tbuckley/cabot-search huggingface dataset:
Dystrophin Isoform Induction In Vivo by Antisense-mediated Alternative Splicing
Authors: Sue Fletcher, Abbie M Adams, Russell D Johnsen, Kane Greer, Hong M Moulton, Steve D Wilton
Journal: Molecular Therapy (2010)

Antisense oligomer-induced manipulation of dystrophin pre-mRNA processing can remove exons carrying mutations, or exclude exons flanking frameshifting mutations, and restore dystrophin expression in dystrophinopathy models and in Duchenne muscular dystrophy (DMD) patients. Splice intervention can also be used to manipulate the normal dystrophin pre-mRNA processing and ablate dystrophin expression in wild-type mice, with signs of pathology being induced in selected muscles within 4 weeks of commencing treatment. The disruption of normal dystrophin pre-mRNA processing to alter the reading frame can be very efficient and offers an alternative mechanism to RNA silencing for gene suppression. In addition, it is possible to remove in-frame exon blocks from the DMD gene transcript and induce specific dystrophin isoforms that retain partial functionality, without having to generate transgenic animal models. Specific exon removal to yield in-frame dystrophin transcripts will facilitate mapping of functional protein domains, based upon exon boundaries, and will be particularly relevant where there is either limited, or conflicting information as to the consequences of in-frame dystrophin exon deletions on the clinical severity and progression of the dystrophinopathy. Antisense oligomer-induced manipulation of dystrophin pre-mRNA processing can remove exons carrying mutations, or exclude exons flanking frameshifting mutations, and restore dystrophin expression in dystrophinopathy models and in Duchenne muscular dystrophy (DMD) patients. Splice intervention can also be used to manipulate the normal dystrophin pre-mRNA processing and ablate dystrophin expression in wild-type mice, with signs of pathology being induced in selected muscles within 4 weeks of commencing treatment. The disruption of normal dystrophin pre-mRNA processing to alter the reading frame can be very efficient and offers an alternative mechanism to RNA silencing for gene suppression. In addition, it is possible to remove in-frame exon blocks from the DMD gene transcript and induce specific dystrophin isoforms that retain partial functionality, without having to generate transgenic animal models. Specific exon removal to yield in-frame dystrophin transcripts will facilitate mapping of functional protein domains, based upon exon boundaries, and will be particularly relevant where there is either limited, or conflicting information as to the consequences of in-frame dystrophin exon deletions on the clinical severity and progression of the dystrophinopathy.
Injection studies of the splenic vasculature in portal hypertension.
Authors: F Manenti, R Williams
Journal: Gut (1966)

EDITORIAL SYNOPSIS Increased blood flow through muscle and skin is known to occur in hepatic cirrhosis.Splenic artery and vein injection studies have shown that the increased size of the spleen found in portal hypertension is accompanied by vascular changes suggesting increased blood flow.These changes consist of an increase in the number of venous and arterial channels as compared with the normal.The increase in arterial vessels was greater than venous and the changes were particularly marked in the smaller arteries.Arteriovenous anastomoses were not found, but aneurysms of the splenic artery or its main branches were found in 50% of cases.The relation of these changes to the development of portal hypertension and to vascular changes in other organs is discussed.
Solitary Papillomas of the Lower Airways: Epidemiological, Clinical, and Therapeutic Data during a 22-Year Period and Review of the Literature
Authors: Stavros Tryfon, Vasiliki Dramba, Fotis Zoglopitis, Dimitris Iakovidis, Leonidas Sakkas, Theodoros Kontakiotis, Nikolaos Galanis
Journal: Journal of Thoracic Oncology (2012)
Hand Difficulties Among Musicians
Authors: Joseph Goodgold
Journal: JAMA (1983)

<h3>To the Editor.—</h3> I read the article by Dr Hochberg and colleagues<sup>1</sup>entitled "Hand Difficulties Among Musicians" with great interest but must comment that what has been a mystery about these problems remains a mystery. I particularly allude to Table 7, the category of nerve disorders, that classified motor control problems as 27% of the cases. It was not possible to perceive how the patients in this group were diagnostically identified with specificity. It is indeed possible that their problems are manifestations of motor system dysfunction, but on the basis of evidence in the article, it is equally possible that the "elegant" comments of some of our illustrious neurological forebearers may not be entirely preposterous in applying the appellation<i>neuroses</i>. It would also be of considerable help to identify the "sophisticated physical therapy" and biofeedback techniques used to attain amelioration. With the latter, at least, there is still more
Genomic and Expression Analysis of the 8p11–12 Amplicon in Human Breast Cancer Cell Lines
Authors: Michael E. Ray, Zeng Quan Yang, Donna Albertson, Celina G. Kleer, Joseph G. Washburn, Jill A. Macoska, Stephen P. Ethier
Journal: Cancer Research (2004)

