tbuckley/cabot-search huggingface dataset:
HER-2 Amplification, HER-1 Expression, and Tamoxifen Response in Estrogen Receptor-Positive Metastatic Breast Cancer
Authors: Grazia Arpino, Stephanie J. Green, D. Craig Allred, Dannika Lew, Silvana Martino, C. Kent Osborne, Richard M. Elledge
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Preclinical data indicate that expression of the ErbB family of receptors, such as HER-2 and HER-1 (EGFR) may be involved in endocrine resistance. Evidence of resistance from clinical studies has been inconsistent. The present study examined whether HER-2 gene amplification or HER-1 expression predicted response to tamoxifen. Patients and Methods: Three hundred and forty nine patients had estrogen receptor (ER)-positive breast cancer and received daily tamoxifen as initial therapy for advanced disease. HER-2 gene amplification, detected by fluorescence in situ hybridization, and HER-1 expression, evaluated by immunohistochemistry, was determined on 136 and 204 patients, respectively. Results: HER-2 amplification was correlated with lower ER (P = 0.02), HER-1 positivity (P = 0.004), and HER-2 protein overexpression (P &amp;lt; 0.00001). The response rate was 56% for HER-2 non-amplified versus 47% for HER-2 amplified tumors (P = 0.38), and 58% for HER-1–negative versus 36% for HER-1–positive (P = 0.05). Time to treatment failure (TTF) was 7 months for non-amplified HER-2 tumors and 5 months (P = 0.007) for amplified HER-2 tumors, and there was a trend toward a better overall survival (OS) in patients with non-amplified HER-2 tumors (median 31 versus 25 months, respectively, P = 0.07). For positive versus negative HER-1 tumors, TTF was 4 versus 8 months (P = 0.08) and median survival was 24 versus 31 months (P = 0.41). Combining HER-1 expression and HER-2 gene status, patients with both negative HER-1 expression and non-amplified HER-2 had longer TTF (P = 0.001) and OS (P = 0.03) than if either were positive. In multivariate analysis, HER-2 was not an independent factor for TTF and OS, although HER-1 was significant for TTF only (P ≤ 0.001). Conclusion: Patients with HER-2 amplification and HER-1 expression had lower ER levels and were modestly less responsive to tamoxifen, suggesting that molecular events in addition to those involving the ErbB receptors are important in determining the endocrine-resistant phenotype.
The Role of the Hospital Consultant in General Practitioner Prescribing
Authors: B Strickland-Hodge, M H Jepson
Journal: Journal of the Royal Society of Medicine (1988)

A questionnaire was designed and posted to 600 general medical practitioners in the West Midlands. The results indicated that the prescribers were reassured by the hospital consultant although independence was maintained in prescribing decisions. The hospital medical team was recognized for its expertise rather than the consultant alone. A table was constructed from the results to show the therapy areas in which doctors prefer to refer their patients. Consultant's influence in prescribing is most likely where communication between GP and consultant is optimal. The generalized influence of the consultant as implied by the Greenfield report remains unproven. Any influence is much more specific and may depend upon therapy area, the consultant specialty, and the standing of the hospital medical team. The innovativeness of the prescriber which was also considered may also have an influence as to how the consultant's recommendations will be accepted.
Cell-Free Embryonic Stem Cell Extract–Mediated Derivation of Multipotent Stem Cells From NIH3T3 Fibroblasts for Functional and Anatomical Ischemic Tissue Repair
Authors: Johnson Rajasingh, Erin Lambers, Hiromichi Hamada, Evelyn Bord, Tina Thorne, Ilona Goukassian, Prasanna Krishnamurthy, Kenneth M. Rosen, Deepali Ahluwalia, Yan Zhu, Gangjian Qin, Douglas W. Losordo, Raj Kishore
Journal: Circulation Research (2008)

The oocyte-independent source for the generation of pluripotent stem cells is among the ultimate goals in regenerative medicine. We report that on exposure to mouse embryonic stem cell (mESC) extracts, reversibly permeabilized NIH3T3 cells undergo dedifferentiation followed by stimulus-induced redifferentiation into multiple lineage cell types. Genome-wide expression profiling revealed significant differences between NIH3T3 control and ESC extract-treated NIH3T3 cells including the reactivation of ESC-specific transcripts. Epigenetically, ESC extracts induced CpG demethylation of Oct4 promoter, hyperacetylation of histones 3 and 4, and decreased lysine 9 (K-9) dimethylation of histone 3. In mouse models of surgically induced hindlimb ischemia or acute myocardial infarction transplantation of reprogrammed NIH3T3 cells significantly improved postinjury physiological functions and showed anatomic evidence of engraftment and transdifferentiation into skeletal muscle, endothelial cell, and cardiomyocytes. These data provide evidence for the generation of functional multipotent stem-like cells from terminally differentiated somatic cells without the introduction of retroviral mediated transgenes or ESC fusion.
Incidence of training-related injuries among marathon runners.
Authors: R. J. Maughan, J. D. Miller
Journal: British Journal of Sports Medicine (1983)

