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A variety of inflammatory proteins have been identified in brains of Alzheimer's disease (AD) patients, including inflammatory cytokines, acute phase proteins and complement components. In the present paper we have investigated the levels of circulating inflammatory mediators as potential biomarkers of this disease, concentrating mostly on transforming growth factor beta (TGF-beta1) in plasma and on nitric oxide synthase (NOS) activity in leukocytes. Plasma and leukocytes were isolated from 48 sporadic AD and 23 healthy control subjects of same age and sex. Since alpha2-Macroglobulin (alpha2M), an acute phase protein possibly involved in AD, is an important modulator of TGF-beta1 activity, binding and targeting this cytokine to its appropriate site of action, we have investigated the possible complex between TGF-beta1 and alpha2M in plasma of the same subjects. The results demonstrate a significant reduction of TGF-beta1 levels in plasma of AD patients. A complex between alpha2M and TGF-beta1 occurred in AD as well as healthy elderly control subjects, however, with no significant differences. Moreover, alpha2M appeared to bind only the inactive form of this cytokine. In contrast, NOS activity increased significantly in leukocytes of AD patients. Therefore, we suggest the combined determination of TGF-beta1 in the plasma and of NOS activity in the leukocytes as biomarkers of AD.

Allograft rejection is a process that depends on T cell receptor-ligand interaction and costimulatory signals generated when accessory molecules binds to their ligands, such as CD28 to the B7 molecules. We investigated the possibility that B7 blockade in vivo by the soluble CD28 receptor homolog CTLA4Ig modulates rejection process in a rat model of kidney allograft. Lewis rats orthotopically transplanted with MHC incompatible kidney from Brown-Norway rats were given an intraperitoneal injection of CTLA4Ig (0.2 or 0.5 mg/day) or a nonspecific immunoglobulin for seven days, starting the day of transplant. While control rats rejected the graft within 10 days, all animals given CTLA4Ig had a prolonged kidney allograft survival, independently from the dose of the fusion protein employed. Actually, at the dose of 0.2 mg/day kidney grafts survived 36 to 50 days (median 44 days), while with the highest dose graft survival was 40 to 60 days (median 50 days). In all CTLA4Ig-treated rats renal grafts were well functioning as documented by serum creatinine concentrations comparable to age- and sex-matched control rats 30 days after transplant. At this time in vitro mixed lymphocyte culture (MLR) experiments showed a significant reduction of proliferation of peripheral blood lymphocytes from CTLA4Ig-treated rats when challenged with BN but not third party Wistar Furth lymphocytes. We have also shown that combining a short course of CTLA4Ig (0.2 mg/day) with a dose of cyclosporine (CsA) low enough to fail to inhibit graft rejection allowed indefinite engraftment of kidney allograft without the need of continuous immunosuppression.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent experiments have shown that exposure of maturing rat thymocytes to donor cells induces a condition of donor-specific unresponsiveness in the recipient that allows indefinite survival of a subsequent kidney transplant without the need for long-term immunosuppressants. Here, studies were performed in Lewis (RT1(1)) rats to determine whether (a) the process of unresponsiveness to kidney allograft induced by intrathymic donor cell inoculation occurred also with a noninbred strain of donor animals, and (b) this technique could allow the elimination of the need for daily immunosuppressive therapy in animals already transplanted with an incompatible kidney. Kidneys from noninbred Sprague-Dawley rats transplanted in incompatible Lewis (RT1(1)) rats, previously injected intrathymically with cells from the same donor, survived indefinitely. Intrathymic inoculation of donor cells into Lewis rats allowed a stabilized, incompatible renal allograft from Brown-Norway (RT1n) rats to survive indefinitely after discontinuation of immunosuppressive treatment with cyclosporine. These findings provide an approach for renal transplantation without immunosuppressive therapy and a potential strategy to overcome side effects related to the use of immunosuppressants in animals already transplanted.

Peripheral blood lymphocytes from 16 mycosis fungoides (MF) patients were studied using OKT series monoclonal antihuman T cell antibodies. The percentage of OKT3+ cells was in normal range for all MF patients compared with controls; the percentage of OKT4+ cells was significantly increased (p less than 0.002) in MF patients versus controls; the percentage of OKT8+ and OKT11+ cells in the MF group did not differ from controls. The OKT4+ cell expansion was apparently not dependent from the clinical stage of disease. These findings suggest that in MF patients there is a circulating OKT4+ cell expansion and, indirectly, that MF could be regarded as a helper T cell neoplasm.

A study on HLA-DR and DQ typing in 40 patients with lichen planus (26 males and 14 females) and in 92 normal blood donors of both sexes was performed. Twenty-seven patients had cutaneous lesions, 11 cutaneous and mucosal involvement and 2 patients had oral erosive lesions. Serological typing revealed a highly significant increase of HLA-DR 1 antigen in the patient group. No difference has been observed on the prevalence of DR1 antigen among the different clinical status of the disease.

The prevalence of serum markers, HBsAg, anti-HBsAg, HBcAg and anti-HBeAg in a group of subjects affected by chronic alcoholism with fatty liver or with cirrhotic stages is reported. An incidence of chronic HBsAg carriers, similar to that found in healthy subjects, was noticed, while an elevated incidence of other serological markers of previous contact with HBV were found. The Authors discuss the significance of this report, on the basis of a greater possibility of contact with HBV, for social-economic situations of those patients. The etiopathogenetic role of HBV in the cirrhotic evolution of alcoholic liver diseases was excluded.

We performed HLA typing in 96 couples affected by recurrent abortion "sine causa". We matched these patients with 124 fertile couples and 204 individuals random paired. No significant difference in HLA sharing was demonstrated in the three study groups. The statistical analysis denoted significant differences in regard to HLA A3, A24, B12, and DR- comparing patients and normal members of fertile couples. The frequencies of HLA Cw5, Cw6 and DR2 were different in patients when compared with their partners.