tbuckley/cabot-search huggingface dataset:
Human lung mast cell heterogeneity
Authors: P. Bradding
Journal: Thorax (2009)

Mast cells are found throughout the human body, both at mucosal surfaces and in the connective tissue of all organs. In fact, they are present in all classes of vertebrates including amphibians, reptiles, birds and mammals, and it has been estimated that the storage of histamine in vertebrate mast cells and its use as an inflammatory mediator was established in primitive reptiles (Lepidosauria) about 276 million years ago.1 This suggests that they mediate functions essential for life rather than representing a vestigial remnant of the immune system. Indeed, mast cells have been implicated in the regulation of many diverse homeostatic and pathological processes. For example, potential beneficial activities include defence against microbial infection with activation of both innate and acquired arms of the immune system, resistance to the effects of toxic venoms and roles in wound healing.2 3 Conversely, they are implicated in the pathophysiology of many diverse diseases such as atherosclerosis,4 allergy and asthma,5 pulmonary fibrosis6 and rheumatoid arthritis.7

Mast cells are able to achieve these diverse tissue effects through the release of numerous vasoactive and bronchospastic autacoid mediators (histamine, leukotriene C4 (LTC4), prostaglandin D2 (PGD2), serine proteases (tryptase, chymase), cytokines and chemokines.2 The release of these mediators is not “all-or-nothing”, but the pattern of molecules released is often tailored to the tissue insult. For example, using gene arrays, Okumura and colleagues showed that activation of cord blood-derived mast cells with anti-IgE, lipopolysaccharide (LPS), LPS + interferon γ (IFNγ) or IFNγ alone induced both core responses but also stimulus-specific responses.8 Furthermore, activation by LPS, for example, is able to induce cytokine secretion but not degranulation.9 It therefore seems likely that the normal role for the mast cell is to sense its external environment, ready to respond early to …
MiTF links Erk1/2 kinase and p21CIP1/WAF1 activation after UVC radiation in normal human melanocytes and melanoma cells
Authors: Feng Liu, Amarinder Singh, Zhen Yang, Angela Garcia, Yu Kong, Frank L Meyskens
Journal: Molecular Cancer (2010)

As a survival factor for melanocytes lineage cells, MiTF plays multiple roles in development and melanomagenesis. What role MiTF plays in the DNA damage response is currently unknown. In this report we observed that MiTF was phosphorylated at serine 73 after UVC radiation, which was followed by proteasome-mediated degradation. Unlike after c-Kit stimulation, inhibiting p90RSK-1 did not abolish the band shift of MiTF protein, nor did it abolish the UVC-mediated MiTF degradation, suggesting that phosphorylation on serine 73 by Erk1/2 is a key event after UVC. Furthermore, the MiTF-S73A mutant (Serine 73 changed to Alanine via site-directed mutagenesis) was unable to degrade and was continuously expressed after UVC exposure. Compared to A375 melanoma cells expressing wild-type MiTF (MiTF-WT), cells expressing MiTF-S73A mutant showed less p21WAF1/CIP1 accumulation and a delayed p21WAF1/CIP1 recovery after UVC. Consequently, cells expressing MiTF-WT showed a temporary G1 arrest after UVC, but cells expressing MiTF-S73A mutant or lack of MiTF expression did not. Finally, cell lines with high levels of MiTF expression showed higher resistance to UVC-induced cell death than those with low-level MiTF. These data suggest that MiTF mediates a survival signal linking Erk1/2 activation and p21WAF1/CIP1 regulation via phosphorylation on serine 73, which facilitates cell cycle arrest. In addition, our data also showed that exposure to different wavelengths of UV light elicited different signal pathways involving MiTF.
Congress acts to resuscitate nation's financially ailing trauma care systems
Authors: A. A. Sholnick
Journal: JAMA (1992)

CONGRESS may soon come to the rescue of the nation's ailing trauma care systems with a new program of federal grants to help defray uncompensated trauma care costs. The federal assistance is aimed primarily at helping trauma centers provide medical care for undocumented aliens and for victims of drug-related violence. The bill (HR 3698), known as the Community Mental Health and Substance Abuse Services Improvement Act of 1992, passed through the Conference Committee in May. John Liu, a legislative aide for Rep Bill Lowery (R, Calif), says quick approval by Congress and by President Bush is expected. Lowery is a major proponent of the legislation. The dramatic increase in drug-related violence, among other factors, has strained overburdened trauma care systems in many urban areas in the United States and has forced many centers to close. Trauma care for victims of gunshot wounds is extremely expensive and many of these patients
Mammography Screening and Overdiagnosis
Authors: Heidi D. Nelson
Journal: JAMA Oncology (2015)

