tbuckley/cabot-search huggingface dataset:
A dose-dependent tug of war involving the NPM1 leukaemic mutant, nucleophosmin, and ARF
Authors: N Bolli, M F De Marco, M P Martelli, B Bigerna, A Pucciarini, R Rossi, R Mannucci, N Manes, V Pettirossi, S A Pileri, I Nicoletti, B Falini
Journal: Leukemia (2008)
Geschichte und Ikonographie des endemischen Kropfes und Kretinismus
Authors: Lester S. King
Journal: JAMA (1972)

The remarkable clinical features of thyroid disease, particularly endemic goiter and cretinism, have long attracted the attention of physicians and laymen, and the striking physical appearances have been repeatedly discussed in medical literature, and illustrated in a wide variety of sources. Professor Merke, in a handsome book, provides a detailed historical account of the writings on the thyroid—the works of anatomists, pathologists, and clinicians. While the first sections of the book discuss particularly the more modern findings on goiter and its geographical distribution, most of the remainder surveys in detail the historical aspects, recounting the descriptions and discussions of thyroid disease as given in a very large range of medical writers, from ancient times, through the Middle Ages and Renaissance, up to modern times. There are good bibliographies. Furthermore there are worthwhile chapters on thyroid disorders as evidenced in literature. Of extreme interest and particular value is the presentation of
Long-Standing Filiform, Blaschkoid Papules
Authors: Ellen Koch, Luke Johnson, Robin Gehris
Journal: JAMA Dermatology (2013)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Dermatology journal
Senescence As an Anticancer Mechanism
Authors: Peter J. Hornsby
Journal: Journal of Clinical Oncology (2007)

Senescence was originally described as a terminal nondividing state of normal human cells reached after many cell divisions in culture. The cause was shown to be shortening of telomeres, leading to telomere dysfunction and cell cycle arrest. Subsequently, a more rapid, nontelomere-dependent form of senescence, often termed stress-induced premature senescence, was described. Mostly importantly, it occurs in response to activated oncogene products. Oncogene-induced senescence has been shown to play a role in tumor suppression in vivo; it does not seem to involve changes in telomeres. A second phenomenon that plays a role in tumor suppression, which does involve progressive telomere shortening, is crisis, the state that cells reach when cell cycle checkpoints are impaired and cells can no longer respond to telomere shortening or oncogene activation by entering senescence. These two processes, oncogene-induced senescence and telomere-based crisis, exert powerful anticancer effects.
A structural transition in class II major histocompatibility complex proteins at mildly acidic pH.
Authors: H A Runnels, J C Moore, P E Jensen
Journal: The Journal of Experimental Medicine (1996)

