tbuckley/cabot-search huggingface dataset:
Myeloid-related protein-8/14 facilitates bacterial growth during pneumococcal pneumonia
Authors: Ahmed Achouiti, Thomas Vogl, Henrik Endeman, Brittany L Mortensen, Pierre-Francois Laterre, Xavier Wittebole, Marieke A D van Zoelen, Yaofang Zhang, Jacobien J Hoogerwerf, Sandrine Florquin, Marcus J Schultz, Jan C Grutters, Douwe H Biesma, Johannes Roth, Eric P Skaar, Cornelis van 't Veer, Alex F de Vos, Tom van der Poll
Journal: Thorax (2014)

<h3>Background</h3> <i>Streptococcus pneumoniae</i> is the most commonly identified pathogen in community-acquired pneumonia (CAP). Myeloid-related protein (MRP) 8/14 is a major component of neutrophils that is released upon infection or injury. MRP8/14 is essential for protective immunity during infection by a variety of micro-organisms through its capacity to chelate manganese and zinc. Here, we aimed to determine the role of MRP8/14 in pneumococcal pneumonia. <h3>Methods</h3> MRP8/14 was determined in bronchoalveolar lavage fluid (BALF) and serum of CAP patients, in lung tissue of patients who had succumbed to pneumococcal pneumonia, and in BALF of healthy subjects challenged with lipoteichoic acid (a component of the gram-positive bacterial cell wall) via the airways. Pneumonia was induced in MRP14 deficient and normal wildtype mice. The effect of MRP8/14 on <i>S. pneumoniae</i> growth was studied in vitro. <h3>Results</h3> CAP patients displayed high MRP8/14 levels in BALF, lung tissue and serum. Healthy subjects challenged with lipoteichoic acid demonstrated elevated MRP8/14 in BALF. Likewise, mice with pneumococcal pneumonia had high MRP8/14 levels in lungs and the circulation. MRP14 deficiency, however, was associated with reduced bacterial growth and lethality, in the absence of notable effects on the inflammatory response. High zinc levels strongly inhibited growth of <i>S. pneumoniae</i> in vitro, which was partially reversed by MRP8/14. <h3>Conclusions</h3> In sharp contrast to its previously reported host-protective role in several infections, the present results reveal that in a model of CAP, MRP8/14 is misused by <i>S. pneumoniae</i>, facilitating bacterial growth by attenuating zinc toxicity toward the pathogen.
Ouabain Inhibits Tubuloglomerular Feedback in Mutant Mice with Ouabain-Sensitive α1 Na,K-ATPase
Authors: John N. Lorenz, Iva Dostanic-Larson, Gary E. Shull, Jerry B. Lingrel
Journal: Journal of the American Society of Nephrology (2006)

Initiation of tubuloglomerular feedback (TGF) depends on Na-K-2Cl co-transport in the macula densa (MD), but it is less clear whether Na,K-ATPase is responsible for establishing the inward Na<sup>+</sup> gradient. It has been proposed that apical colonic H,K-ATPase, perhaps in concert with the Na/H exchanger (NHE2), may account for MD Na<sup>+</sup> exit in these cells. This study evaluated TGF responses by micropuncture in mutant mice with altered ouabain sensitivity of the α1 and α2 Na,K-ATPase isoforms. TGF responses in α1-sensitive/α2-resistant mice were inhibited by intravenous ouabain (control stop-flow pressure = 9.7 ± 0.9 <i>versus</i> 1.6 ± 0.5 mmHg with intravenous ouabain). Subsequent inclusion of cyclohexyladenosine (10 μM) in the tubule perfusate confirmed the ability of the afferent arteriole to contract in the presence of ouabain. In α1-resistant/α2-resistant mice, ouabain infusion had no effect on TGF responses. In separate experiments, loop of Henle perfusion with 50 μM ouabain decreased TGF responses (control stop-flow pressure) from 10.5 ± 1.1 to 3.9 ± 1.0 mmHg in α1-sensitive/α2-resistant mice but had no effect in α1-resistant/α2-resistant mice, and afferent arteriole responsiveness again was confirmed by cyclohexyladenosine. TGF responses in NHE2 and colonic H,K-ATPase knockout mice were not different from those of wild-type mice. These data indicate that TGF requires activity of the α1 Na,K-ATPase, presumably in the MD. Furthermore, the data show that neither NHE2 nor colonic H,K-ATPase is essential for initiation of TGF responses.
International Union of Basic and Clinical Pharmacology. XCIII. The Parathyroid Hormone Receptors—Family B G Protein–Coupled Receptors
Authors: Thomas J. Gardella, Jean-Pierre Vilardaga
Journal: Pharmacological Reviews (2015)

