tbuckley/cabot-search huggingface dataset:
Soluble CD154 Is a Unique Predictor of Nonfatal and Fatal Atherothrombotic Events in Patients Who Have End-Stage Renal Disease and Are on Hemodialysis
Authors: Berthold Hocher, Lutz Liefeldt, Thomas Quaschning, Philipp Kalk, Reinhard Ziebig, Michael Godes, Katharina Relle, Gernot Asmus, Johannes-Peter Stasch
Journal: Journal of the American Society of Nephrology (2007)

Cardiovascular mortality is remarkably high in patients who are on hemodialysis. Soluble CD154 (sCD154), a protein that belongs to the TNF receptor superfamily, has been implicated in the pathogenesis of atheromatous plaque destabilization and thrombotic events. The predictive value of sCD154 as a marker for clinical outcome in patients with ESRD was investigated. A total of 232 patients were prospectively followed for 52 mo. At study entry, clinical characteristics were documented and plasma concentrations of sCD154 and those of conventional risk predictors were analyzed. The time and cause of any hospitalization and death were documented during the entire follow-up. Survival rates were compared by Kaplan-Meier and Cox regression analyses. A total of 122 patients died, 64 of cardiovascular disease, including 20 cases of fatal atherothrombotic diseases (myocardial infarction, stroke, mesenteric ischemia). All 20 cases of fatal atherothrombotic events had high sCD154 plasma levels (cutoff >6.42 ng/ml) at study entry. The total number of fatal and nonfatal atherothrombotic events was 66. Only five atherothrombotic nonfatal events occurred in patients with sCD154 <6.42 ng/ml, whereas 61 fatal and nonfatal events were seen in patients with sCD154 ≥6.42 ng/ml (P < 0.005). This was confirmed by Kaplan-Meier curves for fatal atherothrombotic events (P = 0.0214) and the combined end point fatal and nonfatal atherothrombotic events (P = 0.0039). Cox regression analysis revealed that high sCD154 is an independent predictor (relative risk 6.80; 95% confidence interval 1.64 to 28.26; P = 0.008) for the combined end point death or hospitalization as a result of atherothrombotic events. Death or hospitalizations as a result of any other reason (arrhythmia, heart failure, infectious diseases, and cancer) were not linked to sCD154 plasma concentrations. In conclusion, sCD154 predicts nonfatal and fatal atherothrombotic events (myocardial infarction, stroke, mesenteric ischemia) but not death and hospitalization as a result of any other reason in stable patients who have ESRD and are on hemodialysis.
Diaphragm and body weight in emphysema.
Authors: W M Thurlbeck
Journal: Thorax (1978)

The weight of the diaphragm has been investigated in 103 male patients and 81 female patients, and the relationship between body weight and emphysema has been assessed in 662 male and 431 female patients. Diaphragm weight is related to body weight in both male (r = + 0.76) and female patients (r = +0.77) and is relatively larger in the former. Dissecting the diaphragm free of fat or freeze drying it does not appreciably improve the relationship between body weight and diaphragm weight. Diaphragm weight is better related to body weight than body length and is diminished in emphysema. Patients with emphysema weigh less. This is apparent with only moderate grades of emphysema, and there is no further loss of body weight as emphysema in the lung becomes more severe. The loss of diaphragm weight not only reflects the loss of body weight that occurs in emphysema, but the diaphragm is also less in weight than predicted from body weight. The diaphragm also appears abnormal on gross inspection in some patients with emphysema. Heart weight and diaphragm weight are related, probably because both are related to body weight.
Infection with GB virus C (GBV-C) in patients with fulminant hepatitis
Authors: Yukihiko Tameda, Yoshitane Kosaka, Shinsei Tagawa, Koujirou Takase, Naoto Sawada, Haruhisa Nakao, Fumio Tsuda, Takeshi Tanaka, Hiroaki Okamoto, Yuzo Miyakawa, Makoto Mayumi
Journal: Journal of Hepatology (1996)
Overexpressed P-Cadherin/CDH3 Promotes Motility of Pancreatic Cancer Cells by Interacting with p120ctn and Activating Rho-Family GTPases
Authors: Keisuke Taniuchi, Hidewaki Nakagawa, Masayo Hosokawa, Toru Nakamura, Hidetoshi Eguchi, Hiroaki Ohigashi, Osamu Ishikawa, Toyomasa Katagiri, Yusuke Nakamura
Journal: Cancer Research (2005)

