tbuckley/cabot-search huggingface dataset:
Detection of pulmonary arteriovenous fistulae in patient with cirrhosis by contrast 2D echocardiography.
Authors: C R Hind, C M Wong
Journal: Gut (1981)

A case of multiple pulmonary arteriovenous fistulae associated with cirrhosis of the liver is described. The diagnosis was made by contrast two-dimensional echocardiography and confirmed by cardiac catheterisation and pulmonary angiography. As it is a sensitive and non-invasive technique, contrast two-dimensional echocardiography may be a useful screening test in cyanotic patients with liver disease in whom the presence of pulmonary fistulae is suspected.
Abstract 996: Loss of alpha-dystroglycan laminin binding in epithelium-derived cancers is caused by silencing of <i>LARGE</i>
Authors: Daniel Beltran, Kei-ichiro Inamori, Takako Moriguchi, Christine J. Weydert, Hollie A. Harper, Tobias Willer, William J. Muller, Michael D. Henry, Kevin P. Campbell
Journal: Cancer Research (2010)

Abstract Dystroglycan is a ubiquitously expressed cell membrane receptor that mediates interactions between cells and basement membranes in various epithelia. Dystroglycan is synthesized as a preprotein that is cleaved in two peptides: the transmembranal beta-dystroglycan, and the extracellular laminin receptor alpha-dystroglycan. In many epithelium-derived cancers, beta-dystroglycan is detected but alpha-dystroglycan has been reported to be absent. Here we report that alpha-dystroglycan is correctly expressed and trafficked to the cell membrane but lack its laminin-binding capabilities as a result of the silencing of the glycosyltransferase LARGE in a cohort of highly metastatic epithelial cell lines derived from breast, cervical, and lung cancers. As a result of this glycosylation defect, alpha-dystroglycan presents a lower MW on Western blot analysis. Exogenous expression of LARGE in these cancer cells restores the normal glycosylation and laminin-binding of alpha-dystroglycan leading to enhanced cell adhesion and reduced cell migration in vitro. The relevance of alpha-dystroglycan glycosylation in breast cancer is highlighted by the loss of the functionally active form of the receptor during mammary tumor growth in the mouse model for breast cancer MMTV-Neu(YD). Our findings demonstrate that LARGE repression underlies the defective dystroglycan-mediated cell adhesion that is observed in epithelium-derived cancer cells and uncovers dystroglycan hypo-glycosylation as factor in cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 996.
Thousands of Ebola survivors experience serious medical complications
Authors: Anne Gulland
Journal: BMJ (2015)

The chronic conditions experienced by patients who have recovered from Ebola virus disease have been described as an “emergency within an emergency.”

Daniel Bausch of the World Health Organization’s clinical care team, who was speaking at a telephone press conference in Sierra Leone, said that around half of the 13 000 people who had survived the infection were reporting joint pain. Bausch described the pain as so “serious and debilitating” that it could prevent people going to work and going about their daily lives.

“These are not rare problems: these are common problems,” he said. “It’s an emergency within an emergency,” he added.

About a quarter of …
Immunogenicity of premalignant lesions is the primary cause of general cytotoxic T lymphocyte unresponsiveness
Authors: Gerald Willimsky, Melinda Czéh, Christoph Loddenkemper, Johanna Gellermann, Karin Schmidt, Peter Wust, Harald Stein, Thomas Blankenstein
Journal: The Journal of Experimental Medicine (2008)

Cancer is sporadic in nature, characterized by an initial clonal oncogenic event and usually a long latency. When and how it subverts the immune system is unknown. We show, in a model of sporadic immunogenic cancer, that tumor-specific tolerance closely coincides with the first tumor antigen recognition by B cells. During the subsequent latency period until tumors progress, the mice acquire general cytotoxic T lymphocyte (CTL) unresponsiveness, which is associated with high transforming growth factor (TGF) β1 levels and expansion of immature myeloid cells (iMCs). In mice with large nonimmunogenic tumors, iMCs expand but TGF-β1 serum levels are normal, and unrelated CTL responses are undiminished. We conclude that (a) tolerance to the tumor antigen occurs at the premalignant stage, (b) tumor latency is unlikely caused by CTL control, and (c) a persistent immunogenic tumor antigen causes general CTL unresponsiveness but tumor burden and iMCs per se do not.
Imaging Tumor Acidity: pH-Low Insertion Peptide Probe for Optoacoustic Tomography
Authors: Yana K. Reshetnyak
Journal: Clinical Cancer Research (2015)

