tbuckley/cabot-search huggingface dataset:
7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-Induced DNA Binding and Repair Synthesis in Susceptible and Nonsusceptible Mammary Epithelial Cells in Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L K Tay, J Russo
Journal: JNCI Journal of the National Cancer Institute (1981)

The effect of age and parity on the binding of 7,12-dimethybenz[a]anthracene (DMBA) to DNA and the repair of DMBA-damaged DNA have been demonstrated in logarithmic phase and confluent mammary epithelial cell cultures from young virgin (YV), old virgin (OV), and parous (P) noninbred and inbred Sprague-Dawley rats. Over a dose range of 0.1-0.4 micrograms DMBA/ml, DNA binding was 1.5-to 2.0-fold higher in YV cells than in OV or P cells. In addition, a steeper slope of the dose-response curve was obtained with YV cells, suggesting a greater susceptibility of YV cells to DMBA. Excision repair was determined by measuring, in the presence of hydroxyurea and 5-bromodeoxyuridine, tritiated thymidine incorporation into DNA during the repair process. At high doses od DMBA (0.5-2.0 micrograms/ml), excision repair in YV cells was 1.5 times higher than in OV cells and 2 times higher than in P cells. However, with lower DMBA doses (less than 0.5 micrograms/ml) similar levels of repair were obtained in all 3 groups of rats. Since binding to DNA is higher in YV cells at these low DMBA doses, ti is apparent that OV and P cells exhibit a greater DNA repair per unit damage. These results, therefore, suggest that age and parity not only lower the binding of DMBA to mammary epithelial cell DNA but also increase the efficiency of DNA repair processes, which may explain the lower susceptibility of OV and P rats to DMBA-induced mammary carcinogenesis.
Angiotensin II Decreases a Resting K <sup>+</sup> Conductance in Rat Bulbospinal Neurons of the C1 Area
Authors: Yu-Wen Li, Patrice G. Guyenet
Journal: Circulation Research (1996)

Abstract In the rostral ventrolateral medulla (RVLM), angiotensin II (Ang II) receptors are concentrated in the region that contains neurons innervating sympathetic preganglionic neurons. We sought to determine whether these bulbospinal cells are sensitive to Ang II. Retrogradely labeled bulbospinal RVLM neurons (N=125) were recorded in thin slices from neonatal rats. Most (33 of 46) histologically recovered bulbospinal neurons were C1 cells (immunoreactive for tyrosine hydroxylase [TH-ir] or phenylethanolamine N -methyltransferase [PNMT-ir]). Bulbospinal RVLM neurons were spontaneously active (2.7±0.2 spikes per second, n=69) with ‘resting’ potential of −54±0.4 mV (n=77) and input resistance of 879±53 MΩ (n=47). Ang II (0.3 to 1 μmol/L) increased the spontaneous firing rate of most bulbospinal neurons (+250%, 28 of 39). In current-clamp mode, Ang II (1 μmol/L) produced depolarization (+6.8±0.6 mV, n=59 neurons) and increased input resistance (+21±2%, n=36 neurons). In voltage-clamp mode, Ang II elicited an inward current (9.7±0.9 pA; holding potential, −40 to −55 mV; n=25 neurons) that reversed polarity at the K + equilibrium potential (n=8 neurons) and was barium sensitive (n=4 neurons). Ang II–evoked conductance change was voltage independent (−40 to −140 mV, n=8 neurons). The effects of Ang II were blocked by losartan (9 of 9 neurons) but persisted in low Ca 2+ /high Mg 2+ (7 of 7 neurons). Ang II–sensitive cells were inhibited by α 2 -adrenergic receptor agonists (12 of 15 neurons). Ang II excited 91% (30 of 33) of TH-ir or PNMT-ir cells but 23% (3 of 13) of non–TH-ir neurons. In conclusion, RVLM bulbospinal cells express Ang II type-1 receptors whose activation leads to a reduction in resting K + conductance.
Continual monitoring of intraepithelial lymphocyte immunophenotype and clonality is more important than snapshot analysis in the surveillance of refractory coeliac disease
Authors: H Liu, R Brais, A Lavergne-Slove, Q Jeng, K Payne, H Ye, Z Liu, J Carreras, Y Huang, C M Bacon, R A Hamoudi, V Save, L Venkatraman, P G Isaacson, J Woodward, M-Q Du
Journal: Gut (2009)

