tbuckley/cabot-search huggingface dataset:
Crucial roles of mixed‐lineage leukemia 3 and 4 as epigenetic switches of the hepatic circadian clock controlling bile acid homeostasis in mice
Authors: Dae‐Hwan Kim, Jennifer Chiyeon Rhee, Sujeong Yeo, Rongkun Shen, Soo‐Kyung Lee, Jae W. Lee, Seunghee Lee
Journal: Hepatology (2014)

The histone H3-lysine-4 methyltransferase mixed-lineage leukemia 3 (MLL3) and its closest homolog, MLL4 (aka KMT2D), belong to two homologous transcriptional coactivator complexes, named MLL3 and MLL4 complexes, respectively. MLL3 plays crucial roles in multiple metabolic processes. However, the physiological roles of MLL4 in metabolism and the relationship between MLL3 and MLL4 in metabolic gene regulation are unclear. To address these issues, we analyzed the phenotypes of newly generated MLL4 mutant mice, along with MLL3 mutant and MLL3;MLL4 compound mutant mice. We also performed comparative genome-wide transcriptome analyses in livers of MLL3, MLL4, and MLL3;MLL4 mutant mice. These analyses revealed that MLL3 and MLL4 complexes are key epigenetic regulators of common metabolic processes and the hepatic circadian clock. Subsequent mechanistic analyses uncovered that MLL3/4 complexes function as pivotal coactivators of the circadian transcription factors (TFs), retinoid-related orphan receptor (ROR)-α and -γ, in the hepatic circadian clock. Consistent with disturbed hepatic clock gene expression in MLL4 mutant mice, we found that rhythmic fluctuation of hepatic and serum bile acid (BA) levels over the circadian cycle is abolished in MLL4 mutant mice. Our analyses also demonstrate that MLL4 primarily impinges on hepatic BA production among several regulatory pathways to control BA homeostasis. Together, our results provide strong in vivo support for important roles of both MLL3 and MLL4 in similar metabolic pathways.Both MLL3 and MLL4 complexes act as major epigenetic regulators of diverse metabolic processes (including circadian control of bile acid homeostasis) and as critical transcriptional coactivators of the circadian TFs, RORs.
Molecular Imaging with Bioluminescence and PET Reveals Viral Oncolysis Kinetics and Tumor Viability
Authors: Darshini Kuruppu, Anna-Liisa Brownell, Khalid Shah, Umar Mahmood, Kenneth K. Tanabe
Journal: Cancer Research (2014)

Viral oncolysis, the destruction of cancer cells by replicating virus, is an experimental cancer therapy that continues to be explored. The treatment paradigm for this therapy involves successive waves of lytic replication in cancer cells. At present, monitoring viral titer at sites of replication requires biopsy. However, repeat serial biopsies are not practically feasible for temporal monitoring of viral replication and tumor response in patients. Molecular imaging provides a noninvasive method to identify intracellular viral gene expression in real time. We imaged viral oncolysis and tumor response to oncolysis sequentially with bioluminescence and positron emission tomography (PET), revealing the kinetics of both processes in tumor xenografts. We demonstrate that virus replication cycles can be identified as successive waves of reporter expression that occur ∼2 days after the initial viral tumor infection peak. These waves correspond to virions that are released following a replication cycle. The viral and cellular kinetics were imaged with Fluc and Rluc bioluminescence reporters plus two 18F-labeled PET reporters FHBG [9-(4-18F-fluoro-3-[hydroxymethyl] butyl) guanine] and FLT (18F-3'-deoxy-3-'fluorothymidine), respectively. Correlative immunohistochemistry on tumor xenograft sections confirmed in vivo results. Our findings show how PET can be used to identify virus replication cycles and for real-time measurements of intratumoral replicating virus levels. This noninvasive imaging approach has potential utility for monitoring viral oncolysis therapy in patients.
Structural Analysis Reveals Molecular Basis for Interactions of Group 1 Allergens with Species Specific and Cross-Reactive Antibodies
Authors: Maksymilian Chruszcz, Anna Pomes, Tomasz Osinski, Karolina A. Majorek, Jill Glesner, Wladek Minor, Lisa D. Vailes, Martin D. Chapman
Journal: Journal of Allergy and Clinical Immunology (2013)

