tbuckley/cabot-search huggingface dataset:
Abstract 391: Inflammatory mediators of prostate cancer metastasis
Authors: Magaly Martinez-Ferrer, Ying Qi, Maria M. Sanchez, Neil A. Bhowmick
Journal: Cancer Research (2011)

Abstract Inflammation has been linked to the initiation and metastatic progression of prostate cancer. We previously reported results showing that CX3CL1 and IL-15 were predominantly down-regulated in prostate cancer patients that develop biochemical recurrence following prostatectomy. This study tests the hypothesis that chemokine biomarkers that predict biochemical recurrence of prostate cancer regulate metastatic progression of the cancer. In order to determine the function of the chemokines, PC3 and LNCaP prostate cancer cell lines were used alone and in combination with conditioned media from prostate stromal cells expressing the chemokines of interest. IL-15 and CX3CL1 cDNAs were subcloned into lentiviral constructs. The lentiviral constructs were transduced into prostate stromal cells developed from wild type C57BL/6 mice. Seventy-two hours conditioned media was used to verify the expression of the respective chemokines by ELISA. The individual prostate cancer cell lines (PC3 and LNCaP) were incubated in the respective stromal conditioned media and characterized for measurable characteristics that promote a cancer cell to be metastatic. In this study we show that IL-15 and CX3CL1 significantly decreased (P&amp;lt;0.0001) PC3 proliferation in vitro. Furthermore, IL-15 and CX3CL1 also had the ability to significantly inhibit migration of PC3 prostate cancer cells in vitro (P&amp;lt;0.01). Introducing IL-15 and CX3CL1 into the stromal microenvironment of the androgent independent PC3 cells significantly increased apoptosis (P&amp;lt;0.05). No significant changes were observed in the androgen dependent LNCaP prostate cancer cells. Our results indicate that IL-15 and CX3CL1 may suppress metastasis in vitro by decreasing proliferation and migration, and increasing apoptosis in the highly metastatic PC3 prostate cancer cell line. The studies will help to enable the dissection of the role of the chemokines on cancer cells in the context of its stromal micronvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 391. doi:10.1158/1538-7445.AM2011-391
Experimental Bone and Bone Marrow Metastasis in Laboratory Animals
Authors: FRANCISCO ARGUELLO, CHRISTOPHER N. FRANTZ, RAYMOND B. BAGGS
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Experimental Bone and Bone Marrow Metastasis in Laboratory Animals Get access FRANCISCO ARGUELLO, FRANCISCO ARGUELLO Search for other works by this author on: Oxford Academic PubMed Google Scholar CHRISTOPHER N. FRANTZ, CHRISTOPHER N. FRANTZ Search for other works by this author on: Oxford Academic PubMed Google Scholar RAYMOND B. BAGGS RAYMOND B. BAGGS Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 12, 20 June 1990, Pages 1069–1070, https://doi.org/10.1093/jnci/82.12.1069 Published: 20 June 1990
"Self-Care" Educational Ward for Improved Indigent-Population Health Care Delivery.
Authors: W. Dallas Hall
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971"Self-Care" Educational Ward for Improved Indigent-Population Health Care Delivery.W. Dallas Hall, M.D., J. Willis Hurst, M.D., F.A.C.P.W. Dallas Hall, M.D.Search for more papers by this author, J. Willis Hurst, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-835_5 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA 32-bed ward has been established at Grady Memorial Hospital, Atlanta, Ga., as an innovative type of educational environment and patient care facility. Medical patients who require detailed diagnostic evaluation are electively admitted. Unique features of the program are as follows. Patients are ambulatory and under "self-care," that is, they often serve their own meals, make their beds, take their own medications, and so forth. This requires a minimal degree of paramedical time for supervision and facilitates the speed and thoroughness with which the patient's problems can be approached. Only Senior Medical Residents or Fellows can admit patients to the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Atlanta, Ga. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1971Volume 74, Issue 5Page: 835-836KeywordsHealth careHealth care facilitiesHospitalsPatients Issue Published: 1 May 1971 PDF DownloadLoading ...
Graduate Medical Education in the Changing Environment of Medicine
Authors: Carlos J. M. Martini
Journal: JAMA (1992)

