tbuckley/cabot-search huggingface dataset:
Genome-Wide Analysis of Wilms’ Tumor 1-Controlled Gene Expression in Podocytes Reveals Key Regulatory Mechanisms
Authors: Martin Kann, Sandrine Ettou, Youngsook L. Jung, Maximilian O. Lenz, Mary E. Taglienti, Peter J. Park, Bernhard Schermer, Thomas Benzing, Jordan A. Kreidberg
Journal: Journal of the American Society of Nephrology (2015)

The transcription factor Wilms' tumor suppressor 1 (WT1) is key to podocyte development and viability; however, WT1 transcriptional networks in podocytes remain elusive. We provide a comprehensive analysis of the genome-wide WT1 transcriptional network in podocytes in vivo using chromatin immunoprecipitation followed by sequencing (ChIPseq) and RNA sequencing techniques. Our data show a specific role for WT1 in regulating the podocyte-specific transcriptome through binding to both promoters and enhancers of target genes. Furthermore, we inferred a podocyte transcription factor network consisting of WT1, LMX1B, TCF21, Fox-class and TEAD family transcription factors, and MAFB that uses tissue-specific enhancers to control podocyte gene expression. In addition to previously described WT1-dependent target genes, ChIPseq identified novel WT1-dependent signaling systems. These targets included components of the Hippo signaling system, underscoring the power of genome-wide transcriptional-network analyses. Together, our data elucidate a comprehensive gene regulatory network in podocytes suggesting that WT1 gene regulatory function and podocyte cell-type specification can best be understood in the context of transcription factor-regulatory element network interplay.
Political parties promise more north of the border
Authors: B. Christie
Journal: BMJ (2001)

The arrival of devolution in Scotland means that the coming general election is quite different from anything that has gone before. Health is now run by the Scottish parliament, which means that candidates standing for election will have no direct responsibility for the service.

Moreover, where the manifestos of the main political parties do touch on health, they make different promises in Scotland from those that they make elsewhere. Nowhere is the difference clearer than in the issue of care for elderly people. In Scotland all the main political parties are committed to providing free personal care for the elderly (as recommended by the Sutherland report), but only the Liberal Democrats …
Burden of Hospitalizations Primarily Due to Uncontrolled Diabetes
Authors: Sunny Kim
Journal: Diabetes Care (2007)

This study describes the burden of potentially preventable hospitalizations primarily due to uncontrolled diabetes. Uncontrolled diabetes, if not managed properly, often leads to biochemical imbalances that can cause acute life-threatening events and hospitalizations. Since diabetes management relies heavily on ambulatory care, hospitalizations with uncontrolled diabetes largely reflect the quality of the primary health care provided outside the hospital setting. Therefore, the Agency for Healthcare Research and Quality (AHRQ) selected uncontrolled diabetes as a prevention quality indicator (PQI) where timely and appropriate ambulatory care would have prevented a hospitalization (1). To improve primary health care, it is essential to track an outcome of current status of prevention quality indicators. However, the extent of potentially preventable hospitalizations associated with uncontrolled diabetes and its economic burden in the U.S. remains under-investigated.

A primary diagnosis indicative of uncontrolled diabetes was analyzed using two nationally representative samples of inpatients records. First, to estimate the number of potentially preventable hospitalizations, the National Hospital Discharge Survey (NHDS) was analyzed. The NHDS-2004, the latest annual survey available (2), acquired a probabilistic sample of 370,785 inpatient records from a national sample of ∼500 hospitals. Overall, the hospital response rate was 92% in 2004 (3). Details concerning sampling procedures are published elsewhere (4). Briefly, the NHDS, conducted annually since 1965, is …
Lamivudine/interferon combination therapy in anti-HBe positive chronic hepatitis B patients: a controlled pilot study
Authors: Teresa Santantonio, Grazia Anna Niro, Emanuele Sinisi, Gioacchino Leandro, Maria Insalata, Angela Guastadisegni, Domenico Facciorusso, Eleonora Gravinese, Angelo Andriulli, Giuseppe Pastore
Journal: Journal of Hepatology (2002)
Overexpression of AIB1 negatively affects survival of surgically resected non-small-cell lung cancer patients
Authors: L.-R. He, H.-Y. Zhao, B.-K. Li, L.-J. Zhang, M.-Z. Liu, H.-F. Kung, X.-Y. Guan, X.-W. Bian, Y.-X. Zeng, D. Xie
Journal: Annals of Oncology (2010)
Sleep apnoea severity independently predicts glycaemic health in nondiabetic subjects: the ESADA study
Authors: B. D. Kent, L. Grote, M. R. Bonsignore, T. Saaresranta, J. Verbraecken, P. Levy, P. Sliwinski, R. Tkacova, J.-A. Kvamme, I. Fietze, J. Hedner, W. T. McNicholas
Journal: European Respiratory Journal (2014)

