tbuckley/cabot-search huggingface dataset:
Epithelial and stromal genetic instability contributes to genesis of colorectal adenomas
Authors: K Ishiguro
Journal: Gut (2005)

Previously, we indicated that stromal genetic instability might contribute to tumorigenesis of both sporadic and ulcerative colitis associated colorectal adenocarcinomas. Considering the established adenoma-adenocarcinoma sequence, in this study we analysed genetic instability in colorectal adenoma cells and surrounding stroma.In 164 colorectal tumours (34 hyperplastic polyps, 38 tubular adenomas with low grade dysplasia (TA-L), 51 tubular adenomas with high grade dysplasia (TA-H), and 41 invasive carcinomas), epithelial and stromal genetic instability with National Cancer Institute standard microsatellite markers and chromosome 17 (Chr17) markers, were analysed by a combination of laser capture microdissection and GeneScan approaches.While frequencies of both loss of heterozygosity (LOH) and microsatellite instability (MSI) were extremely low in hyperplastic polyps, LOH in tubular adenomas was detected in both epithelial (TA-L 13.2%, TA-H 27.5%) and stromal (5.3% and 5.9%, respectively) elements, along with MSI (5.3% and 13.7%, and 5.3 and 5.9%, respectively). Frequencies of epithelial alterations were higher in TA-H than in TA-L, and greatest in the carcinoma group. On the other hand, frequencies of stromal LOH or MSI were almost constant (5.3% approximately 17.1%, 5.3% approximately 17.1%, respectively) in adenomas and invasive carcinomas. In addition, p53 was found to be significantly overexpressed in a greater proportion of TA-L with LOH than in those without genetic instability.The results indicate the presence of genetic alterations in stroma from an early stage of carcinogenesis, accompanied by stepwise increasing genetic instability of epithelia with progression to cancer. Thus microenvironmental changes due to genetic alteration in Chr17 markers in stromal cells may play an important role in colon adenoma and adenocarcinoma development.
Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis
Authors: L. Damjanovska, M. M. Thabet, E. W. N. Levarth, G. Stoeken-Rijsbergen, E. I. van der Voort, R. E. M. Toes, T. W. J. Huizinga, A. H. M. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objectives</h3> To evaluates the diagnostic performance of the anti-CCP2, anti-CCP3 and anti-mutated citrullinated vimentin (anti-MCV) tests in differentiating rheumatoid arthritis (RA) from other forms of arthritis in a clinical setting of early arthritis. <h3>Methods</h3> In 917 patients with recent-onset arthritis (566 RA, 351 other diseases) and in 99 healthy controls the anti-MCV, anti-CCP2 and anti- CCP3.1 tests were performed and the test characteristics compared. <h3>Results</h3> Comparison of the tests for differentiating RA from other causes of arthritis showed a lower specificity for anti-MCV (82.9%) than for anti-CCP2 (93.4%) and anti-CCP3.1 (90.0%). Similarly, the positive likelihood ratio for anti-MCV was also lower (3.6, compared with 8.7, 5.8 for anti-CCP2 and anti-CCP3.1). The anti-MCV test had a higher sensitivity (62% vs 56.9% and 58.1%, respectively). In psoriatic arthritis, spondyloarthropathy and other arthritis anti-MCV antibodies had a prevalence of 15.2%, 13.9% and 19.4%. <h3>Conclusion</h3> The diagnostic performance of the anti-MCV test in the differential diagnosis of early arthritis is lower than that of the anti-CCP tests.
CLONAL GROWTH IN VITRO OF EPITHELIAL CELLS FROM NORMAL HUMAN TISSUES
Authors: Philip I. Marcus, Steven J. Cieciura, Theodore T. Puck
Journal: The Journal of Experimental Medicine (1956)

