tbuckley/cabot-search huggingface dataset:
Enhanced Expression of Leptin and Leptin Receptor (OB-R) in Human Breast Cancer
Authors: Makoto Ishikawa, Joji Kitayama, Hirokazu Nagawa
Journal: Clinical Cancer Research (2004)

To evaluate leptin and leptin receptor (OB-R) expression in human breast cancer and determine whether it could be effective for the prevention and treatment of breast cancer.Immunohistochemical staining using specific antibodies was used to evaluate the protein expression of leptin and OB-R in 76 invasive ductal carcinomas and 32 samples of corresponding normal mammary gland, and the relationship between the expression of OB-R and leptin and clinicopathological features was analyzed.Normal mammary epithelial cells did not express a significant level of Ob-R, whereas carcinoma cells showed positive staining for OB-R in 63 (83%) cases. Both normal epithelial cells and carcinoma cells expressed a significant level of leptin. However, overexpression of leptin, as determined by staining intensity, was observed in 70 cancers (92%) but in no normal epithelium. The expression of OB-R showed a significant correlation with the level of leptin expression. Interestingly, distant metastasis was detected in 21 (34%) of 61 OB-R-positive tumors with leptin overexpression, but in none of the 15 tumors that lacked OB-R expression or leptin overexpression (P < 0.05). Consequently, patients with the former tumors showed significantly lower survival than those with the latter.Leptin may have a promoting effect on the carcinogenesis and metastasis of breast cancer, possibly in an autocrine manner. Functional inhibition of leptin may be effective for the prevention and treatment of breast cancer.
Alick Mitchell Reid
Authors: W. L. M. B. D. A. W. Reid
Journal: BMJ (2014)

Alick Mitchell Reid trained in anaesthesia at Edinburgh Royal Infirmary under John Gillies in 1951. He returned to Glasgow in 1957 to become a lecturer in the university department of anaesthesia at the Royal Infirmary and two years later was appointed consultant at that hospital.

An enthusiastic teacher, he became an honorary clinical senior lecturer …
Sildenafil is useful in pulmonary arterial hypertension
Authors: R L Karadi
Journal: Thorax (2006)

▴ Galiè N, Ghofrani HA, Torbicki A, et al . Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med2005;353:2148–57 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Many recent studies, most of them uncontrolled trials, suggest that sildenafil may be beneficial in the treatment of pulmonary arterial hypertension (PAH). A multicentre, double blind, placebo controlled study was performed in 278 patients with symptomatic PAH (either idiopathic, … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DGalie%26rft.auinit1%253DN.%26rft.volume%253D353%26rft.issue%253D20%26rft.spage%253D2148%26rft.epage%253D2157%26rft.atitle%253DSildenafil%2BCitrate%2BTherapy%2Bfor%2BPulmonary%2BArterial%2BHypertension%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa050010%26rft_id%253Dinfo%253Apmid%252F16291984%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa050010&link_type=DOI [3]: /lookup/external-ref?access_num=16291984&link_type=MED&atom=%2Fthoraxjnl%2F61%2F2%2F176.atom [4]: /lookup/external-ref?access_num=000233288600007&link_type=ISI
Subvesical Diathermy Prostatectomy
Authors: R. O. Ward
Journal: BMJ (1938)

I have endeavoured in this article to formulate those principles which seem to me fuLndamental, and to demon- strate that in practice they can be effective. ConclusionsThe principles for the conduct of an epidemic of measles in a self-contained school community are dis- cussed, and their application in practice is illustrated in four epidemics.These principles are:1.That healthy susceptible individuals should be permitted to experience a normal attack of measles after exposure to infection.2. That "delicate susceptibles" should be protected."Delicate susceptibles " fall into two categories: (a) those for whom complete " protection " should be secured; (b) those for whom "'attenuation " should be a sufficient safeguard from undue risks.3. That environmental hygiene must be strictly practised in sick-rooms for all cases.Experiences in the use of protective serum are des.ribedand emphasis is laid upon the inherent diffi- culties of posology.In practice the date of administration should be calculated from the rash of the infecting case.For protecUtioti a maximum dose should be given at the earliest opportunity after exposure and never later than the third day.For attentuatiotn a maximum dose should be given on the sixth day.
Loss of Heterozygosity and Its Correlation with Expression Profiles in Subclasses of Invasive Breast Cancers
Authors: Zhigang C. Wang, Ming Lin, Lee-Jen Wei, Cheng Li, Alexander Miron, Gabriella Lodeiro, Lyndsay Harris, Sridhar Ramaswamy, David M. Tanenbaum, Matthew Meyerson, James D. Iglehart, Andrea Richardson
Journal: Cancer Research (2004)

