DNA analysis for antenatal diagnosis of thalassaemia and haemophilia

Two years' experience with DNA analysis for the antenatal diagnosis of thalassaemia and haemophilia is described. The advantages of DNA testing, including a first-trimester diagnosis and greater availability, must be considered in relation to the problems that are associated with this procedure. In particular, the risk of recombination in DNA polymorphism studies should be understood and explained fully to the patient.     

Active-site architecture and catalytic mechanism of the lipid A deacylase LpxR of Salmonella typhimurium

The lipid A portion of lipopolysaccharide, the major component of the outer leaflet of the outer membrane of Gram-negative bacteria, is toxic to humans. Modification of lipid A by enzymes often reduces its toxicity. The outer-membrane protein LpxR from Salmonella typhimurium is a lipid A-modifying enzyme. It removes the 3′-acyloxyacyl moiety of the lipid A portion of lipopolysaccharide in a Ca²⁺-dependent manner. Here, we present the crystal structure of S. typhimurium LpxR, crystallized in the presence of zinc ions. The structure, a 12-stranded β-barrel, reveals that the active site is located between the barrel wall and an α-helix formed by an extracellular loop. Based on site-directed mutagenesis and modeling of a substrate on the active site, we propose a catalytic mechanism similar to that of phospholipase A2, in which a Ca²⁺ forms the oxyanion hole and a histidine activates a water molecule (or a cascade of two water molecules) that subsequently attacks the carbonyl oxygen of the scissile bond.     

Global electrophysiological and hemodynamic assessment of ventricular pacing employing non-contact mapping

Objective:  

Right ventricular (RV) pacing has been associated with abnormal cardiac electrical and mechanical dyssynchrony, resulting in impaired global and regional ventricular pump function. This study aimed to characterize the relative effects of pacing site on left ventricular (LV) activation patterns and associated hemodynamic performances.     

Myocardial echinococcosis with perforation into the pericardium

Though rare, cardiac echinococcosis should be included in the differential diagnosis of cardiac tumors, particularly in patients originating from endemic areas or with manifestation of hydatid disease in other organs. Diagnosis and localisation of the cysts is best accomplished with non-invasive methods such as 2-D transthoracic and transesophageal echocardiography, computed tomography and NMR. Excision of the cardiac cyst from the interventricular septum in a 21 year old patient with polyvisceral echinococcosis was performed with cardiopulmonary bypass. Adjunctive medical therapy with mebendazol is being continued for 24 months postoperatively. Twelve months after surgery the patient is asymptomatic without echocardiographic signs of recurrence.     

A cell line from a human ovarian carcinoma with amplification of the K-ras gene

We have recently reported that ascitic cells from a human ovarian carcinoma have a 10- to 20-fold K-ras amplification and that the level of such amplification did not change over a 9-month period during which the patient received chemotherapy and underwent clinical progression. Here we describe an ovarian tumor cell line (HOC-8) which has been derived from that tumor and which also shows a similar level of K-ras amplification. The amounts of K-ras specific mRNA and the Mr 21,000 protein encoded by the amplified gene are correspondingly elevated. karyotypic analysis revealed no detectable double minute chromosomes but did show an abnormal banding region on chromosome 6. This cell line may represent a useful model to investigate the significance of the K-ras gene product for the pathogenesis of human tumors.