Molecular and cellular effects of antisickling concentrations of alkylureas

Alkylureas are capable of inhibiting sickling in vitro and the gelation of solutions of hemoglobin S at concentrations between 0.05 and 0.1 M with increasing effectiveness that is directly proportional to the length of the alkyl chain (butyl greater than propyl greater than ethyl greater than methyl). 6The inhibitory effect is independent of pH between 6.5 and 7.5 and is a process driven by entropy. The alkylureas at concentrations of 0.1 M have minimal effects on several erythrocyte functions. Oxygen equilibria, osmotic fragility, reduced glutathione content, and glutathione reductase activity are totally unaffected, while pyruvic kinase activity is decreased only by butylurea by about 20%, and glucose-6-phosphate dehydrogenase activity is decreased progressively to a maximum of 30% in direct proportion to the length of the alkyl chain. Alkylureas not only inhibit sickling but are also capable of desickling erythrocytes that have been maintained in the deoxygenated state. They have little effect on several erythrocyte functions at antisickling concentrations, but their toxicity must be evaluated before they can be examined as potential therapeutic agents for the treatment or prevention of acute episodes in sickle cell anemia.     

Association of the subtype 2 of the Epstein-Barr virus with T-cell non- Hodgkin's lymphoma of the midline granuloma type [see comments]

Lethal midline granuloma (LMG) is associated with Epstein-Barr virus (EBV). The latter has at least two subtypes with different biological properties. The subtypes can be identified by their genomic configuration. Using EBV-RNA (EBER) in situ hybridization and EBV polymerase chain reaction (PCR), we have looked for the presence of EBV in six LMGs and six non-Hodgkin's lymphomas (NHLs) located in the nasopharyngeal region, and determined the subtype of EBV. Six of six LMGs were positive by PCR and EBER in situ hybridization, whereas NHLs were either negative or, in three of six cases, showed few EBER- positive cells considered to be nonneoplastic lymphocytes. The subtype 2 was found in LMG lesions of three of six patients; the remaining three of six patients with LMG had the generally occurring subtype 1. The results indicate that the association of EBV with NHL may depend more on tumor type than on its localization. The occurrence of the rare subtype 2 in LMG may relate to a covert immune defect.     

Studies of circulating hemopoietic progenitor cells in human fetal blood

High levels of committed erythroid and granulocytic/monocytic progenitor cells have been demonstrated in fresh blood obtained at fetoscopy. The fetal progenitor cells were more sensitive to appropriate stimuli (erythropoietin and colony-stimulating factor) than adult progenitor cells grown under the same conditions, and this was shown to be due to intrinsic differences in the progenitor cells at the different developmental stages.     

Potentiation of fibroblast DNA synthesis by a phenytoin-induced mononuclear cell derived factor in vitro

Abstract – Human mononuclear cells purified by Lymphoprep flotation were incubated with phenytoin (PHT) (20 μg/ml) or its metabolite p-HPPH (2 μg/ml) in the presence of Concanaval-in A (10 μg/ml) in vitro. The results indicate that phenytoin and its metabolite p-HPPH induce the release of a mononuclear cell factor(s) that activates quiescent human gingival fibroblast to synthesize DNA.     

Intra-arterial digital subtraction angiography of the spinal cord

Digital subtraction angiography (DSA) of the spinal cord was performed in 6 patients using selective intra-arterial injections of contrast material. Two arteriovenous malformations of the spinal cord, 1 dural fistula, and 1 case of multiple hemangioblastomas were studied. Contrast and spatial resolution were satisfactory for defining normal and abnormal vascularity while reducing examination time, contrast dosage, patient discomfort, and film cost. The only significant limitation was misregistration artifacts seen on lateral views encompassing the diaphragm.