tbuckley/cabot-search huggingface dataset:
CD8+T cell–specific induction of NKG2D receptor by doxorubicin plus interleukin-12 and its contribution to CD8+T cell accumulation in tumors
Authors: Jiemiao Hu, Shiguo Zhu, Xueqing Xia, Liangfang Zhang, Eugenie S Kleinerman, Shulin Li
Journal: Molecular Cancer (2014)

Increased infiltration of CD8+T cells into tumors has a positive impact on survival. Our previous study showed that doxorubicin (Dox) plus interleukin-12 (IL-12) boosted the accumulation of CD8+T cells in tumors and had a greater antitumor effect than did either agent alone. The purpose of this study was to determine the impact of NKG2D expression on CD8+T cell infiltration and antitumor efficacy.Tumor-bearing mice were administered Dox, IL-12 plasmid DNA, or both via intraperitoneal injection or intramuscular electroporation. The induction of NKG2D on CD8+T cells and other lymphocytes was analyzed via flow cytometry, and NKG2D-positive CD8+T cell-specific localization in tumors was determined by using immunofluorescence staining in various types of immune cell-depleted mice.The combination of Dox plus IL-12 specifically increased expression of NKG2D in CD8+T cells but not in other types of immune cells, including NK cells, which naturally express NKG2D. This induced NKG2D expression in CD8+T cells was associated with increased accumulation of CD8+T cells in murine tumors. Administration of NKG2D-blocking antibody or CD8+T cell-depletion antibody abrogated the NKG2D+CD8+T cell detection in tumors, whereas administration of NK cell-depletion antibody had no effect. Increased NKG2D expression in CD8+T cells was associated with increased antitumor efficacy in vivo.We conclude that Dox plus IL-12 induces NKG2D in CD8+T cells in vivo and boosts NKG2D+CD8+T-dependent antitumor immune surveillance. This discovery reveals a novel mechanism for how chemoimmunotherapy synergistically promotes T cell-mediated antitumor immune surveillance.
Still Searching for Better Butter Flavoring
Authors: Carol Potera
Journal: Environmental Health Perspectives (2012)

Food Additives still searching for Better Butter FlavoringAfter diacetyl (2,3-butanedione) was shown to cause bronchiolitis obliterans in workers who inhaled high levels of this volatile butter flavoring at microwave popcorn processing plants, 1,2,3 some manufacturers switched to a substitute assumed to be safer.Recent rodent studies, however, suggest that the substitute, 2,3-pentanedione, may be as damaging to the respiratory tract as the diacetyl it replaced. 4,5ronchiolitis obliterans, or "popcorn lung," is a rare, irreversible, debilitating lung disease in which inflammation and scarring obstruct the smallest airways, the bronchioles.There is no good treatment for the disease short of a lung transplant. 6ronically, lung transplant itself can trigger bronchiolitis obliterans through organ rejection mechanisms, limiting the survival of many transplant patients. 7fter the disease was identified in popcorn workers, researchers at the National Institute for Occupational Safety and Health (NIOSH) reported bronchial epithelial damage in rats inhaling vapors of butter flavoring. 8This type of injury causes fibrosis (thickening and scarring) of the bronchioles, which is the underlying cause of bronchiolitis obliterans.In 2008 some of the same NIOSH researchers narrowed their studies to diacetyl, a major component of butter flavoring vapors, and reported similar acute damage in rats. 9he same year, Daniel Morgan, head of the Respiratory Toxicology Group at the National Institute of Environmental Health Sciences, and colleagues reported that mice develop bronchial epithelial damage after inhaling diacetyl vapors at concentrations equivalent to worker exposures. 6Rats proved even more susceptible than mice and developed full-blown bronchiolitis obliterans after repeated exposure to diacetyl. 4,10ecause diacetyl and 2,3-pentanedione,
Adenosine A2A receptor activation reduces hepatic ischemia reperfusion injury by inhibiting CD1d-dependent NKT cell activation
Authors: Courtney M. Lappas, Yuan-Ji Day, Melissa A. Marshall, Victor H. Engelhard, Joel Linden
Journal: The Journal of Experimental Medicine (2006)