Abstract Gene expression array profiles identify subclasses of breast cancers with different clinical outcomes and different molecular features. The present study attempted to correlate genomic alterations (loss of heterozygosity; LOH) with subclasses of breast cancers having distinct gene expression signatures. Hierarchical clustering of expression array data from 89 invasive breast cancers identified four major expression subclasses. Thirty-four of these cases representative of the four subclasses were microdissected and allelotyped using genome-wide single nucleotide polymorphism detection arrays (Affymetrix, Inc.). LOH was determined by comparing tumor and normal single nucleotide polymorphism allelotypes. A newly developed statistical tool was used to determine the chromosomal regions of frequent LOH. We found that breast cancers were highly heterogeneous, with the proportion of LOH ranging widely from 0.3% to &amp;gt;60% of heterozygous markers. The most common sites of LOH were on 17p, 17q, 16q, 11q, and 14q, sites reported in previous LOH studies. Signature LOH events were discovered in certain expression subclasses. Unique regions of LOH on 5q and 4p marked a subclass of breast cancers with “basal-like” expression profiles, distinct from other subclasses. LOH on 1p and 16q occurred preferentially in a subclass of estrogen receptor-positive breast cancers. Finding unique LOH patterns in different groups of breast cancer, in part defined by expression signatures, adds confidence to newer schemes of molecular classification. Furthermore, exclusive association between biological subclasses and restricted LOH events provides rationale to search for targeted genes.
Should same anaesthetist do preoperative anaesthetic visit and give subsequent anaesthetic? Questionnaire survey of anaesthetists
Authors: B. Simini
Journal: BMJ (2003)

value to dichotomise patients into those with preserved ( ≥ 50%) and those with impaired ( < 50%) function. 4 In all, 522 patients had adequate measurements of ejection fraction, of whom 163 (31%) had values ≥ 50% and 359 (69%) < 50%.Information on deaths was recorded to April 2000, allowing five year survival status to be determined for all patients.The table shows the characteristics of the two groups and statistical methods.Five year mortality was substantial in both groups but significantly greater in patients with impaired left ventricular systolic function (41.5% v 25.2%, P < 0.001).Twenty five per cent of patients with preserved function had non-sustained ventricular tachycardia.Both groups had similar SDNN measurements, which were lower than previously shown in age matched healthy control subjects. 5
High serum levels of TNF-α and IL-6 predict the clinical outcome of treatment with human recombinant erythropoietin in anaemic cancer patients
Authors: I Pavese, F Satta, F Todi, M Di Palma, P Piergrossi, A Migliore, P Piselli, R Borghesi, G Mancino, E Brunetti, A Alimonti
Journal: Annals of Oncology (2009)
A Novel Mutation of LAMB2 in a Multigenerational Mennonite Family Reveals a New Phenotypic Variant of Pierson Syndrome
Authors: Brian G. Mohney, Jose S. Pulido, Noralane M. Lindor, Marie C. Hogan, Mark B. Consugar, Justin Peters, V. Shane Pankratz, Samih H. Nasr, Stephen J. Smith, James Gloor, Vickie Kubly, Dorothy Spencer, Rebecca Nielson, Erik G. Puffenberger, Kevin A. Strauss, D. Holmes Morton, Lama Eldahdah, Peter C. Harris
Journal: Ophthalmology (2011)
Association of TLR7 copy number variation with susceptibility to childhood-onset systemic lupus erythematosus in Mexican population
Authors: H. Garcia-Ortiz, R. Velazquez-Cruz, F. Espinosa-Rosales, S. Jimenez-Morales, V. Baca, L. Orozco
Journal: Annals of the Rheumatic Diseases (2010)