Abstract Gene amplification is an important mechanism of oncogene activation in breast and other cancers. Characterization of amplified regions of the genome in breast cancer has led to the identification of important oncogenes including erbB-2/HER-2, C-MYC, and fibroblast growth factor receptor (FGFR) 2. Chromosome 8p11-p12 is amplified in 10–15% of human breast cancers. The putative oncogene FGFR1 localizes to this region; however, we show evidence that FGFR inhibition fails to slow growth of three breast cancer cell lines with 8p11-p12 amplification. We present a detailed analysis of this amplicon in three human breast cancer cell lines using comparative genomic hybridization, traditional Southern and Northern analysis, and chromosome 8 cDNA microarray expression profiling. This study has identified new candidate oncogenes within the 8p11-p12 region, supporting the hypothesis that genes other than FGFR1 may contribute to oncogenesis in breast cancers with proximal 8p amplification.
Mutant Anthrax Toxin B Moiety (Protective Antigen) Inhibits Angiogenesis and Tumor Growth
Authors: Michael S. Rogers, Kenneth A. Christensen, Amy E. Birsner, Sarah M. Short, Darran J. Wigelsworth, R. John Collier, Robert J. D'Amato
Journal: Cancer Research (2007)

Abstract Bacillus anthracis protective antigen (PA), the B subunit of the binary anthrax toxin, binds to the cellular receptors capillary morphogenesis gene 2 protein and tumor endothelial marker 8 with high affinity. Both receptors are expressed on endothelial cells during angiogenesis. We sought to determine whether one could inhibit angiogenesis by interfering with the binding of these receptors to their endogenous ligands. Here, we show that wild-type PA inhibits both vascular endothelial growth factor–induced and basic fibroblast growth factor–induced angiogenesis at moderate but statistically significant levels. Structure-activity studies identified a PA mutant that exhibited markedly enhanced inhibition of angiogenesis and also inhibited tumor growth in vivo. This mutant, PASSSR, is unable to undergo normal cellular processing and, thus, remains bound to the surface receptor. Further mutation of PASSSR so that it does not bind to these cell surface receptors abolished its ability to inhibit angiogenesis. We conclude that high-affinity anthrax toxin receptor (ATR) ligands, such as PA and PASSSR, are angiogenesis inhibitors and that ATRs are useful targets for antiangiogenic therapy. These results also suggest that endothelial cell-binding proteins from additional pathogens may inhibit angiogenesis and raise the question of the role of such inhibition in pathogenesis. [Cancer Res 2007;67(20):9980–5]
Saddam Hussein's medical examination should not have been broadcast: British television should not have followed suit
Authors: J. M Carter
Journal: BMJ (2004)

Editor—I agree with Roberts (letter above) that it was wrong of the US administration in Iraq to broadcast images of Saddam Hussein undergoing a medical examination.

It was also wrong of British television companies to broadcast those images, and I emailed the BBC immediately to register my complaint. British television companies had the choice whether to broadcast these images. I hope that the medical profession in the United Kingdom will express its strong disapproval of their action.
Memories of Katrina Continue to Hinder Mental Health Recovery in New Orleans
Authors: Rebecca Voelker
Journal: JAMA (2010)

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
Mechanistic Analysis of the Role of BLCA-4 in Bladder Cancer Pathobiology
Authors: Julie M. Myers-Irvin, Thu-Suong Van Le, Robert H. Getzenberg
Journal: Cancer Research (2005)

Analysis of alterations in nuclear structure associated with bladder cancer has revealed specific changes associated with the disease. This includes the identification of six bladder cancer-specific proteins and the successful development of urine-based immunoassays for the detection of two of these biomarkers, BLCA-1 and BLCA-4. The purpose of this study is to examine the functional aspects of BLCA-4 and its potential role in bladder cancer pathobiology. Sequence analysis of BLCA-4 reveals that it is a member of the ETS transcription factor family and that it seems to associate with transcription factors. To examine the effects of this protein, the gene encoding BLCA-4 was stably transfected into human urothelial cells. BLCA-4 expression was confirmed by both PCR and Western blot analysis. BLCA-4 overexpressing clones exhibit a 4.3-fold greater proliferation rate than vector only controls or untransfected cells. Microarray analysis comparing gene expression patterns between overexpressing clones and vector only controls revealed that numerous genes were up-regulated in cells that overexpress BLCA-4. Up-regulated genes included interleukin-1alpha (IL-1alpha), IL-8, and thrombomodulin, and the protein expression of these genes was confirmed by immunoblots. This information has provided a potential model of BLCA-4 action. Overexpression of BLCA-4 seems to increase the growth rate in cells and also causes cells to express a more tumorigenic phenotype.
From the Food and Drug Administration. Interferon alfa approved for Kaposi's sarcoma
Authors: S. L. Nightingale
Journal: JAMA (1989)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Mesure du débit veineux azygos (DVA) par écho endoscopie doppler (EUS). Evaluation non invasive de l'hypertension portale (HTP) en pratique quotidienne. Etude prospective monocentrique. Résultats préliminaires
Authors: P Castellani, C Boustiere, P Beaurain, O Bayle, O Le Bars, M Bourliere
Journal: Endoscopy (2007)

