tbuckley/cabot-search huggingface dataset:
Exacerbation of sleep apnoea by frequent central events in patients with the obstructive sleep apnoea syndrome at altitude: a randomised trial
Authors: Y. Nussbaumer-Ochsner, N. Schuepfer, S. Ulrich, K. E. Bloch
Journal: Thorax (2010)

<h3>Background</h3> Many patients with the obstructive sleep apnoea syndrome (OSA) travel to the mountains for recreational and professional activities while temporarily discontinuing continuous positive airway pressure (CPAP) treatment. A study was undertaken to evaluate the hypothesis that altitude would aggravate their hypoxaemia, sleep-related breathing disturbances and impair daytime performance. <h3>Methods</h3> Thirty-four patients with OSA of median age 62 years (IQR 57–65), median apnoea/hypopnoea index (AHI) 47.5 events/h (IQR 32.4–72.8), residing at &lt;600 m were enrolled. A crossover trial randomised for the sequence of altitude exposure was carried out: patients spent 1 day in Zurich (490 m) and 4 days in the Swiss Alps at 1860 m and 2590 m (2 days each) during which continuous positive airway pressure was discontinued. Daily evaluations included polysomnography, symptom questionnaires, physical examination and driving simulator tests. <h3>Results</h3> Polysomnography revealed median oxygen saturations at 490 m and in the first and second nights at 1860 and 2590 m, respectively, of 94%, 90%, 90%, 86% and 87% (p&lt;0.01 between altitudes). Corresponding median AHI were 47.5, 85.1, 74.6, 90.0 and 90.9 events/h (p&lt;0.01 between altitudes) with ratios of central to obstructive events of 0.1, 0.8, 1.0, 1.9 and 1.9 (p&lt;0.01 between altitudes). Tracking performance during simulated driving was significantly impaired at 2590 m compared with 490 m. Systolic blood pressure and cardiac arrhythmias were increased at altitude. <h3>Conclusions</h3> Altitude exposure in untreated patients with OSA aggravates hypoxaemia, increases sleep-related breathing disturbances due to frequent central apnoeas/hypopnoeas, impairs driving simulator performance and induces cardiovascular stress. These findings have implications for counselling and treating patients with OSA planning to travel to high altitude. <h3>ClinicalTrials.gov identifier</h3> NCT00514826.
Endoscopic papillectomy: a novel approach to difficult cannulation.
Authors: R J Farrell, M I Khan, N Noonan, K O'Byrne, P W Keeling
Journal: Gut (1996)

Selective cannulation of the biliary and pancreatic ducts is considered to be the most difficult and rate limiting aspect of diagnostic endoscopic retrograde cholangiopancreatography (ERCP).A novel technique for difficult cannulation is described and its potential role in relieving malignant duodenal obstruction secondary to ampullary carcinoma. A diagnostic endoscopic papillectomy was performed in 10 patients in whom previous attempts at cannulation had failed. Five patients had exophytic ampullary carcinomas, one had carcinoma of the head of pancreas, two had an oedematous ampulla secondary to low common bile duct stones, while two had protuberant ampullae with ectopic orifices. The technique entails snaring the ampulla flush with the duodenal wall using a polypectomy snare and in a similar fashion to polypectomy removing the ensnared ampulla with diathermy using a coagulation current. The underlying exposed ducts can then be cannulated while the ensnared ampulla can be retrieved to aid histological diagnosis.Successful cannulation was achieved in all 10 cases with significant haemorrhage in one patient (10%). Four of the snared ampullary carcinomas (80%) were retrieved enabling a histological diagnosis to be made.This study demonstrates the potential role for endoscopic papillectomy as a means of cannulation in difficult circumstances, however larger comparative studies are required.
Molecular Load of Pathologically Occult Metastases in Pelvic Lymph Nodes Is an Independent Prognostic Marker of Biochemical Failure After Localized Prostate Cancer Treatment
Authors: Anna C. Ferrari, Nelson N. Stone, Ralf Kurek, Elizabeth Mulligan, Roy McGregor, Richard Stock, Pamela Unger, Ulf Tunn, Amir Kaisary, Michael Droller, Simon Hall, Heiner Renneberg, Kenneth J. Livak, Robert E. Gallagher, John Mandeli
Journal: Journal of Clinical Oncology (2006)