Abstract P-Cadherin/CDH3 belongs to the family of classic cadherins that are engaged in various cellular activities including motility, invasion, and signaling of tumor cells, in addition to cell adhesion. However, the biological roles of P-cadherin itself are not fully characterized. Based on information derived from a previous genome-wide cDNA microarray analysis of microdissected pancreatic ductal adenocarcinoma (PDAC), we focused on P-cadherin as one of the genes most strongly overexpressed in the great majority of PDACs. To investigate the consequences of overexpression of P-cadherin in terms of pancreatic carcinogenesis and tumor progression, we used a P-cadherin–deficient PDAC cell line, Panc-1, to construct a cell line (Panc1-CDH3) that stably overexpressed P-cadherin. Induction of P-cadherin in Panc1-CDH3 increased the motility of the cancer cells, but a blocking antibody against P-cadherin suppressed the motility in vitro. Overexpression of P-cadherin was strongly associated with cytoplasmic accumulation of one of the catenins, p120ctn, and cadherin switching in PDAC cells. Moreover, P-cadherin–dependent activation of cell motility was associated with activation of Rho GTPases, Rac1 and Cdc42, through accumulation of p120ctn in cytoplasm and cadherin switching. These findings suggest that overexpression of P-cadherin is likely to be related to the biological aggressiveness of PDACs; blocking of P-cadherin activity or its associated signaling could be a novel therapeutic approach for treatment of aggressive pancreatic cancers.
Fasting Hypoketotic Coma in a Child with Deficiency of Mitochondrial 3-Hydroxy-3-Methylglutaryl-CoA Synthase
Authors: Geoffrey N. Thompson, Betty Y.L. Hsu, James J. Pitt, Eileen Treacy, Charles A. Stanley
Journal: New England Journal of Medicine (1997)

Fasting is accompanied by a decrease in the availability of glucose for energy use in peripheral tissues and, consequently, an increased reliance of these tissues on the availability of ketone bodies and fatty acids for energy. The availability of ketone bodies depends almost exclusively on hepatic ketogenesis. Failure of ketogenesis may occur in patients with any defect of the enzymes associated with the mitochondrial oxidation of fatty acids.1 These defects are typically manifested by hypoglycemia, which results from the inadequate supply of alternative substrate (ketones). Other clinical features are more variable and may include myopathy, cardiomyopathy, hepatocellular damage, and neuropathies. . . .
Prospective Study of Serum Vitamin E Levels and Esophageal and Gastric Cancers
Authors: P. R. Taylor, Y.-L. Qiao, C. C. Abnet, S. M. Dawsey, C. S. Yang, E. W. Gunter, W. Wang, W. J. Blot, Z.-W. Dong, S. D. Mark
Journal: JNCI Journal of the National Cancer Institute (2003)

Participants in the General Population Trial, a randomized nutrition intervention trial in Linxian, China, who received a combination of selenium, beta-carotene, and vitamin E supplements, had statistically significantly lower cancer mortality rates than those who did not receive the supplements. In the current study, we used a case-cohort design to examine the association between pre-trial serum vitamin E levels and the risks of developing esophageal and gastric cancers during the trial. We measured serum alpha- and gamma-tocopherol and cholesterol levels in 1072 case patients with incident esophageal squamous cell carcinoma (ESCC), gastric cardia cancer (GCC), or gastric noncardia cancer (GNCC) and in 1053 control subjects. The relative risks for comparisons of the highest to the lowest quartiles of serum alpha-tocopherol were 0.63 (95% confidence interval [CI] = 0.44 to 0.91) for ESCC, 0.84 (95% CI = 0.55 to 1.26) for GCC, and 2.05 (95% CI = 0.89 to 4.75) for GNCC. Serum gamma-tocopherol level was not associated with the incidence of any of these cancers. Our findings provide support for the role of alpha-tocopherol in the etiology of upper gastrointestinal cancers.
Tie2 Receptor Expression Is Stimulated by Hypoxia and Proinflammatory Cytokines in Human Endothelial Cells
Authors: Carsten Willam, Petra Koehne, Jan Steffen Jürgensen, Michael Gräfe, Kay Dietrich Wagner, Sebastian Bachmann, Ulrich Frei, Kai-Uwe Eckardt
Journal: Circulation Research (2000)