THE US graduate medical education system has been strongly criticized by policymakers and by private and public agencies for not being responsive to the population's health needs. Comments usually focus on the unwillingness of the accreditation and education systems to generate the proper mix of specialties and to influence a more equitable geographical distribution of physicians. No one disputes the inadequacy of the distribution of medical specialties, particularly in the medical care of underserved populations, but to blame solely the graduate medical education and accreditation systems is to ignore the absence of population-based planning for health services—a governmental responsibility—and the important, though lesser, contributions of other medical education components. Education, accreditation, licensure, certification, and practice, although interrelated, are all directed by different organizations. Changes in only one or two of these components will never be sufficient to solve the health manpower problems of the health care delivery system, which would
Familial dyskeratotic comedones
Authors: N A C Van Geel, M Kockaert, H A M Neumann
Journal: British Journal of Dermatology (1999)

Journal Article Familial dyskeratotic comedones Get access N A C Van Geel, N A C Van Geel University Hospital Maastricht, P.Debyelaan 25, 6202 AZ Maastricht, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar M Kockaert, M Kockaert University Hospital Maastricht, P.Debyelaan 25, 6202 AZ Maastricht, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar H A M Neumann H A M Neumann University Hospital Maastricht, P.Debyelaan 25, 6202 AZ Maastricht, The Netherlands NEUMANN University Hospital Maastricht, P.Debyelaan 25, 6202 AZ Maastricht, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 140, Issue 5, 1 May 1999, Pages 956–959, https://doi.org/10.1046/j.1365-2133.1999.02835.x Published: 01 May 1999
Preoperative Superselective Mesenteric Angiography and Methylene Blue Injection for Localization of Obscure Gastrointestinal Bleeding
Authors: Madhava Pai, Adam E. Frampton, Jagdeep S. Virk, Nyooti Nehru, Charis Kyriakides, Paolo Limongelli, James E. Jackson, Long R. Jiao
Journal: JAMA Surgery (2013)

Localizing obscure gastrointestinal bleeding can be a clinical challenge, despite the availability of various endoscopic, imaging, and visceral angiographic techniques. We reviewed the management of patients presenting with obscure gastrointestinal bleeding during the period from 2005 to 2011. Four patients had preoperative localization of the bleeding site with superselective mesenteric angiography, which was confirmed by the use of intraoperative methylene blue injection. This novel technique allowed us to identify the abnormal pathology, and, consequently, resection of the implicated segment of small bowel was performed without any postoperative complications. Final histology showed that 2 patients had arteriovenous malformations: one had a benign hemangioma of the small bowel, and the other had chronic ischemic ulceration in the ileum. Superselective mesenteric angiography combined with intraoperative localization with methylene blue is an important and innovative technique in the management of patients with unclear sources of gastrointestinal bleeding and allows for effective hemorrhage control with a focused and therefore limited bowel resection.
p21Ras downstream effectors are increased in activity or expression in mouse liver tumors but do not differ betweenRas-mutated andRas-wild-type lesions
Authors: Arno Kalkuhl, Jacob Troppmair, Albrecht Buchmann, Stefan Stinchcombe, Christoph Lars Buenemann, Ulf R. Rapp, Klaus Kaestner, Michael Schwarz
Journal: Hepatology (1998)

