The influence of ethanol feeding on the activities of factors II, VII, VIII, IX and X in rats.

The effect of chronic administration of ethanol to rats in a controlled regimen upon the activities of the coagulation factors II, VII, VIII, IX and X has been studied. No significant differences were found for factor II, IX and X between the ethanol-treated rats and the control group given an isocaloric diet with carbohydrate replacing ethanol. Factor VII activity was somewhat higher and factor VIII activity decreased significantly in the experimental group when ethanol treatment was combined with an approximately two-fold increase in dietary polyunsaturated fatty acid.     

Molecular cytogenetic characterization of two non-MYCN amplified neuroblastoma cell lines with complex t(11;17).

The pediatric tumor neuroblastoma is characterized by a very variable, and at times unpredictable, pattern of clinical behavior, ranging from a benign localized tumor to an aggressive malignancy with poor prognosis. Standard clinical and pathological assessments do not always differentiate reliably between tumor subtypes and, therefore, genetic markers are now playing an increasingly important role in treatment decisions. MYCN oncogene amplification, for example, provides a useful marker of poor prognosis. However, less than one-half of all patients who present with, or who later develop, metastatic disease show MYCN amplification. Consequently, the identification of characteristic patterns of genetic alteration in the remaining tumors is of importance. In this report, we describe two new cell lines that we have established from metastatic, non-MYCN amplified, advanced stage neuroblastomas. These cell lines show a number of features in common, including unbalanced translocation between 11q and 17q, loss of 3p, 4p and 11q and gain of 17q. Therefore, they provide a valuable resource for the characterization of genetic pathways leading to aggressive tumor growth in non-MYCN amplified neuroblastomas.     

Anaplastic large cell lymphoma of bone—is it a bad tumor?

A teenage boy presented with a CD30-positive anaplastic large cell lymphoma (ALCL) affecting his scapula and was successfully treated with chemotherapy. His clinical features and outcome were compared with other cases described in the literature. A further review of 11 ALCL cases with bony involvement treated in the UK since 1990, including two with primary bone disease, did not suggest an unfavorable treatment outcome. This finding will need to be confirmed by further study on a larger patient cohort with primary bone ALCL.     

How nature can exploit nonspecific catalytic and carbohydrate binding modules to create enzymatic specificity

Noncatalytic carbohydrate binding modules (CBMs) are components of glycoside hydrolases that attack generally inaccessible substrates. CBMs mediate a two- to fivefold elevation in the activity of endo-acting enzymes, likely through increasing the concentration of the appended enzymes in the vicinity of the substrate. The function of CBMs appended to exo-acting glycoside hydrolases is unclear because their typical endo-binding mode would not fulfill a targeting role. Here we show that the Bacillus subtilis exo-acting β-fructosidase SacC, which specifically hydrolyses levan, contains the founding member of CBM family 66 (CBM66). The SacC-derived CBM66 (BsCBM66) targets the terminal fructosides of the major fructans found in nature. The crystal structure of BsCBM66 in complex with ligands reveals extensive interactions with the terminal fructose moiety (Fru-3) of levantriose but only limited hydrophobic contacts with Fru-2, explaining why the CBM displays broad specificity. Removal of BsCBM66 from SacC results in a ∼100-fold reduction in activity against levan. The truncated enzyme functions as a nonspecific β-fructosidase displaying similar activity against β-2,1– and β-2,6–linked fructans and their respective fructooligosaccharides. Conversely, appending BsCBM66 to BT3082, a nonspecific β-fructosidase from Bacteroides thetaiotaomicron, confers exolevanase activity on the enzyme. We propose that BsCBM66 confers specificity for levan, a branched fructan, through an “avidity” mechanism in which the CBM and the catalytic module target the termini of different branches of the same polysaccharide molecule. This report identifies a unique mechanism by which CBMs modulate enzyme function, and shows how specificity can be tailored by integrating nonspecific catalytic and binding modules into a single enzyme.     

Quality assurance in preschool surveillance

A quality assurance programme was used to evaluate community and primary care based preschool surveillance using the National Child Health Computer System in 40 examination centres. Quarterly reports were generated from returns from clinical medical officers and general practitioners to list non-attenders, uptake, and timeliness for the four preschool checks. These provided rapid and comparative feedback on personal performance for participating health professionals and led to marked rises in recorded timeliness and uptake against preset targets. Pre-existing uptake was highest at the 6 week check with least overall improvement. Greatest improvements occurred at the 18 month health visitor check but, in general, results plateaued when the programme had been in use for 12 to 18 months. Particular problems such as data legibility and mobile populations were identified and solutions formulated. It is postulated that improvements in performance were due to enhanced professional motivation as no other factors changed. This system provides a valuable contribution in the light of changing patterns of service provision.     

No Effect of Acute Ethanol Administration on Hepatic Protein Synthesis and Export in the Rat in Vivo

Ethanol was administered as a single p.o. dose (2.88 g X kg-1) to male rats (220-265 g body weight) to give blood alcohol concentrations of 40-50 mM for the following 3 hr. Controls were given isoenergetic amounts of either sucrose or lipid. Liver protein synthetic rates were measured during a 20 min interval at the end of the 3 hr period following the administration of diets. Although ethanol caused a 32% reduction of the incorporation of labelled valine into liver protein compared to the sucrose group during the 20 min interval, no such reduction was found when the synthetic rate of stationary liver protein was calculated (182 vs. 214 (not significant) pmol X mg protein-1 X min-1) for same interval. There was no difference between the ethanol and lipid group with regard to either incorporation or synthetic rates. Incorporation of valine into plasma proteins was reduced in the ethanol group compared to the sucrose group, but not compared to the lipid control group, again demonstrating no ethanol-specific effect. When the incorporation into plasma proteins was divided by the specific radioactivity of valyl-tRNA at 20 min, the difference between the ethanol and the sucrose group disappeared. The fraction of newly synthesized proteins exported to the plasma measured 40 min after the injection of labeled valine, was equal in all three treatment groups. It was concluded that acute administration of ethanol has no consistent effect on liver protein synthesis and secretion in vivo.