Abstract —The tyrosine kinase receptor Tie2 (also known as Tek) plays an important role in the development of the embryonic vasculature and persists in adult endothelial cells (ECs). Tie2 was shown to be upregulated in tumors and skin wounds, and its ligands angiopoietin-1 and -2, although they are not directly mitogenic, modulate neovascularization. To gain further insight into the regulation of Tie2, we have studied the effect of hypoxia and inflammatory cytokines, two conditions frequently associated with neoangiogenic processes, on Tie2 expression in human ECs. Exposure to 1% O 2 led to a time-dependent significant rise of Tie2 protein levels in human coronary microvascular endothelial cells (HCMECs) and dermal microvascular ECs (HMEC-1) (3.2- and 2.5-fold within 24 hours), which was reversible after reoxygenation, and induced a less marked increase in human umbilical vein ECs (HUVECs; 1.7-fold). Hypoxia-conditioned medium and d -deoxyglucose did not change Tie2 expression, but desferrioxamine and cobalt, which are known to mimic hypoxia-sensing mechanisms, induced Tie2 at ambient oxygen tensions. Tumor necrosis factor-α induced Tie2 in a time- and dose-dependent fashion in all 3 EC types (HUVEC, 2.3-fold; HMEC-1, 2.8-fold; and HCMEC, 3.0-fold; 10 ng/mL, 24 hours). Enhanced expression was also found after exposure to interleukin-1β (1 ng/mL). Changes in Tie2 protein levels were paralleled by changes in mRNA expression. In accordance with these in vitro findings, immunohistochemistry revealed focal upregulation of Tie2 in capillaries at the border of infarcted human and rat myocardium. In conclusion, the data show that hypoxia and inflammatory cytokines upregulate Tie2, which may contribute to the angiogenic response in ischemic tissues.
Down-regulation of transforming growth factor-β type II receptor (TGF-βRII) protein and mRNA expression in cervical cancer
Authors: Jose Diaz-Chavez, Rogelio Hernandez-Pando, Paul F Lambert, Patricio Gariglio
Journal: Molecular Cancer (2008)

Abstract Background Cervical carcinogenesis is a multistep process initiated by "high risk" human papillomaviruses (HR-HPV), most commonly HPV16. The infection per se is, however, not sufficient to induce malignant conversion. Transforming Growth Factor β (TGF-β) inhibits epithelial proliferation and altered expression of TGF-β or its receptors may be important in carcinogenesis. One cofactor candidate to initiate neoplasia in cervical cancer is the prolonged exposure to sex hormones. Interestingly, previous studies demonstrated that estrogens suppress TGF-β induced gene expression. To examine the expression of TGF-β2, TGF-βRII, p15 and c-myc we used in situ RT-PCR, real-time PCR and immunohistochemistry in transgenic mice expressing the oncogene E7 of HPV16 under control of the human Keratin-14 promoter (K14-E7 transgenic mice) and nontransgenic control mice treated for 6 months with slow release pellets of 17β-estradiol. Results Estrogen-induced carcinogenesis was accompanied by an increase in the incidence and distribution of proliferating cells solely within the cervical and vaginal squamous epithelium of K14-E7 mice. TGF-β2 mRNA and protein levels increased in K14-E7 transgenic mice as compared with nontransgenic mice and further increased after hormone-treatment in both nontransgenic and transgenic mice. In contrast, TGF-βRII mRNA and protein levels were decreased in K14-E7 transgenic mice compared to nontransgenic mice and these levels were further decreased after hormone treatment in transgenic mice. We also observed that c-myc mRNA levels were high in K14-E7 mice irrespective of estrogen treatment and were increased in estrogen-treated nontransgenic mice. Finally we found that p15 mRNA levels were not increased in K14-E7 mice. Conclusion These results suggest that the synergy between estrogen and E7 in inducing cervical cancer may in part reflect the ability of both factors to modulate TGF-β signal transduction.
Comparison of the clinical features of chronic and aggressive periodontitis
Authors: Gary C. Armitage, Mary P. Cullinan
Journal: Periodontology 2000 (2010)

Overall, while most clinicians would agree that aggressive forms of periodontitis exist as clinical entities, the clinical distinction between chronic and aggressive periodontitis (especially generalized) is not clear cut. This may not be all that significant from a treatment perspective, in so far as individualized anti-infective therapies are effective for both forms of the disease. However, from a research perspective, it is essential that these diseases be clearly distinguished in order to gain a complete understanding of their etiology and pathogenesis. The relative lack of clinical inflammation often associated with the localized molar-and-incisor form of aggressive periodontitis has been commented on for almost 100 years, and it is generally accepted that this form of the disease is associated with a thin biofilm, at least in its early stages. In contrast, the presence of clinical inflammation in generalized aggressive periodontitis appears to be similar to that observed in chronic periodontitis, and in this situation age of onset and family history are important additional criteria for either diagnosis or classification. It is also generally recognized that chronic periodontitis may subsequently be superimposed on both localized and generalized forms of aggressive periodontitis. While this may have little bearing on the treatment of such cases, it could have an enormous impact on both the design and interpretation of research studies, whether basic science or clinical. This highlights the essential difference between a diagnosis and a classification, whereby a diagnosis is the clinician's best guess, leading on to a treatment plan, whereas a classification does not allow such flexibility, requiring non-overlapping case definitions for research purposes if the underlying etiology of these diseases is ever to be fully elucidated.
Socioeconomic inequalities in adolescent health 2002–2010: a time-series analysis of 34 countries participating in the Health Behaviour in School-aged Children study
Authors: Frank J Elgar, Timo-Kolja Pförtner, Irene Moor, Bart De Clercq, Gonneke W J M Stevens, Candace Currie
Journal: The Lancet (2015)
Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages
Authors: Ari B. Molofsky, Jesse C. Nussbaum, Hong-Erh Liang, Steven J. Van Dyken, Laurence E. Cheng, Alexander Mohapatra, Ajay Chawla, Richard M. Locksley
Journal: The Journal of Experimental Medicine (2013)

