tbuckley/cabot-search huggingface dataset:
Heat-Related Mortality and Adaptation to Heat in the United States
Authors: Jennifer F. Bobb, Roger D. Peng, Michelle L. Bell, Francesca Dominici
Journal: Environmental Health Perspectives (2014)

Background: In a changing climate, increasing temperatures are anticipated to have profound health impacts. These impacts could be mitigated if individuals and communities adapt to changing exposures; however, little is known about the extent to which the population may be adapting.Objective: We investigated the hypothesis that if adaptation is occurring, then heat-related mortality would be decreasing over time.Methods: We used a national database of daily weather, air pollution, and age-stratified mortality rates for 105 U.S. cities (covering 106 million people) during the summers of 1987–2005. Time-varying coefficient regression models and Bayesian hierarchical models were used to estimate city-specific, regional, and national temporal trends in heat-related mortality and to identify factors that might explain variation across cities.Results: On average across cities, the number of deaths (per 1,000 deaths) attributable to each 10°F increase in same-day temperature decreased from 51 [95% posterior interval (PI): 42, 61] in 1987 to 19 (95% PI: 12, 27) in 2005. This decline was largest among those ≥ 75 years of age, in northern regions, and in cities with cooler climates. Although central air conditioning (AC) prevalence has increased, we did not find statistically significant evidence of larger temporal declines among cities with larger increases in AC prevalence.Conclusions: The population has become more resilient to heat over time. Yet even with this increased resilience, substantial risks of heat-related mortality remain. Based on 2005 estimates, an increase in average temperatures by 5°F (central climate projection) would lead to an additional 1,907 deaths per summer across all cities.Citation: Bobb JF, Peng RD, Bell ML, Dominici F. 2014. Heat-related mortality and adaptation to heat in the United States. Environ Health Perspect 122:811–816; http://dx.doi.org/10.1289/ehp.1307392
Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathway
Authors: Youren Tong, Emilie Giaime, Hiroo Yamaguchi, Takaharu Ichimura, Yumin Liu, Huiqing Si, Huaibin Cai, Joseph V Bonventre, Jie Shen
Journal: Molecular Neurodegeneration (2012)

Dominantly inherited missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease, but its normal physiological function remains unclear. We previously reported that loss of LRRK2 causes impairment of protein degradation pathways as well as increases of apoptotic cell death and inflammatory responses in the kidney of aged mice. Our analysis of LRRK2-/- kidneys at multiple ages, such as 1, 4, 7, and 20 months, revealed unique age-dependent development of a variety of molecular, cellular, and ultrastructural changes. Gross morphological abnormalities of the kidney, including altered size, weight, texture, and color, are evident in LRRK2-/- mice at 3-4 months of age, along with increased accumulation of autofluorescent granules in proximal renal tubules. The ratio of kidney/body weight in LRRK2-/- mice is increased at 1, 4, and 7 months of age (~10% at 1 month, and ~20% at 4 and 7 months), whereas the ratio is drastically decreased at 20 months of age (~50%). While kidney filtration function evaluated by levels of blood urea nitrogen and serum creatinine is not significantly affected in LRRK2-/- mice at 12-14 months of age, expression of kidney injury molecule-1, a sensitive and specific biomarker for epithelial cell injury of proximal renal tubules, is up-regulated (~10-fold). Surprisingly, loss of LRRK2 causes age-dependent bi-phasic alterations of the autophagic activity in LRRK2-/- kidneys, which is unchanged at 1 month of age, enhanced at 7 months but reduced at 20 months, as evidenced by corresponding changes in the levels of LC3-I/II, a reliable autophagy marker, and p62, an autophagy substrate. Levels of α-synuclein and protein carbonyls, a general oxidative damage marker, are also decreased in LRRK2-/- kidneys at 7 months of age but increased at 20 months. Interestingly, the age-dependent bi-phasic alterations in autophagic activity in LRRK2-/- kidneys is accompanied by increased levels of lysosomal proteins and proteases at 1, 7, and 20 months of age as well as progressive accumulation of autolysosomes and lipofuscin granules at 4, 7-10, and 20 months of age. LRRK2 is important for the dynamic regulation of autophagy function in vivo.
Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection
Authors: Ganesh A. Kolumam, Sunil Thomas, Lucas J. Thompson, Jonathan Sprent, Kaja Murali-Krishna
Journal: The Journal of Experimental Medicine (2005)

