tbuckley/cabot-search huggingface dataset:
Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities
Authors: Mayte Suárez-Fariñas, Suzanne J. Tintle, Avner Shemer, Andrea Chiricozzi, Kristine Nograles, Irma Cardinale, Shenghui Duan, Anne M. Bowcock, James G. Krueger, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2011)
House of Lords champions researchers' cause
Authors: J. Warden
Journal: BMJ (1995)

A new deal for the 20000 researchers in Britain who work on contracts has been advocated by the House of Lords Select Committee on Science and Technology. Describing them as a “scientific underclass,” the lords said that contract staff should have the same status and rights as the permanent academic staff in universities, better management of their careers, and funding to bridge the gaps between contracts.

The inquiry reflects concern about the rapid increase in non-tenured staff …
184. Nonvirally Electrotransfected Human Mesenchymal Stem Cells: A Novel Platform for Bone Gene Therapy Based on Autocrine and Paracrine Mechanisms
Authors: Hadi Aslan, Yoram Zilberman, Jin Zhong Li, Gregory A. Helm, Zulma Gazit, Dan Gazit
Journal: Molecular Therapy (2005)

Studies have shown that cell-mediated gene therapy involving virally transduced mesenchymal stem cells (MSCs) can efficiently regenerate nonunion bone defects. In these studies bone tissue regeneration was achieved by using viral gene delivery of osteogenic factors. There have been extensive reports on the limitations of virus-based approaches, most focusing on the humoral immune response generated against viral proteins. An alternative approach is the use of nonviral gene therapy, which is considered safer but lacks the high efficiency of gene transduction provided by viral vectors. DNA electrotransfer (electroporation) may be an efficient physical method of delivering genes into primary stem cells. We tested the hypothesis that in vivo bone regeneration can be achieved via autocrine and paracrine effects exerted by human (h)MSCs that are nonvirally electrotransfected with BMP genes. Primary hMSCs were electrotransfected using a Nucleofector (Amaxa Biosystems), a novel electroporation system. In the first stage of our study we utilized the gene of the enhanced green fluorescent protein (EGFP) to assess the viability of hMSCs and the efficiency of DNA transfer. In the second stage we used the osteogenic genes BMP-2 and BMP-9 to induce osteogenic differentiation via autocrine and paracrine effects. Our in vitro results demonstrated 53% cell viability, up to 70% transfection efficiency, and transgene expression that lasted at least 14 days in vitro. BMP-electrotransfected hMSCs expressing luciferase were detected in vivo by using noninvasive, quantitative bioluminescence imaging following an injection of these cells into the thigh muscles of NOD/SCID mice. Micro-computerized tomography (°CT) demonstrated new bone formation at the injection site 4 weeks postinjection (Fig. 1A & B). The electrotransfected hMSCs differentiated and integrated into the newly formed bone; this was demonstrated by masson's trichrome (Fig. 1C & D) and an anti-human mitochondria immunohistochemical analysis (Fig. 1E & F, arrowheads). Both in vitro and in vivo studies demonstrated a significantly higher osteogenic potency in BMP-9-electrotransfected hMSCs than in BMP-2-electrotransfected hMSCs. We conclude that hMSCs can be effectively transfected using this novel nonviral technique. These findings may pave the way to a safe and efficient gene therapy for human bone regeneration.
Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study
Authors: E. Warensjo, L. Byberg, H. Melhus, R. Gedeborg, H. Mallmin, A. Wolk, K. Michaelsson
Journal: BMJ (2011)