Tissue culture strains of cells from four different normal human tissues-liver, conjunctiva, kidney, and appendix-have been grown by the plating procedure previously developed for the HeLa strain of cervical carcinoma cells. This technique results in colony formation from isolated single cells, in a manner completely analogous to the plating of bacteria in semisolid nutrient media. Clonal cell strains have been isolated from each cell type. All behaved exactly alike in all properties studied except that some differences in plating efficiency were displayed in some of the growth media employed. The cells from normal human tissues resembled the HeLa S3 carcinomatous cell in the following properties:- (a) Single cells displayed a plating efficiency close to 100 per cent in an appropriate medium. (b) They all grew as an epithelial sheet on glass, the cells being closely packed and polygonal in shape. (c) They had mean generation times of 20 to 23 hours in the nutrient media employed, (d) The mitotic frequency was constant, and therefore the duration of mitosis was the same for all the strains studied, (e) The incidence of multinuclearity and giant formation was very low and similar in both types of cells. (f) Both classes of cells had the same total volume, and the same nuclear cross-sectional area. (g) Both also showed a tendency to spread more in the presence of human serum (concentration of 20 per cent or more) than in porcine serum. However, this differential morphological response was much more marked in the HeLa cell than in those from normal tissues. The only difference noted in the behavior of these two groups of cells lay in the tendency of the cells from normal tissues always to exhibit a greater cross-sectional area when spread on glass than the HeLa cell in the same medium. The frequency of occurrence of different types of multinuclearity in the HeLa cell and cells from normal tissues has been measured. The data suggest that multinuclearity depends on two factors: a necessary, predisposing state in the cell, and a random, independent event causing the appearance of an additional nucleus in such a prepared cell.
Effect of Fenretinide and Low-Dose Tamoxifen on Insulin Sensitivity in Premenopausal Women at High Risk for Breast Cancer
Authors: Harriet Johansson, Sara Gandini, Aliana Guerrieri-Gonzaga, Simona Iodice, Massimiliano Ruscica, Bernardo Bonanni, Marcella Gulisano, Paolo Magni, Franca Formelli, Andrea Decensi
Journal: Cancer Research (2008)

Abstract The prevalence of metabolic syndrome is increasing along with breast cancer incidence worldwide. Because fenretinide improves insulin action and glucose tolerance in insulin-resistant obese mice and because tamoxifen has shown to regulate several markers involved in metabolic syndrome, we sought to investigate the effect of fenretinide or tamoxifen at low dose on features linked to insulin resistance in premenopausal women at risk for breast cancer. We randomized 235 women to low-dose tamoxifen (5 mg/daily), fenretinide (200 mg/daily), or their combination or placebo for 2 years. We used the homeostasis model assessment (HOMA; fasting insulin × glucose/22.5) to estimate insulin sensitivity. Women were considered to improve insulin sensitivity when they shifted from a HOMA ≥2.8 to &amp;lt;2.8. There was no effect of fenretinide or tamoxifen on HOMA overall, but overweight women (body mass index, ≥25 kg/m2) had a 7-fold greater probability to normalize HOMA after 2 years of fenretinide treatment [odds ratio (OR), 7.0; 95% confidence interval (95% CI), 1.2–40.5], with 25% of women improving their insulin sensitivity, whereas tamoxifen decreased insulin sensitivity by almost 7 times compared with subjects not taking tamoxifen (OR, 0.15; 95% CI, 0.03–0.88). In this group only, 5% improved their insulin sensitivity. Interestingly, women with intraepithelial or microinvasive neoplasia had higher HOMA (3.0) than unaffected subjects (2.8; P = 0.07). Fenretinide can positively balance the metabolic profile in overweight premenopausal women and this may favorably affect breast cancer risk. Furthermore, features of the metabolic syndrome should be taken into consideration before proposing tamoxifen for breast cancer prevention. The clinical implications of these results require further investigations. [Cancer Res 2008;68(22):9512–8]
Long-Term Survival and Valve-Related Complications in Young Women With Cardiac Valve Replacements
Authors: Robyn A. North, Lynn Sadler, Alistair W. Stewart, Lesley M.E. McCowan, Alan R. Kerr, Harvey D. White
Journal: Circulation (1999)