T cell expansion and memory formation are generally more effective when elicited by live organisms than by inactivated vaccines. Elucidation of the underlying mechanisms is important for vaccination and therapeutic strategies. We show that the massive expansion of antigen-specific CD8 T cells that occurs in response to viral infection is critically dependent on the direct action of type I interferons (IFN-Is) on CD8 T cells. By examining the response to infection with lymphocytic choriomeningitis virus using IFN-I receptor–deficient (IFN-IR0) and –sufficient CD8 T cells adoptively transferred into normal IFN-IR wild-type hosts, we show that the lack of direct CD8 T cell contact with IFN-I causes &amp;gt;99% reduction in their capacity to expand and generate memory cells. The diminished expansion of IFN-IR0 CD8 T cells was not caused by a defect in proliferation but by poor survival during the antigen-driven proliferation phase. Thus, IFN-IR signaling in CD8 T cells is critical for the generation of effector and memory cells in response to viral infection.
Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration
Authors: Kristin J. Meyers, Zhe Liu, Amy E. Millen, Sudha K. Iyengar, Barbara A. Blodi, Elizabeth Johnson, D. Max Snodderly, Michael L. Klein, Karen M. Gehrs, Lesley Tinker, Gloria E. Sarto, Jennifer Robinson, Robert B. Wallace, Julie A. Mares
Journal: Ophthalmology (2015)
Acute Renal Failure in Patients with Sepsis in a Surgical ICU
Authors: Eric A.J. Hoste, Norbert H. Lameire, Raymond C. Vanholder, Dominique D. Benoit, Johan M.A. Decruyenaere, Francis A. Colardyn
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Acute renal failure (ARF) is a common complication in intensive care unit (ICU) patients. Although there are several reports on outcome of septic patients with ARF, there are no data regarding predisposing factors for ARF. Therefore, the incidence of ARF was investigated in 185 sepsis patients admitted in a surgical ICU during a 16-mo period. Variables predisposing to ARF on day 1 of sepsis were evaluated with univariate and multivariable analyses. APACHE II and SOFA scores were compared during a 14-d period. Additionally, the impact of organ failure on mortality was evaluated. ARF developed in 16.2% of the patients, and 70.0% of these needed renal replacement therapy (RRT). Patients with ARF were more severely ill and had a higher mortality. Remarkably, serum creatinine was already increased on day 1. Creatinine > 1 mg/dl and pH < 7.30, both on day 1 of sepsis, were independently associated with ARF. Age, need for vasoactive therapy, mechanical ventilation, and RRT, but not ARF itself, were associated with mortality. In conclusion, ARF was a frequent complication in sepsis. Sepsis patients with ARF were more severely ill and had a higher mortality. Need for RRT was independently associated with mortality. A simple risk model for ARF, on basis of two readily available parameters on day 1 of sepsis, was developed. This model allows initiating specific therapeutic measures earlier in the course of sepsis, hopefully resulting in a lower incidence of ARF and needi for RRT, thereby lowering mortality. E-mail: [email protected]
Effects of STI571 (gleevec) on pancreatic cancer cell growth.
Authors: Junsheng Li, Jörg Kleeff, Junchao Guo, Lars Fischer, Nathalia Giese, Markus W Büchler, Helmut Friess
Journal: Molecular Cancer (2003)

