tbuckley/cabot-search huggingface dataset:
DNA Adducts in Human Urinary Bladder and Other Tissues
Authors: David H. Phillips, Alan Hewer
Journal: Environmental Health Perspectives (1993)

Tobacco smoking is associated with an increased risk of cancer in a number of organs, including bladder and lung. Tobacco smoke contains at least 50 known chemical carcinogens that exert their biological effects through their covalent binding to cellular DNA. Examining human DNA for the presence of altered nucleotides is a means of monitoring exposure to genotoxic chemicals. DNA isolated from 73 human bladder biopsies has been analyzed by 32P-postlabeling for the presence of aromatic/hydrophobic adducts. Butanol extraction of DNA digests resulted in up to a 3-fold greater recovery of adducts than nuclease P1 digestion. Among 16 nonsmokers, adduct levels were in the range 3.2-20.8/10(8) nucleotides (mean 9.7). Eight ex-smokers had values in the range 2.6-12.3 (mean 7.1). Thirteen smokers had adduct levels between 1.3 and 26.7 adducts/10(8) nucleotides (mean 9.5, not different from nonsmokers). Six cigar smokers had higher levels of adducts (mean 12.1, range 7.3-15.0), but pipe smokers did not (five samples, mean 8.6, range 2.9-12.7). A further 8 samples from nonsmokers and 17 from smokers were examined in more detail. Although most of the DNA binding appears not to be smoking related, the levels of one adduct were found to be on average 2-fold higher in smokers (p < 0.005, one-tailed t test). Studies on tissues of the respiratory tract demonstrate a correlation between DNA adduct levels and exposure to tobacco smoke. Evidence to date on the influence of smoking on adducts in peripheral blood cells is equivocal; some studies demonstrate a significant effect, whereas others do not.(ABSTRACT TRUNCATED AT 250 WORDS)
The different autophagy degradation pathways and neurodegeneration
Authors: Angeleen Fleming, Mathieu Bourdenx, Motoki Fujimaki, Cansu Karabiyik, Gregory J. Krause, Ana Lopez, Adrián Martín-Segura, Claudia Puri, Aurora Scrivo, John Skidmore, Sung Min Son, Eleanna Stamatakou, Lidia Wrobel, Ye Zhu, Ana Maria Cuervo, David C. Rubinsztein
Journal: Neuron (2022)
Shall The Journal be Removed to Washington?
Authors: R. Harvey Reed
Journal: JAMA (1891)

<h3>To the Editor:</h3> —Permit me through the columns of your journal to ask our friend Dr. Solomon Solis-Cohen to please verify his assertion under No. 1, to point out the Vol., No. and page ofThe Journal of the American Medical Associationin which said journal has debased itself either in its editorial or news columns as he alleges it to have done. While the doctor is on the stand we would be glad to have him enlighten the thousands of readers ofThe Journalon his 2nd proposition and tell us in what respect Chicago debars the best scientific men in the country from sending the best productions they can produce toThe Journalof the National Association, or in what respect<i>Washington</i>would have any greater magnetic attraction for these articles than the great metropolis of the west. Certainly Washington has never shown any great distinction in the
Part 5: Adult Basic Life Support
Authors: Michael R. Sayre, Rudolph W. Koster, Martin Botha, Diana M. Cave, Michael T. Cudnik, Anthony J. Handley, Tetsuo Hatanaka, Mary Fran Hazinski, Ian Jacobs, Koen Monsieurs, Peter T. Morley, Jerry P. Nolan, Andrew H. Travers, Tom P. Aufderheide, Jocelyn Berdowski, Robert A. Berg, Maaret Castrén, Manya Charette, Sung Phil Chung, David C. Cone, Daniel P. Davis, Csaba Dioszeghy, James V. Dunford, Dana P. Edelson, Peter Fenici, Raúl J. Gazmuri, Laura S. Gold, Anton P.M. Gorgels, Colin A. Graham, Ahamed Idris, Jan L. Jensen, Peter Kohl, Peter J. Kudenchuk, Michael A. Kuiper, Douglas Kupas, E. Brooke Lerner, Bo Løfgren, Raina Merchant, Tommaso Pellis, Gavin D. Perkins, Thomas D. Rea, Andrea Scapigliati, Robert A. Swor, Keiichi Tanaka, Nigel M. Turner, Tyler F. Vadeboncoeur, Christian Vaillancourt, Antonius M.W. van Stipdonk, Barbara Vantroyen
Journal: Circulation (2010)
Ketteler M, Block GA, Evenepoel P, et al. Executive summary of the 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update: what's changed and why it matters. Kidney Int. 2017;92:26–36
Authors: Markus Ketteler, Geoffrey Block, Pieter Evenepoel, Masafumi Fukagawa, Charles Herzog, Linda Mccann, Sharon Moe, Rukshana Shroff, Marcello Tonelli, Nigel Toussaint, Marc Vervloet, Mary Leonard
Journal: Kidney International (2017)

