[Medical practice in the thought of Thomas Aquinas].

In the works of St. Thomas Aquinas there are many examples of medical practice, in the discussion of philosophical and theological questions. St.

IL-10 and the cytokine network in the pathogenesis of human autoimmune hemolytic anemia.

In animal and human autoimmune hemolytic anemia (AIHA) immunologic tolerance loss against RBC self-antigens could be originated by several mechanisms: ignored self-antigens' epitopes, polyclonal lymphocyte activation, molecular mimicry between self- and foreign antigens, central or peripheral tolerance errors, or immunoregulatory disturbances including the alteration of a cytokine network. To identify the immunologic factors contributing to autoimmune onset and maintenance, several murine strains (such as NZB and NZB/NZW) that spontaneously develop a complex autoimmune syndrome, including AIHA, have been extensively studied. In human AIHA, the respective roles of IL-2, IL-4, IFN-gamma, IL-10, and IL-12 were investigated by examining the spontaneous and mitogen-induced (OKT3 or LPS) production of these cytokines.

[Medical practice in Rome during the XVI century].

S. Filippo Neri (1515-1595), founder of the Congregazione dell'Oratorio in Rome, was a longly debated clinic case for his various pathologies. Eminent scientists, like B.

Immunological tolerance loss vs. erythrocyte self antigens and cytokine network disregulation in autoimmune hemolytic anaemia.

Recent studies on animal and human autoimmune hemolytic anaemia (AIHA) suggest that the loss of immunological tolerance vs. erythrocyte (Er) self antigens (Ag) may be primed by different mechanisms: ignorance of Er self Ag, molecular mimicry between self and non-self Ag, polyclonal T and/or B cells activation, errors in central or peripheral tolerance, immunoregulatory disturbances including the alteration of cytokines network. In vitro stimulation by synthetic Rh peptides indicates that ignorant T and/or B cells from patients with AIHA may recognize criptic Er self Ag.

Mechanisms of immunological tolerance loss versus erythrocyte self-antigens and autoimmune hemolytic anemia.

Recent studies on animal and human autoimmune hemolytic anemia (AIHA) suggest that immunological tolerance loss toward red blood cells (RBC) self-antigens may be originate by different, non-mutually exclusive, mechanisms. According to now available data the identified mechanisms may be: ignorance against RBC self-antigens; molecular mimicry; polyclonal T and/or B cells activation; errors in central or peripheral tolerance; immunoregulatory disorders including cytokine network alteration. In some patients with AIHA, stimulation of PMBC by synthetic Rh peptides indicate that ignorant T and/or B cell clones may recognize cryptic RBC self-antigens.

IFN-gamma and TNF-alpha production in gamma-irradiated blood units by mononuclear cells and GVHD prevention.

Gamma-radiation of blood products is considered the mainstay of transfusion-associated graft-versus-host disease prevention. Previous studies have detected lymphocyte inhibition rate in blood components just one time after irradiation but there is evidence of cellular variability with production of cytokines at different storage time which could be related with irradiation activity and cellular damage repair. IFN-gamma, a Th1 cytokine, and TNF-alpha, a pro-inflammatory one, had a central role in the stimulation of cellular and inflammatory reactions.

Cytokine network in autoimmune haemolytic anaemia: new probable targets for therapy.

Aims: Several immunological mechanisms seems to be similar in cancer and autoimmune disease. Studying interleukins production and proliferative response in autoimmune haemolytic anaemia (AIHA), it is possible to observe that manipulation of IL-10/IL-12 balance can have profound effect on the incidence of autoimmune diseases and this might be useful for the control of AIHA.

Methods: Respective role of IL-2, IL-4, IFN-gamma, IL-10 and IL-12 in non-cancer associated AIHA were investigated by examining the spontaneous and mitogen-induced (OKT3 or LPS) synthesis of these cytokines in PBMC cultures by ELISA methods.

Th1 and Th2 cytokine modulation by IL-10/IL-12 imbalance in autoimmune haemolytic anaemia (AIHA).

Recent studies about autoimmune diseases in animal models and in humans focused their attention on lymphocyte activation and in vitro cytokine production. The respective contribution of the Th1 and Th2 cytokines to the pathogenesis of autoimmune diseases is still a matter of debate. In this study the role of IL-2, IL-4, IFN-gamma, IL-10 and IL-12 cytokines were investigated by examining their spontaneous and mitogen-induced (OKT3 and PHA or LPS) synthesis and T-cells proliferative response by peripheral blood mononuclear cells to determine their role in the pathogenesis of AIHA.

Th2 cytokine role in autoimmune haemolytic anaemia (AIHA) pathogenesis.

Background: AIHA is characterised by the destruction of antibody-coated red blood cells, but the mechanism that initiates the production of autoantibodies remains unclear. We have studied the proliferative response and the spontaneous and mitogen-induced (PHA and OKT3) synthesis of IFN-g, IL-2 and IL-4 by peripheral blood mononuclear cells from patients with AIHA before any treatment to investigate the activation of Th1 and Th2 subsets.

Methods: Thirteen AIHA patients, both idiopathic and associated with other diseases, were studied by ELISA methods and H3 thymidine incorporation to determine in vitro cytokine production and T cell proliferative response, respectively.

Enhanced IL-10 production in vitro by monocytes in autoimmune haemolytic anaemia.

Our previous studies on autoimmune haemolytic anaemia (AIHA) have shown a hyperactivation concerning cytokine production in T and B lymphocytes obtained from AIHA patients. In this study the production of interleukin (IL)-10, basal and stimulated by lipopolysaccharide (LPS), was determined in cultured monocytes obtained from patients affected by AIHA, either idiopathic or associated with other autoimmune diseases, e.g.

Lymphocyte activation and cytokine production in autoimmune hemolytic anaemia (AIHA).

We studied 16 patients affected by autoimmune hemolytic anaemia (AIHA), both idiopathic and associated with other diseases (B and T lymphoma, B hepatitis, gastric carcinoma, systemic lupus erythematosus) or alpha-methyldopa therapy, in order to value T- and B-cell activation. We determined the count of T- and B-cell subsets in peripheral blood, the proliferative response of peripheral blood lymphocytes (PBL) to phytohemagglutinin (PHA) and to pokeweed mitogen (PWM), the percentage of CD25+ cells in culture and interleukin (IL)-1alpha, IL-2, IL-4, tumor necrosis factor (TNF)alpha and soluble IL-2 receptor (sIL-2R) levels in sera and in culture. Except for an increase in CD4+ and CD8+ T cell number in a case of AIHA associated with a T lymphoma and an increase in the percentage of CD5+ and PCA1+ B cells in two cases of AIHA associated with B lymphoma and with SLE, no further data showed a relationship with the disease possibly associated with AIHA, so both idiopathic and secondary AIHA cases were analyzed together.

High cytokine serum levels in patients with autoimmune hemolytic anemia (AIHA).

In autoimmune diseases striking abnormalities of T and B cell activation and of cytokine production are present. In 14 patients with autoimmune hemolytic anemia (AIHA), idiopathic or in the course of: lymphoma, B hepatitis, carcinoma, drug therapy (alpha-methyldopa), systemic lupus erythematosus (SLE), and not yet submitted to immunosuppressive therapy, the PBL proliferative response to PHA and the IL1 alpha, IL2, IL4 and IL2R serum levels have been valued. While the stimulation index of PBL was strongly reduced in 10 cases (64 +/- 56 vs 138 +/- 45 in the control group), IL1 alpha, IL2 and IL2R were greatly increased in all the patients, and IL4 in 5 (IL1 alpha :199 +/- 268 pg/ml in patients vs 0.

Peroxidative events in stored platelet concentrates.

Changes in metabolic and functional activity of platelets stored as platelet concentrates in plastic bags highly permeable to gases were investigated. The following parameters were measured daily: pH, pO2, pCO2, HCO3, glucose, lactic acid, lactic dehydrogenase, cellular ATP and platelet aggregation induced by different agents (collagen and ADP). As indexes of lipid peroxidative damage, the cellular levels of conjugated dienes, malonyldialdehyde and some antioxidant molecules such as coenzyme Q10 and vitamin E were determined.

Biochemistry of packed red blood cell concentrates stored in PAGGS-sorbitol solution for 42 days.

We investigated metabolic, blood gas and acid-base balance modifications of erythrocyte concentrates resuspended in PAGGS-sorbitol solution during 6 weeks of storage. Glucose utilization was impaired during the last 2 weeks, while the intraerythrocytic ATP level decreased only 50% from the 1st to the 6th week. The K+ and Hb concentration in the medium showed a progressive increase which was more pronounced during the last 2 weeks.

Biochemical and functional changes of platelet stored for transfusional use.

A protocol for the biochemical study of platelet stored for transfusional use at 22 degrees C and under continuous shaking in a plastic bag highly permeable to gases and with a suitable area/volume ratio, is described. Plasmatic dextrose, lactic acid, lactic dehydrogenase activity, cellular ATP and malonyldialdehyde were monitored during the storage, as well as some acid-base indexes namely: pH, pCO2, HCO3-, pO2. The platelet functional status was checked as aggregating power induced by ADP and collagen and by beta-thromboglobulin release.

Biochemical parameters to assess viability of blood stored for transfusional use.

Blood collected in citrate-phosphate-dextrose-adenine (CPDA-1) containing transfusional bags, was weekly tested throughout a 35 day period. Biochemical assays included plasmatic glucose, electrolytes, free Hb, acid-base balance and hemogasanalysis. Intraerythrocytic ATP and 2,3 DPG were also determined.

T lymphocyte subpopulations and lymphocytotoxic antibodies in patients with autoimmune haemolytic anaemia.

Evaluation of T lymphocyte subpopulations was performed on peripheral blood of patients affected by idiopathic or associated autoimmune haemolytic anaemia. A marked reduction of absolute number of T gamma and T mu cells was observed in 11 of 16 patients; a decrease of both OKT4+ and OKT8+ cells was found in 8 of 10 patients. Circulating cytotoxic antibodies against autologous and allogenic T lymphocytes and/or thymocytes were found in almost all the cases.

IgM plasmacytoma. Report of a case and review of the literature.

IgM paraproteinaemia is described in a patient with diffuse plasmacytoma involving the pleura, lymph nodes, and kidneys. Sixteen cases of pure plasmacellular tumor (diffuse or solitary plasmacytoma and plasmacellular leukaemia) associated with IgM paraproteinaemia have only been reported. These cases and experimental data indicate that neoplastic plasma cells can synthetize IgM as well as other immunoglobulins and that this particular M component is not associated solely with Waldenström's macroglobulinaemia.

Bone marrow amyloid in patients with M-component.

Amyloid substance was looked for in bone marrow aspirates of 28 patients presenting an M-component, in association with different illnesses (plasmocytoma, chronic lymphatic leukemia, lymphocytic lymphoma, "benign monoclonal gammapathy" and liver cirrhosis). Amyloid was detected in 12 out of 20 patients with plasmocytoma (60%) and in 3 out of 8 patients with other illnesses (37.5%); it was found in 9 out of 13 cases (69.

Immune haemolytic anaemia after exchange transfusion.

Two cases of immune haemolytic anaemia in newborn infants who had received exchange transfusion on the first day of life because of hyperbilirubinaemia probably due to a conjugation defect, are reported. The first baby, born in the 30th week of gestation presented erythrocyte-fixed IgM antibodies + C, neutropenia, and circulating leucocytotoxic antibodies. The second baby, born at term to a diabetic mother showed erythrocyte-fixed IgG + IgM antibodies + C and a selective IgA deficit.