The Late-Domain-Containing Protein p6 Is the Predominant Phosphoprotein of Human Immunodeficiency Virus Type 1 Particles

The Gag-derived protein p6 of human immunodeficiency virus type 1 (HIV-1) plays a crucial role in the release of virions from the membranes of infected cells. It is presumed that p6 and functionally related proteins from other viruses act as adapters, recruiting cellular factors to the budding site. This interaction is mediated by so-called late domains within the viral proteins. Previous studies had suggested that virus release from the plasma membrane shares elements with the cellular endocytosis machinery. Since protein phosphorylation is known to be a regulatory mechanism in these processes, we have investigated the phosphorylation of HIV-1 structural proteins. Here we show that p6 is the major phosphoprotein of HIV-1 particles. After metabolic labeling of infected cells with [ortho-32P]phosphate, we found that phosphorylated p6 from infected cells and from virus particles consisted of several forms, suggesting differential phosphorylation at multiple sites. Apparently, phosphorylation occurred shortly before or after the release of p6 from Gag and involved only a minor fraction of the total virion-associated p6 molecules. Phosphoamino acid analysis indicated phosphorylation at Ser and Thr, as well as a trace of Tyr phosphorylation, supporting the conclusion that multiple phosphorylation events do occur. In vitro experiments using purified virus revealed that endogenous or exogenously added p6 was efficiently phosphorylated by virion-associated cellular kinase(s). Inhibition experiments suggested that a cyclin-dependent kinase or a related kinase, most likely ERK2, was involved in p6 phosphorylation by virion-associated enzymes.     

Status of fibrinolysis in systemic lupus erythematosus

In patients with systemic lupus erythematosus (SLE) both a haemorrhagic diathesis and a tendency to thrombosis of the venous and arterial vessels can be observed. In the course of the disease, thrombosis of the leg or pelvic veins developed in 20 per cent of 188 patients. The levels of alpha 2-plasmin inhibitor, plasminogen, fibronectin and of factor VIII complex were increased in patients with SLE compared with a control group. Fifty per cent of the patients showed no increase in fibrinolytic activity after venous occlusion measured with the fibrin plate method. This suggests a reduced fibrinolytic capacity in SLE probably caused by alteration of the endothelial cells through immune complex vasculitis. In addition, the lupus anticoagulant and an acquired antithrombin III deficiency in nephrotic syndrome in SLE are to be considered thrombophilic mechanisms. In the individual case there is an overlapping of hyper- and hypocoagulability.     

Non-secreting plasmacytomas]

In non-secernent plasmocytomas there are no characteristic changes of serum protein. Diagnostic difficulties may be overcome by cytomorphological examinations, immunofluorescence and electron microscopy. By referring to 4 own observations the value of the electron microscopic characteristics of plasma cells is demonstrated. Subtile investigations in protein diagnostics are required for avoiding incomplete monoclonal immunoglobulins which may greatly enter the kidneys to be overlooked. Generally the prognosis of non-secernent plasmocytomas is not worse than that of other forms.     

Effect of cytosine arabinoside on the differentiation of granulocyte-monocyte progenitors (CFU-GM) and myeloid leukemia blasts (CFU-L) in vitro

The serum concentrations of Ara-C are in the range from 10(-6) to 10(-8) M in LD-Ara-C treated patients. The growth of CFU-GM from bone marrow of healthy volunteers was depressed depending on Ara-C-concentration applied in vitro. The growth of CFU-L from peripheral blood of two patients with AML (M 2) and one patient with CML in blast crisis was differently influenced by Ara-C-application in vitro. An elevated proportion of mature cells was observed in smears of cultured cells with Ara-C from two patients. The usefulness of Ara-C for a differentiation inducing therapy is discussed.     

Evaluating the success of blood transfusion with erythrocytes preserved in different ways

In a clinical study 18 patients with an indication to polytransfusion were examined by reason of secondary anaemias in diseases of the haemopoietic system. The efficiency of transfusion on the basis of body height, body mass and sex of the patients and the blood volume resulting from it as well as the exact amount of haemoglobin provided by stored blood and the increase of HB post transfusionem connected with it were found to be the criteria for the success of a transfusion. However, selected clinical parameters (LDH, Hbe, potassium, bilirubin) were constantly checked. The following values for the average efficiency of transfusion were found 16 hours post transfusionem: in washed erythrocyte concentrate 77%; in erythrocyte concentrate c. b. c. 45%; in erythrocyte concentrate GK 36%. Therefore, special emphasis is placed on an accompanying control of haemotherapy.