tbuckley/cabot-search huggingface dataset:
Multiple Antitumor Mechanisms Downstream of Prophylactic Regulatory T-Cell Depletion
Authors: Michele W.L. Teng, Jeremy B. Swann, Bianca von Scheidt, Janelle Sharkey, Nadeen Zerafa, Nicole McLaughlin, Tomoyuki Yamaguchi, Shimon Sakaguchi, Phillip K. Darcy, Mark J. Smyth
Journal: Cancer Research (2010)

Several reports have shown that prophylactic depletion of regulatory T cells (Treg) using various monoclonal antibodies (mAb) in mice can stimulate potent antitumor immune responses and prevent tumor development. These same depletion methods do not significantly suppress tumor growth in a therapeutic setting. Although different strategies to deplete FoxP3(+) Treg have been used, no study has systematically compared these qualitatively for the effector mechanisms they each liberate. Herein, using prophylactic depletion of FoxP3(+) Tregs with either anti-CD4, anti-CD25, or anti-FR4 mAbs, we have compared the cellular and effector requirements for elimination of the renal carcinoma RENCA and prevention of methylcholanthrene-induced fibrosarcoma. Collectively from these two models, it was clear that CD8(+) T cells and natural killer cells played an important role downstream of Treg depletion. However, whereas all three mAbs quantitatively depleted FoxP3(+) T cells to a similar extent, subtle differences in the downstream mechanisms of tumor control existed for all three approaches. In general, neutralization of any lymphocyte subset or effector mechanism was insufficient to alter tumor suppression initiated by Treg depletion, and in some settings, the neutralization of multiple effector mechanisms failed to prevent tumor rejection. These studies reveal that Tregs control multiple redundant elements of the immune effector response capable of inhibiting tumor initiation and underscore the importance of effectively targeting these cells in any cancer immunotherapy.
Leptin modulates the effects of acyl CoA:diacylglycerol acyltransferase deficiency on murine fur and sebaceous glands
Authors: Hubert C. Chen, Steven J. Smith, Bryan Tow, Peter M. Elias, Robert V. Farese
Journal: Journal of Clinical Investigation (2002)

Acyl CoA:diacylglycerol acyltransferase (DGAT) is a ubiquitously expressed enzyme that catalyzes the final reaction in the major pathways of triglyceride synthesis. Mice lacking DGAT1 (Dgat(-/-)) demonstrate significant changes in lipid metabolism in several tissues, including the skin. Here we report the effects of DGAT1 deficiency on fur and sebaceous glands. Adult Dgat(-/-) mice had dry fur and hair loss, which were associated with atrophic sebaceous glands and fur lipid abnormalities. As a result, Dgat(-/-) mice had impaired water repulsion and defective thermoregulation after water immersion. These phenotypes were mostly absent in Dgat(-/-) mice with leptin deficiency, indicating an unexpected role for leptin in modulating the skin phenotype. Our findings indicate that DGAT1 plays an important role in normal fur and sebaceous gland physiology and provide evidence that leptin modulates these processes in the skin.
Chemical Genetic Identification of NDR1/2 Kinase Substrates AAK1 and Rabin8 Uncovers Their Roles in Dendrite Arborization and Spine Development
Authors: Sila K. Ultanir, Nicholas T. Hertz, Guangnan Li, Woo-Ping Ge, Alma L. Burlingame, Samuel J. Pleasure, Kevan M. Shokat, Lily Yeh Jan, Yuh-Nung Jan
Journal: Neuron (2012)
Telomerase activity in bleomycin-induced epithelial cell apoptosis and lung fibrosis
Authors: Z. G. Fridlender, P. Y. Cohen, O. Golan, N. Arish, S. Wallach-Dayan, R. Breuer
Journal: European Respiratory Journal (2007)

