PubMed Health⌕ Search

Biomedical subjects

T F Newcomb

Publications and source records attributed to T F Newcomb.

6 recordsLinked to original sources

Human mononuclear phagocyte transglutaminase activity cross-links fibrin.

The physiologic function of the monocyte transglutaminases is not known. In this study, we detected Factor XIII A-subunit antigen and "tissue" transglutaminase antigen in human monocytes by polyacrylamide gel electrophoresis and immunoblotting techniques. Flow cytometric analysis demonstrated that 27% and 49% of the total Factor XIII antigen in monocytes and human peritoneal macrophages, respectively, are expressed on the surface of the cells. Monocytes maintained in culture for 8 days had a 4-fold increase in Factor XIIIa activity and a 3.2-fold increase in the amount of Factor XIII antigen/mg cell protein. However, there was no increase in the "tissue" transglutaminase activity or antigen levels in cultured monocytes. In addition, we identified a Factor XIII deficient individual who does not express Factor XIII activity or antigen in plasma, platelets, monocytes, lymphocytes or erythrocytes. Intact monocytes from normal donors were able to cross-link fibrin formed in the plasma from the Factor XIII deficient individual. This suggests that transglutaminase activity expressed by peripheral blood monocytes may play a physiologic role in cross-linking fibrin during blood clotting or inflammation.

Antigens, Surface↗

CFU-GEMM correlate with neutrophil and platelet recovery in patients receiving autologous marrow transplantation after high-dose melphalan chemotherapy.

CFU-GEMM, multipotent progenitor cells, give rise to erythroid, granulocyte-macrophage and megakaryocytic cells. We have examined the utility of this assay for predicting hematologic recovery in patients treated with high-dose chemotherapy and autologous marrow rescue with cryopreserved marrow. In marrow samples from 50 patients CFU-E, BFU-E and CFU-GEMM significantly decreased following cryopreservation. The median value for CFU-E declined from 132,659 to 10,648, BFU-E decreased from 36,112 to 3345 and CFU-GEMM decreased from 3242 to 260 colonies per ml of marrow frozen. Once cryopreserved, the number of CFU-E, BFU-E and CFU-GEMM remained stable with prolonged storage in liquid nitrogen. In 48 patients uniformly treated with high-dose melphalan (180 mg/m2) and rescued with cryopreserved autologous marrow, univariate analyses showed that the time to platelet recovery (greater than 50 x 10(9)/l) was correlated with the number of CFU-E, BFU-E and CFU-GEMM infused (p less than 0.05). The time to neutrophil recovery was only correlated with the number of BFU-E and CFU-GEMM infused (p less than 0.01). However, by multivariate analyses, only the number of CFU-GEMM, and not CFU-E and BFU-E, infused correlated both with the time to neutrophil and platelet recovery. These data indicate that the CFU-GEMM assay may be useful for determining the repopulating ability of cryopreserved bone marrow.

Bone Marrow↗

Clot retraction in a factor XIII free system.

The role of Factor XIII in clot retraction was studied using the plasma from Factor XIII-deficient patients. Time course experiments revealed no significant difference in clot retraction between a plasma deficient in Factor XIII and one to which purified Factor XIII had been added. Using Factor XIII-free fibrinogen and Factor XIII-deficient platelets, it is shown that there is no significant difference in clot retraction with or without added Factor XIII.

Clot Retraction↗

Factor XIII.

1. Activated factor XIII is the enzyme that covalently cross-links fibrin monomers into fibrin polymers and results in increased clot strength and resistance of the clot to fibrinolysis. 2. Small amounts (greater than 1% of normal) of factor XIII are necessary for normal in vitro and in vivo activity. 3. Factor XIII deficiency is a rare autosomal recessive illness in which a hemorrhagic diathesis is caused by the virtual absence of the active a subunit of factor XIII. Approximately 100 cases have been described. 4. The disease in homozygotes is characterized by umbilical stump bleeding, a high incidence of fetal wastage, delayed soft tissue hemorrhage, and a high incidence of intracranial bleeding. The heterozygote is asymptomatic. 5. This paper calls attention to the apparent high incidence of oligospermia and small testes seen in homozygote males. Otherwise secondary sex characterics are normal. 6. Because there is no abnormality in thrombin generation and conversion of fibrinogen to fibrin, route coagulation tests (prothrombin time, partial thromboplastin time, thrombin time, etc.) are normal. Platelet function tests are normal. 7. Clots made from recalcified plasma severely deficient in factor XIII are soluble in 5 M urea or 1% monochloroacetic acid. These screening tests are simple and nearly pathognomonic of the illness. 8. More sophisticated and quantitative tests (e.g., dansylcadaverine incorporation) are available for definitive diagnosis and heterozygote detection. 9. Replacement treatment of the illness is simple, effective, and relatively inexpensive. Due to the long half-life of infused factor XIII and the small amounts necessary for normal hemostasis, prophylaxis is feasible and encouraged.

Adult↗