The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD represents a selective update of the prior CKD-MBD Guideline published in 2009.This update, along with the 2009 publication, is intended to assist the practitioner caring for adults and children with chronic kidney disease (CKD), those on chronic dialysis therapy, or individuals with a kidney transplant.This review highlights key aspects of the 2017 CKD-MBD Guideline Update, with an emphasis on the rationale for the changes made to the original guideline document.Topic areas encompassing updated recommendations include diagnosis of bone abnormalities in CKD-mineral and bone disorder (MBD), treatment of CKD-MBD by targeting phosphate lowering and calcium maintenance, treatment of abnormalities in parathyroid hormone in CKD-MBD, treatment of bone abnormalities by antiresorptives and other osteoporosis therapies, and evaluation and treatment of kidney transplant bone disease.
<i>HLA‐DPB1*05:01</i> genotype is associated with poor response to sublingual immunotherapy for Japanese cedar pollinosis
Authors: Masanori Kidoguchi, Wataru Morii, Emiko Noguchi, Atsushi Yuta, Yukiko Ogawa, Takako Nakamura, Hirotaka Kikuoka, Hideaki Kouzaki, Hiroyuki Arai, Rieko Ii, Naoto Adachi, Keisuke Koyama, Takahiro Ninomiya, Yoshimasa Imoto, Masafumi Sakashita, Shigeharu Fujieda
Journal: Allergy (2022)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Structural basis of von Willebrand factor multimerization and tubular storage
Authors: Jianwei Zeng, Zimei Shu, Qian Liang, Jing Zhang, Wenman Wu, Xuefeng Wang, Aiwu Zhou
Journal: Blood (2022)

The von Willebrand factor (VWF) propeptide (domains D1D2) is essential for the assembly of VWF multimers and its tubular storage in Weibel-Palade bodies. However, detailed molecular mechanism underlying this propeptide dependence is unclear. Here, we prepared Weibel-Palade body-like tubules using the N-terminal fragment of VWF and solved the cryo-electron microscopy structures of the tubule at atomic resolution. Detailed structural and biochemical analysis indicate that the propeptide forms a homodimer at acidic pH through the D2:D2 binding interface and then recruits 2 D'D3 domains, forming an intertwined D1D2D'D3 homodimer in essence. Stacking of these homodimers by the intermolecular D1:D2 interfaces brings 2 D3 domains face-to-face and facilitates their disulfide linkages and multimerization of VWF. Sequential stacking of these homodimers leads to a right-hand helical tubule for VWF storage. The clinically identified VWF mutations in the propeptide disrupted different steps of the assembling process, leading to diminished VWF multimers in von Willebrand diseases (VWD). Overall, these results indicate that the propeptide serves as a pH-sensing template for VWF multimerization and tubular storage. This sheds light on delivering normal propeptide as a template to rectify the defects in multimerization of VWD mutants.
Renin inhibitors
Authors: William J. Greenlee
Journal: Medicinal Research Reviews (1990)

Since the early 1980s, an intensive effort has been focused on the development of orally effective and long-acting inhibitors of renin. During this time, in vitro potency has increased greatly, with several transition-state inhibitor designs yielding inhibitors with subnanomolar IC50 values. In the meantime, both the molecular weight and peptide character of the inhibitors has decreased as important binding elements have been focused into smaller and more stable structures. The resulting inhibitors have shown promising activities in several in vivo models and (in two cases) in man. Nevertheless, renin inhibitors reported to date have limited oral bioavailability and short duration of action, and improvements in both will be necessary for them to compete effectively with ACE inhibitors. Renin inhibitors which have entered clinical studies have at least one naturally occurring amino acid and three or more amide bonds. It is reasonable to expect that continued development will produce wholly nonpeptide inhibitors with still lower MW, and it may be these "second-generation" inhibitors which will succeed as therapeutic agents. Development of orally effective and long-acting inhibitors of renin will enable their long-term antihypertensive efficacy and possible advantages over ACE inhibitor to be investigated.
Executive summary
Journal: Allergy (1998)

