tbuckley/cabot-search huggingface dataset:
Quantitative Measurement of Epidermal Growth Factor Receptor Is a Negative Predictive Factor for Tamoxifen Response in Hormone Receptor–Positive Premenopausal Breast Cancer
Authors: Jennifer M. Giltnane, Lisa Rydén, Melissa Cregger, Pär-Ola Bendahl, Karin Jirström, David L. Rimm
Journal: Journal of Clinical Oncology (2007)

Although there is evidence for interaction between epidermal growth factor receptor (EGFR) and estrogen receptor (ER), it is still not clear how this affects response to endocrine therapies like tamoxifen. Here we assess the relationship between EGFR expression and tamoxifen response, with a new quantitative technology.A tissue microarray was constructed from breast cancer from a cohort of 564 patients enrolled in a randomized clinical trial for adjuvant tamoxifen treatment in early breast cancer, with a median follow-up of 14 years. EGFR expression was measured using automated quantitative analysis, a fluorescence-based method for quantitative analysis of in situ protein expression.In ER-positive patients, tamoxifen-treated patients with low EGFR expression (n = 113) showed a significant effect by 2 years of adjuvant tamoxifen (P = .01), in contrast to no treatment effect in the EGFR-high group (n = 73, P = .69). The untreated group showed 49% v 57% 10-year recurrence-free survival for EGFR low versus high (P = .466) in the corresponding group of ER-positive patients. A significant beneficial effect of tamoxifen treatment was seen in the EGFR-low group (hazard ratio [HR] = 0.43 (95% CI, 0.22 to 0.84; P = .013) in contrast to no effect in the EGFR-high group (HR = 1.14; 95% CI, 0.59 to 2.22; P = .7) by using a Cox model.This study provides clinical evidence that confirms the basic work that has shown high EGFR can indicate resistance to tamoxifen. It suggests that careful measurement of EGFR protein expression might define a subset of low-stage patients that could benefit from an alternative therapy.
Osteoclast differentiation independent of the TRANCE–RANK–TRAF6 axis
Authors: Nacksung Kim, Yuho Kadono, Masamichi Takami, Junwon Lee, Seoung-Hoon Lee, Fumihiko Okada, Jung Ha Kim, Takashi Kobayashi, Paul R. Odgren, Hiroyasu Nakano, Wen-Chen Yeh, Sun-Kyeong Lee, Joseph A. Lorenzo, Yongwon Choi
Journal: The Journal of Experimental Medicine (2005)

Osteoclasts are derived from myeloid lineage cells, and their differentiation is supported by various osteotropic factors, including the tumor necrosis factor (TNF) family member TNF-related activation-induced cytokine (TRANCE). Genetic deletion of TRANCE or its receptor, receptor activator of nuclear factor κB (RANK), results in severely osteopetrotic mice with no osteoclasts in their bones. TNF receptor-associated factor (TRAF) 6 is a key signaling adaptor for RANK, and its deficiency leads to similar osteopetrosis. Hence, the current paradigm holds that TRANCE–RANK interaction and subsequent signaling via TRAF6 are essential for the generation of functional osteoclasts. Surprisingly, we show that hematopoietic precursors from TRANCE-, RANK-, or TRAF6-null mice can become osteoclasts in vitro when they are stimulated with TNF-α in the presence of cofactors such as TGF-β. We provide direct evidence against the current paradigm that the TRANCE–RANK–TRAF6 pathway is essential for osteoclast differentiation and suggest the potential existence of alternative routes for osteoclast differentiation.
Unusual Amoebic Liver Abscess
Authors: J. A. M. Cameron
Journal: BMJ (1943)

MEDICAS JRNL329in the rat (Reiss, MacLeod, and Golla, 1943) have shown that corticotrophic hormone, by mobilizing an endogenous supply of adrenal cortical hormones, can similarly influence the capillary permeability and effectively prevent the loss of blood fluid.The haematocrit alone can give a differential diagnosis of the state and fate of the fluid components of the blood.
Immune-driven adaptation of hepatitis B virus genotype D involves preferential alteration in B-cell epitopes and replicative attenuation—an insight from human immunodeficiency virus/hepatitis B virus coinfection
Authors: R.K. Mondal, M. Khatun, S. Ghosh, P. Banerjee, S. Datta, S. Sarkar, B. Saha, A. Santra, S. Banerjee, A. Chowdhury, S. Datta
Journal: Clinical Microbiology and Infection (2015)

