of alloreactivity and the induction of donor-specific unresponsiveness in adult animals.     

Necrotizing fasciitis

Fourteen patients with necrotizing fasciitis seen over a 5 year period at a public hospital are reviewed. Middleaged men predominated. The disease followed such diverse initiating causes as self-injection with heroin, boil, ischiorectal abscess, perforated occult colonic cancer and trivial abrasions. In a few cases there was no evidence of an initiating lesion. Necrotizing fasciitis affected the arms, legs, trunk and neck. Bacteriologic analysis showed that the disease is usually caused by gram-negative bacilli and hemolytic streptococci, alone or in combination. Morbidity and mortality rates in the present series were influenced by associated clinical conditions such as old age, diabetes mellitus, carcinoma and gram-negative bacteremia.     

Humoral immunity in allograft rejection. The role of cytotoxic alloantibody in hyperacute rejection and enhancement of rat cardiac allografts

The role of humoral immunity in graft rejection in the rat model remains controversial. Passive transfer of cytotoxic alloantibody (CAA) has resulted either in hyperacute rejection or in graft enhancement. This study examines the effect of transfer of CAA on cardiac allograft survival in three rat strain combinations that are fully mismatched at the major histocompatibility (MHC) loci. Strain-specific immune responsiveness in donor-recipient pairs varied from low (Lewis-to-ACI) to high (ACI-to-Lewis) as measured by mixed lymphocyte reactions. CAA was obtained from rats sensitized by three successive skin grafts at weekly intervals. Group 1 (high responder recipients), which consisted of Lewis rats presensitized to ACI and had a lymphocytotoxicity titer of 1:512 to 1:2048, rejected ACI cardiac allografts in 10.8 +/- 7.2 hr compared with 6.5 +/- 0.5 days in naive controls (p less than 0.001). Injection of 1 ml of high-titer CAA into naive Lewis rats immediately after ACI cardiac grafting led to hyperacute rejection of ACI hears in 2.1 +/- 0.8 hr while 1 ml of CAA followed by 2 ml of guinea pig complement (GPC) resulted in even faster rejection (mean survival time (MST) of 23.8 +/- 4.7 min). Injection of 2 ml GPC alone or in combination with 1 ml naive Lewis serum had no effect on graft survival. Multiple pretransplant injections of 1 ml of CAA on days -3, -2,-1, and 0 relative to transplantation resulted in significant prolongation of allograft survival (MST of 10.3 +/- 0.3 days; P less than 0.01). In group 2 (intermediate responder recipients), where Lewis rats were presensitized to WF strain and where cytotoxicity titer was 1:16 to 1:256, the recipients rejected WF hearts in 23.8 +/- 5.8 hr compared with 6.8 +/- 0.8 days in unsensitized control recipients (P less than 0.001). Injection of 1 ml of Lewis anti-WF CAA resulted in prolonged graft survival of 9.7 +/- 3.5 days, while injection of 1 ml of CAA followed by 2 ml of GPC caused hyperacute rejection in 104 +/- 61.7 min. Pretransplant injections of CAA on days -3, -2, -1, and 0 resulted in enhancement, with an MST of 16.3 +/- 1.3 days (P less than 0.001). In group 3 (low responder recipients), ACI presensitized to Lewis developed a cytotoxicity titer of 1:2 to 1:32 and rejected Lewis hearts in 5.3 +/- 0.4 days compared with 10.6 +/- 1.0 days in naive recipients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Selective lymphoid irradiation. VI. Effect of palladium-109-labeled lymphocytes on rat cardiac allograft survival

