tbuckley/cabot-search huggingface dataset:
The Arts of Healing
Authors: M J Friedrich
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Delayed graft function and the risk of acute rejection in the modern era of kidney transplantation
Authors: W. Kelly Wu, Olusegun Famure, Yanhong Li, S. Joseph Kim
Journal: Kidney International (2015)

Delayed graft function (DGF) is commonly considered a risk factor for acute rejection, although this finding has not been uniformly observed across all studies. The link between DGF and acute rejection may have changed over time due to advances in immunosuppression and medical management. Here we conducted a cohort study of 645 patients over 12 years to evaluate the association of DGF and biopsy-proven acute rejection (BPAR) in a modern cohort of kidney transplant recipients. DGF was defined as the need for at least one dialysis session in the first week after kidney transplantation. The 1-, 3-, and 5-year cumulative probabilities of BPAR were 16.0, 21.8, and 22.6% in the DGF group, significantly different from the 10.1, 12.4, and 15.7% in the non-DGF group. In multivariable Cox proportional hazards model, the adjusted relative hazard for BPAR in DGF (vs. no DGF) was 1.55 (95% confidence interval (CI): 1.03, 2.32). This association was generally robust to different definitions of DGF. The relative hazard was also similarly elevated for T-cell- or antibody-mediated BPAR (1.52 (0.92, 2.51) and 1.54 (0.85, 2.77), respectively). Finally, the association was consistent across clinically relevant subgroups. Thus DGF remains an important risk factor for BPAR in a contemporary cohort of kidney transplant recipients. Interventions to reduce the risk of DGF and/or its aftereffects remain of paramount importance to improve kidney transplant outcomes.
Fibroblast growth factor 8 induces osteoclast differentiation in vitro and increases experimental bone metastasis of MDA-MB-231 breast cancer cells in vivo in nude mice
Authors: Mirjami M. Mattila, Tiina Laitala-Leinonen, Kalman G. Büki, Katri S. Selander, Johanna M. Tuomela, Sanna S. Virtanen, H. Kalervo Väänänen, Pirkko L. Härkönen
Journal: Cancer Research (2006)

3973  Fibroblast growth factor 8 (FGF8) is involved in regulation of growth of breast and prostate cancer cells which preferentially metastasize to bone. We have previously shown that overexpression of FGF8 (isoform b) in breast cancer cells increases tumor growth and angiogenesis in nude mice. Here we studied the role of FGF8 in formation of breast cancer metastasis in bone. MDA-MB-231 human breast cancer cells forming osteolytic bone metastases were transfected with FGF8 isoforms a, b and e. The in vitro proliferation and invasion of FGF8-transfected MDA-MB-231 cells did not differ from those of vector-transfected control cells (MDA-MB-231-Mock cells), nor did the growth rate of the orthotopical tumors in nude mice. However, when the cells were injected intracardially into nude mice micro x-ray analysis in vivo and histomorphometry of long bones ex vivo showed that FGF8-transfected MDA-MB-231 cells, especially MDA-MB-231-FGF8e cells, formed larger tumor colonies than MDA-MB-231-Mock cells. We studied the possibility that this could be explained by stimulation of osteoclast formation by FGF8 using co-cultures of MDA-MB-231-FGF8 cells with mouse bone marrow cells. We found that in co-cultures MDA-MB-231-FGF8 cells were able to induce increased osteoclast differentiation compared to MDA-MB-231-Mock and MDA-MB-231 wild type cells. Furthermore, FGF8e and FGF8b recombinant proteins were able to stimulate osteoclast differentiation alone when added to mouse bone marrow cultures on bone slices in vitro. Addition of osteoprotegerin (OPG) to the cultures together with FGF8 inhibited stimulation of osteoclast differentiation suggesting that the osteoclastogenic effect of FGF8 was RANKL-mediated. In conclusion, our results show for the first time that FGF8 potently induces osteoclast differentiation in vitro. In addition, it increased formation of experimental bone metastases by MDA-MB-231 cells in nude mice in vivo. Taken together, our results suggest that breast cancer cell produced FGF8 may have a role in the promotion of bone metastasis and formation of lytic lesions of breast cancer by enhancing bone marrow stromal cell -mediated induction of osteoclast differentiation.
Abstract 1459: miR-221: A potential therapeutic target for hepatocellular carcinoma
Authors: Edmund C. Lee, Jessica Xu, Thomas Vincent, Jie Chen, Michael Nelson, Xinqiang Huang, Eric Marcusson, John Androsavich, Scott Davis, Adam Pavlicek, Neil Gibson, Sonya Zabludoff
Journal: Cancer Research (2014)