Obstructive sleep apnoea (OSA) is associated with increased risk of dysglycaemia but the intimate link of these conditions with obesity makes discerning an independent relationship between them challenging. Glycosylated haemoglobin (HbA1c) levels predict adverse cardiovascular outcomes in nondiabetics but there is a lack of population-level data exploring the relationship of HbA1c with OSA. A cross-sectional analysis of 5294 participants in the multinational European Sleep Apnoea Cohort (European Sleep Apnoea Database) study was performed, assessing the relationship of OSA severity with HbA1c levels in nondiabetic subjects, with adjustment for confounding factors. HbA1c levels correlated significantly with OSA severity in univariate analysis. Following adjustment for confounding factors, apnoea–hypopnoea index (AHI) (standardised β 0.158; p&lt;0.001), along with nocturnal hypoxaemia, predicted HbA1c. Adjusted mean HbA1c levels were lower in the lowest AHI quartile (5.24%, 95% CI 5.21–5.27%) than in the second (5.37%, 95% CI 5.34–5.40%), third (5.44%, 95% CI 5.41–5.47%) or highest (5.50%, 95% CI 5.46–5.53%) quartiles. Subjects in the higher quartiles had significantly greater adjusted odds ratios of HbA1c level ≥6.0% than those in the first quartile. In stratified analyses, OSA severity predicted glycaemic health irrespective of sleep study modality, sex, obesity or daytime sleepiness. OSA severity independently predicts glycaemic health in nondiabetic subjects. Further studies should assess the impact of OSA treatment on glycaemic health and elucidate underlying mechanisms.
TNF inhibitors in the treatment of rheumatoid arthritis in clinical practice: costs and outcomes in a follow up study of patients with RA treated with etanercept or infliximab in southern Sweden
Authors: G Kobelt
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objectives:</b> To evaluate costs, benefits, and cost effectiveness of tumour necrosis factor inhibitor treatment over one year in routine clinical practice. <b>Materials and methods:</b> At four rheumatology units in southern Sweden treatment of 160 consecutive patients with RA was started with either etanercept or infliximab. The economic analysis was based on 116 patients with complete data who received treatment for at least one year. Details on drug treatment, functional capacity, disease activity, and laboratory values were available during the entire treatment. Information on resource use and QoL was collected at baseline and throughout the first year. The cost effectiveness analysis was based on changes in outcome and costs compared with the year before treatment. Cost per quality adjusted life year (QALY) gained was calculated for the entire sample and for patients with different levels of functional disability. <b>Results:</b> During the first treatment year direct costs were reduced by 40%, but indirect costs did not change substantially. Patients' QoL improved on treatment—utility increased from an average of 0.28 to 0.65. Assuming that improvement occurred after three months' treatment, the cost per QALY gained is estimated as €43 500. If it occurs after six weeks, in parallel with clinical measures, the cost per QALY is €36 900. Sensitivity analysis, including all 160 patients, gave an estimated cost per QALY of €53 600. The cost per QALY increases for patient groups with less severe disease. <b>Conclusion:</b> For this patient group, cost effectiveness ratios are within the generally accepted threshold of €50 000, but need to be confirmed with larger samples.
The phospholipid requirement of tissue factor in blood coagulation
Authors: Yale Nemerson
Journal: Journal of Clinical Investigation (1968)

Using a coagulation assay specific for tissue factor, we found that removal of 95% of the tissue factor-phospholipid resulted in a loss of 98% of its biological activity. The activity could be restored, with yields in excess of 100% by combining the extracted tissue factor with either mixed brain phospholipids or highly purified phospholipids. Phosphatidylethanolamine was the most active, followed by phosphatidylcholine. Phosphatidylserine, phosphatidylinositol, and sphingomyelin had little or no activity. In addition, a requirement for unsaturation and the presence of two fatty acids was demonstrated. The activity of phosphatidylcholine was also dependent on the presence of the base. Furthermore, it was shown that activity was not a function of binding of phospholipids to tissue factor, as both active and inactive lipids were equally bound.
The role of adenosine in prolonged vasodilation following flow-restricted exercise of canine skeletal muscle.
Authors: F L Belloni, R D Phair, H V Sparks
Journal: Circulation Research (1979)