Pancreatic cancer is an aggressive malignancy characterized by low responsiveness to chemotherapy and radiotherapy. This resistance is partly due to the overexpression of several tyrosine kinase receptors and their ligands. STI571 has specific activity in inhibiting c-kit, PDGF and Abl receptor tyrosine kinases and has proven successful in the treatment of CML and GIST patients. Here, we investigated the potential role of STI571 in pancreatic cancer.The GI50 of STI571 as well as the effects of STI571 on growth factor actions in pancreatic cell lines were analyzed using the MTT assay. FACS analysis using Annexin and PI staining was performed to study cell cycle, apoptosis, and cell death. Western blot analysis was carried out to investigate MAP kinase and receptor tyrosine kinase phosphorylation. STI571 inhibited cell proliferation in pancreatic cancer cell lines with GI50 concentrations ranging from 17 to 31.5 microM. EGF, IGF-1, and FGF-2 but not PDGF exerted growth stimulatory effects in pancreatic cancer cell lines. STI571 only partly blocked these effects on cell growth, and did not abrogate growth factor-induced receptor and MAPK phosphorylation.Our data demonstrate that STI571 inhibits pancreatic cancer cell growth with high GI50 concentrations through tyrosine-kinase receptor independent pathways. The clinical application of STI571 in pancreatic cancer is therefore rather doubtful.
The Stability of the Glomerular Filtration Rate after Renal Transplantation Is Improving
Authors: Sita Gourishankar, Lawrence G. Hunsicker, Gian S. Jhangri, Sandra M. Cockfield, Philip F. Halloran
Journal: Journal of the American Society of Nephrology (2003)

The 6-mo function and the stability of function posttransplantation in 429 cadaver renal transplants was investigated from 1990 to 2000. The 6-mo creatinine clearance (CrCl) and the rate of change of CrCl beyond 6 mo posttransplantation were calculated. The mean 6-mo CrCl was 64.6 +/- 1.1 ml/min and was stable between 1990 and 2000. The net slope of CrCl was -1.4 +/- 0.5 ml/min per yr. The slope has improved in recent years, such that the mean slopes in the period after 1997 are actually positive (+3.5 ml/min per yr). The slope of CrCl beyond 6 mo was not related to the actual value of the 6 mo CrCl, i.e., there was no accelerated loss of function at low CrCl levels. The 6-mo CrCl was independently determined by donor factors (age, gender), recipient factors (age, gender), and immune factors (rejection episodes, regraft status). The slope of the CrCl correlated independently with the transplant year, recipient gender, rejection episodes, diastolic BP, and the choice of immunosuppressive drugs. Cytomegalovirus infection and mismatch status and lipid levels and treatment were not independently associated with slope or 6-mo CrCl. Thus, the most striking change in the course of renal transplants over the past decade is the new stability of function, correlating with reduced rejection and probably due at least in part to the new immunosuppressive agents. Despite continued calcineurin inhibitor use, late improvement in function now occurs in many cadaver kidney transplants, suggesting a previously unappreciated capacity for functional adaptation.
Multiple myeloma cell survival relies on high activity of protein kinase CK2
Authors: Francesco A. Piazza, Maria Ruzzene, Carmela Gurrieri, Barbara Montini, Luca Bonanni, Gino Chioetto, Giovanni Di Maira, Francesca Barbon, Anna Cabrelle, Renato Zambello, Fausto Adami, Livio Trentin, Lorenzo A. Pinna, Gianpietro Semenzato
Journal: Blood (2006)
Eczematous Skin Disease and Recall of Past Diagnoses: Implications for Smallpox Vaccination
Authors: Allison L. Naleway, Edward A. Belongia, Robert T. Greenlee, Burney A. Kieke, Robert T. Chen, David K. Shay
Journal: Annals of Internal Medicine (2003)