Abstract Optoacoustic tomography has been used for the detection of pancreatic ductal adenocarcinoma targeted by pH-low insertion peptide (pHLIP) conjugated to near-infrared fluorescent dye. It was proved that tumor targeting is pH dependent. The approach could have major implication for detection and monitoring of pancreatic and other cancers. Clin Cancer Res; 21(20); 4502–4. ©2015 AACR. See related article by Kimbrough et al., p. 4576
Effect of eating on motility of the pelvic colon in constipation or diarrhoea
Authors: S. L. Waller, J. J. Misiewicz, N. Kiley
Journal: Gut (1972)

Pelvic colonic pressures were recorded before, during, as well as after a meal in patients with non-specific diarrhoea (12) or constipation (14), who were selected according to strict clinical criteria of bowel habit. In the basal state diarrhoeal patients as a group had significantly less colonic activity than constipated patients, but the overlap was considerable. During the meal colonic activity was strikingly increased in diarrhoea, but returned to basal levels immediately after the meal; no such response was observed in constipation. It is suggested that this brief segmental response of the pelvic diarrhoeal colon may be inadequate to prevent entry of faeces into the rectum and the desire to defaecate, following a meal.
Validation of the European Society of Urogenital Radiology Scoring System for Prostate Cancer Diagnosis on Multiparametric Magnetic Resonance Imaging in a Cohort of Repeat Biopsy Patients
Authors: Daniel Portalez, Pierre Mozer, François Cornud, Raphaëlle Renard-Penna, Vincent Misrai, Matthieu Thoulouzan, Bernard Malavaud
Journal: European Urology (2012)
The multiplicity of divergence mechanisms in a single evolving population
Authors: Ram P Maharjan, Thomas Ferenci, Peter R Reeves, Yang Li, Bin Liu, Lei Wang
Journal: Genome biology (2012)

Abstract Background Evolutionary divergence is common within bacterial species and populations, even during a single bacterial infection. We use large-scale genomic and phenotypic analysis to identify the extent of diversification in controlled experimental populations and apply these data to differentiate between several potential mechanisms of evolutionary divergence. Results We defined testable differences between five proposed mechanisms and used experimental evolution studies to follow eight glucose-limited Escherichia coli chemostat populations at two growth rates. Simple phenotypic tests identified 11 phenotype combinations evolving under glucose limitation. Each evolved population exhibited 3 to 5 different combinations of the 11 phenotypic clusters. Genome sequencing of a representative of each phenotypic cluster from each population identified 193 mutations in 48 isolates. Only two of the 48 strains had evolved identically. Convergent paths to the same phenotype occurred, but two pleiotropic mutations were unique to slow-growing bacteria, permitting them greater phenotypic variance. Indeed, greater diversity arose in slower-growing, more stressed cultures. Mutation accumulation, hypermutator presence and fitness mechanisms varied between and within populations, with the evolved fitness considerably more uniform with fast growth cultures. Negative frequency-dependent fitness was shown by a subset of isolates. Conclusions Evolutionary diversity is unlikely to be explained by any one of the available mechanisms. For a large population as used in this study, our results suggest that multiple mechanisms contribute to the mix of phenotypes and evolved fitness types in a diversifying population. Another major conclusion is that the capacity of a population to diversify is a function of growth rate.
Cyclooxygenase-2 Functions as a Downstream Mediator of Lysophosphatidic Acid to Promote Aggressive Behavior in Ovarian Carcinoma Cells
Authors: Jaime Symowicz, Brian P. Adley, Michelle M.M. Woo, Nelly Auersperg, Laurie G. Hudson, M. Sharon Stack
Journal: Cancer Research (2005)