An important driving force behind the sequence diversity of hepatitis B virus (HBV) is viral adaptation to host immune responses. To gain an insight into the impact of host immunity on genetic diversification and properties of HBV, we characterized HBV of genotype D from treatment-naive hepatitis B e antigen-positive (EP) and hepatitis B e antigen-negative (EN) patients with chronic hepatitis B (CHB), where HBV is under stronger immune pressure, with that of HBV derived from human immunodeficiency virus (HIV)/HBV-coinfected individuals, where HIV infection has significantly weakened the immune system. Full-length sequence analysis showed that HBV heterogeneity was most extensive in EN-CHB followed by EP-CHB and HIV/HBV coinfection. The relative magnitude of non-synonymous changes within B-cell epitopes was greater than that in T-cell epitopes of HBV open reading frames (ORFs) in both EP-CHB and EN-CHB. Nine amino acid substitutions were identified in B-cell epitopes and one in a T-cell epitope of HBV in EN-CHB, most of which resulted in altered hydrophobicities, as determined using the Kyte and Doolittle method, relative to wild-type residues found in HBV from the HIV-positive group. Additionally, 19 substitutions occurred at significantly higher frequencies in non-epitope regions of HBV ORF-P in EN-CHB than HIV/HBV-coinfected patients. In vitro replication assay demonstrated that the substitutions, particularly in reverse transcriptase and RNaseH domains of ORF-P, resulted in a decline in replication capacity of HBV. Hence, our results indicate that HBV adapts to increasing immune pressure through preferential mutations in B-cell epitopes and by replicative attenuation. The viral epitopes linked to immune response identified in this study bear important implications for future HBV vaccine studies.
St. Mary's Hospital, Paddington
Authors: V. Z. Cope
Journal: BMJ (1951)

One hundred years ago last month, in the year of the Great Exhibition of 1851, St. Mary's Hospital, Padding- ton, first opened its doors to receive patients.When the Great Western Railway built Paddington Station in 1838 the population of the adjacent suburbs of Paddington Prince Albert laying the foundation-stone of St. Mary's Hospital.and Marylebone was rapidly mounting towards the second hundred thousand, yet the nearest hospitals were St. George's south of Hyde Park and the Middlesex at the other side of Marylebone.In 1843 a committee of local inhabitants set on foot the project for a new hospital, which was to be situated near the terminus of the railway.The Lords Beverley and Manvers were prominent members of the committee which col- lected funds and arranged for the formal laying of the foundation-stone.This was performed on June 28, 1845, by Prince Albert, who gave permission for one of the wards in the projected hos- pital to be named after him.A large company assembled under a marquee "which prevented those assembled from being incommoded and annoyed by the showers and the continual gusts of wind."Within a cavity in the founda- tion-stone the Prince deposited a written record of the event and a bottle containing coins and other objects.The Times
[769] IRON DEPLETION BY PHLEBOTOMY IMPROVES INSULIN RESISTANCE IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE AND HYPERFERRITINEMIA; EVIDENCE FROM A CASE CONTROL STUDY
Authors: L. Valenti, A.L. Fracanzani, P. Dongiovanni, E. Bugianesi, E. Vanni, G. Marches, S. Fargion
Journal: Journal of Hepatology (2007)
Reciprocal Regulation of MicroRNA-1 and Insulin-Like Growth Factor-1 Signal Transduction Cascade in Cardiac and Skeletal Muscle in Physiological and Pathological Conditions
Authors: Leonardo Elia, Riccardo Contu, Manuela Quintavalle, Francesca Varrone, Cristina Chimenti, Matteo Antonio Russo, Vincenzo Cimino, Laura De Marinis, Andrea Frustaci, Daniele Catalucci, Gianluigi Condorelli
Journal: Circulation (2009)

