Susceptibility of in vitro stimulated PBMC to infection with NSI HIV-1 is associated with levels of CCR5 expression and beta-chemokine production

Susceptibility of PHA/rIL-2-stimulated PBMC from 14 healthy blood donors for NSI HIV-1 infection was analyzed in relation to CCR5 expression and beta-chemokine production. After 1 week of culture in the presence of rIL-2, but not at the moment of inoculation, CCR5 surface expression was positively and beta-chemokine production was inversely associated with susceptibility to NSI HIV-1 infection. Surprisingly, no association was observed between CCR5 genotype and in vitro NSI HIV-1 susceptibility, which was in agreement with similar levels of CCR5 surface expression and beta-chemokine production in CCR5Delta32/+ and CCR5 +/+ PBMC after PHA/rIL-2 stimulation. In contrast to what was observed in vitro, CCR5 genotype did associate with CCR5 surface expression levels in vivo in resting as well as in activated CD4(+) T cell populations that were identified by the expression of CD45RO, CD27, HLA-DR, and CD69. The association between CCR5 expression and susceptibility to infection by NSI HIV-1 observed in vitro might offer an explanation for the in vivo observed protective effect of CCR5 polymorphisms that influence CCR5 expression on disease progression.     

Adaptation to promiscuous usage of chemokine receptors is not a prerequisite for human immunodeficiency virus type 1 disease progression.

Fifty percent of individuals infected with human immunodeficiency virus type 1 (HIV-1) progress to AIDS in the presence of only non-syncytium-inducing (NSI) variants. These rapidly replicating NSI isolates are associated with a high viral load. The question of whether disease progression in the absence of syncytium-inducing (SI) HIV-1 variants is associated with an expansion of the coreceptor repertoire of NSI HIV-1 variants was studied. Biological HIV-1 clones were isolated both early and late in infection from progressors and long-term survivors with wild-type or mutant CCR5 or CCR2b genotypes and analyzed for their capacity to use CCR1, CCR2b, CCR3, CCR5, and CXCR4 on U87 cells coexpressing CD4. All HIV-1 clones were restricted to the use of CCR5. Absent replication of all HIV-1 clones in peripheral blood mononuclear cells from a CCR5 Delta32 homozygous blood donor confirmed this result. These findings indicate that an expanded coreceptor repertoire of HIV-1 is not a prerequisite for a progressive clinical course of HIV-1 infection.     

Novel serum biomarkers in carotid artery stenosis: useful to identify the vulnerable plaque?

Objectives

Serum biomarkers representing inflammatory activity in vulnerable carotid plaques may be used to identify high-risk patients for cerebral ischemic events. We aimed to analyze the relationship between concentrations of four novel biomarkers and neurological symptoms: Neopterin, PTX3, sCD163, and sTREM-1. In addition, we analyzed the relationship between these markers and the presence of coronary (CAD) and peripheral (PAD) artery disease.

Design and methods

Serum biomarker levels were determined in 100 patients undergoing carotid endarterectomy; 33 for stroke, 32 for transient ischemic attack, and 23 for amaurosis fugax. 12 Patients were asymptomatic. Risk factors for atherosclerotic disease and history of CAD and PAD were also assessed.

Results

Symptomatic patients did not show significantly elevated biomarker levels compared to asymptomatic patients and levels did not differ among symptomatic subgroups. Neopterin levels were elevated in patients with concomitant coronary and peripheral artery disease (CAD (32%) 10.2 ± 6.6 vs no CAD (68%) 7.6 ± 2.9 nmol/L, PAD (20%) 12.3 ± 7.4 vs no PAD (80%) 7.5 ± 3.0 nmol/L, p < 0.05). sTREM-1 was elevated in patients with CAD (50.8 ± 53.2 vs 28.0 ± 31.6 ng/L, p < 0.05). PTX3 and sCD163 were not significantly elevated in CAD nor PAD.

Conclusion

Our findings suggest that serum neopterin and sTREM-1 levels may be related to the presence of atherosclerotic disease, but not to carotid plaque vulnerability.     

Evaluating a new approach to selecting medical students

Summary. Dissatisfaction with the traditional methods of selecting Australian medical students, which use only secondary school achievement, led to an innovative alternative method at the Newcastle Medical School. This multistage approach uses tests of problem-solving ability, empathy, creativity and moral dilemmas to screen applicants otherwise suitable on academic achievement. In the 5-year trial since its inception, this process appears reasonably reliable and valid. There is some merit in using a composite score for ranking applicants, based on weighted contributions from the psychological tests used in its multifactorial battery. However, the ultimate effectiveness of individual tests of a composite score will depend on their predictive validity, which is yet unmeasured.     

Evaluation of reference regions for (R)-[(11)C]PK11195 studies in Alzheimer's disease and mild cognitive impairment.

Inflammation in Alzheimer's disease (AD) may be assessed using (R)-[(11)C]PK11195 and positron emission tomography. Data can be analyzed using the simplified reference tissue model, provided a suitable reference region is available. This study evaluates various reference regions for analyzing (R)-[(11)C]PK11195 scans in patients with mild cognitive impairment (MCI) and probable AD. Healthy subjects (n=10, 30+/-10 years and n=10, 70+/-6 years) and patients with MCI (n=10, 74+/-6 years) and probable AD (n=9, 71+/-6 years) were included. Subjects underwent a dynamic three-dimensional (R)-[(11)C]PK11195 scan including arterial sampling. Gray matter, white matter, total cerebellum and cerebrum, and cluster analysis were evaluated as reference regions. Both plasma input binding potentials of these reference regions (BP(PLASMA)) and corresponding reference region input binding potentials of a target region (BP(SRTM)) were evaluated. Simulations were performed to assess cluster analysis performance at 5% to 15% coefficient of variation noise levels. Reasonable correlations for BP(PLASMA) (R(2)=0.52 to 0.94) and BP(SRTM) (R(2)=0.59 to 0.76) were observed between results using anatomic regions and cluster analysis. For cerebellum white matter, cerebrum white matter, and total cerebrum a considerable number of unrealistic BP(SRTM) values were observed. Cluster analysis did not extract a valid reference region in 10% of the scans. Simulations showed that potentially cluster analysis suffers from negative bias in BP(PLASMA). Most anatomic regions outperformed cluster analysis in terms of absence of both scan rejection and bias. Total cerebellum is the optimal reference region in this patient category.     

Resistance of surface-dried virus to common disinfection procedures

It is believed that surface-dried viruses can remain infectious and may therefore pose a threat to public health. To help address this issue, we studied 0.1 N NaOH and 0.1% hypochlorite for their capacity to inactivate surface-dried lipid-enveloped (LE) [human immunodeficiency virus (HIV), bovine viral diarrhoea virus (BVDV) and pseudorabies virus (PRV)] and non-lipid-enveloped [NLE; canine parvovirus (CPV) and hepatitis A virus (HAV)] viruses in a background of either plasma or culture medium. In addition, 80% ethanol was tested on surface-dried LE viruses. Without treatment, surface-dried LE viruses remained infectious for at least one week and NLE viruses for more than one month. Irrespective of the disinfectant, inactivation decreased for viruses dried in plasma, which is more representative of viral contaminated blood than virus in culture medium. Inactivation by all disinfectants improved when preceded by rehydration, although the infectivity of CPV actually increased after rehydration and disinfection may thus be overestimated in the absence of rehydration. This is the first comprehensive study of five important (model) viruses in a surface-dried state showing persistence of infectivity, resistance to three commonly used disinfectants and restoration of susceptibility after rehydration. Our results may have implications for hygiene measurements in the prevention of virus transmission.