A questionnaire was sent to all 960 entrants in a major city marathon race to obtain information on training-related injuries. A total of 497 replies were received; of these 287 (58%) had incurred some form of injury during preparation for the race. Seventy-one of these individuals reported more than one injury. Almost all injuries affected the lower limb, with 113 cases (32%) involving pain or disability in the knee. More than half the injured runners (158, 55%) sought no professional advice; approximately half (146, 51%) received no treatment other than rest, which was not generally considered a form of therapy. Only 18 runners (6%) reported no improvement in their condition, while 143 individuals (51%) reported a full recovery. Injury incurred during training was thought by 98 runners (35%) to have had an adverse effect on their racing performance. These results suggest that runners preparing to compete in marathon races can expect their training to be interrupted by injury.
A Molecular Basis for the Control of Preimmune Escape Variants by HIV-Specific CD8+ T Cells
Authors: Kristin Ladell, Masao Hashimoto, Maria Candela Iglesias, Pascal G. Wilmann, James E. McLaren, Stéphanie Gras, Takayuki Chikata, Nozomi Kuse, Solène Fastenackels, Emma Gostick, John S. Bridgeman, Vanessa Venturi, Zaïna Aït Arkoub, Henri Agut, David J. van Bockel, Jorge R. Almeida, Daniel C. Douek, Laurence Meyer, Alain Venet, Masafumi Takiguchi, Jamie Rossjohn, David A. Price, Victor Appay
Journal: Immunity (2013)
THE CELLULAR DISTRIBUTION OF TRANSFERRIN-BOUND IRON IN THE SKIN
Authors: M. R. BEAMISH, K. JOBBINS, I. CAVILL
Journal: British Journal of Dermatology (2006)

SUMMARY.— Transferrin‐bound 55 Fe was injected into the skin of 4 normal subjects. The distribution of 55Fe in autoradiographs from biopsy samples taken over 35 days showed that epidermal iron exchange is confined to the bsal and suprabasal layers. Dermal histiocytes also take up transferrin‐bound iron. These findings showed that iron Ioss by desquamation is negligible.
Human tumor necrosis factor receptor (p55) and interleukin 10 gene transfer in the mouse reduces mortality to lethal endotoxemia and also attenuates local inflammatory responses.
Authors: M A Rogy, T Auffenberg, N J Espat, R Philip, D Remick, G K Wollenberg, E M Copeland, L L Moldawer
Journal: The Journal of Experimental Medicine (1995)

Anticytokine therapies have been promulgated in gram-negative sepsis as a means of preventing or neutralizing excessive production of proinflammatory cytokines. However, systemic administration of cytokine inhibitors is an inefficient means of targeting excessive production in individual tissue compartments. In the present study, human gene transfer was used to deliver to organs of the reticuloendothelial system antagonists that either inhibit tumor necrosis factor-alpha (TNF-alpha) synthesis or block its interactions with cellular receptors. Mice were treated intraperitoneally with cationic liposomes containing 200 micrograms of either a pCMV (cytomegalovirus)/p55 expression plasmid that contains the extracellular domain and transmembrane region of the human p55 TNF receptor, or a pcD-SR-alpha/hIL-10 expression plasmid containing the DNA for human interleukin 10. 48 h later, mice were challenged with lipopolysaccharide (LPS) and D-galactosamine. Pretreatment of mice with p55 or IL-10 cDNA-liposome complexes improved survival (p &amp;lt; 0.01) to LPS-D-galactosamine. In additional studies, intratracheal administration of IL-10 DNA-liposome complexes 48 h before an intratracheal LPS challenge reduced pulmonary TNF-alpha levels by 62% and decreased neutrophil infiltration in the lung by 55% as measured by myeloperoxidase activity (both p &amp;lt; 0.05). Gene transfer with cytokine inhibitors is a promising option for the treatment of both the systemic and local sequelae of septic shock.
A phase I, dose escalation study to determine the maximum tolerated dose of erlotinib when combined with pertuzumab in previously treated non-small-cell lung cancer patients
Authors: E. Felip, M. Ranson, S. Cedres, E. Dean, E. De Droogh, M. Brewster, V. A. McNally, G. Ross, D. Galdermans
Journal: Journal of Clinical Oncology (2008)