Eosinophils in visceral adipose tissue (VAT) have been implicated in metabolic homeostasis and the maintenance of alternatively activated macrophages (AAMs). The absence of eosinophils can lead to adiposity and systemic insulin resistance in experimental animals, but what maintains eosinophils in adipose tissue is unknown. We show that interleukin-5 (IL-5) deficiency profoundly impairs VAT eosinophil accumulation and results in increased adiposity and insulin resistance when animals are placed on a high-fat diet. Innate lymphoid type 2 cells (ILC2s) are resident in VAT and are the major source of IL-5 and IL-13, which promote the accumulation of eosinophils and AAM. Deletion of ILC2s causes significant reductions in VAT eosinophils and AAMs, and also impairs the expansion of VAT eosinophils after infection with Nippostrongylus brasiliensis, an intestinal parasite associated with increased adipose ILC2 cytokine production and enhanced insulin sensitivity. Further, IL-33, a cytokine previously shown to promote cytokine production by ILC2s, leads to rapid ILC2-dependent increases in VAT eosinophils and AAMs. Thus, ILC2s are resident in VAT and promote eosinophils and AAM implicated in metabolic homeostasis, and this axis is enhanced during Th2-associated immune stimulation.
A Cell Culture–Derived MF59-Adjuvanted Pandemic A/H7N9 Vaccine Is Immunogenic in Adults
Authors: Stephan A. Bart, Matthew Hohenboken, Giovanni Della Cioppa, Vas Narasimhan, Philip R. Dormitzer, Niranjan Kanesa-thasan
Journal: Science Translational Medicine (2014)

An MF59-adjuvanted A/H7N9 candidate vaccine shows promise in the face of a possible A/H7N9 pandemic.
Endobronchial pseudo-tumour caused by herpes simplex
Authors: A. Upadya, L. Tilluckdharry, C. D. Nagy, P. Ravichandran, C. Manthous
Journal: European Respiratory Journal (2005)

Herpes simplex virus (HSV) causes tracheobronchitis and pneumonitis; however, to date, there has only been one report of an endobronchial mass caused by HSV type II. This case study describes a 68-yr-old female with severe kyphoscoliosis who was intubated for acute on chronic hypercapnic respiratory failure and developed blood-tinged endotracheal secretions. Fibreoptic bronchoscopy demonstrated an endobronchial mass in the right middle lobe. Cultures grew HSV type I and biopsy specimens demonstrated cytopathological changes consistent with HSV infection. This is the first reported case of HSV type I presenting as an endobronchial tumour.
Osteoporosis in patients with inflammatory bowel disease
Authors: N K Arden
Journal: Gut (2002)

Increased incidence of “fragility” fractures in patients with inflammatory bowel disease

There is consistent evidence that patients with inflammatory bowel disease (IBD) have an increased risk of osteoporosis, defined by reduced bone mineral density (BMD).1 The important clinical end point of osteoporosis however, is fractures; these are associated with significant morbidity and mortality and healthcare costs. The retrospective cohort study of Bernstein et al shows a 40% increase in the risk of fracture among patients with IBD compared with age and sex matched controls.2 The increased risk was similar in patients with Crohn's disease (CD) and ulcerative colitis (UC). These results differ from a large Danish case control study which reported a 2.5-fold increase in the risk of fracture among women with CD but failed to demonstrate a statistically significant increased risk among men with CD or patients with UC.3 The literature on BMD in IBD is also discordant when comparing the risk of osteoporosis in patients with CD with those with UC.1 Further large studies of fracture in these disorders are required to quantify the risk in CD and UC.

