tbuckley/cabot-search huggingface dataset:
P396Improved calcium cycling is associated with microtubule reorganisation in anisotropic cardiomyocyte cultures
Authors: E Humphrey, T Trantidou, C Kane, P Dias, N S Peters, T Prodromakis, C M Terracciano
Journal: Cardiovascular Research (2014)

Neonatal and stem cell-derived cardiomyocytes differ from adult heart cells in their structure and function, limiting their use in pharmacological studies. Establishment of anisotropic cultures can improve the functional properties of cardiomyocytes; however, the mechanism that links functional improvement with ultrastructural reorganisation is unclear. Microtubules act as a link between mechanical stimuli and functional response in cardiac cells but whether they are affected during cellular alignment in culture is unknown. In this study neonatal rat ventricular myocytes were cultured on micropatterned Parylene C constructs, with alternating hydrophilic-hydrophobic parallel lines, to induce cellular alignment. The cells formed an anisotropic monolayer, those on the 10μm thick constructs were more constrained within the lines and cylindrical in shape compared with the cells on 2μm thick constructs (p<0.01). The cells were field stimulated at 2Hz to produce calcium transients which were optically mapped using Fluo-4. Compared with unaligned cultures, cells on the aligned constructs demonstrated a significant decrease in time to peak (tp unaligned=129±7ms, tp aligned=82±4ms, p<0.001, n=34,40 respectively) and 90% decay (t90 unaligned=453±17ms, t90 aligned=270±6ms, p<0.001, n=34,40 respectively). Within the aligned constructs, Parylene's thickness was found to affect calcium cycling parameters. Cells cultured on 2μm thick constructs showed a significant decrease in tp compared to 10μm thick constructs (tp 2μm thick=123±2ms, tp 10μm=107±2ms, p<0.001, n=326,197 respectively) and t90 (t90 2μm=275±1ms, t90 10μm=261±2ms, p<0.001, n=326,197 respectively). Microtubules were identified by immunofluorescence for alpha-tubulin, indicating a significant increase in their density on the aligned constructs compared to unaligned for both thicknesses (2μm thick:area covered aligned=63.1±1.4%, area covered unaligned=55.7±1.3%, p<0.01, n=180 for both; 10μm thick:area covered aligned=68.0±1.5%, area covered unaligned=54.4±1.3%, p<0.001, n=180,150 respectively). Also, cells on the 10μm thick micropatterned constructs had an increased microtubule density compared to the 2μm thick constructs (area covered 10μm thick=68.0±1.5%, area covered 2μm thick 63.1±1.4%, p<0.01, n=180). These results indicate that reorganisation of cardiomyocyte morphology with increased anisotropism causes enhanced calcium cycling, which is associated with increased microtubule density. Further study is required to determine the molecular mechanisms involved and whether microtubules can be targeted directly to favour cardiac cell maturation in culture.
Timing of Sexual Intercourse in Relation to Ovulation — Effects on the Probability of Conception, Survival of the Pregnancy, and Sex of the Baby
Authors: Allen J. Wilcox, Clarice R. Weinberg, Donna D. Baird
Journal: New England Journal of Medicine (1995)

The timing of sexual intercourse in relation to ovulation strongly influences the chance of conception, although the actual number of fertile days in a woman's menstrual cycle is uncertain. The timing of intercourse may also be associated with the sex of the baby.We recruited 221 healthy women who were planning to become pregnant. At the same time the women stopped using birth-control methods, they began collecting daily urine specimens and keeping daily records of whether they had sexual intercourse. We measured estrogen and progesterone metabolites in urine to estimate the day of ovulation.In a total of 625 menstrual cycles for which the dates of ovulation could be estimated, 192 pregnancies were initiated, as indicated by increases in the urinary concentration of human chorionic gonadotropin around the expected time of implantation. Two thirds (n = 129) ended in live births. Conception occurred only when intercourse took place during a six-day period that ended on the estimated day of ovulation. The probability of conception ranged from 0.10 when intercourse occurred five days before ovulation to 0.33 when it occurred on the day of ovulation itself. There was no evident relation between the age of sperm and the viability of the conceptus, although only 6 percent of the pregnancies could be firmly attributed to sperm that were three or more days old. Cycles producing male and female babies had similar patterns of intercourse in relation to ovulation.Among healthy women trying to conceive, nearly all pregnancies can be attributed to intercourse during a six-day period ending on the day of ovulation. For practical purposes, the timing of sexual intercourse in relation to ovulation has no influence on the sex of the baby.
Bureaucracy holds the NHS back
Authors: Kinesh Patel
Journal: BMJ (2013)

