tbuckley/cabot-search huggingface dataset:
NCR3/NKp30 Contributes to Pathogenesis in Primary Sjögren’s Syndrome
Authors: Sylvie Rusakiewicz, Gaetane Nocturne, Thierry Lazure, Michaela Semeraro, Caroline Flament, Sophie Caillat-Zucman, Damien Sène, Nicolas Delahaye, Eric Vivier, Kariman Chaba, Vichnou Poirier-Colame, Gunnel Nordmark, Maija-Leena Eloranta, Per Eriksson, Elke Theander, Helena Forsblad-d’Elia, Roald Omdal, Marie Wahren-Herlenius, Roland Jonsson, Lars Rönnblom, Joanne Nititham, Kimberly E. Taylor, Christopher J. Lessard, Kathy L. Moser Sivils, Jacques-Eric Gottenberg, Lindsey A. Criswell, Corinne Miceli-Richard, Laurence Zitvogel, Xavier Mariette
Journal: Science Translational Medicine (2013)

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by a lymphocytic exocrinopathy. However, patients often have evidence of systemic autoimmunity, and they are at markedly increased risk for the development of non- Hodgkin's lymphoma. Similar to other autoimmune disorders, a strong interferon (IFN) signature is present among subsets of pSS patients, although the precise etiology remains uncertain. NCR3/NKp30 is a natural killer (NK)-specific activating receptor regulating the cross talk between NK and dendritic cells and type II IFN secretion. We performed a case-control study of genetic polymorphisms of the NCR3/NKp30 gene and found that rs11575837 (G>A) residing in the promoter was associated with reduced gene transcription and function as well as protection to pSS. We also demonstrated that circulating levels of NCR3/NKp30 were significantly increased among pSS patients compared with controls and correlated with higher NCR3/NKp30 but not CD16-dependent IFN-γ secretion by NK cells. Excess accumulation of NK cells in minor salivary glands correlated with the severity of the exocrinopathy. B7H6, the ligand of NKp30, was expressed by salivary epithelial cells. These findings suggest that NK cells may promote an NKp30-dependent inflammatory state in salivary glands and that blockade of the B7H6/NKp30 axis could be clinically relevant in pSS.
PHARMACODYNAMIC EFFECTS OF DIFFERENT ASPIRIN DOSING REGIMENS IN TYPE 2 DIABETES MELLITUS PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Davide Capodanno, Aasita Patel, Kodlipet Dharmashankar, Jose Luis Ferreiro, Masafumi Ueno, Murali Kodali, Salvatore D. Tomasello, Piera Capranzano, Naveen Seecheran, Andrew Darlington, Antonio Tello, Bhaloo Desai, Theodore A. Bass, Dominick J. Angiolillo
Journal: Journal of the American College of Cardiology (2011)
Drug-Induced liver injury with hypersensitivity features has a better outcome: A single-center experience of 39 children and adolescents
Authors: Harshad Devarbhavi, Dheeraj Karanth, Prasanna KS, Adarsh CK, Mallikarjun Patil
Journal: Hepatology (2011)

Drug-induced liver injury (DILI) is rare in children and adolescents, and, consequently, data are remarkably limited. We analyzed the causes, clinical and biochemical features, natural history, and outcomes of children with DILI. Consecutive children with DILI from 1997 to 2004 (retrospective) and 2005 to 2010 (prospective) were studied based on standard criteria for DILI. Thirty-nine children constituted 8.7% of 450 cases of DILI. There were 22 boys and 17 girls. Median age was 16 years (range, 2.6-17). Combination antituberculous drugs were the most common cause (n = 22), followed by the anticonvulsants, phenytoin (n = 10) and carbamazepine (n = 6). All of the 16 children (41%) who developed hypersensitivity features, such as skin rashes, fever, lymphadenopathy, and/or eosinophilia, including the 3 with Stevens-Johnson syndrome, survived. Those with hypersensitivity presented earlier (24.5 versus 35 days; P = 0.24) had less severe disease (MELD, 16 versus 29; P = 0.01) and had no mortality (0/16 versus 12/23; P &lt; 0.001), compared to those without hypersensitivity. The 12 fatalities were largely the result of antituberculous DILI (n = 11). The presence of encephalopathy and ascites were associated with mortality, along with hyperbilirubinemia, high international normalized ratio, and serum creatinine. According to the Roussel Uclaf Causality Assessment Method, 18 were highly probable, 14 probable, and 7 possible. Thirty-two children were hospitalized. Conclusion: DILI is not uncommon in children and accounts for 8.7% of all patients with DILI. Antituberculous drugs and anticonvulsants are the leading causes of DILI in India. Overall mortality is high (30.7%), largely accounted by antituberculous drugs. Children with DILI and hypersensitivity features present early, have less severe disease, and, consequently, a better prognosis, compared to those without, and are often associated with anticonvulsants or sulfonamides. (Hepatology 2011;)
Abstract 3781: 3,3′-diindolylmethane(DIM)-induced apoptosis in ovarian cancer cells is mediated by inhibition of EGFR-ERK pathway
Authors: Prabodh K. Kandala, Kartick C. Pramanik, Srinivas Reddy Boreddy, Sanjay K. Srivastava
Journal: Cancer Research (2010)

