tbuckley/cabot-search huggingface dataset:
Self-Expanding Coil Stent with a Long Delivery System for Palliation of Unresectable Malignant Gastric Outlet Obstruction: A Prospective Study
Authors: J H Kim, B M Yoo, K J Lee, K B Hahm, S W Cho, J J Park, S S Kim, H C Park, J H Kim
Journal: Endoscopy (2001)

Peroral intubation of a self-expanding metal stent is usually difficult in patients with unresectable malignant gastric outlet obstruction, because the delivery systems currently available are not long enough and cannot easily pass the angulated gastroduodenal structure. We carried out a prospective study to assess the efficacy of a coil stent with a newly developed long delivery system, for palliation of unresectable malignant gastric outlet obstruction.In 29 patients with unresectable malignant gastric outlet obstruction, caused by gastric cancer (26 patients), pancreatic head cancer (two patients), or duodenal cancer (one patient), peroral intubation of a self-expanding nickel-titanium coil stent was attempted, using a lengthened delivery system of 150 cm, under endoscopic and fluoroscopic guidance.Management was successful in 26 of 29 patients (89.7 %) without immediate major complications. In one patient in whom peroral intubation failed, percutaneous intubation of the coil stent via percutaneous endoscopic gastrostomy was done. After insertion of the coil stent, food ingestion with symptomatic improvement with regard to vomiting was achieved in 26 of 27 patients (96.3 %), including the patient with percutaneous stent insertion. During the follow-up period, dysphagia and Karnofsky scores improved significantly. Stent migration occurred in two patients, and tumor ingrowth in another two; re-intervention was done successfully performed in two instances. The mean survival time was 124 days (range 34 - 310 days) in the 22 patients who had no need for re-intervention during follow-up; among these was a patient who experienced stent occlusion by food material, which was easily corrected with endoscopic flushing.Peroral intubation of a self-expanding coil stent using a long delivery system is a safe and effective palliative technique for unresectable malignant gastric outlet obstruction, and significantly improves the quality of life of patients.
Abstract 245: KIF1Bβ interacts with YME1L1, resulting in apoptosis accompanied by the alteration of mitochondrial morphology
Authors: Koji Ando, Tomoki Tokochi, Akira Mukai, Yoshihiko Maehara, Akira Nakagawara
Journal: Cancer Research (2011)

Abstract We previously reported that KIF1Bβ is a tumor suppressor gene mapped to chromosome 1p36.2, and is related to apoptosis (JBC, 2008). It is known that cell survival and apoptosis have a close relationship with mitochondrial morphology, such as fusion and fragmentation. Cell survival and resistance to pro-apoptotic stimuli is related to mitochondrial fusion. On the other hand, apoptosis is frequently associated with mitochondrial fragmentation. Considering these facts, we hypothesized that KIF1Bβ might play an important role in the morphological change in mitochondria. The mitochondrial morphology was examined by indirect immunofluoresence using MitoTracker Red® and anti-cytochrome c antibody. To quantify the degree of mitochondrial fusion, we used JC-1 probe. Yeast two hybrid screening was performed to identify the interacting proteins of KIF1Bβ. Mitochondrial fusion was facilitated in both NB1 (neuroblastoma cell line which KIF1Bβ is homozygously deleted) and HeLa in which KIF1Bβ was knocked down. This result suggests that KIF1Bβ takes part in the process of morphological change in mitochondria. Those cells were resistant to doxorubicin treatment, demonstrating that apoptosis was prevented accompanied by mitochondrial fusion. Overexpression of KIF1Bβ induced mitochondrial fragmentation, enhanced cytochrome c release into the cytoplasm, and resulted in apoptosis. These results are consistent with the properties of KIF1Bβ as a tumor suppressor described previously. On the other hand, overexpression of KIF1Bβ lacking the death inducing region neither induced mitochondrial fragmentation nor apoptosis, indicating that the death inducing region is essential for the alteration of mitochondrial morphology and induction of apoptosis. Utilizing yeast two hybrid screening, we found several proteins physically interacting with KIF1Bβ. We identified YME1L1, the mitochondrial metalloprotease, which is known to cleave mitochondrial fusion protein OPA1. Overexpression of YME1L1 cleaved OPA1 in the presence of KIF1Bβ. However, OPA1 cleavage was partially inhibited in the absence of KIF1Bβ, suggesting that KIF1Bβ enhances the activity of YME1L1 as a protease to cleave OPA1. Interestingly, high expression of YME1L1 was associated with better survival of neuroblastoma patients (n=101; p=0.046), while high expression of OPA1 was correlated with poor outcome (n=101; p=0.04). These results suggest that the tumor suppressor KIF1Bβ takes part in the alteration of mitochondrial morphology collaborating with an interacting partner YME1L1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 245. doi:10.1158/1538-7445.AM2011-245
Abstract 720: Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2 extracellular domain in human breast cancer cells
Authors: Ryosuke Yoshida, Hiroshi Tazawa, Yuuri Hashimoto, Futoshi Uno, Shunsuke Kagawa, Toshiyoshi Fujiwara
Journal: Cancer Research (2011)

