tbuckley/cabot-search huggingface dataset:
TP53 Alterations Determine Clinical Subgroups and Survival of Patients With Choroid Plexus Tumors
Authors: Uri Tabori, Adam Shlien, Berivan Baskin, Sarah Levitt, Peter Ray, Noa Alon, Cynthia Hawkins, Eric Bouffet, Malgorzata Pienkowska, Lucie Lafay-Cousin, Alexa Gozali, Nataliya Zhukova, Lisa Shane, Ignacio Gonzalez, Jonathan Finlay, David Malkin
Journal: Journal of Clinical Oncology (2010)

Purpose Choroid plexus carcinomas are pediatric tumors with poor survival rates and a strong, but poorly understood, association with Li-Fraumeni syndrome (LFS). Currently, with lack of biologic predictors, most children are treated with aggressive chemoradiation protocols. Patients and Methods We established a multi-institutional tissue and clinical database, which enabled the analysis of specific alterations of the TP53 tumor suppressor and its modifiers in choroid plexus tumors (CPTs). We conducted high-resolution copy-number analysis to correlate these genetic parameters with family history and outcome. Results We studied 64 patients with CPTs. All individuals with germline TP53 mutations fulfilled LFS criteria, whereas all patients not meeting these criteria harbored wild-type TP53 (P &lt; .001). TP53 mutations were found in 50% of choroid plexus carcinomas (CPCs). Additionally, two sequence variants known to confer TP53 dysfunction, TP53 codon72 and MDM2 SNP309, coexisted in the majority of TP53 wild-type CPCs (92%) and not in TP53 mutated CPC (P = .04), which suggests a complementary mechanism of TP53 dysfunction in the absence of a TP53 mutation. High-resolution single nucleotide polymorphism (SNP) array analysis revealed extremely high total structural variation (TSV) in TP53-mutated CPC tumor genomes compared with TP53 wild-type tumors and choroid plexus papillomas (CPPs; P = .006 and .004, respectively). Moreover, high TSV was associated with significant risk of progression (P &lt; .001). Five-year survival rates for patients with TP53-immunopositive and -immunonegative CPCs were 0% and 82 (± 9%), respectively (P &lt; .001). Furthermore, 14 of 16 patients with TP53 wild-type CPCs are alive without having received radiation therapy. Conclusion Patients with CPC who have low tumor TSV and absence of TP53 dysfunction have a favorable prognosis and can be successfully treated without radiation therapy.
Distribution of Blood Flow in the Digestive Tract of the Rat
Authors: SHELDON H. STEINER, GUSTAVE C. E. MUELLER
Journal: Circulation Research (1961)

The rubidium fractionation technique has been used to make comparative measurements of functional perfusion rates in the gastrointestinal tract of relatively undisturbed but fasted and anesthetized rats. The duodenum has the highest functional perfusion rate per unit mass of the entire digestive tract; the stomach is less than half as well perfused. The remainder of the tract to the rectosigmoid shows a progressive decrease. The small intestine shows a progressive increase in functional flow per unit mass from the pylorus to the ligament of Treitz and then a progressive decrease, most marked in the jejunum to the ileocecal valve. Blood flow values to other structures of the gastrointestinal tract are also given.
Role of Chromium in Human Health and in Diabetes
Authors: William T. Cefalu, Frank B. Hu
Journal: Diabetes Care (2004)

Despite widespread use by patients with diabetes and anecdotal reports in the past regarding its efficacy, until recently, data in humans concerning chromium’s effects on insulin action in vivo or on cellular aspects of insulin action were scarce. Consequently, significant controversy still exists regarding the effect of chromium supplementation on parameters assessing human health. Furthermore, elucidating the cellular and molecular mechanisms by which chromium supplements affect carbohydrate metabolism in vivo is necessary before specific recommendations can be made regarding its routine use in the management of diabetes. This review focuses on providing current information about this trace mineral’s specific mechanisms of action and clinical trials in patients with diabetes.

Chromium, one of the most common elements in the earth’s crust and seawater, exists in our environment in several oxidation states, principally as metallic (Cr), trivalent (+3), and hexavalent (+6) chromium. The latter is largely synthesized by the oxidation of the more common and naturally occurring trivalent chromium and is highly toxic. Trivalent chromium, found in most foods and nutrient supplements, is an essential nutrient with very low toxicity.

