tbuckley/cabot-search huggingface dataset:
Calorie-Providing Nutrients and Risk of Breast Cancer
Authors: P. Toniolo, E. Riboli, F. Protta, M. Charrel, A. P. M. Cappa
Journal: JNCI Journal of the National Cancer Institute (1989)

A case-control study was conducted in Italy to investigate the role of diet in breast cancer. Cases were 250 women with breast cancer, and controls were a stratified random sample of 499 women from the general population. A dietary history questionnaire was used to measure the intake of total fat, saturated fat, animal proteins, and other macronutrients. In multivariate analyses, the relative risks of breast cancer for women in the highest quintile of consumption of saturated fat and animal proteins were 3.0 (95% confidence interval, 1.9–4.7) and 2.9 (1.8–4.6), respectively. A reduced risk was found for women who derived <28% of calories from fat versus >36%. A similarly reduced risk was found for women who derived <9.6% of calories from saturated fat or <5.9% from animal proteins. These data suggest that during adult life, a reduction in dietary intake of fat and proteins of animal origin may contribute to a substantial reduction in the incidence of breast cancer in population subgroups with high intake of animal products.
Mitosis-specific phosphorylation of amyloid precursor protein at Threonine 668 leads to its altered processing and association with centrosomes
Authors: Monique Judge, Lisa Hornbeck, Huntington Potter, Jaya Padmanabhan
Journal: Molecular Neurodegeneration (2011)

Abstract Background Atypical expression of cell cycle regulatory proteins has been implicated in Alzheimer's disease (AD), but the molecular mechanisms by which they induce neurodegeneration are not well understood. We examined transgenic mice expressing human amyloid precursor protein (APP) and presenilin 1 (PS1) for changes in cell cycle regulatory proteins to determine whether there is a correlation between cell cycle activation and pathology development in AD. Results Our studies in the AD transgenic mice show significantly higher levels of cyclin E, cyclin D1, E2F1, and P-cdc2 in the cells in the vicinity of the plaques where maximum levels of Threonine 668 (Thr668)-phosphorylated APP accumulation was observed. This suggests that the cell cycle regulatory proteins might be influencing plaque pathology by affecting APP phosphorylation. Using neuroglioma cells overexpressing APP we demonstrate that phosphorylation of APP at Thr668 is mitosis-specific. Cells undergoing mitosis show altered cellular distribution and localization of P-APP at the centrosomes. Also, Thr668 phosphorylation in mitosis correlates with increased processing of APP to generate Aβ and the C-terminal fragment of APP, which is prevented by pharmacological inhibitors of the G1/S transition. Conclusions The data presented here suggests that cell cycle-dependent phosphorylation of APP may affect its normal cellular function. For example, association of P-APP with the centrosome may affect spindle assembly and cell cycle progression, further contributing to the development of pathology in AD. The experiments with G1/S inhibitors suggest that cell cycle inhibition may impede the development of Alzheimer's pathology by suppressing modification of βAPP, and thus may represent a novel approach to AD treatment. Finally, the cell cycle regulated phosphorylation and processing of APP into Aβ and the C-terminal fragment suggest that these proteins may have a normal function during mitosis.
The acute effect of budesonide/formoterol in COPD: a multi-slice computed tomography and lung function study
Authors: Lieve A. De Backer, Wim Vos, Jan De Backer, Cedric Van Holsbeke, Samir Vinchurkar, Wilfried De Backer
Journal: European Respiratory Journal (2011)

