tbuckley/cabot-search huggingface dataset:
Leukemia in AKR mice. I. Effects of leukemic cells on antibody-forming potential of syngeneic and allogeneic normal cells.
Authors: J M Roman, E S Golub
Journal: The Journal of Experimental Medicine (1976)

Cells from the spleen, thymus, lymph node, and liver of leukemic AKR mice suppress in vitro antibody responses of normal syngeneic and semiallogeneic cells. This suppression can be mediated by irradiated leukemic cells, requires cell contact between leukemic and normal cells, and may occur at any time during the in vitro culture period. Leukemic AKR cells do not suppress antibody responses of allogeneic cells, even when allogeneic cells have H-2 or background genes homologous with AKR. Leukemic cells do, however, suppress cells that are unable to respond allogeneically to leukemic AKR cells, such as cells of the F1s of AKR. Suppression of normal AKR antibody responses by leukemic AKR cells may be overcome by addition of irradiated allogeneic cells. The fact that leukemic AKR cells are able to suppress normal lymphocyte responses may be of significance in pathogenesis of leukemia in these mice.
Suicide prevention and developing countries
Authors: M. M Khan
Journal: Journal of the Royal Society of Medicine (2005)

Globally, approximately one million people kill themselves every year.1 The World Health Organization (WHO) has declared suicide a major global public health problem and called on member states to devise and implement national suicide prevention strategies.

While suicide prevention is receiving increased attention in many developed countries, it remains largely ignored in developing countries, where a number of factors impede the implementation of successful preventive programmes.
Female reproduction and type 1 diabetes: from mechanisms to clinical findings
Authors: E. Codner, P.M. Merino, M. Tena-Sempere
Journal: Human Reproduction Update (2012)

The functional reproductive alterations seen in women with type 1 diabetes (T1D) have changed as therapy has improved. Historically, patients with T1D and insufficient metabolic control exhibited a high prevalence of amenorrhea, hypogonadism and infertility. This paper reviews the impact of diabetes on the reproductive axis of female T1D patients treated with modern insulin therapy, with special attention to the mechanisms by which diabetes disrupts hypothalamic-pituitary-ovarian function, as documented mainly by animal model studies.A comprehensive MEDLINE search of articles published from 1966 to 2012 was performed. Animal model studies on experimental diabetes and human studies on T1D were examined and cross-referenced with terms that referred to different aspects of the gonadotropic axis, gonadotrophins and gonadal steroids.Recent studies have shown that women with T1D still display delayed puberty and menarche, menstrual irregularities (especially oligomenorrhoea), mild hyperandrogenism, polycystic ovarian syndrome, fewer live born children and possibly earlier menopause. Animal models have helped us to decipher the underlying basis of these conditions and have highlighted the variable contributions of defective leptin, insulin and kisspeptin signalling to the mechanisms of perturbed reproduction in T1D.Despite improvements in insulin therapy, T1D patients still suffer many reproductive problems that warrant specific diagnoses and therapeutic management. Similar to other states of metabolic stress, T1D represents a challenge to the correct functioning of the reproductive axis.
MicroRNA-21 Regulates the Proliferation and Invasion in Esophageal Squamous Cell Carcinoma
Authors: Yukiharu Hiyoshi, Hidenobu Kamohara, Ryuichi Karashima, Nobutaka Sato, Yu Imamura, Youhei Nagai, Naoya Yoshida, Eiichiro Toyama, Naoko Hayashi, Masayuki Watanabe, Hideo Baba
Journal: Clinical Cancer Research (2009)

MicroRNAs are approximately 22 nucleotide noncoding RNA molecules that posttranscriptionally regulate gene expression. The aim of this study was (a) to determine a role of microRNA-21 in esophageal squamous cell carcinoma and (b) to elucidate the regulation of the programmed cell death 4 (PDCD4) gene by microRNA-21.MicroRNA-21 expression was investigated in 20 matched normal esophageal epitheliums and esophageal squamous cell carcinomas and seven esophageal squamous cell carcinoma cell lines (TE6, TE8, TE10, TE11, TE12, TE14, KYSE30) by TaqMan quantitative real-time PCR and in situ hybridization. To evaluate the role of microRNA-21, cell proliferation and invasion were analyzed with anti-microRNA-21-transfected cells. In addition, the regulation of PDCD4 by microRNA-21 was elucidated to identify the mechanisms of this regulation.Of 20 paired samples, 18 cancer tissues overexpressed microRNA-21 in comparison with matched normal epitheliums. Specifically, patients with lymph node metastasis or venous invasion showed significantly high expression of microRNA-21. In situ hybridization for microRNA-21 showed strong positive staining in paraffin-embedded esophageal squamous cell carcinoma tissues. All seven esophageal squamous cell carcinoma cell lines also overexpressed microRNA-21, and anti-microRNA-21-transfected cells showed significant reduction in cellular proliferation and invasion. The PDCD4 protein levels in esophageal squamous cell carcinoma cells have an inverse correlation with microRNA-21 expression. Anti-microRNA-21-transfected cells increased PDCD4 protein expression without changing the PDCD4 mRNA level and increased a luciferase-reporter activity containing the PDCD4-3' untranslated region construct.MicroRNA-21 targets PDCD4 at the posttranscriptional level and regulates cell proliferation and invasion in esophageal squamous cell carcinoma. It may serve as a novel therapeutic target in esophageal squamous cell carcinoma.
Long- and short-acting beta2 adrenoceptor agonists: interactions in human contracted bronchi
Authors: M Molimard, E Naline, Y Zhang, V Le Gros, B Begaud, C Advenier
Journal: European Respiratory Journal (1998)

