Air particulate matter SRM 1648a primes macrophages to hyperinflammatory response after LPS stimulation

Objective

Exposure to air particulate matter (PM) is associated with chronic inflammatory and autoimmune diseases. Macrophages are responsible for the regulation of chronic inflammation. However, whether PM affects macrophage polarization remains unclear. The aim of this study was to evaluate whether nontoxic concentrations of urban PM are able to prime macrophages to altered inflammatory response upon LPS challenge.

Methods

We used two forms of the urban particulate matter SRM 1648a, intact PM and PM deprived of organic compounds (PM?C). Peritoneal murine macrophages were exposed to different concentrations of PM for 24 h and then challenged with LPS. Production of inflammatory mediators by macrophages was measured to test immunostimulatory/priming capacity of PM.

Results

Particulate matter used at non-cytotoxic concentrations induced a dose-dependent production of proinflammatory cytokines (TNF-α, IL-6, IL-12p40). By contrast, PM?C were not able to stimulate macrophages. However, macrophages primed with both forms of PM show proinflammatory response upon LPS challenge.

Conclusions

Our data indicate that exposure of macrophages to low concentrations of PM may prime the cells to hyperinflammatory response upon contact with LPS. Further studies are necessary to explain whether the exposure of patients suffering from chronic inflammatory diseases to particulate matter is responsible for the exacerbation of clinical symptoms during bacterial infections.

     

Discussions and decisions of the 2012–2014 International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group,January 2012–June 2013

The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group prepares proposals on the classification and nomenclature of filoviruses to reflect current knowledge or to correct disagreements with the International Code of Virus Classification and Nomenclature (ICVCN). In recent years, filovirus taxonomy has been corrected and updated, but parts of it remain controversial, and several topics remain to be debated. This article summarizes the decisions and discussion of the currently acting ICTV Filoviridae Study Group since its inauguration in January 2012.     

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in invasive breast cancer in women

Introduction

Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression are crucial in the biology of breast carcinoma. HER-2/neu gene is amplified and overexpressed in 15-30% of invasive breast cancers. HER-2-positive breast cancers have worse prognosis than HER-2 negative tumors and possess distinctive clinical features. The aim of this study was to assess the expression of HER2 in cancer tissue of patients with invasive breast cancer in correlation with tumor type, histological grade, tumor size, lymph node status, and expression of estrogen receptor and progesterone receptor.

Material and methods

Formalin-fixed, paraffin-embedded tissues from 40 patients with invasive HER-2-positive breast cancer and from 191 patients with HER-2-negative breast cancer were used in this study. HER2 expression was determined using the test HerceptTest™ DAKO.

Results

Among 231 cases of breast cancer, 18 invasive lobular carcinomas and 213 invasive ductal carcinomas were diagnosed. Sixty percent of HER-2-positive breast cancers were ER-positive compared with 77% in the HER-2-negative group (p = 0.002). The expression of PR was observed in 43% of HER-2-positive breast cancers and in 72% of HER2-negative tumors (p = 0.003). Excessive expression of HER2 protein was detected in 60% of patients positive for estrogen receptors, which may worsen prognosis in these patients.

Conclusions

Determination of HER2 overexpression in breast cancer patients, allows for a determination of a group of patients with a worse prognosis.     

Znaczenie modyfikacji epigenetycznych w patogenezie białaczek

Relations between genetic alterations and different types of leukemia lead to understanding that leukemogenesis is a mainly genetic-based phenomenon. However recently role of factors of epigenetic nature is highlighted in research on oncogenic transformation. Epigenetic regulation is defined as heritable patterns that are not related to DNA sequence. There are three major forms of epigenetic regulation: DNA methylation, histone modifications – methylation and acetylation – and regulation through small non-coding RNAs. Epigenetic regulation is important in development of different types of leukemia. Changes in DNA methylation patterns as well as in histone methylation and acetylation were detected in samples from patients with leukemia. In addition different profiles of miRNA, one subtype of noncoding RNAs, were associated with this disease. What is more, alteration in activity of enzymes involved in regulation of DNA and histone modification can also be detected in leukemic cells. Current knowledge of epigenetic regulation allows for better diagnostic of leukemia and better understanding of mechanism involved in its therapy. It also allowed for development of new forms of therapies targeted specifically on mechanisms involved in epigenetic regulation.     

CD38 gene polymorphisms and genetic predisposition to multiple myeloma

Single nucleotide polymorphisms (SNPs) of adhesion and signaling genes may influence the etiopathogenesis of multiple myeloma (MM). CD38 molecule and its ligand CD31 are expressed and interact in malignant plasma cells and MM microenvironment. In this study we evaluated allele frequencies and distribution of two potentially functional CD38 SNPs, intronic rs6449182 (184C>G) and missense rs1800561 (418C>T, Arg¹⁴⁰Trp) in 175 Caucasian patients with MM and 207 healthy blood donors. The carriers of variant G allele of the rs6449182 SNPs were found to have significantly elevated risk of MM as compared to non-carriers; odds ratio = 5.69 (95% confidence interval = 3.7–8.7), p < 0.0001. In contrast, rs1800561 SNP minor T allele was detected at very low and comparable frequencies in patients and controls groups. In conclusion, our data suggest that inherited genetic variation in CD38 gene may impact on the risk of MM development.     

