tbuckley/cabot-search huggingface dataset:
Coal mining and chronic obstructive pulmonary disease: a review of the evidence
Authors: D. Coggon, A. N. Taylor
Journal: Thorax (1998)

The potential of coal mine dust to cause disabling pneumoconiosis has long been recognised, but research now suggests that pneumoconiosis is not the only respiratory hazard of coal mining. Over the last 30 years evidence has accumulated that miners also experience an excess of chronic obstructive pulmonary disease (COPD), and this has led the British Government to classify chronic bronchitis and emphysema in coal miners as an occupational disease for which industrial injuries benefit can be paid. In Germany, too, COPD in miners is now compensated as an occupational disease. However, some scientists have expressed doubts as to whether coal mine dust can cause clinically important loss of lung function in the absence of complicated pneumoconiosis.1 In view of this continuing controversy, it is helpful to review the evidence as it now stands.

The epidemiological investigations that bear on the relation between coal mining and COPD are of four main types: (1) studies comparing lung function in miners and non-miners; (2) studies of the patterns of symptoms and lung function in miners according to their exposure to coal mine dust; (3) analyses of mortality from COPD in relation to coal mining; and (4) analyses of the relation between emphysema in coal miners at necropsy and their previous exposure to dust. In addition, investigations in the laboratory provide information about the toxicological mechanisms whereby coal mine dust might cause obstructive lung disease.

A series of early studies by the MRC Pneumoconiosis Research Unit in South Wales found significantly lower mean levels of indirect maximum breathing capacity (IMBC) in miners and ex-miners than in non-miners of the same age.2 However, there was no clear relation between IMBC and duration of underground or face work. Moreover, in a sample of men who were examined at two surveys five years apart, the …
Treatment of Type 2 Diabetes in Youth
Authors: Amanda Flint, Silva Arslanian
Journal: Diabetes Care (2011)

Type 2 diabetes is becoming more common among youth, in parallel with the increasing prevalence of obesity in pediatrics. Despite this, therapeutic modalities remain extremely limited, with scanty data regarding appropriate treatment, desired glycemic targets, and management of associated comorbidities and complications. Management of type 2 diabetes in youth, both acute and long term, should occur in specialty tertiary care pediatric centers. Health care providers should address the pathophysiological components of insulin resistance and decline in β-cell function, aiming to preserve the latter while improving the former. Addressing comorbidities, namely hypertension and dyslipidemia, which are currently inadequately addressed, should be properly assessed and tracked. Further research is critical to establish treatment goals and develop effective diabetes management strategies that will not only enhance adherence to treatment recommendations, but also effectively manage comorbidities and prevent micro- and macrovascular complications.

With the escalating rates of obesity, type 2 diabetes is increasing (1,2), not only in adults but also in youth. In the SEARCH for Diabetes in Youth study, it is estimated that the number of adolescents per year diagnosed with type 2 diabetes is ~3,700 and increasing (2,3). Despite this, there is a dearth of approved therapeutic options.

The UK Prospective Diabetes Study showed that intensive glucose therapy for adults with newly diagnosed type 2 diabetes was associated with a decreased risk of microvascular complications and, among individuals who were >120% above their ideal body weight, with a decreased risk of myocardial infarction and death from any cause (4). In patients diagnosed with type 2 diabetes at a younger age, there may be more aggressive development of diabetes complications, including myocardial infarction and microalbuminuria (5). Given these considerations, it is critical to have treatment options for adolescents with type 2 diabetes that optimize diabetes control and reduce complications. …
Recurrence-free survival after sentinel node biopsy in melanoma?
Authors: A.J. Hayes, J.M. Thomas
Journal: British Journal of Dermatology (2006)

Journal Article Recurrence‐free survival after sentinel node biopsy in melanoma? Get access A.J. Hayes, A.J. Hayes Sarcoma and Melanoma Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, U.K. E‐mail: andrew.hayes@rmh.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar J.M. Thomas J.M. Thomas Sarcoma and Melanoma Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, U.K. E‐mail: andrew.hayes@rmh.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 3, 1 September 2006, Pages 631–632, https://doi.org/10.1111/j.1365-2133.2006.07373.x Published: 01 September 2006
Depictions of substance use in reality television: a content analysis of <i>The Osbournes</i>
Authors: Nicole A Blair, So Kuen Yue, Ranbir Singh, Jay M Bernhardt
Journal: BMJ (2005)

