tbuckley/cabot-search huggingface dataset:
Abstract 2794: Ex vivo chemoresponse assay using patient-derived tumor xenografts in combination with high content imaging platform as models for oncology drug development.
Authors: Mansi Garg, Martin Vo, Jill Ricono, Thomas Broudy, Cyrus Mirsaidi, Kesavan Nair Praveen
Journal: Cancer Research (2013)

Abstract Current strategies for developing new anticancer drugs rely heavily on preclinical testing in cancer cell lines and their derived in vivo cell line xenograft models. The value of a predictive assay is heavily dependent on the extent to which it can recapitulate the biology of disease. It has been reported that heterogeneity of cell populations within the tumor microenvironment has significant correlation with the efficacy of any treatment regimen. Cell line models fail to recapitulate the heterogeneous nature of tumor. The purpose of this study was to investigate whether the use of patient-derived primary tumor cells (PTC) could be expanded as xenografts for in vitro chemosensitivity assays to predict clinical outcomes in anticancer drug testing. We have developed preclinical cancer models using PTCs grown in 3D cultures that better mimic in vivo conditions. One of the disadvantages of using patient derived cells is the limited number of cells available from biopsy samples. We utilized patient-derived xenografts (PDX) as a strategy to expand the human tumor cells in mice, while taking efforts to retain the actual tumor biology of the patient. We used high content imaging to evaluate colony segmentation, morphological features, proliferative and apoptotic endpoints to determine efficacy of oncology drug candidates. We conducted a retrospective study using PTCs from solid tumor indications including endometrial and lung to evaluate the correlation between various models and usefulness in predicting the outcome of a specific drug candidate. Our results indicate that PDX models in combination with 3D PTC models have predictive value and enable secondary interrogation beyond single agent anti-proliferative activity to better profile the antitumor activity of targeted agents. Improved preclinical models are required to advance our understanding of the molecular aberrations that underpin cancer and are critical for developing and deploying targeted therapies that will improve patients’ lives. Citation Format: Mansi Garg, Martin Vo, Jill Ricono, Thomas Broudy, Cyrus Mirsaidi, Kesavan Nair Praveen. Ex vivo chemoresponse assay using patient-derived tumor xenografts in combination with high content imaging platform as models for oncology drug development. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2794. doi:10.1158/1538-7445.AM2013-2794
Discrimination Against Foreign Graduates
Authors: BHARAT S. SHAH
Journal: Annals of Internal Medicine (1979)

To the editor: I was shocked to see a blatantly discriminatory classified advertisement starting with "Internist—ER Physician: Seeking American medical school graduate. . . ." on the classified pages of the June issue. Your journal has always strived to maintain the highest moral and ethical standards in its editorial and advertisement pages. It has, for reasons unknown, stayed away from discussion of the so-called "FMG-problem," implying that it has no particular policy on FMGs (foreign medical graduates) as such and that they should be treated as any other physician. The appearance of the abovementioned advertisement makes one wonder whether this
Évaluation de la vidéocapsule oesophagienne (VCO) PillCam® pour le dépistage de carcinome épidermoïde ou de lésion dysplasique de l'œsophage chez le sujet à risque élevé
Authors: PN Dhalluin, MG Lapalus, F Cholet, E Ben Soussan, M Gaudric, K Vahedi, JC Saurin, B Filoche, D Heresbach
Journal: Endoscopy (2008)