Ischemia reperfusion injury results from tissue damage during ischemia and ongoing inflammation and injury during reperfusion. Liver reperfusion injury is reduced by lymphocyte depletion or activation of adenosine A2A receptors (A2ARs) with the selective agonist 4- {3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]- prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester (ATL146e). We show that NKT cells are stimulated to produce interferon (IFN)-γ by 2 h after the initiation of reperfusion, and the use of antibodies to deplete NK1.1-positive cells (NK and NKT) or to block CD1d-mediated glycolipid presentation to NKT cells replicates, but is not additive to, the protection afforded by ATL146e, as assessed by serum alanine aminotransferase elevation, histological necrosis, neutrophil accumulation, and serum IFN-γ elevation. Reduced reperfusion injury observed in RAG-1 knockout (KO) mice is restored to the wild-type (WT) level by adoptive transfer of NKT cells purified from WT or A2AR KO mice but not IFN-γ KO mice. Additionally, animals with transferred A2AR−/− NKT cells are not protected from hepatic reperfusion injury by ATL146e. In vitro, ATL146e potently inhibits both anti-CD3 and α-galactosylceramide–triggered production of IFN-γ by NKT cells. These findings suggest that hepatic reperfusion injury is initiated by the CD1d-dependent activation of NKT cells, and the activation of these cells is inhibited by A2AR activation.
Sevelamer Prevents Uremia-Enhanced Atherosclerosis Progression in Apolipoprotein E–Deficient Mice
Authors: Olivier Phan, Ognen Ivanovski, Thao Nguyen-Khoa, Nadya Mothu, Jesus Angulo, Ralf Westenfeld, Markus Ketteler, Natalie Meert, Julien Maizel, Igor G. Nikolov, Raymond Vanholder, Bernard Lacour, Tilman B. Drüeke, Ziad A. Massy
Journal: Circulation (2005)

The novel phosphate binder sevelamer has been shown to prevent the progression of aortic and coronary calcification in uremic patients. Whether it also decreases the progression of atheromatous plaques is unknown. The aim of our study was to examine the effect of sevelamer administration on the development of atherosclerosis and aortic calcification in the uremic apolipoprotein E-deficient mouse as an established model of accelerated atherosclerosis.Female mice were randomly assigned to 4 groups: 2 groups of nonuremic mice (sevelamer versus control) and 2 groups of uremic mice (sevelamer versus control). Sevelamer was given at 3% with chow. The increases in serum phosphorus concentration and calcium-phosphorus product observed in uremic control mice were prevented by sevelamer. Serum total cholesterol was increased in the 2 uremic mouse groups and remained unchanged in response to sevelamer. After 8 weeks of sevelamer treatment, uremic mice exhibited a significantly lower degree of atherosclerosis (P<0.001) and vascular calcification than uremic control mice. Of interest, sevelamer exerted an effect on both intima and media calcification (P=0.005) in uremic mice. Among possible mechanisms involved, we found no evidence for the modulation by sevelamer of inflammation or selected uremic toxins. In contrast, nitrotyrosine staining as a measure of oxidative damage was significantly decreased in response to sevelamer treatment in control and uremic mice (P<0.005).Sevelamer delays not only vascular calcification but also atherosclerotic lesion progression in uremic apolipoprotein E-deficient mice. It opens the possibility of a cholesterol-independent action of sevelamer on atheroma formation via effects on mineral metabolism, oxidative stress, or both.
Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome
Authors: Yong-Seok Lee, Dan Ehninger, Miou Zhou, Jun-Young Oh, Minkyung Kang, Chuljung Kwak, Hyun-Hee Ryu, Delana Butz, Toshiyuki Araki, Ying Cai, J Balaji, Yoshitake Sano, Christine I Nam, Hyong Kyu Kim, Bong-Kiun Kaang, Corinna Burger, Benjamin G Neel, Alcino J Silva
Journal: Nature Neuroscience (2014)
A Randomized Controlled Trial of Interventions to Promote Cervical Cancer Screening Among Chinese Women in North America
Authors: V. M. Taylor
Journal: JNCI Journal of the National Cancer Institute (2002)