<b>Objective</b> To investigate associations between long term dietary intake of calcium and risk of fracture of any type, hip fractures, and osteoporosis. <b>Design</b> A longitudinal and prospective cohort study, based on the Swedish Mammography Cohort, including a subcohort, the Swedish Mammography Cohort Clinical. <b>Setting</b> A population based cohort in Sweden established in 1987. <b>Participants</b> 61 433 women (born between 1914 and 1948) were followed up for 19 years. 5022 of these women participated in the subcohort. <b>Main outcome measures</b> Primary outcome measures were incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort. Diet was assessed by repeated food frequency questionnaires. <b>Results</b> During follow-up, 14 738 women (24%) experienced a first fracture of any type and among them 3871 (6%) a first hip fracture. Of the 5022 women in the subcohort, 1012 (20%) were measured as osteoporotic. The risk patterns with dietary calcium were non-linear. The crude rate of a first fracture of any type was 17.2/1000 person years at risk in the lowest quintile of calcium intake, and 14.0/1000 person years at risk in the third quintile, corresponding to a multivariable adjusted hazard ratio of 1.18 (95% confidence interval 1.12 to 1.25). The hazard ratio for a first hip fracture was 1.29 (1.17 to 1.43) and the odds ratio for osteoporosis was 1.47 (1.09 to 2.00). With a low vitamin D intake, the rate of fracture in the first calcium quintile was more pronounced. The highest quintile of calcium intake did not further reduce the risk of fractures of any type, or of osteoporosis, but was associated with a higher rate of hip fracture, hazard ratio 1.19 (1.06 to 1.32). <b>Conclusion</b> Gradual increases in dietary calcium intake above the first quintile in our female population were not associated with further reductions in fracture risk or osteoporosis.
Federal Funding and Supportive Policies for Research
Authors: John Edward Porter
Journal: JAMA (2005)

TODAY, THE UNITED STATES IS ONLY ONE DECADE REmoved from what was then a forecast of difficult meager times for the national investment in medical and scientific research. In 1995, the US House of Representatives budget resolution called for a cut in funding for the National Institutes of Health (NIH) of 5% for fiscal year (FY) 1996 and a freeze on NIH funding through FY 2000. However, the NIH received an increase of almost 6% for FY 1996, followed by 7% increases in the following 2 years when the economy was not yet strong. Those years of increases were followed by the remarkable feat of doubling the NIH budget over 5 years—FYs 1999-2003. Bad news can be turned into good news, bad numbers into better, even pacesetting ones. Influencing the impact of current political and economic realities on the United States investment in research requires recognition of some somber realities. Now, the nation is engaged in a costly war; is attempting to protect itself from probable terrorist attacks; has an exploding population of senior citizens who, remarkably, given not-so-distant history, now live for decades with chronic diseases; and now has recordbreaking federal budget deficits. Although the priorities in competition for financial resources may be different today than in decades past, the United States has been and will always be a nation with competing priorities. Members of the US Congress and appropriators specifically are charged with establishing priorities for expenditure of the nation’s fiscal resources. The administration and Congress must be continually informed of the very high priority the public consistently assigns to investment in research. Success is achieved by those who fight for what they believe in and who are willing to work to translate beliefs into reality. The enormous promise of medical and scientific research—in both lifesaving and economic terms—will not be realized without the hard work and smart work of a unified constituency committed to advancing science and saving lives.
A2-07: Usefulness of FDG-PET/CT for evaluation of tumor response after stereotactic radiosurgery in primary or metastatic lung cancer
Authors: Jung Hoon Kim, Eun Kyung Choi, Jung Shin Lee, Jin Sook Ryu, Woo-Sung Kim, Tae-Sun Shim, Sang-We Kim, Jin Seong Lee, Si Yeol Song, Hyoung-Uk Je
Journal: Journal of Thoracic Oncology (2007)
Ernest B. Howard, MD
Authors: Malcolm C. Todd
Journal: JAMA (1994)

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
Current Diagnosis and Treatment in Rheumatology
Authors: Daniel Muller
Journal: JAMA (2007)

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
Soluble fibrin degradation products potentiate tissue plasminogen activator-induced fibrinogen proteolysis.
Authors: J I Weitz, B Leslie, J Ginsberg
Journal: Journal of Clinical Investigation (1991)

