tbuckley/cabot-search huggingface dataset:
Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma
Authors: Gentao Liu, Xiangpeng Yuan, Zhaohui Zeng, Patrizia Tunici, Hiushan Ng, Iman R Abdulkadir, Lizhi Lu, Dwain Irvin, Keith L Black, John S Yu
Journal: Molecular Cancer (2006)

Abstract Background Recently, a small population of cancer stem cells in adult and pediatric brain tumors has been identified. Some evidence has suggested that CD133 is a marker for a subset of leukemia and glioblastoma cancer stem cells. Especially, CD133 positive cells isolated from human glioblastoma may initiate tumors and represent novel targets for therapeutics. The gene expression and the drug resistance property of CD133 positive cancer stem cells, however, are still unknown. Results In this study, by FACS analysis we determined the percentage of CD133 positive cells in three primary cultured cell lines established from glioblastoma patients 10.2%, 69.7% and 27.5%, respectively. We also determined the average mRNA levels of markers associated with neural precursors. For example, CD90, CD44, CXCR4, Nestin, Msi1 and MELK mRNA on CD133 positive cells increased to 15.6, 5.7, 337.8, 21.4, 84 and 1351 times, respectively, compared to autologous CD133 negative cells derived from cell line No. 66. Additionally, CD133 positive cells express higher levels of BCRP1 and MGMT mRNA, as well as higher mRNA levels of genes that inhibit apoptosis. Furthermore, CD133 positive cells were significantly resistant to chemotherapeutic agents including temozolomide, carboplatin, paclitaxel (Taxol) and etoposide (VP16) compared to autologous CD133 negative cells. Finally, CD133 expression was significantly higher in recurrent GBM tissue obtained from five patients as compared to their respective newly diagnosed tumors. Conclusion Our study for the first time provided evidence that CD133 positive cancer stem cells display strong capability on tumor's resistance to chemotherapy. This resistance is probably contributed by the CD133 positive cell with higher expression of on BCRP1 and MGMT, as well as the anti-apoptosis protein and inhibitors of apoptosis protein families. Future treatment should target this small population of CD133 positive cancer stem cells in tumors to improve the survival of brain tumor patients.
Ratio of triglycerides to HDL cholesterol is an indicator of LDL particle size in patients with type 2 diabetes and normal HDL cholesterol levels.
Authors: R Boizel, P Y Benhamou, B Lardy, F Laporte, T Foulon, S Halimi
Journal: Diabetes Care (2000)

OBJECTIVE: In patients with type 2 diabetes, a normal HDL cholesterol level does not rule out that LDL particles may be small. Although techniques for analyzing LDL subfractions are not likely to be used in clinical practice, a prediction of LDL size based on a regular lipid profile may be useful for assessment of cardiovascular risk. RESEARCH DESIGN AND METHODS: Sixty patients with type 2 diabetes with acceptable glycemic control and an HDL cholesterol level &amp;gt; or = 1 mmol/l were recruited after cessation of lipid-altering treatments. LDL size was determined by 2-20% PAGE; patients having small LDL (n = 30) were compared with those having intermediate or large LDL (n = 30). RESULTS: Clinical characteristics, pharmacological therapies, lifestyle, and prevalence of diabetes-related complications were similar in both patient groups. LDL size correlated negatively with plasma triglycerides (TGs) (R2 = 0.52) and positively with HDL cholesterol (R2 = 0.14). However, an inverse correlation between the TG-to-HDL cholesterol molar ratio and LDL size was even stronger (R2 = 0.59). The ratio was &amp;gt; 1.33 in 90% of the patients with small LDL particles (95% CI 79.3-100) and 16.5% of those with larger LDL particles. A cutoff point of 1.33 for the TG-to-HDL cholesterol ratio distinguishes between patients having small LDL values better than TG cutoff of 1.70 and 1.45 mmol/l. CONCLUSIONS: The TG-to-HDL cholesterol ratio may be related to the processes involved in LDL size pathophysiology and relevant with regard to the risk of clinical vascular disease. It may be suitable for the selection of patients needing an earlier and aggressive treatment of lipid abnormalities.
Regulation of Endothelial Nitric Oxide Synthase and Postnatal Angiogenesis by Rac1
Authors: Naoki Sawada, Salvatore Salomone, Hyung-Hwan Kim, David J. Kwiatkowski, James K. Liao
Journal: Circulation Research (2008)

