tbuckley/cabot-search huggingface dataset:
Decreases in Ovarian Cytochrome P450c17α Activity and Serum Free Testosterone after Reduction of Insulin Secretion in Polycystic Ovary Syndrome
Authors: John E. Nestler, Daniela J. Jakubowicz
Journal: New England Journal of Medicine (1996)

Insulin resistance and increased ovarian cytochrome P450c17α activity are both features of the polycystic ovary syndrome. P450c17α, which is involved in androgen biosynthesis, has both 17α-hydroxylase and 17,20-lyase activities. Increased activity of this enzyme results in exaggerated conversion of progesterone to 17α-hydroxyprogesterone in response to stimulation by gonadotropin. We hypothesized that hyperinsulinemia stimulates ovarian P450c17α activity.
Elevation of Plasminogen Activator Inhibitor-1 Levels in Sputum and Nasal Lavage Fluids of Asthmatics with Common Colds
Authors: Seong Ho Cho, Seung Hong, Haimei Chen, Ali Habib, David Cho, Il Kim, Sun Hye Lee, Homer A. Boushey, Theresa Ward, Robert P. Schleimer, Pedro C. Avila
Journal: Journal of Allergy and Clinical Immunology (2013)
A Selective Phosphatase of Regenerating Liver Phosphatase Inhibitor Suppresses Tumor Cell Anchorage-Independent Growth by a Novel Mechanism Involving p130Cas Cleavage
Authors: Sherif Daouti, Wen-hui Li, Hong Qian, Kuo-Sen Huang, Janna Holmgren, Wayne Levin, Linda Reik, Debra Lucas McGady, Paul Gillespie, Agostino Perrotta, Hongjin Bian, John F. Reidhaar-Olson, Sarah A. Bliss, Andree R. Olivier, Joseph A. Sergi, David Fry, Waleed Danho, Steve Ritland, Nader Fotouhi, David Heimbrook, Huifeng Niu
Journal: Cancer Research (2008)

Abstract The phosphatase of regenerating liver (PRL) family, a unique class of oncogenic phosphatases, consists of three members: PRL-1, PRL-2, and PRL-3. Aberrant overexpression of PRL-3 has been found in multiple solid tumor types. Ectopic expression of PRLs in cells induces transformation, increases mobility and invasiveness, and forms experimental metastases in mice. We have now shown that small interfering RNA–mediated depletion of PRL expression in cancer cells results in the down-regulation of p130Cas phosphorylation and expression and prevents tumor cell anchorage-independent growth in soft agar. We have also identified a small molecule, 7-amino-2-phenyl-5H-thieno[3,2-c]pyridin-4-one (thienopyridone), which potently and selectively inhibits all three PRLs but not other phosphatases in vitro. The thienopyridone showed significant inhibition of tumor cell anchorage-independent growth in soft agar, induction of the p130Cas cleavage, and anoikis, a type of apoptosis that can be induced by anticancer agents via disruption of cell-matrix interaction. Unlike etoposide, thienopyridone-induced p130Cas cleavage and apoptosis were not associated with increased levels of p53 and phospho-p53 (Ser15), a hallmark of genotoxic drug-induced p53 pathway activation. This is the first report of a potent selective PRL inhibitor that suppresses tumor cell three-dimensional growth by a novel mechanism involving p130Cas cleavage. This study reveals a new insight into the role of PRL-3 in priming tumor progression and shows that PRL may represent an attractive target for therapeutic intervention in cancer. [Cancer Res 2008;68(4):1162–9]
S106 Review Of European Copd Audit Data: Factors Affecting Length Of Stay
Authors: M. Ruparel, J. Lopez-Campos, F. Pozo-Rodriguez, A. Castro-Acosta, S. Hartl, C. Roberts
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> The major cost to health services of COPD care is hospital admission for exacerbation. Reducing length of stay (LOS) will reduce cost, yet there is wide variability across patients and hospitals. We test the hypothesis that these variations may be attributed to either patient characteristics, hospital characteristics and/or the so-called hospital-clustering effect, which indicates that patients with similar characteristics may experience different processes of care and outcomes depending on the hospital to which they are admitted. <h3>Methods</h3> The European COPD Audit which was carried out in 432 hospitals from 13 countries, included data from 16,018 patients admitted over an 8 week period. The recorded variables included information on the patient and disease characteristics, resources available and clinical practice. Variables in each category associated with LOS were evaluated by a multivariate multilevel analysis and expressed as odds ratios (OR). <h3>Results</h3> Mean LOS was 8.7 days (median: 7, standard deviation: 8.3, interquartile range: 4–11). Factors associated with an LOS higher than the median (see figure) were clinical with the highest impact in patients with use of mechanical ventilation (OR: 4.74) and higher oxygen flows (OR 2.63). In-hospital treatments, comorbidities and patient-related variables including GOLD class IV (OR 1.77) were also significant. These relationships were maintained with respect to longer LOS (&gt; 21 days). Neither the day of admission, nor any of the resource variables were associated with significant differences in LOS. The crude variability of LOS between the different countries was reduced after accounting for these clinical factors and the clustering effect. <h3>Conclusions</h3> This study demonstrates a noteworthy reduction in the observed crude inter-hospital variation in LOS after accounting for the hospital-cluster effect and patient related variables. This emphasises the predictor importance of the patients’ clinical conditions and interventions, and understates the impacts of hospital resources and organisational factors. This “real-life” reflection may highlight some valid learning points that may help us to determine which achievable strategies are most relevant to improve outcomes.
Predictors of Relapse and Treatment Resistance in Antineutrophil Cytoplasmic Antibody–Associated Small-Vessel Vasculitis
Authors: Susan L. Hogan, Ronald J. Falk, Hyunsook Chin, Jianwen Cai, Caroline E. Jennette, J. Charles Jennette, Patrick H. Nachman
Journal: Annals of Internal Medicine (2005)

