tbuckley/cabot-search huggingface dataset:
Host Switch Leads to Emergence of Plasmodium vivax Malaria in Humans
Authors: Jianbing Mu, Deirdre A. Joy, Junhui Duan, Yaming Huang, Jane Carlton, John Walker, John Barnwell, Peter Beerli, Michael A. Charleston, Oliver G. Pybus, Xin-zhuan Su
Journal: Molecular Biology and Evolution (2005)

The geographical origin of Plasmodium vivax, the most widespread human malaria parasite, is controversial. Although genetic closeness to Asian primate malarias has been confirmed by phylogenetic analyses, genetic similarities between P. vivax and Plasmodium simium, a New World primate malaria, suggest that humans may have acquired P. vivax from New World monkeys or vice versa. Additionally, the near fixation of the Duffy-negative blood type (FY × Bnull/FY × Bnull) in West and Central Africa, consistent with directional selection, and the association of Duffy negativity with complete resistance to vivax malaria suggest a prolonged period of host-parasite coevolution in Africa. Here we use Bayesian and likelihood methods in conjunction with cophylogeny mapping to reconstruct the genetic and coevolutionary history of P. vivax from the complete mitochondrial genome of 176 isolates as well as several closely related Plasmodium species. Taken together, a haplotype network, parasite migration patterns, demographic history, and cophylogeny mapping support an Asian origin via a host switch from macaque monkeys.
Bone marrow-derived mesenchymal stem cells from early diffuse systemic sclerosis exhibit a paracrine machinery and stimulate angiogenesis in vitro
Authors: S. Guiducci, M. Manetti, E. Romano, B. Mazzanti, C. Ceccarelli, S. Dal Pozzo, A. F. Milia, S. Bellando-Randone, G. Fiori, M. L. Conforti, R. Saccardi, L. Ibba-Manneschi, M. Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2011)

To characterise bone marrow-derived mesenchymal stem cells (MSCs) from patients with systemic sclerosis (SSc) for the expression of factors implicated in MSC recruitment at sites of injury, angiogenesis and fibrosis. The study also analysed whether the production/release of bioactive mediators by MSCs were affected by stimulation with cytokines found upregulated in SSc serum and tissues, and whether MSCs could modulate dermal microvascular endothelial cell (MVEC) angiogenesis.MSCs obtained from five patients with early severe diffuse SSc (SSc-MSCs) and five healthy donors (H-MSCs) were stimulated with vascular endothelial growth factor (VEGF), transforming growth factor β (TGFβ) or stromal cell-derived factor-1 (SDF-1). Transcript and protein levels of SDF-1 and its receptor CXCR4, VEGF, TGFβ(1) and receptors TβRI and TβRII were evaluated by quantitative real-time PCR, western blotting and confocal microscopy. VEGF, SDF-1 and TGFβ(1) secretion in culture supernatant was measured by ELISA. MVEC capillary morphogenesis was performed on Matrigel with the addition of MSC-conditioned medium.In SSc-MSCs the basal expression of proangiogenic SDF-1/CXCR4 and VEGF was significantly increased compared with H-MSCs. SSc-MSCs constitutively released higher levels of SDF-1 and VEGF. SDF-1/CXCR4 were upregulated after VEGF stimulation and CXCR4 redistributed from the cytoplasm to the cell surface. VEGF was increased by SDF-1 challenge. VEGF, TGFβ and SDF-1 stimulation upregulated TGFβ(1), TβRI and TβRII in SSc-MSCs. TβRII redistributed from the cytoplasm to focal adhesion contacts. SSc-MSC-conditioned medium showed a greater proangiogenic effect on MVECs than H-MSCs. Experiments with blocking antibodies showed that MSC-derived cytokines were responsible for this potent proangiogenic effect.SSc-MSCs constitutively overexpress and release bioactive mediators/proangiogenic factors and potentiate dermal MVEC angiogenesis.
Meniscal tissue regeneration in porous 50/50 copoly(l-lactide/ε-caprolactone) implants
Authors: J.H. de Groot, F.M. Zijlstra, H.W. Kuipers, A.J. Pennings, J. Klompmaker, R.P.H. Veth, H.W.B. Jansen
Journal: Biomaterials (1997)
Transepithelial elimination of elastic fibres in the regenerated human epidermis
Authors: M. MIHARA
Journal: British Journal of Dermatology (2006)

