Pentraxin 3 (PTX3) inhibits plasma cell/stromal cell cross‐talk in the bone marrow of multiple myeloma patients

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that binds with high affinity and selectivity to fibroblast growth factor‐2 (FGF2), thus inhibiting its pro‐angiogenic activity. Here we investigated the effects of PTX3 on monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patient‐derived bone marrow (BM) plasma cells (PCs), endothelial cells (ECs), and fibroblasts (FBs), and assessed whether PTX3 can modulate the cross‐talk between PCs and those microenvironment cells. PTX3 and FGF2 expression was evaluated by ELISA. Functional studies, including cell viability, wound healing, chemotaxis, and Matrigel^® assays, were performed on MGUS and MM ECs and FBs upon the PTX3 treatment. Through western blot PTX3‐induced modulation in FGF2/FGF receptor signalling pathways was evaluated in MGUS and MM ECs and FBs through western blot. Co‐cultures between MM ECs/FBs and human PC lines were used to evaluate possible PTX3 indirect effects on MM PCs. Adhesion molecules were studied by flow cytometry. PTX3 provides a direct time‐ and dose‐dependent apoptotic effect on MM ECs and FBs, but not on either MM primary PCs or human PC lines. PTX3 inhibits migration of MM ECs and FBs in a dose‐dependent manner, and impacts in vitro and in vivo FGF2‐mediated MM angiogenesis. Co‐cultures of PCs and ECs/FBs show that PTX3 treatment indirectly impairs PC viability and adhesion. We conclude that PTX3 is an anti‐angiogenic factor in MM and behaves as a cytotoxic molecule on MM cells by inhibiting the cross‐talk between PCs and ECs/FBs. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Letter to the editors: comment on “Emerging themes in idiopathic intracranial hypertension”

Journal of Neurology -     

Non-Epstein–Barr virus associated lymphoepithelioma-like carcinoma of the esophagogastric junction with microsatellite instability,K-ras wild type

A 60-year-old male was admitted to our hospital for gastric cancer. Considering his general condition, total gastrectomy and dissection of regional lymph nodes were performed. Macroscopically, a 45 mm × 20 mm × 10 mm-sized, ulcero-infiltrative tumor located in the esophagogastric junction was described. Microscopically, the tumor consisted of a poorly differentiated adenocarcinoma intermingled with dense lymphoid infiltration predominantly composed of T-cell lymphocytes. The tumor cells infiltrated the submucosa, muscularis and subserosal layers of the stomach, respectively the esophageal adventitia. No metastases were noticed in the 58 regional lymph nodes. Based on the histopathological features, the diagnosis was lymphoepithelioma-like carcinoma, pT3N0 stage. In situ hybridization for Epstein–Barr virus showed no nuclear signal in tumor cells. The p53 expression was observed in fewer than 10% of the tumor cells. Real-time PCR analysis showed microsatellite instability without K-ras mutation in codon 12. No recurrences or metastases were reported 6 months after surgical intervention. No adjuvant therapy was performed.     

Genetic parameters and allele frequencies of five new European Standard Set STR loci (D10S1248, D22S1045, D2S441, D1S1656, D12S391) in the population of Romania

Aim

To establish allele frequencies and genetic parameters for 5 new European Standard Set short tandem repeat (STR) loci in the population of Romania and to compare them with those in other populations.

Methods

DNA was isolated using QIAamp 96 DNA Swab BioRobot Kit and Chelex 100 methods. Polymerase chain reaction amplification was done using Investigator ESSplexPlus Kit (D1S1656, D2S441, D2S1338, D3S1358, D8S1179, D10S1248, D12S391, D16S539, D18S51, D19S433, D21S11, D22S1045, FGA, TH01, and vWA). For DNA typing, Applied Biosystems 3500/3500xL Genetic Analyzer was used. Statistical analysis was done using Powerstats, GDA, and Arlequin software.

Results

Power of discrimination and polymorphism information content was highest for two new ESS loci, D1S1656 and D12S391. Comparison of allele frequencies for 5 new ESS loci in Romanian population with previously published population data showed significant differences for all compared populations, with the exception of Hungary. Geographically more distant populations, such as Spain, Sweden, United Kingdom, Germany, and Portugal differed more than closer populations.