A period of prolonged vasodilation follows flow-restricted exercise of skeletal muscle. We tested the hypothesis that adenosine participates in mediating this vascular response. Vascularly isolated, anterior calf muscles of anesthetized dogs were stimulated to contract at a rate of 4 twitches/sec. Blood flow was held constant at 12.5 +/- 1.3 ml/min per 100 g which was about 14% of the expected free flow for this exercise level. Skeletal muscle tissue adenosine was measured with the an enzymatic, spectophotometric assay of trichloroacetic acid extracts of congruent to 50 mg biopsy samples. Tissue adenosine rose from 2.30 +/- 0.90 nmol/g in resting muscle to 22.5 +/- 5.8 nmol/g by the end of the 22-minute exercise. Following exercise, tissue adenosine fell toward its baseline value with a time course very similar to the early portion of the return of skeletal muscle vascular resistance to its control level. Thus, skeletal muscle adenosine content (1) increases to a sufficient magnitude and (2) falls with an appropriate time course to be at least partly responsible for the early portion of prolonged vasodilation seen after flow-restricted exercise of skeletal muscle.
Gastric secretion and basal gastrin concentration in bilharzial hepatic fibrosis.
Authors: P B Boulos, E T Okosdonossian, H A Elmunshid, S H Elmasri, M A Hassan, M Hobsley
Journal: Gut (1978)

Gastric secretion and fasting plasma gastrin levels were investigated in 26 patients with bilharzial hepatic fibrosis and 26 controls. The groups did not differ in their basal secretion. When stimulated by intravenous infusion of histamine the maximal acid output in patients with bilharzial hepatic fibrosis was significantly less than in the control group. This was unlikely to be a result of neutralisation by reflux of alkaline duodenal contents as the volumes of reflux were not different from control subjects, but was compatible with a true reduction in gastric secretion as assessed by two-component hypothesis. Neither the lowered gastric acidity nor the liver damage in patients with bilharzial hepatic fibrosis correlated with circulating gastrin. The fasting levels of plasma gastrin in these patients were not different from controls. As in other liver diseases the cause of diminished gastric secretion remains unclear.
Sézary syndrome in a patient receiving infliximab for ankylosing spondylitis
Authors: J.N. Dauendorffer, J. Rivet, A. Allard, H. Bachelez
Journal: British Journal of Dermatology (2007)

Infliximab, a tumour necrosis factor (TNF)‐α antagonist, has shown striking efficacy in the treatment of chronic inflammatory rheumatological diseases such as rheumatoid arthritis and ankylosing spondylitis. However, long‐term follow‐up studies support that treatment with infliximab is associated with an increased risk of non‐Hodgkin lymphoma. So far, few cases of cutaneous lymphoma have been reported in patients receiving TNF‐α‐blocking agents. We report a patient who developed Sézary syndrome 17 months after the onset of infliximab therapy for ankylosing spondylitis. Cutaneous lesions partially remitted following infliximab withdrawal and methotrexate treatment. Although the causal link between infliximab and the emergence of Sézary syndrome is uncertain, the present case raises the need for exhaustive long‐term registries of malignancies, including primary cutaneous lymphomas, in patients receiving TNF‐α‐blocking agents.
Apoptotic Speck Protein-Like, a Highly Homologous Protein to Apoptotic Speck Protein in the Pyrin Domain, Is Silenced by DNA Methylation and Induces Apoptosis in Human Hepatocellular Carcinoma
Authors: Takahiko Kubo, Junji Yamamoto, Yuko Shikauchi, Yasuharu Niwa, Kenichi Matsubara, Hirohide Yoshikawa
Journal: Cancer Research (2004)