You’re all slackers! No, it’s not the junior doctors I have in my crosshairs. This time it’s you consultants. Judging from the vitriol published in the newspapers recently about how much less work you all do than your predecessors, it would seem as if you’re all on a voluntary go-slow. Is this a possible reason for the failure to increase productivity in the NHS?⇑

The problem is that these days everything takes more time than before. Take inserting a cannula, for example, one of the most routine tasks performed in hospitals. A decade ago it was just quick …
Abstract 3270: The effect of soy exposure in different ages on the mammary tumor development of the MMTV-ErbB-2 transgenic mice
Authors: Xiaoshan Feng, Jianfeng Hou, Shegan Gao
Journal: Cancer Research (2012)

Abstract Objective:To investigate the effect of different soy exposure timings on the mammary tumor development using MMTV-erbB-2 transgenic mice. Furthermore, the underlying mechanisms were also examined. Methods:120 MMTV-erbB-2 transgenic female mice were randomly divided into four groups:control group, early exposure group, late exposure group and lifelong exposure group. The control group mice were treated with soy free diet from week 3 to week 60, the experiment groups mice were treated with soy diet between week 3 to week 12, week 20 to week 60, week 3 to week 60, respectively. Then, the body weight change of each mice, the latency period, and the growth speed of mammary tumor were recorded. Furthermore, the mammary gland morphology was examined by whole mount at 5 weeks. In order to understand the underlying mechanisms of the mammary tumor development, the signal pathways of c-Fos, erbB2 and p-ERK were also examined in breast cancer tissue using immunohistochemistry. Results:We found that the weight in the four groups had no significant difference. Compared with the control group, the TEB numbers and the growth speed of tumors in the early exposure group and the lifelong exposure group were significantly decreased and the tumor latency periods were significantly prolonged (P&amp;lt;0.05). Furthermore, immunohistochemistry showed that the mice in the early exposure group and the lifelong exposure group displayed decreased expression of c-Fos and p-ERK (P&amp;lt;0.05). The expression of erbB-2 protein among the different groups was not statistically significant (P&amp;gt;0.05). Conclusion: Early or lifelong soy exposure affects the morphological development of mammary gland of MMTV-erbB-2 transgenic mice. Soy may display a preventive effect on the initiation of breast cancer. These obersveration may serve as a guide for soy use in the early prevention of the breast cancer. The c-Fos and and p-ERK may be involved in the development of mammary tumor in the MMTV-erbB-2 transgenic mice. The underlying mechanism warrants further studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3270. doi:1538-7445.AM2012-3270
Abstract 1435: Functional expression of chemokine receptor, CCR10, in patients with gastric cancer
Authors: Jae-Moon Bae, Jun Ho Lee, Myoung Cheorl Kook
Journal: Cancer Research (2010)