The aim of this study was to systematically compare the interaction of the long-acting beta2-adrenoceptor agonists formoterol and salmeterol with short-acting beta2-adrenoceptor agonists in contracted human bronchi. Human bronchi were obtained at thoracotomy from patients with lung cancer. Formoterol or salmeterol at concentrations inducing up to 92 and 94% of their maximal relaxant effect, respectively, were added to bronchial rings contracted with carbachol (10(-6) M). After a time period of 30 min, concentration-response curves for the short-acting beta2-adrenoceptor agonists, salbutamol, terbutaline, isoprenaline and fenoterol were recorded. Administration of equieffective concentrations of salmeterol and formoterol, resulted in only salmeterol inducing a shift to the right of isoprenaline, terbutaline, fenoterol and salbutamol concentration-response curves. The rank order of shift was salbutamol > fenoterol > terbutaline > isoprenaline. Formoterol, up to concentrations of 3x10(-9) M induced submaximal relaxation resulting in no shift in short-acting beta2-adrenoceptor agonist concentration-response curves. Salmeterol but not formoterol appears to antagonize the relaxation of human contracted bronchi induced by short-acting beta2-agonists. These results obtained in vitro cannot be translated in clinical terms. This study, however, highlights the need for clinical studies on the interaction of long-acting and short-acting beta2-adrenoceptor agonists in acute severe asthma.
Class A Scavenger Receptor Deficiency Exacerbates Lung Tumorigenesis by Cultivating a Procarcinogenic Microenvironment in Humans and Mice
Authors: Jingjing Ben, Guangfu Jin, Yan Zhang, Bingqing Ma, Hui Bai, Jiaping Chen, Hanze Zhang, Qixing Gong, Xiaodan Zhou, Hanwen Zhang, Lingling Qian, Xudong Zhu, Xiaoyu Li, Qing Yang, Zhibin Hu, Yong Xu, Hongbing Shen, Qi Chen
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Genetic alterations on 8p22 have been implicated in multiple cancers, including lung cancer. In this region, genetic variants of the class A scavenger receptor (SR-A) gene have been associated with prostate cancer risk and have been highlighted as a potential susceptibility gene of cancer.To determine whether common polymorphisms in the SR-A gene are associated with human lung cancer risk and to clarify the role of SR-A in lung carcinogenesis.The relationship of three potentially functional polymorphisms (T-365C, T+25C, and Ala275Pro) in the SR-A gene with lung cancer risk was evaluated in 1287 lung cancer case subjects and 1261 control subjects from the Chinese population. At the same time, SR-A null mice were used to investigate its role in lung cancer development.The T+25C polymorphism was independently associated with lung cancer risk and significantly correlated with decreased expression of SR-A. The decreased SR-A expression was also found in tumor tissues as compared with normal tissues. Depletion of SR-A boosted the growth and angiogenesis of implanted Lewis lung carcinoma in mice. The cancer-suppressing capability of SR-A was attributable to its expression in bone marrow-derived cells as evidenced by bone marrow transplantation. Further analysis revealed augmented expression of proangiogenic factors including matrix metalloproteinase-9 (MMP9) in SR-A-deficient mice, indicative of a more procarcinogenic microenvironment. Last, zoledronate, an MMP9 inhibitor, abrogated acceleration of tumor growth conferred by SR-A loss-of-function.Evidence from the population study and mouse model strongly indicates that SR-A may function as a tumor modulator to inhibit lung cancer growth through affecting the tumor microenvironment.
Long‐term results of the phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed or refractory Waldenstrom Macroglobulinemia
Authors: Irene M. Ghobrial, Thomas E. Witzig, Morie Gertz, Betsy LaPlant, Suzanne Hayman, John Camoriano, Martha Lacy, P. Leif Bergsagel, Stacey Chuma, Daniel DeAngelo, Steven P. Treon
Journal: American Journal of Hematology (2013)

