tbuckley/cabot-search huggingface dataset:
Prevalence of Lymphedema in Women With Breast Cancer 5 Years After Sentinel Lymph Node Biopsy or Axillary Dissection: Objective Measurements
Authors: Sarah A. McLaughlin, Mary J. Wright, Katherine T. Morris, Gladys L. Giron, Michelle R. Sampson, Julia P. Brockway, Karen E. Hurley, Elyn R. Riedel, Kimberly J. Van Zee
Journal: Journal of Clinical Oncology (2008)

Sentinel lymph node biopsy was adopted for the staging of the axilla with the assumption that it would reduce the risk of lymphedema in women with breast cancer. The aim of this study was to determine the long-term prevalence of lymphedema after SLN biopsy (SLNB) alone and after SLNB followed by axillary lymph node dissection (SLNB/ALND).At median follow-up of 5 years, lymphedema was assessed in 936 women with clinically node-negative breast cancer who underwent SLNB alone or SLNB/ALND. Standardized ipsilateral and contralateral measurements at baseline and follow-up were used to determine change in ipsilateral upper extremity circumference and to control for baseline asymmetry and weight change. Associations between lymphedema and potential risk factors were examined.Of the 936 women, 600 women (64%) underwent SLNB alone and 336 women (36%) underwent SLNB/ALND. Patients having SLNB alone were older than those having SLNB/ALND (56 v 52 years; P < .0001). Baseline body mass index (BMI) was similar in both groups. Arm circumference measurements documented lymphedema in 5% of SLNB alone patients, compared with 16% of SLNB/ALND patients (P < .0001). Risk factors associated with measured lymphedema were greater body weight (P < .0001), higher BMI (P < .0001), and infection (P < .0001) or injury (P = .02) in the ipsilateral arm since surgery.When compared with SLNB/ALND, SLNB alone results in a significantly lower rate of lymphedema 5 years postoperatively. However, even after SLNB alone, there remains a clinically relevant risk of lymphedema. Higher body weight, infection, and injury are significant risk factors for developing lymphedema.
Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy
Authors: Hiroaki Yagyu, Guangping Chen, Masayoshi Yokoyama, Kumiko Hirata, Ayanna Augustus, Yuko Kako, Toru Seo, Yunying Hu, E. Peer Lutz, Martin Merkel, André Bensadoun, Shunichi Homma, Ira J. Goldberg
Journal: Journal of Clinical Investigation (2003)

Lipoprotein lipase is the principal enzyme that hydrolyzes circulating triglycerides and liberates free fatty acids that can be used as energy by cardiac muscle. Although lipoprotein lipase is expressed by and is found on the surface of cardiomyocytes, its transfer to the luminal surface of endothelial cells is thought to be required for lipoprotein lipase actions. To study whether nontransferable lipoprotein lipase has physiological actions, we placed an α-myosin heavy-chain promoter upstream of a human lipoprotein lipase minigene construct with a glycosylphosphatidylinositol anchoring sequence on the carboxyl terminal region. Hearts of transgenic mice expressed the altered lipoprotein lipase, and the protein localized to the surface of cardiomyocytes. Hearts, but not postheparin plasma, of these mice contained human lipoprotein lipase activity. More lipid accumulated in hearts expressing the transgene; the myocytes were enlarged and exhibited abnormal architecture. Hearts of transgenic mice were dilated, and left ventricular systolic function was impaired. Thus, lipoprotein lipase expressed on the surface of cardiomyocytes can increase lipid uptake and produce cardiomyopathy.
Variation of Second Cancer Risk by Family History of Retinoblastoma Among Long-Term Survivors
Authors: Ruth A. Kleinerman, Chu-ling Yu, Mark P. Little, Yi Li, David Abramson, Johanna Seddon, Margaret A. Tucker
Journal: Journal of Clinical Oncology (2012)