Introduction: Le cancer épidermoïde de l'œsophage (CEO) représente 5% des cancers chez l'homme, 1% des cancers chez la femme, et représente le troisième cancer digestif avec 5 200 nouveaux cas par an. Le pronostic du CEO est nettement amélioré lorsqu'il est dépisté précocement. L'objectif de notre étude est d'évaluer la sensibilité de la VCO chez les patients à risque élevé de cancer épidermoïde de l'œsophage.
FRI0479-HPR Measurement of therapeutic effect of ultrasound on knee osteoarthritis; double blind study
Authors: N. Basic-Kapidzic, A. Imsirovic, A. Music
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Therapeutic ultrasound is often used in the treatment of knee osteoarthritis (OS), however, sufficient evidence of its effect is lacking. More scientific evidence is needed to confirm its effect. <h3>Objectives</h3> The aim of this work is to determine the effect of ultrasound therapy on pain, stiffness and functional ability of patients with knee OA. <h3>Methods</h3> This was randomized, double blind, placebo controlled study of continuous effects of ultrasound on knee OA conducted in out-patients clinic for physical medicine and rehabilitation. Examination was conducted on 80 patients with knee OA, mean age of 60 years and average duration of clinical difficulties of 8,3 years. Physical therapy (PT) lasted for three weeks. All patients also had thermotherapy and exercises. Additional therapy with continuous ultrasound, with 0,8 W/cm<sup>2,</sup> that lasted for 5 minutes, was applied to 40 patients (group A) and 50 patients had placebo ultrasound (group B). For objectification of difficulties we used Lekrt's scale for pain evaluation, and Lequesne index and Womac scale with subscales for pain, stiffness and functional disability evaluation. We measured joint circumference, joint movement, and brute muscle strength with manual muscle test before and after PT. Test- retest examination was conducted. <h3>Results</h3> In both group there was significant reduction of pain and improvement of functional ability (p&lt;0, 0001). Difference in pain evaluation before and after treatment was in group A 1,6±0,70, and in group B 1,0±0,71. Reduction in Lequesne index was 4,36±1,75 in group A and 3,43±1.74 in group B. Womac for pain was reduced in group A for 0,83±0.51 and in group B 0,53±0,40; for stiffness in group A 0,83±0,46, and in group B 0,49±0,44; for function in group A 0,61±0,55 and in group B 0,38±0,70. All differences were significantly better in group A. There were no changes in joint circumference and muscle strength was remotly improved; in average for half score in both groups. <h3>Conclusions</h3> Therapy with continuous ultrasound in comparison with placebo showed significant efficacy in treatment of knee OA, because it leads to significant reduction of pain, stiffness and improvement of functional status. <h3>Disclosure of Interest</h3> None Declared
135. AAV-Mediated Gene Delivery To Evaluate the Biology of an Inherited Macular Degeneration
Authors: Nicholas W. Keiser, Daniel C. Chung, Waixing Tang, Zhanyong Wei, Albert Maguire, Jean Bennett, Jeannette L. Bennicelli
Journal: Molecular Therapy (2005)

Malattia Leventinese (ML) is an autosomal dominant inherited macular degeneration with a middle-age onset. Phenotypically, the disease closely resembles Age-related Macular Degeneration (AMD), a condition affecting 20% of the population over age 65 and the leading cause of blindness in the elderly in the Western world. There is no cure for macular degeneration, and the supportive treatments are limited. Patients with ML suffer from decreased visual acuity and have a characteristic radial pattern of spots, called drusen, in their maculas. Clinical exam reveals geographic atrophy, pigmentary changes, and choroidal neovascularization. Histopathology reveals deposits between the retinal pigment epithelium (RPE) and Bruch's membrane, similar to what is found in AMD. A missense mutation, R345W, in the Epidermal Growth Factor Containing Fibrillin-like Extracellular Matrix Protein 1 (EFEMP1) gene is responsible for the disease, and leads to the misfolding and inefficient secretion of the protein. To gain insight into the role of EFEMP1 in the retina in health and disease, we studied the localization of the wild-type Efemp1 protein and mRNA in the developing mouse retina. Efemp1 protein localizes first to the inner retina and RPE of the mouse, with localization to photoreceptors detectable by postnatal day 14. We also found that Efemp1 protein colocalized with TIMP-3 in the inner retina throughout murine ocular development. Efemp1 mRNA was broadly distributed across the developing retina, and then was concentrated in photoreceptors and ganglion cells by adulthood. An AAV2/5 vector carrying FLAG-tagged mutant Efemp1 was delivered into the wild-type mouse retina, and this resulted in the targeting of the fusion protein to the photoreceptors and RPE. There, it was detected in cytoplasmic aggregates by EM immunohistochemistry. We also identified radial lesions resembling those seen in ML patients. Studies involving non-human primates are in progress. Our results demonstrate that EFEMP1 is a component of the inner and outer retina, but that the mutant form aggregates in the cytoplasm and induces lesions by a yet unknown mechanism. Generation of ML-like lesions in mice and non-human primates via gene delivery promises to be useful in generating animal models for macular degenerative disease in order to define the pathogenetics of the disease and to identify therapeutic targets.
Prenatal Exposure to Phthalates and Infant Development at 6 Months: Prospective Mothers and Children’s Environmental Health (MOCEH) Study
Authors: Yeni Kim, Eun–Hee Ha, Eui–Jung Kim, Hyesook Park, Mina Ha, Ja–Hyeong Kim, Yun–Chul Hong, Namsoo Chang, Bung–Nyun Kim
Journal: Environmental Health Perspectives (2011)