Allergic rhinitis is now recognized as a major cause of morbidity that significantly impairs function and quality of life. Moreover, it is now widely held that the pathophysiologic mechanisms causing nasal allergy contribute, or predispose many individuals, to the development of other airway diseases, including asthma. Allergic rhinitis may well be a factor in 24% of children with otitis media with effusion (OME), and perhaps 28% of cases of chronic sinusitis. As many as 78% of persons with asthma aged 15 to 30 years have elevated serum IgE antibodies to five common aeroallergens. In many instances, nasal allergy signals the presence of more severe disease. Considerable evidence now suggests that early and appropriate intervention can improve the quality of life and productivity of patients with allergic rhinitis, enhance the academic performance of children, and reduce the prevalence of airway complications. The goal of treatment has shifted from mere symptom alleviation to blocking the pathophysiologic mechanisms that cause chronic allergic inflammation and leave patients vulnerable to airway infections. The earlier in a patient's life that this can be accomplished, the better the anticipated consequences. A panel of experts was convened in Amsterdam, The Netherlands, on 2 September 1996, to explore these issues and their impact on allergy prevention and treatment in primary care. Their undertaking was supported by an unrestricted educational grant from Schering‐Plough Pharmaceuticals.
Breast Cancer Index Is a Predictive Biomarker of Treatment Benefit and Outcome from Extended Tamoxifen Therapy: Final Analysis of the Trans-aTTom Study
Authors: John M.S. Bartlett, Dennis C. Sgroi, Kai Treuner, Yi Zhang, Tammy Piper, Ranelle C. Salunga, Ikhlaaq Ahmed, Lucy Doos, Sarah Thornber, Karen J. Taylor, Elena F. Brachtel, Sarah J. Pirrie, Catherine A. Schnabel, Daniel W. Rea
Journal: Clinical Cancer Research (2022)

The Breast Cancer Index (BCI) HOXB13/IL17BR (H/I) ratio predicts benefit from extended endocrine therapy in hormone receptor-positive (HR+) early-stage breast cancer. Here, we report the final analysis of the Trans-aTTom study examining BCI (H/I)'s predictive performance.
Pneumomediastinum in COVID-19: a phenotype of severe COVID-19 pneumonitis? The results of the UK POETIC survey
Authors: James Melhorn, Andrew Achaiah, Francesca M. Conway, Elizabeth M.F. Thompson, Erik W. Skyllberg, Joseph Durrant, Neda A. Hasan, Yasser Madani, Prasheena Naran, Bavithra Vijayakumar, Matthew J. Tate, Gareth E. Trevelyan, Irfan Zaki, Catherine A. Doig, Geraldine Lynch, Gill Warwick, Avinash Aujayeb, Karl A. Jackson, Hina Iftikhar, Jonathan H. Noble, Anthony Y.K.C. Ng, Mark Nugent, Philip J. Evans, Robert A. Hastings, Harry R. Bellenberg, Hannah Lawrence, Rachel L. Saville, Nikolas T. Johl, Adam N. Grey, Huw C. Ellis, Cheng Chen, Thomas L. Jones, Nadeem Maddekar, Shahul Leyakathali Khan, Ambreen Iqbal Muhammad, Hakim Ghani, Yadee Maung Maung Myint, Cecillia Rafique, Benjamin J. Pippard, Benjamin R.H. Irving, Fawad Ali, Viola H. Asimba, Aqeem Azam, Eleanor C. Barton, Malvika Bhatnagar, Matthew P. Blackburn, Kate J. Millington, Nicholas J. Budhram, Katherine L. Bunclark, Toshit P. Sapkal, Giles Dixon, Andrew J.E. Harries, Mohammad Ijaz, Vijayalakshmi Karunanithi, Samir Naik, Malik Aamaz Khan, Karishma Savlani, Vimal Kumar, Beatriz Lara Gallego, Noor A. Mahdi, Caitlin Morgan, Neena Patel, Elen W. Rowlands, Matthew S. Steward, Richard S. Thorley, Rebecca L. Wollerton, Sana Ullah, David M. Smith, Wojciech Lason, Anthony J. Rostron, Najib M. Rahman, Rob J. Hallifax
Journal: European Respiratory Journal (2022)