Background— MicroRNAs (miRNAs/miRs) are small conserved RNA molecules of 22 nucleotides that negatively modulate gene expression primarily through base paring to the 3′ untranslated region of target messenger RNAs. The muscle-specific miR-1 has been implicated in cardiac hypertrophy, heart development, cardiac stem cell differentiation, and arrhythmias through targeting of regulatory proteins. In this study, we investigated the molecular mechanisms through which miR-1 intervenes in regulation of muscle cell growth and differentiation. Methods and Results— On the basis of bioinformatics tools, biochemical assays, and in vivo models, we demonstrate that (1) insulin-like growth factor-1 (IGF-1) and IGF-1 receptor are targets of miR-1; (2) miR-1 and IGF-1 protein levels are correlated inversely in models of cardiac hypertrophy and failure as well as in the C2C12 skeletal muscle cell model of differentiation; (3) the activation state of the IGF-1 signal transduction cascade reciprocally regulates miR-1 expression through the Foxo3a transcription factor; and (4) miR-1 expression correlates inversely with cardiac mass and thickness in myocardial biopsies of acromegalic patients, in which IGF-1 is overproduced after aberrant synthesis of growth hormone. Conclusions— Our results reveal a critical role of miR-1 in mediating the effects of the IGF-1 pathway and demonstrate a feedback loop between miR-1 expression and the IGF-1 signal transduction cascade.
Non-tuberculous mycobacteria in patients with bronchiectasis
Authors: M Wickremasinghe
Journal: Thorax (2005)

<b>Background:</b> Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms. Patients with pre-existing lung damage are susceptible to NTM, but their prevalence in bronchiectasis is unknown. Distinguishing between lung colonisation and disease can be difficult. <b>Methods:</b> A prospective study of 100 patients with bronchiectasis was undertaken to evaluate the prevalence of NTM in sputum, and a retrospective analysis of clinical, microbiological, lung function and radiology data of our clinic patients with NTM sputum isolates over 11 years was performed. <b>Results:</b> The prevalence of NTM in this population of patients with bronchiectasis was 2%. Patients in the retrospective study were divided into three groups: bronchiectasis + multiple NTM isolates (n = 25), bronchiectasis + single isolates (n = 23), and non-bronchiectasis + multiple isolates (n = 22). <i>Mycobacterium avium</i> complex (MAC) species predominated in patients with bronchiectasis compared with non-bronchiectasis lung disease (72% <i>v</i> 9%, p&lt;0.0001). Single isolates were also frequently MAC (45.5%). Multiple isolates in bronchiectasis were more often smear positive on first sample than single isolates (p&lt;0.0001). NTM were identified on routine screening samples or because of suggestive radiology. No particular bronchiectasis aetiology was associated with an NTM. <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> were frequently co-cultured. Six (25%) of multiple NTM patients had cavities of which five were due to MAC. Half the patients with multiple isolates were treated, mostly due to progressive radiology. <b>Conclusions:</b> NTM are uncommon in non-cystic fibrosis bronchiectasis. Routine screening identifies otherwise unsuspected patients. MAC is the most frequent NTM isolated.
Angiogenesis and Tumor Metastasis
Authors: Bruce R. Zetter
Journal: Annual Review of Medicine (1998)

Angiogenesis, the recruitment of new blood vessels, is an essential component of the metastatic pathway. These vessels provide the principal route by which tumor cells exit the primary tumor site and enter the circulation. For many tumors, the vascular density can provide a prognostic indicator of metastatic potential, with the highly vascular primary tumors having a higher incidence of metastasis than poorly vascular tumors. Tumor angiogenesis is regulated by the production of angiogenic stimulators including members of the fibroblast growth factor and vascular endothelial growth factor families. In addition, tumors may activate angiogenic inhibitors such as angiostatin and endostatin that can modulate angiogenesis both at the primary site and at downstream sites of metastasis. The potential use of these and other natural and synthetic angiogenic inhibitors as anticancer drugs is currently under intense investigation. Such agents may have reduced toxicity and be less likely to generate drug resistance than conventional cytotoxic drugs. Clinical trials are now underway to develop optimum treatment strategies for antiangiogenic agents.
Biological risk indicators for recurrent non-specific low back pain in adolescents
Authors: M A Jones, G Stratton, T Reilly, V B Unnithan
Journal: British Journal of Sports Medicine (2005)

