VPX is a 16 kDa accessory protein expressed in cells infected with HIV-2 and most SIV strains and is packaged into virus particles. In order to define the requirements for incorporation of VPX into virions, VPX and HIV-2 GAG-POL were expressed independently from a vaccinia virus-based transient expression system. Under these conditions, VPX was exported from transfected cells only when coexpressed with the HIV-2 GAG-POL plasmid. A 27 kDa protein coprecipitating with VPX was found to have an identical electrophoretic mobility as the GAG capsid protein, and reacted with an anti-GAG antiserum. Coexpression of VPX and GAG-POL resulted in virus-like particles containing both proteins, as determined by sucrose gradient analyses. Expression of VPX and HIV-2 GAG without POL gave similar results. VPX association with HIV-2 GAG p27 capsid protein was specific, since no association was found with the HIV-1 GAG p25/p24 capsid protein.

Animals↗

PubMed1994

Effect of dopamine2 blockade on renal function under varied sodium intake.

This study explored the role of the dopamine-2 receptor (DA2) in the control of renal blood flow (RBF) and the influence of variations in sodium intake. These relationships have not been previously defined in man. Seven normotensive male subjects underwent a low dose dopamine (DA) infusion (1 microgram/kg.min) for 3 h, known to activate both DA1 and DA2 receptors. The effect of DA2 receptor on renal hemodynamics was studied using a relatively specific DA2 blocker [domperidone (DOM); 60 mg, orally] alone and with a DA infusion. Systemic and renal hemodynamics parameters were measured noninvasively. Urinary prostacyclin was measured in 3-h urine specimens, obtained during the DA infusion. The DA infusion increased RBF and prostacyclin during both normal and high salt diets, but this effect was attenuated on a low salt diet. DOM alone significantly reduced basal RBF during normal (1304 +/- 48 vs. 1175 +/- 45 mL/min.1.73 m2; P < 0.01) and low salt diets (1402 +/- 80 vs. 1220 +/- 101 mL/min.1.73 m2; P < 0.02), but was without effect during high sodium intake. DOM had no effect on prostacyclin excretion at any level of salt intake. These results suggest that both DA1 and DA2 are activated in renal vessels by DA, and that DA2 receptors play a role in the renal vasodilating action of DA. Changes in sodium balance alter the actions of the two receptors (DA1 and DA2) in a coordinated fashion in the regulation of RBF.

Adult↗

PubMed1994

Hypoaldosteronism.

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Adrenal Gland Diseases↗

PubMed1994

Procoagulant activity in cancer cells is dependent on tissue factor expression.

Procoagulant activity of pairs of cell lines, which were derived from the same original cell type but which possess different growth characteristics and metastatic properties, was examined. The following characteristics were considered suggestive of a greater likelihood of metastatic potential: high histological grade; establishment of the line from a metastatic rather than a nonmetastatic cancer; increased tumorigenicity in nude mice; and/or estrogen receptor-negative mammary cancer. Procoagulant activity was evaluated by a two stage clotting assay. Procoagulant activity was highly variable, with up to a 1,300-fold difference, among the cancer cell lines examined. The rate of clot formation was factor VII dependent and was totally inhibited by an anti tissue factor monoclonal antibody, indicating that tissue factor was the only significant procoagulant present in these cancer cells. Tissue factor antigen expression, evaluated by ELISA, correlated with procoagulant activity. In all pairs of cancer cell lines, those with characteristics of increased proliferative potential had increased tissue factor levels compared to cell lines that originated from the same cell type, but which possess less aggressive characteristics. Tissue factor activity in these cancer cells was increased by cell lysis or by exposure of intact cells to a calcium ionophore, similar to results previously obtained in fibroblasts. Tissue factor mRNA was evaluated by northern blot analysis using a specific probe complementary to tissue factor mRNA. The previously described predominant tissue factor mRNA species of 2.2 kb was identified in the majority of cancer cell lines examined, but tissue factor mRNA species of 3.2 to 3.4 kb were also identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1994

Outcome of surgery for failed endoscopic extraction of common bile duct stones in elderly patients.