The interest in chromium as a nutritional enhancement to glucose metabolism can be traced back to the 1950s, when it was suggested that brewer’s yeast contained a glucose tolerance factor (GTF) that prevented diabetes in experimental animals (1). This factor was eventually suggested to be a biologically active form of trivalent chromium that could substantially lower plasma glucose levels in diabetic mice (2). Interest regarding chromium administration in patients with diabetes was kindled by the observation in the 1970s that it truly was an essential nutrient required for normal carbohydrate metabolism. A patient receiving total parenteral nutrition (TPN) developed severe signs of diabetes, including weight loss and hyperglycemia that was refractory to increasing insulin dosing (3). Based on previous animal studies …
Premetazoan genome evolution and the regulation of cell differentiation in the choanoflagellate Salpingoeca rosetta
Authors: Stephen R Fairclough, Zehua Chen, Eric Kramer, Qiandong Zeng, Sarah Young, Hugh M Robertson, Emina Begovic, Daniel J Richter, Carsten Russ, M Jody Westbrook, Gerard Manning, B Franz Lang, Brian Haas, Chad Nusbaum, Nicole King
Journal: Genome biology (2013)

Metazoan multicellularity is rooted in mechanisms of cell adhesion, signaling, and differentiation that first evolved in the progenitors of metazoans. To reconstruct the genome composition of metazoan ancestors, we sequenced the genome and transcriptome of the choanoflagellate Salpingoeca rosetta, a close relative of metazoans that forms rosette-shaped colonies of cells.A comparison of the 55 Mb S. rosetta genome with genomes from diverse opisthokonts suggests that the origin of metazoans was preceded by a period of dynamic gene gain and loss. The S. rosetta genome encodes homologs of cell adhesion, neuropeptide, and glycosphingolipid metabolism genes previously found only in metazoans and expands the repertoire of genes inferred to have been present in the progenitors of metazoans and choanoflagellates. Transcriptome analysis revealed that all four S. rosetta septins are upregulated in colonies relative to single cells, suggesting that these conserved cytokinesis proteins may regulate incomplete cytokinesis during colony development. Furthermore, genes shared exclusively by metazoans and choanoflagellates were disproportionately upregulated in colonies and the single cells from which they develop.The S. rosetta genome sequence refines the catalog of metazoan-specific genes while also extending the evolutionary history of certain gene families that are central to metazoan biology. Transcriptome data suggest that conserved cytokinesis genes, including septins, may contribute to S. rosetta colony formation and indicate that the initiation of colony development may preferentially draw upon genes shared with metazoans, while later stages of colony maturation are likely regulated by genes unique to S. rosetta.
Pattern of drug resistance in TB patients treated at DR TB unit in tertiary care public sector hospital in Karachi Pakistan
Authors: Saifullah Baig, Shahina Qayyum, Nausheen Saifullal, Nadeem Ahmed, Iftekhar Ahmed
Journal: European Respiratory Journal (2013)

Introduction : Pakistan ranks 4 th  globally in MDR TB. Empirical 2 nd  line treatment is started on the bases of Rifampacin resistance diagnosed by GeneXpert This regimen consists of 04 second line drugs including an injectable and fluoroquinolones(FQ).   Aims and objective : this study was done to observe the drug resistance pattern in DR TB patients in order to rationalize the present empirical treatment regimen.   Method : Patients are registered. DST to first and second line drugs is sent before start of DR TB treatment. Results were recorded in DR TB 01 form and analyzed by Microsoft excel and SPSS 16.   Results : 795 DR-TB patients were registered in years 2010- 2012. males and female were 406(51.1%) and 389(48.9%). Mean age was 32.17 SD± 13.46. Treatment failure of CAT1 (40, 19.6%) and CAT2 (156, 30.8%).total 50.4%. After default, first line Relapse and others were 5.0,% 11.6% and 31.4%.Only 11(1.4%) were new cases.  Resistance to four 1 st  line drugs was present in 80.6% (641) and to.01,02, 04 and 05 first line drugs in 8(1%),25(3.1%) ,79(9.9) and 39(4.9%).  Resistance to 2 nd  line drug was present in 51%. FQ resistance was in 39.6%. To Amikacin, capreomycin, Ethionamide, kanamycin, Ethionamide + kanamycin and FQ+ ethionamide was seen in 5,12, 43,.20.11 and 7 percent respectively. FQ resistance was 40.8% in others. It was 36.4% in new cases.   Conclusion:  Prevalence resistance to 2 nd  line drugs especially FQ is high in our setting therefore FQ cannot be counted as effective drug. After stopping injectable we are left with only 03 effective drugs. Therefore in our setting empirical treatment should be started with 05 second line drug.
Protein & carbohydrate supplementation does not influence functional or molecular responses to resistance training in sarcopenic patients with COPD compared to non-sarcopenic patients
Authors: Linzy Houchen-Wolloff, Manoj Menon, Despina Constantin, Paul Greenhaff, Sally Singh, Michael Steiner
Journal: European Respiratory Journal (2014)