Mouse liver tumors frequently harbor activating ras gene mutations. Downstream effector molecules of p21 Ras include Raf-1 kinase which mediates external signals via kinase signaling pathways to nuclear transcription factors including c-Fos and c-Jun. Mouse liver tumors with differing ras -mutational status were analyzed for alterations in Ras/Raf-1 signal transduction. Tumors were characterized with respect to the presence of base substitutions in the 3 known hot-spot positions at codons 12, 13, and 61 of Ha- ras, Ki- ras, and N- ras. Ha- ras codon 61 or Ki- ras codon 13 mutations, but no N- ras mutations, were detected in 23 out of 33 tumors analyzed, while no ras -mutations were found in 10 of the tumors. There was no significant difference in the expression of p21 Ras proteins between ras -mutated tumors and tumors without detectable ras mutations. To allow for determination of Raf-1 kinase activity in tumors, a sensitive and specific assay was developed for measurements with tissue homogenates. Raf-1 kinase activity was increased about four-fold in liver tumors as compared with normal liver tissue. No significant differences in kinase activity, however, were evident between ras -mutated and ras -wild-type tumors. The same was true with respect to the levels of c- fos and c- jun mRNAs. Moreover, there were no significant differences in cell division (5-bromo-2′-deoxyuridine-labeling indices) of hepatocytes from ras -mutated and ras -wild-type tumors. The similar degree of constitutive activation of the Ras/Raf-1 signaling pathway in liver tumors, with and without detectable ras mutations, suggests that other molecules within the signaling pathway may substitute for ras -mutations during oncogenic conversion of ras -wild-type hepatocytes.
β‐thalassemia in association with a new δ‐chain hemoglobin variant [δ116(g18)Arg→Leu]: Implications for carrier screening and prenatal diagnosis
Authors: John S. Waye, Margaret Patterson, Lynda Walker, Barry Eng, Lisa M. Nakamura, John D. Lafferty, Sui‐Li Yong, John K. Wu, David H.K. Chui
Journal: American Journal of Hematology (2003)

Abstract We describe a complicated genetic counseling and prenatal diagnostic case involving an East Indian couple that had lost two consecutive pregnancies. Hemoglobinopathy screening was conducted to investigate the possibility of Hb Bart's hydrops fetalis or Hb H hydrops fetalis. The initial work‐up indicated that α‐thalassemia was not a contributing factor, with both parents being carriers of single gene deletions (−α 3.7 /αα). However, the Hb electrophoresis results indicated that the couple might be at risk for having children with Hb E/Hb Lepore disease. Subsequent DNA testing demonstrated that the father carried the Hb E mutation, but failed to confirm that the mother carries the Hb Lepore deletion. Sequence analysis revealed that the mother was heterozygous for a common East Indian β 0 ‐thalassemia mutation, yet had a normal level of Hb A 2 . The mother also carried a previously unreported missense mutation of the δ‐globin gene, in cis with the β 0 ‐thalassemia mutation, which gave rise to the minor Hb variant originally misidentified as Hb Lepore. This case illustrates the importance of comprehensive molecular analyses for accurate assessment of genetic risks for hemoglobinopathy syndromes. Am. J. Hematol. 74:179–181, 2003. © 2003 Wiley‐Liss, Inc.
As Discoveries Unfold, a New Urgency to Bring Genetic Literacy to Physicians
Authors: Joan Stephenson
Journal: JAMA (1997)

AT A TIME when every week seems to bring reports of new genes implicated in human disease, many experts fear that most physicians will lack the genetic literacy to apply such findings to medical practice. With the Human Genome Project hurtling toward its goal of sequencing all human genes before the scheduled date of 2005, physicians, other health professionals, and patients are beginning to confront questions concerning how the clinical application of genetic discoveries will be handled. Commercial tests for mutations in at least 15 genes associated with human disease, including breast and colon cancer, cystic fibrosis, fragile X syndrome, Alzheimer disease, and other disorders have already reached the marketplace—but how and when such tests should be used have generated controversy and confusion. The problem is expected to become even more urgent as genes that play a role in common disorders such as heart disease, hypertension, diabetes, and anxiety disorders
Rate Constant for Forced Expiration Decreases with Lung Growth during Infancy
Authors: ROBERT S. TEPPER, MARCUS JONES, STEPHANIE DAVIS, JEFF KISLING, ROBERT CASTILE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Airway caliber and lung volume (Vl) increase many fold between infancy and adulthood; however, these two components of the lung may not increase proportionately during lung growth and development. We evaluated in infants the rate of emptying during forced expiration from near total lung capacity to residual volume. From the flow–volume curves we calculated (1) a rate constant (k) as the change in flow divided by the change in volume between 50% and 75% of expired forced vital capacity (FVC), and (2) the fraction of the FVC expired in 0.5 s (FEV0.5/FVC). Seventeen normal healthy infants were evaluated twice; mean ages (ranges) at first and second tests were 30 (5 to 76) and 58 (28 to 98) wk. Analysis of cross-sectional and longitudinal data indicated that the rate of emptying during forced expiration measured by both parameters was greatest in the youngest infants and decreased during infancy. Our findings are consistent with the concept that younger infants have large airways relative to their Vl and that Vl increases more rapidly than airway caliber early in life.
Steaming through the NHS.
Authors: S. Lock
Journal: BMJ (1989)

