tbuckley/cabot-search huggingface dataset:
Immunoglobulin G deposition to nonhemidesmosomal lamina lucida and early neutrophil involvement are characteristic features in a case of anti-p200 pemphigoid
Authors: A. Shimizu, T. Funakoshi, M. Ishibashi, T. Yoshida, H. Koga, T. Hashimoto, M. Amagai, A. Ishiko
Journal: British Journal of Dermatology (2012)

The ultrastructural characteristics and immunolocalization of in vivo bound immunoglobulin G (IgG) in skin affected by anti-p200 pemphigoid have not been elucidated. To give insight into the mechanism of blister formation we report a new case of anti-p200 pemphigoid, studied with stage-oriented morphological analysis and immunoelectron microscopy. Skin biopsy specimens were evaluated ultrastructurally and histologically with immunohistochemistry. By observing the nonblister site, the blister edge and centre of the blister, we determined that neutrophil infiltration increases gradually at the dermoepidermal junction in association with the destruction of type IV collagen. Ultrastructurally, many neutrophils were observed under the lamina densa, with vacuole formation in the dermis. At the periphery of the blister, the lamina densa became fragmented and was observed either at the roof or the floor of the blister. At the centre of the blister, the lamina densa was mainly observed at the blister floor. Postembedding immunoelectron microscopy demonstrated that the IgG, bound in vivo, localized at the lamina lucida, while the area beneath the hemidesmosomes was spared. Together with the early involvement of neutrophils and the destruction of the basal lamina, we suggest that the binding of autoantibodies to the nonhemidesmosomal lamina lucida may induce inflammation with neutrophils, resulting in blister formation.
CYP2C8 pharmacogenetics and functional characterization of promoter polymorphic variants in Asian population
Authors: Viknesvaran Selvarajan, Balram Chowbay
Journal: Clinical Cancer Research (2007)

A59   The objective of the present study was (1) to determine polymorphic variations in the  CYP2C8  gene in three distinct healthy Asian subjects (Chinese: N=101, Malay: N=91 and Indian: N=90, populations), and (2) to functionally characterize high frequency  CYP2C8  promoter polymorphisms. Screening for genetic variations in the promoter, exons and exon-intron junctions of  CYP2C8  gene was performed by PCR followed by direct DNA sequencing. Seven polymorphisms were identified and their allelic frequencies were as follows: 5’-UTR:  g.-411C>T  (C:0.33;T:0.67) , g.-370T>G  (T:0.72;G:0.28)  and g.-271C>A  (C:0.88;A:0.12) ;  intron 2:  I.-64A>G  (A:0.50;G:0.50),  -13insT  (Wt:0.87;insT:0.13); intron 7:  +49T>A  (T:0.47;A:0.53) and 3’-UTR:  24C>T  (C:0.62;T:0.38). Haplotype analysis revealed fourteen different haplotypes in Chinese, eighteen in Malays, and twenty one in the Indian population. Two haplotype blocks were inferred in each ethnic group based on the solid-spline algorithm. The functional influence of  CYP2C8  promoter polymorphisms were studied by using various combinations of plasmid constructs containing the three polymorphic variants. The different constructs were cloned in pGL3 expression vector and investigated for their activity in driving reporter gene expression in transfected HepG2 cells under optimized conditions. The promoter construct harboring the single  g.-411C>T  variant showed approximately 2-fold higher luciferase activity compared with the reference construct ( P =0.002). The construct harboring the combined  g.-411C>T  and  g.-271C>A  polymorphic variants showed a severe reduction (44-fold) in luciferase activity compared with the construct containing the reference sequence ( P =0.006). Further studies to establish the mechanistic basis for the altered promoter activity due to the promoter polymorphic variants are ongoing.
Researchers discover subclinical form of BSE
Authors: Roger Dobson
Journal: BMJ (2000)

Researchers have found new evidence for the existence of a subclinical form of bovine spongiform encephalopathy (BSE). Cattle, sheep, and other animals that are outwardly healthy may be harbouring the infection, with the risk that BSE could still be getting into the food chain.

In a new study based on a mouse model, researchers at the Medical Research Council Prion Unit took a closer look at the species barrier, which limits the ability of prions to jump from one species to another ( Proceedings of the National Academy of …
Screening for Chronic Kidney Disease
Authors: Milda R. Saunders, Adam Cifu, Monica Vela
Journal: JAMA (2015)

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
Abstract 2616: Facilitation of Triggered Firing in Superfused Canine Pulmonary Veins by Activating Antibodies to Beta Adrenergic and Muscarinic Receptors in Serum From Patients With Graves' Disease
Authors: Stavros Stavrakis, Xichun Yu, Shijun Huang, Madeleine W Cunningham, David C Kem, Eugene Patterson
Journal: Circulation (2009)