Thirty percent of patients treated with curative intent for localized prostate cancer (PC) experience biochemical recurrence (BCR) with rising serum prostate-specific antigen (sPSA), and of these, approximately 50% succumb to progressive disease. More discriminatory staging procedures are needed to identify occult micrometastases that spawn BCR.PSA mRNA copies in pathologically normal pelvic lymph nodes (N0-PLN) from 341 localized PC patients were quantified by real-time reverse-transcriptase polymerase chain reaction. Based on comparisons with normal lymph nodes and PLN with metastases and on normalization to 5 x 10(6) glyceraldehyde-3'-phosphate dehydrogenase mRNA copies, normalized PSA copies (PSA-N) and a threshold of PSA-N 100 or more were selected for continuous and categorical multivariate analyses of biochemical failure-free survival (BFFS) compared with established risk factors.At median follow-up of 4 years, the BFFS of patients with PSA-N 100 or more versus PSA-N less than 100 was 55% and 77% (P = .0002), respectively. The effect was greatest for sPSA greater than 20 ng/mL, 25% versus 60% (P = .014), Gleason score 8 or higher, 21% versus 66% (P = .0002), stage T3c, 18% versus 64% (P = .001), and high-risk group (50% v 72%; P = .05). By continuous analysis PSA-N was an independent prognostic marker for BCR (P = .049) with a hazard ratio of 1.25 (95% CI, 1.001 to 1.57). By categorical analysis, PSA-N 100 or more was an independent variable (P = .021) with a relative risk of 1.98 (95% CI, 1.11 to 3.55) for BCR compared with PSA-N less than 100.PSA-N 100 or more is a new, independent molecular staging criterion for localized PC that identifies high-risk group patients with clinically relevant occult micrometastases in N0-PLN, who may benefit from additional therapy to prevent BCR.
Improvement of psoriasis during glucagon-like peptide-1 analogue therapy in type 2 diabetes is associated with decreasing dermal γδ T-cell number: a prospective case-series study
Authors: M. Buysschaert, M. Baeck, V. Preumont, L. Marot, E. Hendrickx, A. Van Belle, L. Dumoutier
Journal: British Journal of Dermatology (2014)

A few case reports suggest that incretin-based therapies could improve psoriasis in patients with type 2 diabetes, the mechanism(s) of which remain unclear.To determine the effects after 16-20 weeks of treatment with a glucagon-like peptide (GLP)-1 analogue on clinical severity and histopathological aspects of psoriasis in patients with type 2 diabetes, and to examine the presence of γδ T cells and the expression of interleukin (IL)-17 in psoriasis before and after treatment.Seven patients with type 2 diabetes and psoriasis were followed. Psoriasis Area and Severity Index (PASI) was measured at baseline (T0) and after 7 ± 1 (T1) and 18 ± 2 (T2) weeks' treatment with exenatide/liraglutide. The histopathological pattern of psoriasis, and flow cytometry and immunological data (γδ T-cell percentage and IL-17 expression) were obtained from psoriatic and control sites.The mean PASI decreased from 12·0 ± 5·9 to 9·2 ± 6·4 (P = 0·04). Histological analysis showed a reduction in epidermal thickness after treatment. The dermal γδ T-cell percentage was higher in psoriatic lesions than in control specimens (P = 0·03), as was IL-17 expression (P = 0·018). A reduction of γδ T cells from 6·7 ± 4·5% to 2·7 ± 3·8% (P = 0·05) was demonstrated in the six patients with improved/unchanged PASI. A correlation between PASI and γδ T-cell percentage evolution during therapy (T2-T0) was noted (r = 0·894, P = 0·007). IL-17 was reduced in the four patients with the highest PASI reductions.The administration of a GLP-1 analogue improved clinical psoriasis severity in patients with type 2 diabetes. This favourable outcome was associated with a decrease of dermal γδ T-cell number and IL-17 expression. Further studies are needed to establish long-term efficacy in (diabetic) patients with psoriasis.
Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol
Authors: Meritxell Alberich Jordà, Sandra E. Verbakel, Peter J. M. Valk, Yolanda V. Vankan-Berkhoudt, Mauro Maccarrone, Allessandro Finazzi-Agrò, Bob Löwenberg, Ruud Delwel
Journal: Blood (2002)
Effect of Metformin and Rosiglitazone Combination Therapy in Patients With Type 2 Diabetes Mellitus
Authors: V Fonseca, J Rosenstock, R Patwardhan, A Salzman
Journal: JAMA (2000)

