31 research outputs found
Bruton's tyrosine kinase regulates TLR7/8-induced TNF transcription via nuclear factor-κB recruitment
Tumour necrosis factor (TNF) is produced by primary human macrophages in response to stimulation by exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) via Toll-like receptor (TLR) signalling. However, uncontrolled TNF production can be deleterious and hence it is tightly controlled at multiple stages. We have previously shown that Bruton's tyrosine kinase (Btk) regulates TLR4-induced TNF production via p38 MAP Kinase by stabilising TNF messenger RNA. Using both gene over-expression and siRNA-mediated knockdown we have examined the role of Btk in TLR7/8 mediated TNF production. Our data shows that Btk acts in the TLR7/8 pathway and mediates Ser-536 phosphorylation of p65 RelA and subsequent nuclear entry in primary human macrophages. These data show an important role for Btk in TLR7/8 mediated TNF production and reveal distinct differences for Btk in TLR4 versus TLR7/8 signalling
Dendritic and T Cell Response to Influenza is Normal in the Patients with X-Linked Agammaglobulinemia
Introduction Influenza virus is a potential cause of severe disease in the immunocompromised. X-linked agammaglobu-linemia (XLA) is a primary immunodeficiency characterized by the lack of immunoglobulin, B cells, and plasma cells, secondary to mutation in Bruton’s tyrosine kinase (Btk) gene
Fungal Planet description sheets: 1042-1111
Novel species of fungi described in this study include those from various countries as follows: Antarctica, Cladosporium arenosum from marine sediment sand. Argentina, Kosmimatamyces alatophylus (incl. Kosmimatamyces gen. nov.) from soil. Australia, Aspergillus banksianus, Aspergillus kumbius, Aspergillus luteorubrus, Aspergillus malvicolor and Aspergillus nanangensis from soil, Erysiphe medicaginis from leaves of Medicago polymorpha, Hymenotorrendiella communis on leaf litter of Eucalyptus bicostata, Lactifluus albopicri and Lactifluus austropiperatus on soil, Macalpinomyces collinsiae on Eriachne benthamii, Marasmius vagus on soil, Microdochium dawsoniorum from leaves of Sporobolus natalensis, Neopestalotiopsis nebuloides from leaves of Sporobolus elongatus, Pestalotiopsis etonensis from leaves of Sporobolus jacquemontii, Phytophthora personensis from soil associated with dying Grevillea mccutcheonii. Brazil, Aspergillus oxumiae from soil, Calvatia baixaverdensis on soil, Geastrum calycicoriaceum on leaf litter, Greeneria kielmeyerae on leaf spots of Kielmeyera coriacea. Chile, Phytophthora aysenensis on collar rot and stem of Aristotelia chilensis. Croatia, Mollisia gibbospora on fallen branch of Fagus sylvatica. Czech Republic, Neosetophoma hnaniceana from Buxus sempervirens. Ecuador, Exophiala frigidotolerans from soil. Estonia, Elaphomyces bucholtzii in soil. France, Venturia paralias from leaves of Euphorbia paralias. India, Cortinarius balteatoindicus and Cortinarius ulkhagarhiensis on leaf litter. Indonesia, Hymenotorrendiella indonesiana on Eucalyptus urophylla leaf litter. Italy, Penicillium taurinense from indoor chestnut mill. Malaysia, Hemileucoglossum kelabitense on soil, Satchmopsis pini on dead needles of Pinus tecunumanii. Poland, Lecanicillium praecognitum on insects’ frass. Portugal, Neodevriesia aestuarina from saline water. Republic of Korea, Gongronella namwonensis from freshwater. Russia, Candida pellucida from Exomias pellucidus, Heterocephalacria septentrionalis as endophyte from Cladonia rangiferina, Vishniacozyma phoenicis from dates fruit, Volvariella paludosa from swamp. Slovenia, Mallocybe crassivelata on soil. South Africa, Beltraniella podocarpi, Hamatocanthoscypha podocarpi, Coleophoma podocarpi and Nothoseiridium podocarpi (incl. Nothoseiridium gen. nov.) from leaves of Podocarpus latifolius, Gyrothrix encephalarti from leaves of Encephalartos sp., Paraphyton cutaneum from skin of human patient, Phacidiella alsophilae from leaves of Alsophila capensis, and Satchmopsis metrosideri on leaf litter of Metrosideros excelsa. Spain, Cladophialophora cabanerensis from soil, Cortinarius paezii on soil, Cylindrium magnoliae from leaves of Magnolia grandiflora, Trichophoma cylindrospora (incl. Trichophoma gen. nov.) from plant debris, Tuber alcaracense in calcareus soil, Tuber buendiae in calcareus soil. Thailand, Annulohypoxylon spougei on corticated wood, Poaceascoma filiforme from leaves of unknown Poaceae. UK, Dendrostoma luteum on branch lesions of Castanea sativa, Ypsilina buttingtonensis from heartwood of Quercus sp. Ukraine, Myrmecridium phragmiticola from leaves of Phragmites australis. USA, Absidia pararepens from air, Juncomyces californiensis (incl. Juncomyces gen. nov.) from leaves of Juncus effusus, Montagnula cylindrospora from a human skin sample, Muriphila oklahomaensis (incl. Muriphila gen. nov.) on outside wall of alcohol distillery, Neofabraea eucalyptorum from leaves of Eucalyptus macrandra, Diabolocovidia claustri (incl. Diabolocovidia gen. nov.) from leaves of Serenoa repens, Paecilomyces penicilliformis from air, Pseudopezicula betulae from leaves of leaf spots of Populus tremuloides. Vietnam, Diaporthe durionigena on branches of Durio zibethinus and Roridomyces pseudoirritans on rotten wood. Morphological and culture characteristics are supported by DNA barcodes
Relevance of laboratory testing for the diagnosis of primary immunodeficiencies: a review of case-based examples of selected immunodeficiencies