The type-1 parathyroid hormone receptor (PTHR1) is a family B G protein–coupled receptor (GPCR) that mediates the actions of two polypeptide ligands; parathyroid hormone (PTH), an endocrine hormone that regulates the levels of calcium and inorganic phosphate in the blood by acting on bone and kidney, and PTH-related protein (PTHrP), a paracrine-factor that regulates cell differentiation and proliferation programs in developing bone and other tissues. The type-2 parathyroid hormone receptor (PTHR2) binds a peptide ligand, called tuberoinfundibular peptide-39 (TIP39), and while the biologic role of the PTHR2/TIP39 system is not as defined as that of the PTHR1, it likely plays a role in the central nervous system as well as in spermatogenesis. Mechanisms of action at these receptors have been explored through a variety of pharmacological and biochemical approaches, and the data obtained support a basic "two-site" mode of ligand binding now thought to be used by each of the family B peptide hormone GPCRs. Recent crystallographic studies on the family B GPCRs are providing new insights that help to further refine the specifics of the overall receptor architecture and modes of ligand docking. One intriguing pharmacological finding for the PTHR1 is that it can form surprisingly stable complexes with certain PTH/PTHrP ligand analogs and thereby mediate markedly prolonged cell signaling responses that persist even when the bulk of the complexes are found in internalized vesicles. The PTHR1 thus appears to be able to activate the G<i>α</i><sub>s</sub>/cAMP pathway not only from the plasma membrane but also from the endosomal domain. The cumulative findings could have an impact on efforts to develop new drug therapies for the PTH receptors.
Risk of Malignant Progression in Barrett's Esophagus Patients: Results from a Large Population-Based Study
Authors: S. Bhat, H. G. Coleman, F. Yousef, B. T. Johnston, D. T. McManus, A. T. Gavin, L. J. Murray
Journal: JNCI Journal of the National Cancer Institute (2011)

Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005. We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests. After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P < .001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P < .001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P < .001). We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective.
Eosinophils are an insignificant cellular component of rheumatoid synovium in patients with late stage disease: comparative distributions with mast cells and macrophages.
Authors: L C Tetlow, D E Woolley
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVES: To examine the distribution of eosinophils in rheumatoid synovial tissue and to determine whether or not their tissue distribution is related to that of mast cells or macrophages. METHODS: Consecutive tissue sections from 31 specimens of rheumatoid synovial tissue and cartilage-pannus junction were stained for eosinophils, mast cells, and macrophages with monoclonal antibodies and immunolocalisation techniques. RESULTS: Eosinophils were absent in 28 of the 31 specimens; the remaining three showed only the occasional eosinophil. By contrast the mean values for mast cell and macrophage (CD68/KP1 marker) distributions were 24 (SD 22) and 104 (SD 66) per mm2, respectively. CONCLUSION: There are very few eosinophils in inflamed rheumatoid synovial tissue and sites of cartilage erosion despite the presence of appreciable numbers of macrophages and mast cells, the mast cells showing various states of activation. Such findings are at variance with those in allergic inflammation, in which the presence of eosinophils has been reported to be regulated by specific chemokines and adhesion molecules.
Hypoglycemia in Pregnant Women With Type 1 Diabetes
Authors: Lene Ringholm Nielsen, Ulrik Pedersen-Bjergaard, Birger Thorsteinsson, Marianne Johansen, Peter Damm, Elisabeth R. Mathiesen
Journal: Diabetes Care (2007)