Background There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum (PTM). We aimed to determine its incidence among patients hospitalised with COVID-19 in the UK and describe factors associated with outcome. Methods A structured survey of PTM and its incidence was conducted from September 2020 to February 2021. UK-wide participation was solicited via respiratory research networks. Identified patients had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and radiologically proven PTM. The primary outcomes were to determine incidence of PTM in COVID-19 and to investigate risk factors associated with patient mortality. Results 377 cases of PTM in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 PTM was 195 out of 377 (51.7%). PTM in COVID-19 was associated with high rates of mechanical ventilation. 172 out of 377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 PTM at the time of diagnosis and thereafter (p&lt;0.001), along with increasing age (p&lt;0.01) and diabetes mellitus (p=0.08). Switching patients from continuous positive airway pressure support to oxygen or high-flow nasal oxygen after the diagnosis of PTM was not associated with difference in mortality. Conclusions PTM appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom PTM was identified had not been mechanically ventilated at the point of diagnosis.
Membrane digestion
Authors: A. M. Ugolev
Journal: Gut (1972)

Progress report Membrane digestionBy the end of the 1950s the extensive investigations which laid the foundations for certain basic current concepts were complete, namely, the digestive function of the intestinal cells; the integration of the processes of digestion proper and of transport during digestion; and the pathology of enterocytes and other cells.And they may be summarized as follows: (1) the free surface of the enterocyte represents an aggregate of microvillil-14; (2) hydrolysis of oligomers, ie, the final stages of digestion, is being accomplished during absorption by enzymes bound to the enterocyte structures15-20; (3) numerous enzymes, in particular alkaline phosphatase and the aminopeptidases, are concentrated within the brush border zone21-27.The final link in the under- standing of these processes is that oligomers as such penetrate inside the intestinal cells where the final stages of hydrolysis and further transport of monomers take place.The Digestive Functions of Enterocytes Simultaneously, at the end of the 1950s and the beginning of the 1960s, two different hypotheses to explain these facts were presented, namely, (1) the concept of apical intracellular digestion28-32 and (2) that of membrane diges- tion33-.Evidence is increasing to suggest that the first hypothesis is untenable.Membrane digestion, in addition to the two early known types-distant extracellular and intracellular-is considered to be a system of the digestive processes occurring under the influence of the enzymes situated on the external surface of the membrane.We had the good fortune to be able to demonstrate that the external surface of the brush border is a morphological substrate of a new, previously unknown type of digestion (membrane) which appeared to be associated with the adsorption of pancreatic enzymes to the surface of the intestinal mucosa3336,i40,47. (Due to the large size of amylase molecules (molecular weight is about 45 000)48,49 their penetration into the cells was excluded.)Evidence of the rapid and complete loss of enzyme from fluid as it adsorbs onto membrane (desorption) supported our arguments even more forcibly3336'40,47.Adsorbed amylase was shown to hydrolyze intensively the soluble (not colloidal) starch40.In practice, it was found at the same time that enteric enzymes, in particular disaccharidases and dipeptidases, produce their effect not intracellularly but at the external surface of the cell membranes37,40,41,46.In man and mammals, membrane digestion is accomplished at the surface of the microvilli of the enterocyte.This idea was first reported in 1959 and discussed in a number of reports 36,40,50,51-53 Those enzymes which ensure membrane digestion (Fig. I)* may have two
AAV gene therapy for Tay-Sachs disease
Authors: Terence R. Flotte, Oguz Cataltepe, Ajit Puri, Ana Rita Batista, Richard Moser, Diane McKenna-Yasek, Catherine Douthwright, Gwladys Gernoux, Meghan Blackwood, Christian Mueller, Phillip W. L. Tai, Xuntian Jiang, Scot Bateman, Spiro G. Spanakis, Julia Parzych, Allison M. Keeler, Aly Abayazeed, Saurabh Rohatgi, Laura Gibson, Robert Finberg, Bruce A. Barton, Zeynep Vardar, Mohammed Salman Shazeeb, Matthew Gounis, Cynthia J. Tifft, Florian S. Eichler, Robert H. Brown, Douglas R. Martin, Heather L. Gray-Edwards, Miguel Sena-Esteves
Journal: Nature Medicine (2022)
SENP7 senses oxidative stress to sustain metabolic fitness and antitumor functions of CD8+ T cells
Authors: Zhongqiu Wu, Haiyan Huang, Qiaoqiao Han, Zhilin Hu, Xiao-Lu Teng, Rui Ding, Youqiong Ye, Xiaoyan Yu, Ren Zhao, Zhengting Wang, Qiang Zou
Journal: Journal of Clinical Investigation (2022)