ContextMost antidiabetic agents target only 1 of several underlying causes of diabetes. The complementary actions of the antidiabetic agents metformin hydrochloride and rosiglitazone maleate may maintain optimal glycemic control in patients with type 2 diabetes; therefore, their combined use may be indicated for patients whose diabetes is poorly controlled by metformin alone.ObjectiveTo evaluate the efficacy of metformin-rosiglitazone therapy in patients whose type 2 diabetes is inadequately controlled with metformin alone.DesignRandomized, double-blind, placebo-controlled trial from April 1997 and March 1998.SettingThirty-six outpatient centers in the United States.PatientsThree hundred forty-eight patients aged 40 to 80 years with a mean fasting plasma glucose level of 12.0 mmol/L (216 mg/dL), a mean glycosylated hemoglobin level of 8.8%, and a mean body mass index of 30.1 kg/m2 were randomized.InterventionsPatients were assigned to receive 2.5 g/d of metformin plus placebo (n = 116); 2.5 g/d of metformin plus 4 mg/d of rosiglitazone (n = 119); or 2.5 g/d of metformin and 8 mg/d of rosiglitazone (n = 113) for 26 weeks.Main Outcome MeasuresGlycosylated hemoglobin levels, fasting plasma glucose levels, insulin sensitivity, and β-cell function, compared between baseline and week 26, by treatment group.ResultsGlycosylated hemoglobin levels, fasting plasma glucose levels, insulin sensitivity, and β-cell function improved significantly with metformin-rosiglitazone therapy in a dose-dependent manner. The mean levels of glycosylated hemoglobin decreased by 1.0% in the 4 mg/d metformin-rosiglitazone group and by 1.2% in the 8 mg/d metformin-rosiglitazone group and fasting plasma glucose levels by 2.2 mmol/L (39.8 mg/dL) and 2.9 mmol/L (52.9 mg/dL) compared with the metformin-placebo group (P<.001 for all). Of patients receiving 8 mg/d of metformin-rosiglitazone, 28.1% achieved a glycosylated hemoglobin level of 7% or less. Dose-dependent increases in body weight and total and low-density lipoprotein cholesterol levels were observed (P<.001 for both rosiglitazone groups vs placebo). The proportion of patients reporting adverse experiences was comparable across all groups.ConclusionsOur data suggest that combination treatment with once-daily metformin-rosiglitazone improves glycemic control, insulin sensitivity, and β-cell function more effectively than treatment with metformin alone.
Associations between microRNA expression and mesenchymal marker gene expression in glioblastoma
Authors: Xinlong Ma, Koji Yoshimoto, Yaulei Guan, Nobuhiro Hata, Masahiro Mizoguchi, Noriaki Sagata, Hideki Murata, Daisuke Kuga, Toshiyuki Amano, Akira Nakamizo, Tomio Sasaki
Journal: Neuro-Oncology (2012)