<h3>Abstract</h3> The emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19.
Incidence and Determinants of Spontaneous Seroclearance of Hepatitis B e Antigen and DNA in Patients With Chronic Hepatitis B
Authors: Hwai–I Yang, Hsiu–Lian Hung, Mei–Hsuan Lee, Jessica Liu, Chin–Lan Jen, Jun Su, Li–Yu Wang, Sheng–Nan Lu, San–Lin You, Uchenna H. Iloeje, Chien–Jen Chen
Journal: Clinical Gastroenterology and Hepatology (2011)
New look at tennis elbow.
Authors: S Chawla, A P Aluwihare
Journal: BMJ (1971)

1ll carcinoma patients the serum calcium was raised to around the 16 mg/100 ml level and that the classical symptoms of hyper- calcaemia were present; there were no skeletal metastases.It would appear that the low incidence of the hypercalcaemic syndrome in Locks's series and its absence in the Jersey study would tend to support the comments of Drs.von Wichert and Mitchell-Heggs.-Iam, etc.,
Disruption of the purine nucleotide cycle by inhibition of adenylosuccinate lyase produces skeletal muscle dysfunction.
Authors: J L Swain, J J Hines, R L Sabina, O L Harbury, E W Holmes
Journal: Journal of Clinical Investigation (1984)

Controversy exists as to whether the purine nucleotide cycle is important in normal skeletal muscle function. Patients with disruption of the cycle from a deficiency of AMP deaminase exhibit variable degrees of muscle dysfunction. An animal model was used to examine the effect of inhibition of the purine nucleotide cycle on muscle function. When the compound 5-amino-4-imidazolecarboxamide riboside (AICAriboside) is phosphorylated to the riboside monophosphate in the myocyte it is an inhibitor of adenylosuccinate lyase, one of the enzymes of the purine nucleotide cycle. AICAriboside was infused in 28 mice, and 22 mice received saline. Gastrocnemius muscle function was assessed in situ by recording isometric tension developed during stimulation. The purine nucleotide content of the muscle was measured before and after stimulation. Disruption of the purine nucleotide cycle during muscle stimulation was evidenced by a greater accumulation of adenylosuccinate, the substrate for adenylosuccinate lyase, in the animals receiving AICAriboside (0.60 +/- 0.10 vs. 0.05 +/- 0.01 nmol/mumol total creatine, P less than 0.0001). There was also a larger accumulation of inosine monophosphate in the AICAriboside vs. saline-treated animals at end stimulation (73 +/- 6 vs. 56 +/- 5 nmol/mumol total creatine, P less than 0.03). Inhibition of flux through the cycle was accompanied by muscle dysfunction during stimulation. Total developed tension in the AICAriboside group was 40% less than in the saline group (3,023 +/- 1,170 vs. 5,090 +/- 450 g . s, P less than 0.002). An index of energy production can be obtained by comparing the change in total phosphagen content per unit of developed tension in the two groups. This index indicates that less high energy phosphate compounds were generated in the AICAriboside group, suggesting that interruption of the purine nucleotide cycle interfered with energy production in the muscle. We conclude from these studies that defective energy generation is one mechanism whereby disruption of the purine nucleotide cycle produces muscle dysfunction.
Fluvastatin Enhances the Inhibitory Effects of a Selective Angiotensin II Type 1 Receptor Blocker, Valsartan, on Vascular Neointimal Formation
Authors: Masatsugu Horiuchi, Tai-Xing Cui, Zhen Li, Jian-Mei Li, Hironori Nakagami, Masaru Iwai
Journal: Circulation (2003)