Predictors of treatment resistance and relapse have not been well described in antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis.To identify clinical, pathologic, and serologic predictors of treatment resistance and relapse in a community-based cohort of patients with ANCA-associated vasculitis.Cohort of patients identified at or near the time of biopsy diagnosis and followed as clinically indicated.The Glomerular Disease Collaborative Network.350 patients who received a new diagnosis of ANCA-associated vasculitis between 1985 and 2003 and were followed for a median of 49 months.Patients were categorized according to whether they had antiproteinase-3 (anti-PR3) antibodies or antimyeloperoxidase (anti-MPO) antibodies. Organ involvement was determined by biopsy or by well-defined clinical criteria. Treatment resistance was defined as progressive decline in kidney function with active urine sediment or the persistence or appearance of extrarenal manifestations. Relapse was defined as the time to the resurgence of vasculitic symptoms.Treatment resistance affected 23% of 334 treated patients and was associated with female sex, black ethnicity, and presentation with severe kidney disease (odds ratio per serum creatinine elevation of 100 micromol/L [1.13 mg/dL], 1.28 [95% CI, 1.16 to 1.39]). The following factors were associated with relapse in 258 (77%) patients who attained remission: seropositivity for anti-PR3 antibodies (hazard ratio, 1.87 [CI, 1.11 to 3.14]) and disease of the lung (hazard ratio, 1.71 [CI, 1.04 to 2.81]) or upper respiratory tract (hazard ratio, 1.73 [CI, 1.04 to 2.88]). Relapses occurred in 26% of patients with no risk factors versus 73% of patients with all 3 risk factors (hazard ratio, 3.7 [CI, 1.4 to 9.7]). Among 143 patients attaining remission who subsequently stopped all immunosuppressant therapy, relapse rates were similar for those who had received cyclophosphamide therapy for 6 months or less (34%) compared with those treated for a longer duration (35%), even after adjusting for risk factors for relapse (hazard ratio, 1.41 [CI, 0.80 to 2.50]).The cohort mostly included patients with biopsy-proven kidney disease. Patients were not followed with uniform treatment protocols, and only limited information about their clinical course before diagnosis was available.Female or black patients, or those with severe kidney disease, may be resistant to initial treatment more often than other patients with ANCA-associated small-vessel vasculitis. Increased risk for relapse appears to be related to the presence of lung or upper airway disease and anti-PR3 antibody seropositivity.
Organ-focused mutual information for nonrigid multimodal registration of liver CT and Gd–EOB–DTPA-enhanced MRI
Authors: Laura Fernandez-de-Manuel, Gert Wollny, Jan Kybic, Daniel Jimenez-Carretero, Jose M. Tellado, Enrique Ramon, Manuel Desco, Andres Santos, Javier Pascau, Maria J. Ledesma-Carbayo
Journal: Medical Image Analysis (2013)
Premenstrual syndrome: an ancient woe deserving of modern scrutiny
Authors: E. R. Gonzalez
Journal: JAMA (1981)

