University of Tennessee Health Science Center

About: University of Tennessee Health Science Center is a education organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 15716 authors who have published 26884 publications receiving 1176697 citations.

LKB1 modulates lung cancer differentiation and metastasis

Abstract: Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers. Although uncommon in most sporadic cancers, inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell lines. Here we used a somatically activatable mutant Kras-driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer. Although Kras mutation cooperated with loss of p53 or Ink4a/Arf (also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1. Lkb1-deficient tumours demonstrated shorter latency, an expanded histological spectrum (adeno-, squamous and large-cell carcinoma) and more frequent metastasis compared to tumours lacking p53 or Ink4a/Arf. Pulmonary tumorigenesis was also accelerated by hemizygous inactivation of Lkb1. Consistent with these findings, inactivation of LKB1 was found in 34% and 19% of 144 analysed human lung adenocarcinomas and squamous cell carcinomas, respectively. Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer. These studies establish LKB1 as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis.

A network of fast-spiking cells in the neocortex connected by electrical synapses.

Abstract: Encoding of information in the cortex is thought to depend on synchronous firing of cortical neurons1,2. Inhibitory neurons are known to be critical in the coordination of cortical activity3,4,5, but how interaction among inhibitory cells promotes synchrony is not well understood4,6,7,8,9,10,11,12. To address this issue directly, we have recorded simultaneously from pairs of fast-spiking (FS) cells, a type of γ-aminobutyric acid (GABA)-containing neocortical interneuron13. Here we report a high occurrence of electrical coupling among FS cells. Electrical synapses were not found among pyramidal neurons or between FS cells and other cortical cells. Some FS cells were interconnected by both electrical and GABAergic synapses. We show that communication through electrical synapses allows excitatory signalling among inhibitory cells and promotes their synchronous spiking. These results indicate that electrical synapses establish a network of fast-spiking cells in the neocortex which may play a key role in coordinating cortical activity.

Inflammatory markers and onset of cardiovascular events: results from the Health ABC study.

Abstract: Background— Inflammation plays an important role in cardiovascular disease The aim of this study is to investigate the predictive value of several inflammatory markers on the incidence of cardiovascular events in well-functioning older persons Methods and Results— The subjects were 2225 participants 70 to 79 years old, without baseline cardiovascular disease, who were enrolled in the Health, Aging, and Body Composition study Incident coronary heart disease (CHD), stroke, and congestive heart failure (CHF) events were detected during an average follow-up of 36 years Blood levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) were assessed After adjustment for potential confounders, IL-6 was significantly associated with all outcomes (CHD events, per IL-6 SD increase: RR, 127; 95% CI, 110 to 148; stroke events, per IL-6 SD increase: RR, 145; 95% CI, 112 to 186; CHF events, per IL-6 SD increase: RR, 172; 95% CI, 140 to 212) TNF-α showed significant asso

The Metabolic Syndrome, Inflammation, and Risk of Cognitive Decline

Abstract: ContextSeveral studies have reported an association between the metabolic syndrome and cardiovascular disease Despite an increasing awareness that cardiovascular risk factors increase risk of cognitive decline and dementia, there are few data on the metabolic syndrome and cognitionObjectiveTo determine if the metabolic syndrome is a risk factor for cognitive decline and if this association is modified by inflammationDesign and SettingA 5-year prospective observational study conducted from 1997 to 2002 at community clinics at 2 sitesParticipantsA total of 2632 black and white elders (mean age, 74 years)Main Outcome MeasuresAssociation of the metabolic syndrome (measured using National Cholesterol Education Program guidelines) and high inflammation (defined as above median serum level of interleukin 6 and C-reactive protein) with change in cognition (Modified Mini-Mental State Examination [3MS]) at 3 and 5 years Cognitive impairment was defined as at least a 5-point declineResultsCompared with those without the metabolic syndrome (n = 1616), elders with the metabolic syndrome (n = 1016) were more likely to have cognitive impairment (26% vs 21%, multivariate adjusted relative risk [RR], 120; 95% confidence interval [CI], 102-141) There was a statistically significant interaction with inflammation and the metabolic syndrome (P = 03) on cognitive impairment After stratifying for inflammation, those with the metabolic syndrome and high inflammation (n = 348) had an increased likelihood of cognitive impairment compared with those without the metabolic syndrome (multivariate adjusted RR, 166; 95% CI, 119-232) Those with the metabolic syndrome and low inflammation (n = 668) did not exhibit an increased likelihood of impairment (multivariate adjusted RR, 108; 95% CI, 089-130) Stratified multivariate random-effects models demonstrated that participants with the metabolic syndrome and high inflammation had greater 4-year decline on 3MS (P = 04) compared with those without the metabolic syndrome, whereas those with the metabolic syndrome and low inflammation did not (P = 44)ConclusionThese findings support the hypothesis that the metabolic syndrome contributes to cognitive impairment in elders, but primarily in those with high level of inflammation