Executive function in XXY: Comparison of performance‐based measures and rating scales

Few studies have systematically assessed executive functioning (EF) skills in boys with XXY, and these are limited by small samples and restricted EF assessment. This study used a broader battery of performance‐based measures as well as parent‐rating scales of EF in 77 boys and adolescents with XXY (mean age = 12.5 years), recruited from a clinical trial and an outpatient clinic. Exploratory factor analyses were used to create EF domains from performance‐based measures, and similar domains were measured using the Behavior Rating Inventory of Executive Function and Conners Parent‐Rating Scales. The boys with XXY showed a distinct EF profile, with the greatest deficit in attention and more moderate deficits in working memory, switching, and planning/problem solving. Parent ratings showed similar challenges, as well as impaired inhibition. Independent sample t‐tests showed no difference on performance measures between boys diagnosed or not diagnosed with attention‐deficit/hyperactivity disorder (ADHD), although parents of boys diagnosed with ADHD reported more difficulties. There were no differences on performance‐based tests between those diagnosed pre‐ and postnatally, although parents of postnatally diagnosed boys reported more metacognitive problems. Language deficits, cognition, and socio‐economic status did not account for EF deficits.     

Regional distribution of antibodies to herpes simplex virus type 1 (HSV-1) and HSV-2 in men and women in Ontario,Canada

This study estimated the regional and age- and gender-specific seroprevalences of herpes simplex virus type 1 (HSV-1) and HSV-2 in Ontario, Canada. Stored serum specimens from subjects aged 15 to 44 years, including men (n = 979), women not under prenatal care (n = 638), and women under prenatal care (n = 701) submitted for routine viral serology were randomly selected according to regional population size from public health laboratories. HSV-1 and HSV-2 testing was done with the MRL enzyme immunoassay (EIA) (Focus Technologies), and HSV-2 was also tested by the Gull/Meridian EIA. Specimens discordant for HSV-2 antibodies between the two EIAs were resolved by a recombinant immunoblot assay (Focus Technologies). The overall age- and gender-standardized seroprevalences of HSV-1 and HSV-2 were 51.1% (95% confidence interval [CI], 50.1 to 52.1) and 9.1% (95% CI, 8.6 to 9.7), respectively. The seroprevalence of HSV-1 antibodies increased from 26.9 to 54.7% in men between 15 to 16 and 40 to 44 years of age, from 32.0 to 88.7% in women not under prenatal care, and from 55.2 to 69.2% in women under prenatal care. The seroprevalence of HSV-2 increased from 3.8 to 21.3% in men between 15 to 16 and 40 to 44 years of age, from 0 to 18.9% in women not under prenatal care, and from 3.4 to 23.1% in women under prenatal care. HSV-2 results were discordant for 3.3% (76 of 2,318) of specimens. Both types of HSV antibodies appeared to be acquired earlier among women under prenatal care than among men and women not under prenatal care. Antibodies were more prevalent among people in northern Ontario (72.9% of subjects [range, 68.4 to 77.4%] for HSV-1 and 13.7% of subjects [95% CI, 10.2 to 17.2%] for HSV-2) than elsewhere.     

BRCA1 and BRCA2 mutation analysis in breast-ovarian cancer families from northeastern Poland

Sixty high-risk breast and/or ovarian cancer families from North-Eastern Poland were screened for germline mutations in BRCA1 (MIM# 113705) and BRCA2 (MIM# 600185), using a combination of protein truncation test, denaturing high-performance liquid chromatography and direct sequencing. Sixteen (27%) of the families were found to carry nine different BRCA mutations, including 14 families with BRCA1 mutation and two families with BRCA2 mutation. The results suggest the presence of two strong BRCA1 founder mutations in the Polish population - 5382insC (6 families) and 300T>G (Cys61Gly; 3 families). The remaining seven mutations were found in single families and included three previously reported BRCA1 mutations (185delAG, 2682C>T [Gln855Ter] and 3819del5), a novel BRCA1 mutation (IVS14+1G>A), as well as two BRCA2 mutations (4088delA and 7985G>A [Trp2586Ter]) not previously observed in Polish families. We confirm the strong influence of two Central-Eastern European BRCA1 founder mutations in familial breast and/or ovarian cancer in Poland. We also conclude that the Polish population has a more dispersed BRCA mutation spectrum than had been earlier thought. This warrants further careful BRCA mutation screening in order to optimise genetic counselling and disease prevention in affected families.     

Unaffected patients with a homozygous absence of the SMN1 gene

In this report, we present three families in which we identified asymptomatic carriers of a homozygous absence of the SMN1 gene. In the first family, the bialleleic deletion was found in three of four siblings: two affected brothers (SMA type 3a and 3b) and a 25-years-old asymptomatic sister. All of them have four SMN2 copies. In the second family, four of six siblings are affected (three suffer from SMA2 and one from SMA3a), each with three SMN2 copies. The clinically asymptomatic 47-year-old father has the biallelic deletion and four SMN2 copies. In the third family, the biallelic SMN1 absence was found in a girl affected with SMA1 and in her healthy 53-years-old father who had five SMN2 copies. Our findings as well as those of other authors show that an increased number of SMN2 copies in healthy carriers of the biallelic SMN1 deletion is an important SMA phenotype modifier, but probably not the only one.