In order to analyze the antigenic surface of Group 1 allergens we determined structures of complexes of Der f 1 or Der p 1 with monoclonal antibodies. Structures of these complexes provide detailed information about the molecular basis of murine IgG antibodies species specificity and cross-reactivity. This type of analysis may be used to localize IgE epitopes on Group 1 allergens. X-ray diffraction analysis was used to investigate the molecular structures of Der f 1:4C1, Der p 1:4C1, Der p 1:10B9 and Der p 1:5H8 complexes. Structural data revealed that the 4C1 epitope is common to both Der f 1 and Der p 1, and in both allergens the epitope is formed by the same amino acids. The structure of the Der p 1:10B9 complex shows that the epitopes for 4C1 and 10B9 partially overlap. The monoclonal antibody 5H8 binds to a different fragment of Der p 1 and the binding site for this antibody does not overlap with the 10B9 and 4C1 epitopes. Structural analysis of Group 1 allergens in complexes with different antibodies not only revealed the specific amino acid residues involved in cross-reactivity, but also explained why antibodies 10B9 and 5H8 are species specific. Results of the structural studies will be used for the design of experiments allowing for the identification of IgE binding epitopes.
EXPERIMENTAL PRODUCTION OF GROSS ATHEROSCLEROSIS IN THE RAT
Authors: Louis C. Fillios, Stephen B. Andrus, George V. Mann, Frederick J. Stare
Journal: The Journal of Experimental Medicine (1956)

Gross atherosclerosis was produced in the rat by feeding purified diets containing cholesterol, sodium cholate, and thiouracil for periods up to 363 days. In a few weeks a marked increase of the serum cholesterol and beta lipoproteins as well as of the liver lipides was observed. Lesions visible in the gross were found on the intimal surfaces of the vessels of all 46 animals examined. These were most prominent in the heart valves and aortic arch. The earliest lesions, which were seen at 31 days, required Sudan staining for gross demonstration. Older lesions were visible without staining. Microscopic coronary artery lesions were present and in one instance were accompanied by massive myocardial infarction. Vascular lesions were characterized by medial and intimal lipide infiltration and cellular intimal plaque formation. In a part of this study the protein level of the diet was altered at the expense of sucrose. The hypercholesteremic response among the rats varied according to the dietary protein level. The lowest response was observed among those animals receiving the highest level of dietary protein. A difference, however, in the severity and extent of the arterial lesions among these relatively small groups of rats could not be established under these experimental conditions. In all these experiments a close correlation existed between the serum cholesterol levels and beta lipoproteins of the S(f)20-100 range.
A sebotrophic stimulus in benign and malignant breast tumours
Authors: S.K. Goolamali, S. Shuster
Journal: British Journal of Dermatology (1974)

Journal Article A sebotrophic stimulus in benign and malignant breast tumours Get access S.K. Goolamali, S.K. Goolamali Wellcome Laboratories for Research into Skin Disease, University Department of Dermatology, Royal Victoria Infirmary, Newcastle‐upon‐Tyne Search for other works by this author on: Oxford Academic Google Scholar S. Shuster S. Shuster Wellcome Laboratories for Research into Skin Disease, University Department of Dermatology, Royal Victoria Infirmary, Newcastle‐upon‐Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue s10, 1 July 1974, Pages 21–22, https://doi.org/10.1111/j.1365-2133.1974.tb12485.x Published: 01 July 1974
SICKNESS AND MORTALITY IN THE ARMY OF THE UNITED STATES.Read in the Section of State Medicine, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May, 1891.
Authors: JOS. R. SMITH
Journal: JAMA (1891)

All statistics telling the amount of disease and death in any considerable portion of the community, and showing the variations in said amount from year to year, seem properly to belong to State Medicine. As there is no Section of military medicine and surgery in the American Medical Association, I deem it proper to present to the Section on State Medicine the following paper, in which I have collated and compared figures showing the absolute and relative amount of disease, death, and non-effectiveness in the Army of the United States. While these statistics have been collected under conditions of considerable uniformity from year to year, yet it is to be remarked, that they have been collected by a large number of observers, all of them medical officers of education and intelligence, yet each differing from the other in powers of observation, and in mental characteristics or peculiarities. To some, this
Confounding and effect modification in studies of diet and childhood asthma and allergies
Authors: U. Nurmatov, B. I. Nwaru, G. Devereux, A. Sheikh
Journal: Allergy (2012)