To determine the source and slant of messages in a reality television programme that may promote or inhibit health related or risky behaviours.Coding visual and verbal references to alcohol, tobacco, and other drug (ATOD) use in The Osbournes.Three reviewers watched all 10 episodes of the first season and coded incidents of substance use according to the substance used (alcohol, tobacco, or drugs), the way use was portrayed (visually or verbally), the source of the message (the character in the show involved in the incident), and the slant of the incident (endorsement or rejection).The variation in number of messages in an average episode, the slant of messages, and message source.The average number of messages per episode was 9.1 (range 2-17). Most drug use messages (15, 54%) implied rejection of drugs, but most alcohol messages (30, 64%) and tobacco messages (12, 75%) implied endorsements for using these substances. Most rejections (34, 94%) were conveyed verbally, but most endorsements (36, 65%) were conveyed visually. Messages varied in frequency and slant by source.The reality television show analysed in this study contains numerous messages on substance use that imply both rejection and endorsement of use. The juxtaposition of verbal rejection messages and visual endorsement messages, and the depiction of contradictory messages about substance use from show characters, may send mixed messages to viewers about substance use.
ACTION OF ANTIGEN ON FIBROBLASTS IN VITRO
Authors: Albert Fischer
Journal: The Journal of Experimental Medicine (1922)

The action of human ascitic fluid and of dog serum on the immunization of fibroblasts in vitro was investigated. The toxic effect of ascitic fluid upon fibroblasts was slight, while that of dog serum was marked. When a small amount of antigen (1.5 to 2 per cent dog serum, or 8 per cent ascitic fluid) was present in the medium, the resistance of the fibroblasts slowly increased, reached its maximum after about 14 days, and gradually decreased. The curve expressing the phenomena closely resembles that of Jörgensen and Madsen showing the production of antibodies in an animal which received daily injections of antigen. When the antigen was present in the medium in a high concentration (from 5 to 8 per cent dog serum), the resistance reached its maximum in 4 days, and decreased rapidly. It may be concluded that: 1. In the immunization of fibroblasts in vitro against a foreign protein, there is a relation between the amount of antigen, the time of the appearance of immunization, and its duration. 2. When a small amount of antigen is used, immunization slowly reaches its maximum, and slowly decreases. 3. When a large amount of antigen is used, immunization reaches its maximum in a short time, but the protection is of equally short duration.
Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy
Authors: W.P. Sheridan, R.M. Fox, C.G. Begley, D. Maher, K.M. McGrath, C.G. Begley, C.A. Juttner, L.Bik To, J. Szer, G. Mostyn
Journal: The Lancet (1992)
Real-time cardiovascular data-sampling
Authors: B. T. WINCHESTER
Journal: Cardiovascular Research (1972)

A method for real-time partitioning of the cardiac cycle into N equal duration intervals was devised to facilitate digital sampling for computer analysis of cardiovascular data. The particular application is in dividing the cardiac cycle into radix-two intervals in order to apply the 'Fast Fourier Transform' algorithm of Cooley and Tukey (1965) to the data.
Mast Cells Mediate Acute Kidney Injury through the Production of TNF
Authors: Shaun A. Summers, Jacky Chan, Poh-Yi Gan, Lakshi Dewage, Yuji Nozaki, Oliver M. Steinmetz, David J. Nikolic-Paterson, A. Richard Kitching, Stephen R. Holdsworth
Journal: Journal of the American Society of Nephrology (2011)