Abstract Human epidermal growth factor receptor 2 (HER2) is a member of a family of receptors associated with tumor cell proliferation, apoptosis, adhesion, migration, and differentiation. According to numerous preclinical and clinical studies, HER2 can be immunogenic and antibodies against this transmembrane receptor have become in use in individuals with HER2-overexpressing tumors. Trastuzumab, a monoclonal antibody that targets HER2, induces antibody-dependent cellular cytotoxicity (ADCC) and inhibits HER2-mediated signaling. Numerous randomized trials have confirmed the utility of trastuzumab in HER2-overexpressing breast cancer in various clinical scenarios; however, HER2-overexpression has been identified only in approximately 25-30% of primary breast cancers. Moreover, it has been reported that the majority of metastatic breast cancer patients treated with trastuzumab develop acquired resistance within a year. In this study, we analyzed the mechanism of resistance to trastuzumab and examined for molecular sensitization by exogenous expression of HER2 extracellular domain in human breast cancer cells. A long-term exposure to trastuzumab induced its resistance in HER2-positive breast cancer cells. We found that trastuzumab-resistant cells exhibited down-regulation of HER2 expression in cell surface and impaired ADCC activity, suggesting that trastuzumab-resistant cells could be re-sensitized to trastuzumab by exogenous induction of extracellular domain (ECD) of HER2.We constructed the expression vector with HER2-ECD and stably transfected into low HER2-expressing human breast cancer cell line, MCF7. HER2-ECD expression had no apparent effect on the growth and signaling pathway in MCF7 cells; however, ADCC activity was strongly enhanced in HER2-ECD-expressing MCF7 cells compared to parental MCF7 cells. These results suggest that exogenous expression of HER2-ECD might be an appropriate strategy to sensitize HER2-negative or trastuzumab-resistant human breast cancer cells to trastuzumab. The modification of the tumor-specific replication-competent adenovirus (OBP-301, Telomelysin) to contain the HER2-ECD gene for exogenous expression is currently under the investigation. We will further examine the antitumor effects of this virus in the combination with trastuzumab. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 720. doi:10.1158/1538-7445.AM2011-720
The insufficiency of associative learning for explaining development: Three challenges to the associative account
Authors: Bennett I Bertenthal
Journal: Behavioral and Brain Sciences (2014)

