Germline NF1 mutational spectra and loss-of-heterozygosity analyses in patients with pheochromocytoma and neurofibromatosis type 1.

Background: Neurofibromatosis type 1 (NF1) is a pheochromocytoma-associated syndrome. Because of the low prevalence of pheochromocytoma in NF1, we ascertained subjects by pheochromocytoma that also had NF1 in the hope of describing the germline NF1 mutational spectra of NF1-related pheochromocytoma.

Materials And Methods: An international registry for NF1-pheochromocytomas was established.

Loss of alpha-tubulin polyglutamylation in ROSA22 mice is associated with abnormal targeting of KIF1A and modulated synaptic function.

Microtubules function as molecular tracks along which motor proteins transport a variety of cargo to discrete destinations within the cell. The carboxyl termini of alpha- and beta-tubulin can undergo different posttranslational modifications, including polyglutamylation, which is particularly abundant within the mammalian nervous system. Thus, this modification could serve as a molecular "traffic sign" for motor proteins in neuronal cells.

Autosomal dominant polycystic kidney disease: role of the renin-angiotensin system in raised blood pressure in progression of renal and cardiovascular disease.

Raised blood pressure (BP) is extremely common in individuals with autosomal dominant polycystic kidney disease (ADPKD) and is almost invariably raised once they develop renal failure. The underlying mechanisms for the rise in BP in individuals with ADPKD are unclear. The progressive number and enlargement of renal cysts, causing structural damage to the kidneys and, thereby, affecting tubular function as well as causing distortion of the glomeruli and renal ischaemia, is likely to be of primary importance.

Importance of salt in determining blood pressure in children: meta-analysis of controlled trials.

To assess the effect of reducing salt intake on blood pressure in children, we carried out a meta-analysis of controlled trials. Trials were included if participants were children (< or = 18 years), and duration of salt reduction must have been for > or = 2 weeks. Mean effect size was calculated using a fixed-effect model, because there was no significant heterogeneity.

FNDC3A is required for adhesion between spermatids and Sertoli cells.

Symplastic spermatids (sys) male mice are sterile due to a recessive mutation that causes defective adhesion between spermatids and Sertoli cells within the seminiferous epithelium. We show that the mutation in sys mice involves a deletion of 1.24 Mb of chromosome 14.

TTLL7 is a mammalian beta-tubulin polyglutamylase required for growth of MAP2-positive neurites.

Microtubules form a cytoskeletal framework that influences cell shape and provides structural support for the cell. Microtubules in the nervous system undergo a unique post-translational modification, polyglutamylation of the C termini of their tubulin subunits. The mammalian enzymes that perform beta-tubulin polyglutamylation as well as their physiological functions in the neuronal tissue remain elusive.

Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter's syndrome and in adaptation to a high-K diet.

Type II Bartter's syndrome is a hereditary hypokalemic renal salt-wasting disorder caused by mutations in the ROMK channel (Kir1.1; Kcnj1), mediating potassium recycling in the thick ascending limb of Henle's loop (TAL) and potassium secretion in the distal tubule and cortical collecting duct (CCT). Newborns with Type II Bartter are transiently hyperkalemic, consistent with loss of ROMK channel function in potassium secretion in distal convoluted tubule and CCT.

The effect of sodium and angiotensin-converting enzyme inhibition on the classic circulating renin-angiotensin system in autosomal-dominant polycystic kidney disease patients.

Background: It has been suggested that inappropriate stimulation of the renin-angiotensin system (RAS) is responsible for the increase in blood pressure that occurs in autosomal-dominant polycystic kidney disease (ADPKD) before the development of renal failure. However, the interpretation of previous studies in ADPKD patients is confounded by inadequate matching with control populations for blood pressure and renal function, or failure to control the sodium intake of participants.

Methods: A double-blind, placebo-controlled study of two different sodium intakes (350 and 50 mmol/day for 5 days) in a group of 11 hypertensive ADPKD patients and eight matched control subjects with essential hypertension.

Human-specific cystic fibrosis transmembrane conductance regulator antibodies detect in vivo gene transfer to ovine airways.

A panel of 11 human cystic fibrosis transmembrane conductance regulator (hCFTR) antibodies were tested in ovine nasal, tracheal, and bronchial epithelial brushings. Two of these, G449 (polyclonal) and MATG1104 (monoclonal), recognized hCFTR but did not cross react with endogenous sheep CFTR. This specificity allows immunologic detection of hCFTR expressed in gene transfer studies in sheep against the background of endogenous ovine CFTR, thus enhancing the value of the sheep as a model animal in which to study CFTR gene transfer.