The elimination of elastic fibres through the regenerated epidermis of human skin was studied using histochemical, immunofluorescent and electron microscopic techniques. No abnormality was detected in the elastic fibres which were being eliminated, but they were in direct contact with the cytomembranes of some lymphocytes and were captured by histiocytes. It seemed that these elastic fibres were recognized as a foreign substance and provoked inflammation. Lymphocytes and histiocytes may play an important role in the transepithelial elimination of elastic fibres.
Association Between White Blood Cell Count, Epicardial Blood Flow, Myocardial Perfusion, and Clinical Outcomes in the Setting of Acute Myocardial Infarction
Authors: Hal V. Barron, Christopher P. Cannon, Sabina A. Murphy, Eugene Braunwald, C. Michael Gibson
Journal: Circulation (2000)

Background —Elevation of the white blood cell (WBC) count during acute myocardial infarction (AMI) is associated with adverse outcomes. We examined the relationship between the WBC count and angiographic findings to gain insight into this relationship. Results and Methods —We evaluated data from 975 patients in the Thrombolysis In Myocardial Infarction (TIMI) 10A and 10B trials. Patients with a closed artery at 60 and 90 minutes had higher a WBC count than patients with an open artery ( P =0.02). Likewise, the presence of angiographically apparent thrombus was associated with a higher WBC count (11.5±5.2×10 9 /L, n=290, versus 10.7±3.5×10 9 /L, n=648; P =0.008). In addition, a higher WBC count was associated with poorer TIMI myocardial perfusion grades (4-way P =0.04). Mortality rates were higher in patients with a higher WBC count (0% for WBC count 0 to 5×10 9 /L, 4.9% for WBC count 5 to 10×10 9 /L, 3.8% for WBC count 10 to 15×10 9 /L, 10.4% for WBC count &gt;15×10 9 /L; P =0.03). The development of new congestive heart failure or shock was also associated with a higher WBC count (0% for WBC count 0 to 5×10 9 /L, 5.2% for WBC count 5 to 10×10 9 /L, 6.1% for WBC count 10 to 15×10 9 /L, 17.1% for WBC count &gt;15×10 9 /L; P &lt;0.001), an observation that remained significant in a multivariable model that adjusted for potential confounding variables (odds ratio 1.21, P =0.002). Conclusions —Elevation in WBC count was associated with reduced epicardial blood flow and myocardial perfusion, thromboresistance (arteries open later and have a greater thrombus burden), and a higher incidence of new congestive heart failure and death. These observations provide a potential explanation for the higher mortality rate observed among AMI patients with elevated WBC counts and helps explain the growing body of literature that links inflammation and cardiovascular disease.
Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne vulgaris in the community: randomised controlled trial
Authors: Mara Ozolins, E Anne Eady, Anthony J Avery, William J Cunliffe, Alain Li Wan Po, Ciaran O'Neill, Nick B Simpson, Christina E Walters, Ellen Carnegie, Jennifer B Lewis, John Dada, Mary Haynes, Karen Williams, Hywel C Williams
Journal: The Lancet (2004)
Clinical Lecture on the Relation between Laryngeal and Pulmonary Disease
Authors: G. Johnson
Journal: BMJ (1874)

ilistory of a Case o0 Terttiary Syphilis.-Ulceration of the Larynix, followed by Acute Pneumionia.-Symptomis and Physical Signts.-PostAlortein Appearance.-Explanation of the Symptoms and of the Rela- tiont betweenz the Laryngeal and the Pulmonary Disease.-ChronzicLaryn,gitis a frequent Cautse of Disease in thte Lung.-TwoAfodes in which thze Lung mitay be infected by a Primary Disease in the Larynx.-Imnportan'-e of early and ca-refi Treatmnentt in Cases of LaryntgealDisease.
Endocytosis and recycling of the T3-T cell receptor complex. The role of T3 phosphorylation.
Authors: M S Krangel
Journal: The Journal of Experimental Medicine (1987)