In pregnancy with type 1 diabetes, we evaluated occurrence of mild and severe hypoglycemia and analyzed the influence of strict metabolic control, nausea, vomiting, and other potential predictors of occurrence of severe hypoglycemia.A prospective observational study of 108 consecutive pregnant women with type 1 diabetes was conducted. At 8, 14, 21, 27, and 33 weeks of gestation, patients performed self-monitored plasma glucose (SMPG) (eight/day) for 3 days and completed a questionnaire on nausea, vomiting, hypoglycemia awareness, and history of mild (managed by the patient) and severe (requiring assistance from others) hypoglycemia.Forty-nine (45%) women experienced 178 severe hypoglycemic events, corresponding to 5.3, 2.4, and 0.5 events/patient-year in the first, second, and third trimesters, respectively. The incidence of mild hypoglycemia was 5.5 events/patient-week in early pregnancy and decreased throughout pregnancy (P < 0.0001), regardless of presence of severe hypoglycemia. Prevalence of nausea and vomiting, mild hypoglycemia, and fraction of SMPG readings </=3.9 mmol/l did not differ between women with and without severe hypoglycemia. A1C, median SMPG, and fluctuations in SMPG decreased during pregnancy, with no differences between women with and without severe hypoglycemia. Logistic regression analysis identified history of severe hypoglycemia the year preceding pregnancy (odds ratio 3.3 [95% CI 1.2-9.2]) and impaired awareness or unawareness (3.2 [1.2-8.2]) as independent predictors for severe hypoglycemia.In pregnancy with type 1 diabetes, the incidence of mild and severe hypoglycemia was highest in early pregnancy, although metabolic control was tighter in the last part of pregnancy. Predictors for severe hypoglycemia were history of severe hypoglycemia and impaired awareness.
THE EFFECTS OF EXERCISE UPON THE RETARDATION IN CONDITIONS OF DEPRESSION
Authors: Shepherd Ivory Franz, G. V. Hamilton
Journal: American Journal of Psychiatry (1905)

The results of these studies may be summed up as follows: 1. The thresholds of pain and pressure appreciation are higher than normal in a case of retardation. 2. There is a daily improvement in the pressure and pain sensibility coincident with the lessening of the retardation and the depression. 3. The accuracy of movement is not affected by depression and retardation. 4. The speed of movement is lessened in the retarded condition, but it is gradually increased during the period of recovery. 5. Mechanical vibration increases the rapidity of movement, and lowers the pain and the pressure thresholds. 6. The speed of mental processes is increased with improvement in the mental condition of retardation. 7. After moderate exercise there is more improvement than after a similar resting period.
Malaria complicating open-heart surgery.
Authors: C K Mok, K L Cheung, K H Wai, G B Ong
Journal: Thorax (1980)

Two cases of malaria developing immediately after open-heart surgery are reported to illustrate that malaria is one of the rarer causes of postoperative pyrexia. The diagnosis can easily be missed, resulting in unnecessary morbidity and even mortality. It is important for cardiac surgeons to be aware of this possibility in malaria-free as well as malaria-endemic areas as patients or blood donors who come from or have recently visited an endemic area are potential victims or sources of the infection.
Prostaglandin E2 Regulates Tumor Angiogenesis in Prostate Cancer
Authors: Shalini Jain, Goutam Chakraborty, Remya Raja, Smita Kale, Gopal C. Kundu
Journal: Cancer Research (2008)