Peptide binding by class II major histocompatibility complex proteins is generally enhanced at low pH in the range of hydrogen ion concentrations found in the endosomal compartments of antigen-presenting cells. We and others have proposed that class II molecules undergo a reversible conformational change at low pH that is associated with enhanced peptide loading. However, no one has previously provided direct evidence for a structural change in class II proteins in the mildly acidic pH conditions in which enhanced peptide binding is observed. In this study, susceptibility to denaturation induced by sodium dodecyl sulfate (SDS) detergent or heat was used to probe the conformation of class II at different hydrogen ion concentrations. Class II molecules became sensitive to denaturation at pH 5.5-6.5 depending on the allele and experimental conditions. The observed structural transition was fully reversible if acidic pH was neutralized before exposure to SDS or heat. Experiments with the environment-sensitive fluorescent probe ANS (8-anilino-1-naphthalene-sulfonic acid) provided further evidence for a reversible structural transition at mildly acidic pH associated with an increase in exposed hydrophobicity in class II molecules. IAd conformation was found to change at a higher pH than IEd, IEk, or IAk, which correlates with the different pH optimal for peptide binding by these molecules. We conclude that pH regulates peptide binding by influencing the structure of class II molecules.
Purified IgE anti-HIV-1 from healthy nonatopic pediatric long term survivors with severely decreased blood CD4+ T cells mediate cytotoxicity against an HIV-1+ cell line and PBMC from HIV-1+ donors, and inhibit HIV-1 production in vitro
Authors: M.H. Bluth, M.G. Pellegrino, D.J. Volsky, H. Moallem, T.A. Smith-Norowitz, M. Nowakowski, H.G. Durkin
Journal: Journal of Allergy and Clinical Immunology (2005)
Effect of Ultrafiltration on Sleep Apnea and Sleep Structure in Patients with End-Stage Renal Disease
Authors: Owen D. Lyons, Christopher T. Chan, Azadeh Yadollahi, T. Douglas Bradley
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: In end-stage renal disease (ESRD), a condition characterized by fluid overload, both obstructive and central sleep apnea (OSA and CSA) are common. This observation suggests that fluid overload is involved in the pathogenesis of OSA and CSA in this condition.Objectives: To test the hypothesis that fluid removal by ultrafiltration (UF) will reduce severity of OSA and CSA in patients with ESRD.Methods: At baseline, on a nondialysis day, patients with ESRD on thrice-weekly hemodialysis underwent overnight polysomnography along with measurement of total body extracellular fluid volume (ECFV), and ECFV of the neck, thorax, and right leg before and after sleep. The following week, on a nondialysis day, subjects with an apnea–hypopnea index (AHI) greater than or equal to 20 had fluid removed by UF, followed by repeat overnight polysomnography with fluid measurements.Measurements and Main Results: Fifteen patients (10 men) with an AHI greater than or equal to 20 (10 OSA; 5 CSA) participated. Mean age was 53.5 ± 10.4 years and mean body mass index was 25.3 ± 4.8 kg/m2. Following removal of 2.17 ± 0.45 L by UF, the AHI decreased by 36% (43.8 ± 20.3 to 28.0 ± 17.7; P < 0.001) without affecting uremia. The reduction in AHI correlated with the reduction in total body ECFV (r = 0.567; P = 0.027) and was associated with reductions in ECFV of the right leg (P = 0.001), overnight change in ECFV of the right leg (P = 0.044), ECFV of the thorax (P = 0.001), and ECFV of the neck (P = 0.003).Conclusions: These findings indicate that fluid overload contributes to the pathogenesis of OSA and CSA in ESRD, and that fluid removal by UF attenuates sleep apnea without altering uremic status.
A Suppressor T Cell of the Mixed Lymphocyte Reaction Specific for the HLA-D Region in Man
Authors: Edgar G. Engleman, Hugh O. McDevitt
Journal: Journal of Clinical Investigation (1978)

The mixed lymphocyte reaction (MLR) is the proliferative response of one individual's lymphocytes cultured in the presence of another individual's lymphocytes. In man, the MLR is elicited by cell surface antigens coded for by the HLA-D gene locus. This locus is among a cluster of genes which are located on the sixth chromosome and which include genes coding for the major histocompatibility antigens HLA-A, B, and C as well as HLA-D. If the stimulator cell possesses D locus antigens not present in the responder, the lymphocytes of the latter will undergo blast transformation resulting in DNA synthesis which can be measured. A vigorous response in the MLR to allogeneic cells is the rule among healthy individuals. We describe studies of a 23-yr-old man whose lymphocytes respond normally to mitogens and soluble antigens but fail to respond to allogeneic cells in the MLR. His medical history is unremarkable except that he received thymic irradiation as an infant. HLA typing revealed that he is homozygous for HLA-A2, B12, and Cw5 as well as for the D locus antigen Dw4. When his lymphocytes were added to the responder lymphocytes of other persons homozygous for the same HLA antigens, their responses to allogeneic cells but not mitogens were suppressed by 50-95%. Their responses to a soluble antigen, tetanus toxoid, were suppressed to a lesser degree. These inhibitory effects were mediated by a relatively radioresistant thymus-derived (T) lymphocyte. Further studies of the requirements for MLR suppression revealed that only persons heterozygous or homozygous for the Dw4 antigen were inhibited by the suppressor T cell. This effect was not altered by differences in the HLA-A, B, or C antigens between the suppressor and responder. It is concluded that genes in or near the HLA-D locus code not only for antigens (primarily on bone marrow-derived (B) cells), that elicit the MLR, but also for structures on T cells, or possibly macrophages, which are recognized by MLR suppressor T cells.
Racial (black-white) comparisons of the relationship of levels of endogenous sex hormones to serum lipoproteins during male adolescence: the Bogalusa Heart Study.
Authors: S R Srinivasan, D S Freedman, G S Sundaram, L S Webber, G S Berenson
Journal: Circulation (1986)