Everolimus is an oral raptor mTOR inhibitor and has shown activity in patients with Waldenstrom's macroglobulinemia (WM). This study examines a large cohort of patients with relapsed/refractory WM with long‐term follow up for survival. Patients were eligible if they had measurable disease, a platelet count &gt; 75,000 × 10 6 /L, an absolute neutrophil count &gt; 1,000 × 10 6 /L. Patients received everolimus 10 mg PO daily and were evaluated monthly. A success was defined as a complete or partial response (PR); minor responses (MR) were recorded and considered to be of clinical benefit. Sixty patients were enrolled and treated. The overall response rate (ORR) was 50% (all PR); the clinical benefit rate including MR or better was 73% (95% CI: 60–84%) with 23% MR. The median time to response for patients who achieved PR was 2 months (range, 1–26). The median duration of response has not been reached and median progression‐free survival (PFS) was 21 months. Grade 3 or higher toxicities (at least possibly related to everolimus) were observed in 67% of patients. The most common grade 3 or 4 toxicities were anemia (27%), leukopenia (22%), and thrombocytopenia (20%). Other nonhematological toxicities were diarrhea (5%), fatigue (8%), stomatitis (8%) and pulmonary toxicity (5%). Everolimus has a high single‐agent activity of 73% including MR, with a progression free survival of 21 months, indicating that this agent is active in relapsed/refractory WM. Am. J. Hematol. 89:237–242, 2014. © 2013 Wiley Periodicals, Inc
Effect of a Cleavage-Resistant Collagen Mutation on Left Ventricular Remodeling
Authors: Merry L. Lindsey, Jun Yoshioka, Catherine MacGillivray, Suphichaya Muangman, Joseph Gannon, Anjali Verghese, Masanori Aikawa, Peter Libby, Stephen M. Krane, Richard T. Lee
Journal: Circulation Research (2003)

Matrix metalloproteinase–mediated degradation of type I collagen may play a role in cardiac remodeling after strain or injury. To explore this hypothesis, we used mice homozygous (r/r) for a targeted mutation in Col1a1 ; these mice synthesize collagen I that resists collagenase cleavage at Gly975-Leu976. A total of 64 r/r and 84 littermate wild-type mice (WT) underwent experimental pressure overload by transverse aortic constriction (TAC) or myocardial infarction (MI). Echocardiographic, hemodynamic, and histological parameters were evaluated up to 12 weeks after TAC or 21 days after MI. At 4 weeks after TAC, collagen levels, wall thickness, and echocardiographic parameters were similar in the 2 groups. At 12 weeks after TAC, r/r mice had smaller LV dimensions (ESD: 2.7±0.2 mm WT versus 1.7±0.2 mm r/r, P &lt;0.013; EDD: 3.8±0.2 mm WT versus 3.1±0.1 mm r/r, P &lt;0.013); better fractional shortening (30±2% WT versus 46±4% r/r; P &lt;0.013); and lower LV/body weight ratios (7.3±0.6 WT and 5.1±0.5 r/r; P &lt;0.013). Surprisingly, these differences were not accompanied by differences in collagen accumulation, myocyte cross-sectional areas, wall thickness, or microvessel densities. Furthermore, no differences in LV remodeling assessed by echocardiography, fibrosis, or hemodynamic parameters were found between r/r and WT mice after MI. Thus, a mutation that encodes a collagenase cleavage-resistant collagen I does not affect early LV remodeling after TAC or MI, suggesting that collagen cleavage at this site is not the mechanism by which metalloproteinases mediate LV remodeling. Collagen cleavage could, however, have a role in preservation of cardiac function in late remodeling by mechanisms independent of collagen accumulation. We were not able to detect collagen cleavage fragments, and could not, therefore, rule out the possibility of collagen cleavage at additional sites.
Depletion of T lymphocytes from human bone marrow by the use of counterflow elutriation centrifugation
Authors: Yoichi Takaue, Aaron J. Roome, James A. Turpin, Christopher L. Reading
Journal: American Journal of Hematology (1986)