Conclusion

New ESS STR loci are very useful for the analysis of forensic samples (persons or traces) due to their characteristics (shortness and high polymorphism). In comparisons with other common STR markers, they have a higher power of discrimination and also higher polymorphism information content, and could be used in any national DNA database.The establishment of standard sets (or common sets) of short tandem repeat (STR) markers which had first been a necessity for the forensic scientific community, as a result of globalization became a necessity for the worldwide law enforcement agencies. STR markers standard sets facilitate communication and judicial transmission of the forensic DNA typing results between different forensic groups or countries (1).Although several STR sets have been proposed (2), three of them are most frequently used: Interpol Standard Set of Loci – ISS (FGA, TH01, VWA, D3S1358, D8S1179, D18S51, D21S11), US Core Loci – CODIS (CSF1PO, FGA, TH01, TPOX, VWA, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11), and European Standard Set of Loci – ESS (D3S1358, VWA, D8S1179, D21S11, D18S51, TH01, FGA, D1S1656, D2S441, D10S1248, D12S391, D22S1045).The five new European Standard Set STR loci studied in Romanian population are an upgrade of an earlier version of ESS consisiting of 7 STRs (3), adopted by the European Council in 2001. The DNA Working Group of the European Network of Forensic Science Institutes (ENFSI) reviewed the usefulness of the ESS in light of the increased exchange of DNA analysis results in 2009 and recommended the expansion with 5 new ones (4).Romania adopted the new 5 ESS loci and started to use them at the national level at the beginning of 2012 as part of the Investigator ESSplex Plus Kit, which replaced the AmpFlSTR Identifiler PCR Amplification Kit used before for Romanian National DNA Database supplying. As a consequence, and due to the lack of any study involving D10S1248, D22S1045, D2S441, D1S1656, and D12S391 loci in the Romanian population, allele distribution and genetic parameters of these loci have to be determined. The aim of this study was to establish allele frequencies and genetic parameters for 5 new ESS loci in population of Romania and to compare them with those in other populations .     

The nonsense mutation stop+4 model correlates with motor changes in Duchenne muscular dystrophy

The aim was to assess 3-year longitudinal data using 6MWT in 26 ambulant boys affected by DMD carrying nonsense mutations and to compare their results to other small mutations. We also wished to establish, within the nonsense mutations group, patterns of change according to several variables. Patients with nonsense mutations were categorized according to the stop codon type newly created by the mutation and also including the adjacent 5′ (upstream) and 3′ (downstream) nucleotides. No significant difference was found between nonsense mutations and other small mutations (p > 0.05) on the 6MWT. Within the nonsense mutations group, there was no difference in 6MWT when the patients were subdivided according to: Type of stop codon, frame status of exons involved, protein domain affected. In contrast, there was a difference when the stop codon together with the 3′ adjacent nucleotide (“stop+4 model”) was considered (p < 0.05) with patients with stop codon TGA and 3′ adjacent nucleotide G (TGAG) having a more rapid decline. Our finding suggest that the stop+4 model may help in predicting functional changes. This data will be useful at the time of interpreting the long term follow up of patients treated with Ataluren that are becoming increasingly available.     

Early outcomes of migraine after erenumab discontinuation: data from a real-life setting

Neurological Sciences - Monoclonal antibodies targeting the calcitonin gene-related peptide, including erenumab, are migraine-specific preventive treatments, whose long-term effectiveness has still...     

Anxiety,depression, and quality of life in Parkinson’s disease: the implications of multidisciplinary treatment

Anxiety and depression in Parkinson’s disease (PD) reduce well-being of the patients. Emotional alterations influence motor skills and cognitive performance; moreover, they contribute significantly and independently to worsen rehabilitative treatment response. We investigated anxiety, depression, and quality of life in PD patients subjected to multidisciplinary rehabilitative training. The self-controlled study included 100 PD patients (49 males and 51 females with the mean age of 64.66 years) admitted to 60 days hospitalization rehabilitative program, between January 2017 and December 2018. Motor, cognitive, linguistic abilities, and functional independence were evaluated at admission (T0 baseline visit) and 60 days after (T1) the multidisciplinary rehabilitation including motor exercises, speech therapies, and cognitive intervention. The multidisciplinary rehabilitation improved functional status in PD patients and exerted its positive effects on mood, motor abilities, autonomy in the activities of daily life, perception of quality of life, cognitive performance and speech skills. Non-motor symptoms may worsen severe disability and reduce quality of life. They are often poorly recognized and inadequately treated. Nonetheless, multidisciplinary rehabilitative training represents an optimal strategy to improve disease management. The study was approved by Istituito di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro Neurolesi “Bonino-Pulejo” Ethical Committee (approval No. 6/2016) in June 2016.