The cross-sectional relationship of endogenous androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate [DHEA-S]), estrogen (estradiol) and progestin (progesterone) to serum levels of lipoprotein cholesterol (very low-density [VLDL], low-density [LDL], and high-density lipoprotein [HDL]) and apolipoproteins (apo A-I and apo B) were studied in white (n = 251) and black (n = 258) adolescent boys, ages 11 to 17 years, as part of the Bogalusa Heart Study. Black boys had significantly higher levels of estradiol, HDL cholesterol, and apo A-I, and lower levels of androstenedione and VLDL cholesterol than white boys, independent of age and adiposity. Age was correlated strongly with testosterone and androstenedione, and moderately with DHEA-S and estradiol levels in both races. However, only in white boys was age consistently related to VLDL cholesterol (positively), HDL cholesterol (negatively), and apo A-I (negatively). Overall, testosterone was associated inversely with HDL cholesterol and apo A-I in white boys, while progesterone was related positively to apo A-I in both races after adjusting for age and adiposity. However, these relationships were found to differ with age. Partial correlations between levels of sex hormones and lipoproteins adjusted for age and adiposity showed no associations in the 11 to 12 year age group in boys of either race. A significant positive relation of testosterone to VLDL cholesterol, and inverse relations of testosterone to HDL cholesterol and apo A-I and DHEA-S to HDL cholesterol were apparent only in white boys in the 13 to 14 year age group.(ABSTRACT TRUNCATED AT 250 WORDS)
Primary care: choice and opportunity
Authors: M. Pringle
Journal: BMJ (1996)

Cruysberg et al is that delay in diagnosis should be prevented as far as possible.Cruysberg and colleagues offer a helpful definition of "myopia plus" (as myopia associated with skeletal, central nervous, or vascular disease) to alert doctors to request appropriate diagnostic investigations.What are the implications of Cruysberg et al's observations for clinical practice and research?Firstly, their work emphasises the importance of undertaking appropriate tests in any patients with onset of severe myopia in childhood.This view is supported by a study of tests on 7500 urine and 4500 blood samples from 9000 selected patients, which resulted in the detection of four patients with homocystinuria.'8The natural course of homocystinuria is that lens dislocation will have occurred in half ofpatients by about 8 years of age whereas half of patients will have reached 29 years before a thromboembolic event occurs.6There is therefore a window of opportunity of about 21 years to intervene to prevent thrombosis if a diagnosis is made at the time of lens dislocation.Secondly, Cruysberg et al's findings suggest the need for research into identifying suitable tests to undertake mass neo- natal screening.Unfortunately, the use of hyper- methioninaemia for this purpose is unreliable,6 19 and perhaps research would be better directed towards tests based on molecular genetic techniques.
Abstract 5076: Integrative genomic and transcriptomic analysis of metaplastic carcinomas of the breast
Authors: Alan G. Mackay, Rachael Natrajan, Christopher Maher, Maryou Lambros, Britta Weigelt, Daniel Nava-Rodrigues, Paul Wilkerson, Adriana CampionFlora, Iwanka Kozarewa, Kerry Fenwick, James Campbell, Lina Chen, Christopher J. Lord, Arnaud Gauthier, Vidya Pawar, Odette Mariani, Anne Vincent-Salomon, Jorge Reis-Filho
Journal: Cancer Research (2012)