Epithelial cell injury and apoptosis are recognised as early features in idiopathic pulmonary fibrosis and bleomycin-induced fibrosis in mice. Telomerase is a known apoptosis-alleviating factor . The role of telomerase was studied during bleomycin-induced lung epithelial cell (LEC) apoptosis in vitro in a mouse LEC line, and in vivo in LECs isolated from bleomycin-treated mice. The current authors evaluated changes in murine telomerase reverse transcriptase (mTERT) mRNA levels and changes in telomerase activity with the TRAPeze Detection Kit, telomeric length with the TeloTTAGGG Telomere Length Kit, and LEC apoptosis with FACScan and 4,6-diamino-2-phenylindole dihydrochloride stain. There was a significant elevation in mTERT mRNA and a transient 41% increase in telomerase activity 24 h after in vitro bleomycin treatment. At 72 h, telomerase activity had fallen to 26% below levels in untreated cells. Reduction of telomerase activity over time, or by direct inhibition, significantly elevated LEC apoptosis. No change in average telomeric length was noted. In vivo , telomerase activity of LECs from bleomycin-treated mice increased at 7 and 14 days. In conclusion, telomerase activity may play a protective role against robust bleomycin-induced lung epithelial cell apoptosis. Moreover, stabilising telomerase activity may decrease epithelial cell apoptosis and the resulting lung fibrosis.
Meta-analysis of randomised controlled trials of oral mandibular advancement devices and continuous positive airway pressure for obstructive sleep apnoea-hypopnoea
Authors: Linda D. Sharples, Abigail L. Clutterbuck-James, Matthew J. Glover, Maxine S. Bennett, Rebecca Chadwick, Marcus A. Pittman, Timothy G. Quinnell
Journal: Sleep Medicine Reviews (2015)

Obstructive sleep apnoea-hypopnoea (OSAH) causes excessive daytime sleepiness, impairs quality-of-life, and increases cardiovascular disease and road traffic accident risks. Continuous positive airway pressure (CPAP) treatment and mandibular advancement devices (MAD) have been shown to be effective in individual trials but their effectiveness particularly relative to disease severity is unclear. A MEDLINE, Embase and Science Citation Index search updating two systematic reviews to August 2013 identified 77 RCTs in adult OSAH patients comparing: MAD with conservative management (CM); MAD with CPAP; or CPAP with CM. Overall MAD and CPAP significantly improved apnoea-hypopnoea index (AHI) (MAD -9.3/hr (p < 0.001), CPAP -25.4 (p < 0.001)). In direct comparisons mean AHI and Epworth sleepiness scale score were lower (7.0/hr (p < 0.001) and 0.67 (p = 0.093) respectively) for CPAP. There were no CPAP vs. MAD trials in mild OSAH but in comparisons with CM, MAD and CPAP reduced ESS similarly (MAD 2.01 (p < 0.001); CPAP 1.23 (p = 0.012). Both MAD and CPAP are clinically effective in the treatment of OSAH. Although CPAP has a greater treatment effect, MAD is an appropriate treatment for patients who are intolerant of CPAP and may be comparable to CPAP in mild disease.
Diagnostic Testing for Celiac Disease Among Patients With Abdominal Symptoms
Authors: Daniëlle A. W. M. van der Windt, Petra Jellema, Chris J. Mulder, C. M. Frank Kneepkens, Henriëtte E. van der Horst
Journal: JAMA (2010)

BDOMINAL SYMPTOMS AREcommon in primary care, with an annual incidence of 35 to 40 per 1000 individuals. 1Chronic abdominal symptoms can adversely affect daily functioning and quality of life. 2,3For the primary care physician, the diagnostic challenge is to discriminate between patients with functional gastrointestinal problems only and those with organic disease, such as celiac disease.Celiac disease is a gluten-sensitive systemic disorder that primarily affects the small bowel. 4,5Estimates of the prevalence of celiac disease in the population vary widely, but most largescale studies in Western Europe and the United States report prevalence rates between 0.5% and 1.0%. 6,7However, many patients have unrecognized celiac disease. 8,9This may partly be explained by a lack of symptoms in those with latent or silent celiac disease, but the identification of symptomatic celiac disease is also complicated by the broad spectrum of presenting symptoms,
Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein.
Authors: M Navab, S S Imes, S Y Hama, G P Hough, L A Ross, R W Bork, A J Valente, J A Berliner, D C Drinkwater, H Laks
Journal: Journal of Clinical Investigation (1991)