Background: There are increasing concerns over adverse effects of prenatal phthalate exposure on the neurodevelopment of infants.Objectives: Our goal was to explore the association between prenatal di(2-ethylhexyl) phthalate and dibutyl phthalate exposure and the Mental and Psychomotor Developmental Indices (MDI and PDI, respectively) of the Bayley Scales of Infant Development at 6 months, as part of the Mothers and Children's Environmental Health Study.Methods: Between 2006 and 2009, 460 mother–infant pairs from Seoul, Cheonan, and Ulsan, Korea, participated. Prenatal mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MBP) were measured in one urine sample acquired from each mother during the third trimester of pregnancy. Associations with log-transformed creatinine-corrected phthalate concentrations were estimated using linear regression models adjusted for potential confounders.Results: MDI was inversely associated with the natural log concentrations (micrograms per gram creatinine) of MEHHP [β = –0.97; confidence interval (CI), –1.85 to –0.08] and MEOHP (β = –0.95; CI, –1.87 to –0.03), and PDI was inversely associated with MEHHP (β = –1.20; CI, –2.33 to –0.08). In males, MDI was inversely associated with MEHHP (β = –1.46; CI, –2.70 to –0.22), MEOHP (β = –1.57; CI, –2.87 to –0.28), and MBP (β = –0.93; CI, –1.82 to –0.05); PDI was inversely associated with MEHHP (β = –2.36; CI, –3.94 to –0.79), MEOHP (β = –2.05; CI, –3.71 to –0.39), and MBP (β = –1.25; CI, –2.40 to –0.11). No significant linear associations were observed for females.Conclusions: The results suggest that prenatal exposure to phthalates may be inversely associated with the MDI and PDI of infants, particularly males, at 6 months.
Preliminary experience with a hospital blood pressure follow up clinic with nurse practitioner assessment and microprocessor based data retrieval.
Authors: P C Rubin, J L Curzio, A Kelman, H L Elliott, J L Reid
Journal: BMJ (1984)

Experience over two years with 376 hypertensive patients managed at a clinic where the primary observations are made by a trained nurse, clinical information is held on a microprocessor, and treatment follows a standard stepped care approach has been assessed. Blood pressure control after both one and two years was appreciably improved, with over 70% of patients having diastolic pressure below 90 mm Hg compared with 22% of patients when they first attended the new clinic. The non-attendance rate was half that of the conventional hospital outpatient clinic. A computer based record system with a nurse run hypertension clinic is acceptable to patients and offers the possibility of more effective long term control of blood pressure in large numbers of patients.
Risk of posttransfusion hepatitis in the United States. A prospective cooperative study
Authors: G. F. Grady
Journal: JAMA (1972)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
THE AGE AND SEX INCIDENCE AND ANATOMICAL DISTRIBUTION OF ORAL LEUCOPLAKIA AND LICHEN PLANUS.
Authors: H. E. SIMPSON
Journal: British Journal of Dermatology (1957)

Journal Article THE AGE AND SEX INCIDENCE AND ANATOMICAL DISTRIBUTION OF ORAL LEUCOPLAKIA AND LICHEN PLANUS. Get access H. E. SIMPSON, M.D.S. H. E. SIMPSON, M.D.S. Department of Oral Pathology, Sutherland Dental School Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 69, Issue 5, 1 May 1957, Pages 178–180, https://doi.org/10.1111/j.1365-2133.1957.tb13252.x Published: 01 May 1957
Body surface potential maps in patients with pulmonic valvular and aortic valvular stenosis of mild to moderate severity.
Authors: G S Sohi, E W Green, N C Flowers, D E McMartin, R R Masden
Journal: Circulation (1979)