Abstract microRNAs, which control post-transcriptional gene expression by repressing mRNA translation and/or causing mRNA degradation, play important roles in human cancers. miR-221 is one of the two microRNAs in the miR-221/222 cluster located in chromosome-X, targets key cancer pathways and inhibit translation of several tumor suppressors including p27, p57, and PTEN. miR-221 is up-regulated by &amp;gt;2-fold in 55% and &amp;gt;5-fold in 14% of human hepatocellular carcinoma (HCC) tumor samples. Importantly, it has been shown in preclinical HCC models that miR-221 overexpression accelerated tumorigenesis, while miR-221 inhibition reduced tumor growth. To identify novel microRNA antagonists that specifically inhibit miR-221 (refer to as miR-221 anti-miRs) for the treatment of HCC, we have generated a number of chemically-modified oligonucleotides and screened for their ability to inhibit miR-221 functions. A number of potent and metabolically stable miR-221 anti-miRs devoid of proinflammatory potential were identified. These miR-221 anti-miRs were tested in a number of human HCC cell lines that highly express miR-221 compare to normal adult human hepatocytes. We demonstrated the de-repression of both p27 mRNA and p27 protein in HCC cells following treatment with miR-221 anti-miRs. We also showed in HCC cells the de-repression of a novel miR-221 target gene recently identified through an argonuate pull-down assay (Ago-IP), alongside with the enrichment of global miR-221 target seeds (as defined by TargetScan) following miR-221 anti-miRs treatment. We then sought to determine the biologic consequences following miR-221 inhibition in HCC cells. In standard cell proliferation assays, we demonstrated that HCC cells responded to miR-221 anti-miRs treatment with IC50s of 125 to 500nM under free-uptake conditions and IC50s of 5 to 75 nM under transfection conditions. In addition, we also showed that miR-221 anti-miRs treatment disrupted HCC cell cycle transition. Altogether, our data showed that miR-221 inhibition de-repressed p27, blocked cell cycle progression and reduced cell proliferation in HCC cells, and supports the notion of miR-221 as a potential therapeutic target for the treatment of HCC. Further preclinical testing of our miR-221 anti-miRs is currently in progress. Citation Format: Edmund C. Lee, Jessica Xu, Thomas Vincent, Jie Chen, Michael Nelson, Xinqiang Huang, Eric Marcusson, John Androsavich, Scott Davis, Adam Pavlicek, Neil Gibson, Sonya Zabludoff. miR-221: A potential therapeutic target for 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 1459. doi:10.1158/1538-7445.AM2014-1459
Abstract 18947: What Can We Learn from Serial Echocardiographic Evaluation of the Aorta in Tetralogy of Fallot?
Authors: Matthew J Lewis, Jonathan Ginns, Marlon Rosenbaum
Journal: Circulation (2014)

Introduction: Guidelines for management of aortic root (AoR) dilation with known aortopathies recommend surgical repair when the AoR exceeds 5 cm. Patients with tetralogy of Fallot (TOF) may have an associated aortopathy, though aortic dissection is rare. No guidelines exist regarding timing of surgical intervention. We hypothesized that the rate of AoR dilation in adults with repaired TOF would be low and that an AoR &gt; 5 cm would be associated with standard risk factors. Methods: We performed a retrospective study of all adult TOF patients who underwent a transthoracic echocardiogram (TTE) at our Center. Clinical variables and AoR dimension at the sinus of Valsalva were determined. AoR size was treated as an absolute value and as an observed-to-expected ratio based on standard nomograms. Results: 266 patients met inclusion criteria. On initial TTE, 91 (34%) patients had an AoR &gt; 4.0 cm, 9 (3%) patients had an AoR &gt; 5.0 cm, and 28 patients (11%) had an observed-to expected AoR &gt; 1.5. Male gender, hypertension, and TOF repair at &gt;5 years-old were associated with an AoR &gt; 5.0 cm while only TOF repair at &gt;5 years-old was associated with an observed-to-expected AoR &gt; 1.5. 4 patients had aortic valve (AV) surgery. One patient with an AoR of 5.8 cm had an aortic dissection following pulmonary valve replacement. 206 patients (77%) had serial TTEs. Mean age at first echo was 35.5 years. Mean time between studies was 5.5 years, and 106 patients had a &gt;5 year latency between TTEs. The mean rate of change for all patients was +0.4 mm/year. 72 patients (35%) had an increase in AoR size. 25 patients (12%) had an increase in AoR size ≥0.5cm. Only time &gt;5 years between TTEs was significantly associated with an increase in AoR ≥0.5 cm (p = 0.014). There was no significant association with either rate of AoR increase or AoR increase ≥0.5 cm and gender, hypertension, degree of AR, AV surgery, right-sided arch, AoR&gt; 5cm, time of repair, or prior pregnancy. Conclusions: In our cohort of adult patients, AoR dilatation &gt;5.0 cm was uncommon and associated with male gender, hypertension and late repair. The rate of AoR dilation was slow and without clear risk factor. In patients with severe AoR dilation, further study is required to identify significant risk factors for aortic events.
Lecture Notes on Pathology.
Authors: A. D. Thomson, R. E. Cotton
Journal: Annals of Internal Medicine (1969)

