Reptilase test in cirrhosis and hepatocellular carcinoma.
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Biomedical subjects
Publications and source records attributed to R D Barr.
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Idiopathic thrombotic occlusion of the extrahepatic portal vein is one of the commonest causes of portal hypertension in adult Blacks. The condition occurs more frequently in men and may be accompanied by evidence of minor functional impairment of the liver. Associated pancytopenia is quantitatively related to the degree of splenomegaly. Assessment of a spectrum of variables of blood coagulation and fibrinolysis, while failing to shed light on the possible pathogenesis, does suggest a rational basis for thrombolytic therapy.
Viable T lymphocytes stimulate the proliferation of human syngeneic hemopoietic stem cells, but not influence their differentiation. The biological significance of this activity is discussed and its possible physiological role in the regulation of hemopoiesis is considered.
By the use of velocity sedimentation at unit gravity, in combination with methods of cell separation based on differences in density and in surface membrane receptors, it has been possible to obtain concentrates of mononuclear cell subpopulations from normal human peripheral blood. T and non-T lymphocytes have been harvested with a good yield and a high degree of purity. Monocytes may also be efficiently recovered using these procedures.
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The coagulation and fibrinolytic properties of peripheral venous blood was studied in 10 Black patients with chronic ectopic pregnancy. There were significant elevations of plasma fibrinogen and serum fibrin-fibrinogen degradation products (FDP) and prolongation of the euglobulin lysis time. These features are believed to be compatible with chronic inflammation. No evidence of a haemostatic defect was found.
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Activity of the enzyme terminal transferase (TdT) has been localised in normal human bone-marrow lymphocytes. These cells may represent a prothymocyte population, which, on malignant transformation, may give rise to acute lymphoblastic leukaemia, and to some cases of chronic granulocytic leukaemia in the blastic phase.
By selecting, for discussion, some aspects of oncogenesis in human acute leukemia, we hope to focus attention on areas of current interest which promise to provide important advances in our knowledge and understanding of human neoplasia, and, in time, may lead us nearer to the goal of disease control and eventual eradication.
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Acid phosphatase and beta-glucuronidase activities have been determined cytochemically in T, B and null lymphocytes as part of an effort to charaterize the human haemopoietic stem cell. A combination of weak acid phosphatase activity and strong beta glucuronidase staining, in the form of a single large granule, has been shown to be specific for T cells. On the basis of this approach alone, non-T cells could not be further subclassified. Further cytochemical evaluation is being explored.
With a view to simplifying the separation of haemopoietic stem cell concentrates from human peripheral blood, in preparation for their clinical use, the production of lymphocyte concentrates by cotton wool filtration has been investigated. Using the method which is described in detail, highly purified suspensions may be prepared without the selective loss of thymus-independent lymphocytes. Optimal operating conditions are defined. Haemopoietic stem cell concentrates may thereby be harvested, and are shown to be capable of proliferation and differentiation on subsequent culture in vivo.
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The present studies demonstrate that, while erythrocytes preferentially bind hexavalent 51Cr, leukocytes bind the trivalent form with equal avidity. Red cells may be saturated with label in contrast to the binding of 51Cr to leukocytes, which may be described by first-order kinetics. Hexavalent label is rapidly reduced in leukocytes in contradistinction to the finding in red cells. The nonreutilization of label by erythrocytes and leukocytes is not due to inappropriate valency but to protein binding of the label. Unlike nonleukemic cells, leukemic leukocytes elute a large fraction of their label. These factors have been largely overlooked in many previous clinical studies using labeled cells, and they are of sufficient quantitative importance to compromise seriously the validity of numerous earlier reports.
The mechanisms of blood coagulation and fibrinolysis have been evaluated in 28 black adult Africans with primary hepato-cellular carcinoma (HCC). A characteristic pattern of abnormalities has been defined. Dysfibrinogenaemia appears to be a useful biological marker for the disease. The reptilase test (RT) is a simple, reliable and sensitive means of detection of this metabolic abnormality. It is suggested that the RT should be used to screen populations at high risk of developing HCC, such as cirrhotics, in conjunction with alpha fetoprotein determinations, which, alone, are inadequate for the purpose. The haemostatic defect may have relevance to the pathogenesis of HCC, and further suggests a potentially useful, additional, therapeutic modality.
A population of lymphocytes, separable from the great majority by virtue of their larger size and their failure to exhibit the rosetting characteristics of thymus-dependent lymphocytes and bursa-equivalent cells, possess true pluripotentiality. On culture in vivo they proliferate and differentiate into erythrocytic, granulocytic, and megakaryocytic progeny. This may be the first clear demonstration of the primitive progenitor blood cell in man.