Inhibitory Fc Gamma Receptors: From Gene to Disease

Multiple lines of evidence have revealed a key role for inhibitory Fc gamma receptors class IIb (FcgammaRIIb) as negative modulators of innate and adaptive immune responses. Acquired and genetic factors regulate the expression of FcgammaRIIb receptors and modify their inhibitory potential. Recent advances have highlighted the importance of FcgammaRIIb receptors in influencing the development of cancer and autoimmunity. The association of increased FcgammaRIIb expression with tumor development is believed to operate at effector cell level resulting in inhibition of antitumor cytotoxicity. In autoimmune diseases, FcgammaRIIb receptors play a major role in controlling the amplitude of antibody- and immune complex-mediated reactions. Generally, FcgammaRIIb deficiency is associated with increased susceptibility and severity to organ-specific and systemic autoimmunity. This article discusses the proposed mechanisms for FcgammaRIIb deregulation associated with malignant and autoimmune pathology in animal models and human diseases.     

Vλ-light chain genes reconstitute immune responses to defined carbohydrate antigens or haptens by utilizing different VH genes

The contribution of the λ-light chain to the development of peripheral B cell repertoire and generation of specific antibodies to haptens and polysaccharide antigens was studied in genetically manipulated kappa-deficient and λ₂-transgenic mice. The results clearly demonstrate a non-stoichiometric V_H gene family expression in the absence of k-light chain and suggest a non-stochastic pairing between V_H and V_λ genes, expressed in the peripheral B cell repertoire. A shift in V_H gene utilization in the case of Vl_λ⁺ antibodies was evident in response to β2–6 fructosan and TNP hapten. These observations demonstrate the availability of compensatory mechanisms in the absence of V_K genes and are consistent with the hypothesis that V_H gene family expression is controlled by genetic factors from inside the V_H locus. Furthermore, genetic factors from outside the V_H locus, namely restricted available light chain diversity, may lead to a shift in V_H gene utilization in the peripheral B cell repertoire.     

Switching to darunavir/ritonavir 800/100 mg once‐daily containing regimen maintains virological control in fully suppressed pre‐treated patients infected with HIV‐1

The objective of this study was to evaluate the switch to once‐daily darunavir/ritonavir 800/100 mg in treatment‐experienced patients with suppressed HIV‐1 replication on a twice‐daily ritonavir‐boosted protease‐inhibitor (bid PI/r) containing regimen, that is in a setting where genotypic resistance test cannot be performed. In this open label, non‐comparative, multicenter study, patients on a bid PI/r‐containing triple combination, with suppressed viral replication, were switched to once‐daily darunavir/r 800/100 mg containing triple combination. The primary endpoint was the proportion of patients with plasma HIV‐RNA < 50 copies/ml 24 weeks after the switch. Intensive darunavir pharmacokinetic evaluation was performed at Week 4 (W4) in 11 patients. Eighty‐five patients were enrolled. All had HIV‐RNA < 50 copies/ml at screening with a pre‐exposure to a median of 2 PI/r (1–5). By intent‐to‐treat analysis (missing = failure), 78/85 patients (92%, 95% CI [83;96]) maintained an HIV‐RNA < 50 copies/ml at W24. Seven patients experienced protocol‐defined treatment failure between baseline and W24: Two had confirmed low‐level viral rebound, one discontinued study treatment for adverse event, three withdrew their consent, and one was lost to follow‐up. By on‐treatment analysis, 78/80 patients (97%, 95% CI [91;99]) maintained an HIV‐RNA < 50 copies/ml at W24. Results were similar at Week 48. The median area under the darunavir plasma concentration–time curve measured in 11 patients was 61,380 ng hr/ml; darunavir median trough concentration 1,340 ng/ml and darunavir half‐life was 12.2 hr. Tolerability of once‐daily darunavir/r 800/100 mg was excellent. Optimally suppressed, treatment‐experienced patients can switch safely from a twice‐daily PI/r regimen to a once‐daily darunavir/r 800/100 mg containing regimen. J. Med. Virol. 85:8–15, 2012. © 2012 Wiley Periodicals, Inc.     

Photomicrographic evaluation of the apical sealing capacity of three types of gutta-percha master cones: an in vitro study

