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Biomedical subjects

L Zuckerman

Publications and source records attributed to L Zuckerman.

At least 19 recordsLinked to original sources

The CD28 ligand, B7, enhances IL-2 production by providing a costimulatory signal to T cells.

Previous studies demonstrated that a human pre-B acute lymphoblastic leukemia cell line, NALM-6, failed to stimulate a primary MLR, despite expression of class II MHC and adhesion molecules. Here we demonstrate that this is the result of the fact that NALM-6 cells do not express the ligand for CD28, namely B7. NALM-6 transfectants that expressed high levels of B7 gained the capacity to stimulate IL-2 production by class II MHC molecule-specific alloreactive T cells and to costimulate a polyclonal population of purified T cells cultured with immobilized anti-CD3 mAb. In the presence of PMA, NALM-6 cells transfected with B7 polyclonally stimulated T cells in a cyclosporine A-resistant fashion, a property previously attributed only to agonistic anti-CD28 mAb. The gain of these functions could not be explained solely by an increased capacity of the transfectants to form conjugates with T cells, suggesting that the CD28/B7 interaction transduces a costimulatory signal in T cells.

Antigen-Presenting Cells

The effects of prostacyclin on the coagulation of whole blood.

The effects of prostacyclin (PGI2) on mechanical properties of forming clots were investigated by testing human blood samples on a Thrombelastograph. Concentrations greater than 50 ng/ml (blood) caused a biphasic development of clot stiffness. During the first phase, PGI2 partially inhibited the platelet involvement in coagulation causing initial clot formation at a normal time but with reduced clot stiffness. The second phase occurred after neutralization of PGI2 activity and was characterized by recovery of platelet activity to produce a final clot with normal shear modulus. The duration of the inhibitory effects depended on PGI2 concentration and hematocrit. With a normal hematocrit, a PGI2 concentration of 60 ng/ml caused an inhibition for about 40 min whereas a concentration of 100 ng/ml caused inhibition for about 75 min.

Blood Coagulation

Breast carcinoma: expected results with prevailing therapy.

Computer-stored tumor registry data were scanned to produce the set of patients whose breast carcinoma was either diagnosed or first treated at Evanston Hospital between the years 1973 and 1977, inclusive. Of 560 evaluable patients, 184 were less than or equal to age 50 (LE 50), and 376 were greater than age 50 (GT 50). Comparisons of projected survival show that the survival of all patients is 8% at 5 years and 72% at 7 years. The survival of patients LE 50 is nearly identical to that of the GT 50 age group. Survival of Stage III GT 50 patients, however, is better than Stage III LE 50 (P less than 0.001). Comparison with earlier studies shows an historical trend toward better 5-year survival. Data were generated in this study which allow prediction of prognosis based upon age and stage at diagnosis.

Age Factors

Comparison of thrombelastography with common coagulation tests.

Thrombelastography, although proven as a useful research tool has not been evaluated for its clinical utility against common coagulation laboratory tests. In this study we compare the thrombelastographic measurements with six common tests (the hematocrit, platelet count, fibrinogen, prothrombin time, activated thromboplastin time and fibrin split products). For such comparisons, two samples of subjects were selected, 141 normal volunteers and 121 patients with cancer. The data was subjected to various statistical techniques such as correlation, ANOVA, canonical and discriminant analysis to measure the extent of the correlations between the two sets of variables and their relative strength to detect blood clotting abnormalities. The results indicate that, although there is a strong relationship between the thrombelastographic variables and these common laboratory tests, the thrombelastographic variables contain additional information on the hemostatic process.

Blood Coagulation Disorders

The colon influences ileal resection diarrhea.

Fecal mass and electrolyte concentrations from 25 ileectomy and/or colectomy patients on known diets were used to assess those factors most responsible for their diarrhea. In 18 ileectomy patients the severity of diarrhea, expressed as a fecal weight, was a function of both percent of colon and centimeters of ileum removed. Linear regression analysis, however, showed that the extent of missing colon had three times the effect of missing ileum on fecal weight. Patients who lost the ileocecal valve and part of the right colon had more diarrhea than those who lost comparable lengths of ileum but had this area preserved. Fecal ion concentrations seemed independent of diet but were related to fecal weight and the amount of colon and ileum removed. Potassium concentration was strongly dependent on the amount of colon lost, while sodium concentration was more influenced by the length of resected ileum. Choloride was most dependent on fecal weight. As expected, fecal fat correlated strongly with the extent of ileum removed. Regresison equations were constructed from the electrolyte data which described and predicted the extent of lost ileum or colon. Our data were also used to separate patients with less than 100 cm of ileum removed from those with more extensive resections. The severity of diarrhea following ileal resection depends primarily on the amount of contiguous colon removed. Varying loss of ileum and colon produced predictable effects on fecal weight and electrolyte composition. Surgeons should preserve the maximum amount of colon possible to reduce the severity of diarrhea in these patients.

