Oxygen-dependent differentiation of human keratinocytes.

Oxygen is an essential micronutrient. Unlike many internal tissues, human epidermis obtains much of its oxygen supply from the atmosphere (21% oxygen), and it ordinarily experiences higher oxygen levels than internal tissues (estimated approximately 5%). To test whether epidermal cell growth and differentiation depend upon this higher oxygen level, keratinocyte cultures were studied at 21, 5, and 2% oxygen concentrations.

Oxysterol-binding protein-related protein (ORP) 9 is a PDK-2 substrate and regulates Akt phosphorylation.

The oxysterol-binding protein and oxysterol-binding protein-related protein family has been implicated in lipid transport and metabolism, vesicle trafficking and cell signaling. While investigating the phosphorylation of Akt/protein kinase B in stimulated bone marrow-derived mast cells, we observed that a monoclonal antibody directed against phospho-S473 Akt cross-reacted with oxysterol-binding protein-related protein 9 (ORP9). Further analysis revealed that mast cells exclusively express ORP9S, an N-terminal truncated version of full-length ORP9L.

Validation of a novel point-of-care nerve conduction device for the detection of diabetic sensorimotor polyneuropathy.

Objective: The diagnosis of diabetic sensorimotor polyneuropathy using objective electrophysiological tests is hindered by limited access to the specialized laboratories and technicians that perform and interpret them. We evaluated the performance characteristics of a novel portable and automated point-of-care nerve conduction study device, which can be operated by nontechnical personnel, and compared it with conventional nerve conduction studies performed in a specialist setting.

Research Design And Methods: Seventy-two consecutive patients with diabetes (8 type 1, 64 type 2) from a diabetes and a neuropathy outpatient clinic were evaluated concurrently with conventional nerve conduction studies (the reference standard) and the point-of-care device for sural nerve function (sural nerve amplitude potentials in microvolts [microV]).

Sensitivity of repetitive facial-nerve stimulation in patients with myasthenia gravis.

Repetitive stimulation of the facial nerve is commonly performed in cases of suspected myasthenia gravis (MG) because bulbar weakness is often present, but the most sensitive facial muscle is unknown. We compared the sensitivity of repetitive nerve stimulation (RNS) to the frontalis and nasalis muscles in 244 patients with suspected MG. We found no difference in sensitivity of RNS when recording from these muscles in both ocular and generalized MG.

A pilot study to compare the use of the Excorim staphylococcal protein immunoadsorption system and IVIG in chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune mediated neuropathy responding to immunomodulation with IVIG or plasma exchange (PE). We tested the efficacy and safety of selective immunoglobulin removal by Excorim immunoadsorption (IA) in a pilot trial in CIDP patients randomized to monthly IA or IVIG treatments for 6 months. Response rates at 2 and 6 months were greater with IA due to longer disease duration and greater disability at baseline in the patients receiving IVIG.

Low-intensity laser therapy for painful symptoms of diabetic sensorimotor polyneuropathy: a controlled trial.

Objective: Low-intensity laser therapy (LILT) has been advocated for treatment of chronic pain disorders. Although the mechanism of pain relief is uncertain, this therapy has been suggested for relief of painful symptoms of diabetic sensorimotor polyneuropathy (DSP). The objective of this study was to determine whether LILT relieves the pain of DSP.

Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus.

Here, using a genetic approach, we dissect the roles of EphB receptor tyrosine kinases in dendritic spine development. Analysis of EphB1, EphB2, and EphB3 double and triple mutant mice lacking these receptors in different combinations indicates that all three, although to varying degrees, are involved in dendritic spine morphogenesis and synapse formation in the hippocampus. Hippocampal neurons lacking EphB expression fail to form dendritic spines in vitro and they develop abnormal spines in vivo.

Biological activity of inorganic arsenic and antimony reflects oxidation state in cultured human keratinocytes.

Sodium arsenite is much more potent than sodium arsenate in producing adverse effects in animals and in cultured cells. Although arsenate may exhibit toxicity as a phosphate analogue, its potency in vivo appears to be enhanced by reduction to arsenite. To understand the relative importance of this reduction, which is critical in evaluating the responsiveness of cell culture models to the different oxidation states and thus to elucidating the mechanism of arsenic action, present work has correlated the extent of reduction with biological activity in human keratinocytes.

Detection of lupus anticoagulant identifies patients with autoimmune haemolytic anaemia at increased risk for venous thromboembolism.

Venous thromboembolism (VTE) is a well-recognized complication of autoimmune haemolytic anaemia (AIHA), and is a major cause of morbidity and mortality in this disorder. However, the incidence, pathogenesis and risk-factors for VTE in AIHA remain poorly defined. Lupus anticoagulants (LA) and anticardiolipin (ACA) antibodies are autoantibodies directed against epitopes on prothrombin or beta2 glycoprotein I (beta2-GPI).

Conjunctival T-cell subpopulations in Sjögren's and non-Sjögren's patients with dry eye.

Purpose: To examine the conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca (SS-KCS) and non-Sjögren's keratoconjunctivitis sicca (NS-KCS) for evidence of immune-based inflammation.

Methods: Conjunctival biopsy specimens were obtained from 15 patients with SS-KCS and 15 with NS-KCS. Immunohistochemistry was performed on frozen sections to characterize and quantify T-cell subtypes (CD3, CD4, and CD8) and markers of immune activation (major histocompatibility complex [MHC] class II: HLA-DR, HLA-DQ) and inflammation (intercellular adhesion molecule [ICAM]-1).

