tbuckley/cabot-search huggingface dataset:
Psoriasis and extra domain A fibronectin loops
Authors: J.P. McFadden, B.S. Baker, A.V. Powles, L. Fry
Journal: British Journal of Dermatology (2010)

We have previously postulated that as well as T-helper (Th) 1 and Th17 cells, the transforming growth factor (TGF)-beta/fibronectin (FN)/alpha5beta1 pathway is central to psoriasis pathogenesis. EDA+ FN refers to an alternatively spliced isoform of FN with an additional domain known as extra domain A. EDA+ FN has two important properties pertinent to psoriasis lesions: it stimulates keratinocyte hyperproliferation, and, through stimulation of Toll-like receptor (TLR) 4, stimulates production of proinflammatory cytokines. EDA+ FN production induced by TGF-beta stimulation can be maintained in psoriasis lesions via two main feedback loops. Firstly, EDA+ FN stimulates proliferation of keratinocytes, which, in an autocrine fashion, will release more EDA+ FN. Secondly, EDA+ FN stimulates TLR4 expressed by antigen-presenting cells resulting in the production of proinflammatory cytokines such as tumour necrosis factor-alpha, interleukin (IL)-1, IL-6 and IL-12. The resultant promotion of cutaneous inflammation results in the recruitment of Th1 cells, which also produce EDA+ FN. We propose that these 'FN loops' contribute to the maintenance and progression of psoriatic lesions. Finally, although the association between psoriasis and heart/thrombotic disease remains unclear one plausible link may be the promotion of atherosclerosis and thrombotic heart disease by EDA+ FN.
Experimental Hypnosis: A Symposium of Articles on Research by Many of the World's Leading Authorities.
Authors: Leslie Middlekauff LeCron
Journal: JAMA (1953)

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
Clinical Uses of Adrenal Steroids.
Authors: Josiah Brown, Carl M. Pearson
Journal: Annals of Internal Medicine (1962)

This extremely current and inclusive collection of 17 papers belongs to a group of clinical publications sponsored by the University of California Medical Extension Series. The book, written by 22 specialists mainly from California but also some from other medical centers, is divided into 2 sections. The first is concerned with the clinical use of steroids in the treatment of adrenal diseases, of diseases of connective tissue (the collagen diseases) and specific fields of medicine such as allergy, dermatology, lung disease, gastrointestinal disease, renal disease, and neoplastic and hematologic diseases. The second section deals with basic knowledge concerning the biochemistry of steroids, their structuralfunctional relationships, the effects of steroids on water and electrolyte metabolism and renal function, and lastly the effects of steroids on the metabolism of carbohydrate, protein, and fat. These chapters, by S. Roberts, J. M. Koplowitz and C. R. Kleeman, and J. Brown, respectively, are notably clear with ample classical and current references. Also of note is the introductory chapter by P. K. Bondy who presents an extremely objec¬ tive and philosophical approach to the use of steroids in clinical medicine. The book may serve as a guide for both the internist and for the specialist who deals with the use of steroids in certain disease states. The book is particularly useful to the physician with less experience in the use of steroids and to the physician de¬ liberating in a given patient whether steroid therapy should be instituted. George F. Cahill, Jr., M.D.
Abstract 991: The Novel BTB/POZ Protein, RhoBTB3, Regulates Mitochondrial Function Via The Ubiquitin Proteasome System
Authors: Shinsuke Yuasa, Takeshi Onizuka, Shimoji Kenichiro, Yohei Ohno, Masaharu Katayama, Takahide Arai, Fumiyuki Hattori, Mitsushige Murata, Daihiko Hakuno, Kensuke Kimura, Shinji Makino, Motoaki Sano, Satoshi Ogawa, Keiichi Fukuda
Journal: Circulation (2007)