Abstract Ovarian cancer is one of the leading causes of gynaecological deaths in the United States and several other countries. Genetic alterations including overexpression of EGFR (about 70% of ovarian tumors) play a crucial role in the signal transduction pathways that regulate key cellular functions such as cell survival and proliferation and are responsible for comprising traditional chemotherapy. Several epidemiological studies suggested a decreased risk of ovarian cancer in the population consuming Brassica vegetables. 3,3′-diindolylmethane (DIM) is an indole compound present in Brassica vegetables. In our previous studies, we have demonstrated that BR-DIM, a formulated version of DIM suppress the growth of ovarian cancer cells by causing cell cycle arrest. However, the exact mechanism by which DIM suppress the growth of ovarian cancer cells was not clear. In the present study, we delineated the mechanism of DIM in SKOV3, OVCAR-3 and TOV-21G human ovarian cancer cells. Our results show that DIM treatment induces apoptosis in all the cell lines in a dose-dependent manner, as analyzed by flow cytometry. Our western blot analysis reveals that DIM treatment causes significant down regulation of constitutive EGFR and HER2 protein level as well as phosphorylation of EGFR at Tyr992, Tyr845 and Tyr1173 in SKOV-3 and OVCAR-3 cells. To determine whether DIM can suppress the activation of EGFR by activating phosphorylation, cells were treated with EGF after DIM treatment. Our results reveal that DIM treatment block the activation of EGFR induced by EGF in OVCAR-3 and TOV-21G cells. In addition, DIM treatment drastically reduces the phosphorylation of ERK without affecting the protein level. DIM treatment also inhibits the kinase activity of ERK as observed by the down regulation of p-ELK in all the three ovarian cancer cell lines. ERK is known to be regulated by EGFR. Taken together our results indicate that DIM induces apoptosis in ovarian cancer cells by inhibiting EGFR-ERK pathway. Further mechanistic studies are in progress. [Supported in part by RO1 grants CA 106953 and CA129038 (to S.K.S) awarded by the National Cancer Institute]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3781.
Randomized, Double-Blind Crossover Study to Investigate the Effects of Amlodipine and Isosorbide Mononitrate on the Time Course and Severity of Exercise-Induced Myocardial Stunning
Authors: Christopher A. Rinaldi, Andre Z. Linka, Navroz D. Masani, Philip G. Avery, Elizabeth Jones, Helen Saunders, Roger J. C. Hall
Journal: Circulation (1998)