Breast cancer overdiagnosis, the detection of tumors unlikely to becomeclinically apparent in theabsenceof screening, is an important, but elusive, concept. It is importantbecause thediagnosis and treatment of invasive breast cancer and high-risk noninvasive lesions, particularly ductal carcinoma in situ (DCIS), involve potentially harmful procedures and therapies andhave considerablepsychosocial impacts onwomen. Becausemost diagnoses of high-risk lesions,DCIS,andearly invasivebreastcancer followscreeningmammography, overdiagnosis is clinically relevant tomillions ofwomen undergoing screening in the United States each year. Overdiagnosis is elusive because it is ill-defined and inconsistently measured. Currently, there is no accepted standard definition or method for estimating overdiagnosis, although differences in study characteristics, methods, and measures and how they influence estimates of overdiagnosis arewell recognized.1,2 Most estimates have been derived from screening trials, screening programs and registries, epidemiologic data, or statistical models. Estimates are based on data from patient populations with differing ages and risks for breast cancer, screening and follow-up times, screening practices, and underlying cancer incidence trends. Calculations includevarious combinationsof numerators anddenominators anddiffer in their assumptions about lead time andprogressionof invasivecancer,whetherboth invasivebreastcancerandDCIS are included, andwhether they report relativeor absolute changes. The most commonly used methods determine differences between the incidence of cancer in the presence and in the absence of screening ormake inferences about the lead time or natural history of breast cancer to estimate the frequency of overdiagnosis.1 Studiesofoverdiagnosisprovideestimates that rangefromnonexistent to over 50% of diagnosed cases, reflecting the heterogeJAMA INTERNALMEDICINE
Pleural fluid accumulation due to intra-abdominal endometriosis: a case report and review of the literature.
Authors: K. L. Flanagan, N. C. Barnes
Journal: Thorax (1996)

A case is presented of massive ascites and right sided pleural effusion caused by endometriosis. The final diagnosis was not made for a considerable time. Massive ascites and a right sided pleural effusion caused by endometriosis is rare, with fewer than 10 reports in the literature worldwide. Physicians should be aware of this potentially tentially treatable cause, having excluded other possibilities such as malignancy and tuberculosis.
Anaemia in systemic lupus erythematosus: from pathophysiology to clinical assessment
Authors: S Giannouli
Journal: Annals of the Rheumatic Diseases (2005)

Haematological abnormalities are common in systemic lupus erythematosus. Anaemia is found in about 50% of patients, with anaemia of chronic disease being the most common form. Impaired erythropoietin response and presence of antibodies against erythropoietin may contribute to the pathogenesis of this type of anaemia. Patients with autoimmune haemolytic anaemia usually belong to a distinct category, which is associated with anticardiolipin antibodies, thrombosis, thrombocytopenia, and renal disease, often in the context of secondary antiphospholipid syndrome. Autoantibodies, T lymphocytes, and deregulation of the cytokine network can affect bone marrow erythropoiesis, leading to anaemia.
Acute gall bladder perforation--a dilemma in early diagnosis.
Authors: C L Ong, T H Wong, A Rauff
Journal: Gut (1991)

Gall bladder perforation is a rare complication of cholecystitis. A definitive diagnosis is uncommon before surgery and the morbidity and mortality associated with this condition are high. We report six patients with gall bladder perforation to show the difficulty of making an early diagnosis. The history and the clinical findings of these patients are reviewed to highlight diagnostic pitfalls.
Air pollution hampers teenagers' lung development
Authors: A Khan
Journal: Thorax (2004)