Introduction: We have already shown that 8weeks(wks) of quadriceps resistance training(RT) & post-exercise protein & carbohydrate supplementation(PCS) did not augment functional gains or molecular responses, from those seen with RT alone in COPD patients(Constantin et al.2013). Here we aimed to determine whether the responses to RT & PCS were different in sarcopenic(Sc) & non-sarcopenic(NSc) COPD patients.

Methods: This was a subgroup analysis involving 32subjects; 14were Sc, defined as having a height normalised appendicular lean mass(total lean mass of arms&legs/height2:kg/m2) of<7.23 men &<5.67 women(Cruz-Jentoft et al.2010).

RT consisted of 5x30 maximal isokinetic knee extensions at 180°/sec, 3x/wk for 8wks(Cybex). Subjects ingested a PCS after each RT session.

Isometric strength, isokinetic peak torque at 60°/sec(Cybex), thigh lean mass(DEXA) & work done during an incremental cardiopulmonary exercise test(CPET) were measured at baseline & after 4&8 wks of RT. Target proteins known to regulate muscle protein synthesis & breakdown were determined in quadriceps muscle samples taken at rest, at baseline & after 24 hours,4&8wks of RT.

Results: At 8wks, thigh lean mass(2.4 Vs 5.3%), isometric strength(15.1 Vs 20.4%), isokinetic peak torque(19.3 Vs 24.9%) & CPET work(21.8 Vs 18.1%) increased in the Sc and NSc groups respectively, there were no between group differences in the magnitude of response. Also, no between group differences were observed in the molecular responses to RT & PCS.

Conclusions: PCS did not influence functional or molecular responses to RT in Sc COPD patients when compared to NSc patients.
Where There Is No Health Research: What Can Be Done to Fill the Global Gaps in Health Research?
Authors: Martin McKee, David Stuckler, Sanjay Basu
Journal: PLoS Medicine (2012)

As part of a cluster of articles leading up to the 2012 World Health Report and critically reflecting on the theme of "no health without research," Martin McKee and colleagues examine the question of what to do to build capacity in the many countries around the world where health research is virtually non-existent.
HMGA1 Controls Transcription of Insulin Receptor to Regulate Cyclin D1 Translation in Pancreatic Cancer Cells
Authors: Sebastian Kolb, Ralph Fritsch, Dieter Saur, Maximilian Reichert, Roland M. Schmid, Günter Schneider
Journal: Cancer Research (2007)

Abstract The HMGA1 proteins act as architectural transcription factors and are involved in the regulation of genes important in the process of carcinogenesis. Although HMGA1 proteins are overexpressed in most types of cancer, signaling circuits regulated by HMGA1 are not clarified in detail. In this study, we show that HMGA1 proteins promote proliferation of pancreatic cancer cells by accelerating G1 phase progression. Transfection of HMGA1-specific small interfering RNA (siRNA) activates the RB-dependent G1-phase checkpoint due to the impaired expression of cyclin D1. Down-regulation of cyclin D1 after the HMGA1 knockdown is due to translational control and involves the repressor of the eukaryotic translation initiation factor 4E (eIF4E) 4E-BP1. We show that 4E-BP1 and cyclin D1 act downstream of the insulin receptor (IR) in pancreatic cancer cells. At the molecular level transcription of the IR is controlled by a CAAT/enhancer binding protein β (C/EBPβ)/HMGA1 complex. Together, this work defines a novel pathway regulated by HMGA1, which contributes to the proliferation of pancreatic cancer cells. [Cancer Res 2007;67(10):1–8]
Effect of Dialysate Sodium Concentration on Interdialytic Increase of Potassium
Authors: LUCA DE NICOLA, VINCENZO BELLIZZI, ROBERTO MINUTOLO, MARIO CIOFFI, PAOLO GIANNATTASIO, VINCENZO TERRACCIANO, CARMELA IODICE, FRANCESCO UCCELLO, BRUNO MEMOLI, BIAGIO RAFFAELE DI IORIO, GIUSEPPE CONTE
Journal: Journal of the American Society of Nephrology (2000)