North American Chinese women have lower levels of Papanicolaou (Pap) testing than other population subgroups. We conducted a randomized controlled trial to evaluate the effectiveness of two alternative cervical cancer screening interventions for Chinese women living in North America.Four hundred and eighty-two Pap testing underutilizers were identified from community-based surveys of Chinese women conducted in Seattle, Washington, and Vancouver, British Columbia. These women were randomly assigned to one of two experimental arms or control status. Several Chinese-language materials were used in both experimental arms: an education-entertainment video, a motivational pamphlet, an educational brochure, and a fact sheet. Women in the first experimental group (outreach worker intervention) received the materials, as well as tailored counseling and logistic assistance, during home visits by trilingual, bicultural outreach workers. Those in the second experimental group (direct mail intervention) received the materials by mail. The control group received usual care. Follow-up surveys were completed 6 months after randomization to ascertain participants' Pap testing behavior. All statistical tests were two-sided.A total of 402 women responded to the follow-up survey (83% response rate). Of these women, 50 (39%) of the 129 women in the outreach group, 35 (25%) of the 139 women in the direct mail group, and 20 (15%) of the 134 women in the control group reported Pap testing in the interval between randomization and follow-up data collection (P<.001 for outreach worker versus control, P =.03 for direct mail versus control, and P =.02 for outreach worker versus direct mail). Intervention effects were greater in Vancouver than in Seattle.Culturally and linguistically appropriate interventions may improve Pap testing levels among Chinese women in North America.
Cell-mediated immunity: differential maturation of mixed leukocyte reaction and cell-mediated lympholysis.
Authors: S Wu, F H Bach, R Auerbach
Journal: The Journal of Experimental Medicine (1975)

While spleen cells from neonatal B10 (H-2b) are reactive (proliferate) in one-way mixed leukocyte culture, cell-mediated lympholysis reactivity does not arise until 7 days of age. When B10 cells are sensitized to B10.D2 (H-2d), cross-killing of third-party B10.BR (H-2k) target is always lower than the specific killing of B10.D2 targets and is not demonstrable until 27 days after birth.
The demography of primary biliary cirrhosis in ontario, canada
Authors: Helga Witt-Sullivan, Jenny Heathcote, Karen Cauch, Laurence Blendis, Cameron Ghent, Allen Katz, Ruth Milner, Chris S. Pappas, James Rankin, Ian R. Wanless
Journal: Hepatology (1990)

The demographics of primary biliary cirrhosis in Ontario, Canada, are described. Two hundred and twenty–five primary biliary cirrhosis patients were identified by 85 of 502 gastroenterologists (or internists) practicing in Ontario acute care hospitals that have 150 or more beds. Two hundred and six patients were verified as being antimitochondrial antibody–positive, resulting in an incidence of 3.26 per million per year and a prevalence of 22.39 per million. Questionnaire data were obtained on 88.5% of these patients. Twenty–nine percent of the patients were found to be asymptomatic. Geographical clustering and racial predisposition were not seen. No increase in breast cancer prevalence was noted. By the time the diagnosis of primary biliary cirrhosis was established, the patients had consulted a median number of 3.5 physicians. Fatigue was reported as the most disabling symptom. The diagnosis of primary biliary cirrhosis in patients referred from across the province of Ontario was independently confirmed by us, using standard criteria (antimitochondrial antibody testing and liver biopsy), and was found to be reliable. (Hepatology 1990; 12:98-105).
Prolonged Exposure to Glucose Degradation Products Impairs Viability and Function of Human Peritoneal Mesothelial Cells
Authors: JANUSZ WITOWSKI, JUSTYNA WISNIEWSKA, KATARZYNA KORYBALSKA, THORSTEN O. BENDER, ANDRZEJ BREBOROWICZ, GERHARD M. GAHL, ULRICH FREI, JUTTA PASSLICK-DEETJEN, ACHIM JÖRRES
Journal: Journal of the American Society of Nephrology (2001)

