Enhancing Efficacy of TCR-engineered CD4 + T Cells Via Coexpression of CD8α.

Adoptive cell therapy with T cells expressing affinity-enhanced T-cell receptors (TCRs) is a promising treatment for solid tumors. Efforts are ongoing to further engineer these T cells to increase the depth and durability of clinical responses and broaden efficacy toward additional indications. In the present study, we investigated one such approach: T cells were transduced with a lentiviral vector to coexpress an affinity-enhanced HLA class I-restricted TCR directed against MAGE-A4 alongside a CD8α coreceptor.

Supplementation With Carotenoids, Omega-3 Fatty Acids, and Vitamin E Has a Positive Effect on the Symptoms and Progression of Alzheimer's Disease.

Background: Preliminary work by our center has reported behavior and functional benefits in patients with Alzheimer's disease (AD) following targeted micronutritional supplementation.

Objective: To build on the existing exploratory research and investigate the impact of these micronutrients on the natural progression of AD in a randomized controlled trial.

Methods: Patients with mild-moderate AD consumed daily 1 g fish oil (of which 500 mg DHA, 150 mg EPA), 22 mg carotenoids (10 mg lutein, 10 mg meso-zeaxanthin, 2 mg zeaxanthin), and 15 mg vitamin E or placebo for 12 months in a double-blind, placebo-controlled, randomized clinical trial.

Compounded Cyclophosphamide and Piroxicam for the Treatment of a Canine Peripheral Nerve Sheath Tumor: A Case Report.

For many people, companion animals are family members and partners in life. The diagnosis of a life-threatening illness in a beloved pet can present challenges for the patient and cause stress and grief for its owner. A successful therapeutic outcome often requires the use of commercially manufactured medications that are not produced in the doses or dosage forms tolerated by veterinary patients or are unavailable to, unaffordable for, and/or inaccessible by owners.

Tuning T-Cell Receptor Affinity to Optimize Clinical Risk-Benefit When Targeting Alpha-Fetoprotein-Positive Liver Cancer.

Patients with hepatocellular carcinoma (HCC) have a poor prognosis and limited therapeutic options. Alpha-fetoprotein (AFP) is often expressed at high levels in HCC and is an established clinical biomarker of the disease. Expression of AFP in nonmalignant liver can occur, particularly in a subset of progenitor cells and during chronic inflammation, at levels typically lower than in HCC.

Agonist-induced internalization and desensitization of the apelin receptor.

Apelin acts via the G protein-coupled apelin receptor (APJ) to mediate effects on cardiovascular and fluid homeostasis. G protein-coupled receptor (GPCR) trafficking has an important role in the regulation of receptor signalling pathways and cellular functions, however in the case of APJ the mechanisms and proteins involved in apelin-induced trafficking are not well understood. We generated a stable HEK-293 cell line expressing N-terminus HA-tagged mouse (m) APJ, and used a semi-automated imaging protocol to quantitate APJ trafficking and ERK1/2 activation following stimulation with [Pyr]apelin-13.

Information Transfer in Gonadotropin-releasing Hormone (GnRH) Signaling: EXTRACELLULAR SIGNAL-REGULATED KINASE (ERK)-MEDIATED FEEDBACK LOOPS CONTROL HORMONE SENSING.

Cell signaling pathways are noisy communication channels, and statistical measures derived from information theory can be used to quantify the information they transfer. Here we use single cell signaling measures to calculate mutual information as a measure of information transfer via gonadotropin-releasing hormone (GnRH) receptors (GnRHR) to extracellular signal-regulated kinase (ERK) or nuclear factor of activated T-cells (NFAT). This revealed mutual information values <1 bit, implying that individual GnRH-responsive cells cannot unambiguously differentiate even two equally probable input concentrations.

Pulsatile hormonal signaling to extracellular signal-regulated kinase: exploring system sensitivity to gonadotropin-releasing hormone pulse frequency and width.

Gonadotropin-releasing hormone (GnRH) is secreted in brief pulses that stimulate synthesis and secretion of pituitary gonadotropin hormones and thereby mediate control of reproduction. It acts via G-protein-coupled receptors to stimulate effectors, including ERK. Information could be encoded in GnRH pulse frequency, width, amplitude, or other features of pulse shape, but the relative importance of these features is unknown.

