tbuckley/cabot-search huggingface dataset:
Abstract 1416: IGF-1 Gene Transfer Promotes Connexin-43 Expression and Enhances Integration of Bone Marrow Stem Cells in the Infarcted Heart
Authors: Shujia Jiang, Khawaja Haider, Niagara M Idris, Muhammad Ashraf
Journal: Circulation (2008)

For functional benefits, bone marrow stem cells should engraft and develop functional syncitium with the host myocytes in the infarcted heart. We report that IGF-1 overexpression significantly enhances connexin-43 (Cx-43) in mesenchymal stem cells (MSCs) which promotes their survival and functional integration with host myocardium post-engraftment. IGF-1 gene transduced MSCs ( IGF-1 MSCs) expressed higher IGF-1 ( p &lt; 0.001 ) as compared with GFP gene transduced cells ( GFP MSCs). After 8h anoxia, MSCs, H2C9 and endothelial cells treated with IGF-1 MSCs conditioned medium ( IGF-1 CM) showed higher survival ( p &lt; 0.001 vs GFP MSCs conditioned medium ( GFP CM) supported by higher Akt activation which was abolished by wortmannin. Immunodetection showed Cx-43 plaques in the peripheral areas besides punctate distribution in the cytoplasm around the nucleus in IGF-1 MSCs and IGF-1 CM treated MSCs whereas GFP MSCs and GFP CM treated MSCs showed Cx-43 expression in regions of intimate cell to cell contact only. IGF-1 overexpression or IGF-1 CM treatment of MSCs also induced higher level Akt and p27 activation, and Cx-43 expression as compared with GFP MSCs ( p = 0.02 ) which was abolished by wortmannin. For in vivo studies, 70 μ l DMEM without cells (group-1) or containing 1x10 6 GFP MSC (group-2) or IGF-1 MSC (group-3) were injected intramyocardially in female rat model of coronary artery ligation (n=16/group). The animals were harvested on 7 days and 6 weeks after cell engraftment. FISH and sry -gene analysis on 7 day showed extensive survival of the male donor cells in the heart. Real-time PCR and Western blot on the heart tissue showed higher level of Cx-43 and activation of p27 in group-3 ( p &lt; 0.05 vs group-2). The number of TUNEL + cells was lower in group-3 ( p = 0.01 vs group-2). Immunostaining for α -sarcomeric actin and Cx-43 showed extensive myogenic differentiation of IGF-1 MSCs and gap junction formation between adjacent neofibers. Indices of heart function including ejection fraction (63.05±1.37%) and fractional shortening (28.54±0.92%) were improved in group-3 ( p &lt; 0.001 vs group-2 ) . IGF-1 enhances Cx-43 expression in MSCs and promotes their engraftment and functional integration in the heart and improves heart function.
Mutations in the Human Factor XII Gene
Authors: Manfred Schloesser, Sacha Zeerleder, Gerd Lutze, Walter-Michael Halbmayer, Sigrun Hofferbert, Bernd Hinney, Heinz Koestering, Bernhard Lämmle, Gerhard Pindur, Karsten Thies, Michael Köhler, Wolfgang Engel
Journal: Blood (1997)
Lassa Fever
Authors: Joseph B Mccormick, I. J. King, P. A. Webb, C. L. Scribner, R. B. Craven, K. M. Johnson, L. H. Elliott, R. Belmont-Williams
Journal: New England Journal of Medicine (1986)