Evaluer dans une étude prospective monocentrique, la mesure du DVA par EUS, en pratique quotidienne, pour le dépistage, le suivi et la quantification de l'HTP, chez des patients porteurs d'une hépatopathie chronique.
Can we feed the world?
Authors: Karen McColl
Journal: BMJ (2008)

Olivier De Schutter, the UN's new special rapporteur on the right to food, spoke to Karen McColl about the current food crisis and what should be done about it World leaders met in Rome last week to discuss coordinated international action to tackle the food price crisis currently causing widespread hunger and social unrest. The price of food commodities, such as rice and wheat, on international markets rose sharply in 2006 and 2007. Prices rose even more sharply in the first three months of 2008. In developing countries, where families spend as much as 60-80% of their income on food, such price increases have a dramatic impact.1 Low income countries that import more food than they export are worst affected. The UN Food and Agriculture Organisation described 36 countries in crisis and, of these, 21 are African countries.2 Within countries, the poorest groups, both urban and rural, are hardest hit. The crisis is caused by several factors affecting the balance between the demand for food and the available supply. Poor harvests in Australia, some Asian countries, and parts of Europe have contributed. In addition, grain stocks were very low. There are also, however, important long term structural causes. Although experts broadly agree on the factors involved (many of which are interrelated), there is less agreement on which factors have had the greatest impact. #### Understanding the food price crisis ##### Soaring prices ##### Rising demand
The detection of IgG and IgA autoantibodies to desmocollins 1-3 by enzyme-linked immunosorbent assays using baculovirus-expressed proteins, in atypical pemphigus but not in typical pemphigus
Authors: Y. Hisamatsu, M. Amagai, D.R. Garrod, T. Kanzaki, T. Hashimoto
Journal: British Journal of Dermatology (2004)

We have shown previously that human desmocollin (Dsc) 1 is recognized by IgA autoantibodies of subcorneal pustular dermatosis (SPD) type IgA pemphigus. However, the presence of IgG anti-Dsc autoantibodies is still controversial, and antibodies to Dsc2 and Dsc3 have not been clearly identified.To investigate this by producing recombinant proteins consisting of the entire extracellular domains of human Dsc1, 2 and 3 in baculovirus, and to use them to establish an enzyme-linked immunosorbent assay (ELISA).By this ELISA, we examined in total 165 cases of various types of autoimmune bullous diseases, as well as 23 normal controls.None of 45 sera of classical pemphigus showed either IgG or IgA antibodies to any Dsc. In contrast, one atypical pemphigus serum showed both IgG and IgA antibodies to Dsc1, which were adsorbed by incubation with Dsc1 baculoprotein. Furthermore, this ELISA detected both IgA and IgG anti-Dsc3 antibodies in one atypical case, and IgA antibodies to both Dsc2 and Dsc3 in another. This reactivity was confirmed by positive IgA immunofluorescence with Dsc2 and Dsc3 expressed on COS-7 cells. These results show that both IgG and IgA autoantibodies against all of Dsc1-3 are present in the sera of particular cases of nonclassical pemphigus, except for IgG antibodies to Dsc2, but that they are not detected in classical pemphigus. Unexpectedly, although IgA antibodies of all of eight SPD type IgA pemphigus sera reacted with Dsc1 expressed on COS-7 cells, only one serum was positive in Dsc1 ELISA for IgA.This result indicates either that Dscs expressed by baculovirus may not adopt the correct conformation or that Dscs may need association with other molecules to express all the epitopes for autoantibodies.
More than two million homes are cold enough to cause ill health, Shelter says
Authors: O. Dyer
Journal: BMJ (2002)

Thousands of people living in run down housing are becoming ill because of their accommodation, according to a report by the housing charity Shelter. Shelterline, the charity's telephone advice service, receives more calls about health problems than any other issue except threatened evictions and homelessness itself.