Despite its affinity for fibrin, tissue plasminogen activator (t-PA) administration causes systemic fibrinogenolysis. To investigate the mechanism, t-PA was incubated with plasma in the presence or absence of a fibrin clot, and the extent of fibrinogenolysis was determined by measuring B beta 1-42. In the presence of fibrin, there is a 21-fold increase in B beta 1-42 levels. The potentiation of fibrinogenolysis in the presence of fibrin is mediated by soluble fibrin degradation products because (a) the extent of t-PA induced fibrinogenolysis and clot lysis are directly related, (b) once clot lysis has been initiated, fibrinogenolysis continues even after the clot is removed, and (c) lysates of cross-linked fibrin clots potentiate t-PA-mediated fibrinogenolysis. Fibrin degradation products stimulate fibrinogenolysis by binding t-PA and plasminogen because approximately 70% of the labeled material in the clot lysates binds to both t-PA- and plasminogen-Sepharose, and only the bound fractions have potentiating activity. The binding site for t-PA and plasminogen is on the E domain because characterization of the potentiating fragments using gel filtration followed by PAGE and immunoblotting indicates that the major species is (DD)E complex, whereas minor components include high-molecular weight derivatives containing the (DD)E complex and fragment E. In contrast, D-dimer is the predominant species found in the fractions that do not bind to the adsorbants, and it has no potentiating activity. Thus, soluble products of t-PA-induced lysis of cross-linked fibrin potentiate t-PA-mediated fibrinogenolysis by providing a surface for t-PA and plasminogen binding thereby promoting plasmin generation. The occurrence of this phenomenon after therapeutic thrombolysis may explain the limited clot selectivity of t-PA.
Interleukin-10 promoter polymorphism IL10.G and familial early onset psoriasis
Authors: P. Hensen, K. Asadullah, C. Windemuth, F. Ruschendorf, U. Huffmeier, M. Stander, M. Schmitt-Egenolf, T.F. Wienker, A. Reis, H. Traupe
Journal: British Journal of Dermatology (2003)

The anti-inflammatory cytokine interleukin (IL)-10 is considered to play a major role in the pathophysiology of psoriasis, which is characterized by an IL-10 deficiency. Systemic administration of IL-10 has been shown to be an effective therapy for psoriasis. The IL-10 promoter region contains a highly polymorphic microsatellite (IL10.G) and in a recent case-control study the IL10.G13 (144 bp) allele was found to be associated with familial early onset psoriasis (type 1 psoriasis) having a susceptible effect.As it is essential in multifactorial diseases to replicate findings before definite conclusions can be drawn, we decided to perform a follow-up study and to follow a genetic approach analysing allele transmission in families with a positive family history of psoriasis.We studied 137 nuclear families (trio-design) comprising 456 individuals and genotyped the IL10.G marker. For comparison we also genotyped the microsatellite tn62 as a reference marker of the major psoriasis susceptibility locus on chromosome 6p21 (PSORS1). In the present study allele transmission was evaluated using the family-based association test (FBAT) and GENEHUNTER 2.0 based on the transmission/disequilibrium test.The G13 allele (144 bp) had a frequency of 24%, was present in 88 families and clearly showed an even transmission (FBAT, P = 0.753). In contrast, allele 3 (IL10.G9) (136 bp) had a frequency of 39%, was present in 110 families and was transmitted in 43 trios and remained untransmitted in 67 trios (FBAT, P = 0.026), thus showing preferential nontransmission. For the HLA-linked tn62-marker we obtained a P-value of 0.00027 for allele 4 in the same study group.In conclusion, we failed to confirm the susceptible effect of the G13 allele, but provide the first data for a protective effect of allele 3 (IL10.G9) for familial psoriasis. Our results suggest that the IL10.G polymorphism is not a major locus, but acts as a minor locus.
Psychiatric Disorders and Criminality
Authors: Samuel B. Guze, Robert A. Woodruff, Paula J. Clayton
Journal: JAMA (1974)