Leukocyte recruitment contributes to acute kidney injury (AKI), but the mechanisms by which leukocytes promote injury are not completely understood. The degranulation of mast cells releases inflammatory molecules, including TNF, but whether these cells participate in the pathogenesis of AKI is unknown. Here, we induced AKI with cisplatin in mast cell-deficient and wild-type mice. Compared with wild-type mice, deficiency of mast cells attenuated renal injury, reduced serum levels of TNF, and reduced recruitment of leukocytes to the inflamed kidney. Mast cell-deficient mice also exhibited significantly lower intrarenal expression of leukocyte chemoattractants. Mast cell-deficient mice reconstituted with mast cells from wild-type mice exhibited similar cisplastin-induced renal damage and serum levels of TNF as wild-type mice. In contrast, mast cell-deficient mice reconstituted with mast cells from TNF-deficient mice continued to demonstrate significant attenuation of cisplatin-induced renal injury. Furthermore, the mast-cell stabilizer sodium chromoglycate also significantly abrogated renal injury in this model of AKI. Taken together, these results suggest that mast cells mediate AKI through the production of TNF.
Syndecan-4 Knockout Leads to Reduced Extracellular Transglutaminase-2 and Protects against Tubulointerstitial Fibrosis
Authors: Alessandra Scarpellini, Linghong Huang, Izhar Burhan, Nina Schroeder, Muriel Funck, Timothy S Johnson, Elisabetta A M Verderio
Journal: Journal of the American Society of Nephrology (2013)

Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. The interaction of TG2 with the heparan sulfate proteoglycan syndecan-4 (Sdc4) regulates the cell surface trafficking, localization, and activity of TG2 in vitro but remains unstudied in vivo. We tested the hypothesis that Sdc4 is required for cell surface targeting of TG2 and the development of kidney fibrosis in CKD. Wild-type and Sdc4-null mice were subjected to unilateral ureteric obstruction and aristolochic acid nephropathy (AAN) as experimental models of kidney fibrosis. Analysis of renal scarring by Masson trichrome staining, kidney hydroxyproline levels, and collagen immunofluorescence demonstrated progressive fibrosis associated with increases in extracellular TG2 and TG activity in the tubulointerstitium in both models. Knockout of Sdc-4 reduced these effects and prevented AAN-induced increases in total and active TGF-β1. In wild-type mice subjected to AAN, extracellular TG2 colocalized with Sdc4 in the tubular interstitium and basement membrane, where TG2 also colocalized with heparan sulfate chains. Heparitinase I, which selectively cleaves heparan sulfate, completely abolished extracellular TG2 in normal and diseased kidney sections. In conclusion, the lack of Sdc4 heparan sulfate chains in the kidneys of Sdc4-null mice abrogates injury-induced externalization of TG2, thereby preventing profibrotic crosslinking of extracellular matrix and recruitment of large latent TGF-β1. This finding suggests that targeting the TG2-Sdc4 interaction may provide a specific interventional strategy for the treatment of CKD.
HIPK2 modulates p53 activity towards pro-apoptotic transcription
Authors: Rosa Puca, Lavinia Nardinocchi, Ada Sacchi, Gideon Rechavi, David Givol, Gabriella D'Orazi
Journal: Molecular Cancer (2009)

Abstract Background Activation of p53-mediated gene transcription is a critical cellular response to DNA damage and involves a phosphorylation-acetylation cascade of p53. The discovery of differences in the response to different agents raises the question whether some of the p53 oncosuppressor functions might be exerted by different posttranslational modifications. Stress-induced homeodomain-interacting protein kinase-2 (HIPK2) phosphorylates p53 at serine-46 (Ser46) for p53 apoptotic activity; p53 acetylation at different C-terminus lysines including p300-mediated lysine-382 (Lys382) is also required for full activation of p53 transcriptional activity. The purpose of the current study was to evaluate the interplay among HIPK2, p300, and p53 in p53 acetylation and apoptotic transcriptional activity in response to drug by using siRNA interference, p300 overexpression or deacetylase inhibitors, in cancer cells. Results Knockdown of HIPK2 inhibited both adriamycin-induced Ser46 phosphorylation and Lys382 acetylation in p53 protein; however, while combination of ADR and zinc restored Ser46 phosphorylation it did not recover Lys382 acetylation. Chromatin immunoprecipitation studies showed that HIPK2 was required in vivo for efficient p300/p53 co-recruitment onto apoptotic promoters and that both p53 modifications at Ser46 and Lys382 were necessary for p53 apoptotic transcription. Thus, p53Lys382 acetylation in HIPK2 knockdown as well as p53 apoptotic activity in response to drug could be rescued by p300 overexpression. Similar effect was obtained with the Sirt1-inhibitor nicotinamide. Interestingly trichostatin A (TSA), the inhibitor of histone deacetylase complexes (HDAC) did not have effect, suggesting that Sirt1 was the deacetylase involved in p53 deacetylation in HIPK2 knockdown. Conclusion These results reveal a novel role for HIPK2 in activating p53 apoptotic transcription. Our results indicate that HIPK2 may regulate the balance between p53 acetylation and deacetylation, by stimulating on one hand co-recruitment of p300 and p53Lys382 on apoptotic promoters and on the other hand by inhibiting Sirt1 deacetylase activity. We attempted to reactivate p53 apoptotic transcriptional activity by rescuing both Ser46 and Lys382 modification in response to drug. Our data propose combination strategies for the treatment of tumors with dysfunctional p53 and/or HIPK2 that include classical chemotherapy with pharmacological or natural agents such as Sirt1-deacetylase inhibitors or zinc, respectively.
Turning a blind eye: the success of blinding reported in a random sample of randomised, placebo controlled trials
Authors: D. Fergusson
Journal: BMJ (2004)