19134 Background: Pertuzumab (P), a monoclonal antibody, targets the HER2 receptor and prevents dimerization of HER2 and HER2, HER2 and HER1 or HER2 and HER3. P is active against HER2 overexpressing breast cancer (Baselga et al, ASCO 2007) but has no meaningful single agent activity against non-small-cell lung cancer (NSCLC). Erlotinib (E) inhibits HER1 tyrosine kinase signalling, is active against a number of tumour types and is widely registered for the treatment of relapsed NSCLC. By combining E and P signaling via HER1, HER2 and HER3 are inhibited. Inhibition of multiple HER signaling pathways could prove to be clinically useful. Methods: This is a phase I, dose escalating study. Consenting NSCLC patients (pts) with ECOG performance status of 0 or 1, progression after previous chemotherapy and adequate cardiac reserve (baseline LVEF ≥55%) were recruited in 2 cohorts. All pts had tumour specimen for evaluating biomarkers potentially associated with response. The 1st cohort received P at the full dose of 840mg iv loading dose with 420mg iv maintenance every 3 weeks plus E at a dose of 100mg orally daily. If the maximum tolerated dose (MTD) was not reached, a 2nd cohort was to be recruited (these pts were to receive the full dose of P plus E at the full dose of 150mg orally daily). Dose limiting toxicity (DLT) was initially defined as any adverse event (AE) ≥ grade 3; an incidence of DLT in 2 out of 6 pts was defined as MTD. Based on experience with the 1st cohort, the protocol was modified to exclude rash as a DLT (rashes encountered were manageable and responded to interruption or reduction of E). Subsequently a 2nd cohort (9 pts) has been recruited. Results: In the 1st cohort tolerability was good, the common AEs being diarrhea in 3 pts (50%) which was generally mild and self-limiting and rash which was reported by all 6 pts (100%). Rash was severe (grade 3) in 3 pts, but responded to either dose reduction of E to 50 mg orally daily or to withdrawal of treatment. In the 2nd cohort, the combination has been well tolerated with no DLTs reported to date. Conclusions: For Phase II evaluation, a full dose of E (150mg orally daily) with full dose of P appears to be suitable. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Roche Clinical Trial Costs
Visceral leishmaniasis: elimination with existing interventions
Authors: Greg Matlashewski, Byron Arana, Axel Kroeger, Sujit Battacharya, Shyam Sundar, Pradeep Das, Prabhat Kumar Sinha, Suman Rijal, Dinesh Mondal, Dan Zilberstein, Jorge Alvar
Journal: The Lancet Infectious Diseases (2011)
Changing Trends in the Survival of Dialysis Patients with Human Immunodeficiency Virus in the United States
Authors: Tejinder S. Ahuja, James Grady, Shilpi Khan
Journal: Journal of the American Society of Nephrology (2002)

HIV-infected patients with end-stage renal disease have a very high morbidity and mortality. In the last decade, survival of HIV-infected patients in the United States has remarkably improved. To determine whether similar improvement in survival has occurred in HIV-infected dialysis patients, their survival was evaluated by using the United States Renal Data System database. Survival of HIV-infected dialysis patients in the United States was determined and the influence of year of initiation of dialysis, and demographic characteristics on the survival were analyzed by the Kaplan-Meier method. The effects of above variables on survival were also examined in a Cox proportional hazards model. Identified were 6166 HIV-infected patients with end-stage renal disease who received dialysis in the United States. Eighty-nine percent of the patients were black, 7.4% white, and 3% other. From 1990 to 1999, 1-yr survival of HIV-infected patients on dialysis improved from 56 to 74%, and the annual death rates declined from 458 deaths to 240 deaths per 1000 patient-years. The hazard ratio declined significantly in patients who initiated dialysis in years 1999-2000 compared with patients who initiated dialysis < or = 1990 (hazard ratio, 0.49; 95% confidence interval, 0. 40 to 0.60). Survival of HIV-infected dialysis patients has remarkably improved in the United States.
Incorporation of Oleic Acid into Lipid by Foam Cells in Human Atherosclerotic Lesions
Authors: MARK L. WAHLQVIST, ALLAN J. DAY, RONALD K. TUME
Journal: Circulation Research (1969)