Normal donor bone marrow buffy coat (BMBC) cells were fractionated into three subsets by counterflow elutriation centrifugation. Fraction 1 (Fr-1) was lymphocyte-enriched, fraction 2 (Fr-2) was a mixture of lymphocytes and myelomonocytic cells, and fraction 3 (Fr-3) was enriched for myelomonocytic cells. The extent of T cell depletion was determined by limiting dilution analysis of the growth of T cells. The cells in each group were stimulated with phytohemagglutinin and cultured in the presence of interleukin-2. These conditions allowed clonogenic growth of one of three T cells purified from peripheral blood. After a 3-week culture period, replicate wells were scored for growth and precursor frequency was determined. The frequency of T cells in BMBC was 1/22 (n = 4), 1/16 in FR-1 (n = 4), and 1/246 in Fr-2 (n = 2), and in Fr-3 it ranged from 1/3,000 to 1/10,000 (n = 4). For comparison, depletion of T cells from bone marrow by cytofluorographic sorting with OKT-11 and twice E-rosetting yielded 98.1% and 97.4% removal of T cells, respectively. Thus, the clonogenic assay assured that more than 99.3% of the original T cells were depleted by elutriation; however, hematopoietic progenitor assay (CFU-GM, CFU-GEMM, and BFU-E) showed no enrichment in any particular fraction, implying that the progenitors measured in this assay are of diverse sizes. Elutriation represents a useful method for depletion of T cells from human bone marrow. Limiting dilution assay of T cell growth is a sensitive measure to monitor T cell depletion.
Investigation of Optical Coherence Microelastography as a Method to Visualize Cancers in Human Breast Tissue
Authors: Brendan F. Kennedy, Robert A. McLaughlin, Kelsey M. Kennedy, Lixin Chin, Philip Wijesinghe, Andrea Curatolo, Alan Tien, Maxine Ronald, Bruce Latham, Christobel M. Saunders, David D. Sampson
Journal: Cancer Research (2015)

Abstract An accurate intraoperative identification of malignant tissue is a challenge in the surgical management of breast cancer. Imaging techniques that help address this challenge could contribute to more complete and accurate tumor excision, and thereby help reduce the current high reexcision rates without resorting to the removal of excess healthy tissue. Optical coherence microelastography (OCME) is a three-dimensional, high-resolution imaging technique that is sensitive to microscale variations of the mechanical properties of tissue. As the tumor modifies the mechanical properties of breast tissue, OCME has the potential to identify, on the microscale, involved regions of fresh, unstained tissue. OCME is based on the use of optical coherence tomography (OCT) to measure tissue deformation in response to applied mechanical compression. In this feasibility study on 58 ex vivo samples from patients undergoing mastectomy or wide local excision, we demonstrate the performance of OCME as a means to visualize tissue microarchitecture in benign and malignant human breast tissues. Through a comparison with corresponding histology and OCT images, OCME is shown to enable ready visualization of features such as ducts, lobules, microcysts, blood vessels, and arterioles and to identify invasive tumor through distinctive patterns in OCME images, often with enhanced contrast compared with OCT. These results lay the foundation for future intraoperative studies. Cancer Res; 75(16); 3236–45. ©2015 AACR.
Cisplatin Nephrotoxicity Is Mediated by Deoxyribonuclease I
Authors: Alexei G. Basnakian, Eugene O. Apostolov, Xiaoyan Yin, Markus Napirei, Hans Georg Mannherz, Sudhir V. Shah
Journal: Journal of the American Society of Nephrology (2005)

Cisplatin is commonly used for chemotherapy in a wide variety of tumors; however, its use is limited by kidney toxicity. Although the exact mechanism of cisplatin-induced nephrotoxicity is not understood, several studies showed that it is associated with DNA fragmentation induced by an unknown endonuclease. It was demonstrated previously that deoxyribonuclease I (DNase I) is a highly active renal endonuclease, and its silencing by antisense is cytoprotective against the in vitro hypoxia injury of kidney tubular epithelial cells. This study used recently developed DNase1 knockout (KO) mice to determine the role of this endonuclease in cisplatin-induced nephrotoxicity. The data showed that DNase I represents approximately 80% of the total endonuclease activity in the kidney and cultured primary renal tubular epithelial cells. In vitro, primary renal tubular epithelial cells isolated from KO animals were resistant to cisplatin (8 μM) injury. DNase I KO mice were also markedly protected against the toxic injury induced by a single injection of cisplatin (20 mg/kg), by both functional (blood urea nitrogen and serum creatinine) and histologic criteria (tubular necrosis and in situ DNA fragmentation assessed by the terminal deoxynucleotidyl transferase nick end-labeling). These data provide direct evidence that DNase I is essential for kidney injury induced by cisplatin.
Compliance at night with low flow oxygen therapy: a comparison of nasal cannulae and Venturi face masks.
Authors: R W Costello, R Liston, W T McNicholas
Journal: Thorax (1995)

