HIV-1 matrix protein p17 enhances the proliferative activity of natural killer cells and increases their ability to secrete proinflammatory cytokines

We investigated the effects of human immunodeficiency type-1 virus (HIV-1) matrix protein p17 on freshly isolated and purified human natural killer (NK) cells. HIV-1 p17 increased the cytokines interleukin (IL) 2, IL-12 and IL-15, and induced natural killer cell proliferation, but not cytotoxicity. This effect was specific because it was abrogated by anti-p17 monoclonal antibody. Moreover, HIV-1 p17 enhanced the cytokine-induced production of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma by NK cells. IL-4 downregulated IFN-gamma and TNF-alpha secretion in IL-2- and IL-15-treated NK cells. HIV-1 p17 restored the ability of NK cells to produce both cytokines when added to the cultures simultaneously with IL-4. The property of p17 to increase the production of TNF-alpha and IFN-gamma might be a mechanism used by HIV-1 to modulate the immune system to support its replication and spreading.     

Allergy and skin diseases in musicians

In order to define a standard diagnostic protocol for managing allergic dis-eases in musicians, we conducted a literature search on this topic. The most frequent allergic disease in this special category of workers was contact dermatitis, always described in stringed and wind instruments players, involving the mouth and the hands. No other allergic disease directly related to musical instruments was reported. The most frequently reported culprit substances were: colophony, exotic woods, nickel sulphate, varnishes, and propolis (bee glue). Thus, being contact dermatitis the most frequent disease, a correct diagnostic approach to this problem in musicians should involve, in addition to clinical history and examination, the patch test with a specific panel of substances. Finally, allergy in musicians involves additional problems: the virtual impossibility to avoid the offending substance, and the poor adherence to therapy due to lifestyle. In general, this specific allergologic problem seems to be underestimated, underdiagnosed and, as a conquence, poorly managed.     

p16INK4A and p15INK4B gene deletions in primary leukemias

The 9p21 locus has been deleted at a high frequency in a wide variety of tumors. Recently, two genes, p16INK4A and p15INK4B (also called MTS1 and MTS2), have been localized in close proximity at the 9p21 locus, encoding cyclin-dependent kinases 4/6 inhibitors of relative molecular mass 16 kD and 15 kD, respectively and also found to be deleted at a high frequency in tumor cell lines. We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses. The ALL cases showed a relatively high frequency of homozygous deletions (22%, 6 of 27) at the p16INK4A gene locus. Interestingly, of the six cases with p16INK4A homozygous deletions, only three showed homozygous deletions at the p15INK4B gene. In 81 CLL patients, we detected one homozygous and five heterozygous deletions at both the p16INK4A and p15INK4B genes and two heterozygous deletions at the p16INK4A gene alone. Deletion of these two genes in AML cases is relatively low (9%). We did not detect deletions in any of the MDS, HCL, and CML cases examined. Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases. The data presented in this report showed that (1) p16INK4A and p15INK4B genes are preferentially deleted homozygously in ALL and heterozygously in CLL cases with frequent mutation in the second allele, and (2) p16INK4A gene appears to be more frequently deleted than p15INK4B gene.     

The effect of changes in primary attending doctor coverage frequency on orthodontic treatment time and results

Objective:To determine whether changes in primary attending (PA) doctor coverage frequency caused an increase in orthodontic treatment time or a decrease in the quality of treatment results in a postgraduate orthodontic clinic. The effect of T1 Peer Assessment Rating (PAR) scores on PA doctor coverage frequency, treatment times, and results was also evaluated.Materials and Methods:A sample of 191 postorthodontic subjects was divided into three groups based on PA doctor coverage (high, medium, or low). Treatment times, treatment results, and other variables were compared between the three PA coverage groups. Additionally, the sample was divided into three groups based on T1 PAR scores. Attending coverage frequency, treatment times, and results were compared between the T1 PAR groups.Results:No statistically significant differences were found in treatment time (P  =  .128) or results (P  =  .052). There were no statistically significant differences in the mean scores for T1 PAR (P  =  .056), T2 PAR (P  =  .602), patient age at T1 (P  =  .747), total appointments (P  =  .128), missed appointments (P  =  .177), or cancelled appointments (P  =  .183). Statistically significant differences were found between the low T1 PAR group and the medium and high T1 PAR groups (attending coverage, P  =  .008; results, P < .001; treatment time, P  =  .001).Conclusions:Under the conditions of this study, variations in PA doctor coverage frequency did not lengthen orthodontic treatment or reduce the quality of treatment results. Low T1 PAR scores were associated with less PA coverage, less change in PAR, and shorter treatment times.     

Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation

Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 μg/d for 3 months and then uptitrated to 2 µg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8–152.0) to 63.3 (52.0–79.7) pg/ml (P<0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P<0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P<0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P<0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P<0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Long-term studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.     

Independent and additional prognostic value of aminoterminal propeptide of type III procollagen circulating levels in patients with chronic heart failure

BACKGROUND: In chronic heart failure (CHF), changes in the extracellular space contribute to cardiac dysfunction. We aimed to determine whether aminoterminal-propeptide of type III procollagen (PIIINP), a marker of extracellular matrix turnover, might provide prognostic information in CHF patients. METHODS AND RESULTS: A total of 101 consecutive CHF patients (mean age 61.7 +/- 8.7 years, 88% males) were followed up between 1999 and 2001. The combined endpoint of the study was death and hospitalization for heart failure. During follow-up there were 15 deaths and 11 hospitalizations for worsening heart failure. At the survival analysis, age (P = .02), New York Heart Association class (P = .014), s-creatinine (P = .014), plasma-PIIINP (p-PIIINP) levels (P = .005), left ventricular ejection fraction (LVEF) (P = .0002), and a restrictive mitral filling pattern (P = .0003) predicted event-free survival. At the multivariate analysis, p-PIIINP levels predicted outcome independently of other clinical variables, hormones, and echocardiographic and exercise testing variables (P < .05 in all models). In patients with LVEF <31%, the presence of p-PIIINP >4.7 microg/L levels was significantly associated with a higher risk of death and hospitalization as compared with the other patients (event-free survival rate at 12 months: 45% versus 95%; at 24 months: 27% versus 88%; at 36 months: 18% versus 85%, P < .0001). CONCLUSIONS: In patients with CHF, PIIINP levels predict outcome independently of clinical status, hemodynamics and hormonal activation. PIIINP levels provide additional prognostic information to that of left ventricular function alone, suggesting that it may reflect more than cardiac extracellular matrix turnover.