Incubation of cocultures of human aortic endothelial (HAEC) and smooth muscle cells (HASMC) with LDL in the presence of 5-10% human serum resulted in a 7.2-fold induction of mRNA for monocyte chemotactic protein 1 (MCP-1), a 2.5-fold increase in the levels of MCP-1 protein in the coculture supernatants, and a 7.1-fold increase in the transmigration of monocytes into the subendothelial space of the cocultures. Monocyte migration was inhibited by 91% by antibody to MCP-1. Media collected from the cocultures that had been incubated with LDL induced target endothelial cells (EC) to bind monocyte but not neutrophil-like cells. Media collected from cocultures that had been incubated with LDL-induced monocyte migration into the subendothelial space of other cocultures that had not been exposed to LDL. In contrast, media from separate cultures of EC or smooth muscle cells (SMC) containing equal number of EC or SMC compared to coculture and incubated with the same LDL did not induce monocyte migration when incubated with the target cocultures. High density lipoprotein HDL, when presented to cocultures together with LDL, reduced the increased monocyte transmigration by 91%. Virtually all of the HDL-mediated inhibition was accounted for by the HDL2 subfraction. HDL3 was essentially without effect. Apolipoprotein AI was also ineffective in preventing monocyte transmigration while phosphatidylcholine liposomes were as effective as HDL2 suggesting that lipid components of HDL2 may have been responsible for its action. Preincubating LDL with beta-carotene or with alpha-tocopherol did not reduce monocyte migration. However, pretreatment of LDL with probucol or pretreatment of the cocultures with probucol, beta-carotene, or alpha-tocopherol before the addition of LDL prevented the LDL-induced monocyte transmigration. Addition of HDL or probucol to LDL after the exposure to cocultures did not prevent the modified LDL from inducing monocyte transmigration in fresh cocultures. We conclude that cocultures of human aortic cells can modify LDL even in the presence of serum, resulting in the induction of MCP-1, and that HDL and antioxidants prevent the LDL induced monocyte transmigration.
A Newly Classified Vertebrate Calpain Protease, Directly Ancestral to CAPN1 and 2, Episodically Evolved a Restricted Physiological Function in Placental Mammals
Authors: Daniel J. Macqueen, Margaret L. Delbridge, Sujatha Manthri, Ian A. Johnston
Journal: Molecular Biology and Evolution (2010)

The most studied members of the calpain protease superfamily are CAPN1 and 2, which are conserved across vertebrates. Another similar family member called μ/m-CAPN has been identified in birds alone. Here, we establish that μ/m-CAPN shares one-to-one orthology with CAPN11, previously described only in eutherians (placental mammals). We use the name CAPN11 for this family member and identify orthologues across vertebrate lineages, which form a monophyletic phylogenetic clade directly ancestral to CAPN1 and 2. In lineages branching before therians (live-bearing mammals), the CAPN11 coding region has evolved under strong purifying selection, with low nonsynonymous (dN) versus synonymous (dS) substitution rates (dN/dS = 0.076 across pretherians), and its transcripts were detected widely across different tissues. These characteristics are present in CAPN1 and 2 across vertebrate lineages and indicate that pretherian CAPN11 likewise has conserved a wide physiological function. However, an ∼7-fold elevation in dN/dS is evident along the CAPN11 branch splitting eutherians from platypus, paralleled by a shift to "testis-specific" gene regulation. Estimates of dN/dS in eutherians were ∼3-fold elevated compared with pretherians and coding and transcriptional-level evidence suggests that CAPN11 is functionally absent in marsupials. Many CAPN11 sites are functionally constrained in eutherians to conserve a residue with radically different biochemical properties to a fixed state shared between pretherian CAPN11 and CAPN1 and 2. Protein homology modeling demonstrated that many such eutherian-specific residue replacements modify or ablate interactions with the calpain inhibitor calpastatin that are observed in both pretherian orthologues and CAPN1/2. We propose a model akin to the Dykhuizen–Hartl effect, where inefficient purifying selection and increased genetic drift associated with a reduction in effective population size, drove the fixation of mutations in regulatory and coding regions of CAPN11 of a common marsupial–eutherian ancestor. A subset of these changes had a cumulative adaptive advantage in a eutherian ancestor because of lineage-specific aspects of sperm physiology, whereas in marsupials, no advantage was realized and the gene was disabled. This work supports that functional divergence among gene family member orthologues is possible in the absence of widespread positive selection.
In vitro modeling of liver membrane copper transport
Authors: Michael L. Schilsky
Journal: Hepatology (1995)

