tbuckley/cabot-search huggingface dataset:
930. Engineering Human Deoxycytidine Kinase for Improved Prodrug Sensitivity for Cancer Gene Therapy
Authors: Candice L. Willmon, Margaret E. Black
Journal: Molecular Therapy (2006)

Suicide gene therapy, unlike chemotherapy, offers a localized and selective cancer treatment. This is accomplished through the introduction of a gene encoding an enzyme into cancer cells. Upon administration of the prodrug, the enzyme converts the prodrug selectively into its toxic form, thereby resulting in the elimination of cancer cells. However, there are several limitations of the current gene delivery systems as well as the specificity of targeting tumor cells. One approach to circumvent these limitations is to create mutant enzymes with enhanced activity towards the prodrugs. Our studies target the human pyrimidine salvage enzyme deoxycytidine kinase (dCK). Specifically, our goal is to create mutant dCK enzymes with enhanced activity towards the anti-neoplastic nucleoside analog gemcitabine (dFdC). To improve prodrug activity regio-specific random mutagenesis was performed. This approach is especially applicable to structure/function studies of enzymes and can lead to the development of enzymes with altered or novel functions. Over 19,000 transformants were surveyed for enhanced prodrug specificity in an E. coli selection system. Approximately 335 mutants display super-sensitivity towards gemcitabine at the lowest concentration of prodrug examined. The sequences of variants that display increased activity towards gemcitabine reveal particular residues that appear to be important. The altered activity of the super-sensitive mutants was then verified by a semi-quantitative enzyme assay using bacterial cell lysates. From these data eight super-sensitive mutants with over 35,000-fold increased activity to dFdC compared to wild-type dCK were chosen for further evaluation. Determination of the alterations in the kinetic parameters of the best mutant enzymes was assessed with two substrates, deoxycytidine and dFdC. In vitro evaluation of the eight super-sensitive dCK mutants for improved cancer cell killing and bystander effect is ongoing. Data obtained from this mutagenesis study will reveal important structural and functional information regarding catalysis, structural integrity, and substrate specificity that will provide insight for further enzyme improvements and novel anti-cancer drug design. Furthermore, this research is significant because it will provide an exciting, novel alternative gene for suicide gene therapy applications for a wide variety of cancers.
Basal Muscle Amino Acid Kinetics and Protein Synthesis in Healthy Young and Older Men
Authors: Elena Volpi, Melinda Sheffield-Moore, Blake B. Rasmussen, Robert R. Wolfe
Journal: JAMA (2001)

ContextSarcopenia is associated with loss of strength and function, eventually leading to loss of independence. Some studies suggest that basal muscle protein turnover is reduced with aging, but other studies do not confirm this finding.ObjectiveTo determine if aging per se affects basal muscle protein turnover in men.Design and SettingCross-sectional study conducted from June 1997 to July 2000 in a general US community.ParticipantsTwenty-six young (mean [SE] age, 28 [2] years) and 22 older (mean [SE] age, 70 [1] years) men, who were healthy and independent based on activities of daily living, physical examinations, and screening tests. Subjects were excluded if they had cardiac, pulmonary, liver, or kidney disease; any impairment in activities of daily living; or steroid use.Main Outcome MeasuresWe measured basal muscle protein and amino acid kinetics, based on stable isotope techniques with femoral arteriovenous catheterization and muscle biopsies. Three models (arteriovenous balance, three-pool, and fractional synthesis rate) were used to estimate the metabolic parameters.ResultsMean (SE) total leg volume was 9.60 (0.32) L in older men vs 10.83 (0.43) L in younger men, which suggests muscle loss in the older men. Net muscle protein balance was similar in both groups (older men, − 19 [2] nmol/min per 100 mL of leg volume vs younger men, − 21 [2] nmol/min per 100 mL of leg volume; P = .51). Small differences were found in mean (SE) muscle protein synthesis in comparisons of older vs younger men: arteriovenous balance, 48 (5) nmol/min per 100 mL of leg volume vs 32 (3) nmol/min per 100 mL of leg volume; P = .004; three-pool, 58 (5) nmol/min per 100 mL of leg volume vs 43 (4) nmol/min per 100 mL of leg volume; P = .04; and fractional synthesis rate, 0.0601 (0.0046) %/h vs 0.0578 (0.0047) %/h; P = .73. Small differences were also found in mean (SE) muscle protein breakdown: arteriovenous balance, 66 (5) nmol/min per 100 mL of leg volume in older vs 53 (4) nmol/min per 100 mL of leg volume in younger men, P = .045; and three-pool, 76 (6) nmol/min per 100 mL of leg volume vs 64 (5) nmol/min per 100 mL of leg volume, P = .14.ConclusionDifferences in basal muscle protein turnover between older and younger men do not appear to explain muscle loss that occurs with age.
Mobility Limitation in the Older Patient
Authors: Cynthia J. Brown, Kellie L. Flood
Journal: JAMA (2013)