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of chronic obstructive pulmonary disease (COPD) does not always match with other clinical disease descriptors such as exacerbation frequency and quality of life, indicating that forced expiratory volume in 1 s (FEV 1 ) is not a perfect descriptor of the disease. The aim of this study was to find out whether changes in airway geometry after inhalation of the most commonly used inhalation therapy in severe COPD can more adequately be described with an image-based approach than with spirometry. 10 COPD GOLD stage III patients were assessed in a double-blind crossover study. Airway volumes were analysed using segmentation of multi-slice computed tomography (MSCT) images; airway resistance was determined using computational fluid dynamics (CFD). Distal airway volume significantly increased (p=0.011) in patients 4 h after receiving a budesonide/formoterol combination from 9.6±4.67 cm 3 to 10.14±4.81 cm 3 . Also CFD-determined airway resistance significantly decreased (p=0.047) from 0.051±0.021 kPa·s·L −1 to 0.043±0.019 kPa·s·L −1 . None of the lung function parameters showed a significant change. Only functional residual capacity (FRC) showed a trend to decline (p=0.056). Only the image-based parameters were able to predict the visit at which the combination product was administered. This study showed that imaging is a sensitive, complementary tool to describe changes in airway structure.
Impact of Progestin and Estrogen Potency in Oral Contraceptives on Ovarian Cancer Risk
Authors: Joellen M Schildkraut, Brian Calingaert, Polly A Marchbanks, Patricia G Moorman, Gustavo C Rodriguez
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Oral contraceptive (OC) use is associated with a reduced risk of developing ovarian cancer, but the mechanism for the risk reduction has not been well defined. In this study, we investigate the relationship between the progestin and estrogen potency in combination OCs and the risk of developing ovarian cancer. Methods: The study included 390 case subjects with epithelial ovarian cancer and 2865 control subjects, between 20 and 54 years of age, identified from the Cancer and Steroid Hormone Study. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between ovarian cancer risk and combination OC formulations while controlling for potential confounders. All statistical tests were two-sided. Results: With users of high-progestin/high-estrogen potency OC as the referent group, users of low-progestin/high-estrogen potency formulations (adjusted OR = 2.1; 95% CI = 1.2 to 3.7) and low-progestin/low-estrogen potency formulations (adjusted OR = 1.6; 95% CI = 0.9 to 3.0) had a higher risk of ovarian cancer than users of high-progestin/high-estrogen potency formulation. Low-progestin potency OC formulations were associated with a statistically significant higher risk than high-progestin potency formulations (adjusted OR = 2.2; 95% CI = 1.3 to 3.9). This association was seen even among users of short duration. Conclusion: The combination OC formulations with high-progestin potency appear to be associated with a greater reduction in ovarian cancer risk than those with low-progestin potency. Mechanisms underlying this reduction may include inhibition of ovulation and/or some direct biologic effects of the progestin.
How ADAM-9 and ADAM-11 Differentially From Estrogen Receptor Predict Response to Tamoxifen Treatment in Patients with Recurrent Breast Cancer: a Retrospective Study
Authors: Anieta M. Sieuwerts, Marion E. Meijer-van Gelder, Mieke Timmermans, Anita M.A.C. Trapman, Roberto Rodriguez Garcia, Miranda Arnold, Anneke J.W. Goedheer, Henk Portengen, Jan G.M. Klijn, John A. Foekens
Journal: Clinical Cancer Research (2005)

To evaluate the predictive value of the disintegrin and metalloproteinases, ADAM-9, ADAM-10, ADAM-11, and ADAM-12, and of the matrix metalloproteinases, MMP-2 and MMP-9, in patients with recurrent breast cancer treated with tamoxifen.A retrospective study was done on 259 frozen specimens of estrogen receptor-positive primary breast carcinomas from patients who developed recurrent disease and were treated with tamoxifen as the first line of therapy. The expression levels of the biological factors were assessed by real-time quantitative reverse transcriptase PCR.Using log-transformed continuous variables, increasing levels of ADAM-9 [odds ratio (OR) = 1.41; P = 0.015] and decreasing levels of MMP-9 (OR, 0.81; P = 0.035) predicted favorable disease control independent from the traditional predictive factors. Furthermore, when tumors were dichotomized at the median level of 70% tumor cell nuclei, our univariate analysis showed particularly strong results for the group of 153 patients with primary tumors containing 30% or more stromal cells. Although estrogen receptor levels lost their predictive power for this group of patients, high levels of ADAM-9 (OR, 1.59; P = 0.007) and ADAM-11 (OR, 1.65; P = 0.001) were significantly associated with a higher efficacy of tamoxifen therapy.Our results show that especially for primary tumors containing stromal elements, the assessment of mRNA expression levels of ADAM-9 and ADAM-11 could be useful to identify patients with recurrent breast cancer who are likely to benefit or fail from tamoxifen therapy.
Prevalence, Awareness, Treatment, and Control of Hypertension in Rural and Urban Communities in High-, Middle-, and Low-Income Countries
Authors: Clara K. Chow
Journal: JAMA (2013)