Abstract Objectives: There is increasing evidence that chemokines and chemokine receptors are causally involved in the metastasis of cancer. The aim of this study was to investigate the expression of chemokine receptors, CCR10, and its prognostic role in patients with gastric cancer. Methods: We screened the expression of CCR10 in 12 gastric cancer cell lines using the semi-quantitative RT-PCR. The expression of CCR10 was confirmed using Western blot and flow cytometry analysis of twelve gastric cancer cell lines. The function of CCR10 was examined using migration and proliferation assays. Then the migratory response of CCR10 was blocked using blocking antibodies. Finally, the clinical significance of the chemokine receptors was explored using tissue microarray methods and immunohistochemical staining of specimens from 753 gastric cancer patients. Results: We found that twelve out of twelve (100.0%) gastric carcinoma cell lines expressed a functional CCR10 for its ligand, chemokine CCL27 and CCL28, as demonstrated by the migration assays, and the migration was inhibited by anti-CCR10 antibodies. The clinical samples evaluated by immunohistochemical assay of tissue microarrays showed that CCR10-positive carcinoma cells were detected in 22 of 753 (2.9%) cases. We failed to show that the patients with CCR10-positive tumors had significantly poorer prognosis than did those with CCR10-negative tumors. Conclusion: These results suggest that CCR10 and its ligands were associated with increased tumor migration in gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1435.
THU0225 Prevalence of takayasu’s arteritis in IZMIR, turkey: A multicenter study
Authors: Y. Kucukyavas, K. Aksu, D. Solmaz, G. Can, A. Taylan, S. Akar, I. Sari, M. Birlik, F. Onen, N. Akkoc
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Takayasu’s Arteritis (TA) is known to be more common in Japanese, Indian and other East and Southeast Asian populations. Unpublished clinical observations indicate that it is relatively common also in Turkey since it is one of the most frequently diagnosed vasculitic disorders in Turkish population. However, until now no studies have examined its frequency in Turkey. Therefore, we have studied its epidemiology in the residents of Izmir. <h3>Methods</h3> All rheumatology units at two university and two research and training hospitals in central Izmir were contacted for the review of medical charts of the patients diagnosed as having TA. Electronic search was conducted when computerized health records were available by using the international classification of disease (ICD-10) code for TA (M31-4) and/or the name of the disease. The diagnosis of TA was confirmed by a rheumatologist according to the 1990 American College of Rheumatology (ACR) criteria for TA. The address information obtained from the charts was confirmed by phone calls or follow-up controls. Only Patients from central Izmir were included to the study. The population statistics of central Izmir was obtained from Turkish Statistical Institute, Izmir Branch. Incidence rate was calculated based on the newly diagnosed patients from 2006 to 2010 and the prevalence rate was calculated as point prevalence. <h3>Results</h3> Eighty-eight TA patients were detected after the review of medical charts and electronic patient records at university and educational-research hospitals in Izmir. Of these patients, 42 were residents of central Izmir as has been indicated by the review of address records. Based on the population of Central Izmir, minimum prevalence of TA was estimated as 15/million in September 2011 and 14.7/million in December 2010. Over the period from 2006 to 2010, we calculated a minimum incidence rate of 1.0/million (%95 CI 0.5-1.6) in the whole population, and of 0.8/million (%95 CI 0-1.6) in the population below the age of 40. Mean age for onset of symptoms was 33.6±10.8 (13-55) years and female/male ratio was 13/1. Type V and type I were the most frequent types according to angiographic classification, each occurring in about 41% of the patients. <h3>Conclusions</h3> TA seems to be relatively common in Turkish population consistent with the previous clinical observations. <h3>Disclosure of Interest</h3> None Declared
Abstract 3813: Uniparental disomy is associated with embryonal rhabdomyosarcoma in Costello Syndrome and nonsyndromic patients.
Authors: Katherine M. Robbins, Deborah L. Stabley, Katrina Conard, David J. Wu, Hunter Stitik, Edward A. Kolb, Andrew Napper, Robert W. Mason, Karen W. Gripp, Katia Sol-Church
Journal: Cancer Research (2013)

Abstract Embryonal rhabdomyosarcoma (ERMS) is the most prevalent pediatric soft tissue tumor and is characterized at the molecular level by loss of heterozygosity (LOH) at 11p15.5. We aimed to study ERMS in the context of Costello syndrome (CS), a rare syndromic predisposition to ERMS. Because CS arises from a typically paternal germline mutation in the proto-oncogene HRAS, it is considered a rasopathy. CS results in failure to thrive, intellectual disabilities, short stature, coarse facial features, skeletal abnormalities, congenital heart disease, and a predisposition for cancer, most commonly ERMS. We molecularly characterized seven ERMS tumors from six unrelated CS patients, carrying paternally derived HRAS p.G12S (5) or p.G12A (2) mutations. LOH was evaluated in all CS ERMS tumors by microarray and/or using short tandem repeat (STR) markers along both arms of chromosome 11. One patient developed a second primary ERMS tumor showing the ERMS hallmark LOH limited to 11p15.5. The six other CS ERMS tumors displayed paternal uniparental disomy (UPD) of the entire chromosome 11. Paternal UPD was also observed in a pure ERMS cell line, established using fresh tumor sample from one of the patients with a p.G12A germline mutation. This represents, to our knowledge, the first CS ERMS cell line. Additional cell lines derived from non CS patients were used in this study and included two ERMS (RD and RH36), one Alveolar RMS (RH30), and one mixed A/ERMS (RH18). RH36 cells carried an HRAS mutation at position 61 (p.Q61K). Unexpectedly, both ERMS cell lines, RD and RH36, displayed a complete LOH for chromosome 11. The ARMS RH30 cells carried no mutation in HRAS or LOH. RH18 cells derived from an A/ERMS had no HRAS mutation and showed LOH on both, the p and q arm of chromosome 11, except at locus D11S1338. Cytogenetic analysis with fluorescence in situ hybridization (FISH) on three CS tumors revealed multiple copies of chromosome 11 leading to trisomies and tetrasomies in the tumor and cultured cells. Gene expression revealed loss of imprinting in the growth regulating genes H19, IGF2, and CDKN1C on chromosome 11 not only in CS tumors, but also in nonsyndromic ERMS. Citation Format: Katherine M. Robbins, Deborah L. Stabley, Katrina Conard, David J. Wu, Hunter Stitik, Edward A. Kolb, Andrew Napper, Robert W. Mason, Karen W. Gripp, Katia Sol-Church. Uniparental disomy is associated with embryonal rhabdomyosarcoma in Costello Syndrome and nonsyndromic patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3813. doi:10.1158/1538-7445.AM2013-3813
Death after Transplantation of a Liver from a Donor with Unrecognized Ornithine Transcarbamylase Deficiency
Authors: Walter Plöchl, Christian K. Spiss, Engelbert Plöchl
Journal: New England Journal of Medicine (1999)