Objective Variations in gene copy number (CNV) have been recognised as a hereditable source of susceptibility in human complex diseases. Recent studies have shown that Tlr7 gene dosage has a significant contribution in the autoimmune-enhancing effect in mouse models of systemic lupus erythematosus (SLE). A study was therefore performed to investigate whether CNVs in TLR7 contribute to the genetic component of childhood-onset SLE. Methods A case–control association study was performed in 328 Mexican children with SLE and 403 healthy controls. Determination of CNVs of TLR7 was achieved by real-time PCR using the ΔΔCt method. Expression levels of TLR7 and interferon α ( IFNα ) were determined in 23 patients. In addition, a stratification analysis was performed to investigate the association of TLR7 gene copy number (CN) with lupus nephritis. Results A significant increase was found in the relative TLR7 gene CN in females patients with SLE compared with female controls (p<0.0001). However, logistic regression analysis by gender showed a higher OR (OR 6.61, p=0.005) in male patients with >1 copy of TLR7 than in female patients with >2 copies (OR 3.07, p<0.0001). This association was not observed with lupus nephritis. TLR7 mRNA levels correlated significantly with TLR7 CN and with IFNα mRNA levels. Conclusion These results show that an increase in TLR7 CN is a risk factor for childhood-onset SLE and provide new evidence for a role for X-linked gene dosage in SLE susceptibility. There is also evidence to suggest that TLR7 may be involved in the pathogenesis of SLE through the induction of IFNα .
Soluble Klotho Protects against Uremic Cardiomyopathy Independently of Fibroblast Growth Factor 23 and Phosphate
Authors: Jian Xie, Joonho Yoon, Sung-Wan An, Makoto Kuro-o, Chou-Long Huang
Journal: Journal of the American Society of Nephrology (2014)

Cardiac hypertrophy occurs in up to 95% of patients with CKD and increases their risk for cardiovascular death. In the kidney, full-length membranous Klotho forms the coreceptor for fibroblast growth factor 23 (FGF23) to regulate phosphate metabolism. The prevailing view is that the decreased level of Klotho in CKD causes cardiomyopathy through increases in serum FGF23 and/or phosphate levels. However, we reported recently that soluble Klotho protects against cardiac hypertrophy by inhibiting abnormal calcium signaling in the heart. Here, we tested whether this protective effect requires changes in FGF23 and/or phosphate levels. Heterozygous Klotho-deficient CKD mice exhibited aggravated cardiac hypertrophy compared with wild-type CKD mice. Cardiac magnetic resonance imaging studies revealed that Klotho-deficient CKD hearts had worse functional impairment than wild-type CKD hearts. Normalization of serum phosphate and FGF23 levels by dietary phosphate restriction did not abrogate the aggravated cardiac hypertrophy observed in Klotho-deficient CKD mice. Circulating levels of the cleaved soluble ectodomain of Klotho were lower in wild-type CKD mice than in control mice and even lower in Klotho-deficient CKD mice. Intravenous delivery of a transgene encoding soluble Klotho ameliorated cardiac hypertrophy in Klotho-deficient CKD mice. These results suggest that the decreased level of circulating soluble Klotho in CKD is an important cause of uremic cardiomyopathy independent of FGF23 and phosphate, opening new avenues for treatment of this disease.
Molecular dissection of cardiac repolarization by in vivo Kv4.3 gene transfer
Authors: Uta C. Hoppe, Eduardo Marbán, David C. Johns
Journal: Journal of Clinical Investigation (2000)

Heart failure leads to marked suppression of the Ca2+-independent transient outward current (Ito1), but it is not clear whether Ito1 downregulation suffices to explain the concomitant action potential prolongation. To investigate the role of Ito1 in cardiac repolarization while circumventing culture-related action potential alterations, we injected adenovirus vectors in vivo to overexpress or to suppress Ito1 in guinea pigs and rats, respectively. Myocytes were isolated 72 hours after intramyocardial injection and stimulation of the ecdysone-inducible vectors with intraperitoneal injection of an ecdysone analog. Kv4.3-infected guinea pig myocytes exhibited robust transient outward currents. Increasing density of Ito1 progressively depressed the plateau potential in Kv4.3-infected guinea pig myocytes and abbreviated action potential duration (APD). In vivo infection with a dominant-negative Kv4.3-W362F construct suppressed peak Ito1 in rat ventriculocytes, elevated the plateau height, significantly prolonged the APD, and resulted in a prolongation by about 30% of the QT interval in surface electrocardiogram recordings. These results indicate that Ito1 plays a crucial role in setting the plateau potential and overall APD, supporting a causative role for suppression of this current in the electrophysiological alterations of heart failure. The electrocardiographic findings indicate that somatic gene transfer can be used to create gene-specific animal models of the long QT syndrome.
On the Use of Artificial Respiration and Transfusion as a Means of Preserving Life
Authors: T. L. Brunton
Journal: BMJ (1873)