Persons with atopic dermatitis or eczema, regardless of disease severity or activity, may develop eczema vaccinatum if they or their close contacts receive the smallpox vaccine. According to current recommendations, a preexposure vaccination program should identify these persons and exclude them from participating.To determine the prevalence of diagnosed atopic dermatitis and eczema in a defined population and assess the sensitivity of screening questions to identify patients who have received these diagnoses.Population-based prevalence survey and telephone interview.14 ZIP code regions in Wisconsin.Persons given a diagnosis of atopic dermatitis or eczema in 2000 and 2001 were identified from a population-based cohort. Persons with a history of atopic dermatitis diagnosed since 1979 were eligible for the telephone survey.Prevalence of diagnosed atopic dermatitis or eczema; proportions of respondents able to recall a past diagnosis of atopic dermatitis, eczema, or recurrent rash.The prevalence of atopic dermatitis or eczema diagnosis in 2000 or 2001 was 0.8%. At least 2.4% of the cohort would be ineligible for smallpox vaccination because of active skin disease in themselves or household members. Among 94 adult respondents with atopic dermatitis, 55 (59%) correctly self-reported skin disease. Seventy-nine (60%) of 133 household contacts of adults with atopic dermatitis correctly reported the presence of skin disease in a household member. Parental recall of skin disease in children with atopic dermatitis was 70% (123 of 177).Identifying dermatologic contraindications to smallpox vaccination by relying only on a self-reported history of rash illnesses is likely to miss a substantial proportion of individuals who should not receive smallpox vaccine in a preexposure vaccination campaign.
Bcl2 is an independent prognostic marker of triple negative breast cancer (TNBC) and predicts response to anthracycline combination (ATC) chemotherapy (CT) in adjuvant and neoadjuvant settings
Authors: T.M.A. Abdel-Fatah, C. Perry, P. Dickinson, G. Ball, P. Moseley, S. Madhusudan, I.O. Ellis, S.Y.T. Chan
Journal: Annals of Oncology (2013)
Interaction of fiber orientation and direction of impulse propagation with anatomic barriers in anisotropic canine myocardium.
Authors: A Kadish, M Shinnar, E N Moore, J H Levine, C W Balke, J F Spear
Journal: Circulation (1988)

We developed a computer model of the interaction of impulse propagation with anatomic barriers in uniformly anisotropic tissue. Its predictions were confirmed experimentally by using an in vitro cut to create a 6 X 1-mm anatomic barrier in 12 canine epicardial strips. The model predicted that long, thin barriers located parallel to the direction of impulse propagation would have little effect in delaying conduction regardless of the arrangement of cardiac fibers. In this situation, the mean experimental ratio of postcut to control conduction times across the barrier was 1.05:1.00 in 10 tissues. When impulses were proceeding perpendicular to an anatomic barrier, significant distal conduction delay was predicted and found to occur only when the conduction from pacing to recording sites was initially longitudinal to fiber orientation (mean experimental ratio, 2.34:1.00 in five tissues) but not transverse to fiber orientation (ratio, 1.08:1.00 in five tissues). We conclude that the direction of initial impulse propagation and the orientation of myocardial fibers have large effects on the degree to which anatomic barriers delay activation in cardiac tissue. These findings may have implications for the participation of anatomic barriers in reentrant circuits.
Dynamic Model for Predicting Death Within 12 Months in Patients With Primary or Post–Polycythemia Vera/Essential Thrombocythemia Myelofibrosis
Authors: Constantine S. Tam, Hagop Kantarjian, Jorge Cortes, Alice Lynn, Sherry Pierce, Lingsha Zhou, Michael J. Keating, Deborah A. Thomas, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2009)

Purpose Current prognostic tools in myelofibrosis (MF) fail to identify patients at the highest risk of death and are limited by their applicability only to the time of diagnosis. We aimed to define an accelerated phase (AP) in MF by characterizing disease features that can identify patients with median overall survival of ≤ 12 months at any time in the disease course. Patients and Methods Baseline characteristics of 370 consecutive patients with MF from a single center were analyzed to identify features associated with a median overall survival of ≤ 12 months. These putative AP features were then validated by following the course of chronic-phase patients (no AP features at baseline) until the development of one or more AP features and determining their subsequent survival. Results The following three characteristics were associated with poor survival at baseline and were selected as putative AP features: blasts in blood or bone marrow ≥ 10%, platelets less than 50 × 10 9 /L, and chromosome 17 aberrations (median overall survival, 10, 12, and 5 months, respectively). In the validation phase, chronic-phase patients who developed AP features during follow-up were found to have short subsequent survival times (median overall survival, 12, 15, and 6 months, respectively). AP was a necessary step in the progression to blast phase, with leukemic transformation being exceedingly rare (3% risk at 10 years) in patients who remained persistently in chronic phase. Conclusion Blood or bone marrow blasts ≥ 10%, platelets less than 50 × 10 9 /L, and chromosome 17 aberrations defined AP in patients with MF. Patients in AP should be candidates for intensive therapeutic interventions.
Effects of intravenous amino acid infusion and dietary proteins on kidney function in cirrhosis
Authors: Salvatore Badalamenti, Pere Gines, Vicente Arroyo, Josep Llach, Carlos Piera, Antoni Rimola, Wladimiro Jimenez, Joan Gaya, Roser Casamitjana, Francisca Rivera, Joan Rodes
Journal: Hepatology (1990)