The incorporation of 14 C-labeled oleic acid into phospholipid, cholesterol ester, and triglyceride in human arterial intima (normal and atherosclerotic) obtained from kidney transplant donors has been investigated in vitro. Most of the oleic acid was incorporated into phospholipid, in both the normal intima and the atherosclerotic lesion, but a greater proportion of label was diverted to cholesterol ester in the lesion. Representative sections of the vessels used for metabolic studies were taken for radioautography, and these demonstrated localization of 14 C to foam cells, but very little localization in the region of spindle-shaped cells. It was concluded that lipid synthesis in the human atherosclerotic lesion takes place predominantly in the intimal foam cells.
Prevalence of headache in Australian footballers
Authors: P McCrory, J Heywood, C Coffey
Journal: British Journal of Sports Medicine (2005)

Objective: To survey the prevalence and risk factors for headache in a population of elite professional Australian footballers. Methods: A prospective questionnaire based survey was performed on elite Australian footballers participating in a national competition. The survey was designed to assess the prevalence and risk factors for headache using standardised International Headache Society (HIS) criteria. Headache prevalence was compared with that of an age and sex matched community control population. Results: A total of 160 questionnaires were analysed. Headaches were reported by 80% of subjects, with 49% of respondents reporting headaches during competitive match play and 60% during training. There was no significant difference between the footballers and the community sample in the number of headaches ever; however, they did report more headaches in the three months before the survey —that is, during the competitive playing season. In the footballers, 22% of headaches conformed to the strict IHS definition of migraine headaches. When the relaxed definition of “footballer’s migraine” was used, 34% of headaches met these criteria. Footballers were at significantly increased risk of footballer’s migraine than community controls. Conclusions: Headaches are common in Australian footballers, and the prevalence of migraine is increased in relation to community prevalence studies. Furthermore, the strict IHS criteria may not adequately identify the specific subtype of football related headache. This finding has important implications in the management of headache in this setting.
A phase I open-label dose-escalation study of oral BIBF 1120 combined with standard paclitaxel and carboplatin in patients with advanced gynecological malignancies
Authors: A. du Bois, J. Huober, P. Stopfer, J. Pfisterer, P. Wimberger, S. Loibl, V.L. Reichardt, P. Harter
Journal: Annals of Oncology (2009)
Thomas Bryce Dunn
Authors: J. Armstrong
Journal: BMJ (2008)

After qualifying in 1942, Thomas Bryce Dunn (“Tom”) undertook a six month junior post, after which he joined the Royal Army Medical Corps. He was initially on a field ambulance, later a field dressing station, in France from D Day + 1. After the campaign he was posted to Turkey as the only medical practitioner for the embassy in Istanbul. He was demobilised in November 1946.

Following his return to civilian medical life, he took a post as casualty …
Maximal Oxygen Uptake and Severity of Disease in Lymphangioleiomyomatosis
Authors: Angelo M. Taveira-DaSilva, Mario P. Stylianou, Carolyn J. Hedin, Arnold S. Kristof, Nilo A. Avila, Antoinette Rabel, William D. Travis, Joel Moss
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Lymphangioleiomyomatosis (LAM), a disease that occurs primarily in women, is characterized by cystic lung lesions causing respiratory failure, which may require lung transplantation. Lung diffusion (DLCO) and/or FEV1 are decreased, but frequently not in parallel with each other. Because cardiopulmonary exercise testing (CPET) provides information that is not obtainable from resting cardiopulmonary tests, we performed CPET in 217 LAM patients and correlated exercise data with clinical markers of severity, computed tomography scans, lung function, and histology. V̇O2max was decreased in 162 patients, of whom 28 did not reach anaerobic threshold; 29 had low oxygen uptake at anaerobic threshold, and 54 developed hypoxemia. Hypoxemia occurred even in patients with near normal DLCO and FEV1. V̇O2max decreased with an increasing score of histologic LAM severity and was correlated with computed tomography scans, the use of oxygen, and resting PaO2. DLCO and FEV1, however, were the only significant predictors of V̇O2max. We conclude that CPET uncovers the presence of exercise-induced hypoxemia and assists in grading the severity of disease and determining supplemental oxygen requirements in patients with LAM.
Receptors for cold-insoluble globulin (plasma fibronectin) on human monocytes.
Authors: M P Bevilacqua, D Amrani, M W Mosesson, C Bianco
Journal: The Journal of Experimental Medicine (1981)

