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Biomedical subjects

J Cowles

Publications and source records attributed to J Cowles.

9 recordsLinked to original sources

Platelet washing to prevent recurrent febrile reactions to leucocyte-reduced transfusions.

Symptoms of fever and/or rigours after transfusion continue to occur commonly in patients receiving platelets leucocyte-reduced after storage. A cohort of 24 consecutive patients who had experienced severe or repeated febrile nonhaemolytic reactions to post-storage leucocyte-reduced platelet transfusions were treated with saline-washed, post-storage leucocyte-reduced platelets. The frequency of reactions declined from 20% of transfusions (n = 191) to 0.6% (n = 331) after instituting saline-washed, post-storage leucocyte-reduced platelet transfusions. These results support the hypothesis that substances present in the supernatant of stored platelet concentrates mediate febrile nonhaemolytic transfusion reactions, and provide one strategy for preventing their occurrence.

Adolescent↗

Blood transfusion and total joint replacement surgery: T helper 2 (TH2) cytokine secretion and clinical outcome.

Surgery and blood transfusions have both been reported to cause decreases in various measures of cell-mediated immunity. A study of in vitro T helper lymphocyte type 2 (Th2) cytokine secretion after major joint replacement surgery was performed because these cytokines (IL4 and IL10) generally down-regulate cellular immune function. Th1 cytokines such as IL2 tend to up-regulate cellular immunity. Forty-three patients undergoing elective joint replacement surgery had pre- and multiple post-operative levels of IL2, IL4 and IL10 secretion measured and analysed with regard to demographic and clinical outcome data. Total joint replacement alone without allogeneic transfusions led to substantial increases in peak mean IL4 (2.1 times the pre-operative level) and IL10 secretion in vitro (4.3-fold) compared with much more modest increases in IL2 (1.36-fold) (P < 0.0001 for changes from baseline for each cytokine). In 14 patients who received allogeneic transfusions, these changes were greater than those in recipients of only autologous blood for IL4 (5.0-fold; P = 0.0036 vs. no allogeneic transfusion) and IL10 (15.7-fold; P = 0.079) but not for IL2 (1.38-fold; P = 0.38). The dramatic increase in Th2 cytokine secretion and minimal change in Th1 cytokine secretion after total joint replacement, with or without allogeneic transfusions, was seen regardless of type of anaesthetic, duration of surgery or whether knee or hip replacement occurred. These changes in cytokine patterns may contribute to the decreases in cellular immune function seen after surgery. Allogeneic transfusions but not autologous transfusions appear to exacerbate this immune deviation toward a T helper 2 (Th2) type response, and thus probably contribute to down-regulation of cellular immunity in the setting of joint replacement surgery.

Aged↗

Seedling growth and development on space shuttle.

Young pine seedlings, and mung bean and oat seeds were flown on shuttle flights, STS-3 and STS-51F, in March, 1982 and July/August, 1985, respectively. The plant growth units built to support the two experiments functioned mechanically as anticipated and provided the necessary support data. Pine seedlings exposed to the microgravity environment of the space shuttle for 8 days continued to grow at a rate similar to ground controls. Pine stems in flight seedlings, however, averaged 10 to 12% less lignin than controls. Flight mung beans grew slower than control beans and their stems contained about 25% less lignin than control seedlings. Reduced mung bean growth in microgravity was partly due to slower germination rate. Lignin also was reduced in flight oats as compared to controls. Oats and mung beans exhibited upward growing roots which were not observed in control seedlings. Chlorophyll A/B ratios were lower in flight tissues than controls. The sealed PGCs exhibited large variations in atmospheric gas composition but the changes were similar between flight and ground controls. Ethylene was present in low concentrations in all chambers.

Avena↗

Antibodies to plasma proteins: an association with platelet transfusion refractoriness.