Diminished bioavailability of nitric oxide is a hallmark of endothelial dysfunction and is associated with a broad spectrum of vascular disorders such as impaired angiogenesis. Because Rac1, a Rho family member, mediates cellular motility and generation of reactive oxygen species, it could be involved in the regulation of endothelial nitric oxide production. However, the pathophysiological consequences of postnatal endothelial Rac1 deletion on endothelial function have not been determined. We generated endothelial-specific Rac1 haploinsufficient mice (EC-Rac1(+/-)) using Cre-loxP technology. The EC-Rac1(+/-) mice have decreased expression and activity of endothelial nitric oxide synthase (eNOS), impaired endothelium-dependent vasorelaxation, and mild hypertension compared with control (Rac1(+/flox)) mice. Hind limb ischemia model and aortic capillary sprouting assay showed that eNOS activity and angiogenesis was impaired in EC-Rac1(+/-) mice. Indeed, Rac1 promotes eNOS gene transcription through p21-activated kinase but not NADPH oxidase, increases eNOS mRNA stability, and enhances eNOS activity by promoting endothelial uptake of l-arginine. These findings indicate that endothelial Rac1 is essential for endothelium-dependent vasomotor response and ischemia-induced angiogenesis. These effects of Rac1 on endothelial function are largely due to the upregulation of eNOS through multiple mechanisms that are mediated, in part, by p21-activated kinase. Therapeutic strategies to enhance Rac1 function, therefore, may be important for preventing endothelial dysfunction.
Longitudinal histories as predictors of future diagnoses of domestic abuse: modelling study
Authors: B. Y Reis, I. S Kohane, K. D Mandl
Journal: BMJ (2009)

<b>Objective</b> To determine whether longitudinal data in patients' historical records, commonly available in electronic health record systems, can be used to predict a patient's future risk of receiving a diagnosis of domestic abuse. <b>Design</b> Bayesian models, known as intelligent histories, used to predict a patient's risk of receiving a future diagnosis of abuse, based on the patient's diagnostic history. Retrospective evaluation of the model's predictions using an independent testing set. <b>Setting</b> A state-wide claims database covering six years of inpatient admissions to hospital, admissions for observation, and encounters in emergency departments. <b>Population</b> All patients aged over 18 who had at least four years between their earliest and latest visits recorded in the database (561 216 patients). <b>Main outcome measures</b> Timeliness of detection, sensitivity, specificity, positive predictive values, and area under the ROC curve. <b>Results</b> 1.04% (5829) of the patients met the narrow case definition for abuse, while 3.44% (19 303) met the broader case definition for abuse. The model achieved sensitive, specific (area under the ROC curve of 0.88), and early (10-30 months in advance, on average) prediction of patients' future risk of receiving a diagnosis of abuse. Analysis of model parameters showed important differences between sexes in the risks associated with certain diagnoses. <b>Conclusions</b> Commonly available longitudinal diagnostic data can be useful for predicting a patient's future risk of receiving a diagnosis of abuse. This modelling approach could serve as the basis for an early warning system to help doctors identify high risk patients for further screening.
Distinct types of IgG and IgA anti-intercellular autoantibodies from patients with pemphigus and vesiculopustular dermatosis
Authors: K. IWATSUKI, M. TAKIGAWA
Journal: British Journal of Dermatology (1991)

