tbuckley/cabot-search huggingface dataset:
Predictive, preventive, personalized and participatory medicine: back to the future
Authors: Charles Auffray, Dominique Charron, Leroy Hood
Journal: Genome Medicine (2010)

The pioneering work of Jean Dausset on the HLA system established several principles that were later reflected in the Human Genome Project and contributed to the foundations of predictive, preventive, personalized and participatory (P4) medicine. To effectively develop systems medicine, we should take advantage of the lessons of the HLA saga, emphasizing the importance of exploring a fascinating but mysterious biology, now using systems principles, pioneering new technology developments and creating shared biological and information resources.
Patients Presenting With CNS Lesions
Authors: J. Lee Villano, Christopher W. Ryan
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.09.013 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 14581429 Patients Presenting With CNS Lesions CASE 2. SUBDURAL PRESENTATION OF RECURRENT BREAST CANCER J. Lee VillanoxJ. Lee VillanoSearch for articles by this author , Christopher W. RyanxChristopher W. RyanSearch for articles by this author Show More Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL https://doi.org/10.1200/JCO.2003.09.013 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Postcapillary venule endothelial cells in kidney express a multispecific chemokine receptor that is structurally and functionally identical to the erythroid isoform, which is the Duffy blood group antigen.
Authors: T J Hadley, Z H Lu, K Wasniowska, A W Martin, S C Peiper, J Hesselgesser, R Horuk
Journal: Journal of Clinical Investigation (1994)

The human erythrocyte chemokine receptor has recently been shown to be identical to the Duffy blood group antigen and is expressed in multiple organs, including kidney. Here we have examined the molecular properties of the renal isoform. Immunoblot analysis of erythrocyte and kidney detergent lysates, with a monoclonal antibody (Fy6) to the Duffy antigen, revealed that the renal isoform had a molecular mass of 43-45 kD, which could be distinguished from that observed in erythroid cells (38-47 kD). Chemical cross-linking of kidney membranes to 125I-melanoma growth stimulatory activity (MGSA) indicated that the renal chemokine receptor had a molecular mass of 38-45 kD. Binding of 125I-labeled MGSA to kidney membranes was competitively inhibited by the addition of unlabeled MGSA, IL-8, regulated on activation, normal T expressed and secrted, and monocyte chemotactic protein-1. Scatchard analysis of MGSA binding showed that the chemokine receptor from renal tissues had a binding affinity of 3.5 nM similar to that observed for the erythroid isoform (5-10 nM). The primary structure of the renal chemokine receptor predicted from the nucleotide sequence of cDNA from renal tissues is identical to that reported for the erythroid isoform. Immunocytochemical staining of kidney with Fy6 localized expression to endothelial cells present in postcapillary venules. These studies implicate the Duffy antigen/chemokine receptor in the complex interactions between postcapillary endothelial cells and granulocytes, which are modulated by pro-inflammatory chemokines.
A Mutation in the Interferon-γ –Receptor Gene and Susceptibility to Mycobacterial Infection
Authors: Melanie J. Newport, Clare M. Huxley, Sara Huston, Catherine M. Hawrylowicz, Ben A. Oostra, Robert Williamson, Michael Levin
Journal: New England Journal of Medicine (1996)

Genetic differences in immune responses may affect susceptibility to mycobacterial infection, but no specific genes have been implicated in humans. We studied four children who had an unexplained genetic susceptibility to mycobacterial infection and who appeared to have inherited the same recessive mutation from a common ancestor.
Ceacam1L Modulates STAT3 Signaling to Control the Proliferation of Glioblastoma-Initiating Cells
Authors: Sadahiro Kaneko, Yuka Nakatani, Tatsuya Takezaki, Takuichiro Hide, Daisuke Yamashita, Naoki Ohtsu, Takanori Ohnishi, Shunsuke Terasaka, Kiyohiro Houkin, Toru Kondo
Journal: Cancer Research (2015)