Background —The type of cardiac valve replacement associated with the lowest health risks for young women who may undergo pregnancies is unknown. We investigated which valve type was associated with greatest patient and valve survival and the effect of pregnancy on valve loss. Methods and Results —In this retrospective study, all women 12 to 35 years old who underwent valve replacements between 1972 and 1992 at Greenlane Hospital were identified, and follow-up was available in 93%. The 232 women were followed up for 1499 patient-years. Ten-year survival of women with mechanical (n=178), bioprosthetic (n=73), and homograft (n=72) valves was 70% (95% CI, 59% to 83%), 84% (95% CI, 72% to 99%), and 96% (95% CI, 91% to 100%), P =0.002. After adjustment for confounding variables, the relative risk (RR) of death with mechanical compared with bioprosthetic valves was 2.17 (95% CI, 0.78 to 5.88). Thromboembolic events occurred in 45% of women with mechanical valves within 5 years, compared with 13% with bioprosthetic valves, P =0.0001. Valve loss at 10 years was higher in bioprosthetic valves [82% (95% CI, 62% to 92%)] than in mechanical [29% (95% CI, 17% to 39%)] or homograft [28% (95% CI, 12% to 41%)] valves, P =0.0001. Pregnancy was not associated with increased bioprosthetic (RR, 0.96; 95% CI, 0.68 to 1.35), homograft (RR, 0.65; 95% CI, 0.37 to 1.13), or mechanical (RR, 0.54; 95% CI, 0.27 to 1.08) valve loss. Conclusions —Although 10-year valve survival was greater with mechanical than bioprosthetic valves, mechanical valves may be associated with reduced patient survival in young women. Thromboembolic complications, often with long-term sequelae, were common with mechanical valves. Pregnancy did not increase structural deterioration or reduce survival of bioprosthetic valves.
Anyone for tennis?
Authors: M S Turner, B M Pluim
Journal: British Journal of Sports Medicine (2007)

A total of 28 000 kilos of strawberries and 7000 litres of dairy cream have just been consumed at the 2007 Championships, Wimbledon, along with 150 000 glasses of Pimm’s and 17 000 bottles of champagne. The largest single annual sports catering operation in Europe has once again been a resounding success for the organisers, but what about success for the players and more especially for the nations that they represent?

Tennis is an immensely popular global sport with 205 nations affiliated to the international governing body, the International Tennis Federation (ITF), and almost 25 million active players in the USA alone.

Of all the traditional American sports, tennis is the only one that has shown a steady growth in measured sales (+10.3%)1 and a growth in participation (+4.3%)2 over the last 5 years. The 2005 USTA survey shows an increase in the frequency of participation (559 million played on occasion in 2005, compared to 491 million in 2004) as well as an increase in the actual number of participants (+1.1 million).

So, grassroots tennis is booming in the USA but, according to those involved with the elite game, US …
Outpatient overnight glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or conventional insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, randomised controlled trial
Authors: Ahmad Haidar, Laurent Legault, Laurence Matteau-Pelletier, Virginie Messier, Maryse Dallaire, Martin Ladouceur, Rémi Rabasa-Lhoret
Journal: The Lancet Diabetes & Endocrinology (2015)
Hepatitis C virus: epidemiology and genotypes in the north east of England.
Authors: J P Watson, A M Brind, C E Chapman, C L Bates, F K Gould, S J Johnson, A D Burt, J Ferguson, P Simmonds, M F Bassendine
Journal: Gut (1996)

The epidemiology of hepatitis C virus (HCV) infection was studied in an English teaching hospital over an 18 month period. A total of 104 HCV antibody positive patients were referred for further investigation. They were divided into those diagnosed through screening (blood donors and intravenous drug abusers) and those diagnosed for other reasons, and their mean ages, known risk factors for HCV transmission, genotypes, and liver biopsy histology were analysed. Screened patients were significantly younger than the others. No significant difference in age was found between genotypes. Most patients genotyped (69%) were genotype 1. Intravenous drug abusers had a higher proportion of subtype 1a, and patients who acquired HCV through blood transfusion had a higher proportion of subtype 1b. Liver biopsy specimens were scored using a histological activity index for liver inflammation and fibrosis. Patients with subtype 1b had significantly more severe liver disease than other genotypes when the histological activity index scores for fibrosis were analysed (p &lt; 0.05). Liver disease worsened significantly with age according to all three histological activity index scores (portal activity: p &lt; 0.01, acinar activity: p &lt; 0.001, fibrosis: p &lt; 0.0001). Liver disease worsened with increased duration of infection (p &lt; 0.002), and patients who also abused alcohol presented at a significantly younger age (cirrhosis, p &lt; 0.05, hepatocellular carcinoma, p &lt; 0.02).
Rituximab Treatment Prevents the Early Development of Proteinuria following Pig-to-Baboon Xeno-Kidney Transplantation
Authors: Masayuki Tasaki, Akira Shimizu, Isabel Hanekamp, Radbeh Torabi, Vincenzo Villani, Kazuhiko Yamada
Journal: Journal of the American Society of Nephrology (2014)