To evaluate the role of plasma tonicity in the postdialysis increment of plasma potassium (p[K(+)]), the outcome of two hemodiafiltration treatments that differed only in the Na(+) level in dialysate (Na(D))-143 mmol/L (high dialysate sodium concentration [H-Na(D)]) and 138 mmol/L (low dialysate sodium concentration [L-Na(D)])-were compared in the same group of uremic patients from the end of treatment (T0) to the subsequent 30 to 120 min and up to 68 h. Kt/V and intradialytic K(+) removal were comparable. At T0, plasma [Na(+)] was 145+/-1 and 137+/-1 mmol/L after H-Na(D) and L-Na(D), respectively (P<0.001). The difference in plasma tonicity persisted from T0 to T68 h. At T120, p[K(+)] was increased from the T0 value of 3.7+/-0.2 to 4.7+/-0.2 mmol/L (P<0.05) after H-Na(D), whereas it was unchanged after L-Na(D). The change of p[K(+)] was still different after 68 h (+76+/-10% and +50+/-7% in H-Na(D) and L-Na(D), respectively; P<0.05). Of note, in the first 2 h after the end of treatment, bioimpedance analysis revealed only in H-Na(D) a significant 11+/-3% decrement of phase angle that is compatible with a decrease of intracellular fluid volume at the expense of the extracellular volume. Similarly, within the same time frame, in H-Na(D), a significant reduction of mean corpuscular volume of red cells, associated with a 2 +/-1% decrease of the intracellular [K(+)], was observed. In contrast, mean corpuscular volume of red cells did not change and erythrocyte [K(+)] increased by 6+/-1% after L-Na(D) (P<0.005 versus H-Na(D)). Thus, hypertonicity significantly contributes to the increase of p[K(+)] throughout the whole interdialytic period by determining intracellular fluid volume/extracellular volume redistribution of water and K(+).
Gene Expression Signatures Predictive of Early Response and Outcome in High-Risk Childhood Acute Lymphoblastic Leukemia: A Children's Oncology Group Study
Authors: Deepa Bhojwani, Huining Kang, Renee X. Menezes, Wenjian Yang, Harland Sather, Naomi P. Moskowitz, Dong-Joon Min, Jeffrey W. Potter, Richard Harvey, Stephen P. Hunger, Nita Seibel, Elizabeth A. Raetz, Rob Pieters, Martin A. Horstmann, Mary V. Relling, Monique L. den Boer, Cheryl L. Willman, William L. Carroll
Journal: Journal of Clinical Oncology (2008)

To identify children with acute lymphoblastic leukemia (ALL) at initial diagnosis who are at risk for inferior response to therapy by using molecular signatures.Gene expression profiles were generated from bone marrow blasts at initial diagnosis from a cohort of 99 children with National Cancer Institute-defined high-risk ALL who were treated uniformly on the Children's Oncology Group (COG) 1961 study. For prediction of early response, genes that correlated to marrow status on day 7 were identified on a training set and were validated on a test set. An additional signature was correlated with long-term outcome, and the predictive models were validated on three large, independent patient cohorts. Results We identified a 24-probe set signature that was highly predictive of day 7 marrow status on the test set (P = .0061). Pathways were identified that may play a role in early blast regression. We have also identified a 47-probe set signature (which represents 41 unique genes) that was predictive of long-term outcome in our data set as well as three large independent data sets of patients with childhood ALL who were treated on different protocols. However, we did not find sufficient evidence for the added significance of these genes and the derived predictive models when other known prognostic features, such as age, WBC, and karyotype, were included in a multivariate analysis.Genes and pathways that play a role in early blast regression may identify patients who may be at risk for inferior responses to treatment. A fully validated predictive gene expression signature was defined for high-risk ALL that provided insight into the biologic mechanisms of treatment failure.
A phase I trial of liposomal doxorubicin, paclitaxel and valspodar (PSC-833), an inhibitor of multidrug resistance
Authors: R. Advani, B.L. Lum, G.A. Fisher, J. Halsey, D.L. Chin, C.D. Jacobs, B.I. Sikic
Journal: Annals of Oncology (2005)
Effect of sucralfate on gastric mucosal blood flow in rats.
Authors: B W Chen, W M Hiu, S K Lam, C H Cho, M M Ng, C T Luk
Journal: Gut (1989)