Symmetry of nerve conduction studies in different stages of diabetic polyneuropathy.

Nerve conduction studies (NCS) in diabetic sensorimotor polyneuropathy (DSP) are sensitive, noninvasive, and associated with small coefficients of variation, and correlate well with underlying peripheral nerve morphological change. For these reasons, the current reference standard for DSP involves multivariate instruments that emphasize NCS results. However, the interside symmetry of NCS findings in different stages of DSP are unknown, although requirement for symmetry has been suggested in clinical trials of DSP.

Differential expression of transforming growth factor-beta receptors in a rabbit zone II flexor tendon wound healing model.

Flexor tendon repair in zone II is complicated by adhesions that impair normal postoperative gliding. Transforming growth factor-beta (TGF-beta) is a family of growth factors that has been implicated in scar formation. The TGF-beta family of proteins binds to three distinct classes of membrane receptors, termed RI, RII, and RIII.

A tissue sealant based on reactive multifunctional polyethylene glycol.

A rapidly gelling synthetic tissue sealant was developed from tetra-succinimidyl and tetra-thiol-derivatized polyethylene glycol (PEG). The two reagents were dissolved in aqueous buffers at 20% (w/v) solids and sprayed on the tissue site, with the use of a sprayer/mixer device. Good adhesion to collagen membranes, PTFE grafts, and carotid artery was observed in vitro.

Smoking and obesity are associated with the progression of aortic stenosis.

Objective: The purpose of the study was to identify clinical predictors of progression of aortic stenosis.

Background: The natural history of valvular aortic stenosis includes a latency period followed by an unpredictable progression. Recent investigations have shown an association between risk factors for atherosclerosis and the presence of aortic stenosis.

Sensory nerve area measurements in patients with diabetic neuropathy.

Sensory nerve potential area measurements may reflect the properties of underlying nerve fibres better than amplitude or conduction velocity measures. The terminal segment of the sensory curve may contain activity of regenerating nerve fibres. The reliability of area measurements of sensory potentials obtained with surface recording techniques is unknown.

Limits of the sympathetic skin response in patients with diabetic polyneuropathy.

We performed upper- and lower-limb sympathetic skin responses (SSRs) in a series of 337 diabetic patients with and without peripheral polyneuropathy and 38 reference subjects. We did not find any correlations between SSRs and symptoms of pain or autonomic dysfunction. The SSR correlated more strongly with vibration perception threshold (VPT) and sural nerve amplitude than with cooling detection threshold (CDT) or clinical symptoms.

[Acute hepatitis in the course of cyclosporine therapy of Crohn's disease].

Background: Cyclosporin is used for the treatment of corticosteroid-resistant inflammatory bowel disease. Secondary liver disease is a risk.

Case Report: Acute hepatitis with predominant major transaminase elevation occurred in a patient treated with cyclosporin for corticosteroid-resistant Crohnś disease.

Electrophysiological monitoring in clinical trials. Roche Neuropathy Study Group.

Electrophysiological testing remains an important efficacy parameter in clinical neuropathy trials. The quality of nerve conduction studies in reported trials varies greatly, and may be responsible for negative results. We report the utilization of an expert core lab for electrophysiological testing.

p38 mitogen-activated protein kinase expression and activation in smooth muscle.

There is relatively little known about expression and activation of p38 mitogen-activated protein kinases (MAPKs) through G protein-linked, seven-transmembrane-spanning (STM) receptors in mammalian smooth muscle. To investigate the role of p38 MAPK in smooth muscle, we cloned and sequenced the p38 MAPK expressed in canine smooth muscles. A full-length clone of the canine p38 MAPK expressed in colonic smooth muscle was obtained by RT-PCR.

Cloning and characterization of a novel endothelin receptor subtype in the avian class.

Endothelin 3 (EDN 3) and the endothelin receptor B (EDNRB) are involved in the development of neural crest and particularly of the melanocytes and the enteric nervous system. We reported previously that the avian EDNRB gene is expressed in the neural fold before crest cell migration and later on in all the neural crest derivatives except, at any developmental stage, in the melanocytic lineage. However, quail melanoblasts proliferate in response to EDN 3 stimulation in vitro.

The first pathogenic mitochondrial methionine tRNA point mutation is discovered in splenic lymphoma.

We describe a novel point mutation in the mitochondrial DNA transfer RNA methionine gene, a G-to-A transition at position 4450, in a patient with a splenic lymphoma with villous lymphocytes. The patient's lymphocytes were remarkable by the presence of large cytoplasmic inclusions demonstrated as abnormal mitochondria by electron microscopy and led to the discovery of the mutation using denaturing gradient gel electrophoresis as a screening procedure. The pathogenic potential of the mutation was clearly established by the following criteria.

Current perspective on the use of angiotensin-converting enzyme inhibitors in the management of coronary (atherosclerotic) artery disease.

Objective: To review the pathophysiology of atherosclerosis, the role of the renin-angiotensin system in atherogenesis, and studies supporting the potential beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in reducing cardiovascular events with long-term use.

Background: Through its action in converting angiotensin I to angiotensin II and by degrading bradykinin, local tissue ACE exerts many effects that can contribute to the development of atherosclerosis. Therefore, the use of ACE inhibitors can possibly result in antiatherogenic effects.