We previously reported life-supporting α1,3-galactosyltransferase knockout (GalTKO) thymokidney xenograft survival of >2 months in baboons. However, despite otherwise normal renal function, recipients developed proteinuria with morphologic changes (podocyte effacement), a condition that presents a major obstacle to long-term studies in this model. A recent clinical study showed that rituximab therapy after allogeneic transplant prevented proteinuria possibly associated with loss of sphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b). Here, we demonstrate that rituximab prevents the disruption of pig podocytes in an SMPDL-3b-dependent manner in vitro and the early development of proteinuria after xenogeneic kidney transplantation in baboons. Immunofluorescence showed SMPDL-3b expression in pig glomerular epithelium; immunoprecipitation demonstrated rituximab binding to SMPDL-3b in glomeruli. Culture of isolated pig podocytes with naive baboon sera, which has preformed antipig natural antibodies, reduced SMPDL-3b expression, disrupted podocyte morphology, and decreased podocyte proliferation, whereas pretreatment with rituximab prevented these effects. Six baboons received rituximab before transplantation to deplete B cells and again in the peri-transplant period; 18 baboons treated only before transplantation served as historical controls. The onset of post-transplant proteinuria was significantly delayed in a B cell-independent manner in the animals that received peri-transplant rituximab treatment. Although further optimization of this protocol is required, these data provide intriguing clues to the mechanisms of post-transplant proteinuria in xenogeneic kidney transplantation and a potential strategy for its prevention.
Combination Therapy of Insulin-Like Growth Factor Binding Protein-3 and Retinoid X Receptor Ligands Synergize on Prostate Cancer Cell Apoptosis <i>In vitro</i> and <i>In vivo</i>
Authors: Bingrong Liu, Kuk-Wha Lee, Heju Li, Liqun Ma, George L. Lin, Roshantha A.S. Chandraratna, Pinchas Cohen
Journal: Clinical Cancer Research (2005)

Abstract We have previously identified the retinoid X receptor-α (RXRα) as an insulin-like growth factor binding protein-3 (IGFBP-3) nuclear binding partner, which is required for IGFBP-3-induced apoptosis. In the current study, we investigated the biological interactions of the RXR ligand, VTP194204 and rhIGFBP-3, in vitro and in vivo. In vitro, IGFBP-3 and VTP194204 individually induced apoptosis, and suppressed cell growth in prostate cancer cell lines in an additive manner. In vivo, LAPC-4 xenograft–bearing severe combined immunodeficiency mice treated daily with saline, IGFBP-3, and/or VTP194204 for 3 weeks showed no effect of individual treatments with IGFBP-3 or VTP194204 on tumor growth. However, the combination of IGFBP-3 and VTP194204 treatments inhibited tumor growth by 50% and induced a significant reduction in serum prostate-specific antigen levels. In terminal nucleotidyl transferase–mediated nick end labeling immunohistochemistry of LAPC-4 xenografts, there was modest induction of apoptosis with either IGFBP-3 or VTP194204 individual treatment, but combination therapy resulted in massive cell death, indicating that IGFBP-3 and VTP194204 have a synergistic effect in preventing tumor growth by apoptosis induction. In summary, this is an initial description of the successful therapeutic use of IGFBP-3 as a cancer therapy in vivo, and shows that combination treatment of IGFBP-3 and RXR ligand has a synergistic effect on apoptosis induction leading to substantial inhibition of prostate cancer xenograft growth. Taken together, these observations suggest that combination therapy with IGFBP-3 and RXR ligands may have therapeutic potential for prostate cancer treatment.
Results of a 10 week community based strength and balance training programme to reduce fall risk factors: a randomised controlled trial in 65–75 year old women with osteoporosis
Authors: N D Carter, K M Khan, M A Petit, A Heinonen, C Waterman, M G Donaldson, P A Janssen, A Mallinson, L Riddell, K Kruse, J C Prior, L Flicker, H A McKay
Journal: British Journal of Sports Medicine (2001)