Background —Myocardial stunning may cause prolonged left ventricular dysfunction after exercise-induced ischemia that can be attenuated by calcium antagonists in animal models. To assess their effects in humans, we performed a randomized, double-blind crossover study comparing the calcium antagonist amlodipine (10 mg once daily) versus isosorbide mononitrate (ISMN, 50 mg once daily) on postexercise stunning. Methods and Results —Twenty-four men with chronic stable angina and normal left ventricular function underwent serial quantitative exercise stress echocardiography after 3 weeks on each treatment to assess the degree of postexercise stunning with simultaneous sestamibi single-photon emission computed tomography perfusion scans at peak stress to quantify the ischemic burden. Exercise time ( P =1), maximum ST depression ( P =0.48), and sestamibi single-photon emission computed tomography scores ( P =0.17) were unchanged between treatments. Stunning occurred more often with ISMN than amlodipine (82% versus 48%). The global and segmental stress echocardiography parameters of stunning were attenuated in patients while taking amlodipine compared with ISMN. Shortening fractions and ejection fractions were less impaired 30 minutes after exercise in patients receiving amlodipine (3.5±1.4% versus 2.5±1.4%, P =0.014, and 59.7±5.4% versus 54.5±8%, P &lt;0.001); similarly, the isovolumic relaxation period was less prolonged with amlodipine (93±15.5 versus 106.3±14.9 ms, P =0.018). Conclusions —Despite comparable levels of ischemia, amlodipine attenuated stunning when compared with ISMN. This beneficial effect may relate to a prevention of the calcium overload implicated in the pathogenesis of stunning.
Hen's egg, not cow's milk, sensitization in infancy is associated with asthma: 10-year follow-up of the PIAMA birth cohort
Authors: Marga B. Bekkers, Rob C. Aalberse, Ulrike Gehring, Marjan Kerkhof, Gerard H. Koppelman, Johan C. de Jongste, Henriëtte A. Smit, Bert Brunekreef, Alet H. Wijga
Journal: Journal of Allergy and Clinical Immunology (2013)
Scarlet Fever and its Treatment
Authors: C. Dukes
Journal: BMJ (1887)

THE BRIZTISH MEDICAL JOURNAL.67 with as recurrences in cases requiring repeated operation, and as first manifestations in some of the more obscure varieties, and for lupus erythematosus, of which I have had a conspicuous example in hand for the last two years.In that period scraping has been done seven- teen times, at intervals of from twelve days to three months, in a woman aged 35.The disease has lasted fourteen years, during the last ten of which I have frequently seen her.Some years ago her
Airway epithelial cells express toll-like receptor 3 and its ligand stimulates inflammatory cytokines and chemokines through NF-kB and IRF3*1
Authors: S. Matsukura, F. Kokubu, M. Kawaguchi, K. Ieki, M. Kurokawa, S. Suzuki, M. Odaka, S. Watanabe, M. Adachi, R.P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2004)
Professor Sir Ronald Fisher, FRS.
Authors: C Clarke
Journal: BMJ (1990)

If it's significant it hits you in the eye; if it doesn't it isn't."This was spoken by a distinguished surgeon and has cheered up multitudes of hard working clinicians, suggesting to them that they need not after all under- stand the intricacies of statistical language.But they ought to know about the basic techniques for unless they do the danger is that they will just give the statisticians their data and be unable to take part in any discussions. Early daysRonald Aylmer Fisher was born in February 1890, and I have written this summary of his life to show how his brilliance was of great help to medicine.Interestingly, it was a medical disability, severe myopia, which was turned to his advantage.Because of this his mathematics teacher at Harrow taught him without pencil or paper so that Fisher was increasingly able to solve problems in his head resulting later in other statisticians criticising him for using intuition.'At Caius College, Cambridge, Fisher developed strong biological interests and became keenly interested in evolutionary problems, particularly eugenics, and we can edge into his scientific eminence by quoting one of his views (not easily proved mathematically) in which he isolates a single cause for the deterioration of civilisations including our own.It was, as shown by the 1911 census in the United Kingdom, the result of a strong inverse relation between fertility and social position.He argued that this showed that the upper classes owed their status to the advantages of small families and that this would lead to the mating of ability with infertility with long term disastrous results.Interestingly, his parents may have held the same view as they tried to combat the trend: Fisher was the youngest but one of eight children, and he and his wife Eileen (nee Guinness) lived up to the theory by producing eight offspring.
Harold Logan Courtenay
Authors: C. Bradshaw
Journal: BMJ (2003)

Former general practitioner South Shields (b 1927; q Queen's University, Belfast, 1950; DRCOG), died from prostate cancer on 14 September 2002.​2002.




Figure 1




Harold came to South Shields as a principal in 1958 and, in 1964, was one of the founding partners of the medical group that was to become Marsden Road Health Centre. He fully embraced modern medicine with its desktop computers, evidence based practice, and internet research, and he combined his general practice career with a clinical assistantship in genitourinary medicine. He leaves a wife, Sandra; three children; and six grandchildren.
Characterization of the first enzyme in 2,4-dichlorophenoxyacetic acid metabolism.
Authors: R P Hausinger, F Fukumori
Journal: Environmental Health Perspectives (1995)