Background: Increased titers of antibodies activating beta-adrenergic and muscarinic-2 (M-2) receptors (ELISA assays) are present in the serum and purified immunoglobulins (IgG) of patients with Gr...
Role of the family in recovery and major depression
Authors: G I Keitner, C E Ryan, I W Miller, R Kohn, D S Bishop, N B Epstein
Journal: American Journal of Psychiatry (1995)

Major depression is significantly influenced by the family environment of the depressed patient. In order to explore how family functioning relates to this illness, the authors examined changes in family functioning over a 1-year course of major depression. Subjective (Family Assessment Device) and objective (McMaster Clinical Rating Scale) assessments of family functioning were collected at hospitalization and 6 and 12 months after discharge for 45 inpatients diagnosed with major depression and their family members. Patterns of family functioning were examined by subjective and objective perspectives, initial levels of functioning, and reports of patients and other family members. Approximately 50% of families with a depressed member perceived their own family functioning as unhealthy; clinicians rated 70% of the families as unhealthy. While family functioning improved significantly from hospitalization through 12 months after discharge, the improvement was not uniform across all areas of functioning. Further, patients with good family functioning at hospitalization generally maintained their healthy functioning and were more likely to recover by 12 months than patients with poor family functioning. Although steady improvement in family functioning characterized the subjective ratings, objective assessments of family functioning suggested initial improvement followed by a decline from month 6 to month 12. Results show a clear association between family functioning and recovery from major depression. Different aspects of family life respond differently to the depressive illness; no one family dimension was uniquely related to outcome.
Posttraumatic stress disorder after a school shooting: effects of symptom threshold selection and diagnosis by DSM-III, DSM-III-R, or proposed DSM-IV
Authors: E D Schwarz, J M Kowalski
Journal: American Journal of Psychiatry (1991)

The purpose of the study was to investigate the effect of symptom threshold and criteria set selections on the diagnosis of posttraumatic stress disorder (PTSD) in adults and children exposed to a man-made disaster and determine how well DSM-III and its successors agree.Data gathered in the course of a voluntary clinical screening for PTSD in 66 adults and 64 children 6 to 14 months after exposure to a school shooting were analyzed according to DSM-III, DSM-III-R, and proposed DSM-IV criteria for PTSD diagnosis and cluster endorsement using liberal (occurring at least a little of the time), moderate (occurring at least some of the time), and conservative (occurring at least much or most of the time) symptom thresholds.Within DSM-III, DSM-III-R, and proposed DSM-IV, selection of liberal, moderate, and conservative symptom thresholds had robust effects on rates of diagnoses; liberal thresholds allowed the greatest frequencies of diagnosis. Compared with DSM-III and proposed DSM-IV, DSM-III-R generally diagnosed the fewest cases. Agreements between DSM-III-R and proposed DSM-IV were good, while agreements between DSM-III and its successors varied for children and adults.Diagnostic rates and agreements were complexly influenced by interactions among threshold and revisions in symptom clusters. The present study suggests that attempts to refine PTSD classification consider specification of symptom threshold intensity and supports the view that modification of criteria sets be undertaken with caution.
Regulation of human MAPT gene expression
Authors: Marie-Laure Caillet-Boudin, Luc Buée, Nicolas Sergeant, Bruno Lefebvre
Journal: Molecular Neurodegeneration (2015)

The number of known pathologies involving deregulated Tau expression/metabolism is increasing. Indeed, in addition to tauopathies, which comprise approximately 30 diseases characterized by neuronal aggregation of hyperphosphorylated Tau in brain neurons, this protein has also been associated with various other pathologies such as cancer, inclusion body myositis, and microdeletion/microduplication syndromes, suggesting its possible function in peripheral tissues. In addition to Tau aggregation, Tau deregulation can occur at the expression and/or splicing levels, as has been clearly demonstrated in some of these pathologies. Here, we aim to review current knowledge regarding the regulation of human MAPT gene expression at the DNA and RNA levels to provide a better understanding of its possible deregulation. Several aspects, including repeated motifs, CpG island/methylation, and haplotypes at the DNA level, as well as the key regions involved in mRNA expression and stability and the splicing patterns of different mRNA isoforms at the RNA level, will be discussed.
Ethics of randomized clinical trials.
Authors: E J Emanuel, W B Patterson
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.1.365 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9440766 Ethics of randomized clinical trials. E J EmanuelxE J EmanuelSearch for articles by this author , W B PattersonxW B PattersonSearch for articles by this author Show More Dana-Farber Cancer Institute, Boston, MA 02115-6084, USA. [email protected] https://doi.org/10.1200/JCO.1998.16.1.365 First Page PDF © 1998 by American Society of Clinical OncologyKeywords: Biomedical and Behavioral ResearchProfessional Patient Relationship... Show All
Amplification of total RNA from minute amounts of RNA of the thyroid gland for validation of molecular classifiers
Authors: Ana Pagotto, Luiz Reis, Luiz Kowalski, Beatriz Stolf, Alex Carvalho, Eduardo Neves, Miriam Brites
Journal: Clinical Cancer Research (2008)