We have previously shown that pretransplant treatment with palladium-109 hematoporphyrin (Pd-H) and two small doses of antilymphocyte globulin (ALG) leads to donor-specific permanent acceptance of cardiac allografts in weakly histoincompatible rat combinations and significant prolongation of hearts in the ACI-to-Lewis strains. Pd-H also concentrates in nonlymphoid organs to a significant degree that is undesirable, so we have examined, in the present study, the efficacy of Pd-109 attached to lymphocytes in producing selective lymphoid irradiation and compared it with the immunosuppressive effect of Pd-H. Adoptive transfer of syngeneic lymphocytes labeled with palladium-109 (Pd-L) led to significant concentration of radioactivity in the peripheral lymphoid organs relative to the bone marrow (BM), intestine, thymus, and endocrine organs. The concentration of radioactivity in the spleen relative to BM and intestinal mucosa was 23:1 and 58:1, respectively. The immunosuppressive efficacy of a suboptimal dose of 3 mCi (one-third of the dose used in our earlier reports with Pd-H) administered via Pd-L (6 X 10(9) cells) at 4 days combined with 5 mg ALG at 2 days and 1 day prior to transplantation was compared in its effect on cardiac allografts with a similar dose of Pd-H (3 mCi) combined with ALG. The mean survival time (MST) of 6.5 +/- 0.4 days in untreated recipients was moderately prolonged to 14.6 +/- 3.0 days by Pd-H and ALG, and was not significantly different from an MST of 14.1 +/- 0.3 days achieved with 2 doses of ALG alone. Pretransplant treatment of Lewis rats with Pd-L and ALG produced a significant prolongation of ACI heart allografts to 30.5 +/- 3.1 days (P less than 0.001). These results suggest that Pd-L is more effective in prolonging rat cardiac allografts than a similar dose of Pd-H, and thus it may be a new method of selective lymphoid irradiation prior to transplantation.     

Zur Beeinflussung der Nahrungsaufnahme durch Psychopharmaka

Summary The effects of 16 psychotropic drugs on food intake and body weight were studied in female Wistar rats under carefully controlled conditions. After 3 days of placebo treatment the drugs were administered orally 1 hr prior to a 12-hours-per-day feeding period for at least 3 further days. Normal daily feed consumption averaged 6.11 g/100 g BW. Haloperidol, reserpine, chlorpromazine, chlorprothixene, promethazine, azacyclonol, imipramine, and amitriptyline in appropriate doses all reduced both food intake and body weight, but there were marked differences in activity. Small amounts of chlorpromazine may even stimulate feeding behaviour. Chlorpromazine sulfoxide was without influence. The central stimulant Tradon^® evoked anorexia whereas only short-lasting anorexigenic effects if any were observed following the administration of either 2-diethylamino-4-oxo-5-phenyl-oxazoline or pipradol. On the other hand chlordiazepoxide, phenobarbital, and to some extent oxazepam caused the animals to increase their feed consumption and to gain weight. The results are discussed with regard to clinical reports of appetite and weight changes due to psychotropic drugs.     

Selective lymphoid irradiation. I. An approach to transplantation.

The kinetics, distribution, and radiobiologic effects of palladium (Pd)-109-hematoporphyrin were determined in the rat. In addition, we studied the effect on rat heart allograft survival of Pd-109-hematoporphyrin, with and without antilymphocyte serum (ALS). A single sublethal dose of Pd-109-hematoporphyrin (up to 36 muCi/kg) resulted in the following: predominant concentration in lymphoid tissue and proximal bone marrow, complete central and proximal bone marrow ablation with preservation of distal bone marrow, massive depletion of lymphocytes from lymph nodes and spleen, an 80% reduction in peripheral blood lymphocytes which was completed by the addition of ALS, full recovery of lymphoid tissue and blood cellularity within 60 days of administration of radionuclide, and a 100% animal survival rate. This method of selective lymphoid irradiation (SLI) prolongs indefinitely Fisher cardiac allografts in Lewis recipients and significantly prolongs cardiac allograft survival across major histocompatibility barries (ACI to Lewis or to Fisher). Specific tolerance to donor strains was demonstrated by the acceptance of Fisher skin by Lewis recipients carrying 150-day-old Fisher hearts. Third party (ACI) skin allografts were rapidly rejected by the same animals. Further studies of SLI in larger animals are required to determine the optimal safe dose of SLI in man.     

Predicting Serum Vitamin E Concentrations from the Age of Normal and Anticonvulsant Drug-Treated Epileptic Children Using Regression Equations

Serum vitamin E was assayed in 100 patients who were apparently normal, with no medical problems and on no medication, and whose ages ranged from 2 to 12 years. Serum vitamin E was also assayed in 100 patients with grand mal convulsive disorders, on anticonvulsants, but on no other drugs, with no gastrointestinal problems and in a similar age range. In the 100 control children, there was a tendency for serum vitamin E to increase with age. Serum vitamin E concentrations in 100 anticonvulsant drug-treated epileptic children were significantly lower than in the control group and did not increase with age. In the control group, a regression analysis was used to predict serum vitamin E concentrations in different age groups. This information would be useful for population and metabolic studies of serum vitamin E concentrations.