Aberrant activation of intracellular signalling pathways confers malignant properties on cancer cells. Targeting has been a productive strategy for drug development, with several drugs acting already in use and more continually being developed. The JAK/STAT pathway provides an example this paradigm haematological malignancies, the identification JAK2 mutations myeloproliferative neoplasms leading to development specific clinically effective inhibitors, such as ruxolitinib. It is now clear...

<h3>Background</h3> Endoscopic mucosal healing is an established treatment target for UC, yet the value of achieving histological remission remains unclear. <h3>Aims</h3> To evaluate compared to endoscopic predicting patient outcomes in UC. <h3>Methods</h3> Blinded assessment and measures disease activity was performed on patients with UC at baseline. Concordance prognostic values (defined by Baron score ≤1) Truelove Richards' index) corticosteroid use, hospitalisation colectomy were...

Background The JAK/STAT pathway transduces signals from multiple cytokines and controls haematopoiesis, immunity inflammation. In addition, pathological activation is seen in malignancies including the myeloproliferative neoplasms (MPNs). Given this, drug development efforts have targeted with JAK inhibitors such as ruxolitinib. Although effective, high costs side effects limited its adoption. Thus, a need for effective low cost treatments remains. Methods & Findings We used low-complexity...

Comparisons between disease activity indices for ulcerative colitis (UC) are few. This study evaluates three indices, to determine the potential impact of inter-observer variation on clinical trial recruitment or outcome as well their relevance.One hundred patients with UC were prospectively evaluated, each by four specialists, followed videosigmoidoscopy, which was later scored specialist. The Simple Clinical Colitis Activity (SCCAI), Mayo Clinic and Seo compared assigning a category from...

The lymphoid cells of embryonic bursal follicles are engaged in rapid growth and preimmune diversification immunoglobulin genes. Disruption follicular architecture by mechanical dispersion these short-term tissue culture was accompanied continued cell division extensive death apoptosis. Apoptosis suppressed parallel cultures intact follicles. gamma Radiation also triggered apoptosis within a few hours. Preneoplastic stem populations induced v-myc oncogene were hypersensitive to induction...

Variable phenotype is common in neurological disorders with single-gene inheritance patterns. In Huntington's disease, mood and cognitive symptoms are variably co-expressed motor symptoms. There also variable degeneration of neurons the two major neurochemical compartments striatum, striosomes extrastriosomal matrix. To determine whether phenotypic variability disease related to this compartmental organization, we carried out a double-blind study which used GABA(A) receptor...

<h3>Introduction</h3> Acute rheumatic fever (ARF) is usually considered a consequence of group A streptococcus (GAS) pharyngitis, with GAS skin infections not major trigger. The aim was to quantify the risk ARF following GAS-positive or throat swab. <h3>Methods</h3> This retrospective analysis used pre-existing administrative data. Throat and swab data (1 866 981 swabs) from Auckland region, New Zealand antibiotic dispensing were (2010–2017). Incident cases identified using hospitalisation...

<h3>ABSTRACT</h3> Widespread use of anticoagulant drugs for treatment and ­prevention thromboembolic events means it is common to encounter patients requiring reversal anticoagulation management bleeding or invasive procedures. While supportive general measures apply on all agents, recent diversification in the number licensed agents makes an understanding drug-specific strategies essential. Recognising effects upon, limitations of, laboratory coagulation also plays important role. An alone...

Germline predisposition to haematological cancers is increasingly being recognised. Widespread adoption of high-throughput and whole genome sequencing identifying large numbers causative germline mutations. Constitutional pathogenic variants in six genes (DEAD-box helicase 41 [DDX41], ETS variant transcription factor 6 [ETV6], CCAAT enhancer binding protein alpha [CEBPA], RUNX family 1 [RUNX1], ankyrin repeat domain containing 26 [ANKRD26] GATA 2 [GATA2]) are particularly significant...