Purpose To evaluate the risk of second cancer (SC) in long-term survivors of retinoblastoma (Rb) according to classification of germline mutation, based on family history of Rb and laterality. Patients and Methods We assembled a cohort of 1,852 1-year survivors of Rb (bilateral, n = 1,036; unilateral, n = 816). SCs were ascertained by medical records and self-reports and confirmed by pathology reports. Classification of RB1 germline mutation, inherited or de novo, was inferred by laterality of Rb and positive family history of Rb. Standardized incidence ratios and cumulative incidence for all SCs combined and for soft tissue sarcomas, bone cancers, and melanoma were calculated. The influence of host- and therapy-related risk factors for SC was assessed by Poisson regression for bilateral survivors. Results We observed a relative risk (RR) of 1.37 (95% CI, 1.00 to 1.86) for SCs in bilateral survivors associated with a family history of Rb, adjusted for treatment, age, and length of follow-up. The risk for melanoma was significantly elevated for survivors with a family history of Rb (RR, 3.08; 95% CI, 1.23 to 7.16), but risks for bone or soft tissue sarcomas were not elevated. The cumulative incidence of SCs 50 years after diagnosis of bilateral Rb, with adjustment for competing risk of death, was significantly higher for survivors with a family history (47%; 95% CI, 35% to 59%) than survivors without a family history (38%; 95% CI, 32% to 44%; P = .004). Conclusion Rb survivors with bilateral disease and an inherited germline mutation are at slightly higher risk of an SC compared with those with a de novo germline mutation, in particular melanoma, perhaps because of shared genetic alterations.
Arthritogenic SKG T cells are il-2 deficient and demonstrate distinct patterns of Th cell differentiation; reversal of the th17 phenotype by il-2
Authors: O. Smonezi, A. Annenkov, T. Tharmalingam, Y. Chernajowsky, R. Williams, A. Cope
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Emerging data suggest that a growing number of allelic variants in immunologically important genes modify T cell antigen receptor (TCR) signaling thresholds in ways that predispose individuals to autoimmune inflammatory arthritis, including rheumatoid arthritis (RA). SKG mice carry a loss of function spontaneous mutation in the TCR proximal protein tyrosine kinase ZAP-70, and develop a T cell dependent autoimmune inflammatory arthritis resembling RA. The authors set out to explore the mechanisms whereby SKG T cells promote disease, focusing on pathways of T cell activation and differentiation. <h3>Materials and methods</h3> To study antigenic peptide specific responses, SKG mice, on the Balb/c background were crossed to the HNT-TCR transgenic mouse, in which CD4 T cells are specific for a haemagglutin specific peptide, to generate SKG<sup>+/+</sup>HNT-TCR<sup>+</sup> mice. HNT-TCR single transgenic mice were used as controls. Th cell differentiation was studied by stimulating naïve lymph node derived CD4 T cells with specific peptide and cultured for 7–9d prior to restimulation with antigen. Proliferation was measured by CFSE dye dilution and cytokine expression was determined by the cytokine bead array method, and transcription factor expression measured by RT-PCR. Interleukin (IL)-2R signalling was evaluated by p-STAT5 immunoblotting. <h3>Results</h3> SKG T cells proliferate poorly and produce very low levels of IL-2, compared to control T cells. Differentiation of naïve SKG T cells in vitro leads to the preferential generation of cells in which IL-17 is upregulated. Levels of tumour necrosis factor, IL-6 and IFNγ are unchanged, while IL-4 and IL-10 production was substantially reduced. Consistently, levels of T-bet in differentiating SKG T cells are unchanged, expression of GATA-3 is reduced and that of RORc is substantially upregulated, when compared to HNT-TCR single transgenic mice. Restoration of IL-2 production during differentiation of naïve SKG T cells leads to suppression of IL-17 secretion and downregulation of RORc mRNA expression. Finally, exogenous IL-2 restores IL-2Rα expression on SKG T cells. <h3>Conclusions</h3> These data indicate that a state of relative IL-2 deficiency is characteristic of effector T cells with impaired antigen TCR signalling. Lack of IL-2 promotes differentiation of Th17 cells, at the expense of Th2 cells, through failure downregulate expression of the Th17 master transcription factor, RORc.
Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial
Authors: Yi-Long Wu, Jin Soo Lee, Sumitra Thongprasert, Chong-Jen Yu, Li Zhang, Guia Ladrera, Vichien Srimuninnimit, Virote Sriuranpong, Jennifer Sandoval-Tan, Yunzhong Zhu, Meilin Liao, Caicun Zhou, Hongming Pan, Victor Lee, Yuh-Min Chen, Yan Sun, Benjamin Margono, Fatima Fuerte, Gee-Chen Chang, Kasan Seetalarom, Jie Wang, Ashley Cheng, Elisna Syahruddin, Xiaoping Qian, James Ho, Johan Kurnianda, Hsingjin Eugene Liu, Kate Jin, Matt Truman, Ilze Bara, Tony Mok
Journal: The Lancet Oncology (2013)
Stimulation of phosphatidylinositol metabolism in the isolated, perfused rat heart.
Authors: E A Woodcock, L B White, A I Smith, J K McLeod
Journal: Circulation Research (1987)