Abstract In cancer management, the cyclooxygenase (COX)–targeted approach has shown great promise in anticancer therapeutics. However, the use of COX-2 inhibitors has side effects and health hazards; thus, targeting its major metabolite prostaglandin E2 (PGE2)–mediated signaling pathway might be a rational approach for the next generation of cancer management. Recent studies on several in vitro and in vivo models have revealed that elevated expression of COX-2 correlates with prostate tumor growth and angiogenesis. In this study, we have shown the in-depth molecular mechanism and the PGE2 activation of the epidermal growth factor receptor and β3 integrin through E prostanoid 2 (EP2)–mediated and EP4-mediated pathways, which lead to activator protein-1 (AP-1) activation. Moreover, PGE2 also induces activating transcription factor-4 (ATF-4) activation and stimulates cross-talk between ATF-4 and AP-1, which is unidirectional toward AP-1, which leads to the increased expressions of urokinase-type plasminogen activator and vascular endothelial growth factor and, eventually, regulates prostate tumor cell motility. In vivo Matrigel angiogenesis assay data revealed that PGE2 induces angiogenesis through EP2 and EP4. Human prostate cancer specimen analysis also supported our in vitro and in vivo studies. Our data suggest that targeting PGE2 signaling pathway (i.e., blocking EP2 and EP4 receptors) might be a rational therapeutic approach for overcoming the side effects of COX-2 inhibitors and that this might be a novel strategy for the next generation of prostate cancer management. [Cancer Res 2008;68(19):7750–9]
Towards a new developmental synthesis: adaptive developmental plasticity and human disease
Authors: Peter D Gluckman, Mark A Hanson, Patrick Bateson, Alan S Beedle, Catherine M Law, Zulfiqar A Bhutta, Konstantin V Anokhin, Pierre Bougnères, Giriraj Ratan Chandak, Partha Dasgupta, George Davey Smith, Peter T Ellison, Terrence E Forrester, Scott F Gilbert, Eva Jablonka, Hillard Kaplan, Andrew M Prentice, Stephen J Simpson, Ricardo Uauy, Mary Jane West-Eberhard
Journal: The Lancet (2009)
Reduced incidence of alcohol related deaths in subjects with rheumatoid arthritis
Authors: R. Myllykangas-Luosujarvi
Journal: Annals of the Rheumatic Diseases (2000)

It has previously been shown that people with ankylosing spondylitis have an increased incidence of alcohol related deaths from accidents and violence. This study investigated alcohol related deaths in subjects with rheumatoid arthritis (RA).The study covered the subjects, 1666 in number, who had died in 1989 and had been entitled under the nationwide sickness insurance scheme to receive specially reimbursed medication for RA.There were eight alcohol related deaths among the 480 men and three deaths among the 1186 women with RA. The standardised mortality ratios and their 95% confidence intervals (CI) were 0.40 (95% CI 0.20, 0.80) and 0.40 (95% CI 0.13, 1.26), respectively.Alcohol either protects from RA or, subjects with RA curtail their drinking after the manifestation of RA.
Food allergy: A practice parameter update—2014
Authors: Hugh A. Sampson, Seema Aceves, S. Allan Bock, John James, Stacie Jones, David Lang, Kari Nadeau, Anna Nowak-Wegrzyn, John Oppenheimer, Tamara T. Perry, Christopher Randolph, Scott H. Sicherer, Ronald A. Simon, Brian P. Vickery, Robert Wood, Hugh A. Sampson, Christopher Randolph, David Bernstein, Joann Blessing-Moore, David Khan, David Lang, Richard Nicklas, John Oppenheimer, Jay Portnoy, Christopher Randolph, Diane Schuller, Sheldon Spector, Stephen A. Tilles, Dana Wallace, Hugh A. Sampson, Seema Aceves, S. Allan Bock, John James, Stacie Jones, David Lang, Kari Nadeau, Anna Nowak-Wegrzyn, John Oppenheimer, Tamara T. Perry, Christopher Randolph, Scott H. Sicherer, Ronald A. Simon, Brian P. Vickery, Robert Wood
Journal: Journal of Allergy and Clinical Immunology (2014)
Lung Squamous Cell Carcinomas with Basaloid Histology Represent a Specific Molecular Entity
Authors: Christian Brambilla, Julien Laffaire, Sylvie Lantuejoul, Denis Moro-Sibilot, Hélène Mignotte, François Arbib, Anne-Claire Toffart, Fabien Petel, Pierre Hainaut, Sophie Rousseaux, Saadi Khochbin, Aurélien de Reyniès, Elisabeth Brambilla
Journal: Clinical Cancer Research (2014)