The reduction …
Fasting Glucose Level and the Risk of Incident Atherosclerotic Cardiovascular Diseases
Authors: Chanshin Park, Eliseo Guallar, John A. Linton, Duk-Chul Lee, Yangsoo Jang, Dong Koog Son, Eun-Jeong Han, Soo Jin Baek, Young Duk Yun, Sun Ha Jee, Jonathan M. Samet
Journal: Diabetes Care (2013)

Although diabetes increases the risk of cardiovascular disease (CVD) and mortality, the dose-response relationship between fasting glucose levels below those diagnostic of diabetes with cardiovascular events has not been well characterized.A prospective cohort study of more than one million Koreans was conducted with a mean follow-up of 16 years. A total of 1,197,384 Korean adults with no specific medical conditions diagnosed were classified by baseline fasting serum glucose level. Associations of fasting glucose level with CVD incidence and mortality, stroke incidence and mortality, and all-cause mortality were analyzed using multivariate proportional hazards regression.The relationships between fasting glucose levels and CVD risks generally followed J-shape curves, with lowest risk in the glucose range of 85-99 mg/dL. As fasting glucose levels increased to >100 mg/dL, risks for CVD, ischemic heart disease, myocardial infarction, and thrombotic stroke progressively increased, but risk for hemorrhagic stroke did not. Fasting glucose levels <70 mg/dL were associated with increased risk of all stroke (hazard ratio 1.06, 95% CI 1.01-1.11) in men and (hazard ratio 1.11, 1.05-1.17) in women.Both low glucose level and impaired fasting glucose should be considered as predictors of risk for stroke and coronary heart disease. The fasting glucose level associated with the lowest cardiovascular risk may be in a narrow range.
A <i>Toxoplasma</i> dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation
Authors: Laurence Braun, Marie-Pierre Brenier-Pinchart, Manickam Yogavel, Aurélie Curt-Varesano, Rose-Laurence Curt-Bertini, Tahir Hussain, Sylvie Kieffer-Jaquinod, Yohann Coute, Hervé Pelloux, Isabelle Tardieux, Amit Sharma, Hassan Belrhali, Alexandre Bougdour, Mohamed-Ali Hakimi
Journal: The Journal of Experimental Medicine (2013)

Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan parasite that resides inside a parasitophorous vacuole. During infection, Toxoplasma actively remodels the transcriptome of its hosting cells with profound and coupled impact on the host immune response. We report that Toxoplasma secretes GRA24, a novel dense granule protein which traffics from the vacuole to the host cell nucleus. Once released into the host cell, GRA24 has the unique ability to trigger prolonged autophosphorylation and nuclear translocation of the host cell p38α MAP kinase. This noncanonical kinetics of p38α activation correlates with the up-regulation of the transcription factors Egr-1 and c-Fos and the correlated synthesis of key proinflammatory cytokines, including interleukin-12 and the chemokine MCP-1, both known to control early parasite replication in vivo. Remarkably, the GRA24–p38α complex is defined by peculiar structural features and uncovers a new regulatory signaling path distinct from the MAPK signaling cascade and otherwise commonly activated by stress-related stimuli or various intracellular microbes.
Effect of heparin on pulmonary fibroblasts and vascular cells.
Authors: Y Yamashita, K Nakagomi, T Takeda, S Hasegawa, Y Mitsui
Journal: Thorax (1992)

BACKGROUND: There is a large increase in mast cell numbers in fibrotic lung tissue, suggesting that mast cells may play a part in the pathogenesis of pulmonary fibrosis. Glycosaminoglycans, such as heparan sulphate, that are structurally related to heparin (a mast cell product) are part of the extracellular matrix and known to regulate cell growth. Basic fibroblast growth factor is a heparin binding growth factor produced by endothelial cells. METHODS: A study was carried out to examine the effect of heparin, basic fibroblast growth factor, and mast cell products on the proliferation of normal human lung fibroblasts and the effect of adding heparin on the proliferation of lung fibroblasts and pulmonary vascular cells incubated with basic fibroblast growth factor. RESULTS: Heparin at low concentration (0.03, 0.3-1.0 micrograms/ml) stimulated the proliferation of normal human lung fibroblasts in culture whereas a higher concentration (100 micrograms/ml) had an inhibitory effect. Mast cell products also stimulated the proliferation of fibroblasts, and the effect was decreased by pretreatment with heparinase or protamine. Heparin enhanced the growth of both fibroblasts and pulmonary vascular cells induced by low concentrations of basic fibroblast growth factor. CONCLUSIONS: Mast cells in fibrotic lung tissue may regulate fibroblast proliferation by releasing heparin. These results suggest that endothelial cells may interact with mast cells and modulate fibroblast growth by release of basic fibroblast growth factor.