To the Editor: Ornithine transcarbamylase deficiency is the most common inherited disorder of the urea cycle.1,2 It is an X-linked disease that can range in severity from hyperammonemic coma in neonates to the absence of symptoms in adults.1,2 Liver transplantation is an effective treatment for patients with this disease.3 However, this disease has another implication for liver transplantation, as demonstrated by the following case. In December 1998, a 65-year-old woman underwent orthotopic liver transplantation for liver cirrhosis related to hepatitis C infection and hepatocellular carcinoma. She was extubated on the first postoperative day and initially did well ( . . .
Duodenal bleeding caused by pancreatic tuberculosis in a patient with AIDS and disseminated tuberculosis
Authors: C.-W. Cheng, Y.-K. Tsou, G.-W. Fan, K. Wu, C.-C. Yang, W.-Y. Chuang, M.-H. Lee
Journal: Endoscopy (2012)

Pancreatic tuberculosis is a rare but increasingly recognized disease [1]. Its common clinical manifestations include pancreatic masses that can mimic carcinoma, pancreatitis, and obstructive jaundice [2]. We report a unique case of pancreatic tuberculosis presenting with acute upper gastrointestinal bleeding due to duodenal involvement.
Abstract P4-01-05: Lapatinib Resistance Confers Cross-Resistance to Microtubule Inhibitors in ErbB2-Overexpressing Breast Cancer Cells
Authors: K Araki, M Gallas, X Liu, A-M Jegg, T Ward, M. Pegram
Journal: Cancer Research (2010)

