tbuckley/cabot-search huggingface dataset:
Calcium and Inorganic Phosphate Transport in Rat Colon
Authors: D. B. N. Lee, M. W. Walling, U. Gafter, V. Silis, J. W. Coburn
Journal: Journal of Clinical Investigation (1980)

In the small intestine, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] stimulates both calcium (Ca) and inorganic phosphate (Pi) absorption. This is mediated through an increase in mucosal-to-serosal flux (Jms) whereas the serosal-to-mucosal flux (Jsm) remains unchanged. We now report that in rat proximal colon, 1,25(OH)2D3 produces active Ca absorption without affecting Pi transport, and that this induced active Ca absorption is associated with alterations in kinetics of both Jms and Jsm so that both processes demonstrate saturable components. Vitamin D-deficient rats were given daily injections of solvent (−D) or 270 ng 1,25(OH)2D3 (+D) for 3 d. 45Ca and [32P]phosphate fluxes were measured employing the Ussing technique using a modified Krebs-Ringer-HCO3 buffer ([Ca] 1.25, [Pi] 1.18, [glucose] 11 mM). In −D rats there was no net flux (Jnet) of either Ca or Pi. In +D rats net active Ca absorption was observed (−D = 3.3 nmol/cm2 per h ±3.4 (SEM); +D = 27.3 ±3.8, n = 11, P < 0.001) whereas Pi transport was unchanged, i.e., still no Jnet. Pi Jms was not different from Pi Jsm measured at the following buffer [Pi]: 0.0118, 0.118, 1.18, and 2.36 mM. Ca saturation kinetics were estimated using buffer [Ca] from 0.0125 to 5.0 mM. Saturable processes were demonstrated for both Jms and Jsm. Jnet for Ca across colon from +D rats exhibited saturation at [Ca] > 3 mM, with an estimated Vmax of 44.0 nmol/cm2 per h and a Km of 0.9 mM. This colonic model may provide a useful system for studying 1,25(OH)2D3-induced molecular events related to Ca but not Pi transport. The apparent action of 1,25(OH)2D3 on Ca secretory process may furnish new insights into the mechanism of action of vitamin D.
Contribution of Functional <i>LILRA3</i>, but Not Nonfunctional <i>LILRA3</i>, to Sex Bias in Susceptibility and Severity of Anti–Citrullinated Protein Antibody–Positive Rheumatoid Arthritis
Authors: Yan Du, Yong Cui, Xia Liu, Fanlei Hu, Yue Yang, Xinyu Wu, Xu Liu, Xiaoxu Ma, Xianbo Zuo, Yujun Sheng, Xiangyuan Liu, Jianhua Xu, Ping Zhu, Lingyun Sun, Nan Hong, Xuejun Zhang, Jianping Guo, Zhanguo Li
Journal: Arthritis & Rheumatology (2013)

Leukocyte immunoglobulin-like receptor A3 belongs to a family of receptors with inhibitory or activating functions. Since Caucasian individuals lacking LILRA3 have been found to be susceptible to multiple sclerosis and Sjögren's syndrome, we undertook this study to examine whether LILRA3 deletion is a novel genetic risk factor for rheumatoid arthritis (RA) (another autoimmune disease), whether there are sex-specific effects, and whether LILRA3 influences the subtype and severity of RA.The LILRA3 deletion and its tagging single-nucleotide polymorphism rs103294 were genotyped in a Northern Han Chinese cohort (N-Han) (1,618 cases and 1,658 controls) and a Southern Han Chinese cohort (S-Han) (575 cases and 549 controls). Association analyses were performed on the complete data set and subsets. The effect of the nondeleted (functional) LILRA3 allele on radiographic severity and LILRA3 expression was evaluated.In the N-Han discovery cohort, we unexpectedly observed a higher frequency of the functional LILRA3 in RA patients compared with healthy individuals (10.1% versus 6.3%; P = 4.01 × 10(-5) , odds ratio [OR] 1.92). The association was replicated in the S-Han cohort and confirmed by meta-analysis (P = 5.63 × 10(-6) , OR 1.83). Functional LILRA3 conferred greater risk for RA in males (P = 1.09 × 10(-6) , OR 4.47), and was specifically associated with anti-citrullinated protein antibody (ACPA)-positive RA (P = 3.05 × 10(-4) , OR 1.75). Furthermore, functional LILRA3 was associated with higher radiographic scores in ACPA-positive patients with early RA (P = 9.70 × 10(-3) ) and higher LILRA3 messenger RNA levels (P = 3.31 × 10(-8) ).Our study provides the first evidence that functional LILRA3 is a novel genetic risk factor for RA, especially in males. It appears to highly predispose to ACPA-positive RA and confers an increased risk of disease severity in patients with early RA.
DNA Sequence Variants Related to Plasma Triglycerides or High-Density Lipoprotein Cholesterol and Risk of Myocardial Infarction
Authors: Sekar Kathiresan
Journal: Circulation (2009)