Receptor-stimulated phosphatidylinositol turnover has been studied in isolated, perfused, [3H]inositol-labelled rat hearts by measuring accumulation of inositol phosphates in the presence of lithium chloride. Inositol phosphate accumulation was stimulated by norepinephrine (3 X 10(-5) M) and carbachol (10(-3) M), the increases averaging from 931 +/- 59 (n = 6, mean +/- SEM, cpm/g heart) to 4,165 +/- 609 (n = 6, p less than 0.01) for norepinephrine and to 1,853 +/- 354 (n = 6, p less than 0.05) for carbachol. The norepinephrine stimulation was antagonized by prazosin (10(-7) M) but not by propranolol (10(-7) M), indicating mediation via alpha 1-adrenoceptors. The carbachol stimulation was antagonized by atropine (10(-7) M). The stimulation by norepinephrine was significantly higher in right atria (837 +/- 151 to 6,614 +/- 1,210, n = 6, cpm/g tissue) than in other regions of the heart. Both norepinephrine and carbachol stimulated the formation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate with norepinephrine stimulation being detected as early as 15 seconds. Furthermore, the inositol trisphosphate was identified as the -1,4,5 isomer by anion exchange high-performance liquid chromatography. These data are consistent with the hydrolysis of phosphatidylinositol-(4,5)-bisphosphate yielding inositol-(1,4,5)-trisphosphate. Inositol-(1,3,4)-trisphosphate was not detected in heart preparations, suggesting unusual metabolism of inositol-(1,4,5)-trisphosphate in heart tissue.
IMMUNOGLOBULINS ON THE SURFACE OF THYMUS-DERIVED CELLS ENGAGED IN THE INITIATION OF A HUMORAL IMMUNE RESPONSE
Authors: J. F. Lesley, J. R. Kettman, R. W. Dutton
Journal: The Journal of Experimental Medicine (1971)

Preculture treatment of normal spleen cells with antiserum against mouse kappa light chains and complement was found to inhibit in vitro responses of these cells to TNP and erythrocyte (carrier) antigens, primarily by elimination of a thymus-derived helper component required for the response. Spleen populations inactivated in this way could be reconstituted with irradiated, carrier-immune spleen cells or with carrier-educated thymus-derived spleen cells. The ability of helper populations (i.e. irradiated, carrier-immune spleen cells or carrier-educated thymus-derived spleen cells) to enhance the response of normal spleen cells to hapten was eliminated by pretreatment of the helper cells with anti-kappa serum and complement. No significant effect of anti-kappa and complement treatment on precursor cell populations in normal spleen or bone-marrow-derived spleen could be demonstrated. The data are interpreted as evidence for the presence of immunoglobulin components. The function of these molecules is not established but it would be reasonable to assume that they are involved in antigen recognition, on the surface of thymus-derived cells.
Expression of PDGF alpha-receptor in renal arteriosclerosis and rejecting renal transplants.
Authors: J Floege, K L Hudkins, C L Davis, S M Schwartz, C E Alpers
Journal: Journal of the American Society of Nephrology (1998)

Platelet-derived growth factor (PDGF) plays an important role in renal disease. We have recently demonstrated that in healthy mature human kidney, PDGF alpha-receptor expression is largely restricted to interstitial cells. The study presented here assesses the expression of PDGF alpha-receptor in 18 mature adult kidneys with arteriosclerosis from individuals with no clinically evident history of renal disease other than localized neoplasia, in 13 kidneys with irreversible transplant rejection, and in a series of renal transplant biopsies composed of examples of both severe and absent rejection, by in situ hybridization and immunocytochemistry. Strong focal or diffuse expression of PDGF alpha-receptor mRNA and protein was noted in some intimal cells of intrarenal arterial vessels exhibiting signs of arteriosclerosis and/or vascular rejection. By double immunostaining, it could be shown that these cells were neither endothelial cells nor infiltrating leukocytes. The cells were most often identified as smooth muscle by colabeling for the smooth muscle cell-specific protein SM22alpha and less commonly for alpha-smooth muscle actin. There was also a population of PDGF alpha-receptor-expressing cells that failed to colabel with any of these markers, and hence remain of uncertain histogenesis. These intimal cells were generally negative for several other markers of differentiated smooth muscle cells, i.e., calponin and desmin. Near these PDGF alpha-receptor-positive intimal cells, expression of PDGF A-chain, an alpha-receptor ligand, was demonstrated in endothelial, intimal, and/or medial cells. Prominent PDGF alpha-receptor mRNA and protein expression also was noted in areas of interstitial fibrosis and in some glomeruli, in particular those with segmental glomerulosclerosis or fibrotic crescents. Double immunolabeling for PDGF alpha-receptor and alpha-smooth muscle actin confirmed that most of these latter PDGF alpha-receptor-positive cells were interstitial myofibroblasts or mesangial cells, or both. In summary, these data demonstrate widespread expression of PDGF alpha-receptor in renal cell types involved in fibrotic and sclerosing processes. The data also show that PDGF alpha-receptor expression identifies a unique population of phenotypically altered vascular smooth muscle cells, which appear to be involved in the vascular response to injury.
Transapical Transcatheter Aortic Valve Implantation in Humans
Authors: Samuel V. Lichtenstein, Anson Cheung, Jian Ye, Christopher R. Thompson, Ronald G. Carere, Sanjeevan Pasupati, John G. Webb
Journal: Circulation (2006)