A study of 500 psychiatric clinic patients indicated that serious crime (felony conviction) was chiefly associated with sociopathy, alcoholism, and drug dependence. Except for sexually deviant behavior leading to arrest and conviction, other psychiatric disorders are infrequently associated with felonies.
Beyond tricyclics: outlook on antidepressive treatments
Authors: Elizabeth Rasche González
Journal: JAMA (1980)

Tricyclic antidepressants are not for everyone. Because some depressed persons do not respond to these drugs at all or have severe adverse reactions, certain discarded treatments for depression are again finding favor, while new ones proliferate. "Monoamine oxidase inhibitors [MAOIs] have been looked at askance, for example, but they will probably be coming back more and more," says Jan Fawcett, MD, chief of psychiatry at Rush-Presbyterian-St Luke's Medical Center in Chicago. "They didn't seem efficacious in early studies—the dosages in those studies were too low—but in higher dosages they appear to be very effective for many patients who do not respond to tricyclics." Newer pharmacotherapies include a spate of chemicals tested widely in Europe and elsewhere but minimally in the United States, such as the tetracyclics which are popular in England. For the most part, these drugs have proved no more efficacious than tricyclics and are equally toxic
Topical application of imiquimod 5% cream to keloids alters expression genes associated with apoptosis
Authors: S.E. Jacob, B. Berman, M. Nassiri, V. Vincek
Journal: British Journal of Dermatology (2003)

Keloids are benign mesenchymal tumours, usually present at and extending beyond the margins of sites of previous injury. It is reported that keloids display aberrant expression of apoptotic genes: TGFB1 is activated, whereas caspase 8 and 3 are not, thus indicating a block upstream in the apoptosis cascade in keloids. Interferon‐α2b normalizes the excessive synthesis of collagen, glycosaminoglycans and collagenase by keloidal fibroblasts, reduces recurrences following keloid excision, and enhances the expression of native p53 and apoptosis. Imiquimod, a rapid and potent inducer of interferons locally at the site of application to the skin, reduces recurrences following keloid excision and alters gene expression of markers of apoptosis in basal cell carcinoma cells. We investigated the effects with respect to the expression of apoptotic genes in keloidal tissue compared with nontreated controls of imiquimod 5% cream applied topically to keloids. Total RNA was extracted from excised keloidal tissue, cDNA probes synthesized and then hybridized to gene‐specific cDNA fragments spotted on membranes. The expression levels of 96 genes involved in apoptosis, relative to cyclophilin expression, were compared in the imiquimod‐treated and untreated groups. The mean ratio of expression, relative to cyclophilin of caspase 3 and DFFA were significantly enhanced. Caspase 3 was significantly downregulated and DFFA was significantly upregulated in the group of imiquimod‐treated keloids (P < 0·05) compared with the untreated group of keloids. Although imiquimod is capable of altering the expression of these markers of apoptosis in keloids, their role, if any, in the therapeutic response of keloids to imiquimod requires further investigation.
Jaundice in Thalassemia Minor
Authors: Stephen Robinson, Therese Vanier, Jane F. Desforges, Rudi Schmid
Journal: New England Journal of Medicine (1962)

THE term "ineffective erythropoiesis" is used to describe a pathophysiologic state in which a significant fraction of the erythropoietic activity of the bone marrow fails to produce circulating red cells with a measurable life-span.1 , 2 Instead, much of the heme pigment synthesized appears to be destroyed while the maturing erythroid cells are still in the bone marrow or shortly after their release into the circulation.3 This results in a disproportionately low reticulocyte count in the peripheral blood despite marked erythroid hyperplasia in the bone marrow.Studies of plasma iron turnover, radioiron utilization, fecal urobilinogen excretion and myeloid-erythroid ratio in the bone . . .
G Protein Coupled Receptor Kinase 3 (GRK3) - Deficient T Cells Demonstrate Enhanced Migration To CXCL12 And CX3CL1
Authors: L.R. Rothlein, R.G. Timoshchenko, D.J. Fitzhugh, M.W. McGinnis, G. Laroche, D.P. Siderovski, T.K. Tarrant
Journal: Journal of Allergy and Clinical Immunology (2011)
Neutrophils and Host Defense
Authors: Robert I. Lehrer
Journal: Annals of Internal Medicine (1988)