Abstract #1807 Sekar Kathiresan, Benjamin F. Voight, Massachusetts General Hosp, Boston, MA; Myocardial Infarction Genetics Consortium Sekar Kathiresan, 2009 Finalist and Presenting Author
177. Lentiviral Vector Mediated ADA Gene Transfer in ADA-Deficient SCID Mice
Authors: Denise A. Carbonaro, Xiangyang Jin, Dinithi Senadherra, Karen Pepper, Denise Petersen, Xiao-Jin Yu, Dianne Skelton, Donald B. Kohn
Journal: Molecular Therapy (2004)

Genetic deficiency of adenosine deaminase (ADA) is responsible for ~20% of human severe combined immune deficiency (SCID). While promising results have been obtained by Aiuti and co-workers using oncoretroviral vectors to transduce CD34+ cells from the bone marrow of ADA-deficient SCID patients, lentiviral vectors may lead to higher levels of ADA gene transfer that could extend benefits to older subjects with less transducible bone marrow or allow lower dosages of cytoreductive therapy to be used. We have constructed a SIN HIV-1-based lentiviral vector, SMPU-R-MND-ADA, which was produced at high titer (1 × 10e10 i.u./ml after 100-fold concentration) using VSV-G pseudotype and have shown it to express high levels of ADA enzyme activity in human and murine cell lines in vitro. A model of ADA-deficient SCID was produced by Rodney Kellems and co-workers (U.Texas, Houston) by ADA gene knock-out and rescue of neonatal lethality with an ADA mini-gene expressed in the placenta during gestation. These mice die from a non-infectious pulmonary disease within the first month of life, unless maintained on enzyme replacement therapy (ERT) with PEG-ADA. We have determined that transplantation of newborn ADA −/− mice with normal congenic bone marrow allows long-term survival without PEG-ADA and facilitates breeding.
Abstract P1-01-04: Evaluation of tumor response after neoadjuvant chemotherapy in breast cancer patients: Correlation between dynamic contrast-enhanced MRI and pathologic tumor cellularity
Authors: Hak Hee Kim, Won Kyung Kim, Joo Hee Cha, Hee Jung Shin, Eun Young Chae, Woo Jung Choi
Journal: Cancer Research (2015)