Endoscopic sphincterotomy (ES) is the treatment of choice for common bile duct stones in elderly patients. For those in whom endoscopic clearance of the common bile duct fails the treatment options include stenting, dissolution therapy and lithotripsy. Surgery is often avoided because of the reported high morbidity and mortality in elderly patients. We have reviewed the outcome of patients referred for surgery after failed endoscopic clearance of common bile duct stones. Over a 3-year period, 100 patients with common bile duct stones were referred specifically for endoscopic clearance of the common bile duct (median age 69 years, range 19-97 years). In seven patients duct clearance was possible without ES and in five patients ES was considered inappropriate. ES was attempted in 88 patients and was successful in 75 (85%). Of the 13 patients failing ES or stone removal, surgery was performed in nine and four were stented. Of patients having successful ES (n = 75), ten were referred for surgery because of incomplete duct clearance. Surgery was performed to obtain duct clearance in 19 patients (eight male, 11 female, median age 77 years, range 47-90 years). Of the 19, eight had previously undergone a cholecystectomy (42%) and 17 of the 19 had biliary tract drainage preoperatively (90%). The procedures performed consisted of choledocholithotomy in all plus cholecystectomy (11), choledochoduodenostomy (7) and choledochojejunostomy (7). There were no deaths and only one major complication. The median total inpatient stay was 26 days (range 14-75 days) and the median postoperative stay was 12 days (range 7-50 days). We would conclude that open surgery can be performed safely and effectively in elderly patients with retained bile duct stones.

Aged↗

PubMed1993

Renewed US AIDS strategy.

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Acquired Immunodeficiency Syndrome↗

PubMed1993

Attacks on heart diseases.

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Aged↗

PubMed1993

Synthesis of tissue factor messenger RNA and procoagulant activity in breast cancer cells in response to serum stimulation.

The procoagulant activity observed in many types of tissue and cultured cells is due to tissue factor, a 30 kd transmembrane protein. The mRNA for tissue factor is a 2.2-kb species, which in some non-cancer cells can be up-regulated or induced by cytokines or by serum stimulation. In this study, induction of procoagulant activity in cancer cells was evaluated using the breast cancer cell line, MCF-7, and an adriamycin resistant subline, AdrRMCF-7, which has increased tumorigenicity in nude mice compared to the parental cell line. Procoagulant activity was factor VIIa dependent and was inhibited by an anti-tissue factor antibody. MCF-7 cells had minimal tissue factor activity, while AdrRMCF-7 cells had an 10-fold increase compared to the parental line. This increase was not observed in MCF-7 cells transfected with the multi-drug resistant gene, which is associated with adriamycin resistance. Serum stimulation of quiescent MCF-7 cells increased tissue factor activity 5-fold over baseline level, but did not increase activity in cells grown in serum-replete medium. Tissue factor activity of AdrRMCF-7 quiescent cells and AdrMCF-7 cells grown in serum-replete medium was enhanced 2-fold by serum stimulation. The predominant tissue factor mRNA species in MCF-7 cells was a 3.2 to 3.4-kb band, which increased in response to serum stimulation of cells grown in serum-replete medium. The mature 2.2-kb tissue factor mRNA band was detected in quiescent MCF-7 cells within six hours of serum stimulation and remained present 24 hours after stimulation. Synthesis of the 2.2-kb tissue factor mRNA species in MCF-7 and AdrRMCF-7 cells correlated with appearance of procoagulant activity. Thus, while procoagulant activity correlates with the level of the 2.2-kb tissue factor mRNA species in these cancer cells, there are inherent differences in tissue factor activity, antigen, and mRNA levels, as well as in regulation of its synthesis between these cells.

Animals↗

PubMed1993