In a study of Lassa fever in Sierra Leone, West Africa, we identified two variables associated with a high risk of death, and we evaluated the efficacy of ribavirin and Lassa virus-convalescent plasma for the treatment of Lassa fever. A serum aspartate aminotransferase level greater than or equal to 150 IU per liter at the time of hospital admission was associated with a case-fatality rate of 55 percent (33 of 60). Patients with the same risk factor who were treated for 10 days with intravenous ribavirin, begun within the first 6 days after the onset of fever, had a case-fatality rate of 5 percent (1 of 20) (P = 0.0002 by Fisher's exact test). Patients whose treatment began seven or more days after the onset of fever had a case-fatality rate of 26 percent (11 of 43) (P = 0.01). Viremia with levels greater than or equal to 10(3.6) TCID50 per milliliter on admission was associated with a case-fatality rate of 76 percent (35 of 46). Patients with this risk factor who were treated with intravenous ribavirin within the first six days after onset of fever had a case-fatality rate of 9 percent (1 of 11) (P = 0.006), whereas those treated after seven days or more of illness had a fatality rate of 47 percent (9 of 19) (P = 0.035). Oral ribavirin was also effective in patients at high risk of death. Lassa-convalescent plasma did not significantly reduce mortality in any of the high-risk groups. We conclude that ribavirin is effective in the treatment of Lassa fever and that it should be used at any point in the illness, as well as for postexposure prophylaxis.
Panel Endorses Limited Role for CRP Tests
Authors: Mike Mitka
Journal: JAMA (2003)

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
Planning the United Kingdom's medical workforce
Authors: M. Goldacre
Journal: BMJ (1998)

Without an appropriate workforce, health service delivery will fail. The function of medical workforce planning is to ensure, so far as possible, that the right numbers of doctors, in the right specialties and grades, are in the right places. Traditionally national policy in the United Kingdom has been to provide an adequate supply of doctors while avoiding overproduction and unemployment. The policy has also been to train enough doctors for self sufficiency without reliance on net immigration. The main mechanisms for achieving these policies have been through fixing quotas for the number of places in medical schools and through a variety of mechanisms to control the number of NHS medical posts in each grade, specialty, and location.

Several factors tend to increase the demand for health care and for doctors. Population size and structure, notably its ageing, is reasonably straightforward to estimate. Advances in medical knowledge and technology are less predictable. They increase the scope for treatment and increase specialisation, which, in turn, tends to increase the range and number of specialists. Hitherto, technological advances in medicine have generally increased, rather than reduced, costs and the need for medical staff. Public expectations to meet needs and improve quality of care, fuelled by professional aspirations, media …
A REPORT OF IDENTICAL ALBINO TWINS OF NEGRO PARENTS
Authors: Elmer G. Wakefield, Samuel C. Dellinger
Journal: Annals of Internal Medicine (1936)

Case Reports1 February 1936A REPORT OF IDENTICAL ALBINO TWINS OF NEGRO PARENTSELMER G. WAKEFIELD, M.D., SAMUEL C. DELLINGERELMER G. WAKEFIELD, M.D.Search for more papers by this author, SAMUEL C. DELLINGERSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-9-8-1149 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe object of this report is to record identical twins and total albinism occurring in the Negro race. Although such an anomaly in identical twins is exceedingly rare in all races, we believe that the biologic phenomena involved in the production and accidental association of identical twins and albinism have been satisfactorily, if not correctly, explained in the literature on twins, twinning, and albinism. These children were neither pupils nor patients of ours; therefore, the only tests or examinations which could be made were those which are reported here.The twins were girls, aged about eight and a half years...Bibliography1. GARROD AE: Inborn errors of metabolism, 1923. H. Frowde and Hodder and Stoughton, London. Google Scholar2. NEWMAN HH: The biology of twins (mammals), 1917, University of Chicago Press, Chicago. CrossrefGoogle Scholar3. NEWMAN HH: The physiology of twinning, 1922, University of Chicago Press, Chicago. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Fayetteville, Arkansas*From the Division of Medicine, The Mayo Clinic, Rochester, Minnesota; and the Department of Zoology, University of Arkansas, Fayetteville, Arkansas.†Research Series, number 411. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAlbinism in Northern IrelandEineiige Zwillingsmädchen mit konkordantem Albinismus Universalis aus Ehe normalpigmentierter, aber entsprechend belasteter Vettern I. Grades in oberitalienischem Isolat 1 February 1936Volume 9, Issue 8Page: 1149-1153KeywordsBiologicsChildrenMonozygotic twinsRacial and ethnic issuesTwins ePublished: 1 December 2008 Issue Published: 1 February 1936 PDF downloadLoading ...
Abstract P389: Flavonoid intake and incident hypertension in French women
Authors: Martin Lajous, Emilie Rossignol, Florence Perquier, Guy Fagherazzi, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon
Journal: Circulation (2014)