Abstract Objective To propose a comprehensive set of confounders and effect modifiers that should be considered in epidemiologic investigations. Methods Two reviewers independently critiqued studies included in a recent systematic review and extracted data on the confounders and effect modifiers that were considered and the approaches used to justify inclusion. Results Of the 62 studies reviewed, 20 were cohort, 16 case–control, 25 cross‐sectional studies, and one ecologic study. All cohort, cross‐sectional, and ecologic studies had some adjustment for confounding or consideration of effect modification, but this was only the case for 7/16 (44%) case–control studies. Of the 53 studies that considered confounding or effect modification, 39/53 (74%) gave no justification for the inclusion of the variables considered. Studies that justified the inclusion of the variables did so based on empirical evidence ( n = 10), conceptual justification ( n = 7), or a combination of the two ( n = 3). Confounding was handled mainly by using regression modeling, but some case–control studies utilized matching and anova . Ten studies handled effect modification by stratification, eight tested for interaction, and five used both strategies. Conclusions We have found substantial shortcomings in the handling of confounding and effect modification in studies of diet and development of childhood asthma/allergies. Selection of variables should be based on conceptual considerations and empirical evidence. Using this approach, we have proposed a comprehensive set of confounders and effect modifiers that need to be considered in future studies.
Population approach is needed for heart disease prevention to reach more people
Authors: L. Hitchen
Journal: BMJ (2008)

The current approach to preventing cardiovascular disease of focusing on individuals at high risk does “too little, too late for too few,” said experts at a conference in London this week. Instead, they suggest, a population approach aimed at changing lifestyle and treatment strategies is needed to prevent early onset of disease.

Nurses and high school graduates, not doctors, could be trained in this preventive work, Salim Yusuf, director of population health research at McMaster University in Ontario, Canada, told the conference on coronary heart disease in south Asians, which was organised by the South Asian Health Foundation and held …
Drug Disposition in Liver Disease
Authors: David G. Shand
Journal: New England Journal of Medicine (1977)

Several studies, including that by Piafsky and his colleagues on theophylline in the current issue of the Journal, have demonstrated that drug disposition can be altered in patients with liver disease.1 Many of the reported changes can be rationalized in terms of the pathophysiology of disease and the known physiologic determinants of hepatic drug clearance.2 The basic biochemical process involved may be defective as a result of acute or chronic injury. This defect can be quantified as the intrinsic clearance, which may be defined as the volume of liver water cleared of drug in unit time. In addition, plasma . . .
Amelioration of Angina Pectoris in Idiopathic Hypertrophic Subaortic Stenosis with Beta-Adrenergic Blockade
Authors: LAWRENCE S. COHEN, EUGENE BRAUNWALD
Journal: Circulation (1967)

Beta-adrenergic receptor blockade has been demonstrated to reduce obstruction of the left ventricular outflow tract in patients with idiopathic hypertrophic subaortic stenosis (IHSS) and has also proved helpful in reducing angina pectoris due to ischemic heart disease. Accordingly, the effects of oral propranolol on the level and duration of exercise required to produce angina in seven patients with IHSS were compared with a placebo. Improvement in exercise performance was observed in six patients taking propranolol orally in doses ranging from 80 mg to 480 mg daily. Clinical improvement was sustained in the four patients given propranolol since discharge from the hospital for periods up to 15 months, and in three it has been possible to obviate corrective operations. The mechanism by which propranolol is efficacious in this disease is probably related to the diminution of myocardial O 2 requirements resulting from the reduction of wall tension, velocity of contraction, and heart rate induced by beta-adrenergic receptor blockade.
NEWER AIDS TO DIAGNOSIS IN DISEASES OF THE URINARY TRACT.
Authors: M. L. HARRIS
Journal: JAMA (1905)