<h3>Objective</h3> An aberrant immunophenotype and monoclonality of intraepithelial lymphocytes (IELs) are frequently found in refractory coeliac disease (RCD). However, the utility of continual monitoring of IEL immunophenotype and clonality in the surveillance of RCD remains to be studied. <h3>Design</h3> The diagnostic and follow-up biopsies from 33 patients with CD, 7 with suspected RCD, 41 with RCD and 20 with enteropathy-associated T cell lymphoma (EATL) (including 11 evolved from RCD) were investigated by CD3ɛ/CD8 double immunohistochemistry and PCR-based clonality analysis of the rearranged T cell receptor (TCR) genes. <h3>Results</h3> An aberrant immunophenotype (CD3ɛ<sup>+</sup>CD8<sup>−</sup> IELs ≥40%) and monoclonality were detected occasionally in CD biopsies, either transiently in patients with CD not compliant with a gluten-free diet or in those who subsequently developed suspected RCD, RCD or EATL. In contrast, the aberrant immunophenotype and monoclonality were found in 30 of 41 (73%) and 24 of 37 (65%) biopsies, respectively, at the time of RCD diagnosis. Among the patients with RCD who did not show these abnormalities in their diagnostic biopsies, 8 of 10 (80%) and 5 of 11 (45%) cases gained an aberrant immunophenotype and monoclonality, respectively, during follow-up. Irrespective of whether detected in diagnostic or follow-up biopsies, persistence of both abnormalities was characteristic of RCD. Importantly, the presence of concurrent persistent monoclonality and aberrant immunophenotype, especially ≥80% CD3ɛ<sup>+</sup>CD8<sup>−</sup> IELs, was a strong predictor of EATL development in patients with RCD (p=0.001). <h3>Conclusions</h3> Continual monitoring of both immunophenotype and clonality of IELs is more important than snapshot analysis for RCD diagnosis and follow-up, and could provide a useful tool for surveillance of patients at risk of EATL.
Peritoneal Colorectal Carcinomatosis Treated With Surgery and Perioperative Intraperitoneal Chemotherapy: Retrospective Analysis of 523 Patients From a Multicentric French Study
Authors: Dominique Elias, François Gilly, Florent Boutitie, François Quenet, Jean-Marc Bereder, Baudouin Mansvelt, Gérard Lorimier, Pierre Dubè, Olivier Glehen
Journal: Journal of Clinical Oncology (2009)

PURPOSE Peritoneal carcinomatosis (PC) from colorectal cancer traditionally is considered a terminal condition. Approaches that combine cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with that strategy. PATIENTS AND METHODS A retrospective-cohort, multicentric study from French-speaking countries was performed. All consecutive patients with PC from colorectal cancer who were treated with CRS and PIC (with or without hyperthermia) were included. Patients with PC of appendiceal origin were excluded. Results The study included 523 patients from 23 centers in four French-speaking countries who underwent operation between 1990 and 2007. The median follow-up was 45 months. Mortality and grades 3 to 4 morbidity at 30 days were 3% and 31%, respectively. Overall median survival was 30.1 months. Five-year overall survival was 27%, and five-year disease-free survival was 10%. Complete CRS was performed in 84% of the patients, and median survival was 33 months. Positive independent prognostic factors identified in the multivariate analysis were complete CRS, PC that was limited in extent, no invaded lymph nodes, and the use of adjuvant chemotherapy. Neither the grade of disease nor the presence of liver metastases had a significant prognostic impact. CONCLUSION This combined treatment approach against PC achieved low postoperative morbidity and mortality, and it provided good long-term survival in patients with peritoneal scores lower than 20. These results should improve in the future, because the different teams involved will gain experience. This approach, when feasible, is now considered the gold standard in the French guidelines.
Myeloid Differentiation Factor 88 Promotes Growth and Metastasis of Human Hepatocellular Carcinoma
Authors: Beibei Liang, Rui Chen, Tao Wang, Lei Cao, Yingying Liu, Fan Yin, Minhui Zhu, Xiaoyu Fan, Yingchao Liang, Lu Zhang, Yajun Guo, Jian Zhao
Journal: Clinical Cancer Research (2013)