Glioblastoma-initiating cells (GIC) are a tumorigenic cell subpopulation resistant to radiotherapy and chemotherapy, and are a likely source of recurrence. However, the basis through which GICs are maintained has yet to be elucidated in detail. We herein demonstrated that the carcinoembryonic antigen-related cell adhesion molecule Ceacam1L acts as a crucial factor in GIC maintenance and tumorigenesis by activating c-Src/STAT3 signaling. Furthermore, we showed that monomers of the cytoplasmic domain of Ceacam1L bound to c-Src and STAT3 and induced their phosphorylation, whereas oligomerization of this domain ablated this function. Our results suggest that Ceacam1L-dependent adhesion between GIC and surrounding cells play an essential role in GIC maintenance and proliferation, as mediated by signals transmitted by monomeric forms of the Ceacam1L cytoplasmic domain.
Hypertension from targeted ablation of chromogranin A can be rescued by the human ortholog
Authors: Nitish R. Mahapatra, Daniel T. O’Connor, Sucheta M. Vaingankar, Amiya P. Sinha Hikim, Manjula Mahata, Saugata Ray, Eugenie Staite, Hongjiang Wu, Yusu Gu, Nancy Dalton, Brian P. Kennedy, Michael G. Ziegler, John Ross, Sushil K. Mahata
Journal: Journal of Clinical Investigation (2005)

The secretory prohormone chromogranin A (CHGA) is overexpressed in essential hypertension, a complex trait with genetic predisposition, while its catecholamine release-inhibitory fragment catestatin is diminished, and low catestatin predicts augmented adrenergic pressor responses. These findings from studies on humans suggest a mechanism whereby diminished catestatin might increase the risk for hypertension. We generated Chga and humanized mice through transgenic insertion of a human CHGA haplotype in order to probe CHGA and catestatin in vivo. Chga mice displayed extreme phenotypic changes, including: (a) decreased chromaffin granule size and number; (b) elevated BP; (c) loss of diurnal BP variation; (d) increased left ventricular mass and cavity dimensions; (e) decreased adrenal catecholamine, neuropeptide Y (Npy), and ATP contents; (f) increased catecholamine/ATP ratio in the chromaffin granule; and (g) increased plasma catecholamine and Npy levels. Rescue of elevated BP to normalcy was achieved by either exogenous catestatin replacement or humanization of Chga mice. Loss of the physiological "brake" catestatin in Chga mice coupled with dysregulation of transmitter storage and release may act in concert to alter autonomic control of the circulation in vivo, eventuating in hypertension.
Laparoscopic treatment of an isolated gallbladder rupture following blunt abdominal trauma in a schoolboy rugby player
Authors: R Kohler, R Millin, B Bonner, A Louw
Journal: British Journal of Sports Medicine (2002)

Laparoscopic treatment of an isolated gallbladder rupture in a schoolboy rugby player resulting from blunt abdominal trauma has not previously been reported. A case report of this rare occurrence is presented together with a brief review of the literature.
Hidden Dangers: A Cryptic Exon Disrupts <i>BRCA2</i> mRNA
Authors: James D. Fackenthal, Younghee Lee, Olufunmilayo I. Olopade
Journal: Clinical Cancer Research (2012)

The first mutation that disrupts BRCA2 mRNA by including a novel, cryptic exon is reported in this issue. The mutation lies deep within an intron and would not have been detected by conventional screening methods. In the future, more mutations may be discovered by direct mRNA analysis.
Nutritional considerations in designing animal models of metal toxicity in man.
Authors: M R Fox
Journal: Environmental Health Perspectives (1978)

In recent years, exposure of man to increasing amounts of metals has occurred rather generally from industrial contamination and variably from intake of dietary mineral supplements. Adverse effects of individual metals can be markedly altered by dietary levels of other essential and nonessential inorganic elements, essential organic nutrients and other nonessential dietary components. Experimental diets for establishing baseline responses to excess elements should be formulated to meet the animal's requirements only. These reference diets can then be modified to mimic man's average dietary intake as well as meal patterns. Improved animal models should provide better data for assessing hazards of excess metal intake by man.
Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired Anticancer Immunity
Authors: Ningyan Zhang, Hui Deng, Xuejun Fan, Anneliese Gonzalez, Songlin Zhang, Randall J. Brezski, Byung-Kwon Choi, Michael Rycyzyn, William Strohl, Robert Jordan, Zhiqiang An
Journal: Clinical Cancer Research (2015)

