Allelotyping of endometriosis with adjacent ovarian carcinoma reveals evidence of a common lineage

Endometriosis is a common gynecological disease in which tissue similar to the endometrium proliferates at sites outside the uterine cavity. Malignant transformation of endometriosis to endometrioid and clear cell ovarian carcinomas has been documented in histological studies, but no molecular genetic evidence exists to support that endometriosis is the clonal precursor of such malignancies. We examined 14 cases of endometriosis synchronous with ovarian cancer for loss of heterozygosity on 12 chromosome arms, X chromosome inactivation, and TP53 mutation to determine whether they shared genetic alterations. In all four of the cases where the carcinoma had arisen within endometriosis and in five of the seven cases where the carcinoma was adjacent to the endometriosis, common genetic lesions were detected, consistent with a common lineage. A TP53 mutation was also detected in one case of endometriosis adjacent to carcinoma. These findings support the numerous histological observations that endometrioid and clear cell ovarian carcinomas may arise through malignant transformation of endometriotic lesions.     

Susceptibility to atrial fibrillation: a study in an ovine model of pacing-induced early heart failure

INTRODUCTION: The development of susceptibility to atrial fibrillation (AF) is a common consequence of many forms of cardiovascular disease, especially heart failure. In this study we used a sheep model of pacing-induced stable early heart failure to describe, quantify, and relate the level of susceptibility to AF to changes in structural and electrophysiologic parameters. METHODS AND RESULTS: Epicardial electrodes were implanted on the atria and right ventricles of nine sheep. The AF threshold, atrial vulnerability period, atrial effective refractory period (ERP), and interatrial conduction time were examined during control and over a 6-week period of ventricular pacing at 190 beats/min. Left atrial (LA) area and left ventricular (LV) fractional shortening were monitored using echocardiography. There were significant increases in LA susceptibility to AF (P < 0.0003), LA area (P < 0.0002), and LA ERP400 (P < 0.0002). Rate of increase in LA area was related positively to AF susceptibility (P = 0.02) and inversely to LA ERP400 (P = 0.002). LV fractional shortening decreased to approximately 50% of control value (P < 0.00001). No changes were observed in right atrial electrophysiology. CONCLUSION: In this study, susceptibility (the ability of an extrastimulus to induce AF) was rigorously measured within a predetermined format. Significant relationships were found to exist between susceptibility, certain of the observed changes in atrial electrophysiology and structure.     

Modulation of C-type inactivation by K+ at the potassium channel selectivity filter

With prolonged or repetitive activation, voltage-gated K+ channels undergo a slow (C-type) inactivation mechanism, which decreases current flow through the channel. Previous observations suggest that C-type inactivation results from a localized constriction in the outer mouth of the channel pore and that the rate of inactivation is controlled by the-rate at which K+ leaves an unidentified binding site in the pore. We have functionally identified two K+ binding sites in the conduction pathway of a chimeric K+ channel that conducts Na+ in the absence of K+. One site has a high affinity for K+ and contributes to the selectivity filter mechanism for K+ over Na+. Another site, external to the high-affinity site, has a lower affinity for K+ and is not involved in channel selectivity. Binding of K+ to the high-affinity binding site slowed inactivation. Binding of cations to the external low-affinity site did not slow inactivation directly but could slow it indirectly, apparently by trapping K+ at the high-affinity site. These data support a model whereby C-type inactivation involves a constriction at the selectivity filter, and the constriction cannot proceed when the selectivity filter is occupied by K+.     

The Latina Breast Cancer Control Study, year one: factors predicting screening mammography utilization by urban Latina women in Massachusetts

The mechanisms underlying secondary or delayed cell death following traumatic brain injury (TBI) are poorly understood. Recent evidence from experimental models of TBI suggest that diffuse and widespread neuronal damage and loss is progressive and prolonged for months to years after the initial insult in selectively vulnerable regions of the cortex, hippocampus, thalamus, striatum, and subcortical nuclei. The development of new neuropathological and molecular techniques has generated new insights into the cellular and molecular sequelae of brain trauma. This paper will review the literature suggesting that alterations in intracellular calcium with resulting changes in gene expression, activation of reactive oxygen species (ROS), activation of intracellular proteases (calpains), expression of neurotrophic factors, and activation of cell death genes (apoptosis) may play a role in mediating delayed cell death after trauma. Recent data suggesting that TBI should be considered as both an inflammatory and/or a neurodegenerative disease is also presented. Further research concerning the complex molecular and neuropathological cascades following brain trauma should be conducted, as novel therapeutic strategies continue to be developed.     

Three-dimensional structural studies on fragments of fibrinogen and fibrin

Fibrinogen is a 340 kDa glycoprotein found in the blood plasma of all vertebrates. It is transformed into a fibrin clot by the action of thrombin. Recent X-ray structures of core fragments of both fibrinogen and fibrin have revealed many details about this polymerization event. These include structures of a 30 kDa recombinant gammaC domain, an 86 kDa fragment D from human fibrinogen and a cross-linked double-D fragment from fibrin.     

New methods for measuring atlanto-axial vertical subluxation in rheumatoid arthritis by MR imaging]

This communication describes one pediatric neurosurgeon's personal view of the neurosurgical perspectives in pediatric neurooncology. Various roles of surgery, including histological verification, maximum cytoreduction, neurodecompression and restoration of the cerebrospinal fluid pathway, are emphasized. A pediatric neurosurgeon, who is the first person to make decisions on diagnosis and treatment relating to children with brain tumors, should be up to date with advances in diagnostic and therapeutic methods. Particularly, he or she should be familiar with both the efficacy and the side effects of radiation therapy and chemotherapy to allow selection of the optimum treatment for such children.     

Motor performance following a mild traumatic brain injury in children: an exploratory study

Mild Traumatic Brain Injury (TBI) is a common occurrence in the paediatric population and, as the concept of motor performance has not been assessed specifically in this population, the purpose of this study was to determine if motor performance deficits are present and can be objectively identified in a sample of children having sustained a mild TBI (Glasgow Coma Scale score 13-15). Twenty-eight children aged between 5 and 15 years were recruited immediately post-trauma. Subjects were considered normal on standard neurological exam at the time of discharge. They were assessed 13-18 days post-trauma using the Bruininks-Oseretsky Test of Motor Proficiency, a norm referenced clinical standardized assessment tool. Compared to published norms, motor performance was significantly lower in domains of balance, response speed and running speed an agility (t-test p < 0.01), and significantly higher in domains of upper extremity coordination and visual motor control (t-test p < 0.01). Although excellent performance can be observed in domains requiring upper limb coordination, motor planning and execution of motor tasks, deficits in balance and response speed can be identified in a significant number of children even after mild TBI. More specific and sensitive evaluations are necessary to identify the exact nature of the problems and evaluate their functional impact on daily activities.