Mobility limitations are common in older adults, affecting the physical, psychological, and social aspects of an older adult's life.To identify mobility risk factors, screening tools, medical management, need for physical therapy, and efficacy of exercise interventions for older primary care patients with limited mobility.Search of PubMed and PEDro from January 1985 to March 31, 2013, using the search terms mobility limitation, walking difficulty, and ambulatory difficulty to identify English-language, peer-reviewed systematic reviews, meta-analyses, and Cochrane reviews assessing mobility limitation and interventions in community-dwelling older adults. Articles not appearing in the search referenced by reviewed articles were also evaluated.The most common risk factors for mobility impairment are older age, low physical activity, obesity, strength or balance impairment, and chronic diseases such as diabetes or arthritis. Several tools are available to assess mobility in the ambulatory setting. Referral to physical therapy is appropriate, because physical therapists can assess mobility limitations and devise curative or function-enhancing interventions. Relatively few studies support therapeutic exercise to improve mobility limitation. Strong evidence supports resistance and balance exercises for improving mobility-limiting physical weakness and balance disorders. Assessing a patient's physical environment and the patient's ability to adapt to it using mobility devices is critical.Identification of older adults at risk for mobility limitation can be accomplished through routine screening in the ambulatory setting. Addressing functional deficits and environmental barriers with exercise and mobility devices can lead to improved function, safety, and quality of life for patients with mobility limitations.
Shall The Journal be Removed to Washington?
Authors: Luther Brown
Journal: JAMA (1891)

<h3>To the Editor:</h3> —I am most unalterably opposed to the proposed change. It is very evident that the movement for the change from Chicago to Washington has had its origin in the minds of some, who are very reluctant to admit the fact which should be plainly apparent to all, that not only the centre of population but the financial and intellectual centres are surely moving westward. Nothing worthy the name of argument has as yet been advanced in favor of it, neither can there be, for there is none to offer. Some of the reflections which have recently been cast upon the management ofThe Journal, and upon the character of its contents, have been, to say the very least, uncalled for and out of place. The profession as a whole is not only well pleased withThe Journal, but is proud of it, and in my judgment with
Diagnosis of Urethritis: Gonococcal and Nongonococcal
Authors: WARREN H. GULLEN
Journal: Annals of Internal Medicine (1975)