To examine the reporting and success of double blinding in a sample of randomised, placebo controlled trials from leading general medicine and psychiatry journals.Identification of placebo controlled, randomised controlled trials from prespecified general medical and psychiatric journals indexed on Medline between 1 January 1998 and 1 October 2001, from which a random sample of 200 randomised clinical trials was chosen, of which 191 trials were evaluated.Only seven of the 97 (7%) general medicine trials provided evidence on the success of blinding, with five reporting that the success of blinding was imperfect. In trials from psychiatric journals, the success of blinding was reported in eight of the 94 trials, with four reporting that the blinding was imperfect. Overall, only four of the 191 (2%) trials assessed blinding in the participants and either the outcome assessors or the investigators.The current lack of reporting on the success of blinding provides little evidence that success of blinding is maintained in placebo controlled trials. Trialists and editors should make a concerted effort to incorporate, report, and publish such information and its potential effect on study results.
mTOR Signal and Hypoxia-Inducible Factor-1α Regulate CD133 Expression in Cancer Cells
Authors: Kazuko Matsumoto, Tokuzo Arao, Kaoru Tanaka, Hiroyasu Kaneda, Kanae Kudo, Yoshihiko Fujita, Daisuke Tamura, Keiichi Aomatsu, Tomohide Tamura, Yasuhide Yamada, Nagahiro Saijo, Kazuto Nishio
Journal: Cancer Research (2009)

The underlying mechanism regulating the expression of the cancer stem cell/tumor-initiating cell marker CD133/prominin-1 in cancer cells remains largely unclear, although knowledge of this mechanism would likely provide important biological information regarding cancer stem cells. Here, we found that the inhibition of mTOR signaling up-regulated CD133 expression at both the mRNA and protein levels in a CD133-overexpressing cancer cell line. This effect was canceled by a rapamycin-competitor, tacrolimus, and was not modified by conventional cytotoxic drugs. We hypothesized that hypoxia-inducible factor-1 alpha (HIF-1 alpha), a downstream molecule in the mTOR signaling pathway, might regulate CD133 expression; we therefore investigated the relation between CD133 and HIF-1 alpha. Hypoxic conditions up-regulated HIF-1 alpha expression and inversely down-regulated CD133 expression at both the mRNA and protein levels. Similarly, the HIF-1 alpha activator deferoxamine mesylate dose-dependently down-regulated CD133 expression, consistent with the effects of hypoxic conditions. Finally, the correlations between CD133 and the expressions of HIF-1 alpha and HIF-1 beta were examined using clinical gastric cancer samples. A strong inverse correlation (r = -0.68) was observed between CD133 and HIF-1 alpha, but not between CD133 and HIF-1 beta. In conclusion, these results indicate that HIF-1 alpha down-regulates CD133 expression and suggest that mTOR signaling is involved in the expression of CD133 in cancer cells. Our findings provide a novel insight into the regulatory mechanisms of CD133 expression via mTOR signaling and HIF-1 alpha in cancer cells and might lead to insights into the involvement of the mTOR signal and oxygen-sensitive intracellular pathways in the maintenance of stemness in cancer stem cells.
Association of High Serum Creatinine and Anemia Increases the Risk of Coronary Events
Authors: Claudine T. Jurkovitz, Jerome L. Abramson, L. Viola Vaccarino, William S. Weintraub, William M. McClellan
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with chronic kidney disease or anemia. The purpose of this study was to examine whether the association between renal function and risk of CHD is modified by hemoglobin (Hgb) status. Analyses were based on data from the Atherosclerosis Risk in Communities study, a community-based study of risk factors for CHD in middle-aged people. People with known CHD at baseline were excluded from the analysis. Participants were followed for 9 yr for the occurrence of CHD. Anemia was defined as Hgb &lt;13 g/dl in men and &lt;12 g/dl in women. Cox proportional hazards models were used to assess the relative risk (RR) of CHD occurrence according to Hgb status, after adjusting for other risk factors (demographics, lipids, diabetes, hypertension, smoking, body mass index, and carotid intima-media thickness). A total of 13,329 participants were included. The interaction between Hgb concentration and serum creatinine (Scr) was significant ( P = 0.02). Among people with anemia, a Scr ≥1.2 mg/dl in women or ≥1.5 mg/dl in men was associated with a higher risk of CHD (RR, 2.74; 95% confidence interval, 1.42 to 5.28) than those with normal Scr. In contrast, among those without anemia, this association was not noted (RR, 1.20; 95% confidence interval, 0.86 to 1.67). In conclusion, this study indicates that high Scr is associated with almost a threefold risk of CHD among middle-aged people with anemia, whereas no increased risk is found in people with high Scr in the absence of anemia. E-mail: cjurkov@emory.edu
Rheumatoid Arthritis in a Population Sample
Authors: J. H. Kellgren, J. S. Lawrence
Journal: Annals of the Rheumatic Diseases (1956)

