TCDD reduces rat hepatic epidermal growth factor receptor: comparison of binding, immunodetection, and autophosphorylation

Two overlapping cDNA clones for core protein of a biglycan of bovine aorta were isolated from a pSPORT bovine aorta tissue cDNA library. The 2043-bp cDNA contains a 114-bp 5' untranslated region, a 1224-bp cDNA open reading frame and a 705-bp 3' untranslated region. The encoded core preproprotein contains a prepeptide (residues no. -37 to -19) and a propeptide (residues no. -18 to -1), with 369 amino acid residues corresponding to a molecular mass of 41.6 kDa. The deduced amino acid sequence revealed a striking homology to rat vascular smooth muscle cell, human bone and bovine articular cartilage biglycans from cell culture.     

Involvement of D2 dopamine receptors in the nucleus accumbens in the opiate withdrawal syndrome

The nucleus accumbens is prominently implicated in the reinforcing effects of abused drugs, and is an important site for mediating aversive stimulus properties of opiate withdrawal. It is generally thought, however, that the role of the accumbens is negligible in the somatic signs of opiate withdrawal. Contrary to this assumption, we now report that D2 dopaminergic receptor activity in the accumbens area potently regulates somatic symptoms of opiate withdrawal. We find that activation of D2 receptors within the accumbens prevents somatic signs of naloxone-induced opiate withdrawal and, conversely, that blockade of accumbal D2 receptors in opiate-dependent animals elicits somatic withdrawal symptoms. These data indicate that dopamine in the accumbens not only is important in the rewarding effects of abused drugs, but also (via D2 receptors) plays a pivotal role in opiate withdrawal.     

Selective surgical management in penetrating neck injuries

OBJECTIVE: To evaluate selective operative management in penetrating neck trauma. DESIGN: A chart review. SETTING: A university-affiliated hospital in Johannesburg, South Africa. PATIENTS: All adults admitted to the hospital between January 1988 and June 1993 with a penetrating neck wound. Excluded were patients in whom there was no suspicion of an occult injury that might need further investigation. There were 755 patients in the study. INTERVENTIONS: Immediate surgical exploration (group A, 613 patients) and observation with constant monitoring (group B, 142 patients). MAIN OUTCOME MEASURES: Unnecessary explorations in group A and missed significant injuries in group B. RESULTS: In group A there was a 3% incidence of unnecessary explorations, and 4.2% of the patients died. In group B there was a 9.1% incidence of missed injuries, and 2.8% of the patients died as a result of the delayed diagnosis. Overall the death rate was 4%. CONCLUSION: Selective operative intervention for penetrating neck trauma results in fewer negative explorations and a death rate comparable to those of series that support mandatory neck exploration.     

The cost effectiveness of alpha interferon in the treatment of chronic active hepatitis C

OBJECTIVE: To model the costs and effects of alpha interferon in the treatment of chronic active hepatitis C. DESIGN: A Markov modelling process to simulate the costs and outcomes in hypothetical cohorts of patients treated with and without alpha interferon. OUTCOME MEASURES: Costs per life saved and per life-year gained. RESULTS: On the basis of assumptions formulated about the disease processes and response to treatment, treatment with alpha interferon results in a discounted cost per life-year gained of $33,230 in patients with cirrhosis at the start of treatment and $71,950 in patients without advanced liver disease. The result is sensitive to the assumptions made about the long term effectiveness of alpha interferon. CONCLUSIONS: Alpha interferon is an expensive drug. Its effectiveness is clouded by uncertainty about the long term impact of the drug on the natural history of the disease. If adopted, its use should be monitored to allow the long term cost effectiveness of the drug to be evaluated properly.     

The effect of the chemotherapeutic drug VP-16 on poly(ADP-ribosylation) in apoptotic HeLa cells

We have studied the effect of the chemotherapeutic drug VP-16 (etoposide) on the metabolism of HeLa cells by analysing different cellular parameters; in particular we have focused on changes in cellular morphology that are considered as markers of apoptosis. By immunofluorescence experiments we have shown that VP-16 causes the complete disruption of nucleoli and induces chromatin margination and fragmentation. Agarose gel electrophoresis of DNA from cells treated with 10-100 microM VP-16 showed the appearance of a characteristic ladder due to the internucleosomal DNA cleavage. The effect of etoposide on DNA integrity was not prevented by preincubation of cells with the protein synthesis inhibitor cycloheximide. These results provide experimental evidence indicating that the typical features of apoptosis are visible in HeLa cells exposed to VP-16. In this experimental system we have investigated whether the ADP-ribosylation process could be regulated by the presence of DNA fragments. By means of the activity gel technique, which allows the direct evaluation of automodified poly(ADP-ribose)polymerase, we have observed that in extracts from cells where etoposide-induced DNA fragmentation occurred, the autoribosylated form of the enzyme is greatly increased. Ribosylated poly(ADP-ribose)polymerase has been isolated by affinity chromatography on boronate column from cells permeabilized and labelled with [32P]NAD. Drug exposure caused a strong augmentation of modified enzyme. These observations suggest that activation of ADP-ribosylation process occurs in cells that show the typical features of apoptosis.     

Synthesis of porcine brain natriuretic peptide (BNP-26) and an analog

The porcine brain natriuretic peptide (BNP-26) and its analog, (Mpr4,D-Ala6,13) BNP(4-24)-NH2, were synthesized by solid phase method employing the Boc strategy. After HF cleavage to remove the protected groups, the crude linear peptide was air-oxidized under alkaline conditions to form the disulfide bridge. The synthetic peptides, purified by gel filtration and HPLC, were proved to have pharmacological spectra very similar to that of natural BNP such as natriuretic/diuretic, hypotensive and vaso-relaxant activities.     

Computed tomography in duodenal rupture due to blunt abdominal trauma

Computed tomography (CT) has become a useful procedure in the evaluation of abdominal trauma, since it is able to detect abnormalities in contour or tissue density of the major abdominal and retroperitoneal organs and spaces. Cases have been reported demonstrating the usefulness of CT in evaluating splenic, renal, and hepatic hematomas, retroperitoneal hemorrhage, spinal injuries, and traumatic diaphragmatic hernia. We describe a patient with traumatic rupture of the duodenum in whom CT played a key role in the diagnosis.