Diseases due to infections and infestations alimentary system breast cardiovascular system connnective tissue diseases soft tissue tumours ear endocrine glands eye genito-urinary system - kidney, genito-urinary tract, female genital tract liver and biliary tract - liver, biliary tract lympho-reticular system mediastinum musculo-skeletal system nervous system pancreas respiratory system skin.
Clinical characteristics and long-term survival of early breast cancer cases in the American University of Beirut Medical Center, Beirut, Lebanon
Authors: A. Shamseddine, M. Seoud, J. Abbas, M. Charafeddine, Z. Salem, F. Geara, K. Bikhazi, M. Khalifeh, M. Sidani, N. El- Saghir
Journal: Journal of Clinical Oncology (2004)

833 Background: Based on our earlier reports of increased incidence of breast cancer in younger aged-groups at presentation, we decided to review the clinical characteristics, treatment patterns and survival data of our patients (pts) with breast cancer. Patients and Methods: Retrospective review of the medical records of all pts with breast cancer treated at our institution from 1990 to 2001. Patient demographics, clinical characteristics, pathology, staging, and treatment of 1328 pts were reviewed. Follow-up data was analyzed for 810 pts. Results: Total number was 1328 pts. 43.9% were premenopausal (pre-m), and 56.1% postmenopausal (post-m). Mean age at diagnosis was 50.8± 12 years. We had 1006 patients with early stages (In-situ, 69pts, stage I: 190 and stage II: 747 pts). 249 pts stage III and 73 pts stage IV at presentation. 1259 pts (94.8%) had infiltrative breast cancer while in-situ disease was present in only 69 pts (4.2%) Stage I pts: Total number was 190 ps. 49.5% (80 pts) of them were pre-m and 50.5% (96 pts) post-m. Mean age at diagnosis is 51.1±11.8 .57% had breast-conserving surgery and 41.3% had mastectomy. 71% had positive hormonal receptors (ER+/PR+: 47.8%, ER+/PR−16.7%, ER−/PR+ 6.5%) and 29% had negative receptors. Adjuvant chemotherapy was given to 35.4% of pts. Survival analysis showed 97.2% are still alive at 10 years.. Stage II pts: Total number 747 pts. 295 (43.9%) were pre-m and 381 (56.4%) post-m. Mean age at diagnosis was 50.7±12.4. 147 pts (20%) had breast-conserving surgery and 558 pts (78.4%) had mastectomy. 66% had positive hormonal receptors (ER+/PR+: 43.9%, ER+/PR−15.2%, ER−/PR+ 6.9%) and 34% had negative receptors. 68.3% had adjuvant chemotherapy. 93.9% are alive at 2 years, 82.9% after 5 years, and 63.1% at 10 years. Conclusions: We confirm we have a high percentage of younger-aged groups at presentation. We note a trend towards earlier stages and more breast-conserving surgeries. More than two-thirds of our pts with early disease had positive hormonal receptors. Survival is excellent at 97% at 10 years for stage I pts and good at 63.1% for stage II pts. No significant financial relationships to disclose.
Study to the apoptotic pathway responsible for the radiosensitizing effect of gemcitabine
Authors: Bea Pauwels, Veronique Huygelen, Hilde Aj Lambrechts, Greet Go Pattyn, Dirk R. Van Bockstaele, Katrien Vermeulen, Marc Lenjou, Christel Mj De Pooter, Jan B. Vermorken, Filip Lardon
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