Comments and Correction1 October 1975Diagnosis of Urethritis: Gonococcal and NongonococcalWARREN H. GULLEN, M.D., M.P.H., F.A.P.H.A.WARREN H. GULLEN, M.D., M.P.H., F.A.P.H.A.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-4-583 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the January issue (1), Jacobs and Kraus described their study of the laboratory differentiation of gonococcal and nongonococcal urethritis in men. That investigation involved obtaining Gram stains and cultures from the urethras of 400 consecutive men who entered DeKalb County Venereal Disease Clinic with symptoms of urethritis. The technicians were trained by the Communicable Disease Center. The major laboratory findings are reproduced in Table 1.On the basis of their data, those authors state that "a carefully examined Gram stain provides an unequivocal, simple, inexpensive, and rapid differential diagnosis" (presumably because 167/(167 + 4) in line...References1. JACOBSKRAUS NS: Gonococcal and nongonococcal urethritis in men. Clinical and laboratory differentiation. Ann Intern Med 82:7-12, 1975 LinkGoogle Scholar2. GULLENBEARMAN WJ: Observations on the diagnostic capabilities of laboratory tests. Minn Med 50:681-685, 1967 Google Scholar1. MENDENHALL W: Introduction to Probability and Statistics, 3rd ed. Belmont, California, Duxbury Press, 1971, pp. 83-86 Google Scholar2. VOLKKRAUS JS: Nongonococcal urethritis—a venereal disease as prevalent as epidemic gonorrhea. Arch Intern Med 134:511-514, 1974 CrossrefMedlineGoogle Scholar3. KAUFMANJOHNSONREYNOLDS RRG: National gonorrhea therapy monitoring study. I. Treatment results. Program: Fourteenth Interscience Conference on Antimicrobial Agents and Chemotherapy , San Francisco, 11-13 September 1974 Google Scholar4. HOLMESJOHNSONFLOYD KDT: Studies of venereal disease. III. Double-blind comparison of tetracycline hydrochloride and placebo in treatment of nongonococcal urethritis. JAMA 202:138-140, 1967 CrossrefMedlineGoogle Scholar5. CHAPELSMELTZERPRINTZ TMD: An evaluation of commercially supplied Transgrow and Amies media for the detection of Neisseria gonorrhoeae. Health Lab Sci 11:28-33, 1974 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Epidemiology Section Medical College of Georgia Augusta, Georgia 30902 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1975Volume 83, Issue 4Page: 583-584KeywordsResearch laboratoriesSexually transmitted diseasesTechnicians Issue Published: 1 October 1975 PDF DownloadLoading ...
PET Detection of Solitary Distant Skeletal Muscle Metastasis of Esophageal Adenocarcinoma
Authors: G Wu, B Bybel, R Brunken, H Lin, D Neumann
Journal: Clinical Nuclear Medicine (2005)

A 67-year-old man with progressive dysphagia was recently diagnosed with a gastroesophageal junction adenocarcinoma. Contrast-enhanced CT scans of the abdomen and pelvis reported a large GE junction tumor without evidence of metastatic disease. FDG positron emission tomography revealed intense tracer accumulation in the soft tissue mass at the GE junction consistent with the primary neoplasm. In addition, PET scan also identified a solitary focus of intense FDG accumulation at the musculotendinous junction of the right gluteus minimus muscle. Subsequent MRI demonstrated mild enhancement and could not differentiate between tumor versus inflammation. Needle biopsy was performed and confirmed metastatic esophageal adenocarcinoma. A case of skeletal muscle metastases from late-stage (IV) gastroesophageal adenocarcinoma was previously reported. However, a solitary metastasis to a distant skeletal muscle without evidence of other lymphatic and hematogenous metastasis is quite unusual. The case supports the previous report that PET is superior in detecting distant metastases for initial staging of esophageal carcinoma over CT.
THE NATURAL METHOD OF TEACHING THE SUBJECT OF MEDICINE.
Authors: WILLIAM OSLER
Journal: JAMA (1901)

There are three great groups of studies in the medical school. The first includes the mechanism of the normal body; the second, a knowledge of the abnormal; the third, a knowledge whereby deviations from the normal may be prevented and rectified. To become acquainted with the structure and functions of the normal body, the student spends two or more years in the laboratories, and this part of his work has, within the past quarter of a century, not only increased enormously, but a complete revolution has been effected in the methods of instruction. Much more difficult is it to give to the student a thorough training in the other great groups of studies, and I think among teachers there is a feeling that the work along these lines has not progressed quite so satisfactorily as it has in the subjects embraced in the first group. I wish to tell a
Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis
Authors: Joanne C Masterson, Eóin N McNamee, Sophie A Fillon, Lindsay Hosford, Rachel Harris, Shahan D Fernando, Paul Jedlicka, Ryo Iwamoto, Elizabeth Jacobsen, Cheryl Protheroe, Holger K Eltzschig, Sean P Colgan, Makoto Arita, James J Lee, Glenn T Furuta
Journal: Gut (2014)