The urinary tract may be subdivided into four parts, namely, the kidneys or secreting part, the ureters or conducting part, the bladder or receptacle, and the urethra with its accessories in the male. Each of these parts may be the subject of pathologic changes and at times it may be very difficult or even impossible from the symptoms alone to determine to which part or parts the disease is confined. The mere presence of pus or of blood in the urine affords no evidence as to its origin, and when the symptoms do not indicate the origin some means must be employed which will enable one to investigate each portion of the urinary tract separately. A number of ingenious devices have been invented recently by the use of which one is enabled to obtain information of the greatest importance concerning the condition of the various portions of the urinary tract.
Diffuse panbronchiolitis as a pulmonary complication in patients with adult T‐cell leukemia
Authors: Kazutoshi Ono, Yoshinori Shimamoto, Miwako Matsuzaki, Masayuki Sano, Tsuneko Yamaguchi, Osamu Kato, Hozumi Yamada, Masaya Yamaguchi
Journal: American Journal of Hematology (1989)

Abstract Forty‐three cases of adult T‐cell leukemia (ATL) admitted to our hospital between 1982 and 1987 were studied. Three of those were found to be complicated with diffuse panbronchiolitis (DPB). The incidence of DPB is considered to be significantly higher in patients with ATL. The three DPB‐complicated cases composed one case each of the smoldering, chronic, and acute type of ATL. In each type, DPB preceded overt ATL and Candida afbicans was found in sputa following detection for bacteria. The DPB complication apparently worsened the prognosis of the ATL patients. We have discussed a possible relationship between ATL and DPB.
Mutations of the epigenetics-modifying gene (DNMT3a, TET2, IDH1/2) at diagnosis may induce FLT3-ITD at relapse in de novo acute myeloid leukemia
Authors: S Wakita, H Yamaguchi, I Omori, K Terada, T Ueda, E Manabe, S Kurosawa, S Iida, T Ibaraki, Y Sato, T Todoroki, T Hirakawa, T Ryotokuji, K Arai, T Kitano, Y Mitamura, F Kosaka, K Dan, K Inokuchi
Journal: Leukemia (2012)
T cell recognition of carbohydrates on type II collagen.
Authors: E Michaëlsson, V Malmström, S Reis, A Engström, H Burkhardt, R Holmdahl
Journal: The Journal of Experimental Medicine (1994)

A critical event in an immune response is the T cell recognition of peptides bound to major histocompatibility complex (MHC) molecules on the surface of an antigen presenting cell (APC). Although the majority of eukaryotic proteins are glycosylated, it has not yet been shown that T cell recognition of such proteins involves recognition of the bound carbohydrates. Type II collagen (CII), the major protein constituent of joint cartilage, is posttranslationally modified by hydroxylation and glycosylation of lysines. In this report we show that posttranslational modifications of the immunodominant peptide CII(256-270) generate a structural determinant that is distinct from the determinant represented by the corresponding synthetic peptide. Elimination of carbohydrates, present on CII, by two different biochemical methods revealed that the carbohydrates, O-linked to the hydroxylysines within the CII(256-270) determinant, were crucial for the reactivity towards the posttranslationally modified peptide. Furthermore, a T cell hybridoma specific for the glycosylated determinant was stimulated by tryptic CII-peptides presented by fixed APCs, thus showing that the carbohydrates are involved in the trimolecular complex T cell receptor/peptide/MHC. Finally, the importance of the bound carbohydrates for the arthritogenicity of CII was investigated by comparing the development of arthritis after immunization with carbohydrate-depleted and glycosylated CII, respectively. Incidence, time of onset, and severity of the disease were significantly affected by the elimination of carbohydrates, whereas no significant difference in anti-CII antibody titers was seen.
Budesonide/formoterol for maintenance and reliever therapy in the management of moderate to severe asthma
Authors: M. Humbert, T. L. G. Andersson, R. Buhl
Journal: Allergy (2008)