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
Generalized verrucosis in a patient with<i>GATA2</i>deficiency
Authors: E.S. West, M.Y. Kingsbery, E.M. Mintz, A.P. Hsu, S.M. Holland, P.L. Rady, S.K. Tyring, M.E. Grossman
Journal: British Journal of Dermatology (2013)

Generalized verrucosis is a characteristic of several genetic and immunodeficiency disorders including epidermodysplasia verruciformis; warts, hypogammaglobulinaemia, infections and myelokathexis (WHIM) syndrome; warts, immunodeficiency, lymphoedema and anogenital dysplasia (WILD) syndrome; severe combined immune deficiency and HIV, among others. In recent years, it has been consistently recognized in patients with GATA2 deficiency, a novel immunodeficiency syndrome characterized by monocytopenia, B-cell and natural killer-cell lymphopenia, and a tendency to develop myeloid leukaemias and disseminated mycobacterial, human papillomavirus (HPV) and opportunistic fungal infections. Mutations in GATA2 cause haploinsufficiency and track in families as an autosomal dominant immunodeficiency. GATA2 is a transcription factor involved in early haematopoietic differentiation and lymphatic and vascular development. We describe a case of generalized verrucosis with HPV type 57 presenting in a young man with GATA2 deficiency. GATA2 deficiency is a novel dominant immunodeficiency that is often recognized later in life and should be considered in the differential diagnosis of patients with generalized verrucosis.
Analysis of the expression pattern of the latent transforming growth factor ? binding protein isoforms in normal and diseased human liver reveals a new splice variant missing the proteinase-sensitive hinge region
Authors: Kristin Michel, Sylke Roth, Christian Trautwein, WenRong Gong, P. Flemming, Axel M. Gressner
Journal: Hepatology (1998)

Latent transforming growth factor beta binding protein (LTBP), a component of the extracellular matrix (ECM) of various tissues, is important for the secretion of TGF-beta and, furthermore, for the storage of TGF-beta in ECM. The proteolytic cleavage of LTBP is assumed to be the prerequisite for the activation of TGF-beta. We investigated the mRNA expression pattern of the three LTBP isoforms (LTBP-1, -2, -3) and the protein distribution of the components of the large latent TGF-beta complex, namely LTBP-1 and -2, latency-associated protein (LAP), and TGF-beta, in human liver using reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemical alkaline phosphatase anti-alkaline phosphatase (APAAP) staining. Parts of explanted livers diagnosed as hepatitis B, hepatitis C, primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC) and normal liver tissue were examined. LTBP transcripts were detected in the same manner in all liver specimens. Interestingly, we found a new splice variant of LTBP-1 (LTBP-1D), in which the sequence coding for the proteinase-sensitive hinge region is deleted. The corresponding parts of the human LTBP-2 and LTBP-3 cDNA coding for the hinge region were sequenced and show neither similar proteinase cleavage sites nor deleted cDNA sequences. The proposed proteinase cleavage site of mouse LTBP-3 seems not to be conserved in the human LTBP-3 gene. By immunohistochemistry, LTBP-1, -2, and LAP were detectable in normal and diseased livers and showed a different staining pattern for both LTBP isoforms. By contrast, TGF-beta showed a spotted staining pattern in diseased livers only, predominantly in the area of parenchymal cells that are close to fibrotic tissue. This strongly suggests the release of active TGF-beta from preexisting latent complexes. The LTBP-1D splice variant, which is probably less sensitive against proteolytic degradation and therefore may protect TGF-beta from activation, may have importance for modulating the biological activity of TGF-beta in normal and diseased liver.
Make social care free at end of life to help more people die at home, say MPs
Authors: Z. Kmietowicz
Journal: BMJ (2015)

All people in England who are at the end of their life should be entitled to free social care to allow more of them to die at home with the appropriate support, MPs have recommended.