Objective —To test the efficacy of a community based 10 week exercise intervention to reduce fall risk factors in women with osteoporosis. Methods —Static balance was measured by computerised dynamic posturography (Equitest), dynamic balance by timed figure of eight run, and knee extension strength by dynamometry. Subjects were randomised to exercise intervention (twice weekly Osteofit classes for 10 weeks) or control groups. Results —The outcome in 79 participants (39 exercise, 40 control) who were available for measurement 10 weeks after baseline measurement is reported. After confounding factors had been controlled for, the exercise group did not make significant gains compared with their control counterparts, although there were consistent trends toward greater improvement in all three primary outcome measures. Relative to the change in control subjects, the exercise group improved by 2.3% in static balance, 1.9% in dynamic balance, and 13.9% in knee extension strength. Conclusions —A 10 week community based physical activity intervention did not significantly reduce fall risk factors in women with osteoporosis. However, trends toward improvement in key independent risk factors for falling suggest that a study with greater power may show that these variables can be improved to a level that reaches statistical significance.
Learning to identify CNS drug action and efficacy using multistudy fMRI data
Authors: Eugene P. Duff, William Vennart, Richard G. Wise, Matthew A. Howard, Richard E. Harris, Michael Lee, Karolina Wartolowska, Vishvarani Wanigasekera, Frederick J. Wilson, Mark Whitlock, Irene Tracey, Mark W. Woolrich, Stephen M. Smith
Journal: Science Translational Medicine (2015)

Existing functional brain imaging data sets were used to identify neural signatures that confirm pharmacological action and predict clinical efficacy of test compounds.
Wheeze, asthma diagnosis and medication use in developing countries
Authors: M R Becklake
Journal: Thorax (2005)

Sociodemographic, environmental, and medical predictors in a national adult survey conducted in South Africa

Standardised population based health surveys have produced much useful information on the prevalence and determinants of asthma in children (International Study of Asthma and Allergy in Children (ISAAC) study)1 and adults (European Community Respiratory Health Study (ECRHS) study).2 Most sites participating in these studies have been in high income countries and, because some centres took part at their own expense, the populations studied were probably not representative of their countries as a whole. In addition, a number of national health surveys such the US National Health and Nutrition Survey (NHANES),3 the Canadian National Health Survey,4 and National Birth Cohort Studies (UK, New Zealand)5,6 have been conducted, all in high income countries.

In this issue of Thorax Ehrlich et al ,7 in what is one of the first such studies in a developing (in this case middle income) country, describe the results of a national health survey conducted among 13 826 South Africans aged 15 years and over to determine the national prevalence and predictors of three outcomes: (1) wheezing symptoms, (2) an asthma diagnosis, and (3) use of asthma medication. This was an ambitious undertaking (and a remarkably successful one) given the racial, linguistic, and socioeconomic heterogeneity of the population and its quadruple burden of HIV, other infections (including tuberculosis), chronic non-communicable disease, and injury. What is surprising is not that the findings in this paper7 and in its companion paper on chronic bronchitis8 were different from those published for developed (high income) countries, but that in how many respects they were similar.

Great care was taken by Ehrlich and colleagues to maximise the quality of the data gathered, as evidenced by (1) the use of a …
STUDIES OF ARTHRITIS AND OTHER LESIONS INDUCED IN RATS BY INJECTION OF MYCOBACTERIAL ADJUVANT
Authors: Carl M. Pearson, Byron H. Waksman, John T. Sharp
Journal: The Journal of Experimental Medicine (1961)

A generalized disease is induced experimentally in the rat by administration of Freund's adjuvant. The primary clinical and pathologic lesions are arthritis, periarthritis, peritendinitis, and periostitis in the joints of the extremities and tail. Accompanying the arthritis in some cases, and never observed in its absence, are other specific tissue lesions including iridocyclitis, nodular lesions in the glabrous skin (ear, genitalia, feet, tail), transient rashes, a chronic skin disease, genitourinary lesions, and diarrhea. These make up a striking and characteristic picture. The arthritis usually precedes the other lesions and, together with the skin disease may show a prolonged and fluctuating course. Visceral lesions do not occur. Histologically, the basic lesion is a lymphocytic and histiocytic infiltration, initially perivascular and subsequently more disseminated. In addition, in the region of the joints and in the corpora cavernosa of the penis, there is extensive proliferation of mesenchymal cells, especially fibroblasts. Foci of fibrinoid necrosis are seen in the articular and nodular lesions, and destructive lesions of the joints are common. Such a combination of tissue lesions has not previously been described in experimental pathology. The experimental disease is shown to have both similarities to and differences from Reiter's syndrome, rheumatoid arthritis, and certain other disorders which occur in man.