<h3>Objective</h3> Eosinophils reside in the colonic mucosa and increase significantly during disease. Although a number of studies have suggested that eosinophils contribute to the pathogenesis of GI inflammation, the expanding scope of eosinophil-mediated activities indicate that they also regulate local immune responses and modulate tissue inflammation. We sought to define the impact of eosinophils that respond to acute phases of colitis in mice. <h3>Design</h3> Acute colitis was induced in mice by administration of dextran sulfate sodium, 2,4,6-trinitrobenzenesulfonic acid or oxazolone to C57BL/6J (control) or eosinophil deficient (<i>PHIL</i>) mice. Eosinophils were also depleted from mice using antibodies against interleukin (IL)-5 or by grafting bone marrow from <i>PHIL</i> mice into control mice. Colon tissues were collected and analysed by immunohistochemistry, flow cytometry and reverse transcription PCR; lipids were analysed by mass spectroscopy. <h3>Results</h3> Eosinophil-deficient mice developed significantly more severe colitis, and their colon tissues contained a greater number of neutrophils, than controls. This compensatory increase in neutrophils was accompanied by increased levels of the chemokines CXCL1 and CXCL2, which attract neutrophils. Lipidomic analyses of colonic tissue from eosinophil-deficient mice identified a deficiency in the docosahexaenoic acid-derived anti-inflammatory mediator 10, 17- dihydroxydocosahexaenoic acid (diHDoHE), namely protectin D1 (PD1). Administration of an exogenous PD1-isomer (10S, 17S-DiHDoHE) reduced the severity of colitis in eosinophil-deficient mice. The PD1-isomer also attenuated neutrophil infiltration and reduced levels of tumour necrosis factor-α, IL-1β, IL-6 and inducible NO-synthase in colons of mice. Finally, in vitro assays identified a direct inhibitory effect of PD1-isomer on neutrophil transepithelial migration. <h3>Conclusions</h3> Eosinophils exert a protective effect in acute mouse colitis, via production of anti-inflammatory lipid mediators.
Single, Total Paracentesis for Tense Ascites: Sequential Hemodynamic Changes and Right Atrial Size
Authors: Marios Z. Panos, Kevin Moore, Panayiotis Vlavianos, John B. Chambers, John V. Anderson, Alexander E.S. Gimson, Jeremy D.H. Slater, Lesley H. Rees, David Westaby, Roger Williams
Journal: Hepatology (1990)

Hemodynamic changes induced by a single, total paracentesis were evaluated in 21 patients with tense ascites from whom 4 to 16 L of ascites were drained over 2 to 8 hr with no serious complications. At 60 min, compared to baseline, there was an increase in cardiac output (7.7 +/- 0.5 to 8.5 +/- 0.6 L/min, p less than 0.02) and a tendency for right atrial pressure to decrease (9.3 +/- 0.8 to 7.50 +/- 0.8 mm Hg, NS), with no change in pulmonary capillary wedge pressure (10.9 +/- 0.9 to 10.7 +/- 0.9 mm Hg). Between 3 and 12 hr later, there was a drop in right atrial pressure, pulmonary capillary wedge pressure and cardiac output to 5.6 +/- 0.6 (p less than 0.02), 7.2 +/- 0.8 mm Hg (p less than 0.002) and 7.2 +/- 0.6 L/min (NS) respectively, indicative of the development of relative hypovolemia and suggesting that therapeutic plasma expansion is appropriate at this time. Two-dimensional echocardiography before paracentesis (n = 8) showed a reduction in the right to left atrium area ratio as compared with values in patients with minimal ascites (0.54 +/- 0.04 vs 0.82 +/- 0.02, p less than 0.0001). This technique may help in identifying patients with right atrial compression caused by tense ascites.
Clinical Significance of Peroxisome Proliferator-Activated Receptor Γ and MED1/TRAP220 in Patients with Operable Colorectal Cancer
Authors: S.Y. Oh, S.H. Kim, S. Lee, J.H. Lee, H.-J. Choi, K.-J. Park, H.-J. Kim, M.S. Roh, J. Yun
Journal: Annals of Oncology (2013)
Endoscopic Ultrasonography in the Diagnosis and Staging of Neoplasms of the Head and Neck
Authors: S. M. Wildi, W. E. Fickling, T. A. Day, C. D. Cunningham III, N. Schmulewitz, S. Varadarajulu, S. S. Roberts, B. Ferguson, B. J. Hoffman, R. H. Hawes, M. B. Wallace
Journal: Endoscopy (2004)

