Pamela Lear

University of Oxford | OX

Background: Acromegaly is produced by excess growth hormone secreted cells (ACRO). First-line therapy, surgery and adjuvant therapy with There is no predictive factor of resistance to therapy. New therapies are cells in acute primary cultures in standard conditions where the cells do not that do not maintain the full somatotroph phenotype. The...

Two-pore channels (TPCs or TPCNs) are novel voltage-gated ion channels that have been postulated to act as Ca²⁺ and/or Na⁺ channels expressed exclusively in acidic organelles such as endosomes and lysosomes. TPCNs participate in the regulation of diverse biological processes and recently have been proposed to be involved in the pathophysiology of m...

Autophagy participates in physiological and pathological remodelling of the heart. The endolysosomal two-pore channels (TPCs), TPC1 and TPC2, have been implicated in the regulation of autophagy. The present study aimed to investigate the role of TPC1 and TPC2 in basal and induced cardiac autophagic activity. In cultured cardiomyocytes, starvation i...

Rationale: Autophagy participates in physiological and pathological remodeling of the heart. The endolysosomal two-pore channels TPC1 and TPC2 have been implicated in the regulation of autophagy. Objective: To study the role of TPC1 and TPC2 in basal and induced cardiac autophagic activity. Methods and results: In cultured cardiomyocytes, star...

Ca2+ signals regulate a wide range of physiological processes. Intracellular Ca2+ stores can be mobilized in response to extracellular stimuli via a range of signal transduction mechanisms, often involving recruitment of diffusible second messenger molecules. The Ca2+ mobilizing messengers InsP3 and cADPR release Ca2+ from the endoplasmic reticulum...

Intracellular calcium-permeable channels have been implicated in thermogenic function of murine brown and brite/beige adipocytes, respectively transient receptor potential melastin-8 (TRPM8) and vanilloid-4 (TRPV4). Since the endo-lysosomal two-pore channels (TPCs) have also been ascribed with metabolic functionality, we studied the effect of simul...

Krüpel-like factor 4 (KLF4) is a zinc-finger-type transcription factor expressed in a range of tissues that plays multiple functions. We report that hypothalamic KLF4 represents a new transcription factor specifically modulating agouti–related protein (AgRP) expression in vivo. Hypothalamic KLF4 colocalizes with AgRP neurons and is modulated by nut...

The role of ghrelin in regulating metabolism and energy balance has been a subject of intense focus ever since its discovery. Ghrelin regulates energy balance in the short term by induction of appetite and in the longer term by increasing body weight and adipos-ity. It is the only known peripheral orexigenic hormone and one of the most potent endog...

The sirtuins are a family of highly conserved nicotine adenine dinucleotide (NAD+)-dependent deacetylases that act as cellular sensors to detect energy availability and regulate metabolic processes. Sirtuin 1 (SIRT1) is one of the family members that is activated in response to caloric restriction, acting on multiple targets in a wide range of tiss...

Background: To determine the prognostic value of pro B-type natriuretic peptide (pro-BNP) to predict mortality after transcatheter aortic valve implantation (TAVI). Logistic EuroSCORE (LES) overestimates observed mortality after TAVI. A new risk score specific to TAVI is needed to accurately assess mortality and outcome. Methods: Eighty-five pat...

Background Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA) uptake and oxidation or in calcium-(Ca2+)-handling in the human heart.MethodsRT-qPCR was used to quantify mRNA expression and immunobl...

This study sought to compare the in-hospital prognostic values of the original and updated GRACE (Global Registry of Acute Coronary Events) risk score (RS) and the AR-G (ACTION [Acute Coronary Treatment and Intervention Outcomes Network] Registry and the GWTG [Get With the Guidelines] Database) RS in acute coronary syndromes (ACS). To evaluate the...

Haemorrhagic complications are strongly linked with adverse outcomes in acute coronary syndrome (ACS) patients. Various risk scores (RS) are available to predict bleeding risk in these patients. We compared the performance of three contemporary bleeding RS in ACS. We studied 4500 consecutive patients with ACS. We calculated the ACTION, CRUSADE, and...

Embryonic, adult, artificially reprogrammed, and cancer…- there are various types of cells associated with stemness. Do they have something fundamental in common? Are we applying a common name to very different entities? In this review, we will revisit the characteristics that define 'pluripotency', the main property of stem cells (SCs). For each m...

Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA) uptake and oxidation or in calcium-(Ca(2+))-handling in the human heart. RT-qPCR was used to quantify mRNA expression and immunoblotting to confi...

The aim of the study is to describe the natural history of an unselected population of patients with atrial fibrillation (AF) currently attending primary care services in a single health-service area in Galicia, north-western Spain. AFBAR is a transverse prospective study in which 35 general practitioners within one health-service area have enrolle...

We investigated whether the direct renin inhibitor aliskiren can affect metabolism in cardiomyocytes from rat, mouse and human sources. At 10-50 μmol/L, aliskiren significantly increased medium-chain-fatty-acid uptake in primary-cultured neonatal-rat and HL-1 adult-mouse-derived cardiomyocytes (BODIPY-induced fluorescence intensity). The fatty-acid...

Obesity is a major risk factor for a plethora of diseases including joint disorders associated with cartilage destruction. Recently, it has been demonstrated that adipose tissue might contribute to degenerative joint diseases via the secretion of potent bioactive molecules termed adipokines. To study expression of the novel adipokines chemerin, lip...

The current study aimed to compare the effects of the peptide hormone ghrelin and des-G, its unacylated isoform, on glucose and fatty acid uptake and to identify des-G-specific binding sites in cardiomyocytes. In the murine HL-1 adult cardiomyocyte line, ghrelin and des-G had opposing metabolic effects: des-G increased medium-chain fatty acid uptak...

To understand causes of developmental abnormalities of the pancreas, it is essential to understand its normal embryonic development. Current understanding of the development of pancreatic exocrine tissue is that it develops solely from embryonic epithelium, while the role of the surrounding mesenchyme is to signal to this epithelium and form connec...

Current interest in the potential use of pancreatic stem-cells in the treatment of insulin dependent diabetes mellitus has led to increased research into normal pancreatic development. Pancreatic organogenesis involves branching morphogenesis of undifferentiated epithelium within surrounding mesenchyme. Current understanding is that the pancreatic...

L'auteur s'attache ici a decouvrir les fondements de la science en tant qu'institution sociale, domaines depuis toujours ignores, comme par exemple l'importance du travail d'equipe en recherche et le role des techniciens en laboratoire...

The nephric duct of the chick embryo starts to form at about stage 10 of Hamburger and Hamilton ([1951] J. Morphol. 88:49-92) and extends posteriorly, fusing with the cloaca at about the end of the third day of incubation (HH stage 17). Evidence from the literature suggests that the extension involves active migration of the posterior tip. This inv...

The chick embryo has been used to address questions concerning morphogenesis of the urinary tissues (nephrogenesis) of vertebrates. Although of considerable biological and clinical significance, the early nephrogenic tissues in particular have been under-utilised in modern developmental analyses. The overall aims of the present study have been to i...