Inefficient cationic lipid-mediated siRNA and antisense oligonucleotide transfer to airway epithelial cells in vivo.

Background: The cationic lipid Genzyme lipid (GL) 67 is the current "gold-standard" for in vivo lung gene transfer. Here, we assessed, if GL67 mediated uptake of siRNAs and asODNs into airway epithelium in vivo.

Methods: Anti-lacZ and ENaC (epithelial sodium channel) siRNA and asODN were complexed to GL67 and administered to the mouse airway epithelium in vivo Transfection efficiency and efficacy were assessed using real-time RT-PCR as well as through protein expression and functional studies.

Subunit-subunit interactions are critical for proton sensitivity of ROMK: evidence in support of an intermolecular gating mechanism.

The tetrameric K channel ROMK provides an important pathway for K secretion by the mammalian kidney, and the gating of this channel is highly sensitive to changes in cytosolic pH. Although charge-charge interactions have been implicated in pH sensing by this K channel tetramer, the molecular mechanism linking pH sensing and the gating of ion channels is poorly understood. The x-ray crystal structure KirBac1.

Fruit and vegetable consumption and stroke: meta-analysis of cohort studies.

Background: Increased consumption of fruit and vegetables has been shown to be associated with a reduced risk of stroke in most epidemiological studies, although the extent of the association is uncertain. We quantitatively assessed the relation between fruit and vegetable intake and incidence of stroke in a meta-analysis of cohort studies.

Methods: We searched MEDLINE, EMBASE, the Cochrane Library, and bibliographies of retrieved articles.

WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1).

The serine-threonine kinase WNK3 modulates Cl- transport into and out of cells through its regulation of SLC12A cation/Cl- cotransporters, implicating it as (one of) the long-sought Cl-/volume-sensitive kinase(s). Integrators in homeostatic systems regulate structurally diverse but functionally coupled elements. For example, the related kinase WNK4 regulates the Na-Cl co-transporter (NCC), paracellular Cl- flux, and the K+ channel ROMK1 (Kir1.

Importance of controlling blood pressure.

Cardiovascular disease is the leading cause of death and disability world-wide. Blood pressure, throughout the range seen in developed countries, is the most important risk factor for cardiovascular disease. Lowering blood pressure within the whole population by lifestyle interventions, such as reducing dietary salt intake and increasing the consumption of fruit and vegetables, will be of great benefit.

Breath condensate ammonium is lower in children with chronic asthma.

Exhaled breath condensate pH and ammonium reflect asthmatic status and acute exacerbations in adults. The aim of this study was to assess whether pH and ammonium could reflect asthma and its severity in children. The current study comprised two parts: 1) a cross-section of 74 children with asthma (median age 10.

Phosphorylation-regulated endoplasmic reticulum retention signal in the renal outer-medullary K+ channel (ROMK).

The renal outer-medullary K+ channel (ROMK; Kir1.1) mediates K+ secretion in the renal mammalian nephron that is critical to both sodium and potassium homeostasis. The posttranscriptional expression of ROMK in the plasma membrane of cells is regulated by delivery of protein from endoplasmic reticulum (ER) to the cell surface and by retrieval by dynamin-dependent endocytic mechanisms in clathrin-coated pits.

Modest salt reduction reduces blood pressure and urine protein excretion in black hypertensives: a randomized control trial.

High blood pressure and proteinuria are the major risk factors for cardiovascular and renal disease. In black individuals, there is an increased risk of hypertension, stroke, heart failure, and kidney disease. There are no controlled studies of the effects of reducing salt intake on blood pressure and urine protein excretion in black individuals.

Modest salt reduction lowers blood pressure in isolated systolic hypertension and combined hypertension.

Many randomized trials have shown that a reduction in salt intake lowers blood pressure in hypertensive individuals. However, few have looked at the effects according to hypertension category. A recent analysis of the third and fourth National Health and Nutrition Examination Survey suggests that salt intake may not be related to blood pressure in isolated systolic or combined hypertension.

Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension.

Some evidence suggests that long-term angiotensin-converting enzyme (ACE) inhibition may become less effective, thereby increasing angiotensin II levels, which could be inhibited by the addition of an angiotensin receptor blocker. We conducted a meta-analysis of randomized trials with searches of MEDLINE, EMBASE, and Cochrane databases. Overall, the combination of an ACE inhibitor and an angiotensin receptor blocker reduced ambulatory blood pressure by 4.