The report found that 14% of households in England live in housing that is unfit, in substantial disrepair, or in need of substantial modernisation. These 2 794 000 households include 750 000 children. …
Abstract 2782: Expression of IGF1R in normal breast tissue and subsequent risk of breast cancer
Authors: Rulla M. Tamimi, Yihong Wang, Laura C. Collins, Rong Hu, Stuart J. Schnitt, Graham A. Colditz, James L. Connolly
Journal: Cancer Research (2010)

Abstract The growth hormone and insulin-like growth factor (IGF) axis plays an essential role in the growth and development of the mammary gland. More recently it has become evident that IGF1 and IGF1 receptor (IGF1R) may play a role in the early transformation of mammary cells. Using a nested case-control design, we examined the association between IGF1R expression in normal breast tissue from benign biopsies and subsequent risk of breast cancer within the Nurses' Health Study. We constructed tissue microarrays (TMAs) containing normal terminal ductal lobular units (TDLUs) from benign breast biopsies. Immunostains for IGF1R were performed on sections cut from the TMAs. A total of 312 women had both normal TDLUs included in the TMAs and evaluable IGF1R staining; 75 subsequently developed breast cancer (cases) and 237 did not (controls). The epithelial cells in the normal TDLUs were scored for both cytoplasmic and membranous staining for IGF1R. Membranous IGF1R expression in normal TDLU epithelial cells was inversely associated with subsequent breast cancer risk (OR= 0.49; 95%CI 0.26-0.93) independent of type of benign breast disease (BBD). In contrast, the presence of cytoplasmic IGF1R expression was positively associated with subsequent risk of breast cancer (OR=2.88, 95% CI 1.60-5.19). Women in which TDLU epithelial cells showed little or no membrane expression of IGF1R but high levels of cytoplasmic IGF1R were at the highest breast cancer risk and were 15 times more likely to develop subsequent breast cancer when compared with women who had little or no membranous or cytoplasmic IGF1R expression in their TDLU epithelium (OR=15.1, 95% CI 3.2-70.2). It has been demonstrated that stimulation of cells with IGF1 results in altered localization of IGF1R expression. Upon stimulation, IGF1R levels on the cell membrane decrease while internalized levels increase. Studies of other receptor tyrosine kinases indicate that chronic stimulation by the ligand results in increased internalization of the receptor. In this study, IGF1R expression patterns in the epithelial cells of normal TDLUs were associated with an increased risk of subsequent breast cancer. The results of this study support the hypothesis that the IGF1 pathway plays an important role in the early development of breast cancer and suggest that there may be opportunities for breast cancer chemoprevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2782.
Dissecting Linkage Disequilibrium in African-American Genomes: Roles of Markers and Individuals
Authors: S. Xu, W. Huang, H. Wang, Y. He, Y. Wang, Y. Wang, J. Qian, M. Xiong, L. Jin
Journal: Molecular Biology and Evolution (2007)

Substantial increases of linkage disequilibrium (LD) both in magnitude and in range have been observed in recently admixed populations such as African-American (AfA). On the other hand, it has also been shown that LD in AfAs was very similar to that of African. In this study, we attempted to resolve these contradicting observations by conducting a systematic examination of the LD structure in AfAs by genotyping a sample of AfA individuals at 24,341 single nucleotide polymorphisms (SNPs) spanning almost the entire chromosome 21, with an average density of 1.5 kb/SNP. The overall LD in AfAs is similar to that in African populations and much less than that in European populations. Even when the ancestry-informative markers (AIMs) were used, extended LD in AfA was found to be limited to certain magnitude range (0.2 ≤ r2 ≤ 0.8) and certain distance range, that is, between-marker distance more than 200 kb. Furthermore, the inclusion of AfA individuals with predominant African ancestry was found to reduce the overall magnitude of LD. Elevation of LD in the AfA population, compared with its parental populations, can only be observed at the markers with large allele frequency differences between 2 parental populations at limited scenario. AfA individuals of wholly African ancestry contribute little to the extended LD in the AfA population, and further genotyping or association analysis conducted using only admixed individuals may lead to higher statistical power and possibly reduced cost.
More on Diagnosis by Mail
Authors: Richard P. Huemer
Journal: JAMA (1965)

To the Editor:—  Robert G. Austin, MD, and Observer ( JAMA  192 :64 [April 5] 1965) infer correctly that my hypothesis explaining the Fact phenomena is not the only possible one; conceivably as many as 1,189 explanations are needed. The single unifying hypothesis is, however, the simplest explanation: entia non sunt multiplicanda praeter necessitatem , and all that.  Observer uses the term mail-order diagnosis imprecisely, and also has difficulty in defining extremism, which is not the issue. The question is whether there exists an absolute standard by which the merit of a man's political convictions can be judged; if so, we can profitably replace the voting public with a panel of suitably-trained experts.