The subclassification of glioblastoma (GBM) into clinically relevant subtypes using microRNA (miRNA)and messenger RNA (mRNA) -based integrated analysis has been attempted.Because miRNAs regulate multiple gene-signaling pathways, understanding miRNA-mRNA interactions is a prerequisite for understanding glioma biology.However, such associations have not been thoroughly examined using high-throughput integrated analysis.To identify significant miRNA-mRNA correlations, we selected and quantified signature miRNAs and mRNAs in 82 gliomas (grade II: 14, III: 16, IV: 52) using real-time reverse-transcriptase polymerase chain reaction.Quantitative expression data were integrated into a single analysis platform that evaluated the expression relationship between miRNAs and mRNAs.The 21 miRNAs include miR-15b, -21, -34a, -105, -124a, -128a, -135b, -184, -196a-b, -200a-c, -203, -302a-d, -363, -367, and -504.In addition, we examined 23 genes, including proneural markers (DLL3, BCAN, and OLIG2), mesenchymal markers (YKL-40, CD44, and Vimentin), cancer stem cell-related markers, and receptor tyrosine kinase genes.Primary GBM was characterized exclusively by upregulation of mesenchymal markers, whereas secondary GBM was characterized by significant downregulation of mesenchymal markers, miR-21, and -34a, and by upregulation of proneural markers and miR-504.Statistical analysis showed that expression of miR-128a, -504, -124a, and -184 each negatively correlated with the expression of mesenchymal markers in GBM.Our functional analysis of miR-128a and -504 as inhibitors demonstrated that suppression of miR-128a and -504 increased the expression of mesenchymal markers in glioblastoma cell lines.Mesenchymal signaling in GBM may be negatively regulated by miR-128a and -504.
Human Papillomavirus Type 16/18 Up-Regulates the Expression of Interleukin-6 and Antiapoptotic Mcl-1 in Non–Small Cell Lung Cancer
Authors: Ya-Wen Cheng, Huei Lee, Ming-Yuh Shiau, Tzu-Chin Wu, Tsung-Teng Huang, Yih-Hsin Chang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Human papillomavirus (HPV) 16/18 infection is reported to be associated with nonsmoking Taiwanese female lung cancer. In this study, we attempted to further reveal the association between HPV infection with Mcl-1 and interleukin (IL)-6 expressions and to elucidate the roles of HPV infection in lung tumorigenesis. Experimental Design: IL-6 and Mcl-1 expressions were investigated in 79 tumor tissues from lung cancer patients by immunohitochemistry. Secreting IL-6 levels and Mcl-1 expressions were examined by ELISA and Western blot, respectively, in HPV 16/18 E6- and E7-transfected A549 human lung cancer cells, as well as in the HPV16-infected TL-1 lung cancer cells established from lung cancer patients. Results: Lung tumors (70.9% and 57.0%) had positive IL-6 and Mcl-1 immunostainings, respectively. Significant correlation between IL-6 and Mcl-1 expression were observed (P &amp;lt; 0.0001). Both IL-6 and Mcl-1 expression were significantly associated with HPV 16/18 infection (P = 0.014 and P = 0.004, respectively). IL-6 and Mcl-1 protein levels were not only elevated in HPV 16/18 E6- and E7-transfected A549 cells but also in TL-1 cells. Phosphatidylinositol-3-OH kinase pathway was the major pathway contributing to the up-regulation of Mcl-1 by IL-6 in HPV-infected lung cancer cells. Conclusions: The up-regulating effects of HPV 16/18 E6 and E7 to IL-6 and Mcl-1 expressions were observed in E6- and E7-transfected A549 cells and in HPV16-infected TL-1 cells, mainly through the phosphatidylinositol-3-OH kinase pathway. The involvement of HPV infection in lung tumorigenesis may be partly through a concomitant increased expression of autocrine and/or paracrine IL-6 and the downstream Mcl-1.
Chest pains complicating an artificial therapeutic pneumothorax
Authors: G Devouassoux, S Lantuejoul, C Pison, F Capron, PY Brichon, C Brambilla, E Brambilla
Journal: European Respiratory Journal (1997)