Background— The present studies were undertaken to investigate the potential effect of a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) to enhance the inhibitory effect of an angiotensin (Ang) II type 1 (AT 1 ) receptor blocker (ARB) on vascular neointimal formation and to explore the cellular mechanism of cross-talk of the AT 1 receptor and statin in vascular smooth muscle cells (VSMCs). Methods and Results— Neointimal formation and the proliferation of VSMCs induced by cuff placement around the femoral artery were significantly inhibited by treatment with an ARB, valsartan, at a dose of 0.1 mg · kg −1 · d −1 and with fluvastatin at a dose of 1 mg · kg −1 · d −1 , which did not influence mean arterial blood pressure or plasma cholesterol level, whereas valsartan or fluvastatin alone at these doses did not affect neointimal formation or the proliferation of VSMCs. Pretreatment with fluvastatin (≈5 μmol/L) for 24 hours significantly inhibited Ang II (1 μmol/L)–mediated DNA synthesis and c-fos promoter activity in cultured VSMCs. Moreover, pretreatment of VSMCs with fluvastatin significantly inhibited Ang II–mediated extracellular signal-regulated kinase (ERK) activation and tyrosine- and serine-phosphorylation of signal transducer and activator of transcription (STAT)1 and STAT3. AT 1 receptor–mediated recruitment of Rac-1 to Janus kinase (Jak) family/STATs was also inhibited by fluvastatin. Consistent with these in vitro results, phosphorylation of ERK, STAT1, and STAT3 was attenuated by the coadministration of valsartan and fluvastatin even at low doses in vivo. Conclusion— These results suggest that the cholesterol-independent inhibition of AT 1 receptor–mediated VSMC proliferation by statins may contribute to the beneficial effects of statins combined with an ARB on vascular diseases.
Utility of Hippocrates' prognostic aphorism to predict death in the modern era: prospective cohort study
Authors: P. D. St John, P. R. Montgomery
Journal: BMJ (2014)

<b>Objective</b> To determine if one of Hippocrates' aphorisms, identifying good cognition and good appetite as two prognostic factors, predicts death in community living older adults in the modern era. <b>Design</b> Secondary analysis of an existing population based cohort study. <b>Setting</b> Manitoba Study of Health and Aging. <b>Participants</b> 1751 community living adults aged more than 65 enrolled in the Manitoba Study of Health and Aging in 1991 and followed over five years. <b>Main outcome measure</b> Time to death. <b>Methods</b> We recreated the hippocratic prognosticator using an item that measures appetite drawn from the Center for Epidemiologic Studies-depression subscale, and the mini-mental state examination, with a score of &gt;25 being considered as normal. People with normal cognition and appetite were compared with those with either poor cognition or poor appetite. We constructed Cox regression models, adjusted for age, sex, education, and functional status. <b>Results</b> The prognostic aphorism predicted death, with an unadjusted hazard ratio of 2.37 (95% confidence interval 1.93 to 2.88) and a hazard ratio of 1.71 (1.37 to 2.12) adjusted for age, sex, and education. Both poor appetite and poor cognition predicted death. The sensitivity and specificity were not, however, sufficient for the measure to be used alone. <b>Conclusion</b> An aphorism devised by Hippocrates millennia ago can predict death in the modern era.
Risk Factors for Treatment-Related Death Associated with Chemotherapy and Thoracic Radiotherapy for Lung Cancer
Authors: Yuko Minami-Shimmyo, Yuichiro Ohe, Seiichiro Yamamoto, Minako Sumi, Hiroshi Nokihara, Hidehito Horinouchi, Noboru Yamamoto, Ikuo Sekine, Kaoru Kubota, Tomohide Tamura
Journal: Journal of Thoracic Oncology (2011)
Orbital Angiosarcoma with Subconjunctival Presentation
Authors: Thierry Hufnagel, LIH MA, Tseng-Tong Kuo
Journal: Ophthalmology (1987)

An otherwise healthy 37-year-old woman had, over the course of 2 years, a recurring subconjunctival lesion associated with blepharoptosis. Computed tomography (CT) demonstrated a large anterior and superior orbital mass. A diagnosis of angiosarcoma (AS) was made from biopsy material. The patient is alive and well 18 months after exenteration and radiation therapy. The clinical and histopathologic features of this tumor are discussed with emphasis on the differential diagnosis of malignant vascular tumors of the orbit.
Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments
Authors: Ilona Kryczek, Mousumi Banerjee, Pui Cheng, Linhua Vatan, Wojciech Szeliga, Shuang Wei, Emina Huang, Emily Finlayson, Diane Simeone, Theodore H. Welling, Alfred Chang, George Coukos, Rebecca Liu, Weiping Zou
Journal: Blood (2009)