Abstract Three challenges to the sufficiency of the associative account for explaining the development of mirror mechanisms are discussed: Genetic predispositions interact with associative learning, infants show predispositions to imitate human as opposed to nonhuman actions, and early and later learning involve different mechanisms. Legitimate objections to an extreme nativist account are raised, but the proposed solution is equally problematic.
SAT0320 High frequency of cardiovascular disease in patients with knee osteoarthritis in a primary care setting:
Authors: N. Navarro, C. Orellana, I. Vázquez, E. Casado, J. Gratacόs, M. Larrosa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with knee osteoarthritis (KOA), due to age, walking functional impairment and/or a high prevalence of obesity, are at a high risk of metabolic disorders and cardiovascular (CV) comorbidities, especially in patients referred to rheumatologists or orthopedic surgeons because of advanced disease for symptom control or surgery. <h3>Objectives</h3> To evaluate the frequency of metabolic disorders and CV comorbidity in patients with symptomatic KOA referred to a rheumatologist in a primary care setting. <h3>Methods</h3> Consecutive patients aged &gt;50 y referred period to a rheumatology practice in a primary care setting because of symptomatic KOA during a 12-month period. Diagnostics related to CV comorbidity and/or glycemic or lipid disorders (hypertension, diabetes, ischemic heart disease, heart failure, cerebrovascular disorder, venous insufficiency or dyslipemia) were obtained for each patient from the HC3 (Història Clínica Compartida de Catalunya), a computerized database from the public health service. Patients with soft tissue disorders (e.g. shoulder tendinitis, plantar fasciitis, etc) adjusted for age were used as control group. Patients with soft tissue disorders (e.g. shoulder tendinitis, plantar fasciitis, etc) adjusted for age were used as control group. <h3>Results</h3> One hundred and eighty-four patients with KOA and 254 with soft tissue conditions were included in this cross-sectional study. Patients with KOA but additional OA in other joints (hip, hands) were excluded. The frequencies of hypertension, hyperglycemia/diabetes and obesity significantly higher in patients with KOA compared to the control group (Table). However, diabetes/hyperglycemia and/or dyslipemia rates were not different between groups. Metabolic syndrome was also significantly more prevalent among patients with KOA (Table). When analyzing the history of complications of cardiovascular disease such as ischemic heart disease or cerebrovascular complications, patients with KOA also showed a significantly higher rate as compared with the control group (16/184 (8.7%) vs. 9/254 (3.5%), p&lt;0.05). [Table] <h3>Conclusions</h3> In a primary care setting patients with knee OA showed a high frequency of cardiovascular risk factors and metabolic syndrome and what is more important cardiovascular disease complications appeared to be also more frequent in this population. <h3>Disclosure of Interest</h3> None Declared
Treatment of Severe Fluid Overload by Ultrafiltration
Authors: Marc Eliot Silverstein, Cheryl A. Ford, Michael J. Lysaght, Lee W. Henderson
Journal: New England Journal of Medicine (1974)

A recently developed ultrafiltration cell was clinically evaluated and found to remove excess sodium and water efficiently, rapidly, and inexpensively from fluid-overloaded patients on chronic hemodialysis. The extracorporeal circuit is designed to run in series with the artificial kidney or as a separate unit. With constant blood flow, ultrafiltration flux rate increased as a linear function of transmembrane pressure up to 200 mm Hg. Ultrafiltration rates of 300 to 800 ml per hour were readily achievable, and the fluid removal rate was quantitated and adjusted as the clinical picture dictated. Complications of ultrafiltration were rare and included leg cramps and orthostatic hypertension. The solute concentrations in the ultrafiltrate were identical to plasma water, thereby avoiding electrolyte and acid-base disturbances. This therapy is simpler and safer than peritoneal dialysis or hemodialysis; we speculate that it could logically be extended to patients with refractory chronic edematous states or with pulmonary edema. (N Engl J Med 291:747–751, 1974
Are Dietary Fat and Vasectomy Risk Factors for Prostate Cancer?
Authors: R. B. Hayes
Journal: JNCI Journal of the National Cancer Institute (1995)

Prostate cancer is the most commonly diagnosed malignancy among US males. Its incidence, however, varies markedly from 2 per 100,000 per year in Shanghai, China, to 62 and 82, respectively, for US Whites and Blacks. Mortality due to prostate cancer is twice as high among US Blacks than among US Whites. A familial component is important in determining prostate cancer risk, but does not appear to explain the variation in rates between US Blacks and Whites. Dietary fat, the consumption of which varies on a national basis in parallel with prostate cancer rates, may be a major risk factor for the disease. A study by Whittemore et al. involved more than 1500 cases and controls including Whites, Blacks, Chinese-Americans, and Japanese-Americans in five cities in the US and Canada. On the basis of detailed dietary interviews, Whittemore shows that prostate cancer risk increases with higher intake of saturated fat. The effect holds true for both younger and older men. The risk was significantly elevated for Asian-Americans, and less pronounced for Blacks and Whites, yet nonetheless consistent with an overall excess. Risk was unrelated to the intake of other macronutrients, intake of vitamin A, intake of fruits and vegetables, body mass, or physical activity. Among Asian-Americans, long-term residents in the US were at greatest risk of prostate cancer independent of dietary fat intake. A study by John et al. has found vasectomy to not be related to the development of prostate cancer. Reasons why the finding of this study is opposite from the general body of evidence supporting an increased risk of prostate cancer following vasectomy are not apparent.
Renal Scintigraphy in a Patient With Retroperitoneal Fibrosis
Authors: JAMIL MOHSIN, CHUN K. KIM
Journal: Clinical Nuclear Medicine (1996)