BACKGROUND--The factors that influence nocturnal compliance among patients prescribed low flow oxygen therapy were determined and tolerance of nasal cannulae and Venturi face masks compared. METHODS--Two studies were performed: (1) a prospective study of 99 hospitalised patients prescribed low flow oxygen therapy, 49 on nasal cannulae and 50 on Venturi face mask; and (2) a prospective study of 20 separate patients with an acute respiratory disorder requiring low flow oxygen therapy who were given nasal cannulae and Venturi face mask on successive nights in random order. RESULTS--In study 1, 49 patients dislodged their device at least once during the night. Those using Venturi face masks and those over 75 years of age had the most dislodgements. In study 2 patients also dislodged Venturi face masks more frequently (mean (SD) 2.0 (2.4)) than nasal cannulae (0.7 (1.4)). Most patients expressed a preference for nasal cannulae. CONCLUSIONS--Nocturnal tolerance of nasal cannulae is superior to Venturi face masks, and this factor should be considered when choosing the method of oxygen delivery.
One-Year Outcomes of Cohort 1 in the Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) Registry
Authors: Martyn Thomas, Gerhard Schymik, Thomas Walther, Dominique Himbert, Thierry Lefèvre, Hendrik Treede, Holger Eggebrecht, Paolo Rubino, Antonio Colombo, Rüdiger Lange, Rebecca R. Schwarz;, Olaf Wendler
Journal: Circulation (2011)

Transcatheter aortic valve implantation was developed to provide a therapeutic option for patients considered to be ineligible for, and to mitigate mortality and morbidity associated with, high-risk surgical aortic valve replacement.The Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) Registry was designed to assess initial post commercial clinical transcatheter aortic valve implantation results of the Edwards SAPIEN valve in consecutive patients in Europe. Cohort 1 consists of 1038 patients enrolled at 32 centers. One-year outcomes are presented. Patients with the transapical approach (n=575) suffered more comorbidities than transfemoral patients (n=463) with a significantly higher logistic EuroSCORE (29% versus 25.8%; P=0.007). These groups are different; therefore, outcomes cannot be directly compared. Total Kaplan Meier 1-year survival was 76.1% overall, 72.1% for transapical and 81.1% for transfemoral patients, and 73.5% of surviving patients were in New York Heart Association (NYHA) class I or II at 1 year. Combined transapical and transfemoral causes of death were cardiac in 25.1%, noncardiac in 49.2%, and unknown in 25.7%. Pulmonary complications (23.9%), renal failure (12.5%), cancer (11.4%), and stroke (10.2%) were the most frequent noncardiac causes of death. Multivariable analysis identified logistic EuroSCORE, renal disease, liver disease, and smoking as variables with the highest hazard ratios for 1-year mortality whereas carotid artery stenosis, hyperlipidemia, and hypertension were associated with lower mortality.The SOURCE Registry is the largest consecutively enrolled registry for transcatheter aortic valve implantation procedures. It demonstrates that with new transcatheter aortic techniques excellent 1-year survival in high-risk and inoperable patients is achievable and provides a benchmark against which future transcatheter aortic valve implantation cohorts and devices can be measured.
Modelling cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer: a mandate for clinical trials
Authors: Julie Parsonnet, Ryan A Harris, Howard M Hack, Douglas K Owens
Journal: The Lancet (1996)

Background It is unknown whether eradication of Helicobacter pylori infection prevents development of gastric adenocarcinoma. To determine whether screening and treatment trials are warranted, we conducted a cost-effectiveness analysis to estimate the costs and benefits associated with screening for H pylori at age 50 and treating those individuals infected with antibiotics. Methods We compared two interventions: (1) screen for H pylori and treat those with a positive test, and (2) do not screen and do not treat. Estimates of risks and costs were obtained by review of published reports. Since the efficacy of H pylori therapy in cancer prevention is unknown, we did sensitivity analyses, varying this estimate widely. In our base-case analysis, we assumed that H pylori treatment prevented 30% of attributable gastric cancers. Findings In the base-case analysis, 11 646 000 persons in the US would be screened and 4 658 400 treated, at a cost of $996 million. Cost-effectiveness was $25 000 per year of life saved. Cost-effectiveness was sensitive to the efficacy of the cancer prevention strategy. At low efficacy rates (<10%), the screening programme was more expensive (>$75 000 per year of life saved). In a high-risk group such as Japanese-Americans, however, screening and treatment required less than $50 000 per year of life saved, even at 5% treatment efficacy. Interpretation Screening and treatment for H pylori infection is potentially cost-effective in the prevention of gastric cancer, particularly in high-risk populations. Cancer prevention trials are strongly recommended.