Abstract Purpose: The objective of the study was to analyze whether the measurement of changes of the tumor on magnetic resonance imaging (MRI), could be applied to predict pathologic response after neoadjuvant chemotherapy. Methods: Between January 2013 and October 2013, 155 patients (age range, 31-74 years; mean age, 47.6 years) with pathologically proven breast cancer who underwent neoadjuvant chemotherapy followed by surgery were retrospectively enrolled. Pre-and post-treatment measurements and changes in tumor size and dynamic curve pattern of MRI were analyzed. Histological regression was scored on the residual overall tumor cellularity based on Miller-Payne grading system. Results: The change of maximal diameter (ρ = 0.681, p &amp;lt; 0.001), angio-volume of tumor (ρ = 0.683, p &amp;lt; 0.001) and washout ratio of dynamic curve (ρ = 0.607, p &amp;lt; 0.001) measured on MRI showed strong correlation with histological regression. Among them, the correlation factor was highest in the change of angio-volume. The change of plateau ratio of dynamic curve showed moderate correlation (ρ = 0.574, p &amp;lt; 0.001) with histological regression. However, the change of persistent ratio of dynamic curve showed weak correlation (ρ = 0.206, p = 0.011). Conclusions: The change of maximal diameter, angio-volume of tumor and washout ratio of dynamic curve measured on MRI showed strong correlation with residual cellularity in lesions after neoadjuvant chemotherapy and could be applied to predict pathologic response. Citation Format: Hak Hee Kim, Won Kyung Kim, Joo Hee Cha, Hee Jung Shin, Eun Young Chae, Woo Jung Choi. Evaluation of tumor response after neoadjuvant chemotherapy in breast cancer patients: Correlation between dynamic contrast-enhanced MRI and pathologic tumor cellularity [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-01-04.
The Breast Cancer and the Environment Research Centers: Transdisciplinary Research on the Role of the Environment in Breast Cancer Etiology
Authors: Robert A. Hiatt, Sandra Z. Haslam, Janet Osuch
Journal: Environmental Health Perspectives (2009)

We introduce and describe the Breast Cancer and the Environment Research Centers (BCERC), a research network with a transdisciplinary approach to elucidating the role of environmental factors in pubertal development as a window on breast cancer etiology. We describe the organization of four national centers integrated into the BCERC network.Investigators use a common conceptual framework based on multiple levels of biologic, behavioral, and social organization across the life span. The approach connects basic biologic studies with rodent models and tissue culture systems, a coordinated multicenter epidemiologic cohort study of prepubertal girls, and the integration of community members of breast cancer advocates as key members of the research team to comprise the network.Relevant literature is reviewed that describes current knowledge across levels of organization. Individual research questions and hypotheses in BCERC are driven by gaps in our knowledge that are presented at genetic, metabolic, cellular, individual, and environmental (physical and social) levels.As data collection on the cohort, animal experiments, and analyses proceed, results will be synthesized through a transdisciplinary approach.Center investigators are addressing a large number of specific research questions related to early pubertal onset, which is an established risk factor for breast cancer. BCERC research findings aimed at the primary prevention of breast cancer will be disseminated to the scientific community and to the public by breast cancer advocates, who have been integral members of the research process from its inception.
Abstract 304: The Effects of Compression Waveforms on the Outcomes of Cardiopulmonary Resuscitation in a Porcine Model of Cardiac Arrest
Authors: Xiaobo Wu, Zhengfei Yang, Wanchun Tang
Journal: Circulation (2014)

Background: Previous studies have demonstrated that different mechanical compression waveforms yield different hemodynamic efficacy. In the present study, we investigated the effects of two different compression waveforms on the hemodynamics and defibrillation efficacy in a pig model of CPR. Methods: Ventricular fibrillation was electrically induced in ten male domestic pigs weighing between 35 - 40 kg and untreated for 7 mins. The animals were then randomized to receive chest compression with either trapezoidal (TW) or sinusoidal (SW) waveform. After a total 5 mins of CPR, defibrillation was attempted. ECG, aortic blood pressure (AP), right atrium blood pressure (RAP) and carotid blood flow (CBF) were continuously record and analyzed after the experiments were completed. Results: All animals were resuscitated. The total defibrillation attempts in the TW group were significantly fewer than the SW group (1.6±0.9 vs. 11±7.8, p=0.03) prior to successful resuscitation. Amplitude spectrum analysis (AMSA) and signal integral were significantly greater in each minute of CPR in the TW group when compared with the SW group (Figure 1). Significantly greater CPPs were observed in the TW group during the last 3 mins of CPR. Mean CBF showed no difference during CPR between the two groups, but the dynamic forward CBF in the first 4 mins of CPR was significantly greater in the TW group (Figure 2). Conclusions: Chest compression with trapezoidal waveform improved hemodynamics and defibrillation efficacy in the pig model of CPR. Compression waveform therefore became another important factor to be considered during mechanical chest compression.
Abstract 2776: Overexpression of HGF is an effective indicator for Met-targeting therapy in hepatocellular carcinoma
Authors: Qian Xie
Journal: Cancer Research (2014)