Background: Flavonoids have been shown to lower blood pressure, however, there is limited information on the relation of long-term intake of flavonoids and the incidence of hypertension. Methods and Results: We evaluated the relations of total flavonoid and flavonoid subclasses (flavonols, flavones, flavanones, anthocyanins, flavan-3-ols and polymers) intake to self-reported hypertension in a prospective cohort study among 40,574 disease-free French women in the E3N cohort, a component of the EPIC cohort. Diet was assessed in 1993 using a validated diet history questionnaire. We used the Phenol-Explorer database to estimate total flavonoid and flavonoid subclass intake and categorized them in quintiles. Between 1993 and 2007, 9,348 cases of incident self-reported hypertension were identified using follow-up questionnaires. The validity of self-reported hypertension was evaluated using a health claims database and the positive predictive value was 82%. In multivariable analyses we adjusted for age, education, smoking, BMI, physical activity, menopausal status, hormone use, diabetes, hypercholesterolemia and intake of calories, alcohol, processed meat, caffeine, magnesium, potassium and omega-3. In multivariable Cox regression models, comparing the highest quintile of total flavonoid intake to the lowest, high flavonoid intake was inversely associated with the rate of self-reported hypertension (HR=0.91; 95%CI 0.85, 0.98; p-trend=0.01). When comparing extreme quintiles of intake, we observed inverse associations with flavonols (HR=0.90; 95%CI 0.84, 0.97; p-trend=0.03), anthocyanins (HR=0.91; 95%CI 0.84, 0.97; p-trend=0.008) and polymers (HR=0.91; 95%CI 0.85, 0.97; p-trend=0.005). We evaluated these relations restricting analyses to individuals ≤ 60 years and results did not change. The main foods contributing to total flavonoid intake were tea, chocolate, plums and wine. Comparing the highest to the lowest quintile of plum intake we observed a 14% lower rate of self-reported hypertension (HR=0.86; 95%CI 0.81, 0.93; p-trend=&lt;0.0001). No associations were observed for the other main contributors. Conclusion: In this large prospective cohort of French women, we observed a weak association between intake of total flavonoid, flavonols, anthocyanins and polymers intake and self-reported hypertension. Plum consumption appears to be associated with a lower rate of hypertension.
Comparative pharmacokinetics, tissue distribution and excretion of free versus liposomal vincristine in rats.
Authors: Rostam Namdari, Rhonda Oshanek, Naoko Yasuda, Andrea Janse, Mike Luksic, Valentia Lee-Brotherton, Patrick M. Tam, Clay Flowers
Journal: Cancer Research (2004)

2041  Vincristine sulfate is a cell-cycle specific anti-mitotic agent used in the treatment of Non-Hodgkins Lymphoma. Its encapsulation into liposomes extends the systemic circulation of the drug and mediates prolonged exposure of the drug to tumour sites. Prolonged exposure of cell-cycle specific anti-mitotic drugs such as vincristine would benefit from liposomal drug delivery. Vincristine Sulfate Liposomes Injection (VSLI) is vincristine encapsulated in sphingomyelin/ cholesterol liposomes. In these studies, a single iv bolus dose of VSLI or VCR was administered to Sprague-Dawley rats at 2.0 mg/m2. Blood, tissues, urine and bile/feces samples were collected at specific time points and analyzed by LSC. Following VSLI administration, total vincristine concentrations in plasma exhibits mono-exponential decline whereas the corresponding profile in VCR-treated rats exhibit bi-exponential decline with a rapid initial phase followed by a slower elimination phase. The volume of distribution and clearance of total vincristine in VSLI-treated rats was significantly less than that of the free drug resulting in radically greater AUC. Tissue distribution data show that liposomal vincristine accumulated preferentially in tissues of the RES (e.g., liver, spleen) as demonstrated by higher tissue AUC in VSLI-treated rats. Despite the differences in plasma PK and tissue distribution in VSLI- vs VCR-treated rats, the major route of vincristine elimination is the same (i.e. biliary excretion); however vincristine excretion was delayed in VSLI-treated rats. In conclusion, VSLI increases circulation longevity of vincristine and causes preferential accumulation of liposomal drug in tissues with permeable vasculature including tumour.
Abstract P124: Ideal Cardiovascular Health During Adult Life and Cardiovascular Structure and Function among the Elderly
Authors: Amil M Shah, Brian Claggett, Aaron R Folsom, Pamela L Lutsey, Scott D Solomon
Journal: Circulation (2015)