Case reportA 56 yr old nonsmoking woman was admitted to hospital in 1985 with left sided chest pain and weight loss.She had a history of pulmonary tuberculosis 35 yrs previously.An extrapleural therapeutic pneumothorax had been performed at that time and was complicated several years later by chronic pyothorax.On admission in 1985, she had no dyspnoea or cough.Physical exam-ination showed decreased breath sounds in the upper left chest.No superficial lymphadenopathy was found.A peripheral white cell count revealed 10.5×10 9 •L -1 leucocytes, of which 9.15×10 9 •L -1 were polymorphonuclear cells and 0.6×10 9 •L -1 were lymphocytes.The erythrocyte sedimentation rate was 60 mm in the first hour.A chest radiograph (fig. 1) and computed tomographic (CT) scan (fig.2) are shown.
Active lambda and kappa antibody gene rearrangement in Abelson murine leukemia virus-transformed pre-B cell lines.
Authors: D M Persiani, J Durdik, E Selsing
Journal: The Journal of Experimental Medicine (1987)

The two Abelson murine leukemia virus (A-MuLV)-transformed cell lines, BM18-4 and ABC-1, undergo immunoglobulin L-chain gene recombination during passage in tissue culture. BM18-4 cells are capable of kappa gene recombination, whereas ABC-1 cells are capable of both kappa and lambda gene recombination. The expression of H chains is apparently not necessary for continuing L chain gene recombination in either of these cells, although H-chain expression may have been involved in the initiation of L-chain gene recombination. All ABC-1 cells that have lambda gene rearrangements also display recombined kappa alleles, supporting the hypothesis that kappa and lambda gene recombination are initiated in an ordered, developmentally regulated manner in maturing B cells. However, analyses of the ABC-1 line indicate that pre-B cells that have initiated lambda gene recombination do not terminate kappa gene rearrangement. The lambda gene recombinations that occur in the ABC-1 cell line indicate that the germline order of lambda gene segments is: 5' ... V lambda 2 ... J lambda 2C lambda 2-J lambda 4C lambda 4 ... V lambda 1 ... J lambda 3C lambda 3-J lambda 1C lambda 1 ... 3'. In addition, the frequencies of lambda 1, lambda 2, and lambda 3 gene recombinations among ABC-1 cells are quite different than the frequencies of B cells producing lambda 1, lambda 2, and lambda 3 L-chains in the mouse. RS DNA recombinations also occur in the BM18-4 and ABC-1 cell lines, supporting the notion that Ig gene recombinases are involved in RS rearrangement. Recombined RS segments are infrequent among BM 18-4 cells but common among ABC-1 cells, suggesting that RS recombinational events often occur in maturing pre-B cells just before initiation of lambda gene rearrangements. This developmental timing is consistent with the hypothesis that RS recombination may be involved in the initiation of lambda gene assembly.
Integrative Genomic Analysis Implicates Gain of<i>PIK3CA</i>at 3q26 and<i>MYC</i>at 8q24 in Chronic Lymphocytic Leukemia
Authors: Jennifer R. Brown, Megan Hanna, Bethany Tesar, Lillian Werner, Nathalie Pochet, John M. Asara, Yaoyu E. Wang, Paola dal Cin, Stacey M. Fernandes, Christina Thompson, Laura MacConaill, Catherine J. Wu, Yves Van de Peer, Mick Correll, Aviv Regev, Donna Neuberg, Arnold S. Freedman
Journal: Clinical Cancer Research (2012)

The disease course of chronic lymphocytic leukemia (CLL) varies significantly within cytogenetic groups. We hypothesized that high-resolution genomic analysis of CLL would identify additional recurrent abnormalities associated with short time-to-first therapy (TTFT).
Genetic susceptibility to HIV-associated nephropathy
Authors: Susan E. Quaggin
Journal: Journal of Clinical Investigation (2009)