Abstract The success of molecular targeted therapy against cancer depends on discovering the essential pathways that contribute to carcinogenesis and cancer progression and the molecular targets that control the pathway activity. By using genetically engineered mouse models, we show that overexpression of Hepatocyte growth factor (HGF) stimulated HBV surface antigen (HBsAg) production and accelerated the HCC progression. HGF transgenic mouse model produced spontaneous HCC with genomic profiles similar to that HBV-positive HCC patients with poor prognosis. Mechanistically, MET receptor expression is required for repair of virus-induced liver damage and HCC development. Importantly, HGF overexpression induces an autocrine activation which determines the sensitivity to small-molecule Met inhibitors. MET inhibitors are entering clinical trials against cancer, and our data provide a molecular basis for targeting the Met pathway in hepatitis B-induced HCC. Our results demonstrate that HGF is a driver of HBV-induced HCC progression and may serve as an effective biomarker for Met-targeted therapy, and that hgf-transgenic mouse model serves as a good tool for studying human HCC biology and preclinical evaluating therapeutics. Citation Format: Qian Xie. Overexpression of HGF is an effective indicator for Met-targeting therapy in hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2776. doi:10.1158/1538-7445.AM2014-2776
英国帕金森病研究小组对联合应用左旋多巴和司来吉林治疗早期、轻型帕金森病致额外死亡的研究:随机和可信的深入研究
Authors: Ben-Shlomo, Churchyard, Hurwitz, Overstall, Ockelford, 秦斌, 曾湘豫, 刘士民
Journal: BMJ (1998)

目的:探讨是否可用帕金森病修订的诊断、自主神经作用、心血管作用、更快的疾病进展或药物相互作用来解释服用左旋多巴和司来吉林随机试验病人的额外死亡。设计:采用开放、随机试验、双盲对照和对死亡原因重新再分组的方法进行研究,病人来源于1985～1990年间93所医院,统计截止于1993年12月前死亡的病人,分第一组和第二组。组织单位:英国研究对象:624例没有接受过多巴胺制剂治疗的早期帕金森病病人和在试验期间死亡的120例。研究方法:第一组服用左旋多巴和多巴脱羧酶抑制剂;第二组服用左旋多巴和多巴脱羧酶抑制剂并联合应用司来吉林;第三组单独服用溴隐亭。主要数据:第一、二组520例及由第三组随机分到第一、二组的104例病人的死亡原因。根据专家组意见、修订的诊断和疾病残疾程度、自主神经和心血管疾病记录的证据、死前其它临床特征和药物相互作用,分析死于原来第一、二组病例的特殊额外死因。结果:将随访延期到1995年9月底(平均6.8年),当第二组试验停止时,第二组的危险比与第一组相比是1.32(95%可信范围在0.98～1.79之间)。将第三组病例随机分入第二组后,其危险比是1.54(0.83～2.87)。当包括全部病例时,其危险比是1.33(1.02～1.74),调整其它基本因素后其危险比是1.30(0.99～1.72)。其额外死亡似乎在随访至第三或四年时为最高。病因特异性死亡率显示额外死亡仅源于帕金森病(其危险率是2.5(1.3～4.7))。修订的诊断、疾病的残疾记分、自主神经或心血管意外、其它临床特征或药物相互作用等均未发现有明显差异。第二组与第一组相比,发现第二组病人在死亡前多合并有可能的痴呆和摔倒史。结论:这些结果一致地显示服用左旋多巴和司来吉林联合治疗的病人有额外死亡。修订的诊断、自主神经和心血管意外或药物的相互作用都不能
Abstract 3957: RGDS-Epitope Presenting Peptide Amphiphile Nanofibers Enhance Regenerative Potency of Cell-based Strategies in Ischemic Tissue
Authors: Joern Tongers, Matthew J Webber, Marie-Ange Renault, Jerome G Roncalli, Samuel I Stupp, Douglas W Losordo
Journal: Circulation (2008)