Abstract Purpose: To investigate the expression of myeloid differentiation factor 88 (MyD88) in hepatocellular carcinoma (HCC) and its prognostic value in patients with HCC. Experimental Design: Expression of MyD88 was detected by immunohistochemistry in surgical HCC specimens (n = 110). The correlation of MyD88 expression to clinicopathologic characteristics was analyzed. The involvement of MyD88 in tumor growth and invasion was investigated. Results: The expression of MyD88 was significantly higher in HCC tumors than that in adjacent nontumor tissues. Particularly, high expression of MyD88 was found in HCCs with late tumor stage (P = 0.029). Patients with high MyD88 staining revealed a higher recurrence rate (65% vs. 40%; P = 0.008). Kaplan–Meier analysis showed that recurrence-free survival (RFS; P = 0.011) and overall survival (OS; P = 0.022) were significantly worse among patients with high MyD88 staining. Univariate and multivariate analyses revealed that MyD88 was an independent predictor for OS and RFS. Ectopic expression of MyD88 promoted HCC cell proliferation and invasion in vitro. Suppression of MyD88 expression with lentivirus encoding short hairpin RNA reduced tumor growth and invasion, as well as lung metastasis. Finally, silencing of MyD88 inhibited the activation of NF-κB and AKT in HCC cells, whereas forced expression of MyD88 was able to enhance the activation of NF-κB and p38/extracellular signal–regulated kinase without Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) signaling. Conclusion: Elevated expression of MyD88 may promote tumor growth and metastasis via both TLR/IL-1R–dependent and –independent signaling and may serve as a biomarker for prognosis of patients with HCC. Clin Cancer Res; 19(11); 2905–16. ©2013 AACR.
Functional role of estrogen in pituitary tumor pathogenesis
Authors: Anthony P. Heaney, Manory Fernando, Shlomo Melmed
Journal: Journal of Clinical Investigation (2002)

Pituitary hyperplasia and lactotroph replication are induced by estrogen. The product of the pituitary tumor transforming gene (PTTG) exhibits in vitro and in vivo transforming activity and induces basic bFGF secretion, thereby modulating pituitary angiogenesis and tumor formation. We demonstrated previously that pituitary pttg is induced by estrogen and bFGF, the latter being expressed in a concordant fashion with pttg in experimental and human pituitary adenomas. We now elucidate the role of estrogen in paracrine regulation of pituitary tumorigenesis by PTTG. Coincident with the circulating rat estradiol surge and maximal pituitary proliferation, pituitary pttg mRNA, bFGF, and VEGF expression increased approximately threefold during proestrus and estrus. Osmotic mini-pump coinfusion of estrogen and antiestrogen abrogated estrogen-induced pituitary pttg expression in vivo, suppressed serum PRL concentrations by 88%, and attenuated prolactin-secreting pituitary tumor growth by 41% in rats. Antiestrogen treatment of primary human pituitary tumor cultures reduced PTTG expression approximately 65%. Pituitary pttg, bFGF, and VEGF are cyclically expressed during the rat estrus cycle, concordantly with estrogen levels. Because anti-estrogens reduced PTTG expression in human pituitary tumors in vitro and suppressed experimental tumor growth in vivo, concomitantly with reduced PRL secretion, these results indicate a role for selective antiestrogens in treating pituitary tumors.
Estimated GFR, Albuminuria, and Complications of Chronic Kidney Disease
Authors: Lesley A. Inker, Josef Coresh, Andrew S. Levey, Marcello Tonelli, Paul Muntner
Journal: Journal of the American Society of Nephrology (2011)

Higher levels of albuminuria associate with increased risk for adverse outcomes independent of estimated GFR (eGFR), but whether albuminuria also associates with concurrent complications specific to chronic kidney disease (CKD) is unknown. Here, we assessed the association of spot albumin-to-creatinine ratio with anemia, acidosis, hyperphosphatemia, hypoalbuminemia, hyperparathyroidism, and hypertension among 30,528 adult participants in NHANES 1988-1994 and 1999-2006. After multivariable adjustment including eGFR, higher albumin-to-creatinine ratios associated with anemia, acidosis, hypoalbuminemia, hyperparathyroidism, and hypertension but only weakly associated with acidosis and anemia. Furthermore, the associations between albumin-to-creatinine ratio and both anemia and acidosis were not consistent across eGFR strata. Higher albumin-to-creatinine ratio levels did not associate with hyperphosphatemia. Lower eGFR associated with higher prevalence ratios for all complications, and these associations were stronger than those observed for the albumin-to-creatinine ratio; after multivariable adjustment, however, the associations between eGFR and both hypoalbuminemia and hypertension were NS. In conclusion, albuminuria and eGFR differentially associate with complications of CKD.
Eniluracil’s Need for a Targeted Approach: A Lesson in Drug Development
Authors: Michael Castro
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.99.310 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12202681 Eniluracil’s Need for a Targeted Approach: A Lesson in Drug Development Michael CastroxMichael CastroSearch for articles by this author Show More Charles Wood Cancer Center, Glenn Falls Hospital, Glenn Falls, NY https://doi.org/10.1200/JCO.2002.99.310 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Television viewing and asthma: spurious relationship?
Authors: J. C. van der Wouden
Journal: Thorax (2010)