Although BTB/POZ family proteins play a critical role in the development of various organs, and are recently known as a substrate adaptor of CUL3 ubiquitin ligases, the involvement of these proteins in heart development remains unknown. We recently isolated the novel protein, RhoBTB3, an 83-kD protein which comprises an N-terminal Rho GTPase resembling domain and two tandem BTB domains. The purpose of this study was to investigate the molecular and functional characteristics of this protein in mice heart. [Methods and Results] RhoBTB3 was faintly expressed in the embryonic heart, but was strongly expressed in the adult heart. It was weakly expressed in adult brain and testis. RhoBTB3-GFP fusion protein cDNA was transfected into primary cultured rat cardiomyocytes using adenovirus. Fluorescence microscopy revealed that RhoBTB3 was located at the cytoplasm of living cardiomyocytes. HA-tagged RhoBTB3 and MYC-tagged CUL family proteins (1 – 5) were co-transfected into COS7 cells. RhoBTB3 was co-immunoprecipitated with CUL3 in vitro , but not with other CUL proteins. The various mutant RhoBTB3 and wild type CUL3 protein were examined by immunoprecipitation assay. Both the first BTB domain and second BTB domain can bind to CUL3 protein independently. It was difficult to detect RhoBTB3 in protein analysis. To determine whether or not RhoBTB3 itself could be the Cul3 ubiquitin target, RhoBTB3 protein was measured under the presence of proteasome inhibitor MG132 and protein synthesis inhibitor cycloheximide. The RhoBTB3 protein was immediately degraded and dropped below the detection level within 2 hours. The transgenic mice which overexpressed the heart-restricted RhoBTB3 were healthy at a young age. But after 3 months, they gradually showed heart failure and finally fell into sudden death. Interestingly before heart failure, electron microscopy demonstrated that mitochondria dramatically increased in number and showed deformity in RhoBTB3 transgenic hearts. [Conclusions] RhoBTB3 is mainly expressed in the adult heart, and its protein was rapidly degraded with the CUL3-mediated ubiquitin proteasome system in the heart. The overexpression of RhoBTB3 caused a marked increase in abnormal mitochondria, followed by severe heart failure.
Pesticide Exposure at Schools and Acute Illnesses
Authors: Barbara M Kirrane, Robert S Hoffman
Journal: JAMA (2005)

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
Economic Behavior and Informed Consent—Reply
Authors: Laura B. Dunn, Nora E. Gordon
Journal: JAMA (2005)

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
Further Studies on Isoantigenic Variation in Mouse Carcinomas and Sarcomas&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Eva Klein, George Klein, K. E. Hellström
Journal: JNCI Journal of the National Cancer Institute (1960)

Further studies have been made on the occurrence and nature of isoantigenic variant formation in sarcomas, carcinomas, and lymphomas arising in F1 hybrid mice derived from the outcross of 2 isogenic-resistant (IR) lines, which have confirmed the individuality of different tumors of the same type. No variants have been obtained in a small number of estrogen-induced and dependent testicular tumors. Variants compatible with a parental strain could also be isolated from tumors arising in F1 hybrids derived from crossing 2 unrelated inbred strains of mice.
300. Targeted Gene Correction in Mouse Embryonic Stem Cells Using Helper-Dependent Adenoviral Vectors
Authors: Fumi Ohbayashi, Michael A. Balamotis, Ko Mitani
Journal: Molecular Therapy (2004)

Integration of a therapeutic gene into random sites on host chromosomes could potentially lead to serious problems such as cellular transformation and gene silencing. Gene targeting, the process of homologous recombination between exogenous and chromosomal DNA, would achieve safe, transcriptionally active and stable expression of an integrated gene. However, the low frequency of homologous recombination in mammalian cells prevents therapeutic application of this strategy. Recombinant adenoviral vectors (AdVs) might be an ideal vehicle for homologous recombination because of their highly efficient delivery of double-stranded DNA genomes into the nucleus of almost any cell type. We examined the ability of AdVs to correct an insertional mutation in exon 3 of the hypoxanthine phosphoribosyl transferase (Hprt) locus in male mouse embryonic stem (ES) cells. The cells were infected with four types of Hprt targeting AdVs (E1-deleted vectors with 1.7-kb and 6.7-kb wild-type Hprt sequences and helper-dependent (HD) AdVs with 6.7-kb and 18.6-kb wild-type Hprt sequences) at multiplicities of infection (MOI) of 10, 100 and 1000 genomes per cell. The ES cells that might have undergone homologous recombination and thus restored their HPRT activity were detected by HAT selection. The HD AdVs also encode the beta-geo marker gene, which flanks the Hprt sequence. Therefore, randomly integrated vectors could also be detected by G418 selection. The frequency of homologous recombination in cells infected with HD AdVs with an 18.6-kb homology was nearly 0.02%, an 800-fold increase compared to those cells infected by an E1-deleted vector with the 6.7-kb homology. No homologous recombination was detected with the E1-deleted vector with the 1.7-kb Hprt sequence. In contrast to the homologous recombination frequency, which showed an MOI-dependent increase, the random integration frequency reached maximum levels at an MOI of 100 and was similar between the HD AdVs. The ratio of random to targeted integration was 61% with the 18.6-kb HD AdV at an MOI of 1000. Treatment of the infected cells with trichostatin A, a histone deacetylase inhibitor, enhanced only the random integration frequency but had no effect on the frequency of targeted integration. The majority of HAT-resistant cell clones showed a pattern of faithful gene targeting. No randomly integrated vectors were observed in the cells with targeted vector integration, as analyzed by PCR. These findings suggest that adenovirus-mediated homologous recombination might be applicable for ex vivo gene therapy.
The combined actins of NK and T lymphocytes are necessary to reject a transplantable mesenchymal tumor through mechanisms partly dependent on KG2D
Authors: Ainhoa Arina, Eduardo Huarte, Oihana Murillo, Iñigo Tirapu, Arantza Azpilikueta, Carlos Alfaro, Jose L. Perez-Gracia, David H. Raulet, Ignacio Melero
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

