Activation of signal transducers and activators of transcription 1 and 3 by leukemia inhibitory factor, oncostatin-M, and interferon-γ in adipocytes

We have recently demonstrated that signal transducers and activators of transcription (STATs) 1, 3, 5A, 5B, and 6 are expressed in both cultured and native adipocytes. Our current studies have focused on the activation of STATs 1 and 3 by leukemia inhibitory factor (LIF), oncostatin-M (OSM), and interferon-γ, (IFNγ) in 3T3-L1 adipocytes. IFNγ is shown to be a potent activator of STAT 1 as indicated by both tyrosine phosphorylation and nuclear translocation. However, LIF and OSM, which are potent inducers of STAT 3, are less potent activators of STAT 1 as measured by both tyrosine phosphorylation and nuclear translocation. Both STATs 1 and 3 were translocated to the nucleus in a time-dependent fashion following LIF treatment. In addition, IFNγ resulted in a time- and dose-dependent effect on STATs 1 and 3 nuclear translocation. Growth hormone, a potent activator of STATs 5A and 5B, had a minimal effect on STAT 1 and STAT 3 tyrosine phosphorylation. Preincubation with either insulin or growth hormone had no detectable effects on the tyrosine phosphorylation or nuclear translocation of STATs 1 and 3 induced by LIF, OSM, or IFNγ. The effects of LIF and IFNγ on STAT 1 and 3 tyrosine phosphorylation and nuclear translocation were confirmed in native rat adipocytes. In 3T3-L1 adipocytes, a low level of serine phosphorylation of STAT 3 on residue 727 was observed and was markedly enhanced by insulin, LIF, or OSM. This increase in STAT 3 Ser727 phosphorylation was dependent upon the activation of MAPK, since the MAPK kinase inhibitor (PD98059) reduced STAT 3 Ser727 phosphorylation to basal levels. The inhibition of MAPK had no effect on the ability of STATs 1 and 3 to be tyrosine-phosphorylated or translocate to the nucleus. These studies demonstrate the highly specific and quantitative activation of STATs 1 and 3 by LIF, OSM, and IFNγ in adipocytes and indicate that STAT 3 is a substrate for MAPK in adipocytes

On the association of terrestrial gamma-ray bursts with lightning and implications for sprites

Includes bibliographical references (page [1020]).Measurements of ELF/VLF radio atmospherics (sferics) at Palmer Station, Antarctica, provide evidence of active thunderstorms near the inferred source regions of two different gamma-ray bursts of terrestrial origin [Fishman et al., 1994]. In one case, a relatively intense sferic occurring within ±1.5 ms of the time of the gamma-ray burst provides the first indication of a direct association of this burst with a lightning discharge. This sferic and many others launched by positive cloud-to-ground (CG) discharges and observed at Palmer during the periods studied exhibit 'slow tail' waveforms, indicative of continuing currents in the causative lightning discharges. The slow tails of these sferics are similar to those of sferics originating in positive CG discharges that are associated with sprites

In Situ Probes of the First Galaxies and Reionization: Gamma-ray Bursts

The first structures in the Universe formed at z>7, at higher redshift than all currently known galaxies. Since GRBs are brighter than other cosmological sources at high redshift and exhibit simple power-law afterglow spectra that is ideal for absorption studies, they serve as powerful tools for studying the early universe. New facilities planned for the coming decade will be able to obtain a large sample of high-redshift GRBs. Such a sample would constrain the nature of the first stars, galaxies, and the reionization history of the Universe.Comment: 8 pages, 3 figures, science white paper submitted to the US Astro2010 Decadal Surve

Longitudinal change in the BODE index predicts mortality in severe emphysema

Rationale: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients. Objectives: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival. Methods: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components. Measurements and Main Results: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91943/1/2008 AJRCCM Longitudinal change in the BODE index predicts mortality in severe emphysema.pd

Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis

OBJECTIVE: The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP). METHODS: We determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations. RESULTS: Of 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups. CONCLUSIONS: Obesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up