Bioincompatibility of peritoneal dialysis fluids (PDF) has been linked to the presence of glucose degradation products (GDP). Previous experiments have shown that short-term exposure to several GDP at concentrations found in commercially available PDF had no significant effect on human peritoneal mesothelial cells (HPMC). During continuous ambulatory peritoneal dialysis, however, cells are continually exposed to GDP for extended periods of time. Thus, the impact of GDP on HPMC during long-term exposure was assessed. HPMC were cultured for up to 36 d in the presence of 6 identified GDP (acetaldehyde, formaldehyde, furaldehyde, glyoxal, methylglyoxal, and 5-HMF) at doses that reflect their concentrations in conventional PDF. At regular time intervals, the ability of HPMC to secrete cytokines (interleukin-6 [IL-6]) and extracellular matrix molecules (fibronectin) was evaluated. In addition, cell viability, morphology, and proliferative potential were assessed. Exposure to GDP resulted in a significant reduction in mesothelial IL-6 and fibronectin release. Approximately 80% of this decrease occurred during the first 12 d of the exposure and was paralleled by a gradual loss of cell viability and development of morphologic alterations. After 36 d of exposure, the number of cells in GDP-treated cultures was reduced by nearly 60%. However, GDP-treated cells were able to resume normal proliferation when transferred to a normal GDP-free medium. HPMC viability and function may be impaired during long-term exposure to clinically relevant concentrations of GDP, which suggests a potential role of GDP in the pathogenesis of peritoneal membrane dysfunction during chronic peritoneal dialysis.
Relationship of Variability in Residual Symptoms With Recurrence of Major Depressive Disorder During Maintenance Treatment
Authors: Jordan F. Karp, Daniel J. Buysse, Patricia R. Houck, Christine Cherry, David J. Kupfer, Ellen Frank
Journal: American Journal of Psychiatry (2004)

To investigate how residual symptoms from an index episode of major depressive disorder may be associated with recurrence, the authors conducted a trial involving four maintenance treatment approaches and examined 1) whether the level and variability of residual symptoms differed among the maintenance treatment conditions and 2) whether greater symptom variability is associated with a higher likelihood of recurrence and more rapid recurrence.Patients enrolled in a maintenance treatment study (N=114) were randomly assigned to one of four maintenance treatment conditions: imipramine plus interpersonal psychotherapy, imipramine alone, interpersonal psychotherapy alone, or no active treatment. Residual symptoms were characterized both as continuous variables (mean values and coefficients of variation for Hamilton Depression Rating Scale and Global Assessment Scale [GAS] scores) and as a categorical variable, the percentage of maintenance evaluations with a Hamilton depression scale score > or =8 (e.g., with a symptom peak).Analysis of variance revealed no differences among the four treatment conditions in patients' levels of residual symptoms or symptom variability assessed as a continuous variable, but patients in the combined treatment group had fewer symptom peaks, compared to those in the placebo and interpersonal psychotherapy groups. Cox proportional hazards modeling showed that higher coefficients of variation for both the Hamilton depression scale and the GAS scores and a greater percentage of evaluations with symptom peaks were associated with shorter survival times.A higher level of symptom variability during maintenance treatment is associated with higher risk for recurrence of depression and may provide a specific target for maintenance treatments.
Recurrent papilloedema and early onset optic atrophy in Behcet's syndrome.
Authors: L S Teh, G M O'Connor, M M O'Sullivan, J C Pandit, L Beck, B D Williams
Journal: Annals of the Rheumatic Diseases (1990)