Journal Article Distinct types of IgG and IgA anti‐intercellular autoantibodies from patients with pemphigus and vesiculopustular dermatosis Get access K. IWATSUKI, K. IWATSUKI Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan Dr. K. Iwatsuki, Department of Dermatology. Hamamatsu University School of Medicine, 3600 Hand acho, Hamamatsu 431–31, Japan. Search for other works by this author on: Oxford Academic Google Scholar M. TAKIGAWA M. TAKIGAWA Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 4, 1 October 1991, Pages 335–339, https://doi.org/10.1111/j.1365-2133.1991.tb14167.x Published: 01 October 1991
OIDIOMYCOSIS OF THE NAILS
Authors: J. AVIT SCOTT
Journal: British Journal of Dermatology (1927)

Journal Article OIDIOMYCOSIS OF THE NAILS Get access J. AVIT SCOTT, M.B. J. AVIT SCOTT, M.B. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 39, Issue 3, 1 March 1927, Pages 119–122, https://doi.org/10.1111/j.1365-2133.1927.tb10057.x Published: 01 March 1927
The noise of chaos
Authors: Zbigniew J. Kowalik
Journal: Behavioral and Brain Sciences (2001)

When theoreticians talk about noise, they frequently forget about the idealization coupled with this term. Another implicit and rarely mentioned assumption is that the tools of mathematics used are idealizations, too. Though some of Tsuda's ideas are similar to mine (e.g., we both believe that nonlinearity is one of the main reasons why the brain works the way it does; Kowalik et al. 1996), some critical remarks are in order.
Endogenous prolactin-releasing peptide regulates food intake in rodents
Authors: Yuki Takayanagi, Hirokazu Matsumoto, Masanori Nakata, Takashi Mera, Shoji Fukusumi, Shuji Hinuma, Yoichi Ueta, Toshihiko Yada, Gareth Leng, Tatsushi Onaka
Journal: Journal of Clinical Investigation (2008)

Food intake is regulated by a network of signals that emanate from the gut and the brainstem. The peripheral satiety signal cholecystokinin is released from the gut following food intake and acts on fibers of the vagus nerve, which project to the brainstem and activate neurons that modulate both gastrointestinal function and appetite. In this study, we found that neurons in the nucleus tractus solitarii of the brainstem that express prolactin-releasing peptide (PrRP) are activated rapidly by food ingestion. To further examine the role of this peptide in the control of food intake and energy metabolism, we generated PrRP-deficient mice and found that they displayed late-onset obesity and adiposity, phenotypes that reflected an increase in meal size, hyperphagia, and attenuated responses to the anorexigenic signals cholecystokinin and leptin. Hypothalamic expression of 6 other appetite-regulating peptides remained unchanged in the PrRP-deficient mice. Blockade of endogenous PrRP signaling in WT rats by central injection of PrRP-specific mAb resulted in an increase in food intake, as reflected by an increase in meal size. These data suggest that PrRP relays satiety signals within the brain and that selective disturbance of this system can result in obesity and associated metabolic disorders.
Community-Based Screening for Diabetes in Michigan
Authors: Bahman P. Tabaei, Ray Burke, Ann Constance, Jean Hare, Glenda May-Aldrich, Sandra A. Parker, Ann Scott, Anne Stys, Jean Chickering, William H. Herman
Journal: Diabetes Care (2003)