Multiple-lead surface potential maps were compared throughout ventricular activation in nine patients with mild-to-moderate pulmonic stenosis and in 12 patients with mild-to-moderate aortic stenosis. Abnormal patterns of potential distribution were found in aortic stenosis, including three patients without electrocardiographic evidence of left ventricular enlargement. When related to the onset of depolarization, abnormal departures started later, peaked later, lasted longer, and were more intense, more uniform and discrete in aortic stenosis. In pulmonic stenosis, abnormal departures started earlier, but were more dispersed in timing and location than in aortic stenosis. The left ventricle appears to be the more remote, though more powerful and compact, generator. The right ventricular shell, however, is nearer to the surface, and is more anatomically extended in surface area, permitting much wider shifts in wavefront location and orientation as a result of small differences in pressure, or volume, or location of the heart in the thorax.
The Prevalence of Clinical Cross-reactivity of Non-peanut Legumes to Peanut in Patients with Persistent Peanut Allergy
Authors: D.L. Neuman-Sunshine, J.A. Eckman, C.A. Keet, E.C. Matsui, R.D. Peng, P.J. Lenehan, R.A. Wood
Journal: Journal of Allergy and Clinical Immunology (2012)
Hepatic mitochondrial proliferation in rats with secondary biliary cirrhosis: Time course and mechanisms
Authors: M Forestier, M Solioz, F Isbeki, C Talos, J Reichen, S Krahenbuhl
Journal: Hepatology (1997)

It is well known that the hepatic mitochondrial protein content is increased in rats 4 weeks after bile duct ligation. In the present study, we measured the time course of this increase and assessed the levels of selected mitochondrial messenger RNA (mRNA) species and the rate of mitochondrial protein synthesis by isolated mitochondria. Three days after surgery, the mitochondrial protein content was not significantly different between bile duct-ligated (BDL) and control rats, averaging 1,140 ± 220 mg/liver in BDL and 1,260 ± 50 mg/liver in sham-operated control rats. However, in comparison with control rats, it was increased in BDL rats by 35% at 7 days, by 81% at 14 days, and by 27% at 28 days after surgery. In vitro mitochondrial protein synthesis, which was assessed as the fractional incorporation of [35S]-methionine into mitochondrial protein, was not different between BDL and control rats at 3 days after surgery, but was decreased in BDL rats by 63% at 7 days, by 55% at 14 days, and by 36% at 28 days after surgery. Northern blot analysis revealed an increase in the mRNA levels of adenosine triphosphate (ATP)ase subunit 6 and apocytochrome b in BDL rats at day 7, but no significant differences between BDL and control rats in mitochondrial mRNA and ribosomal RNA species 14 and 28 days after surgery. These results show that the hepatic mitochondrial protein content rises early after surgery in BDL rats, but this rise cannot be ascribed to elevated rates of mitochondrial protein synthesis. Thus, increased synthesis of nuclearly encoded mitochondrial proteins and/or decreased degradation of mitochondrial proteins appear likely mechanisms that lead to the observed increase in the hepatic mitochondrial protein content in BDL rats.
Control of G1 arrest after DNA damage.
Authors: M B Kastan, S J Kuerbitz
Journal: Environmental Health Perspectives (1993)

The temporal relationship between DNA damage and DNA replication may be critical in determining whether the genetic changes necessary for cellular transformation occur after DNA damage. Recent characterization of the mechanisms responsible for alterations in cell-cycle progression after DNA damage in our laboratory have implicated the p53 (tumor suppressor) protein in the G1 arrest that occurs after certain types of DNA damage. In particular, we found that levels of p53 protein increased rapidly and transiently after nonlethal doses of gamma irradiation (XRT) in hematopoietic cells with wild-type, but not mutant, p53 genes. These changes in p53 protein levels were temporally linked to a transient G1 arrest in these cells. Hematopoietic cells with mutant or absent p53 genes did not exhibit this G1 arrest, through they continued to demonstrate a G2 arrest. We recently extended these observations of a tight correlation between the status of the endogenous p53 genes and this G1 arrest after XRT and this cell-cycle alteration after XRT was then established by transfecting cells lacking endogenous p53 genes with a wild-type gene and observing acquisition of the G1 arrest and by transfecting cells processing endogenous wild-type p53 genes with a mutant p53 gene and observing loss of the G1 arrest after XRT. These observations and their significance for our understanding of the mechanisms of DNA damage-induced cellular transformation are discussed.
Evaluation of Tubeless Gastric Analysis
Authors: Frederick P. Becker, Morris Maslon
Journal: New England Journal of Medicine (1953)