Means testing for social care should be phased out for people who have been recognised as being in the last days, weeks, or months of their life, said a report from the cross party House of Commons Health Committee into how end of life care has progressed since the independent review of the Liverpool care pathway, chaired by Julia Neuberger in 2013.1

Speaking to journalists ahead of the report’s publication Sarah Wollaston, a former GP who is the Conservative MP for Totnes and chair of the committee, said that wrangling over how social care is funded kept many people in …
A SEARCH FOR THE PRESENCE OF PATHOGENIC BACTERIA AND FUNGI IN THE INTERDIGITAL SPACES OF THE FOOT.
Authors: MARY J. MARPLES, MARGARET J. BAILEY
Journal: British Journal of Dermatology (1957)

Journal Article A SEARCH FOR THE PRESENCE OF PATHOGENIC BACTERIA AND FUNGI IN THE INTERDIGITAL SPACES OF THE FOOT. Get access MARY J. MARPLES, MARY J. MARPLES Department of Microbiology, University of Otago, New Zealand Search for other works by this author on: Oxford Academic Google Scholar MARGARET J. BAILEY MARGARET J. BAILEY Department of Microbiology, University of Otago, New Zealand Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 69, Issue 11, 1 November 1957, Pages 379–388, https://doi.org/10.1111/j.1365-2133.1957.tb13778.x Published: 01 November 1957
In vivo effects of chromium.
Authors: C Witmer, E Faria, H S Park, N Sadrieh, E Yurkow, S O'Connell, A Sirak, H Schleyer
Journal: Environmental Health Perspectives (1994)

The production of reactive oxygen species on addition of hexavalent chromium (potassium dichromate, K2Cr2O7) to lung cells in culture was studied using flow cytometer analysis. A Coulter Epics Profile II flow cytometer was used to detect the formation of reactive oxygen species after K2Cr2O7 was added to A549 cells grown to confluence. The cells were loaded with the dye, 2',7'-dichlorofluorescein diacetate, after which cellular esterases removed the acetate groups and the dye was trapped intracellularly. Reactive oxygen species oxidized the dye, with resultant fluorescence. Increased doses of Cr(VI) caused increasing fluorescence (10-fold higher than background at 200 microM). Addition of Cr(III) compounds, as the picolinate or chloride, caused no increased fluorescence. Electron paramagnetic resonance (EPR) spectroscopic studies indicated that three (as yet unidentified) spectral "signals" of the free radical type were formed on addition of 20, 50, 100, and 200 microM Cr(VI) to the A549 cells in suspension. Two other EPR "signals" with the characteristics of Cr(V) entities were seen at field values lower than the standard free radical value. Liver microsomes from male Sprague-Dawley rats treated intraperitoneally with K2Cr2O7 (130 mumole/kg every 48 hr for six treatments) had decreased activity of cytochromes P4503A1 and/or 3A2, and 2C11. Hepatic microsomes from treated female Sprague-Dawley rats, in contrast, had increased activities of these isozymes. Lung microsomes from male Sprague-Dawley rats had increased activity of P4502C11.
Hexafluoro-1,25-dihydroxyvitamin D<sub>3</sub>has markedly increased potency in inhibiting proliferation of cultured human keratinocytes compared with 1,25-dihydroxyvitamin D<sub>3</sub>
Authors: T.C. Chen, M.F. Holick
Journal: British Journal of Dermatology (2000)

Background Although topical 1,25-dihydroxyvitamin D3 (calcitriol, 1,25(OH)2D3) and its analogues, calcipotriol and tacalcitol, are effective for patients with psoriasis, some patients show little or no response. There is a need to develop more potent analogues of 1,25(OH)2D3. Hexafluoro-1,25(OH)2D3 (F6-1,25(OH)2D3) is at least 10 times more potent than 1,25(OH)2D3 on calcium metabolism. Objectives We were interested in whether F6-1,25(OH)2D3 was also more potent than 1,25(OH)2D3 in inhibiting normal human and psoriatic keratinocyte proliferation. Methods The antiproliferative activity of F6-1,25(OH)2D3 and 1,25(OH)2D3 was determined by 3H-thymidine incorporation into keratinocyte DNA and by counting basal cells. Results F6-1,25(OH)2D3 was approximately 10-fold more active and had a longer lasting antiproliferative effect than 1,25(OH)2D3 on normal human keratinocytes, and was about 100-fold more potent than 1,25(OH)2D3 on human psoriatic keratinocytes as determined by 3H-thymidine incorporation. F6-1,25(OH)2D3 also caused a dose-dependent decrease in the number of basal cells and was 100-fold more active than 1,25(OH)2D3. Conclusions The increased potency and the long-lasting effects of F6-1,25(OH)2D3 suggest that F6-1,25(OH)2D3 may be a potent candidate agent for treating psoriasis.
MAJOR THROMBOCYTOPENIA AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Hasan Jilaihawi, Niraj Doctor, Tarun Chakravarty, Omar R. Sadruddin, Mohammad Kashif, Wen Cheng, Mamoo Nakamura, Jasminka Stegic, Tracy Salseth, Mitch Gheorghiu, Raj Makkar
Journal: Journal of the American College of Cardiology (2013)
Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix
Authors: Barbara Carnemolla, Laura Borsi, Enrica Balza, Patrizia Castellani, Raffaella Meazza, Alexander Berndt, Silvano Ferrini, Hartwig Kosmehl, Dario Neri, Luciano Zardi
Journal: Blood (2002)
When I use a word: Patient centred verbs
Authors: J. Aronson
Journal: BMJ (2002)