Group A Streptococcus (GAS) can trigger an immune-mediated response resulting in acute rheumatic fever (ARF). Historically, ARF has been considered a consequence of preceding GAS pharyngitis, but increasing evidence suggests that skin infections may be driver. Data on the primary care burden infection are limited. This paper aims to describe and compare prevalence distribution detection swabs rates Auckland population.This cross-sectional study used all laboratory swab data from people who...

There has been increasing recognition of heterogeneity in blood platelets and their responses, particularly recent years, where next-generation technologies advanced bioinformatic tools that interrogate "big data" have enabled large-scale studies RNA protein expression across a growing list disease states. However, pioneering platelet biologists clinicians were already hypothesizing upon investigating (and megakaryocyte) activity metabolism aggregation over half century ago. Building on...

Cytokine receptors often act via the Janus kinase and signal transducer activator of transcription (JAK/STAT) pathway to form a signalling cascade that is essential for processes such as haematopoiesis, immune responses tissue homeostasis. In order transduce ligand activation, cytokine must dimerise. However, mechanisms regulating their dimerisation are poorly understood. better understand receptor levels, activity dimerisation, we analysed highly conserved JAK/STAT in Drosophila, which acts...

Human papillomavirus (HPV) infection is causally related to a subset of oropharyngeal carcinomas (OPC) and linked more favourable prognosis compared HPV-negative OPC. The mechanisms underlying this effect on are not fully understood, but interactions with the tumour microenvironment may be pivotal. Here, we investigated role in HPV-positive cancer using 2D 3D modelling OPC stromal fibroblasts. HPV-negative, HPV-positive, OPC-derived cell lines induced rapid fibroblast secretory response that...

<h3>Introduction</h3> Remission is the goal of therapy in ulcerative colitis (UC) and a primary endpoint clinical trials. Disparity between clinical, endoscopic histological assessments activity has long been recognised, but since definition remission affects regulatory decisions, disparity impact on outcome needs re-evaluation. <h3>Methods</h3> Consecutive patients requesting an early appointment were assessed by 4 gastroenterologists, before videosigmoidoscopy mucosal biopsy. Each scored...

Objective To evaluate the risk of post-transfusion and postoperative non-A non-B hepatitis in Australia immediately before introduction screening for C. Design Retrospective testing blood samples from a prospective study cardiac surgery patients. Samples were taken transfusion recipients non-transfused controls at regular intervals 12 months after during 1987-1989. For all donor, recipient control samples, alanine aminotransferase (ALT) levels measured tests antibody to B (anti-HBc,...

Lymphoblasts of the normal embryonic follicles chicken bursa Fabricius undergo rapid apoptosis when exposed to gamma-radiation or cell-cell contacts are disrupted by mechanical dispersion in short term culture. We have observed previously that overexpression v-myc sensitizes preneoplastic bursal lymphoblasts induction cell death, whereas resistance induced death is acquired during progression neoplasia. In this study we extensive DNA degradation large majority lymphoblast population within...

Primary lymphoproliferative disorders of the uterus are rare, with majority being B-cell diseases or aggressive T-cell disease. We present case a 31-yr old in whom an Indolent disorder (iTCLPD) was identified resection chippings for suspected fibroid, following presentation menorrhagia. Laboratory investigations revealed oligoclonal infiltrate immunophenotype nonactivated cytotoxic T cells, and proliferative fraction 10% to 15%. There no clinical radiologic evidence systemic disease, patient...

B-cell lymphoma arising in the bursa of Fabricius chickens is both a naturally occurring neoplasm commercial importance and an experimental system which has contributed significantly to knowledge about role retroviruses oncogenes tumorigenesis. The salient features this tumor have recently been reviewed (Neiman 1994). Briefly, lymphoid population embryonic follicles composed large cycling lymphoblasts expressing surface IgM (Thompson et al. 1987). This includes stem-cell compartment cells...