The functional integrity of CD8+ T cells is tightly coupled to metabolic reprogramming, but how oxidative stress directs CD8+ T cell metabolic fitness in the tumor microenvironment (TME) remains elusive. Here, we report that SUMO-specific protease 7 (SENP7) senses oxidative stress to maintain the CD8+ T cell metabolic state and antitumor functions. SENP7-deficient CD8+ T cells exhibited decreased glycolysis and oxidative phosphorylation, resulting in attenuated proliferation in vitro and dampened antitumor functions in vivo. Mechanistically, CD8+ T cell-derived ROS triggered cytosolic SENP7-mediated PTEN deSUMOylation, thereby promoting PTEN degradation and preventing PTEN-dependent metabolic defects. Importantly, lowering T cell-intrinsic ROS restricted SENP7 cytosolic translocation and repressed CD8+ T cell metabolic and functional activity in human colorectal cancer samples. Our findings reveal that SENP7, as an oxidative stress sensor, sustains CD8+ T cell metabolic fitness and effector functions and unveil an oxidative stress-sensing machinery in tumor-infiltrating CD8+ T cells.
CONDITIONS IN THE INDIAN MEDICAL SERVICE
Journal: JAMA (1920)

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
Alveolar Ventilation
Authors: W. M. ARNOTT
Journal: Annals of Internal Medicine (1968)

Evidence is presented that the design of the air passages in respect of dimensions and the ratios of diameters of parent to daughter branches and angles of branching closely approximate the theoretical optimum for mass movement of gas down to the level of terminal bronchioles (0.6 mm in diameter). Distal to this point, the geometry of the passages support the hypothesis that gas movement is by molecular diffusion. The single-breath nitrogen washout experiment using oxygen indicates an inhomogeneity of gas mixing. Studies of the pattern of inhomogeneity using neon, sulphahexafluoride, and an aerosol of di-2-ethylhexyl sebacate as an indicator gas—along with varying periods of breath holding—indicate that about two thirds of the inhomogeneity is due to stratification or imperfect diffusion. The remaining third is due to regional inhomogeneity consequent upon variations in the transit times of mass movement of gas. A detailed analysis of the multiple-breath nitrogen washout procedure points to stratified inhomogeneity as the major cause of departure from uniformity of distribution of ventilation. Evidence points to stratified or diffusion inhomogeneity as the major ventilatory defect in chronic bronchitis, especially when centrilobular emphysema is present.
Books Received
Journal: JNCI Journal of the National Cancer Institute (1972)

Books Received Get access Cancer Chemotherapy (Elkerbout F, Thomas P., Zwavel-ing A., eds.). Baltimore, Williams & Wilkins Co., 1971, 410 pp, $17.25. The Platelet (Brinkhous KM., Shermer RW., Mostofi FK., eds.). Baltimore, Williams & Wilkins Co., 1971, 420 pp, $25.50. Inhibition of Carcinogenesis (Van Duuren BL., Rubin BA., eds.). Basel, New York, Karger, 1971, 241 pp. Linder F.: Diagnostische und therapeutische Fortschritte in der Krebschirurgie (neoplasms and surgery). Berlin, New York, Springer-Verlag, 1971, 260 pp. Maramorosch K.: Comparative Virology. New York, Academic Press Inc., 1971, 584 pp, $27.50. National Panel of Consultants on the Conquest of Cancer. Washington, D.C., U.S. Govt Print Off, 1971, 376 pp, $1.50. Nauchno-issledovatel'skii institut onkologii im (neoplasms). Leningrad, $2.50. Opukholi golovnogo mozga (brain neoplasms). Moskva, 1970, 110 pp, 80 cents. Ponten J.: Spontaneous and Virus Induced Transformation in Cell Culture. Vienna, New York, Springer-Verlag, 1971, 253 pp. Symposium on Current Concepts in the Management of Lymphoma and Leukemia (Ultmann JE., ed.). Berlin, New York, Springer-Verlag, 1971, 198 pp. Ubaldi P.: Orientaciones terapéuticas y patogénesis del cáncer (neoplasms—etiology and therapy). Montevideo, 1968, 95 pp. Wahi PN.: Histological Typing of Oral and Oropharyngeal Tumours. Geneva, World Health Organization, 1971, 20 pp. JNCI: Journal of the National Cancer Institute, Volume 48, Issue 2, February 1972, Page 573, https://doi.org/10.1093/jnci/48.2.573 Published: 01 February 1972