This investigation focused on the role played by cold-insoluble globulin (CIg, plasma fibronectin) in monocyte function. Surface-bound CIg mediated a concentration-dependent of human blood monocytes to gelatin-coated surfaces. CIg also mediated the binding of gelatin-coated particles such as latex beads or tanned erythrocytes to surface-bound human monocytes. However, CIg did not mediate particle ingestion. Subfractionated CIg that was highly enriched in monomeric forms (zone II CIg, mol wt 190,000-235,000) was less effective than were fractions enriched in dimeric forms (zone I CIg, mol wt 450,000) in promoting monocyte attachment. Binding of CIg to a gelatin or plastic surface occurred in the absence of divalent cations, but monocyte attachment to CIg-coated surfaces required divalent cations, Mg++ being much more effective than Ca++. Cation-dependent cell attachment was reversible in that bound cells could be released by treatment with EDTA. Serum-mediated binding of monocytes to gelatin-coated plastic dishes was a result of its content of CIg because the binding activity was abolished by removal of CIg from serum, and could be restored by readdition of purified CIg. Treatment of monocytes with trypsin abolished subsequent cell attachment to CIg-gelatin surfaces or particles. Expression of certain other known monocyte membrane receptors (Fc and C3b) was markedly enhanced as a result of CIg-monocyte interaction. These several observations indicate that monocytes bear membrane receptors (termed receptor cold-insoluble globulin) for surface-bound CIg.
Aerophagia, gastric, and supragastric belching: a study using intraluminal electrical impedance monitoring
Authors: A J Bredenoord
Journal: Gut (2004)

<b>Background:</b> Patients with aerophagia are believed to have excessive belches due to air swallowing. Intraluminal impedance monitoring has made it possible to investigate the validity of this concept. <b>Methods:</b> The authors measured oesophageal pH and electrical impedance before and after a meal in 14 patients with excessive belching and 14 healthy controls and identified patterns of air transport through the oesophagus. The size of the gastric air bubble was measured radiographically. In four patients prolonged oesophageal manometry was performed simultaneously. <b>Results:</b> In all subjects, impedance tracings showed that a significant amount of air is propulsed in front of about a third of the swallow induced peristaltic waves. Two types of retrograde gas flow through the oesophagus (belch) were observed. In the first type air flowed from the stomach through the oesophagus in oral direction (“gastric belch”). In the second type air entered the oesophagus rapidly from proximal and was expulsed almost immediately in oral direction (“supragastric belch”). The incidence of air-containing swallows and gastric belches was similar in patients and controls but supragastric belches occurred exclusively in patients. There was no evidence of lower oesophageal sphincter relaxation during supragastric belches. Gastric air bubble size was not different between the two groups. <b>Conclusions:</b> In patients with excessive belching the incidence of gaseous reflux from stomach to oesophagus is similar to that in healthy subjects. Their excess belching activity follows a distinct pattern, characterised by rapid antegrade and retrograde flow of air in the oesophagus that does not reach the stomach.
Alanine Aminotransferase, γ-Glutamyltransferase, and Incident Diabetes
Authors: Abigail Fraser, Ross Harris, Naveed Sattar, Shah Ebrahim, George Davey Smith, Debbie A. Lawlor
Journal: Diabetes Care (2009)

OBJECTIVE To estimate and compare associations of alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) with incident diabetes. RESEARCH DESIGN AND METHODS ALT and GGT were studied as determinants of diabetes in the British Women's Heart and Health Study, a cohort of 4,286 women 60–79 years old (median follow-up 7.3 years). A systematic review and a meta-analysis of 21 prospective, population-based studies of ultrasonography, which diagnosed nonalcoholic fatty liver disease (NAFLD), ALT, and GGT as determinants of diabetes, were conducted, and associations of ALT and GGT with diabetes were compared. RESULTS Ultrasonography-diagnosed NAFLD was associated with more than a doubling in the risk of incident diabetes (three studies). ALT and GGT both predicted diabetes. The fully adjusted hazard ratio (HR) for diabetes per increase in one unit of logged ALT was 1.83 (95% CI 1.57–2.14, I2 = 8%) and for GGT was 1.92 (1.66–2.21, I2 = 55%). To directly compare ALT and GGT as determinants of diabetes, the fully adjusted risk of diabetes in the top versus bottom fourth of the ALT and GGT distributions was estimated using data from studies that included results for both markers. For ALT, the HR was 2.02 (1.59–2.58, I2 = 27%), and for GGT the HR was 2.94 (1.98–3.88, I2 = 20%), suggesting that GGT may be a better predictor (P = 0.05). CONCLUSIONS Findings are consistent with the role of liver fat in diabetes pathogenesis. GGT may be a better diabetes predictor than ALT, but additional studies with directly determined liver fat content, ALT, and GGT are needed to confirm this finding.