Fusion-competent vaccines: broad neutralization of primary isolates of HIV

Current recombinant human immunodeficiency virus (HIV) gp120 protein vaccine candidates are unable to elicit antibodies capable of neutralizing infectivity of primary isolates from patients. Here, "fusion-competent" HIV vaccine immunogens were generated that capture the transient envelope-CD4-coreceptor structures that arise during HIV binding and fusion. In a transgenic mouse immunization model, these formaldehyde-fixed whole-cell vaccines elicited antibodies capable of neutralizing infectivity of 23 of 24 primary HIV isolates from diverse geographic locations and genetic clades A to E. Development of these fusion-dependent immunogens may lead to a broadly effective HIV vaccine.     

A model to predict survival following liver retransplantation

In the current era of critical-organ shortage, one of the most controversial questions facing transplantation teams is whether hepatic retransplantation, which has historically been associated with increased resource utilization and diminished survival, should be offered to a patient whose first allograft is failing. Retransplantation effectively denies access to orthotopic liver transplantation (OLT) to another candidate and further depletes an already-limited organ supply. The study group was comprised of 1,356 adults undergoing hepatic retransplantation in the United States between 1990 and 1996 as reported to the United Network for Organ Sharing (UNOS). We analyzed numerous donor and recipient variables and created Cox proportional-hazards models on 900 randomly chosen patients, validating the results on the remaining cohort. Five variables consistently provided significant predictive power and made up the final model: age, bilirubin, creatinine, UNOS status, and cause of graft failure. Although both hepatitis C seropositivity and donor age were significant by univariate and multivariate analyses, neither contributed independently to the estimation of prognosis when added to the final model. The final model was highly predictive of survival (whole model chi2 = 139.63). The risk scores for individual patients were calculated, and patients were assigned into low-, medium-, and high-risk groups (P <.00001). The low degree of uncertainty in the probability estimates as reflected by confidence intervals, even in our high-risk patients, underscores the applicability of our model as an adjunct to clinical judgment. We have developed and validated a model that uses five readily accessible "bedside" variables to accurately predict survival in patients undergoing liver retransplantation.     

How the Wastewater Discharge Fee Might Become a Tool of River-Basin Management

The Federal German Water Law of 1976 postulated for the first time that a licence for the discharge of wastewater into public watercourses might only be granted when the wastewater, prior to discharge, is treated according to laid-down standards. In 1976 it was also decided that for the residual pollution load in sewage-treatment plant effluents a pollution fee has to be paid.
At present three pollution units have to be paid per capita and annually for untreated domestic wastewater. One pollution unit is assessed at 17/annum, but the price will be increased to 30/annum in future.
Since the pollution units encompass COD, nitrogen, phosphorus, heavy metals, and chlorinated hydrocarbon compounds, the pollution unit is a good tool to compare the effectiveness of treatment. For different drainage systems the residual pollution units (per litre and second) can also be calculated for low-flow conditions.     

The crying infant

The crying infant is a common presenting complaint and a difficult diagnostic dilemma that may represent the primary manifestation of a serious or even life-threatening condition. Although many children experience an exacerbation of the normal crying tendencies or minor ailments typical of the early months of life, a significant number of infants have underlying pathologic conditions requiring immediate intervention. This article briefly reviews current and past research on this phenomenon and presents differential diagnoses and recommendations for the evaluation and management of the acute crying episode.     

Isolation and characterization of the Saccharomyces cerevisiae DPP1 gene encoding diacylglycerol pyrophosphate phosphatase

Diacylglycerol pyrophosphate (DGPP) is involved in a putative novel lipid signaling pathway. DGPP phosphatase (DGPP phosphohydrolase) is a membrane-associated 34-kDa enzyme from Saccharomyces cerevisiae which catalyzes the dephosphorylation of DGPP to yield phosphatidate (PA) and then catalyzes the dephosphorylation of PA to yield diacylglycerol. Amino acid sequence information derived from DGPP phosphatase was used to identify and isolate the DPP1 (diacylglycerol pyrophosphate phosphatase) gene encoding the enzyme. Multicopy plasmids containing the DPP1 gene directed a 10-fold overexpression of DGPP phosphatase activity in S. cerevisiae. The heterologous expression of the S. cerevisiae DPP1 gene in Sf-9 insect cells resulted in a 500-fold overexpression of DGPP phosphatase activity over that expressed in wild-type S. cerevisiae. DGPP phosphatase possesses a Mg2+-independent PA phosphatase activity, and its expression correlated with the overexpression of DGPP phosphatase activity in S. cerevisiae and in insect cells. DGPP phosphatase was predicted to be an integral membrane protein with six transmembrane-spanning domains. The enzyme contains a novel phosphatase sequence motif found in a superfamily of phosphatases. A dpp1Delta mutant was constructed by deletion of the chromosomal copy of the DPP1 gene. The dpp1Delta mutant was viable and did not exhibit any obvious growth defects. The mutant was devoid of DGPP phosphatase activity and accumulated (4-fold) DGPP. Analysis of the mutant showed that the DPP1 gene was not responsible for all of the Mg2+-independent PA phosphatase activity in S. cerevisiae.     

Is excess intensive care mortality in the United Kingdom concealed by ICU mortality prediction models?

Eleven viruses isolated between 1993 and 1997 from outbreaks of classical swine fever in the neighbouring countries of Slovakia, The Czech Republic and Austria were compared after partial sequencing of the NS5B and E2 genes. Viruses collected from South-Central and West Slovakia were indistinguishable during a period of four years, even when associated with outbreaks of variable severity. Outbreaks that occurred in the Czech Republic in 1996 involved two types of virus, one of which was related to the Slovakian outbreaks, and the other to Austrian outbreaks. The results show that the molecular-genetic approach can reveal epizootiological relationships between outbreaks that would not otherwise be apparent. Furthermore, the relative genetic stability of the classical swine fever virus in the field, means that quite small sequence differences can have epizootiological significance.