Abstract ErbB2 gene amplification occurs in approximately 20% of all breast cancers and is associated with an aggressive subtype with poor clinical prognosis. Acquired resistance to erbB2-targeted therapies is a common occurance even in patients who show an initial clinical response to trastuzumab or lapatinib-based regimens. Optimal treatment for relapsed disease following erbB2 targeted therapies has not been defined. Therefore, we sought to evaluate whether cytotoxic agents have cross-resistance to lapatinib in cell lines that have acquired resistance to lapatinib. Here we established a model of acquired lapatinib resistance derived from erbB2 overexpressing breast cancer cell lines, BT474 and SKBR3. Lapatinib resistant cell lines, BTLapR and SKLapR, were generated by growth in the continuous presence of 2.6 uM lapatinib (peak plasma concentration in human subjects) resulting in IC50 of 4.72 uM (BTLapR) and 0.083 uM (BT474) (P&amp;lt;0.0001). IC50 of SKLapR and SKBR3 were 17.72 uM and 0.1637 uM (P&amp;lt;0.0001), respectively. Next, resulting cells were treated with different classes of chemotherapeutics (2 taxanes, 2 vinca-alkaloids, 1 epothilone, 1 anthracycline, 1 antimetabolite, 2 platinums, and 1 alkylating agent) in order to address cross-resistance to lapatinib. BT474 and BTLapR as well as SKBR3 and SKLapR were exposed to each chemotherapeutic agent and cell viability was evaluated at 72h using a cell proliferation assay (AlamarBlue®). We found that BTLapR was significantly cross-resistant to 5 microtubule inhibitors (paclitaxel, docetaxel, vinorelbine, vinblastine, and ixabepilone), but SKLapR was not (shown in table below). IC 50 of Significant Drugs on Lapatinib Resistant BT474 cells Previous studies have shown that resistance to lapatinib can switch cell survival signaling from the erbB2 to ER pathway, and that ER signaling can stimulate beta III tubulin expression. We therefore hypothesize the differential responses to microtubule inhibitors in BTLapR and SKLapR might be explained by the fact that BT474 has both estrogen (ER) and progesterone receptor (PR), but SKBR3 express neither. Moreover, beta-III tubulin is known to be a key resistance mechanism of microtubule inhibition. Western blot analysis of baseline protein expression in both acquired lapatinib-resistant and parental cells indicates that ER signaling is involved in stimulating beta III tubulin and is linked to the development of resistance to microtubule inhibitors. These findings point to a potential mechanism to address cross resistance between lapatinib and microtubule-interacting agents, which could have potential clinical implications when considering salvage therapies following lapatinib treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-01-05.
Researchers Gain Insights Into Suppressor Gene Function
Authors: J. Bowersox
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Researchers Gain Insights Into Suppressor Gene Function Get access John Bowersox John Bowersox Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 16, 19 August 1992, Pages 1233–1234, https://doi.org/10.1093/jnci/84.16.1233 Published: 19 August 1992
AB0328 Factors associated with normalized physical function and clinical remission defined with simplified disease activity index by 1-yaear infliximab treatment in patients with rheumatoid arthritis
Authors: R. Matsudaira, N. Tamura, T. Watanabe, M. Matsushita, M. Ogasawara, K. Yamaji, Y. Takasaki
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> We previously reported that the presence of anti-Ro/SS-A antibody (anti-Ro) was an independent factor for poor clinical response to TNF-alpha inhibitors in patients with rheumatoid arthritis (RA). <h3>Objectives</h3> To investigate factors associated with normalized physical function, and clinical remission determined by simplified disease activity index (SDAI) at 54 weeks of infliximab (IFX) treatment in patients with RA. <h3>Methods</h3> We studied 114 patients with RA treated with IFX, and prospectively examined SDAI, Disease Activity Score in 28 joints (DAS28)/CRP, and modified Health Assessment Questionnaire Disability Index (mHAQ-DI). The clinical remission was defined with simplified disease activity index (SDAI) ≤3.3, and normal physical function was defined by mHAQ-DI&lt;0.5. The baseline characteristics of categorical variables, including (anti-Ro), were compared at 54 weeks. <h3>Results</h3> Among 114 patients, 20 patients were withdrawn from this study because they had discontinued by 54 weeks (one was infection, one was reaction of allergy, and others were stopped IFX because of no efficacy). Age, gender, duration, SDAI and DAS28 at baseline were 50.14±13.15, 79 female/15male, 9.40±7.98, 4.19±1.14, and 25.43±12.78, respectively. In 94 patients, 17 (18.1%) and 33 (35.1%) were achieved remission defined with SDAI and DAS28/CRP, respectively. Normalized physical function, mHAQ&lt;0.5, was recognized in 65 patients (69.1%, HAQ remission group). Logistic regression analysis revealed that characteristics mHAQ ≥0.5, the presence of secondary Sjogren's syndrome, and positive anti-Ro at baseline were significantly associated with normalized physical function (OR 5.83; 95%CI 1.96-17.26, OR 3.62; 95%CI 1.12-11.67, and OR 4.28; 95%CI 1.35-13.53, respectively). As regards other baseline characteristics: age, gender, duration, dose of methotrexate, dose of prednisolone, SDAI, DAS28, titer of anti-cyclic citrullinated peptide antibody and values of rheumatoid factor, there was no significant difference between the groups. On the other hand, low mHAQ, and low ESR, were independently associated with achievement of SDAI remission at 54 weeks (p=0.0098, and p=0.027, respectively). <h3>Conclusions</h3> The prevalence of secondary SS and the presence of anti-Ro/SS-A antibodies before IFX treatment might associate with the outcome of poor physical function. To attain SDAI remission and normal physical function, tight control is necessary to prevent irreversible physical dysfunction. <h3>Disclosure of Interest</h3> None Declared