Aortic valve replacement with cardiopulmonary bypass is currently the treatment of choice for symptomatic aortic stenosis but carries a significant risk of morbidity and mortality, particularly in patients with comorbidities. Recently, percutaneous transfemoral aortic valve implantation has been proposed as a viable alternative in selected patients. We describe our experience with a new, minimally invasive, catheter-based approach to aortic valve implantation via left ventricular apical puncture without cardiopulmonary bypass or sternotomy.A left anterolateral intercostal incision is used to expose the left ventricular apex. Direct needle puncture of the apex allows introduction of a hemostatic sheath into the left ventricle. The valve prosthesis, constructed from a stainless steel stent with an attached trileaflet equine pericardial valve, is crimped onto a valvuloplasty balloon. The prosthetic valve and balloon catheter are passed over a wire into the left ventricle. Positioning within the aortic annulus is confirmed by fluoroscopy, aortography, and echocardiography. Rapid ventricular pacing is used to reduce cardiac output while the balloon is inflated, deploying the prosthesis within the annulus. Transapical aortic valve implantation was successfully performed in 7 patients in whom surgical risk was deemed excessive because of comorbidities. Echocardiographic median aortic valve area increased from 0.7 +/- 0.1 cm2 (interquartile range) to 1.8 +/- 0.8 cm2 (interquartile range). There were no intraprocedural deaths. At a follow up of 87 +/- 56 days, 6 of 7 patients remain alive and well.This initial experience suggests that transapical aortic valve implantation without cardiopulmonary bypass is feasible in selected patients with aortic stenosis.
Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques
Authors: Xia Jin, Daniel E. Bauer, Sarah E. Tuttleton, Sharon Lewin, Agegnehu Gettie, James Blanchard, Craig E. Irwin, Jeffrey T. Safrit, John Mittler, Leor Weinberger, Leondios G. Kostrikis, Linqi Zhang, Alan S. Perelson, David D. Ho
Journal: The Journal of Experimental Medicine (1999)

To determine the role of CD8(+) T cells in controlling simian immunodeficiency virus (SIV) replication in vivo, we examined the effect of depleting this cell population using an anti-CD8 monoclonal antibody, OKT8F. There was on average a 99.9% reduction of CD8 cells in peripheral blood in six infected Macaca mulatta treated with OKT8F. The apparent CD8 depletion started 1 h after antibody administration, and low CD8 levels were maintained until day 8. An increase in plasma viremia of one to three orders of magnitude was observed in five of the six macaques. The injection of a control antibody to an infected macaque did not induce a sustained viral load increase, nor did it significantly reduce the number of CD8(+) T cells. These results demonstrate that CD8 cells play a crucial role in suppressing SIV replication in vivo.
SMALL INTESTINAL MUCOSAL CELL PROLIFERATION AND BACTERIAL FLORA IN THE CONVENTIONALIZATION OF THE GERMFREE MOUSE
Authors: Kenneth A. Khoury, Martin H. Floch, Theodore Hersh
Journal: The Journal of Experimental Medicine (1969)