Studies have demonstrated that cancer-associated matrix metalloproteinases (MMP) can generate single peptide bond cleavages in the hinge region of immunoglobulin G1 (IgG1). This study investigated the cleavage of endogenous IgGs by MMPs in the tumor microenvironment and the consequences of the IgG hinge cleavage for humoral immunity.We investigated the occurrence of single peptide bond cleaved IgGs (scIgG) in tumor tissues and plasma samples collected from a cohort of breast cancer patients (n = 60). Samples from healthy people (n = 20) were used as the control. Antibody hinge cleavage was detected by multiple assays, including IHC, ELISA, and flow cytometry. A correlation analysis was conducted between scIgG levels and patient clinical parameters.Levels of scIgGs in tumors were significantly higher than in normal tissues. In addition, scIgG levels in tumors were enriched compared with that in the plasma of the same patients. The appearance of scIgGs in tumor tissues was associated with altered host IgG content and decreased IgG1. Increased tumor scIgGs were found to be positively correlated with adverse clinical factors, such as elevated tumor-associated macrophages, increased expression of MMP9 and other MMPs, and local metastasis to axillary lymph nodes.The study contributes to mounting evidence for the presence of hinge-cleaved antibodies with reduced Fc immune effector function in the tumor microenvironment. The results highlight a link between tumor scIgGs and poor patient outcomes, and reveal a component of compromised humoral immunity within tumors that could point to new immunotherapeutic strategies to rescue host immunity.
Echo-Doppler mitral flow monitoring: an operative tool to evaluate day-to-day tolerance to and effectiveness of beta-adrenergic blocking agent therapy in patients with chronic heart failure
Authors: Soccorso Capomolla, GianDomenico Pinna, Oreste Febo, Angelo Caporotondi, Giampaolo Guazzotti, Maria Teresa La Rovere, Marco Gnemmi, Andrea Mortara, Roberto Maestri, Franco Cobelli
Journal: Journal of the American College of Cardiology (2001)
Analysis of glucocorticoid receptors in human hepatocellular carcinoma and HepG2 cells
Authors: Wing-Yiu Lui, Fang-Ku P’Eng, Yuh-Fang Chang, Tai-Jay Chang, Ting-Fan Tsai, Mei-Ling Hsu, Tsung-Sheng Su, Shyh-Haw Tsay, Chew-Wun Wu, Tsung-Yun Liu, Chin-Wen Chi
Journal: Hepatology (1993)

Hepatocellular carcinoma is the leading cause of male cancer death in Taiwan. We have found that the level of glucocorticoid receptor in hepatocellular carcinoma is significantly higher than that in the peritumoral tissue. In this study, we used a rat liver glucocorticoid receptor complementary DNA probe to examine the expression of glucocorticoid receptor gene in 15 paired samples of hepatocellular carcinoma and their peritumoral tissues. No differences in genomic DNA patterns of the glucocorticoid receptor gene were found between the tumor and peritumoral tissues. The amount of glucocorticoid receptor was found to be significantly higher in hepatoma samples than in peritumoral liver samples. The levels of glucocorticoid receptor messenger RNAs were increased in most tumors compared with their peritumoral samples. To examine the function of glucocorticoid receptors in hepatoma, we examined the expression of glucocorticoid receptor and its relation to cell-cycle progression in human HepG2 cells. Using specific monoclonal antibodies and flow cytometric study, we found glucocorticoid receptor to be expressed constitutively in all cell-cycle phases. In addition, hydrocortisone treatment of HepG2 cells resulted in increased expression of glucocorticoid receptors and increased secretion of alpha-fetoprotein. RU-486, a glucocorticoid antagonist, blocked the hydrocortisone effect, indicating that glucocorticoid receptors are functional in HepG2 cells. Taken together, our data suggest that glucocorticoids and their receptors play an important role in the growth of hepatoma.
An investigation of the chest radiographs in a controlled trial of busulphan, cyclophosphamide, and a placebo after resection for carcinoma of the lung.
Authors: H Stott, R Stephens, W Fox, G Simon, D C Roy
Journal: Thorax (1976)

<h3>Abstract</h3> The present work studies the reactions of citizens from United States of America (USA) during the first cases of Bubonic Plague in the territory on August 2020, during pandemic generated by Covid-19. The interest of the study is analyze the posts of users from all the states of USA following a Text Mining approach. The collection of data is performed through Twitter Application Program Interface (API) of Twitter, considering keywords: bubonic plague and black death. The results show the states with highest number of coronavirus has more publication than others and the interest about treatments, political issues and public health.
Regulation of Vascular L-type Ca <sup>2+</sup> Channels by Phosphatidylinositol 3,4,5-Trisphosphate
Authors: Catherine Le Blanc, Chantal Mironneau, Caroline Barbot, Morgana Henaff, Tzvetanka Bondeva, Reinhard Wetzker, Nathalie Macrez
Journal: Circulation Research (2004)