This paper reviews the properties of the Alcaligenes eutrophus JMP134 tfdA gene product, the enzyme responsible for the first step in 2,4-dichlorophenoxyacetic acid (2,4-D) biodegradation. The gene was overexpressed in Escherichia coli and several of its enzymatic properties were characterized. Although this enzyme catalyzes a hydroxylation reaction, it is not a monooxygenase. Rather, TfdA is an Fe(II) and alpha-ketoglutarate-dependent dioxygenase that metabolizes the latter cosubstrate to succinate and carbon dioxide. A variety of other phenoxyacetates and alpha-ketoacids can be used by the enzyme, but the greatest catalytic efficiencies were found using 2,4-D and alpha-ketoglutarate. The enzyme possesses multiple essential histidine residues, whereas catalytically essential cysteine and lysine groups do not appear to be present.
The First Professional Organization.
Authors: E. L. B. Godfrey
Journal: JAMA (1893)

Camden, N. J., Oct. 23, 1893. <h3>To the Editor:</h3> —In the issue of October 21, there appeared an article credited to the<i>Norwich</i>(Conn.)<i>Bulletin</i>, on "The First Pr fessional Organization," which states "that the first step toward professional organization and protection in Connecticut was taken by Norwich physicians," who met on March 24, 1774, pursuant to an advertisement of March 3, to consider and prefer a memorial to the General Assembly to regulate the practice of physic. It is stated that "their demand was for the appointment of a committee legally authorized to examine and approve candidates, if found qualified," and that "the movement, which was in advance of the age, was negatived in the Lower House." It is also claimed that this was "the initiative step in a series of efforts which have since resulted in the permanent establishment of flourishing State and National Associations, which separate the
Breast cancer risk and environmental exposures.
Authors: M S Wolff, A Weston
Journal: Environmental Health Perspectives (1997)

Although environmental contaminants have potential to affect breast cancer risk, explicit environmental links to this disease are limited. The most well-defined environmental risk factors are radiation exposure and alcohol ingestion. Diet is clearly related to the increased incidence of breast cancer in developed countries, but its precise role is not yet established. Recent studies have implicated exposure to organochlorines including DDT as a risk factor for breast cancer in the United States, Finland, Mexico, and Canada. Other investigations have discovered associations between breast cancer risk and exposures to chemical emissions and some occupational exposures. Several points must be considered in evaluating the relationship of environmental exposure to breast cancer. Among these considerations are the mechanism of tumorigenesis, timing of environmental exposure, and genetic modulation of exposure. Epidemiologic and ecologic investigations must take into account the very complex etiology of breast cancer and the knowledge that tumorigenesis can arise from different mechanisms. Thus crucial exposures as well as reproductive events related to breast cancer may occur years before a tumor is evident. Moreover, environmental contaminants may alter reproductive development, directly or indirectly, and thereby effect the course of tumorigenesis. Such alterations include change in gender, change in onset of puberty, and inhibition or promotion of tumor formation. Timing of exposure is therefore important with respect to mechanism and susceptibility. Finally, genetic polymorphisms exist in genes that govern capacity to metabolize environmental contaminants. Higher risk may occur among persons whose enzymes either are more active in the production of procarcinogens or fail to detoxify carcinogenic intermediates formed from chemicals in the environment.
Neurotoxicity of Metronidazole
Authors: THEODORE A. ALSTON
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 July 1985Neurotoxicity of MetronidazoleTHEODORE A. ALSTON, M.D., Ph.D.THEODORE A. ALSTON, M.D., Ph.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-103-1-161_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In their review of antibiotic neurotoxicity, Snavely and Hodges (1) mention that the neurotoxicity of isoniazid stems largely from antagonism of vitamin B6. However, they point out that the mechanisms of central and peripheral neurotoxicity of metronidazole are not understood. This problem is vexing because adverse neurologic reactions limit the chronic use of metronidazole in the control of Crohn disease and limit use of high-dose metronidazole for control of life-threatening anaerobic infections or radiosensitization of tumors (1, 2).The neurotoxicity of metronidazole may involve metabolic reduction of its nitro substituent, in which case the neurotoxic action may...References1. SNAVELYHODGES SG. The neurotoxicity of antibacterial agents Ann Intern Med. 1984;101:92-104. Google Scholar2. FRYTAKMOERTELCHILDSALBERS SCDJ. Neurologic toxicity associated with high-dose metronidazole therapy. Ann Intern Med. 1978;88:361-2. LinkGoogle Scholar3. NAJJARHOLT VL. The biosynthesis of thiamine in man. JAMA. 1943;123:683-4. CrossrefGoogle Scholar4. FUJITA A. Thiaminase. Adv Enzymol. 1954;15:389-422. MedlineGoogle Scholar5. VON ROGULJAKOVACSCHMID PWH. Metronidazol-Encephalopathie der Ratte. Acta Neuropathol. 1973;25:36-45. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: THEODORE A. ALSTON, M.D., Ph.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byReversible optic neuropathy secondary to metronidazoleMetronidazoleNeurotoxicity with Antimicrobials in the Elderly: A ReviewNeurologic Complications of MetronidazoleANTIPROTOZOAL AND ANTIHELMINTHIC DRUGSMetronidazoleNeuropathy Caused by DrugsMetronidazole and Mental ConfusionToxicities of Antimicrobial Agents Used to Treat OsteomyelitisAntiprotozoal drugs 1 July 1985Volume 103, Issue 1Page: 161-161KeywordsAdverse reactionsAntibioticsCrohn's diseaseInfectious disease controlIsoniazid ePublished: 1 December 2008 Issue Published: 1 July 1985 PDF downloadLoading ...
PET scans 'relate clinical picture to more specific nerve function'
Authors: Terra Ziporyn
Journal: JAMA (1985)