A matched case-control study was carried out to evaluate biological risk indicators for recurrent non-specific low back pain in adolescents.Adolescents with recurrent non-specific low back pain (symptomatic; n = 28; mean (SD) age 14.9 (0.7) years) and matched controls (asymptomatic; n = 28; age 14.9 (0.7) years) with no history of non-specific low back pain participated. Measures of stature, mass, sitting height, sexual maturity (Tanner self assessment), lateral flexion of the spine, lumbar sagittal plane mobility (modified Schober), hip range of motion (Leighton flexometer), back and hamstring flexibility (sit and reach), and trunk muscle endurance (number of sit ups) were performed using standardised procedures with established reliability. Backward stepwise logistic regression analysis was performed, with the presence/absence of recurrent low back pain as the dependent variable and the biological measures as the independent variables.Hip range of motion, trunk muscle endurance, lumbar sagittal plane mobility, and lateral flexion of the spine were identified as significant risk indicators of recurrent low back pain (p<0.05). Follow up analysis indicated that symptomatic subjects had significantly reduced lateral flexion of the spine, lumbar sagittal plane mobility, and trunk muscle endurance (p<0.05).Hip range of motion, abdominal muscle endurance, lumbar flexibility, and lateral flexion of the spine were risk indicators for recurrent non-specific low back pain in a group of adolescents. These risk indicators identify the potential for exercise as a primary or secondary prevention method.
High Correlation of Whole-Body Red Fluorescent Protein Imaging and Magnetic Resonance Imaging on an Orthotopic Model of Pancreatic Cancer
Authors: Michael Bouvet, Joseph Spernyak, Matthew H. Katz, Richard V. Mazurchuk, Shinako Takimoto, Ralph Bernacki, Youcef M. Rustum, Abdool R. Moossa, Robert M. Hoffman
Journal: Cancer Research (2005)

Abstract We have developed genetically fluorescent orthotopic models of human pancreatic cancer. In these models, noninvasive fluorescent protein imaging (FPI) of internal primary tumors and metastatic deposits has been carried out. Whole-body tumor images are easily and inexpensively obtained using FPI, permitting both detection and quantification of tumor load. In this study, we simultaneously compared single mice with a highly fluorescent, red fluorescent protein–expressing orthotopic pancreatic cancer xenografts with both FPI and high-resolution magnetic resonance imaging (MRI). Images were acquired at multiple time points after tumor implantation in the pancreas. Indwelling pancreatic primary tumors and metastatic foci were detected by both FPI and MRI. Moreover, a strong correlation existed between images taken with these two technologies. FPI permitted rapid, high-throughput imaging without the need for either anesthesia or contrast agents. Both FPI and MRI enabled accurate imaging of tumor growth and metastasis, although MRI enabled tissue structure to be visualized as well. FPI has high resolution and is exceedingly rapid with instant image capture. We suggest a complimentary role for these two imaging modalities.
Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells
Authors: Jason M. Brenchley, Nitin J. Karandikar, Michael R. Betts, David R. Ambrozak, Brenna J. Hill, Laura E. Crotty, Joseph P. Casazza, Janaki Kuruppu, Stephen A. Migueles, Mark Connors, Mario Roederer, Daniel C. Douek, Richard A. Koup
Journal: Blood (2003)
Early Childhood Depression
Authors: Joan L. Luby
Journal: American Journal of Psychiatry (2009)

Although empirical evidence has recently validated clinical depression in children as young as age 3, few data are available to guide treatment of early childhood depression. Considering this gap in the literature, a novel dyadic psychotherapeutic model, Parent Child Interaction Therapy–Emotion Development, based on a well-known and effective manualized treatment for disruptive preschoolers, is currently being tested for use in depression. To balance safety and efficacy, dyadic developmental approaches are currently recommended as the first line of treatment for preschool depression. In the absence of data on the safety and efficacy of antidepressants in preschool depression, these agents are not recommended as a first- or second-line treatment at this time. This article provides an illustrative case example of preschool depression, outlines key considerations in differential diagnosis, and describes this novel form of treatment. It also clarifies parameters for the rare situations in which antidepressants may be tried when psychotherapeutic options fail and depression is severe and impairing.
CLCN5 chloride-channel mutations in six new North American families with X-linked nephrolithiasis
Authors: R R Hoopes, P A Hueber, R J Reid, G L Braden, P R Goodyer, A R Melnyk, J P Midgley, D I Moel, A M Neu, S K VanWhy, S J Scheinman
Journal: Kidney International (1998)
Intracellular Antimicrobial Activity in the Absence of Interferon-γ: Effect of Interleukin-12 in Experimental Visceral Leishmaniasis in Interferon-γ Gene-disrupted Mice
Authors: Alice P. Taylor, Henry W. Murray
Journal: The Journal of Experimental Medicine (1997)