The Global Initiative for Asthma (GINA) guidelines aim at improving asthma control and preventing future risk. For patients with moderate to severe asthma an inhaled corticosteroid (ICS) or an ICS/long‐acting β 2 ‐agonist (LABA) combination with a short‐acting β 2 ‐agonist (SABA) as reliever is recommended. Despite the availability of effective maintenance therapies, a large proportion of patients still fail to achieve guideline‐defined asthma control, and overuse of SABA reliever medication at the expense of ICS is commonly observed. New simplified treatment approaches may offer a solution and assist physicians to achieve overall asthma control. One such treatment approach, which is recommended in the GINA guidelines, is budesonide/formoterol for both maintenance and reliever therapy. This treatment strategy significantly reduces the rate of severe asthma exacerbations compared with ICS/LABA plus SABA and achieves equivalent daily symptom control compared with higher doses of ICS/LABA plus separate SABA for relief. These benefits are achieved at a lower overall steroid load, and budesonide/formoterol maintenance and reliever therapy is well tolerated in patients with moderate to severe asthma. This review discusses current asthma management in patients with moderate to severe disease and examines the evidence for alternative asthma management approaches.
DSM-IV Guidebook
Authors: Carl C. Bell
Journal: JAMA (1995)

ABSTRACT Unlike the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), which many will use as a reference tome, and Diagnostic Criteria From DSM-IV, which many will use as a diagnostic handbook, the DSM-IV Guidebook was meant to be read cover to cover. The function of this publication is to give an overview and explanation of how to use DSM-IV and the historical context and controversies from which DSM-IV arose. As a result, most of the criticisms directed at the DSM's criteria-based diagnostic system raised in Philosophical Perspectives on Psychiatric Diagnostic Classification (Baltimore, Md:Johns Hopkins University Press; reviewed in JAMA, December 14,1994) regarding its ahistorical, prototypic approach are addressed.... DSM-IV should not be thought of as a bible but rather as a stepping stone to a better system of diagnosis.The book begins with an exquisite, concise chronicle of psychiatric classification, which underscores the significant historical influences that
Chætognath transcriptome reveals ancestral and unique features among bilaterians
Authors: Ferdinand Marlétaz, André Gilles, Xavier Caubit, Yvan Perez, Carole Dossat, Sylvie Samain, Gabor Gyapay, Patrick Wincker, Yannick Le Parco
Journal: Genome biology (2008)

Abstract Background The chætognaths (arrow worms) have puzzled zoologists for years because of their astonishing morphological and developmental characteristics. Despite their deuterostome-like development, phylogenomic studies recently positioned the chætognath phylum in protostomes, most likely in an early branching. This key phylogenetic position and the peculiar characteristics of chætognaths prompted further investigation of their genomic features. Results Transcriptomic and genomic data were collected from the chætognath Spadella cephaloptera through the sequencing of expressed sequence tags and genomic bacterial artificial chromosome clones. Transcript comparisons at various taxonomic scales emphasized the conservation of a core gene set and phylogenomic analysis confirmed the basal position of chætognaths among protostomes. A detailed survey of transcript diversity and individual genotyping revealed a past genome duplication event in the chætognath lineage, which was, surprisingly, followed by a high retention rate of duplicated genes. Moreover, striking genetic heterogeneity was detected within the sampled population at the nuclear and mitochondrial levels but cannot be explained by cryptic speciation. Finally, we found evidence for trans-splicing maturation of transcripts through splice-leader addition in the chætognath phylum and we further report that this processing is associated with operonic transcription. Conclusion These findings reveal both shared ancestral and unique derived characteristics of the chætognath genome, which suggests that this genome is likely the product of a very original evolutionary history. These features promote chætognaths as a pivotal model for comparative genomics, which could provide new clues for the investigation of the evolution of animal genomes.
A Case of Early-Onset Rapidly Progressive Dementia
Authors: David Cachia, Thomas Smith, David Paydarfar, Grazyna Pomorska
Journal: JAMA Neurology (2014)

A 62-year-old man presented with rapidly progressive cognitive decline associated with ataxia, spasticity, and eventually seizures. Multiple bihemispheric foci of calcification in the brain were seen on computed tomography scan, with magnetic resonance imaging (MRI) showing relatively symmetrical areas of enhancement in the brain corresponding mostly to the areas of calcification. Cerebrospinal fluid analysis and 2 brain biopsy specimens showed no evidence of an infectious, inflammatory, or malignant process. Despite being treated empirically with high-dose corticosteroids, the patient continued to deteriorate, with the family deciding for hospice care. The final autopsy diagnosis and the approach to the clinical data are discussed.