Sucralfate possesses site protective and cytoprotective actions and heals ulcers effectively, but its effect on gastric mucosal blood flow is unknown. Using an ex vivo gastric chamber preparation, we studied the effect of sucralfate on gastric mucosal blood flow in rats by laser doppler flowmetry. Under both fasting and fed states, measurements of gastric mucosal blood flow and damage were made in rats after topical application of absolute ethanol alone or after pretreatment with sucralfate. Gastric mucosal damage was assessed by measuring the total area of haemorrhagic mucosal lesions. Ethanol induced gastric mucosal lesions were significantly less with sucralfate pretreatment than without (p less than 0.008). Mucosal blood flow significantly fell after ethanol application (p less than 0.001). The fall was significantly less in fed than in fasted rats (p less than 0.05), and after pretreatment with sucralfate 100 mg or 200 mg than without in both fasted (p less than 0.0008 and 0.00001, respectively) and fed (p less than 0.002 and 0.001, respectively) rats. Graded doses of sucralfate (25-400 mg) resulted in an increase in gastric mucosal blood flow in a dose dependent manner (r = 0.731, p less than 0.001). In conclusion that sucralfate increases gastric mucosal blood flow in rats and lessens the fall in blood flow in rats treated with ethanol, and this action may contribute to its protection against the vascular damage of mucosa by ethanol.
Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial
Authors: David Preiss, Suzanne M Lloyd, Ian Ford, John J McMurray, Rury R Holman, Paul Welsh, Miles Fisher, Chris J Packard, Naveed Sattar
Journal: The Lancet Diabetes & Endocrinology (2013)

BackgroundMetformin reduces cardiovascular risk in patients with type 2 diabetes seemingly independent of lowering blood glucose concentration. We assessed the cardiovascular effects of metformin in individuals without type 2 diabetes.MethodsWe did a single-centre, double-blind, placebo-controlled trial at the Glasgow Clinical Research Facility (Glasgow, UK). We enrolled patients taking statins who did not have type 2 diabetes but who did have coronary heart disease and large waist circumferences. Participants were randomly assigned (1:1) by computer to either metformin (850 mg twice daily) or matching placebo in block sizes of four. Patients, investigators, trial staff, and statisticians were masked to treatment allocation. The primary endpoint was progression of mean distal carotid intima-media thickness (cIMT) over 18 months in the modified intention-to-treat population. Secondary endpoints were changes in carotid plaque score (in six regions), measures of glycaemia (HbA1c, fasting glucose, and insulin concentrations, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and concentrations of lipids, high sensitivity C-reactive protein, and tissue plasminogen activator. The trial was registered at ClinicalTrials.gov, number NCT00723307.FindingsWe screened 356 patients, of whom we enrolled 173 (86 in the metformin group, 87 in the placebo group). Average age was 63 years. At baseline, mean cIMT was 0·717 mm (SD 0·129) and mean carotid plaque score was 2·43 (SD 1·55). cIMT progression did not differ significantly between groups (slope difference 0·007 mm per year, 95% CI −0·006 to 0·020; p=0·29). Change of carotid plaque score did not differ significantly between groups (0·01 per year, 95% CI −0·23 to 0·26; p=0·92). Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose. 138 adverse events occurred in 64 patients in the metformin group versus 120 in 60 patients in the placebo group. Diarrhoea and nausea or vomiting were more common in the metformin group than in the placebo group (28 vs 5).InterpretationMetformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk, taking statins. Further evidence is needed before metformin can be recommended for cardiovascular benefit in this population.FundingChief Scientist Office (Scotland).
AID TO PEOPLE WITH DISABILITIES: Medicaid's Growing Role
Authors: Alicia L. Carbaugh, Risa Elias, Diane Rowland
Journal: Annual Review of Public Health (2005)

Medicaid is the nation's largest health care program providing assistance with health and long-term care services for millions of low-income Americans, including people with chronic illness and severe disabilities. This article traces the evolution of Medicaid's now-substantial role for people with disabilities; assesses Medicaid's contributions over the last four decades to improving health insurance coverage, access to care, and the delivery of care; and examines the program's future challenges as a source of assistance to children and adults with disabilities. Medicaid has shown that it is an important source of health insurance coverage for this population, people for whom private coverage is often unavailable or unaffordable, substantially expanding coverage and helping to reduce the disparities in access to care between the low-income population and the privately insured.
Rheumatoid synovial cells in culture produce a growth inhibitor.
Authors: C A Smith
Journal: Annals of the Rheumatic Diseases (1978)

Cultures of synovial cells obtained at surgery from patients with rheumatoid arthritis produced a protein which inhibits the mitosis of normal rabbit and human synovial cells, and of human lung fibroblasts. This mitotic inhibitory effect can be transferred to rabbit synovial cells by intra-articular injection of the animals with rheumatoid synovial cell cultures.