An assay has been developed to assess the dynamics of cell surface glycoproteins, in which neuraminidase digestion of intact cells is used to determine the fate of cell surface molecules initially labelled via lactoperoxidase-catalyzed iodination. This approach has been used to demonstrate the constitutive endocytosis and recycling of the T3-T cell receptor (T CR) complex on the human T leukemic cell line HPB-MLT. Stable populations of both phosphorylated and nonphosphorylated forms of the T3 gamma peptide have been identified in these cells. Whereas the former are constitutively endocytosed, the latter appear to be excluded from this pathway. The results presented indicate that T3 gamma phosphorylation may control the endocytosis and recycling of the T3-TCR complex on this cell line.
Pre–B cell receptor–mediated cell cycle arrest in Philadelphia chromosome–positive acute lymphoblastic leukemia requires <i>IKAROS</i> function
Authors: Daniel Trageser, Ilaria Iacobucci, Rahul Nahar, Cihangir Duy, Gregor von Levetzow, Lars Klemm, Eugene Park, Wolfgang Schuh, Tanja Gruber, Sebastian Herzog, Yong-mi Kim, Wolf-Karsten Hofmann, Aihong Li, Clelia Tiziana Storlazzi, Hans-Martin Jäck, John Groffen, Giovanni Martinelli, Nora Heisterkamp, Hassan Jumaa, Markus Müschen
Journal: The Journal of Experimental Medicine (2009)

B cell lineage acute lymphoblastic leukemia (ALL) arises in virtually all cases from B cell precursors that are arrested at pre–B cell receptor–dependent stages. The Philadelphia chromosome–positive (Ph+) subtype of ALL accounts for 25–30% of cases of adult ALL, has the most unfavorable clinical outcome among all ALL subtypes and is defined by the oncogenic BCR-ABL1 kinase and deletions of the IKAROS gene in &amp;gt;80% of cases. Here, we demonstrate that the pre–B cell receptor functions as a tumor suppressor upstream of IKAROS through induction of cell cycle arrest in Ph+ ALL cells. Pre–B cell receptor–mediated cell cycle arrest in Ph+ ALL cells critically depends on IKAROS function, and is reversed by coexpression of the dominant-negative IKAROS splice variant IK6. IKAROS also promotes tumor suppression through cooperation with downstream molecules of the pre–B cell receptor signaling pathway, even if expression of the pre–B cell receptor itself is compromised. In this case, IKAROS redirects oncogenic BCR-ABL1 tyrosine kinase signaling from SRC kinase-activation to SLP65, which functions as a critical tumor suppressor downstream of the pre–B cell receptor. These findings provide a rationale for the surprisingly high frequency of IKAROS deletions in Ph+ ALL and identify IKAROS-mediated cell cycle exit as the endpoint of an emerging pathway of pre–B cell receptor–mediated tumor suppression.
Butter, Corn Oil and Fibrinolysis in Rats
Authors: ROOSEVELT L. TILLMAN, ROBERT M. O'NEAL, WILBUR A. THOMAS, BARBARA BARTELS HIXON
Journal: Circulation Research (1960)