Acute intravenous amino acid infusion or a highprotein diet increases renal plasma flow and the glomerular filtration rate in healthy subjects. Conversely, a low-protein diet reduces renal plasma flow and glomerular filtration rate. The aim of this study was to investigate the effect of intravenous amino acid infusion and dietary proteins on kidney function in cirrhosis. Protocol 1: renal plasma flow and glomerular filtration rate were measured before and during intravenous administration of a 10% amino acid solution (0.043 ml/kg/min) to eight compensated cirrhotic patients (group 1), nine nonazotemic cirrhotic patients with ascites (group 2) and seven cirrhotic patients with ascites and functional renal failure (group 3). Amino acid administration induced a significant increase in renal plasma flow and glomerular filtration rate in all groups studied. Renal plasma flow and glomerular filtration rate increased by 16% and 14%, and 21% in group 3. Protocol 2: Renal plasma flow and glomerular filtration rate were measured in nine cirrhotic patients with ascites after 11 days on a low-protein diet (0.5 gm/kg body weight/day) and also after the patients followed for 11 days a moderately high-protein diet (1.5 gm/kg body weight/day). The moderately high-protein diet was associated with a significant increase in renal plasma flow (12%) and glomerular filtration rate (13%) compared with values obtained while the patients followed the low-protein diet. Plasma glucagon levels increased markedly during the intravenous administration of amino acid and the intake of the moderately highprotein diet. However, no correlation existed between changes in renal plasma flow and glomerular filtration rate induced by intravenous amino acid or dietary proteins and changes in plasma glucagon levels. The renal effects of intravenous amino acid or dietary proteins were not associated with significant changes in plasma renin and norepinephrine levels and urinary excretion of 6-keto-prostaglandin-F1α. In conclusion, a moderately high-protein diet or intravenous amino acid administration increases renal plasma flow and glomerular filtration rate in cirrhosis. (HEPATOLOGY 1990; 11: 379–386.)
Gαi2-mediated protection from ischaemic injury is modulated by endogenous RGS proteins in the mouse heart
Authors: Rachael E. Waterson, Corbin G. Thompson, Nathaniel W. Mabe, Kuljeet Kaur, Jeffery N. Talbot, Richard R. Neubig, Boyd R. Rorabaugh
Journal: Cardiovascular Research (2011)

Regulator of G protein signalling (RGS) proteins act as molecular 'off switches' that terminate G protein signalling by catalyzing the hydrolysis of Gα-bound GTP to GDP. Many different Gαi-coupled receptors have been implicated in the cardioprotective effects of ischaemic preconditioning. However, the role of RGS proteins in modulating cardioprotection has not been previously investigated. We used mice that were homozygous (GS/GS) or heterozygous (GS/+) for a mutation in Gαi2 rendering it RGS-insensitive (G184S) to determine whether interactions between endogenous RGS proteins and Gαi2 modulate Gαi-mediated protection from ischaemic injury. Langendorff-perfused mouse hearts were subjected to 30 min global ischaemia and 2 h reperfusion. Infarcts in GS/GS (14.5% of area at risk) and GS/+ (22.6% of AAR) hearts were significantly smaller than those of +/+ hearts (37.2% of AAR) and recovery of contractile function was significantly enhanced in GS/GS and GS/+ hearts compared with +/+ hearts. The cardioprotective phenotype was not reversed by wortmannin or U0126 but was reversed by 5-hydroxydecanoic acid and HMR 1098, indicating that RGS-insensitive Gαi2 protects the heart through a mechanism that requires functional ATP-dependent potassium channels but does not require acute activation of extracellular-regulated kinase or Akt signalling pathways. This is the first study to demonstrate that Gαi2-mediated cardioprotection is suppressed by RGS proteins. These data suggest that RGS proteins may provide novel therapeutic targets to protect the heart from ischaemic injury.