It is not surprising, in these patient centred days, that some verbs that refer to inanimate objects associated with the patient, are used to refer to the patient instead. I have come across the following uses:

However, it was not the patient but the disease that was diagnosed, the seriousness that was explained, the chemotherapy that was prescribed, and the vincristine that was administered.

The problem lies in the misuse of the construction known as the indirect passive. Verbs can be either transitive or intransitive—a transitive verb governs an object, whereas an intransitive verb does not. Now some transitive verbs have the luxury …
Community care. I: Problems.
Authors: E Murphy
Journal: BMJ (1987)

7 Immelman K. Role of the environment in reproduction as source of predictive information. In: Farner DS, ed. Breeding biology of birds. Washington DC: National Academy of Sciences, 1973:121-47. 8 Hoffman K. Photoperiodism in vertebrates. In: Aschoff J, ed. Handbook of behavioural neurobiology. New York: Plenum Press, 1981:449-73. 9 Moore RY. The innervation of the mammalian pineal gland. In: Reiter RJ, ed. The pineal gland and reproduction. Basel: Karger, 1978:1-29. 10 Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Markey SP. Light suppresses melatonin secretion in humans. Science 1980?10:1267-9. 11 Hastings MH, Herbert J, Martensz ND, Roberts AC. Melatonin and the brain in photoperiodic mammals. In: Evered D, Clark D, eds. Photoperiodism, melatonin and the pineal. London: Pitman, 1985:57-77. 12 Wehr TA, Jacobson FM, Sack DA, Arendt J, Tamarkin L, Rosenthal NE. Phototherapy of seasonal affective disorder. Arch Gen Psychiatry 1986;43:870-5. 13 Murphy D, Abas M, Checkley SA. Sensitivity to light in seasonal affective disorder. In: Thompson C, Silverstone T, eds. Seasonal affective disorder. London: CNS Neurosciences (in press). 14 Winton F, Corn T, Huson LW, Franey C, Arendt J, Checkley SA. Effects of light treatment upon mood and melatonin in patients with seasonal affective disorder. In: Thompson C, Silverstone T, eds. Seasonal affective disorder. London: CNS Neurosciences (in press).
Significance of prostaglandin E2 in acute necrotising pancreatitis in rats.
Authors: B van Ooijen, W J Kort, C J Tinga, J H Wilson, D L Westbroek
Journal: Gut (1989)

Acute necrotising pancreatitis in rats was induced by injecting 5% sodium taurocholate into the pancreatic duct. Prostaglandin E2 (100 micrograms/kg subcutaneously twice) decreased the mortality rate from 100% to 60% (NS). When treatment with prostaglandin E2 was combined with simultaneous administration of either dazmegrel (UK 38,485, 50 mg/kg bodyweight) or Sibelium (Flunarizine R 14,950, 0.2 mg/kg body weight) a significant decrease in the mortality rate (p less than 0.05) was recorded. Dazmegrel is a selective thromboxane A2 synthetase inhibitor and prevents the formation of thromboxane A2. Flunarizine (a calcium entry blocker) decreases thromboxane A2 formation and also inhibits the effects of raised thromboxane A2 concentrations. As plasma thromboxane B2 (the stable metabolite of thromboxane A2) concentrations increase and the plasma prostaglandin E2 concentrations decrease in acute necrotising pancreatitis in rats, the results of the present study indicate that these prostaglandins play a role in the pathophysiology of the disease. It is suggested that restoration of the balance in prostanoid concentrations will have a beneficial effect on the course of acute necrotising pancreatitis.