We have recently reported a dietary method for the production of thrombosis and infarcts in rats and have suggested that part of the mechanism of thrombosis in these animals was interference by the diet with some hematologic factor, possibly fibrinolysis. In the study reported herein, we have developed a method for studying fibrinolysis in rats in vitro, utilizing an electronic device called the Thrombelastograph. Results of this study correlate well with the previously demonstirated thrombogenic properties of 2 of the diets. Rats on a "butter-thiouracil-cholesterol-bile salt" diet (known to produce thrombi and infarcts) have prolonged clotlysis times, as compared with rats on a similar diet (and not thus far associated with thrombi and infarcts) in which corn oil is substituted for butter. Although the in vitro test is performed under highly artificial conditions, they are carefully standardized and the fact that the results correlate well with previously demonstrated thrombogenic properties of the diet would suggest that it has practical value for the study of thrombogenic effects of various diets in experimental animals. It is possible that it will prove to be even more useful in the study of fibrinolysis in man.
Wet markets—a continuing source of severe acute respiratory syndrome and influenza?
Authors: Robert G Webster
Journal: The Lancet (2004)

Live-animal markets (wet markets) provide a source of vertebrate and invertebrate animals for customers in tropical and subtropical regions of the world. Wet markets sell live poultry, fish, reptiles, and mammals of every kind. Live-poultry markets (mostly chicken, pigeon, quail, ducks, geese, and a wide range of exotic wild-caught and farm-raised fowl) are usually separated from markets selling fish or red-meat animals, but the stalls can be near each other with no physical separation. Despite the widespread availability of affordable refrigeration, many Asian people prefer live animals for fresh produce. Wet markets are widespread in Asian countries and in countries where Asian people have migrated. Live-poultry markets were the source of the H5N1 bird-influenza virus that transmitted to and killed six of 18 people in Hong Kong.Yi Guan and colleagues (Science 2003; 302: 276-78) recently reported the isolation of severe acute respiratory syndrome (SARS) coronavirus (CoV) from Himalayan palm civets (Paguna larvata) in wet markets in Shenzen, southern China. These researchers also found serological evidence of infection in raccoon dogs (Nyctereutes procuyoinboides). Serological evidence for SARS CoV in human beings working in these markets, taken together with the earliest cases of SARS in restaurant workers, supports the contention of a potential zoonotic origin for SARS. WHERE NEXT? Will SARS reappear? This question confronts public-health officials worldwide, particularly infectious disease personnel in those regions of the world most affected by the disease and the economic burden of SARS, including China, Taiwan, and Canada. Will the virus re-emerge from wet markets or from laboratories working with SARS CoV, or are asymptomatic infections ongoing in human beings? Similar questions can be asked about a pandemic of influenza that is probably imminent. Knowledge of the ecology of influenza in wet markets can be used as an early-warning system to detect the reappearance of SARS or pandemic influenza.
High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial
Authors: Andrés JM Ferreri, Michele Reni, Marco Foppoli, Maurizio Martelli, Gerasimus A Pangalis, Maurizio Frezzato, Maria Giuseppina Cabras, Alberto Fabbri, Gaetano Corazzelli, Fiorella Ilariucci, Giuseppe Rossi, Riccardo Soffietti, Caterina Stelitano, Daniele Vallisa, Francesco Zaja, Lucía Zoppegno, Gian Marco Aondio, Giuseppe Avvisati, Monica Balzarotti, Alba A Brandes, José Fajardo, Henry Gomez, Attilio Guarini, Graziella Pinotti, Luigi Rigacci, Catrina Uhlmann, Piero Picozzi, Paolo Vezzulli, Maurilio Ponzoni, Emanuele Zucca, Federico Caligaris-Cappio, Franco Cavalli
Journal: The Lancet (2009)
Plasma carboxypeptidase B downregulates inflammatory responses in autoimmune arthritis
Authors: Jason J. Song, Inyong Hwang, Kyung H. Cho, Michael A. Garcia, Arthur J. Kim, Tiffany H. Wang, Tamsin M. Lindstrom, Annette T. Lee, Toshihiko Nishimura, Lei Zhao, John Morser, Michael Nesheim, Stuart B. Goodman, David M. Lee, S. Louis Bridges, Peter K. Gregersen, Lawrence L. Leung, William H. Robinson
Journal: Journal of Clinical Investigation (2011)

