Activation of fibrin-bound plasminogen by pro-urokinase and its complementariness with that by tissue plasminogen activator.

Single chain urokinase (SC-UK) is a precursor of 55 kd two-chain UK (TC-UK). Treatment with catalytic proportions of plasmin or kallikrein converts SC-UK to TC-UK as a consequence of cleavage of its Lys158-Ile159 peptide bond. This plasmin-mediated activation of SC-UK induces a positive feedback secondary reaction and complicates measurement of its activity against its natural substrate, Glu-plasminogen.

Prefrontal cortical blood flow and cognitive function in Huntington's disease.

To examine the relationship between cortical physiology and dementia in Huntington's disease, rCBF during three different behavioural conditions, one of which emphasised prefrontal cognition, was determined by xenon-133 inhalation in 14 patients with Huntington's disease and in matched controls. Cortical rCBF was not reduced in Huntington's disease patients even while they manifested overt prefrontal-type cognitive deficits. Caudate atrophy on CT and rCBF were significantly correlated, but only during the prefrontal behaviour where the correlation was positive.

B-lymphocytes as a source of cell surface growth-promoting factors for hematopoietic progenitors.

Although B cells reside in the bone marrow, little is known concerning their functional role in hematopoiesis. We have measured the effects of surface membrane factors released from unstimulated, circulating B cells of normal donors and patients with chronic lymphocytic leukemia on human hematopoiesis in vitro. Leukemic cells augment erythroid burst formation by allogeneic blood cells (p less than 0.

Experiences with pro-urokinase and potentiation of its fibrinolytic effect by urokinase and by tissue plasminogen activator.

Pro-urokinase is a single chain, precursor form of two chain, 54,000 Mr urokinase. Although originally isolated from urine, pro-urokinase is also found in blood, where it is believed to participate in natural fibrinolysis alongside tissue plasminogen activator (t-PA). These two plasminogen activators share the property of inducing fibrin-selective plasminogen activation, but many of their other properties, including their modes of action, are dissimilar.

Purification of a membrane-derived human erythroid growth factor.

We have purified erythroid burst-promoting activity (BPA) from human lymphocyte plasma membranes by detergent extraction followed by gel-filtration, ion-exchange, and hydroxylapatite chromatography. BPA is a heat-stable integral membrane glycoprotein of Mr 28,000 by gel filtration whose activity is eluted from NaDodSO4/polyacrylamide gels as a broad band at Mr 25,000-29,000. The growth stimulator appears to be erythroid-specific, stimulating proliferation of the human erythroid burst-forming unit (BFU-E) by up to 600% of control values when tested in serum-free bone marrow culture.

Synthesis and assembly of membrane skeletal proteins in mammalian red cell precursors.

The synthesis of membrane skeletal proteins in avian nucleated red cells has been the subject of extensive investigation, whereas little is known about skeletal protein synthesis in bone marrow erythroblasts and peripheral blood reticulocytes in mammals. To address this question, we have isolated nucleated red cell precursors and reticulocytes from spleens and from the peripheral blood, respectively, of rats with phenylhydrazine-induced hemolytic anemia and pulse-labeled them with [35S]methionine. Pulse-labeling of nucleated red cell precursors shows that the newly synthesized alpha- and beta-spectrins are present in the cytosol, with a severalfold excess of alpha-spectrin over beta-spectrin.

Hereditary elliptocytosis, spherocytosis and related disorders: consequences of a deficiency or a mutation of membrane skeletal proteins.

The membrane skeleton, a protein lattice that laminates the internal side of the red cell membrane, contains four major proteins: spectrin, actin, protein 4.1 and ankyrin. By mass, the most abundant of these proteins is spectrin, a fibre-like protein composed of two chains, alpha and beta, which are twisted along each other into a heterodimer.

Degenerative diseases of the metacarpophalangeal joints.

Degenerative arthritis of the finger metacarpophalangeal joints is uncommon and, when seen, a specific etiology should be sought. MP joint arthritis in the absence of a history of trauma may signal an underlying systemic disease. The clinical and radiographic findings may be subtle.

Cell type-specific association between two types of spectrin and two types of intermediate filaments.

We have demonstrated a differential association between two types of spectrin, from erythrocytes and brain, with two types of intermediate filaments, vimentin filaments and neurofilaments. Electron microscopy showed that erythrocyte spectrin promoted the binding of vimentin filaments to red cell inside-out vesicles via lateral associations with the filaments. In vitro binding studies showed that the association of spectrin with vimentin filaments was apparently saturable, increased with temperature, and could be prevented by heat denaturation of the spectrin.

Lipids, lipoproteins, fibrinogen and fibrinolytic activity in angiographically assessed coronary heart disease.

Plasma lipids, lipoproteins, fibrinogen and fibrinolytic activity (FA) were measured in 202 consecutive patients undergoing coronary angiography. Twenty-one patients, 13 men and 8 women with a mean age of 52.8 years and 56.

Attenuating actions of diazepam on the photomyoclonic reflex.

The photomyoclonic reflex (PMR), consisting of a one- or two-component blink reflex associated with the flash electroretinogram (ERG), is sensitive to the acute effect of intravenously administered diazepam. In the 29% (two of seven) of normal volunteers who had a PMR, diazepam reduced it to a nonobservable level. Diazepam also had a significant attenuating effect on the a- and b-waves of the ERG; the magnitude of attenuation in normal volunteers, however, probably would not alter a clinical diagnosis based on ERG.

Clinical expression of alpha spectrin mutants in hereditary elliptocytosis.

The group of disorders manifesting as hereditary elliptocytosis/pyropoikilocytosis (HE/HPP) represent a unique group of experiments of nature that result from molecular defects of alpha spectrin. At the level of protein structure, these alpha spectrins can be identified by analysis of peptides generated by limited tryptic digestion. Such an approach reveals that the peptide containing alpha spectrin self-association site (the alpha I domain, molecular mass of 80 daltons) is cleaved to peptides of smaller size, presumably due to changes in the primary structure that lead to increased susceptibility of existing cleavage sites or the opening of new sites.

Upregulation of the mu-noncompetitive delta binding site by chronic morphine administration: effect of preincubating membranes in 400 nM sodium chloride.

Rats treated chronically with morphine were found to have an increased number of mu-noncompetitive delta binding sites. The increase in the Bmax was 39% and the enhancement was blocked by pre-incubation in 50 mM Tris, pH 7.4 with 400 mM NaCl for one hour at 25 degrees C.

DISC VARIANCE OF THE HARKEN MITRAL PROSTHESIS: THE CONTRIBUTION OF ASSOCIATED AORTIC REGURGITATION.

Four cases of severe mitral regurgitation due to disc variance of the Harken disc prosthesis in the mitral position are described. The valve occluder actually escaped into the left atrium in two patients, and neither survived despite emergency valve replacement. In the other two, disc malfunction was identified by flouroscopy, the prosthesis was replaced, and both patients survived.

Police as a community mental health resource.

In their pathways to the state mental hospital, almost 50% of mentally ill patients and their families from Baltimore utilize the police as a community resource. To better understand why so many people use the police for help with mental problems, a comparison was made between first admission patients who used the police (N=17) and those who used more conventional medical resources (N=35). The results indicate that families decide to call the police because other, more appropriate, resources are not as accessible and will not offer services to recalcitrant patients.