Introduction:  The AHA has identified seven ideal cardiovascular (CV) health metrics to target primary prevention of CV disease, including heart failure. The relationship between the consistent attainment of these metrics in adulthood and CV structure and function in late-life is not well described.   Hypothesis:  We hypothesized that the greater number of ideal CV health metrics consistently achieved in adulthood will be associated with better cardiac and arterial function when elderly.   Methods:  The following six ideal CV health metrics were assessed in Atherosclerosis Risk in Communities (ARIC) study participants at 5 exam visits between 1987 and 2013 (visits 1-4 in 1987-98, visit 5 in 2011-13): nonsmoking, body mass index    Results:  At Visit 5, median age was 75.2 years (IQR 71.7, 79.7), 42% were male, and 21% black. At least 4 metrics were consistently attained in 6%, with 3, 2, 1, and 0 metrics consistently attained in 14%, 35%, 35%, and 12% respectively. Greater number of metrics consistently attained was associated with better LV structure, systolic and diastolic function, less arterial stiffness, and lower NT-proBNP and high sensitivity troponin T at Visit 5 (Table).   Conclusions:  In this community-based cohort, greater number of ideal CV health metrics consistently attained over an approximately 26 year span was associated with better cardiovascular structure and function when elderly.
92. Metabolically Biotinylated Adeno-Associated Virus (AAV) Types 1, 2, 3, 4 and 5 for Scalable Purification and Vector Retargeting
Authors: Yong Hong Chen, Beverly L. Davidson
Journal: Molecular Therapy (2004)

Adeno-associated virus (AAV) is an attractive vector for gene delivery because of its low toxicity and ability to express transgenes for many months. Collectively, the different serotypes of AAV show broad tissue and cell tropism. Despite this, AAV does not efficiently transduce endothelia. In our approaches to develop gene therapy for the CNS manifestations of the lysosomal storage diseases (mucopolysaccharidoses; [e.g., beta-glucuronidase deficiency]) and the ceroid lipofuscinoses (e.g., CLN2 or tripeptidyl protease I [TPP-1] deficiency) endothelia remain an attractive target. Endothelial expression of TPP-1 or beta-glucuronidase results in both apical and basolateral secretion of enzyme; in the brain, this would allow exposure of recombinant enzyme to the underlying brain parenchyma. As a first step in developing endothelial-targeted AAV, we panned, in vivo, for brain specific epitopes by phage display. Beta-Glucuronidase deficient and age matched wildtype littermates were used for panning. This was accomplished by canulating the internal carotid artery, injecting phage, and perfusing the mice 5 min later with DMEM. Phage were recovered by homogenizing the brain and incubating the homogenate with bacteria and culture media. After five rounds of panning we isolated a panel of targeting peptides that bound selectively and efficiently to brain endothelia. The motifs isolated from beta-glucuronidase deficient mice were distinct from those panned from heterozygous littermates. Selective peptides have been genetically incorporated into AAV2 VP1 capsid protein at amino acid position 587, a site previously shown to accommodate peptide insertion for directed gene transfer. Recombinant viruses will be assessed for specific delivery to brain relative to AAV2 with native VP1 capsid, in beta-glucuronidase and wildtype mice. Our studies provide possible strategies for correction of CNS deficiencies associated with metabolic diseases, by retargeting AAV2 to brain endothelia with motifs identified in vivo from phage display libraries.
Abstract 2870: ZGPAT gene expression in non-tumor hepatocellular carcinoma tissue is a likely biomarker for survival risk
Authors: Mitsuhiro Hishida, Shuji Nomoto, Yoshikuni Inokawa, Nao Takano, Mitsuro Kanda, Naoki Iwata, Chie Tanaka, Daisuke Kobayashi, Yoko Nishikawa, Suguru Yamada, Goro Nakayama, Tsutomu Fujii, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Cancer Research (2014)