Abstract Background Metaplastic breast carcinomas (MBCs) are characterised by neoplastic cells that display differentiation towards squamous epithelium or mesenchymal elements. These tumours are of triple-negative phenotype and have an aggressive clinical behaviour. The aims of this study were to characterise a series of MBCs at the genomic and transcriptomic level to identify potential drivers of this breast cancer special type. Design Twenty-five frozen MBCs and two MBC cell lines (HCC1569 and Hs578T) were subjected to genotyping (Affymetrix SNP6), 32K BAC microarray comparative genomic hybridisation (aCGH), microarray gene expression profiling (Illumina HT12) and massively parallel mRNA-sequencing (RNA-seq, Illumina GAII). Novel chimaeric transcripts were identified using Chimerascan v0.4.3. 10 cases with available germline DNA were subjected to targeted exomic sequencing (Illumina HiSeq). Somatic variants were called using the Genome Analysis Toolkit (GATK) using best practice guidelines. Fusion genes and mutations were validated using (RT)-PCR and Sanger sequencing, respectively. Results MBCs displayed a complex pattern of gene copy number aberrations, with multiple copy number gains and losses throughout the genome. Recurrent amplifications/ high-level gains at 3q25.2-q27.1, 8p11.21-q24.3 and 12p13.33 and recurrent homozygous deletions on 9p21.3 (CDKN2A/2B) and 10q23.31 (PTEN) were found. Unsupervised clustering of gene expression showed that MBCs associated with chondroid differentiation separated into a distinct cluster, whereas MBC's with spindle and epithelial morphology did not cluster apart. Integration of SNP6 copy number and gene expression data identified 198 genes overexpressed when amplified. RNA-seq revealed 1025 unique nominated fusion gene events (43-119 per tumour), including 254 fusions predicted to be in-frame. These included a promoter swap involving TBXLR1 fused to PIK3CA and a recurrent promoter swap involving NF1 that was also seen in the MBC cell line Hs578T. Targeted exome sequencing identified 402 somatic coding variants (12-96 per tumour), including recurrent mutations in TP53 (5/10) and genes involved in PI3K signaling. Conclusion Our results demonstrate that MBCs have complex genomes and are heterogeneous at both the genomic and transcriptomic levels. TP53, CDKN2A/2B and PTEN mutations and/ or homozygous deletions, and activation of the PI3K pathway are recurrent events in these tumours. 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 5076. doi:1538-7445.AM2012-5076
Medicine is war: and other medical metaphors.
Authors: P Hodgkin
Journal: BMJ (1985)

When I worked in a paediatric casualty department children were forever being told that after being stitched, x rayed, or covered in plaster they would be "bionic."The desire to be more machine like is apparently widespread-inevitably perhaps, in an age when technology is both idolised and feared.Medicine is strewn with mechanistic language and concepts, and the metaphor "the body is a machine" suffuses much of the language of pathology and physi-
Laparoscopic Radical Prostatectomy - the Experience of the German Laparoscopic Working Group
Authors: Jens Rassweiler, Jens Stolzenburg, Tullio Sulser, Serdar Deger, Jürgen Zumbé, Georg Hofmockel, Hubert John, Günther Janetschek, Jean-Luc Fehr, Martin Hatzinger, Michael Probst, Karl-Heinz Rothenberger, Vassilis Poulakis, Michael Truss, Gralf Popken, Jens Westphal, Uwe Alles, Paolo Fornara
Journal: European Urology (2005)
Splinter Haemorrhages, Pitting, and Other Findings in Fingernails of Healthy Adults
Authors: J. C. Robertson, M. L. Braune
Journal: BMJ (1974)

Splinter haemorrhages, pitting, transverse grooving, ridging, and flaking occur often in the fingernails of the healthy. While they may occur more often in certain diseases they have little diagnostic value in the absence of proper methods of measurement and examination and without a range of normal values for the sexes and age groups.
New Insights Into Alzheimer's Disease Amyloid Inhibition: Nanosized Metallo‐Supramolecular Complexes Suppress Aβ‐Induced Biosynthesis of Heme and Iron Uptake in PC12 Cells
Authors: Meng Li, Chuanqi Zhao, Taicheng Duan, Jinsong Ren, Xiaogang Qu
Journal: Advanced Healthcare Materials (2013)

Nanosized metallo-supramolecular compounds, [Ni2 L3 ](4+) and [Fe2 L3 ](4+) , can not only strongly inhibit Aβ aggregation but also reduce the peroxidase activity of Aβ-heme. Further studies demonstrate that through blocking the heme-binding site, these two compounds can suppress Aβ-induced biosynthesis of heme and iron uptake in PC12 cells. This work provides new insights into molecular mechanisms of Aβ inhibitors on Aβ-mediated neurotoxicity.
Regulatory T Cell-Derived Interleukin-10 Limits Inflammation at Environmental Interfaces
Authors: Yuri P. Rubtsov, Jeffrey P. Rasmussen, Emil Y. Chi, Jason Fontenot, Luca Castelli, Xin Ye, Piper Treuting, Lisa Siewe, Axel Roers, William R. Henderson, Werner Muller, Alexander Y. Rudensky
Journal: Immunity (2008)
SPONTANEOUS ARTERIAL DEGENERATION IN RABBITS.
Authors: AMY B. MILES
Journal: JAMA (1907)