A28   Fine-needle aspiration biopsy (FNAB) is the gold standard for preoperative diagnostic test of malignant thyroid nodules. However, this procedure is not capable of discriminating between adenomas and follicular carcinomas. Suspicious nodules are usually removed surgically and it requires inspection of the entire capsule in order to differentiate a follicular carcinoma from an adenoma. A precise and reliable method for distinguishing between benign and malignant thyroid nodules prior to surgery may help to reduce the number and extent of thyroidectomies. Data from gene expression analysis of postsurgical samples of adenoma and follicular carcinoma obtained by cDNA microarrays assays were submitted to Fisher linear discriminant analysis and expression signatures of individual samples of adenomas and follicular carcinomas were used to identify molecular classifiers that precisely distinguish between malignant and nonmalignant lesions. Fourteen trios of genes were able to perform the correct classification of samples. The robustness of these trios was verified by using leave-1-out cross-validation and bootstrap analyses. In order to validate this test using an independent set of samples we are current applying two strategies. First, we used FNAB of nodules after surgical removal of the gland (58 samples), in order to establish a reliable RNA amplification protocol starting from minute amounts of RNA. Second, we used material derived FNAB from patients with suspicious lesions (20 samples) representing normal thyroid, adenomas, papillary carcinomas, and follicular carcinomas. The latter procedure was approved by our Institutional Review Board and no extra manipulation of the patient was necessary. Needles that were used in diagnostic FNAB were washed with guanidinum thiocyanate-phenol solution before being discarded and these washings were used for RNA extraction. Considering the variability in cellularity from these samples, it was necessary to adapt our protocol for RNA extraction. Total RNA was extracted from all types of samples, including those with low cellularity. Samples were submitted to one round of amplification, according to a protocol previously published by our group (Gomes et al, 2003), starting from as little as 20ng of total RNA. Amplification efficiency ranged from 258 to 300 fold. A second round of amplification will be done and results of validation using these independent samples will be presented.
A Study of Medical Problems Associated with Transients
Authors: Charles Fred Blankenship
Journal: JAMA (1941)

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
A view from Washington through the eyes of an AAP physician-scientist
Authors: Anthony S. Fauci
Journal: Journal of Clinical Investigation (2007)

Thank you very much, John [Gallin], for your kind comments. It is at the same time a great honor and a humbling experience to be recognized by one’s peers. It serves to remind me that I did not get here in a vacuum; I was helped along the way by many talented and generous people and organizations. Due to time constraints, I cannot name them all but some deserve special mention. From the earliest days of my memory my parents ensured an environment of love and warmth and planted the seed in my mind and heart of the attractiveness and substance of a life of public service. I am forever in their debt.
Commentary: Patient's view
Authors: Kenneth Neville, Mark Fox
Journal: BMJ (2006)

As a child I remember eating well and enjoying my food, although I did get heartburn now and again. That all changed in 2001 when I started to bring up what I ate. At first this was occasional, but then my stomach settled into a new routine. On eating even small amounts I felt unpleasantly full, then I had to belch and the food came back to my mouth. I usually spat this out, but sometimes I swallowed it again. If I tried to eat larger amounts my stomach hurt and I had to vomit everything up. …
Physiology, pathology and pharmacology of the male reproductive system
Authors: Michael Mawhinney, Angelo Mariotti
Journal: Periodontology 2000 (2012)

Abstract The male reproductive system consists of the testes, a ductal system and sex accessory organs. Production of sperm by the testes combined with fluids formed by the sex accessory organs (e.g. seminal vesicles, prostate and bulbourethral glands) produce a secretion that supports the survival of spermatozoa and provides a medium through which they can move through the reproductive ducts (e.g. epididymis, vas deferens, ejaculatory duct and urethra) for ejaculation of viable sperm into the female reproductive tract. Summarized herein are the essentials of normal male reproductive physiology, disorders of male sexual differentiation, pharmacological therapy of common diseases of the male genitourinary tract and the impact of drugs of abuse on the male reproductive system.
Tuberous Sclerosis Associated with Spontaneous Hypoglycaemia
Authors: A. Gutman, M. Leffkowitz
Journal: BMJ (1959)