OBJECTIVE—To describe and evaluate a community-based diabetes screening program supported by the Michigan Department of Community Health. RESEARCH DESIGN AND METHODS—Between 1 June 1999 and 31 December 1999, community screening for diabetes was conducted by voluntary organizations using a standard protocol, American Diabetes Association (ADA) questionnaires, and ADA capillary plasma glucose criteria. RESULTS—A total of 3,506 individuals were screened, 14% of whom did not meet criteria for screening. Of the 3,031 individuals appropriately screened, 57% were classified as being at high risk based on the ADA questionnaire and 5% had positive screening tests based on ADA capillary plasma glucose criteria. Despite systematic follow-up, the screening program’s yield of individuals with undiagnosed diabetes was &amp;lt;1%. CONCLUSIONS—Community screening for diabetes conducted according to ADA recommendations was extremely inefficient at identifying individuals with undiagnosed diabetes. The ADA diabetes screening questionnaire resulted in many false positive tests, and the ADA criteria for positive plasma glucose tests likely missed a substantial portion of individuals with undiagnosed diabetes. Relying on biochemical tests such as random plasma glucose, changing the criteria for a positive plasma glucose test, targeting racial and ethnic minority groups, and targeting medically underserved individuals might improve the yield of community-based diabetes screening.
The JAMA Peer Review Report for 2001
Authors: Elaine S. Williams
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Leptospira Outer Membrane Protein LipL32 Induces Tubulointerstitial Nephritis-Mediated Gene Expression in Mouse Proximal Tubule Cells
Authors: Chih-Wei Yang, Mai-Szu Wu, Ming-Jeng Pan, Wang-Ju Hsieh, Alain Vandewalle, Chiu-Ching Huang
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Tubulointerstitial nephritis is a main renal manifestation caused by pathogenic leptospira that accumulate mostly in the proximal tubules, thereby inducing tubular injury and tubulointerstitial nephritis. To elucidate the role of leptospira outer membrane proteins in tubulointerstitial nephritis, outer membrane proteins from pathogenic Leptospira shermani and nonpathogenic Leptospira patoc extracted by Triton X-114 were administered to cultured mouse proximal tubule cells. A dose-dependent increase of monocyte chemoattractant protein–1 (MCP-1), RANTES, nitrite, and tumor necrosis factor–α (TNF-α) in the culture supernatant was observed 48 h after incubating Leptospira shermani outer membrane proteins with mouse proximal tubule cells. RT competitive-PCR experiments showed that Leptospira shermani outer membrane proteins (0.2 μg/ml) increased the expression of MCP-1, nitric oxide synthase (iNOS), RANTES, and TNF-α mRNA by 3.0-, 9.4-, 2.5-, and 2.5-fold, respectively, when compared with untreated cells. Outer membrane proteins extract from avirulent Leptospira patoc did not induce significant effects. The pathogenic outer membrane proteins extract contain a major component of a 32-kD lipoprotein (LipL32), which is absent in the nonpathogenic leptospira outer membrane. An antibody raised against LipL32 prevented the stimulatory effect of Leptospira shermani outer membrane proteins extract on MCP-1 and iNOS mRNA expression in cultured proximal tubule cells, whereas recombinant LipL32 significantly stimulated the expression of MCP-1 and iNOS mRNAs and augmented nuclear binding of nuclear factor–κB (NF-κB) and AP-1 transcription factors in proximal tubule cells. An antibody raised against LipL32 also blunted the effects induced by the recombinant LipL32. This study demonstrates that LipL32 is a major component of pathogenic leptospira outer membrane proteins involved in the pathogenesis of tubulointerstitial nephritis.
The fine-scale architecture of structural variants in 17 mouse genomes
Authors: Binnaz Yalcin, Kim Wong, Amarjit Bhomra, Martin Goodson, Thomas M Keane, David J Adams, Jonathan Flint
Journal: Genome biology (2012)