The immune and coagulation systems are both implicated in the pathogenesis of rheumatoid arthritis (RA). Plasma carboxypeptidase B (CPB), which is activated by the thrombin/thrombomodulin complex, plays a procoagulant role during fibrin clot formation. However, an antiinflammatory role for CPB is suggested by the recent observation that CPB can cleave proinflammatory mediators, such as C5a, bradykinin, and osteopontin. Here, we show that CPB plays a central role in downregulating C5a-mediated inflammatory responses in autoimmune arthritis. CPB deficiency exacerbated inflammatory arthritis in a mouse model of RA, and cleavage of C5a by CPB suppressed the ability of C5a to recruit immune cells in vivo. In human patients with RA, genotyping of nonsynonymous SNPs in the CPB-encoding gene revealed that the allele encoding a CPB variant with longer half-life was associated with a lower risk of developing radiographically severe RA. Functionally, this CPB variant was more effective at abrogating the proinflammatory properties of C5a. Additionally, expression of both CPB and C5a in synovial fluid was higher in patients with RA than in those with osteoarthritis. These findings suggest that CPB plays a critical role in dampening local, C5a-mediated inflammation and represents a molecular link between inflammation and coagulation in autoimmune arthritis.
Methylation of the <i>hTERT</i> Promoter: A Novel Cancer Biomarker for Leptomeningeal Metastasis Detection in Cerebrospinal Fluids
Authors: Stéphanie Bougel, Benoit Lhermitte, Gabrielle Gallagher, Jeanne-Chantal de Flaugergues, Robert C. Janzer, Jean Benhattar
Journal: Clinical Cancer Research (2013)

The diagnosis of leptomeningeal metastases is usually confirmed by the finding of malignant cells by cytologic examination in the cerebrospinal fluid (CSF). More sensitive and specific cancer biomarkers may improve the detection of tumor cells in the CSF. Promoter methylation of the human telomerase reverse transcriptase (hTERT) gene characterizes most cancer cells. The aim of this study was to develop a sensitive method to detect hTERT methylation and to explore its use as a cancer biomarker in CSF.In 77 CSF specimens from 67 patients, hTERT promoter methylation was evaluated using real-time methylation-sensitive high-resolution melting (MS-HRM) and real-time TaqMan PCR and MS-HRM in a single-tube assay.Real-time MS-HRM assay was able to detect down to 1% hTERT-methylated DNA in a background of unmethylated DNA. PCR products were obtained from 90% (69/77) of CSF samples. No false positive hTERT was detected in the 21 non-neoplastic control cases, given to the method a specificity of 100%. The sensitivity of the real-time MS-HRM compared with the cytologic gold standard analysis was of 92% (11/12). Twenty-six CSFs from 22 patients with an hTERT-methylated primary tumor showed cytologic results suspicious for malignancy; in 17 (65%) of them, a diagnosis of leptomeningeal metastases could be confirmed by the hTERT methylation test.The hTERT real-time MS-HRM approach is fast, specific, sensitive, and could therefore become a valuable tool for diagnosis of leptomeningeal metastases as an adjunct to the traditional examination of CSF.
Management of Chronic Disease by Patients
Authors: Noreen M. Clark
Journal: Annual Review of Public Health (2003)