Retroperitoneal fibrosis is a rare disease. Approximately two thirds of patients with this disease develop renal failure secondary to ureteral obstruction. Although urography is diagnostic in most of these cases, varying urographic appearances have been described. For the evaluation of overall renal function and obstruction before and after surgical intervention in these cases, renal scintigraphy can play an important role, particularly in the presence of renal function compromise. The authors present a renal scan and urography performed after ureterolysis and lateralization of the ureters in a patient with retroperitoneal fibrosis.
Abstract C38: Metformin inhibits cancer cell growth in an AMP kinase-independent and -dependent manner
Authors: Ramandeep Rattan, Shailendra Giri, Lynn C. Hartmann, Viji Shridhar
Journal: Cancer Research (2009)

Abstract Metformin is the most widely used drug for type 2 diabetes. Metformin activates AMP-activated protein kinase (AMPK), which regulates cellular energy metabolism via its upstream kinase LKB1. Activation of AMPK has been shown extensively to cause growth arrest in multiple tumor types by inhibiting the TSC-mTOR (mammalian target of rapamycin) pathway as well as by inducing cell cycle arrest. Our data indicate that metformin exerts an anti-proliferative effect on several chemo-responsive and -resistant ovarian cancer cell lines (A2780, CP70, C200, OV202, OVCAR3 and SKVO3ip, PE01, PE04), which is accompanied by activation of AMPK and cell cycle arrest. Interestingly, we have also determined that metformin is able to inhibit proliferation of ovarian cancer cells when AMPK is silenced by siRNA, where both the expression and activation of AMPK is significantly reduced. Also, metformin was able to attenuate proliferation of AMPK (−/−) mefs, although to a lesser degree in AMPK (+/+) mefs. Additional results indicate that metformin activates p21 and inhibits cyclinD1 activities partially in AMPK (−/) mefs. These data suggest a novel mechanism of metformin action, namely, an AMPK independent pathway which can modulate proliferation and possibly cell cycle regulated events in ovarian cancer. Whether the AMPK independent effects of metformin require LKB1 activity is currently under investigation. Collectively, our preliminary observations indicate that metformin can modulate proliferation and cell cycle arrest in an AMPK independent manner. Citation Information: Cancer Res 2009;69(23 Suppl):C38.
SAT0158 Assessment of Systolic and Diastolic Cardiac Function by Tissue Echo Doppler in Ambulatory Patients with Rheumatoid Arthritis
Authors: J.P. Vinicki, F. Cintora, A. Saad, S. Berensztein, G. Nasswetter
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid Arthritis (RA) is a chronic inflammatory disease that affects 1% of the world9s population. Patients with RA are at increased risk of cardiovascular disease (CVD) and they have lower survivals than the general population mainly due to an accelerated atherosclerosis caused by inflammatory mechanisms. The early detection of subclinical CVD could allow a more aggressive treatment of risk factors. <h3>Objectives</h3> The purpose of this study was to analyze systolic and diastolic cardiac function by echocardiography and tissue Doppler imaging in patients with RA as well as to compare them with a control group. <h3>Methods</h3> Eighty two patients with RA (ACR/EULAR, 2010) and 17 of the control group were studied. Patients with atrial fibrillation, diabetes and known structural heart disease of any etiology were excluded. A 2D echocardiography, echo-Doppler and tissue Doppler were achieved following the recommendations of the American Society of Echocardiography. Categorical variables were compared with χ<sup>2</sup> test while the continuous ones were compared with the T test. A p&lt;0.05 was considered statistically significant. <h3>Results</h3> Seventy-five patients with RA (mean age 55±13 years, 95% female) and 16 controls (mean age 51±18 years, 88% female) were included. Median time from diagnosis of RA 10.7 (±9.2) years. There were no differences in sex, age, prevalence of cardiovascular risk factors, arterial pressure and anthropometric measures between the two groups. Patients with RA had greater left atrium dimensions, higher systolic pulmonary pressure and higher E/e ratio in both ventricles than the control group. On the contrary, patients with RA had a lower tricuspid and mitral systolic annular plane excursion and a lower systolic left ventricular tissue Doppler velocity. In the following table we describe the most relevant findings. <h3>Conclusions</h3> Presence of premature disturbances in both systolic and diastolic heart function was found in RA patients compared with control group. Early detection of patients at increased risk of coronary artery disease would allow early treatment and improved survival. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6060
P2-08-02: Magnetic Resonance Imaging as a Predictor of Pathologic Response in Patients Treated with Neoadjuvant Systemic Treatment for Operable Breast Cancer (TBCRC 017).
Authors: Los Santos J De, A Cantor, K Mcguire, M Golshan, F Meric-Bernstam, J Horton, R Nanda, K Amos, A Forero, C Hudis, I Meszoely, S Hwang
Journal: Cancer Research (2011)

