Characterization of FcepsilonRI-bearing CD123 blood dendritic cell antigen-2 plasmacytoid dendritic cells in atopic dermatitis

BACKGROUND: The high-affinity receptor for IgE (FcepsilonRI) on myeloid dendritic cells has been shown to play a major role in atopic dermatitis (AD). Plasmacytoid dendritic cells (pDCs), which are instrumental in the defense of viral infections, are present in reduced amounts in the skin of patients with AD, which is characterized by a high susceptibility to viral infections. OBJECTIVE: We explored phenotypical and functional characteristics of pDC in the peripheral blood of patients with AD and healthy individuals. METHODS: Blood dendritic cell antigen-2+CD123+ pDCs were enriched from the peripheral blood of patients with AD and studied in functional assays. RESULTS: Skin-homing molecules such as cutaneous lymphocyte antigen and L-selectin CD62L were expressed in lower levels on pDCs of patients with AD. pDCs expressed high amounts of IgE-occupied FcepsilonRI. Further, FcepsilonRI aggregation on pDCs impaired the surface expression of MHC I and II, induced the production of IL-10, and enhanced the apoptosis of pDCs. Importantly, FcepsilonRI preactivated pDC produced less IFN-alpha and IFN-beta after stimulation with CpG motifs and enhanced the outcome of immune responses of the TH2 type. CONCLUSION: From these data, we conclude that FcepsilonRI-bearing pDCs from patients with AD (1) are different from pDCs of healthy individuals, (2) might be important in the pathophysiology of AD, and (3) contribute to the enhanced susceptibility of patients with AD to viral infections.     

Morphological and morphometric characteristics of choroid plexus psammoma bodies during the human aging

Psammoma bodies are one of many choroid plexus aging changes which origin is still enigma for the scientists. During our investigation psammoma bodies were studied on 30 postmortem brains by light microscopy. They stained red with HE, and were PAS and AB PAS positive. The largest number of lamellas were stained blue with Mallory's connective tissue stain, except peripheral and next to the center lamella which stained red. During the aging, psammoma bodies became larger and more irregular, which was followed with group area and perimeter, single psammoma body average area and average perimeter, average diameter and contour index increase. Psammoma bodies mearged in the second and the third age group and mearging process led to larger and more irregular structures formation. The results of this investigation suggest that psammoma bodies are more frequent in choroid plexus of healthy older people and during the aging they obtain larger dimensions, more irregular contours, which is the result of their mutual mearging.     

Hemodialysis Treatment in Patients with Balkan Endemic Nephropathy: An Epidemiological Study

Aim. To analyze hemodialysis (HD) treatment of patients with Balkan endemic nephropathy (BEN) from five endemic villages in the South Morava Region of Serbia. Analyses of patterns of incidence may generate hypotheses about the underlying causes of BEN, and prevalence data provide information on the current and likely future burden on health services for managing BEN. Methods. A total of 143 end-stage kidney disease patients (ESKD) with BEN were admitted to the renal replacement program from 1974 to 2004: 121 to HD, 15 peritoneal dialysis, and 7 kidney transplantation. As a control group, 117 patients with other kidney disease (chronic pyelonephritis, glomerulonephritis, and ischemic nephropathy) admitted to HD at the time of BEN patients and matched by age and gender were studied. Results. Most of the BEN patients (93.4%) treated by HD were born from 1917 to 1941. The majority of patients (79.3%) started HD from 1977 to 1991 (period of 15 years). The mean age of BEN patients starting HD treatment was 49.1 years in the period from 1974 to 1978, and increased steadily in the following years, being 72.5 years in the last period of study (2004–2006) The mean survival time of BEN males was 4.70 (95% CI 3.66–5.75) and for females was 5.02 (95% CI 1.47–4.53). Difference between males and females was not statistically significant (log rank 0.14, p?=?0.7, P > 0.5). Mean survival times of 4.84 (95% CI 3.97–5.70) in BEN patients and 3.1 (95% CI 2.78–3.84) in other kidney disease patients were found. Difference between BEN patients and controls was statistically significant (log rank 8.38, p?=?0.0038, P < 0.01). Conclusion. The population of endemic villages around the South Morava River admitted to HD treatment after 1974 was exposed to environmental toxicant(s) from 1917 to 1941. The most intense effect of environmental exposure was in that period, with ESKD in patients in their forties. The exposure to environmental toxicants has diminished, so ESKD of BEN has become less frequent and manifested in the older age, mean 72.5 in the period from 2004 to 2006. Different type of exposure was registered in some other endemic regions in Serbia and abroad.     