Neutrophils, the predominant phagocytes of circulating blood, are the first cells to arrive at sites of infection. Although neutropenia has long been recognized to predispose to infection, recently other syndromes marked by frequent infections have been shown to be caused by an underlying neutrophil dysfunction. Efforts to define the molecular pathology of such disorders have helped delineate the molecular basis of normal neutrophil function. Advances have been made in defining the roles of the neutrophil's varied receptors in recognition, movement, and adhesive phenomena. Progress in establishing the pathogenesis of chronic granulomatous disease has provided important insights into the enzymatic machinery that normal neutrophils use to produce antimicrobial oxidants. The identification and precise characterization of antimicrobial components, such as defensins, have outlined the potential roles of "natural antibiotics" in neutrophil-mediated host-defense functions. These areas of neutrophil function will be reviewed and placed in a clinical context to guide physicians in evaluating children and adults with frequent or unusual infections.
Abstract 2196: Upregulation of survivin during immortalization is linked to repression of p16INK4a and confers resistance to oxidative stress
Authors: Carlotta Petti, Chin-Yi Kan, Philipp A. Dietrich, Bracken Lauryn, Ning Xu, Jun Yuan, Tao Liu, Karen L. MacKenzie
Journal: Cancer Research (2012)

Abstract Survivin is an essential component of the chromosomal passenger complex and a member of the Inhibitor of Apoptosis (IAP) family. It is expressed at high levels in a large variety of malignancies, where it is implicated in cytoprotection and drug resistance. Nevertheless, the pathways that mediate the cytoprotective functions of survivin and the mechanisms underlying its upregulation in cancer have not been fully elucidated. Results from our past investigations revealed that survivin was upregulated during telomerase-mediated immortalization of human myofibroblasts (MRC-5) (1). Since the immortalization process is an essential step in human carcinogenesis, upregulation of survivin during immortalization may explain why survivin is abundant in virtually all cancers. The present study aimed to characterize the mechanism responsible for the upregulation of survivin during immortalization, and the functional consequences of its over expression in immortal cells. Results from whole genome expression analyses and qRT-PCR demonstrated that the upregulation of survivin during immortalization was paralleled by increased expression of the transcription factor E2F1. The chromatin immunoprecipitation (ChIP) assay confirmed that E2F1 directly interacted with the survivin gene (BIRC5) promoter in immortal cells. Moreover, it was shown that E2F1 binding to BIRC5 was corresponded with repression of tumor suppressor p16INK4a, an event that commonly occurs during immortalization and human tumorigenesis. Survivin and p16INK4a were also functionally linked by assays that showed either upregulation of survivin or repression of p16INK4a rendered telomerase-transduced MRC-5 cells resistant to oxidative stress. Conversely, siRNA-mediated down regulation of survivin activated caspases and enhanced the sensitivity of immortal MRC-5 cells to oxidative stress. Together these data show that repression of p16INK4a contributes to the upregulation of survivin, and thereby provides a survival advantage to cells that are subject to oxidative stress during immortalization. 1. Yuan et al., Oncogene (2009) 28, 2678-2689. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2196. doi:1538-7445.AM2012-2196
Potential hepatoprotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas
Authors: Rade Injac, Martina Perse, Natasa Obermajer, Vukosava Djordjevic-Milic, Matevz Prijatelj, Aleksandar Djordjevic, Anton Cerar, Borut Strukelj
Journal: Biomaterials (2008)
A Phase II Study of Intermittent Sunitinib Malate as Second-Line Therapy in Progressive Malignant Pleural Mesothelioma
Authors: Anna K. Nowak, Michael J. Millward, Jenette Creaney, Roslyn J. Francis, Ian M. Dick, Arman Hasani, Agatha van der Schaaf, Amanda Segal, Arthur W. Musk, Michael J. Byrne
Journal: Journal of Thoracic Oncology (2012)