were a slight hardness and fulness in a situation corresponding to that of the tumour on the right side, and deeper in could be felt some very small nodules of har(lenied glands.The larynx was slightly thrust towards the left side h but no (leep-seated tumour which could produce this was detected, and the tumour on the sterno-mastoid certainly did not pass inwards sufficiently to account for it.The patient's great distress arose from his dyspncea, which at times, especially when he lay down, was very urgent, while at other times he was comparatively easy.The re- spiration was always croupous, and the noise was such as to keep him- * Fontana, Traits sur le vinins de la vi,z?re, szsr ieshSoiso,s Ams'ricains, sur le
EASL- and mRECIST-Evaluated Responses to Combination Therapy of Sorafenib with Transarterial Chemoembolization Predict Survival in Patients with Hepatocellular Carcinoma
Authors: Lei Liu, Weijuan Wang, Hui Chen, Yan Zhao, Wei Bai, Zhanxin Yin, Chuangye He, Jia Jia, Man Yang, Jielai Xia, Daiming Fan, Guohong Han
Journal: Clinical Cancer Research (2014)

Published studies have not investigated the suitability of Response Evaluation Criteria in Solid Tumors (RECIST), European Association for the Study of the Liver (EASL) criteria, and modified RECIST (mRECIST) for assessing the response of patients with hepatocellular carcinoma to treatment with sorafenib combined with transarterial chemoembolization. Here, we aimed to define the earliest time at which the response to combination therapy could be accurately assessed and validate the prognostic value of these criteria at this early posttherapy time point.A total of 114 consecutive patients with hepatocellular carcinoma receiving combination therapy were retrospectively enrolled. The therapy response at different time points was assessed using RECIST, EASL, and mRECIST. Cox regression analysis and Kaplan-Meier curves were used to assess overall survival (OS) in the responders and nonresponders.At the third follow-up (median, 94 days; range, 89-102 days) after therapy, the response rates obtained using EASL (50.6%) and mRECIST (51.6%) were greater than that obtained using RECIST (16.5%). The agreement was strong between the mRECIST and EASL results (k = 0.9) but weak between mRECIST and RECIST (k = 0.3). The EASL and mRECIST responses significantly correlated with survival. Risk reductions of 52% and 50% were observed for EASL and mRECIST responders, respectively, compared with nonresponders. However, no significant association between the treatment response and survival was observed using RECIST.The earliest time to evaluate the response to combination therapy is 3 months (median, 94 days) after therapy. EASL and mRECIST responses are independent predictors for OS at this early time point.
Metabolic-network-driven analysis of bacterial ecological strategies
Authors: Shiri Freilich, Anat Kreimer, Elhanan Borenstein, Nir Yosef, Roded Sharan, Uri Gophna, Eytan Ruppin
Journal: Genome biology (2009)

Abstract Background The growth-rate of an organism is an important phenotypic trait, directly affecting its ability to survive in a given environment. Here we present the first large scale computational study of the association between ecological strategies and growth rate across 113 bacterial species, occupying a variety of metabolic habitats. Genomic data are used to reconstruct the species' metabolic networks and habitable metabolic environments. These reconstructions are then used to investigate the typical ecological strategies taken by organisms in terms of two basic species-specific measures: metabolic variability - the ability of a species to survive in a variety of different environments; and co-habitation score vector - the distribution of other species that co-inhabit each environment. Results We find that growth rate is significantly correlated with metabolic variability and the level of co-habitation (that is, competition) encountered by an organism. Most bacterial organisms adopt one of two main ecological strategies: a specialized niche with little co-habitation, associated with a typically slow rate of growth; or ecological diversity with intense co-habitation, associated with a typically fast rate of growth. Conclusions The pattern observed suggests a universal principle where metabolic flexibility is associated with a need to grow fast, possibly in the face of competition. This new ability to produce a quantitative description of the growth rate-metabolism-community relationship lays a computational foundation for the study of a variety of aspects of the communal metabolic life.
A mutant human histocompatibility leukocyte antigen DR molecule associated with invariant chain peptides.
Authors: E Mellins, P Cameron, M Amaya, S Goodman, D Pious, L Smith, B Arp
Journal: The Journal of Experimental Medicine (1994)