The effect of the various adrenalin preparations in producing degenerative changes in the vascular system has received much attention during the past few years. The work of Josué in 1903 gave impetus to investigations alone this line, although changes had been noted in the various organs of rabbits used for experimental work as early as 1880, and definite lesions are said to have been produced in the vascular system as early as 1889 by the injection of micro-organisms or their toxins. Since Josué's articles appeared a considerable literature has accumulated on the subject, practically all investigators agreeing, to a greater or less extent, that arterial lesions followed the administration of adrenalin to rabbits. As to whether the ill effects were due to the toxic action of the drug, to the increase of blood pressure occasioned by it, to the cachexia resulting when the drug is given in large doses and
MAST CELL SENSITIZING ANTIBODIES IN EXPERIMENTAL MYOSITIS
Authors: JEANNA SCHWARTZ, ANDRE EYQUEM, ANDRE SOBEL
Journal: Allergy (1976)

Mast cell sensitizing antibodies, direct mast cell degranulation and positive delayed skin tests were detected in guinea pigs and rats during experimental paralysis provoked by inoculation with acetylcholine receptors from the Electrophorus electricus. The animals also developed fluorescent antibodies to the sarcolemma, and massive myositis with histological changes in muscles similar to those characterizing clinical polymyositis.
Comparative effects of pacing-induced and flow-limited ischemia on left ventricular function.
Authors: R J Applegate, R A Walsh, R A O'Rourke
Journal: Circulation (1990)

We compared left ventricular (LV) myocardial blood flow and function accompanying severe demand ischemia (rapid atrial pacing in the presence of critical bilateral coronary stenoses) and supply ischemia (complete bilateral coronary occlusion) of the same ischemic regions in 14 pentobarbital-anesthetized dogs. Pacing-induced ischemia resulted in pronounced reductions in average regional epicardial blood flow (0.8 +/- 0.4 vs. control 1.2 +/- 0.4 [+/- SD] ml/g/min, p less than 0.05) and endocardial blood flow (0.4 +/- 0.1 vs. control 1.3 +/- 0.3 ml/g/min, p less than 0.05). More severe reductions in average regional epicardial and endocardial blood flow were seen after bilateral coronary occlusion (BCO) (0.3 +/- 0.3 and 0.1 +/- 0.1 vs. control 1.3 +/- 0.3 ml/g/min, p less than 0.05, respectively). Hemodynamics of postpacing ischemia (PPi) were consistently characterized by systolic impairment including depressed systolic contractile performance [(+)dP/dtmax 1,281 +/- 442 vs. control 2,173 +/- 775 mm Hg/sec, p less than 0.05], ventricular dilation (left ventricular [LV] end-diastolic dimension [EDD] 47.6 +/- 7.8 vs. control 44.7 +/- 8.6 mm, p less than 0.05), and an increase in LV end-diastolic pressure (EDP) (14.4 +/- 2.8 vs. control 4.2 +/- 2.8 mm Hg, p less than 0.05). Abnormalities in early and late diastolic function with PPi included increased time constant of isovolumic relaxation (78.0 +/- 40.4 vs. control 46.4 +/- 20.5 msec, p less than 0.05) and increased chamber stiffness (1.9 +/- 0.77 vs. control 0.81 +/- 0.55 mm Hg/mm, p less than 0.05), respectively. The LV diastolic pressure-dimension relation, however, shifted upward and to the right in eight of nine animals, whereas an upward shift was observed in only one animal. Thus, in this model of postpacing ischemia, we observed contractile failure and passive changes in diastolic function. Alterations in ventricular function occurred consistently earlier and to a greater extent during BCO than PPi, including higher LVEDP (25.3 +/- 8.1 vs. 14.9 +/- 6.6 mm Hg, p less than 0.05), greater ventricular dilation (delta LVEDD 4.9 +/- 2.5 vs. 3.5 +/- 2.8 mm, p less than 0.05), and reduced minor-axis dimension shortening (3.3 +/- 3.1% vs. 6.5 +/- 3.6%, p less than 0.05). To detect potential qualitative differences in ventricular function between the two types of ischemia, we evaluated hemodynamics at comparable loading conditions (30 seconds to 1 minute of BCO).(ABSTRACT TRUNCATED AT 400 WORDS)