The purpose of this study was to compare the apical sealing capacity of three types of gutta-percha master cones of the same apical size and different tapers following root canal preparation with nickel–titanium ProTaper Universal rotary instruments and microstructural replication with System B and Obtura III. Thirty extracted human incisors having one single straight root canal (type I Weine) were instrumented with rotary ProTaper to an F3 (30/.09) and gauged to confirm a final apical size of #30. Teeth were divided into three groups (n = 10) to be obturated as follows: Group 1: master cone Meta 0.06 taper/AH Plus, Group 2: master cone fine-medium Autofit 0.08 taper/AH Plus, and Group 3: master cone ProTaper F3 0.09 taper/AH Plus. The chosen technique was the continuous wave of compaction (System B and Obtura III). Teeth were embedded in acrylic and incrementally reduced at 0.5 and 1.0 mm from the apical foramina in a grinding machine for metallographic samples. Sections were examined and digitally photographed under a metallographic optical microscope in normal and polarized light and the images were processed. The total cross-sectional area of the root canal, the gutta-percha/sealer/voids’ areas were quantified for each sample and statistically compared using one-way ANOVA and Kruskal–Wallis tests. No statistically significant differences between groups were observed (P > 0.05); however, the mean percentage of the gutta-percha-filled area was slightly higher in Group 1 at both levels of observation. Despite different tapers, all the three types of cones provided a good sealing capacity in the last apical millimeter of the root canal, with good gutta-percha–sealer ratio and few or no voids.     

Cleft posterior mitral valve leaflet in an adult with turner syndrome diagnosed with the use of 3-dimensional transesophageal echocardiography

Turner syndrome is a monosomy (45,X karyotype) in which the prevalence of cardiovascular anomalies is high. However, this aspect of Turner syndrome has received little attention outside of the pediatric medical literature, and the entire spectrum of cardiovascular conditions in adults remains unknown.We present the case of a 34-year-old woman who had Turner syndrome. When she was a teenager, her native bicuspid aortic valve was replaced with a mechanical prosthesis. Fifteen years later, during preoperative examination for prosthesis-patient mismatch, severe mitral regurgitation was detected, and a congenital cleft in the posterior leaflet of the mitral valve was diagnosed with use of 3-dimensional transesophageal echocardiog-raphy. The patient underwent concurrent mitral valve repair and aortic valve replacement. To our knowledge, this is the first report of a cleft in the posterior mitral valve leaflet as a cardiovascular defect observed in Turner syndrome, and the first such instance to have been diagnosed with the use of 3-dimensional echocardiography.     

Surgical repair of atrial septal defect with severe pulmonary hypertension during pregnancy: a case report with literature review

We are reporting a case of a 37-year-old pregnant woman with a large secundum atrial septal defect with left-to-right shunt and severe pulmonary hypertension. Her atrial septal defect was undiagnosed before this pregnancy. After carefully considering all the options, we repaired her atrial septal defect with an open heart surgical closure at 20 weeks of gestation. A substantial and consistent reduction in pulmonary arterial pressure after the surgery and subsequent uneventful delivery indicate that surgical repair of atrial septal defects is a viable option that should be considered for such patients.     

Influence of inorganic filler content on the radiopacity of dental resin cements

Digital radiography was used to measure the radiopacity of 18 resin cements to determine the influence of inorganic filler content on radiopacity. Four disk specimens (n=4) of each light-curing cement were digitally radiographed alongside an aluminum step wedge using an intraoral sensor (XIOS Plus, Sirona, Germany), and their mean gray value measured. Percentage of filler by weight was determined using an analytical combustion furnace. Data were statistically analyzed using one-way ANOVA and Tukey's test (α=0.05). All materials were more radiopaque than dentin and 12 materials were more radiopaque than enamel. Filler percentage ranged between 17.36 to 53.56 vol% and radiopacity between 1.02 to 3.40 mm Al. There were no statistically significant differences in inorganic filler percentage and radiopacity among the different shades of the same material (p>0.05), but the highest radiopacity was measured for the material which contained a higher percentage of filler.     

Evaluation of cardiovascular events and progression to end-stage renal disease in patients with dyslipidemia and chronic kidney disease from the North-Eastern area of Romania

International Urology and Nephrology - The aim of this prospective cohort study was: to identify the association between different biomarkers [proprotein convertase subtilisin/kexin 9-PCSK9,...     

Engagement in care among youth living with parenterally-acquired HIV infection in Romania

ABSTRACT

Transition from adolescent to adult care can be challenging for youth living with HIV. We conducted a cohort study of youth born between 1985 and 1993 and infected with HIV parenterally, followed by the same medical team from age 15 years or first clinic visit until age 25 years or 30 November 2016. A longitudinal continuum-of-care was constructed, categorizing individuals’ status for each month of follow-up as: engaged in care (EIC); not in care (NIC: no clinic visits within past year); lost-to-follow-up (LTFU: NIC and did not return to clinic); or died. Five hundred and forty-five individuals (52% male) were followed for 4775 person-years. At age 15, 92% were EIC, decreasing to 84% at age 20 and 74% at age 25. Of those EIC, HIV outcomes improved with age: 79% and 52% had a CD4 ≥200 cells/µl and VL <400 cps/ml at age 15; increasing to 86% and 73% at age 20 and 87% and 80% at age 25. We conclude that youth infected during early childhood tended to disengage from care, even when followed by the same medical team for a lengthy period of time. For those that did engage in care, HIV-related outcomes improved from adolescence through adulthood.