▪ Abstract Chronic conditions dominate health care in most parts of the world, including the United States. Management of a disease by the patient is central to control of its effects. A wide range of influences in the person's social and physical environments enhance or impede management efforts. Interventions to improve management by patients can produce positive outcomes including better monitoring of a condition, fewer symptoms, enhanced physical and psychosocial functioning, and reduced health care use. Successful programs have been theory based. Self-regulation is a promising framework for the development of interventions. Nonetheless, serious gaps in understanding and improving disease management by patients remain because of an emphasis on clinical settings for program delivery, neglect of the factors beyond patient behavior that enable or deter effective management, limitations of study designs in much work to date, reliance on short-term rather than long-term assessments, and failure to evaluate the independent contribution of various program components.
AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network
Authors: Antero Salminen, Kai Kaarniranta
Journal: Ageing Research Reviews (2011)

Efficient control of energy metabolic homeostasis, enhanced stress resistance, and qualified cellular housekeeping are the hallmarks of improved healthspan and extended lifespan. AMPK signaling is involved in the regulation of all these characteristics via an integrated signaling network. Many studies with lower organisms have revealed that increased AMPK activity can extend the lifespan. Experiments in mammals have demonstrated that AMPK controls autophagy through mTOR and ULK1 signaling which augment the quality of cellular housekeeping. Moreover, AMPK-induced stimulation of FoxO/DAF-16, Nrf2/SKN-1, and SIRT1 signaling pathways improves cellular stress resistance. Furthermore, inhibition of NF-κB signaling by AMPK suppresses inflammatory responses. Emerging studies indicate that the responsiveness of AMPK signaling clearly declines with aging. The loss of sensitivity of AMPK activation to cellular stress impairs metabolic regulation, increases oxidative stress and reduces autophagic clearance. These age-related changes activate innate immunity defence, triggering a low-grade inflammation and metabolic disorders. We will review in detail the signaling pathways of this integrated network through which AMPK controls energy metabolism, autophagic degradation and stress resistance and ultimately the aging process.
Higher concentrations of matrix metalloproteinases in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome.
Authors: K Torii, K Iida, Y Miyazaki, S Saga, Y Kondoh, H Taniguchi, F Taki, K Takagi, M Matsuyama, R Suzuki
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

This study was designed to investigate possible involvement of type IV collagenolytic matrix metalloproteinases (MMPs; 72-kDa type IV collagenase [MMP-2], 92-kDa type IV collagenase [MMP-9]), and the respective specific tissue inhibitors of these MMPs (TIMP-2 and TIMP-1) in the development of adult respiratory distress syndrome (ARDS). We determined the concentrations of these enzymes in the bronchoalveolar lavage fluid (BALF) from patients with ARDS using newly developed sensitive one-step sandwich enzyme immunoassay methods. BALF obtained from the 17 patients and eight healthy volunteer control subjects were also used for the analysis of the number of the cellular component. Concentrations of the 7S portion of type IV collagen and laminin in the BALF were measured as markers of basement membrane disruption. In the BALF from the ARDS patients, the concentrations of MMP-2 (66.7 +/- 57.0 ng/ml versus < 7.0 ng/ml for controls, p < 0.01) and MMP-9 (118.0 +/- 309.3 ng/ml versus 9.0 +/- 9.5 ng/ml for controls, p < 0.05), and the specific inhibitor of MMP-9 (TIMP-1) (161.0 +/- 145.0 ng/ml versus < 50 ng/ml for controls, p < 0.01) were significantly higher compared with those for healthy control subjects. In the ARDS patients, the concentrations of MMP-2 correlated both with those of 7S collagen and laminin; MMP-9 with the concentration of 7S collagen and the number of neutrophils. These findings suggest that the increased concentration of collagenolytic MMPs in lung plays a role in the pathogenesis of ARDS.
2007 Guideline for the Management of Ureteral Calculi
Authors: Glenn M. Preminger, Hans-Göran Tiselius, Dean G. Assimos, Peter Alken, A. Colin Buck, Michele Gallucci, Thomas Knoll, James E. Lingeman, Stephen Y. Nakada, Margaret Sue Pearle, Kemal Sarica, Christian Türk, J. Stuart Wolf
Journal: European Urology (2007)