Myocardial fibrosis is associated with biventricular dysfunction in patients with hypertrophic cardiomyopathy

Aims: To assess left (LV) and right ventricular (RV) function by two‐dimensional (2D) speckle tracking echocardiography and its relation to myocardial fibrosis in hypertrophic cardiomyopathy (HCM). Methods: We enrolled 50 HCM patients (30 male; 47.3 ± 9.9 years) in our study. Each patient received echocardiography with modern high‐end scanners. For speckle tracking analysis of LV and RV function the dedicated software was used. The presence of myocardial fibrosis was detected by cardiac magnetic resonance imaging (MRI). Results: For intraobserver variability of RV global longitudinal strain, we found a correlation of r = 0.89 (p < 0.001) with a minor bias of 4.9 ± 2.9%. On cardiac MRI 30 patients (60%) demonstrated late gadolinium‐enhancement (LGE) of the LV. Of these patients only 7% showed LGE of the RV. HCM patients with myocardial fibrosis had less global longitudinal LV strain in comparison to patients without myocardial fibrosis (?12.8 ± 2.2 vs ?21.1 ± 2.6, P < 0.001), thicker interventricular septums (23.7 ± 4.0 vs 19.2 ± 5.1, P < 0.001), larger left atria (34.9 ± 7.1 vs 23.9 ± 5.1, P < 0.001), and impaired diastolic function (E/A‐ratio: 1.02 ± 0.22 vs 1.15 ± 0.18, P < 0.01). Comparable results were found for RV function. LV and RV strain correlated with r = 0.85 (p < 0.001). Conclusions: HCM is not only a disease of the LV. LGE in HCM is associated with both LV and RV dysfunction. Although RV LGE occurs only in a minority of patients with HCM and LV fibrosis, speckle tracking echocardiography is feasible for evaluating LV and RV dysfunction in these patients. (Echocardiography 2012;29:438‐444)     

Topographic Distribution and Progression of Soft Drusen Volume in Age-Related Macular Degeneration Implicate Neurobiology of Fovea

PurposeTo refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated topographic distribution and growth rates of drusen by optical coherence tomography (OCT). We compared results to retinal features with similar topographies (cone density and macular pigment) in healthy eyes.MethodsIn a prospective study, distribution and growth rates of soft drusen in eyes with AMD were identified by human observers in OCT volumes and analyzed with computer-assistance. Published histologic data for macular cone densities (n = 12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n = 31; 62 paired eyes, averaged) were revisited. All values were normalized to Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas.ResultsSixty-two eyes of 44 patients were imaged for periods up to 78 months. Soft drusen volume per unit volume at baseline is 24.6-fold and 2.3-fold higher in the central ETDRS subfield than in outer and inner rings, respectively, and grows most prominently there. Corresponding ratios (central versus inner and central versus outer) for cone density in donor eyes is 13.3-fold and 5.1-fold and for MPOD, 24.6 and 23.9-fold, and 3.6 and 3.6-fold.ConclusionsNormalized soft drusen volume in AMD eyes as assessed by OCT is ≥ 20-fold higher in central ETDRS subfields than in outer rings, paralleling MPOD distribution in healthy eyes. Data on drusen volume support this metric for AMD risk assessment and clinical trial outcome measure. Alignment of different data modalities support the ETDRS grid for standardizing retinal topography in mechanistic studies of drusen biogenesis.     

Progression of Kidney Damage in Balkan Endemic Nephropathy: A 15-Year Follow-Up of Patients with Kidney Biopsy Examination

Progression of kidney damage was studied in 18 patients with Balkan endemic nephropathy (BEN), with a mean 15-year follow-up after renal biopsy. According to kidney function, estimated by ^99mTc-DTPA clearance, patients were divided into three groups: with apparently normal kidney function (clearance 103.5 ± 21.3 mL/min/1.73 m²), with incipient renal failure (clearance 65.5 ± 11.3), and with advanced renal failure (clearance 28.0 ± 6.2). The mean yearly decrease of glomerular filtration rate was 2.74 mL/min. In two patients, an increase of kidney function was recorded. Six patients become dialysis dependent, two from the group with incipient renal failure, but all four from the group with advanced renal failure. Three patients died after 8 to 12 years of follow-up, one from causes unrelated to kidney disease and two from end-stage renal failure. This study has shown that BEN is characterized by a slow course and prolonged evolution, modified by medical supervision and treatment.     

Isolation,biochemical characterization and anti-bacterial activity of BPIFA2 protein

Objective

Human BPIFA2 (parotid secretory protein) is a ubiquitous soluble salivary protein, which belongs to the PLUNC family of proteins. Having sequence similarity to bactericidal/permeability-increasing protein and lipopolysaccharide-binding protein, PLUNC proteins are probably involved in local antibacterial response at mucosal sites, such as oral cavity. The aim of the study was to isolate and characterize human BPIFA2.

Design

In this paper, we report one-step affinity chromatography method for BPIFA2 purification from whole human saliva. The isolated BPIFA2 was identified by trypsin mass fingerprinting and characterized by electrophoretic methods. Antibacterial activity of BPIFA2 against model microorganism Pseudomonas aeruginosa was shown in minimum inhibitory concentration and time kill study assays.

Results

The protein showed microheterogeneity, both in molecular weight and pI value. BPIFA2 inhibited the growth of P. aeruginosa in microgram concentration range determined by minimum inhibitory concentration assay. In the time kill study, 32 μg/mL BPIFA2 showed clear bactericidal activity and did not cause any aggregation of bacteria.

Conclusion

Affinity chromatography is well suited for isolation of functional BPIFA2 with a potent bactericidal activity against P. aeruginosa.