The sequential appearance of the thymocyte subpopulations and TCR gene messages occurred in the thymus of AKR mice (H-2k, Mlsa) from 7 to 14 days after sublethal irradiation. The thymocytes on day 7 after irradiation were composed of a large number of CD4+CD8+ blast-like cells and a relatively high proportion of CD4-CD8- cells (15 to 25%) but few CD3highCD4+CD8-/CD4-CD8+ cells. Approximately 22% of the CD4-CD8- cells were CD3high and -27% of the CD3highCD4-CD8- cells (-6% of whole CD4-CD8- cells) were F23.1+. The thymocytes on day 7 expressed a large amount of gamma- and delta-chain gene transcripts but reduced levels of alpha- and beta-chain gene transcripts. The V gene repertoire of 18 functional beta-chain cDNA derived from the thymocytes on day 7 was compared with those of 20 functional beta-chain cDNA derived from the thymocytes on day 14 which were composed of a large number of CD3lowCD4+CD8+ small-sized cells and a small number of CD3highCD4+CD8- cells. It is noteworthy that the distribution of V beta genes expressed in the thymocytes on day 7 was much the same as that in the thymocytes on day 14 but significantly different from that in normal BALB/c thymocytes as previously described. Interestingly, neither V beta 8.1 nor V beta 6 genes, which are important for recognition of the product of the Mlsa locus, was detected in these two cDNA libraries. These results suggest that clonal selection of TCR V beta repertoire, irrespective of positive or negative selection, appears to occur at the early stage of T cell differentiation, i.e., on the blast-like CD4+CD8+ thymocytes.
Access to scrotal ultrasonography
Authors: B. Sizer
Journal: Journal of the Royal Society of Medicine (2005)

In their letter about access to scrotal ultrasonography (November 2004, JRSM1) Mr Pocock and his colleagues refer to a large number of inappropriate primary care referrals. Like his, our service has noted increasing referrals for scrotal ultrasound and our assumption was that the majority of these arose from primary care. However, our audit of 569 ultrasound scans performed in the 18 month period from 1 April 2000 to 30 September 2001 showed that general practitioners (GPs) accounted for only 129 (22.7%); by far the largest source of requests was urologists (n=282, 49.6%), followed by general surgeons (n=109, 19.2%). Further analysis of the secondary care requests showed that 46.3% were by consultants, 34.7% specialist registrars or staff grades and 19% junior medical staff.

The median wait for scrotal ultrasound was 36 days, leading to a range of 'journey times' from initial GP referral to diagnosis at orchidectomy up to 127 days: in total, 11 patients in this period were diagnosed by this modality with testicular malignancy. To improve this, we identified the most timely and direct route for referrals, nominated a lead uro-oncologist, and instituted a reduction in the number of clinicians who could request scrotal ultrasonography. These scans are now reported the same day and if testicular tumour is suspected on ultrasound, the para-aortic nodes, kidneys and liver are visualized at the same investigation. The most important point may be to account for the relatively low number of patients diagnosed with testicular tumours both in our audit and in the original paper by Allen et al. (June 2004 JRSM2) which looked specifically at two-week-wait referrals, with only 1 positive diagnosis via this route. Reviewing our practice in the past 12 months we find that 15 patients have been diagnosed with testicular tumours (seminoma 10, teratoma 3, non-Hodgkin lymphoma 2) of whom only 7 (47%) came by two-week referral; 3 were by urgent GP referral, 1 by routine GP referral, 2 by direct GP ultrasound request, with 1 each from oncology (for a second testicular tumour) and general surgery. Reassuringly, median time from ultrasound to inguinal orchidectomy was only 13 days (range 2–19).