▴ Gauderman WJ, Avol E, Gilliland F, et al . The effect of air pollution on lung development from 10 to 18 years of age. N Engl J Med2004;351:1057–67 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] The Children’s Health Study recruited 1759 children from schools in Southern California and prospectively followed up these children from the age of 10 to 18 years, measuring lung function annually. FVC, FEV1, and maximal mid expiratory flow rate (MMEF) were used as markers … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DGauderman%26rft.auinit1%253DW.%2BJ.%26rft.volume%253D351%26rft.issue%253D11%26rft.spage%253D1057%26rft.epage%253D1067%26rft.atitle%253DThe%2BEffect%2Bof%2BAir%2BPollution%2Bon%2BLung%2BDevelopment%2Bfrom%2B10%2Bto%2B18%2BYears%2Bof%2BAge%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa040610%26rft_id%253Dinfo%253Apmid%252F15356303%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa040610&link_type=DOI [3]: /lookup/external-ref?access_num=15356303&link_type=MED&atom=%2Fthoraxjnl%2F59%2F12%2F1045.atom [4]: /lookup/external-ref?access_num=000223733900005&link_type=ISI
Carcinogenicity of Aflatoxlcol in Fischer 344 Rats2, 3, 4
Authors: J. E. Nixon, J. D. Hendricks, N. E. Pawloswki, P. M. Loveland, R. O. Sinnhuber
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Carcinogenicity of Aflatoxlcol in Fischer 344 Rats, , Get access J. E. Nixon, J. E. Nixon Search for other works by this author on: Oxford Academic PubMed Google Scholar J. D. Hendricks, J. D. Hendricks Search for other works by this author on: Oxford Academic PubMed Google Scholar N. E. Pawloswki, N. E. Pawloswki Search for other works by this author on: Oxford Academic PubMed Google Scholar P. M. Loveland, P. M. Loveland Search for other works by this author on: Oxford Academic PubMed Google Scholar R. O. Sinnhuber R. O. Sinnhuber Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 66, Issue 6, June 1981, Pages 1159–1163, https://doi.org/10.1093/jnci/66.6.1159 Published: 01 June 1981 Article history Received: 12 August 1980 Accepted: 24 November 1980 Published: 01 June 1981
The Effects of Nonpharmacologic Interventions on Blood Pressure of Persons With High Normal Levels
Authors: Paul K. Whelton
Journal: JAMA (1992)

To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure.Randomized control multicenter trials.Volunteers recruited from the community, treated and followed up at special clinics.Of 16,821 screenees, 2182 men and women, aged 30 through 54 years, with diastolic blood pressure from 80 through 89 mm Hg were selected. Of these, 50 did not return for follow-up blood pressure measurements.Three life-style change groups (weight reduction, sodium reduction, and stress management) were each compared with unmasked nonintervention controls over 18 months. Four nutritional supplement groups (calcium, magnesium, potassium, and fish oil) were each compared singly, in double-blind fashion, with placebo controls over 6 months.Primary: change in diastolic blood pressure from baseline to final follow-up, measured by blinded observers. Secondary: changes in systolic blood pressure and intervention compliance measures.Weight reduction intervention produced weight loss of 3.9 kg (P less than .01), diastolic blood pressure change of -2.3 mm Hg (P less than .01), and systolic blood pressure change of -2.9 mm Hg (P less than .01). Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h (P less than .01), diastolic blood pressure by 0.9 mm Hg (P less than .05), and systolic blood pressure by 1.7 mm Hg (P less than .01). Despite good compliance, neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly (P greater than .05).Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons. Sodium reduction is also effective. The long-term effects of weight reduction and sodium reduction, alone and in combination, require further evaluation.
Sports physicians, ethics and antidoping governance: between assistance and negligence
Authors: Nenad Dikic, Michael McNamee, Heinz Günter, Snezana Samardzic Markovic, Bojan Vajgic
Journal: British Journal of Sports Medicine (2013)