576 

Both in clinical and preclinical studies it is shown that gemcitabine has clear radiosensitizing properties. This radiosensitizing effect is dependent of the cell cycle effect, an early S phase block followed by a G2/M block, and an increased induction of apoptosis. This study was performed to clarify the apoptotic pathway responsible for radiosensitization by gemcitabine. We investigated the activation of caspase 8 and 9, both initiator caspases of the extrinsic or intrinsic pathway, respectively. The cell lines used for this study were ECV304 (mt-p53), a human bladder cancer cell line and H292 (wt-p53), a human mucoepidermoid lung cancer cell line. The cells were treated with gemcitabine (IC25 and IC90) during 24 h, radiotherapy (γ-Co60, 0-6 Gy, room temperature), or with the combination, i.e. gemcitabine immediately followed by radiation. 72h after treatment, apoptotic cell death is determined using TUNEL assay, Annexin V staining and caspase 3 activity assay. Caspase 8 and 9 activation is determined by Western blot at different time points (0-72h) after gemcitabine or radiotherapy and 72 h after the combination. Using the mitochondria-selective probe (tetramethylrhodamine methylester) and flow cytometry, the mitochondrial membrane potential (Ψ) was determined. 72 h after treatment, the combination of gemcitabine and radiotherapy resulted in a clear increase of apoptosis in both cell lines. At that moment, both procaspase 8 and 9 cleaving was observed with Western blot. In addition, Ψ was reduced when the amount of annexin V positive cells increases. To determine the order of caspase 8 and 9 activation, caspase cleaving was determined at different time points after gemcitabine or radiotherapy. In both settings, caspase 8 activation was observed at the different time points after treatment, while no cleaving products of caspase 9 could be shown. In conclusion, treatment of ECV304 and H292 cells under radiosensitizing conditions resulted in an increased induction of apoptosis with caspase 8 and 9 cleaving and a reduction of Ψ. This means that both the extrinsic and the intrinsic pathway is activated. However, treatment with gemcitabine or radiotherapy alone resulted only in activation of the extrinsic pathway. Further research is necessary to investigate the caspase 9 activation under radiosensitizing conditions. This could be a result of the increased apoptosis by the combination of gemcitabine and radiation or by Bid activation, the link between the intrinsic and the extrinsic pathway. The Belgian Federation against cancer supported this work .
Abstract 307: The Velocity of Increasing End-Tidal CO <sub>2</sub> Immediately Following Resuscitation Is Associated with Postresuscitation Myocardial Function
Authors: Lu Yin, Jie Qian, Min Yang, Ping Gong, Zhengfei Yang, Xiaobo Wu, Jena Cahoon, Wanchun Tang
Journal: Circulation (2014)

Introduction: End-tidal CO2 (ETCO2) serves as a sensitive indicator of hemodynamic efficacy during CPR and therefore predicts the success of resuscitation. In the present study, we investigated the relationship between the velocity of increasing ETCO2 immediately after successful resuscitation and post resuscitation myocardial function. Hypothesis: The velocity of increasing ETCO2 immediately following resuscitation is associated with the severity of post resuscitation myocardial dysfunction. Methods: Twenty rats were randomly assigned to one of two groups: (1) short duration of cardiac arrest (CA) (n = 10): ventricular fibrillation (VF) was untreated for 4 mins prior to 6 mins of CPR; (2) long duration of CA (n = 10): VF was untreated for 8 mins followed by 8 mins of CPR. After successful resuscitation, the first 20 secs of ETCO2 were analyzed. The velocity of ETCO2 changes was defined as the difference of the maximum and minimum ETCO2 value divided by the duration between the two ETCO2 values. Ejection fraction (EF) was measured by echocardiography at 8 hrs after resuscitation. Results: Increasing ETCO2 immediately following successful resuscitation was observed in all rats. However, the velocity of ETCO2 increasing in the group of short duration of CA was significantly faster than the group of long duration. This was associated with significantly greater EF at 8 hrs after resuscitation (Table). A close correlation between the velocity of increasing ETCO2 and EF was demonstrated (r=0.70, p&lt;0.01) (Figure). Conclusion: The velocity of increasing ETCO2 immediately following resuscitation is associated with post resuscitation myocardial function.
Polarization and interaction of adhesion molecules P-selectin glycoprotein ligand 1 and intercellular adhesion molecule 3 with moesin and ezrin in myeloid cells
Authors: José L. Alonso-Lebrero, Juan M. Serrador, Carmen Domı́nguez-Jiménez, Olga Barreiro, Alfonso Luque, Miguel A. del Pozo, Karen Snapp, Geoffrey Kansas, Reinhard Schwartz-Albiez, Heinz Furthmayr, Francisco Lozano, Francisco Sánchez-Madrid
Journal: Blood (2000)
Abstract 3744: High-throughput in vitro screening of glioma stem cell lines: Evaluation of over 350 tyrosine kinase inhibitors
Authors: Craig Thomas, Ji Liang, Yuji Piao, Nghi Nguyen, Erik Sulman, Clifford Stephan, Alfred Yung, John F. de Groot
Journal: Cancer Research (2014)