We hypothesized that antibodies to HLA-linked polymorphic plasma proteins could be involved in platelet refractoriness by an 'innocent bystander' or immune complex mechanism. Employing a kinetic enzyme-linked immunosorbent assay (ELISA) technique the ability of IgG from the plasma of refractory patients to bind to albumin, fibrinogen, complement components C2 and C4 was measured. As compared with controls a high percentage of refractory patients had increased IgG capable of binding to all four plasma proteins: C2 (83%), C4 (83%), albumin (75%), fibrinogen (34%). In the presence of exogenous plasma proteins these antibodies mediated increased deposition of IgG onto normal donor platelets. The plasma protein binding IgG consisted both of monomeric IgG and a broad range of high molecular weight complexes. IgG anti-plasma protein antibody could be eluted from platelets of refractory patients. The development of anti-plasma protein IgG was studied during the course of platelet transfusion therapy and found to increase progressively so that by the 20th transfusion greater than 90% of samples were positive. The presence of plasma protein binding activity correlated with the development of increased levels of platelet bound IgG and refractoriness. Multiple platelet transfusions lead to sensitization to polymorphic determinants on C2 and C4 as well as the formation of high molecular weight complexes. These antibodies and complexes contribute to the deposition of IgG on platelets and may contribute to refractoriness.

Albumins↗

Detection of IgG anti-Lewis (a) antibodies in cord sera by kinetic Elisa.

Lewis blood group antibodies rarely, if ever, cause hemolytic disease of the newborn. This observation has been attributed to the absence both of Lewis antigens on fetal cells and of maternal IgG Lewis antibody. In the present study, sera from 13 mother-infant pairs were tested for the presence of anti-Lewis (a) by hemagglutination and by a sensitive and specific kinetic enzyme-linked immunosorbent assay. By routine hemagglutination methods, anti-Lea was present in all maternal samples but absent in all cord samples. By kinetic enzyme-linked immunosorbent assay, IgG anti-Lea was present in 13 of 13 maternal samples and in 12 of 13 cord samples. These results indicate that IgG anti-Lea antibodies are common and do cross the placenta. This suggests that they do not cause hemolytic disease of the newborn because of the low levels of Lewis antigens on fetal red cells.

Enzyme-Linked Immunosorbent Assay↗

Correlation of humoral immunity to Lewis blood group antigens with renal transplant rejection.

Recent studies suggest that the Lewis blood group antigens are important for human renal transplantation. A possible mechanism by which Lewis blood group incompatibility could influence allograft rejection was investigated by measuring Lewis antibodies in sera from renal transplant recipients and appropriate controls using conventional hemagglutination and a sensitive and specific kinetic enzyme-linked immunosorbent assay (k-ELISA). The two methods yielded identical results with 14 positive control sera known to contain Lewis antibodies and with 43 sera from negative controls. Antibody was not detected in 16 Lewis-positive transplant patients. However, antibody was detected by k-ELISA in 4/11 Lewis-negative transplant candidates and in 8/8 Lewis-negative recipients of Lewis-incompatible grafts. All 8 grafts were rejected. The one Lewis-negative recipient of a Lewis-negative graft did not develop Lewis antibody nor reject his graft. Of the 12 renal patients in whom antibody was detected by k-ELISA, in only 4 was antibody also demonstrable by hemagglutination. These results indicate that hemagglutination may not be sensitive enough for antibody detection and that Lewis antibodies may play a role in renal allograft rejection.

Blood Group Incompatibility↗

A new technique in quantitative immunohematology: solid-phase kinetic enzyme-linked immunosorbent assay.

A solid-phase kinetic enzyme-linked immunosorbent assay has been developed to measure binding of antibodies to purified or synthetic blood group antigens and tested in the Lewis blood group system. Chemically synthesized Lewis a antigen is used as the target for the binding of serum antibody in this sandwich-type assay. Kinetic, rather than endpoint, determinations are used to calculate the amount of specific antibody. Data are presented showing the assay to be quantitative, sensitive, and specific. It can separately quantitate the amount of IgG or IgM anti-Lewis a present in patient sera. The assay uses commercially available reagents and is semiautomated. Thus, it will be useful for studies in quantitative immunohematology as other blood group antigens become available in purified form.

Antibody Specificity↗