Autoantibodies to hLAMP-2 in ANCA-negative pauci-immune focal necrotizing GN.

Pauci-immune focal necrotizing GN (piFNGN) is usually associated with ANCAs that are thought to be pathogenic. However, 10%-15% of patients are ANCA negative and the cause of their injury is unknown. We previously reported a high frequency of autoantibodies to human lysosome-associated membrane protein-2 (hLAMP-2) in ANCA-associated piFNGN, and have now investigated whether the same is true in ANCA-negative patients.

A critical role for suppressor of cytokine signalling 3 in promoting M1 macrophage activation and function in vitro and in vivo.

Macrophages respond to their microenvironment and develop polarized functions critical for orchestrating appropriate inflammatory responses. Classical (M1) activation eliminates pathogens while alternative (M2) activation promotes regulation and repair. M1 macrophage activation is strongly associated with suppressor of cytokine signalling 3 (SOCS3) expression in vitro, but the functional consequences of this are unclear and the role of SOCS3 in M1-macrophage polarization in vivo remains controversial.

The immune system and kidney disease: basic concepts and clinical implications.

The kidneys are frequently targeted by pathogenic immune responses against renal autoantigens or by local manifestations of systemic autoimmunity. Recent studies in rodent models and humans have uncovered several underlying mechanisms that can be used to explain the previously enigmatic immunopathology of many kidney diseases. These mechanisms include kidney-specific damage-associated molecular patterns that cause sterile inflammation, the crosstalk between renal dendritic cells and T cells, the development of kidney-targeting autoantibodies and molecular mimicry with microbial pathogens.

Classification of frequency response areas in the inferior colliculus reveals continua not discrete classes.

A differential response to sound frequency is a fundamental property of auditory neurons. Frequency analysis in the cochlea gives rise to V-shaped tuning functions in auditory nerve fibres, but by the level of the inferior colliculus (IC), the midbrain nucleus of the auditory pathway, neuronal receptive fields display diverse shapes that reflect the interplay of excitation and inhibition. The origin and nature of these frequency receptive field types is still open to question.

Differences between men and women in the regulation of adipose 11β-HSD1 and in its association with adiposity and insulin resistance.

This study explored sex differences in 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity and gene expression in isolated adipocytes and adipose tissue (AT), obtained via subcutaneous biopsies from non-diabetic subjects [58 M, 64 F; age 48.3 ± 15.3 years, body mass index (BMI) 27.

Ulerythema ophryogenes and Noonan syndrome.

We describe a patient with Noonan syndrome (NS) presenting with ulerythema ophrygenes (UO)--an association initially suggested in a single case series of five patients by Pierini and Pierini in 1979. Recognition of the association of UO with NS by pediatric dermatologists is important because of the high incidence of cardiovascular anomalies in NS. Therefore, in infants and children presenting with UO, clinicians should maintain a high index of suspicion for NS and refer for further workup.

What is the value of routinely testing full blood count, electrolytes and urea, and pulmonary function tests before elective surgery in patients with no apparent clinical indication and in subgroups of patients with common comorbidities: a systematic review of the clinical and cost-effective literature.

Background: The evidence base which supported the National Institute for Health and Clinical Excellence (NICE) published Clinical Guideline 3 was limited and 50% was graded as amber. However, the use of tests as part of pre-operative work-up remains a low-cost but high-volume activity within the NHS, with substantial resource implications. The objective of this study was to identify, evaluate and synthesise the published evidence on the clinical effectiveness and cost-effectiveness of the routine use of three tests, full blood counts (FBCs), urea and electrolytes tests (U&Es) and pulmonary function tests, in the pre-operative work-up of otherwise healthy patients undergoing minor or intermediate surgery in the NHS.

Deactivation of the inferior colliculus by cooling demonstrates intercollicular modulation of neuronal activity.

The auditory pathways coursing through the brainstem are organized bilaterally in mirror image about the midline and at several levels the two sides are interconnected. One of the most prominent points of interconnection is the commissure of the inferior colliculus (CoIC). Anatomical studies have revealed that these fibers make reciprocal connections which follow the tonotopic organization of the inferior colliculus (IC), and that the commissure contains both excitatory and, albeit fewer, inhibitory fibers.

What is the evidence for antibodies to LAMP-2 in the pathogenesis of ANCA associated small vessel vasculitis?

Purpose Of Review: This review critically analyses the data implicating antibodies to lysosome associated membrane protein-2 (hLAMP-2) in ANCA-associated vasculitis (AAV). It addresses recent controversies over prevalence of anti-hLAMP-2 antibodies as well as their potential for diagnosis and monitoring disease activity.

Recent Findings: Anti-hLAMP-2 antibodies were first described in the 1990s and have become the focus of intense clinical interest in the past 4 years.

Pressures on the marine environment and the changing climate of ocean biogeochemistry.

The oceans are under pressure from human activities. Following 250 years of industrial activity, effects are being seen at the cellular through to regional and global scales. The change in atmospheric CO(2) from 280 ppm in pre-industrial times to 392 ppm in 2011 has contributed to the warming of the upper 700 m of the ocean by approximately 0.

Effects of a novel school-based cross-curricular physical activity intervention on cardiovascular disease risk factors in 11- to 14-year-olds: the activity knowledge circuit.

Purpose: This study investigates cardiovascular disease risk factor response in adolescents following introduction of brisk walking into curriculum lessons.

Design: Quasi-experimental.

Setting: School-based.

A systematic review of contextual factors relating to smokeless tobacco use among South Asian users in England.

Introduction: Certain types of smokeless tobacco (ST) are popular among some people of South Asian origin in England; however, little is known about the contextual factors surrounding use in this population. This systematic review explores the factors associated with ST use among people of South Asian origin in England.

Methods: An iterative search strategy in targeted databases and grey literature sources was conducted in the summer of 2011.

Novel acidic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor with reduced acyl glucuronide liability: the discovery of 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid (AZD8329).

Inhibition of 11β-HSD1 is viewed as a potential target for the treatment of obesity and other elements of the metabolic syndrome. We report here the optimization of a carboxylic acid class of inhibitors from AZD4017 (1) to the development candidate AZD8329 (27). A structural change from pyridine to pyrazole together with structural optimization led to an improved technical profile in terms of both solubility and pharmacokinetics.

ROC generated thresholds for field-assessed aerobic fitness related to body size and cardiometabolic risk in schoolchildren.

Objectives: 1. to investigate whether 20 m multi-stage shuttle run performance (20mSRT), an indirect measure of aerobic fitness, could discriminate between healthy and overweight status in 9-10.9 yr old schoolchildren using Receiver Operating Characteristic (ROC) analysis; 2.

Keeping mum about dad: "contracts" to protect gamete donor anonymity.

This article considers the legal status of so-called contracts for anonymity between fertility clinics and donors of gametes that were made in the period before legislation authorising disclosure. It notes that while clinics frequently cite the existence of these "contracts" to argue against retrospective legislation authorising disclosure of the donor's identity, they may be nothing more than one-sided statements of informed consent. However, the article notes that even if an agreement between a donor and a clinic is not contractual, it does not follow that a person conceived through assisted reproductive technology has any right of access to the identity of the donor.

Characterisation of tumour-infiltrating macrophages: impact on response and survival in patients receiving primary chemotherapy for breast cancer.

The role of the tumour microenvironment and complex cellular interactions has attracted interest in responses to primary chemotherapy. Of particular interest are tumour-infiltrating T cells and tumour-infiltrating macrophages (TIMs). We evaluated TIMs and their key activation markers in patients with breast cancer undergoing primary chemotherapy related to response and survival.