The field of primary immunodeficiencies (PIDs) is one of several in the area of clinical immunology that has not been static, but rather has shown exponential growth due to enhanced physician, scientist and patient education and awareness, leading to identification of new diseases, new molecular diagnoses of existing clinical phenotypes, broadening of the spectrum of clinical and phenotypic presentations associated with a single or related gene defects, increased bioinformatics resources, and utilization of advanced diagnostic technology and methodology for disease diagnosis and management resulting in improved outcomes and survival. There are currently over 200 PIDs with at least 170 associated genetic defects identified, with several of these being reported in recent years. The enormous clinical and immunological heterogeneity in the PIDs makes diagnosis challenging, but there is no doubt that early and accurate diagnosis facilitates prompt intervention leading to decreased morbidity and mortality. Diagnosis of PIDs often requires correlation of data obtained from clinical and radiological findings with laboratory immunological analyses and genetic testing. The field of laboratory diagnostic immunology is also rapidly burgeoning, both in terms of novel technologies and applications, and knowledge of human immunology. Over the years, the classification of PIDs has been primarily based on the immunological defect(s) ("immunophenotype") with the relatively recent addition of genotype, though there are clinical classifications as well. There can be substantial overlap in terms of the broad immunophenotype and clinical features between PIDs, and therefore, it is relevant to refine, at a cellular and molecular level, unique immunological defects that allow for a specific and accurate diagnosis. The diagnostic testing armamentarium for PID includes flow cytometry - phenotyping and functional, cellular and molecular assays, protein analysis, and mutation identification by gene sequencing. The complexity and diversity of the laboratory diagnosis of PIDs necessitates many of the above-mentioned tests being performed in highly specialized reference laboratories. Despite these restrictions, there remains an urgent need for improved standardization and optimization of phenotypic and functional flow cytometry and protein-specific assays. A key component in the interpretation of immunological assays is the comparison of patient data to that obtained in a statistically-robust manner from age and gender-matched healthy donors. This review highlights a few of the laboratory assays available for the diagnostic work-up of broad categories of PIDs, based on immunophenotyping, followed by examples of disease-specific testing
Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: An international cohort study
Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p<00001), age 70 years or older versus younger than 70 years (230 [165-322], p<00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p<00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research
Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research
Assessment of antioxidants by HPLC-MS in grapevine seeds
It is well known, that grapevine seeds are rich in significant antioxidants. However, the issue of dealing with the analysis and comparison of antioxidant components in the seeds of Vitis vinifera L. in individual cultivars has not yet been sufficiently studied. The experiment was performed with extracts of three varieties (Blaufränkish, Italian Riesling and Cabernet Moravia) and three interspecific cultivars (Nativa, Marlen and Kofranka). Contents of nine major flavonoids (apigenin, astragalin, hyperoside, isorhamnetin, kaempferol, myricetin, quercetin, quercitrin and rutin) and two procyanidins (procyanidin A2 and procyanidin B1) were assessed by the HPLC/MS method. The highest contents of antioxidants were found out in interspecific cultivars Marlen and Nativa while the lowest one was assessed in the cultivar Cabernet Moravia. The most represented flavonoid was hyperoside (cultivar Marlen – 15.66 mg∙l–1), least represented was kaempferol (cultivar Cabernet Moravia – 1.81 µg∙l–1)
A study of equatorial noise gyroharmonics frequency values with Cluster wave data
International audienc
In vitro assessment of dendritic cells pulsed with apoptotic tumor cells as a vaccine for ovarian cancer patients
Surgery and chemotherapy are standard treatments in ovarian cancer, but patients have a high rate of relapse. Dendritic cell (DC)-based vaccines are a new treatment option for elimination of residual tumor disease. We aim to explore the feasibility and immunogenicity of DC vaccines pulsed with autologous irradiated tumor cells from ovarian cancer patients. Monocyte-derived DC were generated and pulsed with autologous tumor-derived bodies, matured and subsequently cocultured with autologous lymphocytes. The ability of DC to activate lymphocytes was evaluated by proliferation and IFN-γ ELISPOT. Induction of tumor cell apoptosis was optimal at 24 h, and DC pulsing optimal at 4 h. Maturation of DC and proliferation of lymphocytes were achieved in 75% of patients tested. Lymphocyte IFN-γ production increased in response to tumor antigen-pulsed DC. We show the feasibility of preparing individual DC-based vaccines in ovarian cancer patients and the potential for induction of lymphocyte responses