Two patients with Behçet9s syndrome and intracranial hypertension are reported. One developed a recurrence of papilloedema while receiving treatment but eventually made a full recovery, whereas the other developed optic atrophy within three months of onset despite treatment.
Type 5 Adenylyl Cyclase Disruption Alters Not Only Sympathetic But Also Parasympathetic and Calcium-Mediated Cardiac Regulation
Authors: Satoshi Okumura, Jun-ichi Kawabe, Atsuko Yatani, Gen Takagi, Ming-Chih Lee, Chull Hong, Jing Liu, Ikuyo Takagi, Junichi Sadoshima, Dorothy E. Vatner, Stephen F. Vatner, Yoshihiro Ishikawa
Journal: Circulation Research (2003)

In a genetically engineered mouse line with disruption of type 5 adenylyl cyclase (AC5-/-), a major cardiac isoform, there was no compensatory increase in other isoforms of AC in the heart. Both basal and isoproterenol (ISO)-stimulated AC activities were decreased by 30% to 40% in cardiac membranes. The reduced AC activity did not affect cardiac function (left ventricular ejection fraction [LVEF]) at baseline. However, increases in LVEF after ISO were significantly attenuated in AC5-/- (P<0.05, n=11). Paradoxically, conscious AC5-/- mice had a higher heart rate compared with wild-type (WT) mice (613+/-8 versus 523+/-11 bpm, P<0.01, n=14 to 15). Muscarinic agonists decreased AC activity, LVEF, and heart rate more in WT than in AC5-/-. In addition, baroreflex-mediated, ie, neuronally regulated, bradycardia after phenylephrine was also attenuated in AC5-/-. The carbachol-activated outward potassium current (at -40 mV) normalized to cell capacitance in AC5-/- (2.6+/-0.4 pA/pF, n=16) was similar to WT (2.9+/-0.3 pA/pF, n=27), but calcium (Ca2+)-mediated inhibition of AC activity and Ca2+ channel function were diminished in AC5-/-. Thus, AC5-/- attenuates sympathetic responsiveness and also impairs parasympathetic and Ca2+-mediated regulation of the heart, indicating that those actions are not only regulated at the level of the receptor and G-protein but also at the level of type 5 AC.
Highlights of the 2007 Scientific Sessions of the American Society of Nuclear Cardiology
Authors: Raymond R. Russell, Brian G. Abbott, James A. Arrighi, Frank M. Bengel, Mylan C. Cohen, Ernest V. Garcia, Robert C. Hendel, Thomas A. Holly, Jennifer H. Mieres, Leslee J. Shaw, Gregory S. Thomas, Randall C. Thompson, Frans J. Th. Wackers, Jeroen J. Bax
Journal: Journal of the American College of Cardiology (2007)
Molecular Phylogeny and Divergence Time Estimates for Major Rodent Groups: Evidence from Multiple Genes
Authors: Ronald M. Adkins, Eric L. Gelke, Diane Rowe, Rodney L. Honeycutt
Journal: Molecular Biology and Evolution (2001)