The relationship between intestinal colonization and the small bowel mucosal cellular proliferation rate during conventionalization of the germfree mouse was examined. 16 mice were maintained under standard germfree conditions, and 54 others were conventionalized. Migration of the small bowel epithelial cells was followed by radioautography with administration of tritiated thymidine. Colonization was followed by qualitative and quantitative bacteriological fecal analyses. The percentages of the villi labeled (as determined by cell count) 24, 48, and 72 hr following thymidine administration showed immediate progression in the conventionalized animals from the germfree villus migration time (4 days) toward the conventional villus migration time (2 days). The epithelial migration rate of animals conventionalized for 8 days was comparable to that of conventional animals. After conventionalization, aerobic and anaerobic organisms undergo a period of extensive multiplication; however, 72 hr later the number of these microorganisms cultured in the stool decrease and are similar to those recovered from normal animals. Coliforms and streptococci are recovered in large numbers only in the first days after conventionalization, while the Bacteroides are first recovered in significant numbers on the fifth day of conventionalization. Except for smaller numbers of Bacteroides, the bacterial populations in the stools of the conventionalized animals are qualitatively and quantitatively similar by the eighth day of conventionalization to those of true conventional mice. Adaptive balance between cell proliferation and sloughing, and thus migration rate, begins immediately after conventionalization of germfree animals as bacterial populations establish themselves throughout the gastrointestinal tract, and results in a doubling of the mucosal cell turnover after 8 days. At this time both the small intestinal epithelial cell migration rate and the intestinal microflora are similar to those of conventional animals.
Reactions to aspirin and food additives in patients with chronic urticaria, including the physical urticarias*
Authors: H.M.G. DOEGLAS
Journal: British Journal of Dermatology (2006)

In 131 patients with chronic urticaria, including physical urticarias, oral provocation tests were done with aspirin. A total of thirty-one patients showed a reaction on aspirin challenge. Reactions were seen in 35% of patients with idiopathic urticaria, 52% of patients with cholinergic urticaria, and 43% of those with pressure urticaria. The patients with reactions to aspirin were also tested with tartrazine, sodium benzoate, 4-hydroxy benzoic acid, sodium- and phenyl salicylate and the analgesics indomethacin, paracetamol and mefenamic acid. In nineteen of twenty three aspirin sensitive patients, positive reactions to one or more of these substances were observed. Indomethacin and tartrazine had the highest scores. There was no statistically significant correlation between aspirin reactions and the presence of nasal polyposis, sinusitis, asthma or atopy.
General practice sport and exercise medicine in a strange new world: the role of Sports Doctors Australia and international primary care colleagues
Authors: Gavan L White
Journal: British Journal of Sports Medicine (2012)

This edition of BJSM serves the primary care sports doctor as well as the generalist primary care doctor. Articles cover sports injury and the role of exercise as treatment. How life has changed for the procedural or full-service general practitioner. Twenty-five years ago, we focused on being technically good at our craft. The emergency room was full of accidents, infectious disease and the smattering of coronary artery disease and cerebro-vascular disease. We aimed to improve pregnancy outcomes through attentive antenatal care and well-honed obstetric skills in the delivery suite.

General Practice in Australia now focuses on lifestyle and the ‘new’ neglect – self-neglect. Counselling skills including motivational interviewing, risk factor modification, chronic disease management and morbidity control, have replaced the practical skills of fracture management, suturing and acute illness management. Obstetric management means preventing gestational diabetes, macrosomia and managing labour in the obese patient.

This issue is the first shaped by BJSM 's newest member society, Sports Doctors Australia (SDrA). It provides valuable tips relating to exercise in daily GP practice. Exercise prescription is not an easy thing to do in an ad-hoc way that …
Distinct mechanisms of neonatal tolerance induced by dendritic cells and thymic B cells.
Authors: M Inaba, K Inaba, M Hosono, T Kumamoto, T Ishida, S Muramatsu, T Masuda, S Ikehara
Journal: The Journal of Experimental Medicine (1991)

To assess the role of different types of antigen-presenting cells (APC) in the induction of tolerance, we isolated B cells, macrophages, and dendritic cells from thymus and spleen, and injected these into neonatal BALB/c mice across an Mls-1 antigenic barrier. One week after injection of APC from Mls-1-incompatible mice or from control syngeneic mice, we measured the number of thymic, Mls-1a-reactive, V beta 6+ T cells and the capacity of thymocytes to induce a graft-vs.-host (GVH) reaction in popliteal lymph nodes of Mls-1a mice. Injection of thymic but not spleen B cells deleted thymic, Mls-1a-reactive V beta 6+ T cells and induced tolerance in the GVH assay. The thymic B cells were primarily of the CD5+ type, and fluorescence-activated cell sorter-purified CD5+ thymic B cells were active. Injection of dendritic cells from spleen or thymus also induced tolerance, but the V beta 6 cells were anergized rather than deleted. Macrophages from thymus did not induce tolerance. Dendritic cells and thymic B cells were also effective in inducing tolerance even when injected into Mls-, major histocompatibility complex-incompatible, I-E- mice, but only thymic B cells depleted V beta 6-expressing T cells. Therefore, different types of bone marrow-derived APC have different capacities for inducing tolerance, and the active cell types (dendritic cells and CD5+ thymic B cells) can act by distinct mechanisms.