Abstract Background: Increased pathologic complete response (pCR) rates observed with neoadjuvant chemotherapy for invasive breast cancer has prompted interest in whether patients with pCR can be identified preoperatively and potentially spared the morbidity of surgery. This multicenter retrospective study was performed to determine the accuracy of preoperative MRI in predicting pCR in the breast and whether MRI performance differs by molecular subtype, histology, and treatment regimen. Methods: 770 women from 8 institutions were retrospectively identified as having received neoadjuvant systemic therapy with MRI obtained at baseline and after completion of systemic treatment. Tumor phenotypes were defined on the basis of estrogen and progesterone receptor (ER/PR or HR) and HER2 receptor status. Univariate and multivariate analyses of factors influencing radiographic complete response (rCR) and pCR were recorded, with rCR defined as resolution of any abnormal enhancement, mass, or distortion on MRI, and pCR defined as resolution of both invasive disease and DCIS. Results: rCR and pCR for the total group were 182/746 (24%) and 179/746 (24%), respectively, with the highest rate of pCR seen among the triple-negative (TN; 57/155; 37%) and HR-/HER2+ (38/101; 38%) subtypes. Covariates significantly associated with rCR included T stage (p=0.0002), tumor grade (p=0.005), IHC phenotype (p=0.005), and chemotherapy regimen (p&amp;lt;0.0001). On multivariate analysis, only tumor phenotype was independently associated with likelihood of rCR, with both TN (OR = 2.00, 95% CI 1.20−3.33) and HR-HER2+ (OR=2.30, 95% CI 1.09–4.83) more likely to achieve rCR than HR+HER- (reference group). Overall accuracy of MRI for prediction of pCR was 74%. Sensitivity, NPV, PPV, and accuracy differed significantly among tumor subtypes, with the greatest NPV in the HR-/HER2+ and TN subtypes (table1). Among patients with rCR, ER- status (OR=6.4, 95% CI 1.1 to 35.6), PR- status (OR=3.8, 95% CI 1.2 to 11.4), and tumor grade of 3 vs 1 or 2 (OR=2.49, 95% CI 1.22−5.07) were independently associated with likelihood of pCR. Discussion: MRI performance for predicting pCR in patients with invasive breast cancer receiving neoadjuvant systemic therapy differed significantly among breast cancer subtypes; however this difference is likely due to subtype differences in frequency of pCR and not to intrinsically better or worse MRI detection. The relatively low NPV of MRI following neoadjuvant systemic therapy does not support using MRI rCR alone to accurately identify those patients that can safely avoid surgery. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-02.
Enzyme-Substitution Therapy with the Yeast<i>Saccharomyces cerevisiae</i>in Congenital Sucrase-Isomaltase Deficiency
Authors: Hinrich-Karsten Harms, Rose-Marie Bertele-Harms, Dorothea Bruer-Kleis
Journal: New England Journal of Medicine (1987)

Sucrase–isomaltase deficiency is an inherited disaccharidase deficiency that leads to malabsorption of sucrose, with resulting diarrhea and abdominal distention and cramps. We investigated the sucrose-splitting effect of viable yeast cells in eight children with congenital sucrase–isomaltase deficiency, by means of the sucrose hydrogen breath test. This test is based on the fact that hydrogen is released from the malabsorbed sucrose by the colonic microflora. We found that 0.3 g of lyophilized Saccharomyces cerevisiae, given after loading with 2 g of sucrose per kilogram of body weight, reduced hydrogen excretion in all patients, on average by 70 percent, in parallel with a complete loss or evident reduction of clinical symptoms. In vitro, lyophilized and fresh S. cerevisiae (fresh baker's yeast) had appreciable sucrase activity, a low isomaltase and maltase activity, and virtually no lactase activity. The sucrase activity was more inhibited by undiluted than by diluted gastric juice. We conclude that patients with congenital sucrase–isomaltase deficiency who intentionally or unintentionally consume sucrose can ameliorate the malabsorption by subsequently ingesting a small amount of viable yeast cells, preferably on a full stomach. (N Engl J Med 1987; 316: 1306–9.)