We have studied translational control in the model of 48 h of fasting in the rat. Our initial observations showed a paradoxical increase in ribosomal protein S6 (rpS6) phosphorylation and a decrease in eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation. These effects, which would favor an increase in protein synthesis, could be attributed to increased circulating concentrations of branched-chain amino acids in fasting.
View Article and Find Full Text PDFObjectives: To study TRPV1 immunoreactivity in the urothelium of patients with neurogenic detrusor overactivity (NDO) before and after treatment with resiniferatoxin (RTX) and controls. Functional capsaicin TRPV1 receptors have been demonstrated in urothelial cells of rodent urinary bladder, and TRPV1-knockout mice exhibit diminished nitric oxide and stretch-evoked adenosine triphosphate release from urothelial cells. In patients with NDO, TRPV1 suburothelial nerve density is increased, which is reversed by successful treatment with intravesical RTX.
View Article and Find Full Text PDFIn the absence of adequate levels of cellular acidic phospholipids, Escherichia coli remain viable but are arrested for growth. Expression of a DnaA protein that contains a single amino acid substitution in the membrane-binding domain, DnaA(L366K), in concert with expression of wild-type DnaA protein, restores growth. DnaA protein has high affinity for ATP and ADP, and in vitro lipid bilayers that are fluid and contain acidic phospholipids reactivate inert ADP-DnaA by promoting an exchange of ATP for ADP.
View Article and Find Full Text PDFFetal growth retardation, a common end point for a variety of conditions affecting mother and fetus, is associated with reduced liver mass. We have performed studies to determine the mechanism for decreased liver mass in a maternal starvation model of fetal growth restriction in the rat. Pregnant dams were deprived of food for 48 h before delivery on embryonic day 19 (E19).
View Article and Find Full Text PDFJ Clin Pediatr Dent
December 2004
Clinicopathologic studies on the granular cell tumor, a submucosal benign soft-tissue neoplasm, have not addressed the pediatric and adolescent population. This study of patients from birth to 19 years of age describes clinically and microscopically 10 new cases and combines them with 24 well-documented pediatric cases previously published in the English-language literature. Of the 34, patient ages ranged from 3 to 19 years (mean age 14.
View Article and Find Full Text PDFSubstantial debate on the appropriate foundations of economic evaluation in health-care has been conducted between welfarists and non-welfarists in the health economics literature. This has focussed on defining and measuring appropriate outcomes. However, there has been little discussion of the importance of procedures.
View Article and Find Full Text PDFThis paper provides an introduction to a collection of articles concerning the relevance of Amartya Sen's work, the capability approach and related ethical claims, to health-care rationing.
View Article and Find Full Text PDFBMC Bioinformatics
October 2004
Background: Multiple sequence alignment algorithms are very important tools in molecular biology today. Accurate alignment of proteins is central to several areas such as homology modelling, docking studies, understanding evolutionary trends and study of structure-function relationships. In recent times, improvement of existing progressing programs and implementation of new iterative algorithms have made a significant change in this field.
View Article and Find Full Text PDFEur J Gastroenterol Hepatol
September 2004
Background: Gastro-oesophageal reflux disease (GORD) patients commonly describe symptoms of heartburn and chest pain. The capsaicin receptor vanilloid receptor 1 (TRPV1) (VR1) is a cation channel expressed by sensory neurones and activated by heat, acid pH and ethanol, which may trigger burning pain.
Aim: To study the distribution of TRPV1-expressing nerve fibres in oesophageal mucosal biopsies from patients with symptomatic oesophagitis and in control subjects.
Objectives: The ATP-gated purinergic receptor P2X3 is expressed by small diameter sensory neurons and has been identified in normal and neurogenic human bladder suburothelial fibres. Animal models have shown that ATP is released by the urothelium during bladder distension, suggesting a mechanosensory role for P2X3 receptors in normal bladder function. Successful treatment of spinal neurogenic detrusor overactivity (NDO) with intravesical resiniferatoxin (RTX), which partly acts on suburothelial C fibres, provides evidence for the emergence of a C fibre-mediated spinal reflex.
View Article and Find Full Text PDFVoltage-gated sodium channel alpha-subunits play a key role in pain pathophysiology, and are modulated by beta-subunits. We previously reported that beta1- and beta2-subunits were decreased in human sensory neurons after spinal root avulsion injury. We have now detected, by immunohistochemistry, beta3-subunits in 82% of small/medium and 67% of large diameter sensory neurons in intact human dorsal root ganglia: 54% of beta3 small/medium neurons were NGF receptor trkA negative.
View Article and Find Full Text PDFThis 9-year-old boy sustained a complete right-sided C5-T1 brachial plexus avulsion injury in a motorcycle accident. He underwent surgery 4 weeks after the accident. The motor-related nerve roots in all parts of the avulsed brachial plexus were reconnected to the spinal cord by reimplantation of peripheral nerve grafts.
View Article and Find Full Text PDFUnilateral avulsion of lumbar ventral roots kills approximately 50% of injured motoneurons within 2 weeks of surgery. Immediate treatment involving surgical reimplantation of the ventral root (VRI) or intrathecal glial cell line-derived neurotrophic factor (GDNF) delivery or intraperitoneal injection of riluzole for 2 weeks ameliorates motoneuron death to 80% of control but combining the different treatment paradigms did not further enhance survival except when GDNF was combined with VRI. At 3 months, all combined treatments provided a neuroprotective effect compared to avulsion only, but the neuroprotective effect of surgical reimplantation alone was not maintained unless combined with riluzole and GDNF treatment.