Abstract Elevated levels of the bioactive lipid lysophosphatidic acid (LPA) are detectable in the majority of patients with both early- and late-stage ovarian cancer, suggesting that LPA promotes early events in ovarian carcinoma dissemination. LPA contributes to the development, progression, and metastasis of ovarian cancer in part by inducing the expression of genes that contribute to proliferation, survival, or invasion, including cyclooxgenase-2 (COX-2) and matrix metalloproteinase–2 (MMP-2). We have previously shown that LPA promotes proMMP-2 activation and MMP-2–dependent migration and invasion in ovarian cancer cells. The purpose of the current study was to determine whether the effect of LPA on acquisition of the metastatic phenotype in ovarian cancer cells is mediated via a COX-2–dependent mechanism. Immunohistochemical analysis of 173 ovarian tumors showed strong COX-2 immunoreactivity in 63% of tumor specimens, including 50% of borderline tumors. LPA increased COX-2 protein expression in a time- and concentration-dependent manner in two of three immortalized borderline ovarian epithelial cells as well as in four of six ovarian cancer cell lines. This was accomplished by both activation of the Edg/LPA receptor and LPA-mediated transactivation of the epidermal growth factor receptor, which increased COX-2 expression via the Ras/mitogen-activated protein kinase pathway. COX-2 also played a role in LPA-induced invasion and migration, as treatment with the COX-2 specific inhibitor NS-398 reduced LPA-induced proMMP-2 protein expression and activation and blocked MMP-dependent motility and invasive activity. These data show that COX-2 functions as a downstream mediator of LPA to potentiate aggressive cellular behavior.
The influence of Gelatin/PCL ratio and 3-D construct shape of electrospun membranes on cartilage regeneration
Authors: Rui Zheng, Huichuan Duan, Jixin Xue, Yu Liu, Bei Feng, Shifang Zhao, Yueqian Zhu, Yi Liu, Aijuan He, Wenjie Zhang, Wei Liu, Yilin Cao, Guangdong Zhou
Journal: Biomaterials (2013)
The diagnostic utility of serum IgG4 concentrations in IgG4-related disease
Authors: Mollie N Carruthers, Arezou Khosroshahi, Tamara Augustin, Vikram Deshpande, John H Stone
Journal: Annals of the Rheumatic Diseases (2014)

We evaluated the sensitivity, specificity and positive and negative predictive values of elevated serum IgG4 concentrations for the diagnosis of IgG4-RD.Between 2001 and 2011, 190 unique patients had elevated serum IgG4 measurements. We reviewed electronic medical records to determine the indication for IgG4 measurement and underlying clinical diagnosis. Additionally, we reviewed the records of 190 other randomly selected patients from a pool of 3360 with normal results, to evaluate test characteristics of the IgG4 measurement.Among 380 patients analysed, 72 had either probable or definite IgG4-RD. Sixty-five of the 72 IgG4-RD patients had elevated serum IgG4 concentrations (mean: 405 mg/dL; range 140-2000 mg/dL), for a sensitivity of 90%. Among the 308 subjects without IgG4-RD, 125 had elevated IgG4 (mean: 234 mg/dL; range 135-1180 mg/dL) and 183 had normal IgG4 concentrations, for a specificity of 60%. The negative predictive value of a serum IgG4 assay was 96%, but the positive predictive value only 34%. Analysis of the serum IgG4/total IgG ratio did not improve these test characteristics. Doubling the cutoff for IgG4 improved specificity (91%) but decreased sensitivity to 35%.Multiple non-IgG4-RD conditions are associated with elevated serum IgG4, leading to poor specificity and low positive predictive value for this test. A substantial subset of patients with biopsy-proven IgG4-RD do not have elevated serum IgG4. Neither doubling the cutoff for serum IgG4 nor examining the serum IgG4/IgG ratio improves the overall test characteristics for the diagnosis of IgG4-RD.
ENERGY AND PROTEIN REQUIREMENTS DURING LACTATION
Authors: Kathryn G. Dewey
Journal: Annual Review of Nutrition (1997)