Despite permitting uncontrolled intracellular visceral infection for 8 wk, interferon-γ (IFN-γ) gene knockout (GKO) mice infected with Leishmania donovani proceeded to reduce liver parasite burdens by 50% by week 12. This late-developing IFN-γ–independent antileishmanial mechanism appeared to be dependent largely on endogenous tumor necrosis factor-α (TNF-α): L. donovani infection induced TNF-α mRNA expression in parasitized GKO livers and neutralization of TNF-α reversed control at week 12. 7 d of treatment of infected GKO mice with interleukin-12 (IL-12) readily induced leishmanicidal activity and also partially restored the near-absent tissue granulomatous response, observations that for the first time expand the antimicrobial repertoire of IL-12 to include IFN-γ–independent effects. The action of IL-12 against L. donovani was TNF-α dependent and required the activity of inducible nitric oxide synthase. These results point to the presence of an IFN-γ–independent antimicrobial mechanism, mediated by TNF-α, which remains quiescent until activated late in the course of experimental visceral leishmaniasis. However, as judged by the effect of exogenous IL-12 this quiescent mechanism can readily be induced to rapidly yield enhanced intracellular antimicrobial activity.
Cardiovascular Risk Associated with Celecoxib in a Clinical Trial for Colorectal Adenoma Prevention
Authors: Scott D. Solomon, John J.V. McMurray, Marc A. Pfeffer, Janet Wittes, Robert Fowler, Peter Finn, William F. Anderson, Ann Zauber, Ernest Hawk, Monica Bertagnolli
Journal: New England Journal of Medicine (2005)

Selective cyclooxygenase-2 (COX-2) inhibitors have come under scrutiny because of reports suggesting an increased cardiovascular risk associated with their use. Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern.We reviewed all potentially serious cardiovascular events among 2035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for the prevention of colorectal adenomas. All deaths were categorized as cardiovascular or noncardiovascular, and nonfatal cardiovascular events were categorized in a blinded fashion according to a prespecified scheme.For all patients except those who died, 2.8 to 3.1 years of follow-up data were available. A composite cardiovascular end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure was reached in 7 of 679 patients in the placebo group (1.0 percent), as compared with 16 of 685 patients receiving 200 mg of celecoxib twice daily (2.3 percent; hazard ratio, 2.3; 95 percent confidence interval, 0.9 to 5.5) and with 23 of 671 patients receiving 400 mg of celecoxib twice daily (3.4 percent; hazard ratio, 3.4; 95 percent confidence interval, 1.4 to 7.8). Similar trends were observed for other composite end points. On the basis of these observations, the data and safety monitoring board recommended early discontinuation of the study drug.Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure. In light of recent reports of cardiovascular harm associated with treatment with other agents in this class, these data provide further evidence that the use of COX-2 inhibitors may increase the risk of serious cardiovascular events.
Dual-Frequency Proton Spin Relaxation Measurements on Tissues From Normal and Tumor-Bearing Mice
Authors: Barry A. Coles
Journal: JNCI Journal of the National Cancer Institute (1976)

Measurements of pulsed nuclear magnetic resonance relaxation times T1 and T2 were made at 2.7 MHz and 15 MHz on water protons in liver, kidney, spleen, muscle, and brain tissue from normal A.SW mice, and in the same tissues and tumors from A.SW mice developing MSWBS tumors (an ascites sarcoma) following dorsal sc implantation of tumor fragments. The measurement precision obtained from improved spectrometer design made it possible to show that T1 and T2 in all tissues except brain were increased by the presence of the tumor in the animal. The responses exhibited by T1 and T2 in liver and kidney were proportional to the size of the tumor. The smaller responses shown by T1 in spleen (15 MHz) and T1 and T2 in muscle (2.7 MHz) also showed a significant correlation with tumor size. The relaxation times for tumor (T1 at 2.7 MHz, T2 at 2.7 and 15 MHz) showed a significant negative correlation with tumor size: The times decreased as tumor size increased. The results were analyzed by use of the two-phase fast exchange model and were consistent with the effects expected if tissue water content increased and tumor water content decreased as tumor size increased. The analysis indicated that the effects arose primarily through changes in b, the fraction of water bound to fast exchange sites on the protein, with important modifications from changes in the correlation times Tc and Tm;Tr controlled the frequency that must be chosen for specific diagnostic applications.
MAP Kinases in the Immune Response
Authors: Chen Dong, Roger J. Davis, Richard A. Flavell
Journal: Annual Review of Immunology (2002)

MAP kinases are among the most ancient signal transduction pathways and are widely used throughout evolution in many physiological processes. In mammalian species, MAP kinases are involved in all aspects of immune responses, from the initiation phase of innate immunity, to activation of adaptive immunity, and to cell death when immune function is complete. In this review, we summarize recent progress in understanding the function and regulation of MAP kinase pathways in these phases of immune responses.