620 

Better understanding of the mechanisms that mediate spontaneous immune rejections of mouse tumors ought to be important in the quest for improvements in immunotherapy of cancer. A set of intraperitoneal tumors of mesenchymal origin that had been chemically induced in ubiquitously expressing EGFP transgenic mice provided a model in which both T and NK cells were absolutely required for tumor rejection. Tumor cells were green fluorescent and readily grafted in RAG1-/- immunodeficient mice, while they were majoritarily rejected in syngeneic C57BL/6 and EGFP-transgenic mice. Tumor cell clones with the highest EGFP expression tended to be rejected in immunocompetent mice, but a direct involvement of EGFP as the antigen recognized for the immune rejections was ruled out. Rejections were absolutely dependent on NK cells as well as on CD4+ and CD8+ T lymphocytes. The effects of IFN-γ were required only at the malignant cell level. The progressing variants of the tumor in syngeneic mice were rejected in (C57BL/6 x BALB/c) CB6F1 mice in a NK dependent fashion, indicating that semiallogeneic NK cells were superior at the rejection of these tumors. NK recognition of tumor cells was at least in part mediated by the NKG2D activating receptor, but blocking its function in vivo only partially interfered with the rejection in syngeneic mice, indicating the in vivo activity of additional NK receptors. Rejection needs a concerted set of activities that are mediated by NK and T cells, that on the NK part include early destruction of tumor cells, and provision of cell debris for T-cell crosspriming by DC, as well as production of proinflammatory cytokines. NK cells were also readily detected in the tumor-rejecting leukocyte infiltrates.
Abstract 16469: Human Immunodeficiency Virus (HIV)-Transgenic Rats Display Induced Expression of Vascular Factors Associated With Atherosclerosis
Authors: Amie K Lund, JoAnn Lucero, Lindsay M Herbert, Jay S Naik
Journal: Circulation (2011)

Multiple epidemiological studies have reported that HIV-infected individuals have a significantly increased risk of cardiovascular disease and clinical events. Study findings report cardiovascular ...
bmjlearning.com: Menorrhagia
Authors: Gavin Yamey
Journal: BMJ (2004)

BMJ Learning offers interactive online learning resources to help you with your appraisal and revalidation. We aim to publish new modules every month, and we have recently published a module about diagnosing and treating menorrhagia.

Menorrhagia is an important part of a general practitioner's workload, accounting for 1 in 20 consultations in the United Kingdom. Objectively, it is defined as a menstrual blood loss of at least 80 ml per menstruation, but there is no simple primary care tool for objectively measuring blood loss. About 60% of women who say they have heavy periods are found to have normal periods when their blood loss is measured. Taking a detailed history can help prevent women with normal periods from having unnecessary treatments, including hysterectomy.

Most women with menorrhagia can be successfully treated in primary care if you prescribe the most effective drugs. Unfortunately, there is no good evidence of effectiveness for many commonly used treatments for menorrhagia. For example, oral progestogens are one of the most commonly prescribed treatments and yet are one of the least effective. They may even increase blood loss. Tranexamic acid and non-steroidal anti-inflammatory drugs are the treatments that work best.

Surgery is an option for the minority of women who get little benefit from medical treatment. Hysterectomy and endometrial destruction are both associated with high rates of satisfaction in the long term. Women who have endometrial destruction are more likely to need repeat surgery, but the benefits of this technique include shorter duration of surgery, shorter hospital stay, and quicker time to return to work compared with hysterectomy. Myomectomy and dilatation and curettage are not helpful treatments for menorrhagia.