▪ Abstract Additional energy needs for an exclusively breastfeeding woman are approximately 670 kcal/day. If one allows for gradual weight loss, the net increment needed is about 500 kcal/day. There is little evidence of energy-sparing adaptations in basal metabolic rate or dietary-induced thermogenesis during lactation, although physical activity may be reduced during the early postpartum period. In women with adequate fat reserves, moderately negative energy balance is not likely to affect lactation. The recommended increment in protein intake during lactation has been estimated to be about 15 g/day, based on a milk protein concentration of 11 g/liter. However, if one takes into account the protein cost of non-protein nitrogen in human milk, the recommended increment in protein is about 20 g/day. The latter value is consistent with data from nitrogen balance studies in lactating women. Low protein intakes are unlikely to affect milk volume but may alter certain fractions of milk nitrogen.
Hypertension, transmural pressure, and vascular smooth muscle response in rats.
Authors: T R Hansen, D F Bohr
Journal: Circulation Research (1975)

The effect of transmural pressure on the responsiveness of vascular smooth muscle was studied using rats with chronic occlusion of one external iliac artery. The arterial pressure in the occluded leg was reduced to approximately half of that in the contralateral unoccluded leg. Helical strips from the low- and high-pressure femoral arteries of spontaneously hypertensive rats and rats with deoxycorticosterone acetate-induced (DOCA) hypertension were compared with corresponding tissues from normotensive controls. The sensitivity of both low- and high-pressure artery strips from the spontaneously hypertensive rat was greater than that of controls when strontium or lanthanum was used as the agonist. The sensitivity of strips from both low- and high-pressure arteries from the DOCA-hypertensive rat was greater than that of controls when potassium, epinephrine, or calcium was the agonist. There was no difference in sensitivity between strips from the low- and high-pressure arteries in any group of rats. Maximum contractile force (contractility) was reduced in femoral artery strips from both legs of all hypertensive rats. The KCl-induced contraction of vascular smooth muscle from both femoral arteries of either form of hypertensive rat was not as readily depressed by high calcium concentrations as was that from the normotensive rat. Changes in sensitivity and contractility associated with hypertension could not be reversed by lowering blood pressure in one leg of a spontaneously hypertensive rat or prevented by protecting one leg from high pressure prior to the induction of DOCA hypertension. The altered sensitivity and contractility of arterial strips in these models of hypertension are not, then, secondary to the increase in wall stress.
Systematic review of water fluoridation
Authors: M. S McDonagh
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To review the safety and efficacy of fluoridation of drinking water. <b>Design:</b> Search of 25 electronic databases and world wide web. Relevant journals hand searched; further information requested from authors. Inclusion criteria were a predefined hierarchy of evidence and objectives. Study validity was assessed with checklists. Two reviewers independently screened sources, extracted data, and assessed validity. <b>Main outcome measures:</b> Decayed, missing, and filled primary/permanent teeth. Proportion of children without caries. Measure of effect was the difference in change in prevalence of caries from baseline to final examination in fluoridated compared with control areas. For potential adverse effects, all outcomes reported were used. <b>Results:</b> 214 studies were included. The quality of studies was low to moderate. Water fluoridation was associated with an increased proportion of children without caries and a reduction in the number of teeth affected by caries. The range (median) of mean differences in the proportion of children without caries was −5.0% to 64% (14.6%). The range (median) of mean change in decayed, missing, and filled primary/permanent teeth was 0.5 to 4.4 (2.25) teeth. A dose-dependent increase in dental fluorosis was found. At a fluoride level of 1 ppm an estimated 12.5% (95% confidence interval 7.0% to 21.5%) of exposed people would have fluorosis that they would find aesthetically concerning. <b>Conclusions:</b> The evidence of a beneficial reduction in caries should be considered together with the increased prevalence of dental fluorosis. There was no clear evidence of other potential adverse effects.
Randomized, Double-Blind, Dose-Ranging Study of TAK-875, a Novel GPR40 Agonist, in Japanese Patients With Inadequately Controlled Type 2 Diabetes
Authors: Kohei Kaku, Takahiro Araki, Ryoji Yoshinaka
Journal: Diabetes Care (2012)