Abstract [Background &amp; Aim] Hepatocellular carcinoma (HCC) often recurs after surgery and multicentric occurrence is more common than intrahepatic metastasis. We therefore examined factors in non-tumor liver tissue in HCC. [Material &amp; Methods] Control samples, termed super normal liver tissues (SN), were taken from 11 cases of metastatic liver cancer. One of corresponding samples of normal tissues (CN) was selected for comparison from a typical specimen with chronic hepatitis C and HCC. We performed expression profiling and methylation arrays on these samples, identified genes that differed between SN and CN. We analyzed the identified genes using quantitative real-time reverse-transcriptase polymerase chain reaction on SN from 11 cases of metastatic liver cancer and CN from 109 cases of HCC. [Results] We found the zinc finger, CCCH-type with G patch domain (ZGPAT) gene to have expression decreased 4.198-fold in CN, and higher methylation status in CN (0.718), than in SN (0.360). The average expression value of the ZGPAT gene (ZGPAT value ×103 / GAPDH) decreased in CN (9.94 ± 10.68) relative to SN (28.55 ± 22.05). Compared with other patients, those with strongly reduced ZGPAT expression (&amp;lt; 1.5) in their non-tumor liver samples had significantly shorter overall survival (P = 0.024), but not recurrence-free survival (P = 0.515). [Discussion &amp; Conclusion] Our results indicate that expression of the ZGPAT gene in non-tumor liver tissue is a good biomarker for the risk of HCC development. ZGPAT gene is reportedly a transcription repressor that negatively regulates expression of epidermal growth factor receptor, which in turn, mediates cell proliferation, survival, migration. In treating HCC, detection of both prognostic factors from non-tumor liver tissue and malignant factors of the primary cancer lesion is important. Citation Format: Mitsuhiro Hishida, Shuji Nomoto, Yoshikuni Inokawa, Nao Takano, Mitsuro Kanda, Naoki Iwata, Chie Tanaka, Daisuke Kobayashi, Yoko Nishikawa, Suguru Yamada, Goro Nakayama, Tsutomu Fujii, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera. ZGPAT gene expression in non-tumor hepatocellular carcinoma tissue is a likely biomarker for survival risk. [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 2870. doi:10.1158/1538-7445.AM2014-2870
Inhibition of Src kinase in mesothelioma cell lines leads to cytotoxicity, inhibition of migration, and decreased invasion
Authors: Srinivasa Bakkannagari, Babita Saigal, Dandan He, Ignacio Wistuba, Waun K. Hong, Faye M. Johnson, Anne S. Tsao
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3795 

Unresectable malignant mesothelioma is a challenging disease that responds poorly to chemotherapy. As such, there is a need for the identification of new targets for therapy. Src is a non-receptor tyrosine kinase that has been implicated in several processes that drive the development and progression of human malignancies, including tumor cell transformation, proliferation, angiogenesis, and altered motility. In epithelial tumors, increasing levels of Src overexpression and activation correlate with disease progression. However, the role of Src in malignant mesothelioma is not defined. We performed immunohistochemistry staining on 10 paraffin embedded tissue specimens for phosphorylated Src (pSrc, Y418). Half of the specimens expressed pSrc by this technique. In addition, we tested dasatinib (BMS-354825), a novel, oral, potent, multi-targeted kinase inhibitor of Src. As shown in the [table][1], dasatinib IC50 values for all four mesothelioma cell lines were below serum levels achieved in humans. Dasatinib also inhibited migration and invasion in the four cell lines in vitro at low doses (<100 nM). These results indicate that inhibiting Src in malignant mesothelioma may be an important therapeutic strategy. To the best of our knowledge, this is the first published report that explores the role of Src inhibition in malignant mesothelioma.



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 [2]: pending:yes
Prescription for a Healthy Nation: A New Approach to Improving Our Lives by Fixing Our Everyday WorldTomFarley. and DeborahCohen. . Prescription for a Healthy Nation: A New Approach to Improving Our Lives by Fixing Our Everyday World. . 2005. . Beacon Press. : Boston, MA. . ISBN: ISBN: 0-8070-2116-4. . <b>$24.95</b>
Authors: Rudolph Rull
Journal: Environmental Health Perspectives (2005)