Abstract Despite the availability of hundreds of drugs, there is little data on the efficacy of these agents in the extremely heterogeneous populations of tumor cells observed in glioblastoma. A high-throughput compound-screening assay was used to identify drug sensitivities in a panel of glioma stem cell (GSC) lines to 350 tyrosine kinase inhibitors (GSK PKIS1) with varying cellular targets and mechanisms of kinase inhibition. Twelve glioma stem cell lines, which are representative of the classic TCGA molecular subtypes, were screened. Cell lines were screened in 384-well plates at a density of 1000 cells/well with drug concentrations of either 5 or 0.5 µM. Cell viability measurements were taken using Cell-Titer Glo five days after drug treatment and compared to control wells to calculate percentage inhibition. Compounds were defined as highly active (&amp;gt;90 % inhibition at 5µM; &amp;gt; 50% inhibition at 0.5µM), moderately active (&amp;gt;70% inhibition at 5µM; &amp;gt;30% inhibition at 0.5µM), or weakly active (&amp;gt;50% inhibition at 5µM; &amp;gt;15% inhibition at 0.5µM.) We identified three compounds that were highly active against eleven cell lines, three more compounds that were highly effective against at least seven cell lines, and seven additional compounds that were highly effective against at least four cell lines. The compounds in the screen were further analyzed by testing their inhibition efficacy against 220 kinases. A separate set of compounds containing molecularly targeted agents to TGF-beta, STAT3, PI3K and Notch were used for comparison of drug efficacy. Ongoing experiments are being performed to fully characterize the molecular phenotypes of the different GSC's by analyzing RNAseq, miRNA, the whole exome, the proteome, DNA methylation, and copy number variation. Integrating this information with the kinase and growth inhibition data will allow us to have a complete picture of the underlying mechanisms which drive resistance/sensitivity in GSC's. After determining which kinases are the most effective targets for the treatment of glioblastoma, promising compounds will be validated in intracranial in vivo xenograft models. Citation Format: Craig Thomas, Ji Liang, Yuji Piao, Nghi Nguyen, Erik Sulman, Clifford Stephan, Alfred Yung, John F. de Groot. High-throughput in vitro screening of glioma stem cell lines: Evaluation of over 350 tyrosine kinase inhibitors. [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 3744. doi:10.1158/1538-7445.AM2014-3744
Family Medicine: Principles and Practice
Authors: Robert B. Taylor
Journal: Annals of Internal Medicine (1989)

This updated and revised edition presents topics in common family medicine with a new format that features 120 short chapters on: common problems of the elderly, care of acute lacerations, care of the patient with chronic pain, ocular trauma, ischemic heart disease, cardiovascular emergencies, and much more. New and timely topics include the management and care of the HIV-infected patient, environmental and occupational diseases, substance abuse, contraception and menopause. This reference is geared to the office setting and mirrors the unique perspective of the family physician. It emphasizes practical detail and, arranged by organ system, provides clear diagnostic and treatment guidelines.
Abstract 9085: Matrixmetalloproteinase-12 Regulates the Antiviral Immune Response During Viral Myocarditis Through Interaction With Gene Regulatory Regions
Authors: David J Marchant, Caroline Cheung, Samuel Wadsworth, Jon Carthy, Julie Ng, Karl Heilbron, Zongshu Luo, Richard G Hegele, Christopher M Overall, Bruce M McManus
Journal: Circulation (2010)

Matrix Metalloproteinase (MMP)-12 activity has been attributed to cleavage of cytokines, and digestion of extracellular matrix components related to the pathogenesis of diverse conditions, includin...