Cell-based therapies have emerged as a promising therapeutic option, however autologous approaches may be limited by the impaired potency of cells collected from patients with advanced vascular disease. Advances in bionanotechnology have led to the development of biomaterials that may offer solutions to overcome certain limitations and to enhance the therapeutic potency of cell-therapies. We evaluated a peptide amphiphile (PA) nanofiber that self-assembles 3-dimensionally, mimicing the extracellular matrix, and incorporates bioactive epitopes of interest. Based on the importance of fibronectin for endothelial progenitor cell (EPC) adhesion, motility and survival, the RGDS-epitope that functionally mimics the integrin-binding sequence of fibronectin was integrated for presentation (RGDS PA). For in vitro studies, EPCs were expanded from the bone marrow derived mononuclear cell fraction under endothelial culture conditions. Incubation with RGDS-PA (0.2w%) reduced H 2 O 2 induced apoptosis of EPCs significantly (0.20±0.02 TUNEL + /TUNEL − EPCs) compared to control cells without RGDS-PA (0.64±0.09, n= 5–7, P&lt;0.01). RGDS-PA also induced proliferation of EPC in vitro (MTS assay; RGDS-PA 356±42% vs. 100% control, n= 5–9, P&lt;0.01). Pre-incubation/Culture of EPCs with RGDS-PA led to an increase in adherent cells on uncoated (32±10 vs. 3±1, P&lt;0.05), vitronectin (130±18 vs. 5±3, P&lt;0.01) and fibronectin (109±12 vs. 39±2, P&lt;0.05) coated but not on collagen coated surfaces compared to control cells. Hind-limb ischemia was surgically induced in 8 week-old, male FVB/N mice by complete ligation of the proximal femoral artery including all superficial and deep branches; postoperatively ischemia was verified by laser Doppler imaging. Suspension of subtherapeutic cell-doses in RGDS-PA solution for combined application enhanced recovery of laser Doppler-derived blood flow (ischemic vs. non-ischemic limb ratio: RGDS-PA 0.67±0.06 vs. saline 0.55±0.04) and reduced the amputation rate compared to cells alone at day 28 (amputation score: RGDS-PA 3.6±0.2 vs. saline 3.0±0.1; n=5– 8/group, P&lt;0.05).In conclusion, the RGDS-epitope presenting PA nanofiber enhances survival, proliferation and adhesion of EPCs and augments potency for ischemic tissue repair.
N-3 Fatty Acids for the Prevention of Atrial Fibrillation After Coronary Artery Bypass Surgery
Authors: Leonardo Calò, Leopoldo Bianconi, Furio Colivicchi, Filippo Lamberti, Maria Luisa Loricchio, Ermenegildo de Ruvo, Antonella Meo, Claudio Pandozi, Mario Staibano, Massimo Santini
Journal: Journal of the American College of Cardiology (2005)
Abstract A23: eIF4F is a key and targetable convergence nexus of multiple mechanisms of resistance to anti-BRAF and anti-MEK cancer therapies
Authors: Lise Boussemart, Helene Malka-Mahieu, Isabelle Girault, Delphine Allard, Oskar Hemmingson, Nyam Kamsu-Kom, Sandrine Agoussi, Alexander Eggermont, Laurent Desaubry, Caroline Robert, Stephan Vagner
Journal: Clinical Cancer Research (2015)