HIV-1-associated nephropathy (HIVAN) is a common complication of HIV-1 infection, and its skewed incidence in certain ethnic groups suggests that there is a genetic basis to HIVAN susceptibility. In their study reported in this issue of the JCI, Papeta and colleagues used a combination of gene expression profiling and linkage analysis to identify three genomic loci that regulate a network of genes expressed by podocytes - cells that are crucial to the filtration of fluid and waste by the kidney (see the related article beginning on page 1178). Surprisingly, two of these loci confer disease susceptibility in a transgenic mouse model of HIVAN. This report confirms the central role of podocytes in the pathogenesis of HIVAN and demonstrates the power of this combination of genomic analysis techniques in elucidating the pathogenesis of glomerular disease.
Welcome Reassurance About GLP-1 Drugs—But They Are Still Young and Not Fully Grown
Authors: Matthew C. Riddle
Journal: Diabetes Care (2015)

An excellent article in this issue of Diabetes Care by Yu et al. (1) provides reassurance about the safety of therapies related to GLP-1. This is welcome because of the current uncertainty and anxiety about the use of these agents, which appear very promising yet not without potential risks. To understand the study’s relevance at this stage of development of these agents, consider the process of development of new therapies in general.

Like people, therapeutic agents come in families with individual members and a typical life history. A new class of drugs begins as a pathophysiological insight, a gleam in a scientist’s eye. A new drug’s childhood consists of testing in animal (preclinical) studies and small human (phase 1 and 2) studies. Moving into larger clinical studies (phase 3), an adolescent drug must show consistent therapeutic effects and a lack of alarming side effects over 6 to 12 months of use in a broader population of people. Good results can lead to approval for clinical practice after which further (phase 4) studies and observation of clinical experience may explore specific clinical indications and safety during more prolonged use. Because drugs are, by necessity, launched when young and without long-term experience, there can be distressing surprises that lead to later restriction of usage. Full understanding of any drug’s best uses requires years of experience after its introduction.

The family of antidiabetes agents based on the actions of GLP-1 emerged from studies of this hormone that began just over 20 years ago (2,3). About 10 years ago, drugs designed to exploit the metabolic and weight-regulating effects of the native hormone entered clinical evaluation. The first were peptides capable of activating GLP-1 receptors (GLP-1 receptor agonists, or GLP-1RAs) (4–7). These peptide drugs significantly improve glucose control and favor weight …
Cooperation Between Secretory Phospholipase A<sub>2</sub>and TNF-Receptor Superfamily Signaling
Authors: Lucía Fuentes, Marita Hernández, Francisco Jesús Fernández-Avilés, Mariano Sánchez Crespo, María Luisa Nieto
Journal: Circulation Research (2002)

Atherogenesis is the consequence of a variety of effector mechanisms rather than the result of a single functional molecule. In this connection, type IIA secretory phospholipase A 2 (sPLA 2 ) is an acute-phase reactant, which accumulates in atherosclerotic arterial walls, elicits several effects on monocytes, and has been related to the development of atherosclerosis. CD40/CD40 ligand pair is also a strong proatherogenic system. sPLA 2 produced an increase of the surface expression of CD40 in THP-1 monocytes and enhanced the effect of CD40 ligation on the expression of both Fas and FasL, thus indicating the existence of a positive cooperation between sPLA 2 and different elements of the TNF-receptor superfamily. Activation of the CD40/CD40L dyad with anti-CD40 antibody produced a small release of arachidonic acid and lacked any significant effect on the induction of cyclooxygenase-2, whereas the secretion of the chemokine MCP-1 and the surface display of CD11b, the α chain of the integrin Mac-1, were upregulated. Engagement of CD40 did not influence the survival of THP-1 monocytes, but coincubation of THP-1 monocytes pretreated with anti-CD40 antibody and Jurkat cells induced a significant increase of the number of Jurkat cells showing binding of annexin-V, and nuclear condensation and fragmentation, thus indicating that this treatment might trigger a juxtacrine/paracrine mechanism of apoptotic death in sensitive cell types. This data indicates the existence of overlapping routes for the response to CD40, TNF-α, and sPLA 2 , thus allowing the development of distinct patterns of response in monocytic cells.