The process of hepatobiliary copper (Cu) secretion is still poorly understood Cu secretion as a complex with glutathione and transport via a lysosomal pathway have been proposed. The recent cloning and sequencing of the gene for Wilson disease indicates that Cu transport in liver cells may be mediated by a Cu transporting Ptype ATPase. Biochemical evidence for ATP-dependent Cu transport in mammalian systems, however, has not been reported so far. We have investigated Cu transport in rat liver plasma membrane vesicles enriched in canalicular or basolateral membranes in the presence and absence of ATP (4 mM) and an ATP-regenerating system. The presence of ATP clearly stimulated uptake of radiolabeled Cu (64Cu, 10 μM) into canalicular plasma membrane vesicles and, to a lesser extent, also into basolateral plasma membrane vesicles. ATP-dependent Cu transport was dose-dependently inhibited by the P-type ATPase inhibitor vanadate, and showed saturation kinetics with an estimated Km of 8.6 μM and a Vmax of 6.9 nmol/min/mg protein. ATP-stimulated Cu uptake was similar in canalicular membrane vesicles of normal Wistar rats and those of mutant GY rats, expressing a congenital defect in the activity of the ATP-dependent canalicular glutathione-conjugate transporter (cMOAT). These studies demonstrate the presence of an ATP-dependent Cu transporting system in isolated plasma membrane fractions of rat liver distinct from cMOAT. (J. Clin. Invest. 1995.95:412–416.) Key words: copper · bile secretion · P-type ATPase · vesicle transport · Wilson disease. (Reproduced from The Journal of Clinical Investigation, 1995, vol. 95, pp. 412–416 by copyright permission of The Society for Clinical Investigation.).
Long-Term Results of CCG 5942: A Randomized Comparison of Chemotherapy With and Without Radiotherapy for Children With Hodgkin's Lymphoma—A Report From the Children's Oncology Group
Authors: Suzanne L. Wolden, Lu Chen, Kara M. Kelly, Philip Herzog, Gerald S. Gilchrist, John Thomson, Richard Sposto, Marshall E. Kadin, Raymond J. Hutchinson, James Nachman
Journal: Journal of Clinical Oncology (2012)

In 1995, the Children's Cancer Group (CCG) opened a trial for patients with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation therapy (IFRT) improved event-free survival (EFS) for patients achieving a complete response after chemotherapy. We present the long-term study outcome using final data through March 2007.
Molecular profiling of angiogenesis in hypericin mediated photodynamic therapy
Authors: Ramaswamy Bhuvaneswari, Yik Y Gan, Sasidharan S Lucky, William WL Chin, Seyed M Ali, Khee C Soo, Malini Olivo
Journal: Molecular Cancer (2008)

Abstract Background Photodynamic therapy (PDT) involves the administration of a tumor-localizing photosensitizing drug, which is activated by light of specific wavelength in the presence of molecular oxygen thus generating reactive oxygen species that is toxic to the tumor cells. PDT selectively destroys photosensitized tissue leading to various cellular and molecular responses. The present study was designed to examine the angiogenic responses at short (0.5 h) and long (6 h) drug light interval (DLI) hypericin-PDT (HY-PDT) treatment at 24 h and 30 days post treatment in a human bladder carcinoma xenograft model. As short DLI targets tumor vasculature and longer DLI induces greater cellular damage, we hypothesized a differential effect of these treatments on the expression of angiogenic factors. Results Immunohistochemistry (IHC) results showed minimal CD31 stained endothelium at 24 h post short DLI PDT indicating extensive vascular damage. Angiogenic proteins such as vascular endothelial growth factor (VEGF), tumor necrosis growth factor-α (TNF-α), interferon-α (IFN-α) and basic fibroblast growth factor (bFGF) were expressed to a greater extent in cellular targeting long DLI PDT compared to vascular mediated short DLI PDT. Gene expression profiling for angiogenesis pathway demonstrated downregulation of adhesion molecules – cadherin 5, collagen alpha 1 and 3 at 24 h post treatment. Hepatocyte growth factor (HGF) and Ephrin-A3 (EFNA3) were upregulated in all treatment groups suggesting a possible activation of c-Met and Ephrin-Eph signaling pathways. Conclusion In conclusion, long DLI HY-PDT induces upregulation of angiogenic proteins. Differential expression of genes involved in the angiogenesis pathway was observed in the various groups treated with HY-PDT.
Points: Long term follow up of untreated primary hyperparathyroidism
Authors: C N. de Deuxchaisnes
Journal: BMJ (1985)