Background and Study Aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a minimally invasive and highly accurate method of detecting mediastinal lymph-node metastases in gastrointestinal and lung cancer. Little information is available regarding the use of EUS-FNA to stage tumors in the head and neck region. This study reports experience with EUS in the diagnosis and staging of these tumors and their mediastinal spread. Patients and Methods: The records of patients who underwent EUS for diagnosis and/or staging of head and neck tumors were reviewed. Referral criteria were suspected invasion of the esophagus by a lower-neck mass on cervical computed tomography (CT) or magnetic resonance imaging (MRI), or mediastinal lymphadenopathy > 10 mm on a chest CT. Results: Thirty-two patients (23 men, nine women; mean age 65 years, range 44 - 80) were referred and underwent 35 EUS examinations. In one patient, EUS was not possible due to a benign esophageal stricture. In 17 patients with suspected esophageal invasion on CT scans, EUS demonstrated invasion of the esophagus in four cases and of the pleura in one; 12 tumors showed no visible invasion of adjacent structures. The other 17 examinations were carried out for suspected mediastinal metastatic disease. In eight cases, EUS-FNA confirmed metastatic disease, whereas only benign changes were shown in the other nine cases. EUS-FNA also provided the first tissue diagnosis in two primary tumors and identified malignancy in one patient with no CT suspicion of positive mediastinal lymph nodes. EUS avoided the need for more invasive investigations in all patients with mediastinal lymphadenopathy, and it changed the management in 12 of the 17 patients (71 %) with suspected esophageal invasion and in eight of the 17 patients (47 %) with suspected mediastinal disease. Conclusions: EUS with FNA provides a viable approach to the diagnosis and staging of tumors in the head and neck region when there is a suggestion of esophageal invasion on CT or MRI, or enlarged mediastinal lymph nodes. EUS with FNA may avoid the need for mediastinoscopy or other more invasive techniques for staging of these neoplasms.
Model Reveals Drug Combinations to Overcome Resistant Cancers
Authors: Tracy Hampton
Journal: JAMA (2015)

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
Dependence of spatial heterogeneity of myocardial blood flow on mean blood flow rate in the rabbit heart
Authors: R. S CONWAY, H. R WEISS
Journal: Cardiovascular Research (1985)

Journal Article Dependence of spatial heterogeneity of myocardial blood flow on mean blood flow rate in the rabbit heart Get access ROBERT S CONWAY, ROBERT S CONWAY From the Department of Physiology and Biophysics, Heart and Brain Circulation Laboratory, University of Medicine and Dentistry of New Jersey, Rutgers Medical School, Piscataway, New Jersey Search for other works by this author on: Oxford Academic PubMed Google Scholar HARVEY R WEISS HARVEY R WEISS * From the Department of Physiology and Biophysics, Heart and Brain Circulation Laboratory, University of Medicine and Dentistry of New Jersey, Rutgers Medical School, Piscataway, New Jersey *Address to reprint requests: Dr Harvey R Weiss, PhD, Department of Physiology and Biophysics, Heart and Brain Circulation Laboratory, UMDNJ-Rutgers Medical School, PO Box 101, Piscataway, New Jersey 08854, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 19, Issue 3, March 1985, Pages 160–168, https://doi.org/10.1093/cvr/19.3.160 Published: 01 March 1985
Abstract LB-54: HOXB7 regulates breast cancer stem cells via induction of TGFβ2
Authors: Shou Liu, Sarah Johnson, Hexin Chen
Journal: Cancer Research (2014)

Abstract HOX genes encode a family of homeodomain-containing transcription factors involved in the determination of cell fate and identity during embryonic development. HOXB7 is overexpressed in more than 70% of breast cancers. Overexpression of HOXB7 in breast epithelial cells and induces epithelial-mesenchymal transition. In this study, we found that overexpression of the HOXB7 gene in breast cell lines increases cancer stem cell populations and promotes cell invasion, in contrast, knockdown of HOXB7 expression decreases the proportions of cancer stem cells. Colonogenic assay and xenograft transplantation experiments further confirmed that overexpression of HOXB7 in breast cancer cells increases their tumorigenecity both in vitro and in vivo. Mechanistically we found that HOXB7 strongly induces TGFβ2 expression and activates the canonical TGFβ/SMAD signaling pathways, which may be responsible for induction of EMT leading to expansion of cancer stem cell population. Overall, our results suggest that HOXB7 may be a critical factor which regulates the self-renewal and differentiation of breast cancer stem cells and therefore a potential therapeutic target in breast cancer. Citation Format: Shou Liu, Sarah Johnson, Hexin Chen. HOXB7 regulates breast cancer stem cells via induction of TGFβ2. [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 LB-54. doi:10.1158/1538-7445.AM2014-LB-54