OBJECTIVE Assessment of the efficacy and safety of TAK-875 (a novel GPR40 agonist) in Japanese patients with type 2 diabetes inadequately controlled by diet/exercise. RESEARCH DESIGN AND METHODS This was a phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled, 12-week dose-ranging evaluation of TAK-875 (6.25–200 mg once daily) with the primary end point of change in A1C at week 12. A nonblinded group received 1 mg glimepiride once daily as an active control. RESULTS A total of 396 patients were randomized to receive TAK-875 (n = 299), placebo (n = 48), or glimepiride (n = 49). The least square mean changes in A1C at week 12 from baseline were as follows: 0.09% in the placebo group; −0.54, −0.67, −0.88, −1.27, −1.29, and −1.40% in the 6.25-, 12.5-, 25-, 50-, 100-, and 200-mg TAK-875 groups, respectively; and −1.32% in the 1-mg glimepiride group. All TAK-875 groups had statistically significant reductions in A1C compared with placebo (P &amp;lt; 0.0001), and those receiving ≥50 mg TAK-875 achieved reductions in A1C equivalent to those with glimepiride. Results for other glycemic parameters, including improvements during a meal tolerance test, mirrored these positive findings with TAK-875. There were no significant differences in incidence of adverse events among the groups and no dose-dependent changes in tolerability. Hypoglycemic episodes were reported in 0.7% of patients in the TAK-875 groups and in 4.1% of the glimepiride group. CONCLUSIONS TAK-875 produced clinically and statistically significant improvements in glycemic control in patients with type 2 diabetes inadequately controlled by diet and exercise, and it was well tolerated with a lower propensity to cause hypoglycemia.
Platelet function defects in chronic alcoholism.
Authors: D P Mikhailidis, W J Jenkins, M A Barradas, J Y Jeremy, P Dandona
Journal: BMJ (1986)

Platelet function in alcoholic patients was assessed on admission and during abstinence in hospital.On admission platelets from these patients were significantly less responsive (percentage aggregation and thromboxane A2 release) to conventional in vitro aggregating agents (adrenaline, adenosine diphosphate, and collagen) than platelets from healthy, moderate drinkers.Initially, platelet counts in platelet rich plasma tended to be low and the Simplate H bleeding times frequently prolonged.Platelet aggre- gation and thromboxane A2 release, however, were inhibited even in patients with normal platelet counts on admission.Platelet aggregation and thromboxane A2 release returned to normal or became hyper-responsive during two to three weeks of abstinence.Platelet counts rose during this period, the largest responses occurring in those patients with the lowest counts on admission.Bleeding times reverted to normal during abstinence and correlated significantly with changes in platelet aggregation, thromboxane A2 release, and platelet count and with the esti- mated ethanol consumption during the week before admission.Chronic, heavy alcohol ingestion evidently exerts an inhibitory effect on platelet function even in the absence of alcohol in the blood, and this phenomenon is reversible on abstaining.The impaired platelet function, together with the reduced platelet count, may contribute to the bleeding diathesis associated with chronic alcoholism and to the increased incidence and recur- rence of gastrointestinal haemorrhage associated with excessive alcohol intake.
Prognostic Factors in Older AML Patients Receiving Intensive and Non-Intensive Therapy: Analysis of the UK AML11 and AML14 Trials.
Authors: Keith Wheatley, Cassey L. Brookes, Robert K. Hills, Anthony H. Goldstone, Donald W. Milligan, Archie G. Prentice, Anthony V. Moorman, Alan K. Burnett
Journal: Blood (2005)
Palliative treatment of obstructive jaundice by transpapillary introduction of large bore bile duct endoprosthesis.
Authors: K Huibregtse, G N Tytgat
Journal: Gut (1982)

The endoscopic techniques for introducing a large calibre (3.2 mm) biliary endoprosthesis to relieve jaundice are described. In 45 patients such an endoprosthesis was successfully introduced. The median survival time in 18 patients was 41 days (range three to 187). Twenty-six patients are still alive after a median of 28 days (range seven to 244). One patient had a surgical bypass after 24 days. Short-term complications were cholangitis and fever in 11 patients. Late complications were recurrent jaundice in four, upward migration of the endoprosthesis in two, and clogging of the endoprosthesis in one patient. The risk of cholangitis, which used to be a major problem with transpapillary introduced prostheses of smaller calibre, seems definitely diminished by using one with a large calibre.