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis.

The apelin receptor (APJ; gene symbol APLNR) is a member of the G protein-coupled receptor gene family. Neural gene expression patterns of APJ, and its cognate ligand apelin, in the brain implicate the apelinergic system in the regulation of a number of physiological processes. APJ and apelin are highly expressed in the hypothalamo-neurohypophysial system, which regulates fluid homeostasis, in the hypothalamic-pituitary-adrenal axis, which controls the neuroendocrine response to stress, and in the forebrain and lower brainstem regions, which are involved in cardiovascular function.

Use of Hyperbaric Oxygen as Adjunct in Salvage of Near-complete Ear Amputation.

There have been several cases of microvascular repair of traumatically avulsed or amputated ears in the literature. It seems that, if possible at the time of operation, microsurgical techniques yield the best results. However, because of the nature, complexity, and acuity of traumatic injuries, this option is not always feasible.

"Stroke Nav": a wireless data collection and review system to support stroke care delivery.

"Stroke Nav" is a novel system to support the care of stroke patients. The system contains purpose-built web-based software to facilitate accurate near-real time data collection by clinicians throughout the complex care settings traversed by patients. Tools are included to facilitate pre-defined and bespoke data review with graphical dashboards showing performance metrics and other aggregate data.

Central and peripheral apelin receptor distribution in the mouse: species differences with rat.

The G protein-coupled apelin receptor (APJ) binds the endogenous peptide apelin and has been shown to have roles in many physiological systems. Thus far, distribution studies have predominantly been conducted in the rat and there is limited knowledge of the cellular distribution of APJ in mouse or human tissues. As recent functional studies have been conducted in APJ knock-out mice (APJ KO), in this study we undertook to characterize APJ mRNA and I(125)[Pyr(1)]apelin-13 binding site distribution in mouse tissues to enable correlation of distribution with function.

G protein-coupled receptors in the hypothalamic paraventricular and supraoptic nuclei--serpentine gateways to neuroendocrine homeostasis.

G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors in the mammalian genome. They are activated by a multitude of different ligands that elicit rapid intracellular responses to regulate cell function. Unsurprisingly, a large proportion of therapeutic agents target these receptors.

Specialist medication review does not benefit short-term outcomes and net costs in continuing-care patients.

Objectives: to evaluate specialist geriatric input and medication review in patients in high-dependency continuing care.

Design: prospective, randomised, controlled trial.

Setting: two residential continuing care hospitals.

Abnormal fluid homeostasis in apelin receptor knockout mice.

The apelinergic system, comprised of apelin and its G protein-coupled receptor (APJ; APLNR as given in MGI Database), is expressed within key regions of the central nervous system associated with arginine vasopressin (AVP) synthesis and release as well as in structures involved in the control of drinking behaviour, including the magnocellular neurones of the hypothalamus, circumventricular organs, and the pituitary gland. This localisation is indicative of a possible functional role in fluid homeostasis. We investigated a role for APJ in the regulation of fluid balance using mice deficient for the receptor.

The effects of apelin on hypothalamic-pituitary-adrenal axis neuroendocrine function are mediated through corticotrophin-releasing factor- and vasopressin-dependent mechanisms.

The apelinergic system has a widespread expression in the central nervous system (CNS) including the paraventricular nucleus, supraoptic nucleus and median eminence, and isolated cells of the anterior lobe of the pituitary. This pattern of expression in hypothalamic nuclei known to contain corticotrophin-releasing factor (CRF) and vasopressin (AVP) and to co-ordinate endocrine responses to stress has generated interest in a role for apelin in the modulation of stress, perhaps via the regulation of hormone release from the pituitary. In this study, to determine whether apelin has a central role in the regulation of CRF and AVP neurones, we investigated the effect of i.

National trends in utilization and in-hospital outcomes of bariatric surgery.

In view of recent enthusiasm for surgery to treat morbid obesity, we examined national changes in utilization and in-hospital outcomes of bariatric surgery over time. With the use of International Classification of Diseases (ICD-9) codes, we identified all bariatric procedures (n = 12,203) performed on adults from 1990 to 1997 in hospitals participating in the Nationwide Inpatient Sample. We then applied sampling weights and United States Census data to calculate the national population-based rates of bariatric surgery procedures for each year and examined secular trends in utilization.