Since the early 1960s, neurologists have recognized the severely reduced neostriatal dopamine content in patients with Parkinson's disease. But only in the past year or two have radionuclides used in conjunction with positron emission tomography (PET) allowed visualization of dopamine metabolism in dopaminergic nerve endings as well as dopamine receptors. Besides enhancing understanding of the natural history of Parkinson's disease, these new techniques have the potential to show effects of pharmacologic manipulations on disease progression as well as to elucidate effects of treatment. Until about May 1983, PET scans measured only the bioenergetics of either glucose or oxygen metabolism (<i>JAMA</i>[MEDICAL NEWS] 1983;249:857-867 and 1982; 248:627-632). Patients were given minute amounts of a radioactively labeled glucose or oxygen compound, and radiation from the positron-emitting label was detected by the scanner, fed through a computer, and transformed into colorful images of brain function that appear as slices through the brain, similar
A STUDY OF DUST-INDUCED LYMPHOCYTE BLASTOGENESIS
Authors: T. J. YOO, C. Y. KUO, C. HEATH
Journal: Allergy (1977)

The in vitro measurement of dust allergen-stimulated lymphocyte blastogenesis by the incorporation of H3-thymidine can be a useful measurement for the evaluation of the cellular immune function in dust allergy patients. Dust allergy patients receiving immunotherapy had lower lymphocyte responses than those not receiving immunotherapy. Additionally, dust allergy patients as a whole showed higher lymphocyte stimulation indices than normal control.
The electrophoretic pattern of normal human gastric juice and of the gastric juice of patients with gastric ulcer and gastric cancer
Authors: D. W. Piper, M. C. Stiel, J. E. Builder
Journal: Gut (1963)

This study reports the electrophoretic pattern of the proteins in human gastric juice of control patients and patients with gastric ulcer and gastric carcinoma. Autodigestion was prevented by intragastric neutralization. The statistical limits of normal are defined and the changes found in the gastric juice of gastric ulcer and gastric patients with gastric carcinoma described.
Abstract 6130: Prospective Multicenter Trial Comparing Novel High-speed Myocardial Perfusion SPECT to Conventional SPECT: Quantitative Results of Myocardial Perfusion and Left Ventricular Function
Authors: Tali Sharir, Marcelo F Di Carli, Jack A Ziffer, William H Martin, Sean W Hayes, James Gerlach, Dalia Dickman, Piotr J Slomka, Daniel S Berman
Journal: Circulation (2008)
GMC calls for Europe-wide cooperation on malpractice after Spanish doctor is suspended
Authors: C. Dyer
Journal: BMJ (2010)

An Argentinian doctor who was convicted in 2009 of the manslaughter of a patient in Spain in 2005 has been working in the United Kingdom as a hospital doctor and police surgeon while the General Medical Council was unaware of the Spanish prosecution and conviction.

The GMC, which has now suspended Marcos Hourmann pending a full investigation, renewed its call for a mandatory requirement on European regulators to tell each other when action is taken against a doctor. Its Spanish equivalent had left …