Recent positive doping cases and a series of mistakes of medical doctors of the International Federation of Basketball have reopened the debate about the role of medical doctor in elite sport. This study shows that some sports physicians involved in recent positive doping cases are insufficiently aware of the nuances of doping regulations and, most importantly, of the list of prohibited substances. Moreover, several team doctors are shown to have exercised poor judgement in relation to these matters with the consequence that athletes are punished for doping offences on the basis of doctors’ negligence. In such circumstances, athletes’ rights are jeopardised by a failure of the duty of care that (sports) physicians owe their athlete patients. We argue that, with respect to the World Anti Doping Code, antidoping governance fails to define, with sufficient clarity, the role of medical doctors. There is a need for a new approach emphasising urgent educational and training of medical doctors in this domain, which should be considered prior to the revision of the next World Anti Doping Code in 2013 in order to better regulate doctor's conduct especially in relation to professional errors, whether negligent or intentional.
Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env
Authors: Ke-Qin Xin, Yuka Hoshino, Yoshihiko Toda, Shizunobu Igimi, Yoshitsugu Kojima, Nao Jounai, Kenji Ohba, Akira Kushiro, Mayumi Kiwaki, Kenji Hamajima, Dennis Klinman, Kenji Okuda
Journal: Blood (2003)
Myeloproliferative Defects following Targeting of the <i>Drf1</i> Gene Encoding the Mammalian Diaphanous–Related Formin mDia1
Authors: Jun Peng, Susan M. Kitchen, Richard A. West, Robert Sigler, Kathryn M. Eisenmann, Arthur S. Alberts
Journal: Cancer Research (2007)

Abstract Rho GTPase-effector mammalian diaphanous (mDia)–related formins assemble nonbranched actin filaments as part of cellular processes, including cell division, filopodia assembly, and intracellular trafficking. Whereas recent efforts have led to thorough characterization of formins in cytoskeletal remodeling and actin assembly in vitro, little is known about the role of mDia proteins in vivo. To fill this knowledge gap, the Drf1 gene, which encodes the canonical formin mDia1, was targeted by homologous recombination. Upon birth, Drf1+/− and Drf1−/− mice were developmentally and morphologically indistinguishable from their wild-type littermates. However, both Drf1+/− and Drf1−/− developed age-dependent myeloproliferative defects. The phenotype included splenomegaly, fibrotic and hypercellular bone marrow, extramedullary hematopoiesis in both spleen and liver, and the presence of immature myeloid progenitor cells with high nucleus-to-cytoplasm ratios. Analysis of cell surface markers showed an age-dependent increase in the percentage of CD11b+-activated and CD14+-activated monocytes/macrophages in both spleen and bone marrow in Drf1+/− and Drf1−/− animals. Analysis of the erythroid compartment showed a significant increase in the proportion of splenic cells in S phase and an expansion of erythroid precursors (TER-119+ and CD71+) in Drf1-targeted mice. Overall, knocking out mDia1 expression in mice leads to a phenotype similar to human myeloproliferative syndrome (MPS) and myelodysplastic syndromes (MDS). These observations suggest that defective DRF1 expression or mDia1 function may contribute to myeloid malignancies and point to mDia1 as an attractive therapeutic target in MDS and MPS. [Cancer Res 2007;67(16):7565–71]
Chimpanzee, Orangutan, Mouse, and Human Cell Cycle Promoters Exempt CCAAT Boxes and CHR Elements from Interspecies Differences
Authors: G. A. Muller, F. Heissig, K. Engeland
Journal: Molecular Biology and Evolution (2006)

Mechanisms regulating the cell division cycle are well conserved among all eukaryotes. Consistently many proteins regulating the cell cycle are functionally interchangeable between many organisms. Cell division control is regulated on different levels of which the transcriptional level appears to be particularly important for controlling synthesis of many cell cycle proteins. We had earlier described transcription factor–binding sites essential for regulating genes important for the transition from the G2 phase to mitosis. A tandem repressor site named cell cycle–dependent element (CDE) and cell cycle genes homology region (CHR) are responsible for the correct expression during the cell cycle. Another feature of these G2/M-specific promoters is the activation through 2 or 3 CCAAT boxes binding the transcription factor nuclear factor-Y (NF-Y). These major activating sites have to be spaced 32 or 33 bp apart to be fully functional. We were interested in looking at the evolutionary changes in regulatory elements and overall promoter structure of 3 well-characterized cell cycle genes. Here, we compare the DNA sequences and functional features of the cdc25C, cyclin B1, and cyclin B2 promoters from humans, mouse, chimpanzee, and orangutan. We find numerous differences in the nucleotide sequence between mouse and primate promoters. However, CHR and CCAAT boxes stand out in that they are perfectly conserved in all promoters tested. The CDE site contains nucleotide exchanges between mouse and primate promoters. Comparing sequences and functions of chimpanzee, orangutan, and human promoters, we observe a complete conservation in nucleotide sequence of the regulatory elements. Functional assays of the cyclin B1, cyclin B2, and cdc25C promoters yield moderate variations in activity and thereby a good conservation of function. Although we find nucleotide differences in cell cycle promoters between orangutan and humans of about 5%, there are never changes in any of the CCAAT boxes or CDE/CHR sites in the cyclin B1, cyclin B2, and cdc25C promoters. Furthermore, we describe the influence of the tumor suppressor p53 and the transcriptional activator NF-Y on regulation of the newly cloned primate promoters.
Semantic Dysfunction in Women With Schizotypal Personality Disorder
Authors: Margaret A. Niznikiewicz, Martha E. Shenton, Martina Voglmaier, Paul G. Nestor, Chandlee C. Dickey, Melissa Frumin, Larry J. Seidman, Christopher G. Allen, Robert W. McCarley
Journal: American Journal of Psychiatry (2002)