Abstract We have identified a novel gene encoding a pyrin domain protein of 89 amino acids that is expressed in various tissues including liver, brain, and spleen. The protein is highly homologous to the pyrin domain of apoptosis-associated speck-like protein (ASC). Therefore, we termed it ASC-like (ASCL). We found that ASCL gene was densely and frequently (80%) methylated in hepatocellular carcinoma (HCC) cell lines. In contrast, normal liver samples did not show any significant methylation. This aberrant methylation correlated well with the suppression of RNA expression. Furthermore, a demethylating agent, 5-aza-2′-deoxycytidine, reactivated the ASCL expression in the methylation-silenced cells, indicating that ASCL is silenced by the associated DNA methylation. ASCL methylation was also found in primary HCC (4 of 17 samples), although the frequency was less than that in cell lines. In addition, we found that ASC was also methylated in primary samples (6 of the 17). Interestingly, either ASCL or ASC methylation was observed in 53% (9 of the 17) of primary HCC samples. Significantly, the restoration of ASCL in the methylation-silenced cells demonstrated growth suppression in colony formation assay. This growth suppression effect of ASCL was supported by apoptotic changes observed in ASCL-transfected cells in which annexin-V binding was positive and caspase-3 was activated. Based on the methylation-silencing and the growth suppression activity, we propose that ASCL plays a significant role in the development of HCC.
Airway remodelling assessed by sputum and high-resolution computed tomography in asthma and COPD
Authors: A.M. Vignola, F. Paganin, L. Capieu, N. Scichilone, M. Bellia, L. Maakel, V. Bellia, P. Godard, J. Bousquet, P. Chanez
Journal: European Respiratory Journal (2004)

It is not known whether sputum elastase, metalloproteinase (MMP)-9 and tissue-inhibitor metalloproteinase (TIMP)-1 are related to structural changes of the airways, as assessed by high-resolution computed tomography (HRCT) scan. The relationships between these markers and the magnitude of structural changes of the airways in asthma and chronic obstructive pulmonary disease (COPD) were assessed. Induced sputum and HRCT scan were performed in 30 asthmatics (14 mild and 16 severe) and in 12 patients with COPD. A greater extent of HRCT scan abnormalities was found in COPD than in severe and mild asthmatics. HRCT scan abnormalities correlated with the degree of airway obstruction in COPD and in severe asthma. HRCT scan abnormalities also correlated with the levels of sputum elastase both in COPD and in severe asthma. HRCT scan abnormalities were associated with sputum MMP-9/TIMP-1 ratio in mild asthma, severe asthma and COPD. In conclusion, this study demonstrates that sputum elastase and the metalloproteinase-9/tissue-inhibitor metalloproteinase-1 ratio are associated with the magnitude of high-resolution computed tomography scan abnormalities of the airways in asthma and chronic obstructive pulmonary disease, and suggests that the levels of these markers reflect the extent of structural changes of the airways.
Giant gastric ulcer: an endoscopic roller coaster
Authors: A O Laosebikan
Journal: Gut (2005)

Background: Hereditary diffuse gastric cancer (HDGC) is defined by germline mutations in the E-cadherin gene, CDH-1.The first family in which CDH-1 mutations were identified was a large Maori kindred, where lifetime penetrance is 70%.Prophylactic gastrectomy is an unacceptable option for many mutation carriers.The results of annual chromoendoscopic surveillance using the methylene blue/congo red technique in 33 mutation carriers over a five year period are described.Patients and methods: Thirty three confirmed CDH-1 mutation carriers (18 males, 15 females), median age 32 years (range 14-69), were enrolled in 1999-2003.Medical records, endoscopy, and pathology were reviewed retrospectively.Results: Over five years, 99 surveillance endoscopies were performed, of which 93 were chromo-dye enhanced.Sixty nine chromoendoscopies were normal.In 24 procedures, 1-6 pale areas/stomach (size 2-10 mm) were detected post chromo-dye application (totalling 56 pale lesions).One biopsy was taken from each pale lesion: 23 lesions (41%) showed signet ring cell carcinoma (10 patients), 10 lesions (18%) gastritis (four patients), and 23 (41%) normal mucosa (10 patients).No chromo-dyes were used in six procedures with macroscopic lesions (two HDGC, four ulceration).Total gastrectomies from patients with carcinoma were macroscopically normal but pathological mapping showed multiple microscopic foci of early signet ring cell carcinoma.Correlation of chromoendoscopic and gastrectomy findings showed that congo red/methylene blue detected carcinoma foci 4-10 mm in size but not foci ,4 mm.Conclusions: The use of chromoendoscopy following normal white light gastroscopy facilitated detection of early gastric carcinoma foci not visible with white light gastroscopy.If these findings are validated in other HDGC kindred, chromogastroscopy represents an improved surveillance technique that can be safely considered alongside prophylactic gastrectomy.
Astrocytes Are an Early Target in Osmotic Demyelination Syndrome
Authors: Fabrice Gankam Kengne, Charles Nicaise, Alain Soupart, Alain Boom, Johan Schiettecatte, Roland Pochet, Jean Pierre Brion, Guy Decaux
Journal: Journal of the American Society of Nephrology (2011)