The paper by Dr F Chedru and colleagues (23 March, p 896) describing four cases of sensory neuropathv associated with almitrine is of interest.Almitrine will be used principally in the treatment of severe hypoxia caused by chronic obstructive airways disease.It is an interesting new respiratory
Chronic lymphocytic leukemia of Eμ-TCL1 transgenic mice undergoes rapid cell turnover that can be offset by extrinsic CD257 to accelerate disease progression
Authors: Thomas Enzler, Arnon P. Kater, Weizhou Zhang, George F. Widhopf, Han-Yu Chuang, Jason Lee, Esther Avery, Carlo M. Croce, Michael Karin, Thomas J. Kipps
Journal: Blood (2009)
The Infectiousness of Tuberculosis Patients Coinfected with HIV
Authors: A. Roderick Escombe, David A. J Moore, Robert H Gilman, William Pan, Marcos Navincopa, Eduardo Ticona, Carlos Martínez, Luz Caviedes, Patricia Sheen, Armando Gonzalez, Catherine J Noakes, Jon S Friedland, Carlton A Evans
Journal: PLoS Medicine (2008)

The current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB.
Effect of glucocorticoids on gastrin secretion in man.
Authors: S Seino, Y Seino, S Matsukura, H Kurahachi, M Ikeda, M Yawata, H Imura
Journal: Gut (1978)

In order to investigate the effect of glucocorticoids on gastrin secretion, plasma gastrin levels were measured by radioimmunoassay in patients with Cushing9s syndrome and those treated with glucocorticoids. Fasting plasma gastrin levels were significantly higher in these patients than in normal subjects, with exaggerated response to food. Conversely, short-term treatment or intravenous infusion of glucocorticoids had no significant influence on gastrin secretion in normal subjects. The possible mechanism by which glucocorticoids cause hypergastrinaemia are discussed.
The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in
Authors: Armin Ehninger, Andreas Trumpp
Journal: The Journal of Experimental Medicine (2011)

Stem cell niches are defined as the cellular and molecular microenvironments that regulate stem cell function together with stem cell autonomous mechanisms. This includes control of the balance between quiescence, self-renewal, and differentiation, as well as the engagement of specific programs in response to stress. In mammals, the best understood niche is that harboring bone marrow hematopoietic stem cells (HSCs). Recent studies have expanded the number of cell types contributing to the HSC niche. Perivascular mesenchymal stem cells and macrophages now join the previously identified sinusoidal endothelial cells, sympathetic nerve fibers, and cells of the osteoblastic lineage to form similar, but distinct, niches that harbor dormant and self-renewing HSCs during homeostasis and mediate stem cell mobilization in response to granulocyte colony-stimulating factor.
A Community-wide Outbreak of Cryptosporidiosis Associated With Swimming at a Wave Pool
Authors: Jeremy M. McAnulty
Journal: JAMA (1994)

<h3>Objective.</h3> —To determine the cause of a community-wide outbreak of cryptosporidiosis. <h3>Design.</h3> —A matched case-control study. <h3>Setting.</h3> —General community of Lane County, Oregon. <h3>Patients and Other Participants.</h3> —Persons with<i>Cryptosporidium</i>detected in their stool from June to October 1992 were identified by contacting laboratories serving the area. Exposures of the first 18 case patients identified were compared with those of 18 age- and neighborhood-matched controls selected from a reverse telephone directory. <h3>Main Outcome Measures.</h3> —Reported exposures to risk factors for cryptosporidiosis and abatement of cryptosporidiosis outbreak. <h3>Results.</h3> —Fifty-five patients with cryptosporidiosis were detected, including 37 who were the first individuals ill in their households. The case-control study involving the first 18 case patients showed no association between illness and attendance at day care or drinking municipal water or drinking untreated surface waters (river or lake water) in the 2 weeks before onset of illness. However, nine of 18 case patients reported swimming at a local wave pool, compared with none of 18 controls. We ultimately identified 17 case patients who reported swimming at the same wave pool during their incubation periods, whose exposure dates spanned a 2-month period. Inspection of the pool's filtration system did not detect any abnormalities. The outbreak subsided after the pool water was drained and replaced. <h3>Conclusions.</h3> —This prolonged outbreak of cryptosporidiosis was likely caused by exposure to fecally contaminated wave pool water. Since<i>Cryptosporidium</i>is highly chlorine resistant and inadequately removed by sand filters, such outbreaks may represent an unrecognized hazard of wave pools, where the likelihood of inadvertent water ingestion is high. Such outbreaks may go undetected in areas where cryptosporidiosis is not reportable or laboratory screening is infrequent. (<i>JAMA</i>. 1994;272:1597-1600)