Modulation of voltage-gated L-type Ca 2+ channels by phosphoinositide 3-kinase (PI3K) regulates Ca 2+ entry and plays a crucial role in vascular excitation-contraction coupling. Angiotensin II (Ang II) activates Ca 2+ entry by stimulating L-type Ca 2+ channels through Gβγ-sensitive PI3Kγ in portal vein myocytes. Moreover, PI3K and Ca 2+ entry activation have been reported to be necessary for receptor tyrosine kinase-coupled and G protein-coupled receptor-induced DNA synthesis in vascular cells. We have previously shown that tyrosine kinase-regulated class Ia and G protein-regulated class Ib PI3Ks are able to modulate vascular L-type Ca 2+ channels. PI3Ks display 2 enzymatic activities: a lipid-kinase activity leading to the formation of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P 3 or PIP3] and a serine-kinase activity. Here we show that exogenous PIP3 applied into the cell through the patch pipette is able to reproduce the Ca 2+ channel-stimulating effect of Ang II and PI3Ks. Moreover, the Ang II-induced PI3K-mediated stimulation of Ca 2+ channel and the resulting increase in cytosolic Ca 2+ concentration are blocked by the anti-PIP3 antibody. Mutants of PI3Kγ transfected into vascular myocytes also revealed the essential role of the lipid-kinase activity of PI3Kγ in Ang II-induced Ca 2+ responses. These results suggest that PIP3 is necessary and sufficient to activate a Ca 2+ influx in vascular myocytes stimulated by Ang II.
Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis
Authors: C. V. Ananth, K. M. Keyes, R. J. Wapner
Journal: BMJ (2013)

To estimate the contributions of biological aging, historical trends, and birth cohort effects on trends in pre-eclampsia in the United States.Population based retrospective study.National hospital discharge survey datasets, 1980-2010, United States.120 million women admitted to hospital for delivery.Temporal changes in rates of mild and severe pre-eclampsia in relation to maternal age, year of delivery, and birth cohorts. Poisson regression as well as multilevel age-period-cohort models with adjustment for obesity and smoking were incorporated.The rate of pre-eclampsia was 3.4%. The age-period-cohort analysis showed a strong age effect, with women at the extremes of maternal age having the greatest risk of pre-eclampsia. In comparison with women delivering in 1980, those delivering in 2003 were at 6.7-fold (95% confidence interval 5.6-fold to 8.0-fold) increased risk of severe pre-eclampsia. Period effects declined after 2003. Trends for severe pre-eclampsia also showed a modest birth cohort effect, with women born in the 1970s at increased risk. Compared with women born in 1955, the risk ratio for women born in 1970 was 1.2 (95% confidence interval 1.1 to 1.3). Similar patterns were also evident for mild pre-eclampsia, although attenuated. Changes in the population prevalence of obesity and smoking were associated with period and cohort trends in pre-eclampsia but did not explain the trends.Rates of severe pre-eclampsia have been increasing in the United States and age-period-cohort effects all contribute to these trends. Although smoking and obesity have driven these trends, changes in the diagnostic criteria may have also contributed to the age-period-cohort effects. Health consequences of rising obesity rates in the United States underscore that efforts to reduce obesity may be beneficial to maternal and perinatal health.
Soluble Thrombomodulin Protects Ischemic Kidneys
Authors: Asif A. Sharfuddin, Ruben M. Sandoval, David T. Berg, Grant E. McDougal, Silvia B. Campos, Carrie L. Phillips, Bryan E. Jones, Akanksha Gupta, Brian W. Grinnell, Bruce A. Molitoris
Journal: Journal of the American Society of Nephrology (2009)