Abrupt osmotic changes during rapid correction of chronic hyponatremia result in demyelinative brain lesions, but the sequence of events linking rapid osmotic changes to myelin loss is not yet understood. Here, in a rat model of osmotic demyelination syndrome, we found that massive astrocyte death occurred after rapid correction of hyponatremia, delineating the regions of future myelin loss. Astrocyte death caused a disruption of the astrocyte-oligodendrocyte network, rapidly upregulated inflammatory cytokines genes, and increased serum S100B, which predicted clinical manifestations and outcome of osmotic demyelination. These results support a model for the pathophysiology of osmotic brain injury in which rapid correction of hyponatremia triggers apoptosis in astrocytes followed by a loss of trophic communication between astrocytes and oligodendrocytes, secondary inflammation, microglial activation, and finally demyelination.
Managing Budd-Chiari syndrome: a retrospective review of percutaneous hepatic vein angioplasty and surgical shunting
Authors: N C Fisher, I McCafferty, M Dolapci, M Wali, J A C Buckels, S P Olliff, E Elias
Journal: Gut (1999)

The role of percutaneous hepatic vein angioplasty in the management of Budd-Chiari syndrome has not been well defined. Over a 10 year period at our unit, we have often used this technique in cases of short length hepatic vein stenosis or occlusion, reserving surgical mesocaval shunting for cases of diffuse hepatic vein occlusion or failed angioplasty.To review the outcome of angioplasty and surgical shunting to define their respective roles.All patients treated by angioplasty or surgical shunting for non-malignant hepatic vein obstruction over a ten year period from 1987 to 1996.A case note review of pretreatment features and clinical outcome.Angioplasty was attempted in 21 patients with patent hepatic vein branches and was successful in 18; in three patients treatment was unsuccessful and these patients had surgical shunts. Fifteen patients were treated by surgical shunting only. Mortality according to definitive treatment was 3/18 following angioplasty and 8/18 following surgery; in most cases this reflected high risk status prior to treatment. Venous or shunt reocclusion rates were similar for both groups and were associated with subtherapeutic warfarin in half of these cases. Most surviving patients in both groups are asymptomatic although one surgical patient has chronic hepatic encephalopathy.With appropriate case selection, many patients with Budd-Chiari syndrome caused by short length hepatic vein stenosis or occlusion may be managed successfully by angioplasty alone. Medium term outcome is good following this procedure provided that anticoagulation is maintained. Further follow up is required to assess for definitive benefits but we suggest that this should be included as a valid initial approach in the algorithm for management of Budd-Chiari syndrome.
ABO/Secretor genetic complex and susceptibility to asthma in childhood
Authors: F. Ronchetti, M.P. Villa, R. Ronchetti, E. Bonci, L. Latini, R. Pascone, N. Bottini, F. Gloria-Bottini
Journal: European Respiratory Journal (2001)

A positive association has recently been reported in adult subjects between O/nonSecretor phenotype and asthma. To confirm this association, this study investigated the joint ABO/Secretor phenotype in a cohort of 165 asthmatic children. Three-hundred and sixty-two consecutive newborn infants from the same population were also studied as controls. The proportion of O/nonSecretor in asthmatic children was higher than in controls, thus confirming the association found in adults. The association was more marked in males than in females. In males, the pattern of association between the joint ABO/Secretor phenotype and asthma is dependent on the age at on-set of symptoms. Since the oligosaccharide composition of cell membrane and mucosal secretions is controlled by the cooperative interaction of ABO and Secretor genes, and since such composition influences the adhesion of infectious agents, the age pattern could reflect a more general interaction between developmental maturation and oligosaccharide structure concerning their effects on susceptibility to viral and bacterial agents.