This study examined whether early or late processes in semantic networks were abnormal in women with a diagnosis of schizotypal personality disorder. The N400 component of the EEG event-related potentials was used as a probe of semantic processes.Word pairs were presented with short and long stimulus-onset asynchronies to investigate, respectively, early and late semantic processes in 16 women with schizotypal personality disorder and 15 normal female comparison subjects. Event-related potentials were recorded in response to the last words in a pair.With the short stimulus-onset asynchrony, the N400 amplitude was less negative in the schizotypal personality disorder group than in the normal comparison group. No group differences were found with the long stimulus-onset asynchrony.The finding of a less negative than normal N400 amplitude with the short stimulus-onset asynchrony in women with schizotypal personality disorder supports the hypothesis that persons with this disorder evince an overactivation of semantic networks. The absence of group differences with the long stimulus-onset asynchrony, which is primarily sensitive to processes involved in context integration, suggests that in this group of schizotypal personality disorder subjects, additional demands on working memory may be necessary to bring out the semantic dysfunction.
Genetic alterations in hereditary breast cancer
Authors: G. Cipollini, S. Tommasi, A. Paradiso, P. Aretini, F. Bonatti, I. Brunetti, M. Bruno, G. Lombardi, F. Schittulli, E. Sensi, M. Tancredi, G. Bevilacqua, M.A. Caligo
Journal: Annals of Oncology (2004)
Specific inhibition by prostaglandins E2 and I2 of histamine-stimulated [14C]aminopyrine accumulation and cyclic adenosine monophosphate generation by isolated canine parietal cells.
Authors: A H Soll
Journal: Journal of Clinical Investigation (1980)

The effects of prostaglandins E2 and I2 on accumulation of [14C]aminopyrine and the generation of cyclic AMP by fractions of dispersed canine gastric mucosal cells, enriched in their content of parietal cells, have been studied. The parietal cell content of the fractions was enriched to between 43 and 70% using an elutriator rotor. The accumulation of [14C]aminopyrine was used as the index of parietal cell response to stimulation. Prostaglandin E2 (PGE2, 0.1 nM-0.1 mM) inhibited histamine stimulated aminopyrine uptake but did not block the response to carbachol, gastrin, or dibuturyl cyclic AMP. PGE2 did, however, inhibit aminopyrine uptake stimulated by carbachol and gastrin when the response to these agents was potentiated by histamine. PGE2 (0.1 NM-0.1 mM) inhibited histamine-stimulated cyclic AMP production in a dose-dependent fashion with maximal inhibition at 1 microM PGE2. Prostacyclin also inhibited both histamine-stimulated aminopyrine accumulation and histamine-stimulated cyclic AMP production. In the absence of added histamine, PGE2 in concentrations above 1 microM and prostacyclin in concentrations above 10 microM stimulated cyclic AMP production, probably by acting on the nonparietal cells as shown in previous studies. These present data are consistent with the hypothesis that prostaglandins E2 and I2 inhibit the response of isolated parietal cells to histamine by specifically blocking histamine-stimulated cyclic AMP production.
Plant mating systems in a changing world
Authors: Christopher G. Eckert, Susan Kalisz, Monica A. Geber, Risa Sargent, Elizabeth Elle, Pierre-Olivier Cheptou, Carol Goodwillie, Mark O. Johnston, John K. Kelly, David A. Moeller, Emmanuelle Porcher, Richard H. Ree, Mario Vallejo-Marín, Alice A. Winn
Journal: Trends in Ecology & Evolution (2009)