The basaloid carcinoma (pure) and the (mixed) basaloid variant of lung squamous cell carcinoma (SCC) have a dismal prognosis but their underlying specific molecular characteristics remain obscure and no therapy has proven to be efficient.To assess their molecular specificity among other lung SCCs we analyzed DNA copy number aberrations and mRNA expression pangenomic profiles of 93 SCCs, including 42 basaloid samples (24 pure, 18 mixed).Supervised analyses reveal that pure basaloid tumors display a specific mRNA expression profile, encoding factors controlling the cell cycle, transcription, chromatin, and splicing, with prevalent expression in germline and stem cells, while genes related to squamous differentiation are underexpressed. From this signature, we derived a 2-genes (SOX4, IVL) immunohistochemistry-based predictor that discriminated basaloid tumors (pure and mixed) from non-basaloid tumors with 94% accuracy in an independent series. The pure basaloid tumors are also distinguished through unsupervised analyses. Using a centroid-based predictor, the corresponding molecular subtype was found in 8 independent public datasets (n = 58/533), and was shown to be associated with a very poor survival as compared with other SCCs (adjusted HR = 2.45; P = 0.000001).This study enlightens the heterogeneity of SCCs that can be subclassified in mRNA expression subtypes. This study demonstrates for the first time that basaloid SCCs constitute a distinct histomolecular entity, which justifies its recognition and distinction from non-basaloid SCCs. In addition, their characteristic molecular profile highlights their intrinsic resistance to cytotoxic chemotherapy and could serve as a guide for targeted therapies.
Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility
Authors: Dewi Astuti, Mark R Morris, Wendy N Cooper, Raymond H J Staals, Naomi C Wake, Graham A Fews, Harmeet Gill, Dean Gentle, Salwati Shuib, Christopher J Ricketts, Trevor Cole, Anthonie J van Essen, Richard A van Lingen, Giovanni Neri, John M Opitz, Patrick Rump, Irene Stolte-Dijkstra, Ferenc Müller, Ger J M Pruijn, Farida Latif, Eamonn R Maher
Journal: Nature Genetics (2012)
Life threatening chylous pleural and pericardial effusion in a patient with Behcet's syndrome.
Authors: L Coplu, S Emri, Z T Selcuk, F Kalyoncu, F Balkanci, A A Sahin, Y I Baris
Journal: Thorax (1992)

Chylothorax and chylopericardium secondary to thrombosis of the superior vena cava and the innominate and subclavian veins were diagnosed in a patient with Behçet9s syndrome. Immunosuppressive treatment, diet, and underwater seal drainage led to a diminished volume of pleural fluid and pericardial fluid and to a diminished concentration of triglyceride in them; pleurodesis with tetracycline was then performed.
Temporal Trends in Fracture Rates and Postdischarge Outcomes among Hemodialysis Patients
Authors: Anne C. Beaubrun, Ryan D. Kilpatrick, Janet K. Freburger, Brian D. Bradbury, Lily Wang, M. Alan Brookhart
Journal: Journal of the American Society of Nephrology (2013)

Patients with ESRD have a substantially increased risk of bone fractures, but the burden of fractures has not been sufficiently characterized in this population. Here, we analyzed fracture rates and postdischarge outcomes using Medicare data from hemodialysis patients in the United States between 2000 and 2009. We assessed adjusted quarterly fracture rates (inpatient and outpatient) and consequences of postfracture hospitalization for seven categories of fracture location. Pelvis/hip, vertebral, and lower leg fractures were the most prevalent fracture types. Pelvis/hip fractures declined slightly from 29.6 to 20.6 per 1000 patient-years between early 2000 and late 2009, but the incidence rates for all other fracture types remained relatively constant. Median lengths of stay for the primary fracture hospitalization ranged from 5 days (interquartile range [IQR], 3-9 days) for forearm/wrist fractures to 8 days (IQR, 5-12 days) for femur fractures. The proportion of patients discharged from the primary hospitalization to a skilled-nursing facility ranged from 28% (ribs/sternum) to 47% (pelvis/hip). A negative binomial regression model suggested that patients had an adjusted mean of 3.8-5.2 additional hospitalizations during the year after discharge from the index hospitalization, varying by fracture type, comprising a mean of 33-52 inpatient days. Case-mix-adjusted mortality rates after discharge ranged from 0.43 to 0.91 per patient-year and were highest for vertebral, pelvis/hip, and femur fractures. In conclusion, fractures in the dialysis population are common and are associated with a substantially increased risk for death and hospitalization.
Efficacy of HPV DNA Testing With Cytology Triage and/or Repeat HPV DNA Testing in Primary Cervical Cancer Screening
Authors: P. Naucler, W. Ryd, S. Tornberg, A. Strand, G. Wadell, K. Elfgren, T. Radberg, B. Strander, O. Forslund, B.-G. Hansson, B. Hagmar, B. Johansson, E. Rylander, J. Dillner
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundPrimary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective.