Abnormalities of in vitro immunoglobulin synthesis by peripheral blood lymphocytes from untreated patients with Hodgkin''s disease

The immunoglobulin-synthesizing activities of peripheral blood mononuclear cells from 57 untreated patients with Hodgkin's disease and 47 normal subjects were compared. Cumulative amounts of IgM and IgG synthesized and secreted by unstimulated and pokeweed mitogen-stimulated cells over a 7-d period were determined in a solid-phase radioimmunoassay. Synthesis of IgM in unstimulated cultures and of both IgM and IgG in cultures stimulated with pokeweed mitogen was markedly reduced in patients with Hodgkin's disease, whereas the mean level of the spontaneous IgG synthesis was enhanced. The degree and frequency of in vitro abnormalities were not influenced by disease stage or histology. Depression of pokeweed mitogen-induced immunoglobulin synthesis did not correlate with excessive number of monocytes and it was unaffected by removal of phagocytic cells or addition to the cultures of monocytes from normal individuals. On the other hand, monocytes isolated from blood of patients with Hodgkin's disease were even more effective than normal monocytes in supporting pokeweed mitogen-induced immunoglobulin synthesis by normal phagocyte-depleted mononuclear cells. Synthesis of both IgM and IgG induced by pokeweed mitogen remained subnormal after addition to patient B cell cultures of autologous irradiated T cells or allogeneic normal T lymphocytes. T cells from patients with Hodgkin's disease appeared at least as effective as normal T cells in helping pokeweed mitogen-induced immunoglobulin production by normal B cells. However, when normal T cells were co-cultured with B cells from patients with Hodgkin's disease, spontaneous IgG synthesis declined, whereas the addition of patient T cells to normal B cells resulted in an increase of spontaneous IgG synthesis. In patients showing depression of pokeweed mitogen-induced immunoglobulin synthesis the lymphoproliferative response and immunoglobulin synthesis stimulated by Staphylococcus aureus bacteria of the Cowan first strain, a T cell independent B cell mitogen, were also markedly reduced. These studies demonstrate impairment of immunoglobulin synthesis by cultured lymphocytes from untreated patients with Hodgkin's disease after stimulation with polyclonal B cell activators and suggest that the in vitro abnormalities may be, at least in part, the result of a preexisting in vivo activation of lymphocytes in Hodgkin's disease patients.     

Ketoprofen controlled release from composite microcapsules for cell encapsulation: effect on post-transplant acute inflammation.

Cell encapsulation technology raises hopes in medicine and biotechnology. Encapsulated pancreatic islets is a promising approach for the final solution of Type 1 diabetes. Unfortunately, evidence of long-term encapsulated islet graft survival and functional competence lies behind expectancy. Failure was often ascribed to the lack of biocompatibility generating inflammatory response, or limited immunobarrier competence or hypoxia or finally, low beta-cell replication. In order to prevent severe inflammation at early stages after implantation, composite microcapsules were designed. Biodegradable microspheres containing ketoprofen were enveloped into the well established alginate/poly-L-ornithine/alginate capsules. Polyester microspheres were prepared, by solvent evaporation, and characterized for encapsulation efficiency, particle size and in vitro release. Biocompatibility and efficacy to prevent the inflammatory response were studied in vivo. Good encapsulation efficiency and the desired particle size were achieved. In vitro release studies evidenced a high burst effect probably due to a plasticizing effect of both water and ketoprofen. The composite systems showed good biocompatibility and capacity to completely avoid the inflammatory response and the pericapsular cell overgrowth. In conclusion, the inflammatory response in the immediate post-transplant period can be circumvented using multicompartment microcapsules releasing non-steroidal anti inflammatory drugs.     

Skin reactivity and specific IgE levels in the evaluation of allergic sensitivity to common allergens for epidemiological purposes

An investigation was conducted to test the validity of the skin-prick test (SPT) with eleven common allergens (Lofarma series proposed by Italian National Research Council for epidemiological studies) as a method for predicting the presence of specific antibodies in serum. The relationship between SPT, evaluated by two different methods (MWD = mean weal diameter, AHWR = allergen histamine weal ratio), and specific IgE levels (RAST) has been investigated in 101 patients tested consecutively for suspected allergic disease. Sensitivity, specificity and overall efficiency were assessed for different criteria of SPT positivity (greater than or equal to 4 mm or greater than or equal to 5 mm using MWD; ++ or using AHWR). For pollens and moulds, a weal diameter greater than or equal to 5 mm gave better results than 4 mm, whereas for mites a MWD greater than or equal to 4 mm showed a better sensitivity and overall efficiency than 5 mm. Danders showed low sensitivity when either 5 or 4 mm criterion was considered. AHWR evaluation gave no better results, except for animal danders. Correlation coefficients between weal size and RAST class showed a good relationship for mites and pollens using both methods of SPT evaluation; a moderate relationship was observed with MWD criterion for moulds and with AHWR for danders. We conclude that a weal diameter greater than or equal to 5 mm can be assumed to to predict RAST positivity for pollens and moulds, and for mites, a weal greater than or equal to 4 mm can be a more accurate criterion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative study of the effects of acebutolol,atenolol, d-propranolol and dl,-propranolol on the alterations in energy metabolism caused by ischemia and reperfusion: A 31P NMR study on the isolated rat heart

Summary 31-P NMR spectroscopy data recorded for the isolated heart were analyzed, in conjunction with functional and biochemical variables, in order to investigate the effect observed for several different beta-adrenoceptor antagonists on the alterations provoked by global partial ischemia (37°C, 24 minutes, 1% residual coronary flow) and reperfusion in the metabolism of the myocardium. During ischemia: intracellular acidosis, adenosine triphosphate (ATP) degradation, and inorganic phosphate (Pi) accumulation were found to be reduced whether the perfusion fluid contained: acebutolol 2.7×10^-5 M, atenolol 10^-5 M, d-propranolol 10^-5 M, or dl-propranolol 10^-5 M. On reperfusion metabolic and functional variables were variously affected by the different drugs, except the Pi level which was, in all series, significantly lower compared with control hearts. The adenylate charge and the glycogen stores were protected in the acebutolol, dl-propranolol, and d-propranolol groups. The ATP level was higher than in controls only in the acebutolol and atenolol groups. The intracellular pH recovered to values non-significantly different from preischemic values in the acebutolol and dl-propranol-treated hearts only. The mechanical performance, expressed as the rate-pressure product, was unaltered by the ischemia-reperfusion sequence in the acebutolol and d-propranolol series, while decreasing significantly in controls and in the atenolol group. In dl-propranolol-treated hearts the mechanical activity, which in normoxic conditions was already halved during the effect of the drug, remained at this same level after ischemia. From these observations, it appears that the nonspecific properties of the drugs, as distinct from beta-blockade, play an important part in attenuating the ischemia-induced alteration in myocardial metabolism. Thus, it can be postulated that (1) the metabolic effects of dl-propranolol probably result largely from the reduction of heart work induced by this drug; (2) the maintenance of energy metabolism associated with the preservation of the myocardial activity, as observed in the case of acebutolol and d-propranolol, is possibly a consequence of the existence of a membrane-stabilizing activity.