The order Rodentia contains half of all extant mammal species, and from an evolutionary standpoint, there are persistent controversies surrounding the monophyly of the order, divergence dates for major lineages, and relationships among families. Exons of growth hormone receptor (GHR) and breast cancer susceptibility (BRCA1) genes were sequenced for a wide diversity of rodents and other mammals and combined with sequences of the mitochondrial 12S rRNA gene and previously published sequences of von Willebrand factor (vWF). Rodents exhibit rates of amino acid replacement twice those observed for nonrodents, and this rapid rate of evolution influences estimates of divergence dates. Based on GHR sequences, monophyly is supported, with the estimated divergence between hystricognaths and most sciurognaths dating to about 75 MYA. Most estimated dates of divergence are consistent with the fossil record, including a date of 23 MYA for Mus-Rattus divergence. These dates are considerably later than those derived from some other molecular studies. Among combined and separate analyses of the various gene sequences, moderate to strong support was found for several clades. GHR appears to have greater resolving power than do 12S or vWF. Despite its complete unresponsiveness to growth hormone, Cavia (and other hystricognaths) exhibits a conservative rate of change in the intracellular domain of GHR.
Nuclear antigens reacted with sera and ascites of hepatocellular carcinoma patients
Authors: Yi-Ming Chen, Cheng-Po Hu, Pao-Huei Chen, Ming-Huey H. Chu, Yang-Te Tsai, Shou-Dong Lee, Chungming Chang
Journal: Hepatology (1988)

In order to study hepatocellular carcinoma-associated antigens, screening of sera and ascites was done from hepatocellular carcinoma patients having antibodies reactive with three hepatocellular carcinoma cell lines (PLC/PRF/5, Hep 3B and HA22T/VGH). The indirect immunofluorescent antibody test was used. Ten of 86 (11.6%) sera and 3 of 14 (21.4%) ascites from hepatocellular carcinoma patients showed positive bindings, whereas only 1 of 35 (2.8%) sera, none of 4 (0%) ascites from chronic hepatitis patients and 3 of 60 (5%) normal human sera had positive immunofluorescent antibody activity. The binding specificities of these positive specimens were further defined by other human cancer cell lines and mouse NIH/3T3 fibroblasts. The antinuclear antibody test against mouse liver sections was also performed. The results suggested that antigens identified by the two tests may not be identical. The nature of nuclear antigens reactive with one of the serum samples, S83, and ascites A83 were characterized. These antigens were sensitive to trypsin but not to RNase A and DNase I. Further studies by radioimmunoprecipitation and two-dimensional gel electrophoresis with serum S83 and ascites A83 showed two acidic phosphorylated antigens with molecular weights of 77 and 79 kd, which had a pI around pH 5.2. The presence of a large amount of these two phosphorylated proteins in 5 of 7 human hepatocellular carcinoma cell lines suggests that these two antigens might play some roles in the carcinogenesis or progression of human hepatocellular carcinoma.
Respiratory mechanics in patients ventilated for critical lung disease
Authors: L Beydon, C Svantesson, K Brauer, F Lemaire, B Jonson
Journal: European Respiratory Journal (1996)

Respiratory mechanics, using flow interruption, was previously studied during the complete breath in healthy ventilated man, numerical techniques relieving constraints regarding flow pattern. The classical linear model of non-Newtonian behaviour was found to be valid. The present study was extended to subjects with critical lung disease. Subjects with acute lung injury (ALI; n = 2), acute respiratory distress syndrome (ARDS; n = 4), and chronic obstructive pulmonary disease (COPD; n = 3) were studied with and without positive end-expiratory pressure (PEEP). Functional residual capacity (FRC) was measured with sulphur hexafluoride (SF6) wash-out. The static pressure-volume (P-V) curve was linear at zero end-expiratory pressure (ZEEP), but nonlinear at PEEP. Its hysteresis was nonsignificant. In ALI/ARDS, PEEP increased lung volume by distension and recruitment, but only by distension in COPD. In ALI/ARDS, resistance was increased, at ZEEP. In COPD, resistance became extremely high during expiration at ZEEP. In ALI/ARDS at ZEEP, non-Newtonian behaviour, representing tissue stress relaxation and pendel-luft, complied with the classical linear model. At PEEP, the non-Newtonian compliance became volume-dependent to an extent correlated to the nonlinearity of the static P-V curve. In COPD, non-Newtonian behaviour was adequately explained only with a model with different inspiratory and expiratory behaviour. The classical model of the respiratory system is valid in ALI/ARDS at ZEEP. More advanced models are needed at PEEP and in COPD.