Population StudiedIn 1949-50 rheumatic complaints were studied amongst the adult inhabitants of a I in 10 sample of houses in Leigh, an industrial town in Lancashire with a population of some 48,000.For the present investigation all individuals included in this sample who were in the age group 50-59 years in 1949-50 were selected for study.The second survey was carried out in the autumn of 1954, when the individuals studied were 5 years older and with few exceptions came within the age group 55-64 years.2A
Prevalence of Mutations in Renal Developmental Genes in Children with Renal Hypodysplasia
Authors: Stefanie Weber, Vincent Moriniere, Tanja Knüppel, Marina Charbit, Jirí Dusek, Gian Marco Ghiggeri, Augustina Jankauskiené, Sevgi Mir, Giovanni Montini, Amira Peco-Antic, Elke Wühl, Aleksandra M. Zurowska, Otto Mehls, Corinne Antignac, Franz Schaefer, Remi Salomon
Journal: Journal of the American Society of Nephrology (2006)

Renal hypodysplasia (RHD) is characterized by a reduced nephron number, small kidney size, and disorganized renal tissue. A hereditary basis has been established for a subset of affected patients, suggesting a major role of developmental genes that are involved in early kidney organogenesis. Gene mutations that have dominant inheritance and cause RHD, urinary tract anomalies, and defined extrarenal symptoms have been identified in TCF2 (renal cysts and diabetes syndrome), PAX2 (renal-coloboma syndrome), EYA1 and SIX1 (branchio-oto-renal syndrome), and SALL1 (Townes-Brocks syndrome). For estimation of the prevalence of these events, an unselected cohort of 99 unrelated patients with RHD that was associated with chronic renal insufficiency were screened for mutations in TCF2, PAX2, EYA1, SIX1, and SALL1. Mutations or variants in the genes of interest were detected in 17 (17%) unrelated families: One mutation, two variants, and four deletions of TCF2 in eight unrelated patients; four different PAX2 mutations in six families; one EYA1 mutation and one deletion in two patients with branchio-oto-renal syndrome; and one SALL1 mutation in a patient with isolated RHD. Of a total of 27 patients with renal cysts, six (22%) carried a mutation in TCF2. It is interesting that a SIX1 sequence variant was identified in two siblings with renal-coloboma syndrome as a result of a PAX2 mutation, suggesting an oligogenic inheritance. Careful clinical reevaluation that focused on discrete extrarenal symptoms and thorough family analysis revealed syndrome-specific features in nine of the 17 patients. In conclusion, 15% of patients with RHD show mutations in TCF2 or PAX2, whereas abnormalities in EYA1, SALL1, and SIX1 are less frequent.