This is the group of patients for whom one would imagine the two-week-wait-referral mechanism was designed specifically to help. It is of concern, then, that at least half our patients who are found to have testicular tumours are still not being referred through this route. However, by streamlining ultrasonography practices, one can greatly lessen journey times from referral to definitive surgery.
Particulate Matter Exposure in Cars Is Associated with Cardiovascular Effects in Healthy Young Men
Authors: Michael Riediker, Wayne E. Cascio, Thomas R. Griggs, Margaret C. Herbst, Philip A. Bromberg, Lucas Neas, Ronald W. Williams, Robert B. Devlin
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Exposure to fine airborne particulate matter (PM2.5) is associated with cardiovascular events and mortality in older and cardiac patients. Potential physiologic effects of in-vehicle, roadside, and ambient PM2.5 were investigated in young, healthy, nonsmoking, male North Carolina Highway Patrol troopers. Nine troopers (age 23 to 30) were monitored on 4 successive days while working a 3 P.M. to midnight shift. Each patrol car was equipped with air-quality monitors. Blood was drawn 14 hours after each shift, and ambulatory monitors recorded the electrocardiogram throughout the shift and until the next morning. Data were analyzed using mixed models. In-vehicle PM2.5 (average of 24 μg/m3) was associated with decreased lymphocytes (−11% per 10 μg/m3) and increased red blood cell indices (1% mean corpuscular volume), neutrophils (6%), C-reactive protein (32%), von Willebrand factor (12%), next-morning heart beat cycle length (6%), next-morning heart rate variability parameters, and ectopic beats throughout the recording (20%). Controlling for potential confounders had little impact on the effect estimates. The associations of these health endpoints with ambient and roadside PM2.5 were smaller and less significant. The observations in these healthy young men suggest that in-vehicle exposure to PM2.5 may cause pathophysiologic changes that involve inflammation, coagulation, and cardiac rhythm.
Global variations in the uptake of single embryo transfer
Authors: A. Maheshwari, S. Griffiths, S. Bhattacharya
Journal: Human Reproduction Update (2010)

Single embryo transfer (SET) is the most effective way of reducing multiple pregnancy rates associated with assisted reproductive technology (ART). Despite published evidence suggesting that the judicious use of elective SET can lead to near-elimination of multiples without compromising cumulative live birth rates, the uptake of this strategy has been variable. Medline, EMBASE and the Cochrane Database of Systematic Reviews (1978–2010) were searched using appropriate MeSH headings. Leading fertility journals along with appropriate cross references were hand searched and information retrieved from national ART registers and websites of national fertility societies in order to determine current rates of SET. We explored social, economic and clinical factors determining the uptake of SET. It was not possible to distinguish elective from non-elective SET from national ART reports. Data from 31 countries suggest that there has been a gradual increase in SET rates over a 3 year period (2003–2005) but major geographical differences were noted. SET rates are highest in Sweden (69.4%) but are as low as 2.8% in the USA. Access to public funding for ART, availability of good cryopreservation facilities and legislation appear to be the most important reasons favouring the uptake of SET. Personal choice plays a significant role as many subfertile couples have a strong preference for twins. Awareness that double embryo transfer (DET) increases live birth per fresh treatment cycle, inability to accurately identify women at high risk for twins and limitations of existing embryos selection criteria are barriers to a wider acceptance of SET. The current variation in the uptake of elective SET is likely to persist until there are major changes in the way ART is viewed, funded and legislated.
Benign folie à deux: The social construction of positive illusions
Authors: Dennis L. Krebs, Kathy Denton
Journal: Behavioral and Brain Sciences (2009)

Abstract McKay &amp; Dennett (M&amp;D) have done an admirable job of distinguishing among various forms of misbelief and evaluating the idea that they stem from evolved mental mechanisms. We argue that a complete account of misbeliefs must attend to the role that others play in creating and maintaining positive illusions.
Promoter Polymorphisms −359T/C and −303A/G of the Catalytic Subunit p110β Gene of Human Phosphatidylinositol 3-Kinase Are Not Associated With Insulin Secretion or Insulin Sensitivity in Finnish Subjects
Authors: Maija Kossila, Jussi Pihlajamäki, Päivi Kärkkäinen, Raija Miettinen, Päivi Kekäläinen, Ilkka Vauhkonen, Seppo Ylä-Herttuala, Markku Laakso
Journal: Diabetes Care (2003)

OBJECTIVE—Phosphatidylinositol (PI) 3-kinase activity is required for insulin-stimulated translocation of GLUT4 transporters and glucose uptake and utilization. Therefore, genes encoding the subunits of PI 3-kinase are promising candidate genes for insulin resistance and type 2 diabetes. We recently cloned the catalytic subunit p110β gene of human PI 3-kinase and reported two nucleotide polymorphisms, −359T/C and −303A/G, in the promoter region of this gene. In this study, we determined the effects of these polymorphisms on insulin secretion and insulin sensitivity. RESEARCH DESIGN AND METHODS—We studied two separate groups of Finnish nondiabetic subjects. Insulin secretion was evaluated by intravenous glucose tolerance test and insulin sensitivity by hyperinsulinemic-euglycemic clamp. RESULTS—Our results showed that the −359T/C and −303A/G polymorphisms did not have a significant effect on fasting plasma insulin levels, insulin secretion, or insulin sensitivity. CONCLUSIONS—It is unlikely that the promoter polymorphisms −359T/C and −303A/G of the catalytic subunit p110β gene of human PI 3-kinase have a major impact on insulin secretion, insulin sensitivity, or the risk of type 2 diabetes in Finnish subjects.