Altered coagulation and inflammation contribute to the pathogenesis of ischemic renal injury. Thrombomodulin is a necessary factor in the anticoagulant protein C pathway and has inherent anti-inflammatory properties. We studied the effect of soluble thrombomodulin (sTM) in a hypoperfusion model of ischemic kidney injury. To markedly reduce infrarenal aortic blood flow and femoral arterial pressures, we clamped the suprarenal aorta of rats, occluding them 90%, for 60 min. Reversible acute kidney injury (AKI) occurred at 24 h in rats subjected to hypoperfusion. Histologic analysis at 24 h revealed acute tubular necrosis (ATN), and intravital two-photon microscopy showed flow abnormalities in the microvasculature and defects of endothelial permeability. Pretreatment with rat sTM markedly reduced both I-R-induced renal dysfunction and tubular histologic injury scores. sTM also significantly improved microvascular erythrocyte flow rates, reduced microvascular endothelial leukocyte rolling and attachment, and minimized endothelial permeability to infused fluorescence dextrans, assessed by intravital quantitative multiphoton microscopy. Furthermore, sTM administered 2 h after reperfusion protected against ischemia-induced renal dysfunction at 24 h and improved survival. By using an sTM variant, we also determined that the protective effects of sTM were independent of its ability to generate activated protein C. These data suggest that sTM may have therapeutic potential for ischemic AKI.
Chronic Humoral Rejection
Authors: SHAMILA MAUIYYEDI, PATRICIA DELLA PELLE, SUSAN SAIDMAN, A. BERNARD COLLINS, MANUEL PASCUAL, NINA E. TOLKOFF-RUBIN, WINFRED W. WILLIAMS, A. BENEDICT COSIMI, EVELINE E. SCHNEEBERGER, ROBERT B. COLVIN
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The pathogenesis of chronic renal allograft rejection (CR) remains obscure. The hypothesis that a subset of CR is mediated by antidonor antibody was tested by determining whether C4d is deposited in peritubular capillaries (PTC) and whether it correlates with circulating antidonor antibodies. All cases (from January 1, 1990, to July 31, 1999) that met histologic criteria for CR and had frozen tissue (28 biopsies, 10 nephrectomies) were included. Controls were renal allograft biopsies with chronic cyclosporine toxicity ( n = 21) or nonspecific interstitial fibrosis ( n = 10), and native kidneys with end-stage renal disease ( n = 10) or chronic interstitial fibrosis ( n = 5). Frozen sections were stained by two-color immunofluorescence for C4d, type IV collagen and Ulex europaeus agglutinin I. Antidonor HLA antibody was sought by panel-reactive antibody analysis and/or donor cross matching in sera within 7 wk of biopsy. Overall, 23 of 38 CR cases (61%) had PTC staining for C4d, compared with 1 of 46 (2%) of controls ( P &lt; 0.001). C4d in PTC was localized at the interface of endothelium and basement membrane. Most of the C4d-positive CR tested had antidonor HLA antibody (15 of 17; 88%); none of the C4d-negative CR tested (0 of 8) had antidonor antibody ( P &lt; 0.0002). The histology of C4d-positive CR was similar to C4d-negative CR, and 1-yr graft survival rates were 62% and 25%, respectively ( P = 0.05). Since August 1998, five of six C4d-positive CR cases have been treated with mycophenolate mofetil ± tacrolimus with a 100% 1-yr graft survival, versus 40% before August 1998 ( P &lt; 0.03). These data support the hypothesis that a substantial fraction of CR is mediated by antibody (immunologically active). C4d can be used to separate this group of CR from the nonspecific category of chronic allograft nephropathy and may have the potential to guide successful therapeutic intervention.
p16INK4a protects against dysfunctional telomere–induced ATR-dependent DNA damage responses
Authors: Yang Wang, Norman Sharpless, Sandy Chang
Journal: Journal of Clinical Investigation (2013)

Dysfunctional telomeres limit cellular proliferative capacity by activating the p53-p21- and p16(INK4a)-Rb-dependent DNA damage responses (DDRs). The p16(INK4a) tumor suppressor accumulates in aging tissues, is a biomarker for cellular senescence, and limits stem cell function in vivo. While the activation of a p53-dependent DDR by dysfunctional telomeres has been well documented in human cells and mouse models, the role for p16(INK4a) in response to telomere dysfunction remains unclear. Here, we generated protection of telomeres 1b p16-/- mice (Pot1bΔ/Δ;p16-/-) to address the function of p16(INK4a) in the setting of telomere dysfunction in vivo. We found that deletion of p16(INK4a) accelerated organ impairment and observed functional defects in highly proliferative organs, including the hematopoietic system, small intestine, and testes. Pot1bΔ/Δ;p16-/- hematopoietic cells exhibited increased telomere loss, increased chromosomal fusions, and telomere replication defects. p16(INK4a) deletion enhanced the activation of the ATR-dependent DDR in Pot1bΔ/Δ hematopoietic cells, leading to p53 stabilization, increased p21-dependent cell cycle arrest, and elevated p53-dependent apoptosis. In contrast to p16(INK4a), deletion of p21 did not activate ATR, rescued proliferative defects in Pot1bΔ/Δ hematopoietic cells, and significantly increased organismal lifespan. Our results provide experimental evidence that p16(INK4a) exerts protective functions in proliferative cells bearing dysfunctional telomeres.