View Article and Find Full Text PDFObjective: To compare PGP9.5 and transient receptor potential vanilloid receptor (TRPV1) suburothelial immunoreactivity between controls and patients with spinal neurogenic detrusor overactivity (NDO) before and after treatment with intravesical resiniferatoxin, as suburothelial PGP9.5-staining nerve fibres decrease in patients with spinal NDO who respond to intravesical capsaicin, and TRPV1 is present on these suburothelial nerve fibres in normal and overactive human urinary bladder.
View Article and Find Full Text PDFMol Cell Biochem
March 2004
Cholesterol-mediated mycobacteria entry into and survival within macrophages has added a new dimension to Tuberculosis research. The molecular mechanism through which cholesterol initiates this process is still poorly understood. The present study addressed to resolve this mechanism revealed that Mycobacterium tuberculosis possesses cholesterol-specific Receptor 'Ck'-like molecule responsible for mycobacterial entry into macrophages.
View Article and Find Full Text PDFIn September 2001, a Task Force was set up under the auspices of the European Federation of Neurological Societies with the aim of evaluating the existing evidence about the methods of assessing neuropathic pain and its treatments. This review led to the development of guidelines to be used in the management of patients with neuropathic pain. In the clinical setting a neurological examination that includes an accurate sensory examination is often sufficient to reach a diagnosis.
View Article and Find Full Text PDFVulvodynia is characterised by painful burning sensation, allodynia and hyperalgesia in the region of the vulval vestibulus. While in many patients the cause of vulvodynia remains uncertain, we and others have previously shown increased intraepithelial and papillary innervation in vulvodynia. The vanilloid receptor VR1 (TRPV1) is expressed by nociceptors, and is triggered by capsaicin, noxious heat, protons, and chemicals produced during inflammation.
View Article and Find Full Text PDFRoot avulsion from the spinal cord occurs in brachial plexus lesions. It is the practice to repair such injuries by transferring an intact neighbouring nerve to the distal stump of the damaged nerve; avulsed dorsal root ganglia (DRG) are removed to enable nerve transfer. Such avulsed adult human cervical DRG ( [Formula: see text] ) obtained at surgery were compared to controls, for the first time, using GeneChip oligonucleotide arrays.
View Article and Find Full Text PDFClinical practice and scientific research may soon lead to treatments designed to repair spinal cord injury. Repair is likely to be partial in the first trials, extending only one or two segments below the original injury. Furthermore, treatments that are becoming available are likely to be applied to the thoracic spinal cord to minimise loss of function resulting from damage to surviving connections.
View Article and Find Full Text PDFInflammation associated with nerve injury produces a number of pathogenic chemical mediators of which prostanoids are a potent component. Cyclooxygenases (Cox-1 and Cox-2) are the enzymes responsible for prostanoid production. We have investigated Cox-2 immunoreactivity (Cox-2-IR) and glial activation in human injured (n = 16) and uninjured (n = 8) nerves and in the chronic constriction injury (CCI) model of nerve injury in the rat, using immunohistological and autoradiographic methods.
View Article and Find Full Text PDFWe studied 27 patients with low back pain and unilateral L5 or S1 spinal nerve root pain. Significant radiological changes were restricted to the symptomatic root level, when compared with controls. Low back and leg pain were graded on a visual analogue scale.
View Article and Find Full Text PDFObjective: To investigate endothelial nitric oxide synthase (eNOS) immunoreactivity in bladder biopsies from patients with neurogenic detrusor overactivity (NDO) before and after treatment with intravesical resiniferatoxin, and compare this with control material; the distribution of two other vascular markers, von Willebrand Factor (vWF) and the vascular endothelial growth factor (VEGF), was also studied.
Patients And Methods: Flexible cystoscopic bladder biopsies from eight controls investigated for asymptomatic microhaematuria and 19 patients with refractory spinal NDO enrolled in a clinical trial of intravesical treatment with escalating doses of resiniferatoxin were immunostained with polyclonal rabbit antibodies for eNOS, vWF and VEGF. Fewer baseline NDO specimens (eight) were available for vWF and VEGF staining.
Prog Brain Res
February 2004
Neurotrophic factors may play key roles in pathophysiological mechanisms of human neuropathies. Nerve growth factor (NGF) is trophic to small-diameter sensory fibers and regulates nociception. This review focuses on sensory dysfunction and the potential of neurotrophic treatments.
View Article and Find Full Text PDFBiochem Biophys Res Commun
October 2003
Recently, gene coding for tryptophan-aspartate containing coat protein (TACO) has been recognized to play a crucial role in the survival of Mycobacterium tuberculosis within human macrophages. Since regulation of TACO gene is still poorly understood, the present study was addressed to explore the role of vitamins (A, C, D, and E) in TACO gene transcription. Such a study revealed that synergistic action of vitamin D(3) and retinoic acid (RA) had inherent ability to down-regulate TACO gene transcription in human macrophages.
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