From a human histocompatibility leukocyte antigen (HLA)-DR/DQ hemizygous, B lymphoblastoid progenitor, we isolated a cell line, 10.24.6, with a DR alpha missense mutation (96P--&amp;gt;96S), which results in an N-linked carbohydrate addition at position 94 in the DR alpha 2 domain. Several features of 10.24.6 cells suggest that the mutation disrupts normal intracellular formation of peptide/DR complexes. The mutant HLA-DR dimers, though expressed at the cell surface, lack the conformation of the mature, peptide-loaded class II molecules of the progenitor cell, as assessed by their loss of binding of certain antibodies and by the lack of stability in detergent (sodium dodecyl sulfate) solution. In addition, presentation of endocytosed antigen to HLA-DR-restricted T cells is defective in the mutant, but can be restored by transfection of a wild type DRA gene. Assays with synthetic peptides indicate that the 10.24.6 phenotype is not due to an intrinsic inability of the mutant DR molecules to bind peptides. Therefore, to directly evaluate peptide occupancy of the mutant molecules, we analyzed acid-eluted, HLA-DR-associated peptides. The predominant species from the 10.24.6 mutant is a nested set of invariant chain (Ii)-derived peptides that are undetectable in the DR eluate from progenitor cells. The region of DR alpha altered in the mutant molecules is thus implicated in normal formation of peptide/DR complexes. Further, the same set of Ii peptides associated with the DR molecules is present in the eluate from an antigen presentation mutant with a defect in an major histocompatibility complex (MHC)-linked gene. These results suggest that DR molecules in 10.24.6 and in certain presentation mutants are affected at the same or related steps in class II molecule biosynthesis, raising the possibility that class II molecules interact with an MHC-encoded accessory molecule during antigen presentation.
Masked Hypertension Associates with Left Ventricular Hypertrophy in Children with CKD
Authors: Mark Mitsnefes, Joseph Flynn, Silvia Cohn, Joshua Samuels, Tom Blydt-Hansen, Jeffrey Saland, Thomas Kimball, Susan Furth, Bradley Warady
Journal: Journal of the American Society of Nephrology (2009)

Left ventricular hypertrophy (LVH) associates with increased risk for cardiovascular disease. Hypertension leads to LVH in adults, but its role in the pathogenesis of LVH in children is not as well established. To examine left ventricular mass and evaluate factors associated with LVH in children with stages 2 through 4 chronic kidney disease (CKD), we analyzed cross-sectional data from children who had baseline echocardiography (n = 366) and underwent ambulatory BP monitoring (n = 226) as a part of the observational Chronic Kidney Disease in Children (CKiD) cohort study. At baseline, 17% of children had LVH (11% eccentric and 6% concentric) and 9% had concentric remodeling of the left ventricle. On the basis of a combination of ambulatory and casual BP assessment (n = 198), 38% of children had masked hypertension (normal casual but elevated ambulatory BP) and 18% had confirmed hypertension (both elevated casual and ambulatory BP). There was no significant association between LVH and kidney function. LVH was more common in children with either confirmed (34%) or masked (20%) hypertension compared with children with normal casual and ambulatory BP (8%). In multivariable analysis, masked (odds ratio 4.1) and confirmed (odds ratio 4.3) hypertension were the strongest independent predictors of LVH. In conclusion, casual BP measurements alone are insufficient to predict the presence of LVH in children with CKD. The high prevalence of masked hypertension and its association with LVH supports early echocardiography and ambulatory BP monitoring to evaluate cardiovascular risk in children with CKD.