Case 2.-A patient aged 34 was suffering from severe pain in the right side of the thorax, which radiated into the right hypochondrium.X-ray examination revealed no pulmonary lesion, but the right dome of the diaphragm was raised and moved imperceptibly with respiration.A diagnosis of sub- diaphragmatic disease, most probably amoebic hepatitis, was made, and examination of the stools revealed the presence of E. histolytica.After five days' treatment with 400 mg. of furazolidone per 24 hours the chest pain disappeared and the diaphragm was moving almost normally.After a further five days' treatment the patient was very much improved, and no amoebae could be found on repeated examination of the stools.The curative value of furazolidone in this case is certainly not established, and investigations are still in progress. DiscussionOf a total of 58 patients suffering from diarrhoea due to various causes, 54 were restored to normal within a week of being treated.There is no doubt that some
947. RNAi-Mediated Bcl-XL Depletion Sensitizes Pancreatic Cancer Cells to TNFα Induced Apoptosis
Authors: Jirong Bai, Mark P. Callery
Journal: Molecular Therapy (2004)

Pancreatic cancer is lethal because it is invasive, rapidly progressive and profoundly resistant to chemotherapy and radiation therapy. Abnormal NF-κB signaling protects tumor cells from chemical induced apoptosis through the engagement of tumor necrosis factor family receptors. In this study, we demonstrate that pancreatic cancer cell lines Panc-1 and Mia PaCa-2 simultaneously express high levels of TNF-R1, TRAIL-R2 and Fas but are strongly resistant to apoptosis triggered by relevant ligands. These cell lines express multiple anti-apoptotic protein factors Bcl-XL, cIAP-1 and Survivin but not cIAP-2 and Fap-1. To determine whether a precise silencing of a specific NF-κB dependent anti-apoptotic factor could sensitize pancreatic cancer cells to ligand induced apoptosis, we have developed a self-inactivating retroviral-based RNAi expression vector (SINeG-XRi) for the genetic inactivation of Bcl-XL. SINeG-XRi transduction completely suppressed Bcl-XL expression in both cell lines. However, Bcl-XL depletion did not indefinitely disable this anti-apoptotic mechanism since Bcl-XL expression was reconstituted over time due to TNFα mediated NF-κB activation. When 26S proteasome inhibition (10nM PS-341) blocked NF-κB activation, TNFα drove apoptosis in SINeG-XRi transduced pancreatic cancer cells in a dose-dependent manner. TRAIL-R2 and Fas mediated killing was not enhanced, however, suggesting diverse anti-apoptotic mechanisms linked to these death receptors. Caspase assays demonstrated that Bcl-XL blocked both intrinsic and extrinsic apoptotic pathways. Our results indicates that Bcl-XL plays an important role in chemoresistance in pancreatic cancer and RNAi mediated Bcl-XL depletion provides a novel gene therapy strategy to defeat chemoresistance.
Abstract 10348: Discovery of Novel Mechanosensitive mRNA and miRNA in Vivo Using Mouse Carotid Artery Endothelium Exposed to Disturbed Flow
Authors: Chih-Wen Ni, Haiwei Qiu, Amir Rezvan, Kihwan Kwon, Douglas Nam, Dong Ju Son, Hanjoong Jo
Journal: Circulation (2010)

Recently, we showed that disturbed flow caused by a partial ligation of mouse carotid artery rapidly induces atherosclerosis, demonstrating direct causal link between flow and atherosclerosis. The mechanisms, however, by which disturbed flow induces atherosclerosis is still unclear. Here, we identified mechanosensitive genes, both mRNAs and miRNAs, in vivo, through a genome-wide microarray study using mouse endothelial RNAs directly isolated from the flow-disturbed left and the undisturbed right common carotid artery (LCA and RCA). We found 62 and 523 mRNAs that changed significantly by 12hr and 48hr post-ligation. The results were validated by qPCR for 44 of 46 tested mRNAs. This array study discovered numerous novel mechanosensitive genes including Lmo4, klk10 and dhh, while confirming well-known ones such as Klf2, eNOS, and BMP4. Comparison of in vivo, ex vivo, and in vitro endothelial mRNA expression profiles indicates that numerous in vivo mechanosensitive mRNAs appear to be lost or dysregulated duri...
The politics of risk: the case of BSE
Authors: R. Klein
Journal: BMJ (2000)

News p 1097 

There are two ways of reading the Phillips report1 on how an epidemic affecting cattle became a major public health hazard, all the more threatening because of uncertainty about how many more lives may be claimed by it. The first is to see the policies adopted from 1988, when bovine spongiform encephalopathy (BSE) was first identified in cattle, to 1996, when the link with variant Creutzfeldt-Jacob disease (vCJD) in humans was officially acknowledged, as a qualified success story for British government. The second is to see the report as an indictment of the policy process: to interpret the evidence as demonstrating a failure by government to react with sufficient urgency to a tragedy in the making.

The Phillips report provides sustenance for both views. On the one hand, it concludes, “Because the right policy decisions were taken, BSE is today within reach of eradication and millions have received a high degree of protection from the risk of ingestion of potentially infective products or by-products of the cow.” On the other hand, it documents failures …