IN 1950 Segal and his associates1 introduced a method for determining free gastric hydrochloric acid based on release of quininium cation from a synthetic ion-exchange resin by the hydrogen ion in gastric secretion. The resin granules were given orally, in a dosage of 2 gm. Two-hourly urine samples were then analyzed for quinine, the presence of quinine in appreciable concentration indicating free gastric hydrochloric acid. Later, Segal et al.2 described the procedure in greater detail, reporting results in 106 patients. The test was found to have a high degree of accuracy when compared with gastric analyses conducted previously on samples . . .
Antioxidant Ceruloplasmin Is Expressed by Glomerular Parietal Epithelial Cells and Secreted into Urine in Association with Glomerular Aging and High-Calorie Diet
Authors: Jocelyn E. Wiggins, Meera Goyal, Bryan L. Wharram, Roger C. Wiggins
Journal: Journal of the American Society of Nephrology (2006)

Biologic aging is accelerated by high-calorie intake, increased free radical production, and oxidation of key biomolecules. Fischer 344 rats that are maintained on an ad libitum diet develop oxidant injury and age-associated glomerulosclerosis by 24 mo. Calorie restriction prevents both oxidant injury and glomerulosclerosis. Ceruloplasmin (Cp) is a copper-containing ferroxidase that functions as an antioxidant in part by oxidizing toxic ferrous iron to nontoxic ferric iron. Glomerular Cp mRNA and protein expression were measured in ad libitum-fed and calorie-restricted rats at ages 2, 6, 17, and 24 mo. In ad libitum-fed rats, Cp mRNA expression increased six-fold (P < 0.01) and protein expression increased five-fold (P = 0.01) between 2 and 24 mo of age. In calorie-restricted rats, Cp mRNA expression increased three-fold (P < 0.01) and protein expression increased 1.6-fold (NS) between 2 and 24 mo of age. Both the cell-associated alternately spliced variant and secreted variants of Cp were expressed. Immunofluorescent analysis showed that Cp was expressed by the parietal epithelial cells that line the inner aspect of Bowman's capsule in the glomerulus. Cp also was present in urine, particularly of old ad libitum-fed rats with high tissue Cp expression. Cp expression by Bowman's capsule epithelial cells therefore occurred in direct proportion to known levels of oxidant activity (older age and high-calorie diet) and is secreted into the urine. It is suggested that Cp expression at this site may be part of the repertoire of the glomerular parietal epithelial cell to protect the glomerular podocytes and the downstream nephron from toxic effects of filtered molecules, including ferrous iron.
Shared Ethnic Scotoma
Authors: EDITH T. SHAPIRO, HENRY PINSKER
Journal: American Journal of Psychiatry (1973)

A number of writers have advanced the opinion that it is beneficial to a patient to have a therapist of the same ethnic background. The authors point out that this may lead to "blind spots" that prevent the therapist from seeing the irrationality of certain of the patient's attitudes. They give three case examples that illustrate this point.
T Cell Affinity Maturation by Selective Expansion during Infection
Authors: Dirk H. Busch, Eric G. Pamer
Journal: The Journal of Experimental Medicine (1999)

T lymphocyte recognition of infected cells is mediated by T cell receptors (TCRs) interacting with their ligands, self–major histocompatibility complex (MHC) molecules complexed with pathogen-derived peptides. Serial TCR interactions with potentially small numbers of MHC/ peptide complexes on infected cells transmit signals that result in T lymphocyte expansion and activation of effector functions. The impact of TCR affinity for MHC/peptide complexes on the rate or extent of in vivo T cell expansion is not known. Here we show that in vivo expansion of complex T cell populations after bacterial infection is accompanied by an increase in their overall affinity for antigen. T cell populations that have undergone additional rounds of in vivo expansion express a narrower range of TCRs, have increased sensitivity for antigen in cytotoxic T lymphocyte assays, and bind MHC/peptide complexes with greater affinity. The selective expansion of higher affinity T cells provides an in vivo mechanism for optimizing the early detection of infected cells.