Abstract Background Accurate catalogs of structural variants (SVs) in mammalian genomes are necessary to elucidate the potential mechanisms that drive SV formation and to assess their functional impact. Next generation sequencing methods for SV detection are an advance on array-based methods, but are almost exclusively limited to four basic types: deletions, insertions, inversions and copy number gains. Results By visual inspection of 100 Mbp of genome to which next generation sequence data from 17 inbred mouse strains had been aligned, we identify and interpret 21 paired-end mapping patterns, which we validate by PCR. These paired-end mapping patterns reveal a greater diversity and complexity in SVs than previously recognized. In addition, Sanger-based sequence analysis of 4,176 breakpoints at 261 SV sites reveal additional complexity at approximately a quarter of structural variants analyzed. We find micro-deletions and micro-insertions at SV breakpoints, ranging from 1 to 107 bp, and SNPs that extend breakpoint micro-homology and may catalyze SV formation. Conclusions An integrative approach using experimental analyses to train computational SV calling is essential for the accurate resolution of the architecture of SVs. We find considerable complexity in SV formation; about a quarter of SVs in the mouse are composed of a complex mixture of deletion, insertion, inversion and copy number gain. Computational methods can be adapted to identify most paired-end mapping patterns.
The CXCL10/CXCR3 Axis Mediates Human Lung Mast Cell Migration to Asthmatic Airway Smooth Muscle
Authors: Christopher E. Brightling, Alaina J. Ammit, Davinder Kaur, Judith L. Black, Andrew J. Wardlaw, J. Margaret Hughes, Peter Bradding
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Mast cell microlocalization within the airway smooth muscle bundle is an important determinant of the asthmatic phenotype. We hypothesized that mast cells migrate toward airway smooth muscle in response to smooth muscle-derived chemokines. In this study, we investigated (1) chemokine receptor expression by mast cells in the airway smooth muscle bundle in bronchial biopsies from subjects with asthma using immunohistology, (2) the concentration of chemokines in supernatants from stimulated ex vivo airway smooth muscle cells from subjects with and without asthma measured by enzyme-linked immunosorbent assay, and (3) mast cell migration toward these supernatants using chemotaxis assays. We found that CXCR3 was the most abundantly expressed chemokine receptor on human lung mast cells in the airway smooth muscle in asthma and was expressed by 100% of these mast cells compared with 47% of mast cells in the submucosa. Human lung mast cell migration was induced by airway smooth muscle cultures predominantly through activation of CXCR3. Most importantly, CXCL10 was expressed preferentially by asthmatic airway smooth muscle in bronchial biopsies and ex vivo cells compared with those from healthy control subjects. These results suggest that inhibition of the CXCL10/CXCR3 axis offers a novel target for the treatment of asthma.
Progression-Free Survival Is a Surrogate for Survival in Advanced Colorectal Cancer
Authors: Marc Buyse, Tomasz Burzykowski, Kevin Carroll, Stefan Michiels, Daniel J. Sargent, Langdon L. Miller, Gary L. Elfring, Jean-Pierre Pignon, Pascal Piedbois
Journal: Journal of Clinical Oncology (2007)

The traditional end point for assessing efficacy of first-line chemotherapies for advanced cancer is overall survival (OS), but this end point requires prolonged follow-up and is potentially confounded by the effects of second-line therapies. We investigated whether progression-free survival (PFS) could be considered a valid surrogate for OS in advanced colorectal cancer.Individual patient data were available from 10 historical trials comparing fluouracil (FU) + leucovorin with either FU alone (1,744 patients) or with raltitrexed (1,345 patients) and from three validation trials comparing FU + leucovorin with or without irinotecan or oxaliplatin (1,263 patients). Correlation coefficients were estimated in historical trials between the end points of PFS and OS, and between the treatment effects on these end points. Treatment effects on OS were predicted in validation trials, and compared with the observed effects.In historical trials, 1,760 patients (57%) had progressed or died at 6 months, and 1,622 (52%) had died at 12 months. The rank correlation coefficient between PFS and OS was equal to 0.82 (95% CI, 0.82 to 0.83). The correlation coefficient between treatment effects on PFS and on OS ranged from 0.99 (95% CI, 0.94 to 1.04) when all trials were considered to 0.74 (95% CI, 0.44 to 1.04) after exclusion of one highly influential trial. In the validation trials, the observed OS hazard ratios were within the 95% prediction intervals. A hazard ratio of 0.77 or lower in terms of PFS would predict a benefit in terms of OS.PFS is an acceptable surrogate for OS in advanced colorectal cancer.
The Clinical Profile and Pathophysiology of Atrial Fibrillation
Authors: Jason Andrade, Paul Khairy, Dobromir Dobrev, Stanley Nattel
Journal: Circulation Research (2014)

Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%–26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca 2+ -handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca 2+ -handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management.