Impaired reactivity of burn patient lymphocytes to phytohemagglutinin in autologous serum: failure to improve responsiveness by washing in vitro.
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Biomedical subjects
Publications and source records attributed to M B Constantian.
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Either an anomalous extensor indicis proprius muscle or an extensor digitorum brevis manus may coexist with a dorsal wrist ganglion. To assure relief of symptoms, treatment must include division of the fourth dorsal extensor compartment in the case of the former muscle, and excision in the case of the latter.
One hundred ninety serum samples from 51 burned patients were tested for immunosuppressive activity which might explain decreased host immune competence following thermal injury. The serum from a variable but significant percentage of these patients suppressed the response of normal human peripheral blood lymphocytes to phytohemagglutinin. The occurrence of immunosuppressive activity paralleled the severity of the injury. Ten of ten severely burned patients (severity index greater than 40), but only 20 of 30 patients with index 10--39.9, and three of 11 patients with Index 0--9.9 developed suppressive serum. Differences between these groups were significant (p less than .05). In all 19 patients who became septic, immunosuppressive serum activity immediately preceded or coincided with the septic episode. In contrast to the effect on lymphocytes, burn sera stimulated fibroblast proliferation. Immunosuppressive activity did not correlate with serum cortisol levels, blood transfusion, protein-calorie malnutrition, or anesthesia. Suppressive sera were not cytotoxic. A majority of the active serum factor(s) was contained in a low molecular weight (less than 10,000 daltons) polypeptide subfraction.
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The serum from 109 traumatized patients was examined for immunosuppressive activity which might explain diminished host immune responsiveness following operative or accidental injury. Twenty-eight fo 31 (90%) severely tralmatized patients, 25 of 60 (42%) moderately traumatized patients, and 0 of 18 minimally traumatized patients developed serum which suppressed the response of normal human lymphocytes to phytohemagglutinin. The degree and duration of serum immunosuppressive activity paralleled the severity of the clinical course but did not correlate with serum cortisol or barbiturate levels. Suppressive sera were not cytotoxic. The immunosuppressive factor(s) was contained in a low molecular weight (less than 10,000 daltons) peptide fraction and was present in 5--10 times the amount recoverable from normal serum. By size and activity the trauma serum factor resembled immunoregulatory alpha globulin, a naturally-occurring serum inhibitor of T-lymphocyte reactions. Thus, depressed immunoreactivity following trauma may be due in part to high concentrations of an endogenous immunosuppressive polypeptide.
Heterologous anti-immunoglobulin is a potent immunosuppressive agent that prolongs H-2- and H-3-incompatible skin graft survival. In conjunction with antithymocyte serum, anti-immunoglobulin promotes greater graft life than either antiserum used alone, without evidence of toxicity to recipient animals. Combination treatment with anti-immunoglobulin, antithymocyte serum, and donor spleen cells produces long-term allograft survival to the lifetime of the host and can result in antigen-specific immune unresponsiveness of sufficient strength to permit acceptance of a second-set graft. Anti-immunoglobulin complexes formed in treated mice appear to be localized primarily in the lymphatic reticuloendothelial system.
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Heterologous anti-immunoglobulin (AI) is a potent immunosuppressive agent which compares favorably to anti-thymocyte serum (ATS) in inhibiting E and EAC-rosette formation and diminishing the secondary antibody response to sheep erythrocytes and E. coli lipopolysaccharide. AI prolongs H-2 incompatible skin allograft survival than either antiserum used alone, without evidence of toxicity to recipient mice. AI does not cause significant immune complex glomerular or renovascular deposition and may act by interference with antigen binding.
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An immunosuppressive peptide fraction was isolated by means of gel filtration, membrane partition, and ion-exchange chromatography from the sera of patients hospitalized for cancer. The resulting peptide fraction, which was heterogeneous as judged by high-voltage electrophoresis, was found to suppress both phytohemagglutinin-induced proliferation of lymphocytes in vitro and the in vivo induction of splenic plaque-forming cells in mice. The specific activity of the peptide fraction, which was isolated from the sera of cancer patients, was significantly increased over that of the unfractionated starting material. Moreover, in control experiments, when the sera of normals or non-cancer-bearing hospitalized individuals were subjected to the same chromatographic techniques, no active peptide fraction could be obtained.
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