Adult

Plasma cholinesterase activity in bank blood.

Plasma cholinesterase activity was periodically measured in bank blood. Of the initial plasma cholinesterase activity 87% was retained after 21 days of storage at 4 C in citrate-phosphate-dextrose solution. In addition, plasma frozen for 7 weeks at -70 C showed no decrease in enzyme activity. No difference could be demonstrated in the stability of the enzyme related to whether the blood was stored in citrate-phosphate-dextrose or in acid-citrate-dextrose solution. Bank blood transfusion prior to or during succinylcholine administration should not significantly alter the duration of action of succinylcholine, and would probably be effective in the management of prolonged apnea resulting from a deficiency of this enzyme.

Adult

Disseminated intravascular multiple systems activation (DIMSA) following thermal injury.

Seventy-seven major thermal injury victims were studied with a number of hematologic and immunologic tests initially and sequentially during the first postburn month. The patients were grouped by initial prognostic index as well as by ultimate survival. Pairs were grouped by initial prognostic index as well as by ultimate survival. Pairs of test data from subjects studied at successive time intervals were compared with prognostic index and ultimate survival. Statistically significant changes in coagulation, fibrinolytic, complement, and kinin tests all occurred within these groups. These findings strongly suggest that intravascular contamination occurs following thermal injury in proportion to the extent of the burn, because of the occurrence and persistence of statistically significant multiple system changes. Regrouping all of the blood data according to ultimate death or survival reinforced the concept of intravascular contamination and provided the basis by which one can compute laboratory prognostic indices. The combination of plasminogen, C'3 complement, C'H50, one-minute kinin, and TEG index discriminated between death and survival with 91% accuracy by the end of the first postburn week. These data offer the potential for select blood measurements in refining current prognostic indicators. This may provide an objective data base for the analysis of new treatment programs in thermal injury victims.

Blood Cell Count

Variation of cold agglutinin levels.

Cold agglutinin levels were determined in 120 individuals ranging in age from 1 to 64 years using untreated and ficin-treated group O erythrocytes. The geometric mean titer for untreated cells was 5.7 +/- 1.1 SEM and for ficin-treated cells 18.7 +/- 1.1 SEM. The mean titers and scores for various blood groups were not significantly different. Titers and scores correlated significantly to total serum IgM concentration (p less than 0.001). Females had significantly higher cold agglutinin levels than males (p less than 0.001). A significant decrease of cold agglutinins occurred in the 26- to 64-year age group as compared to the 11- to 25-year age group (p less than 0.01). The data should contribute to a clearer understanding of the biological impact of cold agglutinins.

Adolescent

Effect of platelet count and hematocrit on the coagulability of heparinized blood.

The coagulability of heparinized blood is shown to be a function of platelet and red cell concentrations. Thrombelastrographic tests were conducted on celite-activated fabricated whole blood samples with heparin concentrations ranging from zero to 1.46 units per ml of plasma, hematocrits from zero to 50% and platelet counts from zero to 300,000/mm3. The thrombelastograph provides three useful parameters of coagulability in native and heparinized blood: clot time, rate of clot stiffening and final clot stiffness. Of these, only the clot time is determined with the common clotting tests, while the rate and final clot stiffness are measures of clot quality that are found to be particularly sensitive to thrombocytopenia. The test results indicate (i) increases of platelet concentration produce the expected decrease in clot time, increase in rate of stiffening, and increase in final stiffness; (ii) increases of the red cell concentration from zero to 20% hematocrit, produce nonlinear increases in clotability, while further increases beyond 20% hematocrit produce no additional effects if the heparin concentration is less than 1.2 units/ml. Quantative relations are derived between the thrombelastographic variables, heparin concentration, and platelet concentration for those samples with hematocrits greater than 20%. These data indicate further experiments for the study of possible interaction between cellular blood elements and heparin.

Animals