ABSTRACT
Familial Mediterranean fever (FMF), inherited in an autosomal recessive manner, is a systemic auto-inflammatory disorder characterized by recurrent attacks of fever with peritonitis, pleuritis, synovitis and erysipeloid rash. The marenostrin-encoding fever (MEFV) gene, located on chromosome 16p13.3, is the only gene in which mutations are currently known to cause FMF. To correlate specific genotypes with adverse phenotypes of affected populations residing in the Western United States, a retrospective case series review was conducted of all MEFV gene mutation testing completed at UCLA Clinical Molecular Diagnostic Laboratory between February 2002 and February 2012, followed by clinical chart review of all subjects who either have a single or double mutation. All 12 common mutations in the MEFV gene were analyzed and the M694V variant was found to be associated with an adverse FMF clinical outcome in the Armenian-American population, manifested by earlier onset of disease, increased severity of disease, and renal amyloidosis.
Subject(s)
Chromosomes, Human, Pair 16 , Cytoskeletal Proteins/genetics , Familial Mediterranean Fever/ethnology , Familial Mediterranean Fever/genetics , Mutation , Adolescent , Age of Onset , California/epidemiology , Ethnicity , Female , Genes, Recessive , Heterozygote , Homozygote , Humans , Male , Pyrin , Retrospective Studies , Severity of Illness IndexABSTRACT
The firing properties of dopamine (DA) neurons in the substantia nigra (SN) pars compacta are strongly influenced by the activity of apamin-sensitive small conductance Ca(2+)-activated K(+) (SK) channels. Of the three SK channel genes expressed in central neurons, only SK3 expression has been identified in DA neurons. The present findings show that SK2 was also expressed in DA neurons. Immuno-electron microscopy (iEM) showed that SK2 was primarily expressed in the distal dendrites, while SK3 was heavily expressed in the soma and, to a lesser extent, throughout the dendritic arbor. Electrophysiological recordings of the effects of the SK channel blocker apamin on DA neurons from wild type and SK(-/-) mice show that SK2-containing channels contributed to the precision of action potential (AP) timing, while SK3-containing channels influenced AP frequency. The expression of SK2 in DA neurons may endow distinct signaling and subcellular localization to SK2-containing channels.
Subject(s)
Action Potentials/physiology , Dopaminergic Neurons/physiology , Small-Conductance Calcium-Activated Potassium Channels/metabolism , Action Potentials/drug effects , Animals , Apamin/pharmacology , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Mice , Mice, Knockout , Small-Conductance Calcium-Activated Potassium Channels/genetics , Substantia Nigra/drug effects , Substantia Nigra/metabolismABSTRACT
The present epidemic of carcinoma of the lung is a consequence of society's indulence of cigarette smoking. Most of the progress in treatment has resulted from more accurate staging of the cancer at the time of diagnosis and the selection of the safest therapy. Future progress hinges on the public health measures to stop smoking, and to a much lesser degree on earlier diagnosis and advances in radiotherapy and chemotherapy.
Subject(s)
Lung Neoplasms , Adenocarcinoma/pathology , Adenocarcinoma, Bronchiolo-Alveolar/pathology , Adult , Carcinoma, Small Cell/pathology , Carcinoma, Squamous Cell/pathology , Female , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Neoplasm Invasiveness , Neoplasm Metastasis , Smoking/complicationsABSTRACT
A new complication of transvenous pacing is described. Twists developing in an endocardial lead indicate that the pulse generator pocket is too large. Pacemaker failure because of electrode dislodgement or lead fracture will ensue.