Abstract The V600E mutation in BRAF is the most frequent oncogenic mutation in human cancers, and can be targeted by specific anti-BRAF agents. However, several mechanisms of resistance have been identified, leading to reactivation of the initially blocked MAP-kinase pathway (known as ERK-dependent mechanisms) or reactivation of alternative ones, like the PI3K-AKT-mTOR pathway, or inhibition of the apoptotic cascade (ERK-independent). These pathways converge to regulate the formation of the eIF4F translation initiation complex that binds to the 7-methylguanosine cap at the 5′ end of mRNAs, thereby modulating mRNA translation of specific mRNAs. We addressed the potential role of the eIF4F eukaryotic translation initiation complex in resistance or sensitivity to anti-BRAF and anti-MEK agents in several BRAF mutant cells, xenografts and tumors. Our data demonstrate that the formation of the eIF4F complex is associated with most resistance mechanisms to these targeted therapies, independently of their capacity to reactivate or not the MAP-kinase pathway. Formation of this complex can be explored in tumor samples using a new in situ technology. Inhibitors of the eIF4F complex synergize with anti-BRAF agents and can thus reverse resistance. Citation Format: Lise Boussemart, Helene Malka-Mahieu, Isabelle Girault, Delphine Allard, Oskar Hemmingson, Nyam Kamsu-Kom, Sandrine Agoussi, Alexander Eggermont, Laurent Desaubry, Caroline Robert, Stephan Vagner. eIF4F is a key and targetable convergence nexus of multiple mechanisms of resistance to anti-BRAF and anti-MEK cancer therapies. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A23.
Managing the Patient with Venous Ulcers
Authors: Tami de Araujo, Isabel Valencia, Daniel G. Federman, Robert S. Kirsner
Journal: Annals of Internal Medicine (2003)

Venous disease is the most common cause of leg ulcers. The refractory nature of venous ulcers affects the quality of life and work productivity of those persons afflicted. This, in combination with the high costs of long-term therapy, makes venous ulcers a major health problem in developed countries. Management of venous leg ulcers is based on understanding pathophysiologic abnormalities. In recent years, identifying prognostic factors for healing and developing novel therapeutic approaches for venous ulcers have offered valuable tools for the management of patients with this disorder.
Treatment for erythropoietic protoporphyria
Authors: J.G. Langendonk
Journal: British Journal of Dermatology (2015)

Journal Article Treatment for erythropoietic protoporphyria Get access J.G. Langendonk J.G. Langendonk Department of Internal Medicine Netherlands Porphyria Centre Center for Lysosomal and Metabolic Diseases Erasmus MC Rotterdam the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 6, 1 June 2015, Pages 1481–1482, https://doi.org/10.1111/bjd.13769 Published: 01 June 2015
Benign prostatic hyperplasia
Authors: R. Kirby
Journal: BMJ (1999)

<h3>ABSTRACT</h3> <h3>Background</h3> Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDD) and Multiple Sclerosis (MS). <h3>Methods</h3> Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse – Central Nervous System) programme. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender. <h3>Results</h3> Participants with MDD (N=255) and MS (N=214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. Lower mean HR and HR variation were observed between pre and during lockdown during the day for MDD and during the night for MS. HR variation during rest periods also decreased between pre-and post-lockdown in both clinical conditions. We observed a reduction of physical activity for MDD and MS upon the introduction of lockdowns. The group with MDD exhibited a net increase in social interaction via social network apps over the three periods. <h3>Conclusions</h3> Behavioral response to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDD and MS.
Stress Testing: Principles and Practice.
Authors: Myrvin H. Ellestad
Journal: Annals of Internal Medicine (1988)

History of stress testing cardiovascular and pulmonary responses to exercise extra-cardiac effects of exercise physiology of cardiac ischemia stress testing protocol ECG patterns and their significance rhythm and conduction disturbances in stress testing stress testing in women sports medicine and rehabilitation paediatric exercise testing metabolic abnormalities and drugs.
A memorable patient: An effective reproof
Authors: A. Elkington
Journal: BMJ (1998)

The man in the wheelchair was in his 70s. The ravages of longstanding rheumatoid arthritis had played havoc with his joints. He wanted advice about his dry eyes. One of the students took a careful history and another gave a detailed description of the gross deformity of the patient's hands. I ventured that he must find everyday manual …