To find out more about the diagnosis and treatment of menorrhagia, try our new learning module on bmjlearning.com
Anxiety and depression measured by HASD questionnaire are related to failure in 4 week smoking cessation program
Authors: Frederico Fernandes, Gustavo Prado, Ubiratan Santos, João Paulo Lotufo, Mirian Fukuoka, Edinalva Souza
Journal: European Respiratory Journal (2011)

Anxiety and depression are common among smokers and are perceived barriers to smoking cessation. Our goal in this study was to evaluate if anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS) was greater in patients who failed to quit in our 4 week hospital based smoking cessation program.  All patients enrolled in our program since 2009 were invited to answer the 14 question HADS. Patients were divided in 2 groups, those who quit smoking (Q) and those that continued to smoke (NQ) after the end of the 4 week program. All patients were treated with behavioral therapy, nicotine replacement and/or bupropion. A score of 8 to 10 in each HADS category is considered borderline and a score of more than 10 is regarded as significant anxiety or depression.  From 447 patients screened, 197 patients answered the questionnaire. Fagerstrom Test for Nicotine Dependence scored 6.2±2.0. Mean age was 49±10 years, 79 were males and 118 females. 62% had borderline or significant anxiety and 34% scored 8 or more in depression questions. Both Q (N=58) and NQ (N=139) groups were similar regarding age, sex and Fagerstrom score. Those in group Q scored a median of 4 in depression score while group NQ scored 6 (p  We found a statistic significant difference in anxiety and depression scores between those who succeeded and those who failed in quitting at the end of our 4 week program. Anxiety and depression were more accurate in predicting failure than the nicotine dependence score. This reinforces the need for screening psychiatric conditions during a smoking cessation program.
Abstract 5578: Breast cancer cell growth regulatory mechanisms of tamoxifen metabolites
Authors: T. Thomas, Huichen Hsu, PingAr Yang, Mervi T. Hyvonen, Tuomo A. Keinanen
Journal: Cancer Research (2014)

Abstract The proliferation of estrogen receptor alpha (ERalpha)-positive breast cancer cells is stimulated by estradiol. Tamoxifen [(Z)-2-[4-(1,2-diphenylbut-1-enyl)phenoxy]-N,N-dimethylethanamine] is the most commonly used endocrine treatment for ERalpha-positive breast cancer in pre- and post-menopausal women. Tamoxifen is metabolized to 4-hydroxytamoxifen and endoxifen. ICI 182780 (Faslodex or Fulvestrant) is a pure antiestrogen targeted to the ERalpha. We investigated the effects of endoxifen and 4-hydroxytamoxifen on ERalpha-positive MCF-7 breast cancer cells using cell growth assay, oncogene expression and polyamine regulatory pathways. Polyamines are ubiquitous cellular components and are essential for cell growth and differentiation. Treatment of cells for 1-5 days with 4 nM estradiol increased cells number, whereas the addition of endoxifen, 4-hydroxytamoxifen or ICI 182780 in combination with estradiol suppressed cell growth in a concentration- and time-dependent manner. Real time quantitative polymerase chain reaction (RT-qPCR) experiments showed that the addition of 4 nM estradiol to MCF-7 cells increased the expression of c-myc, c-fos and Tiff1 genes significantly, while the addition endoxifen, 4-hydroxytamoxifen, or ICI 182780 suppressed estradiol-mediated increase in gene expression. Polyamine biosynthetic enzymes were also affected by tamoxifen metabolites. Estradiol increased the activities of the polyamine biosynthetic enzyme, ornithine decarboxlase (ODC) and S-adenosylmethionine decarboxlase (AdoMetDC), whereas the antiestrogens suppressed ODC and AdoMetDC activities in a concentration- and time-dependent manner. However, these agents had little effect on the activity of the polyamine catabolic enzyme, spermidine/spermine N1-acetyl transferase (SSAT). The change in biosynthetic enzyme activities was reflected in polyamine pools, as decreased putrescine and spermidine levels. There was no significant change in spermine level. These results suggest that the mechanism of action of tamoxifen metabolites involves multiple cell growth regulatory pathways. In addition, endoxifen can act as an antiestrogen and suppress cell growth stimulatory effects of estradiol on ERalpha-positive breast cancer cells in a manner similar to that of ICI 182780. Note: This abstract was not presented at the meeting. Citation Format: T. Thomas, Huichen Hsu, PingAr Yang, Mervi T. Hyvonen, Tuomo A. Keinanen. Breast cancer cell growth regulatory mechanisms of tamoxifen metabolites. [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 5578. doi:10.1158/1538-7445.AM2014-5578
Have a Healthy Autumn
Authors: Rebecca Voelker
Journal: JAMA (1998)

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