<h3>Importance</h3> Hypertension is the most important preventable cause of morbidity and mortality globally, yet there are relatively few data collected using standardized methods. <h3>Objective</h3> To examine hypertension prevalence, awareness, treatment, and control in participants at baseline in the Prospective Urban Rural Epidemiology (PURE) study. <h3>Design, Setting, and Participants</h3> A cross-sectional study of 153 996 adults (complete data for this analysis on 142 042) aged 35 to 70 years, recruited between January 2003 and December 2009. Participants were from 628 communities in 3 high-income countries (HIC), 10 upper–middle-income and low–middle-income countries (UMIC and LMIC), and 4 low-income countries (LIC). <h3>Main Outcomes and Measures</h3> Hypertension was defined as individuals with self-reported treated hypertension or with an average of 2 blood pressure measurements of at least 140/90 mm Hg using an automated digital device. Awareness was based on self-reports, treatment was based on the regular use of blood pressure–lowering medications, and control was defined as individuals with blood pressure lower than 140/90 mm Hg. <h3>Results</h3> Among the 142 042 participants, 57 840 (40.8%; 95% CI, 40.5%-41.0%) had hypertension and 26 877 (46.5%; 95% CI, 46.1%-46.9%) were aware of the diagnosis. Of those who were aware of the diagnosis, the majority (23 510 [87.5%; 95% CI, 87.1%-87.9%] of those who were aware) were receiving pharmacological treatments, but only a minority of those receiving treatment were controlled (7634 [32.5%; 95% CI, 31.9%-33.1%]). Overall, 30.8%, 95% CI, 30.2%-31.4% of treated patients were taking 2 or more types of blood pressure–lowering medications. The percentages aware (49.0% [95% CI, 47.8%-50.3%] in HICs, 52.5% [95% CI, 51.8%-53.2%] in UMICs, 43.6% [95% CI, 42.9%-44.2%] in LMICs, and 40.8% [95% CI, 39.9%-41.8%] in LICs) and treated (46.7% [95% CI, 45.5%-47.9%] in HICs, 48.3%, [95% CI, 47.6%-49.1%] in UMICs, 36.9%, [95% CI, 36.3%-37.6%] in LMICs, and 31.7% [95% CI, 30.8%-32.6%] in LICs) were lower in LICs compared with all other countries for awareness (<i>P </i>&lt;.001) and treatment (<i>P </i>&lt;.001). Awareness, treatment, and control of hypertension were higher in urban communities compared with rural ones in LICs (urban vs rural,<i>P </i>&lt;.001) and LMICs (urban vs rural,<i>P </i>&lt;.001), but similar for other countries. Low education was associated with lower rates of awareness, treatment, and control in LICs, but not in other countries. <h3>Conclusions and Relevance</h3> Among a multinational study population, 46.5% of participants with hypertension were aware of the diagnosis, with blood pressure control among 32.5% of those being treated. These findings suggest substantial room for improvement in hypertension diagnosis and treatment.
Mucin associated Tn and sialosyl-Tn antigen expression in colorectal polyps.
Authors: S H Itzkowitz, E J Bloom, T S Lau, Y S Kim
Journal: Gut (1992)

Sialosyl-Tn antigen and its immediate precursor, Tn antigen, are carbohydrate structures associated with the earliest steps of mucin O-linked glycosylation. Both antigens have been shown previously to be highly sensitive and specific markers of colorectal cancer. One hundred and three colorectal polyps (79 adenomatous; 24 hyperplastic) were examined for expression of Tn antigen using vicia villosa isolectin B4, and for sialosyl-Tn antigen by monoclonal antibody TKH2. Tn antigen was expressed by all of the polyps studied. Sialosyl-Tn, on the other hand was expressed weakly by a few cells in 7 of 24 (29%) hyperplastic polyps. Among the adenomatous polyps, 56% expressed sialosyl-Tn and expression correlated with larger adenoma size, greater villous component, and more severe grades of dysplasia. In individuals with two or more synchronous adenomas, the level of sialosyl-Tn expression within an adenoma was associated with the severity of cytological atypia. All the adenomas that contained a focus of invasive carcinoma expressed sialosyl-Tn. These results indicate that colorectal polyps manifest incomplete glycosylation, exposing antigens in the innermost region of mucin oligosaccharides. In addition, the correlation of sialosyl-Tn antigen expression with the adenoma-carcinoma sequence may make this a useful marker for studying malignant progression in the colon.
Further issues in neurolinguistic preconditions
Authors: Wendy K. Wilkins, Jennie Wakefield
Journal: Behavioral and Brain Sciences (1996)

Abstract This response to continuing commentary addresses brain-hand relationships in Cebus apella (as introduced in West-ergaard's commentary), the evolutionary and acquisition parallels between music and language (suggested by Lynch), and the potential behavioral linguistic consequences of the evolutionary neurobiology in Australopithecus africanus and Homo habilis (discussed by Tobias). Finally, we reiterate the importance of well informed, multidisciplinary approaches to the study of the emergence of human species-specific cognition, especially linguistic capacity.
Diagnosis of colorectal lesions with a novel endocytoscopic classification – a pilot study
Authors: S-E Kudo, K. Wakamura, N. Ikehara, Y. Mori, H. Inoue, S. Hamatani
Journal: Endoscopy (2011)

<b>Background and study aims:</b> Recent advances in endocytoscopy have enabled in vivo evaluation not on ly of structural atypia, but also of cellular atypia with observation of lumens and nuclei in the surface layer of the mucosa. The aim of this prospective pilot study was to evaluate the usefulness of our novel endocytoscopic classification in colorectal lesions. <b>Patients and methods:</b> A total of 206 consecutive patients were enrolled in the study and underwent endocytoscopic examination. Endocytoscopic images were stored electronically and two endoscopists blinded to the findings at live examination assigned them diagnoses using the endocytoscopic (EC) classification. The endocytoscopic diagnosis was then compared to the final histopathological diagnosis. <b>Results:</b> In all, 196 patients with 213 specimens were available for analysis. All normal mucosae were classified as EC1a and all hyperplastic polyps as EC1b. Dysplasias were mainly classified as EC2, while massively invasive submucosal cancers (SMm) or worse, which have the possibility of metastasis, were mainly EC3b. Assuming that an EC1b classification was diagnostic of hyperplastic polyps, we were able to differentiate nonneoplastic from neoplastic lesions with a sensitivity of 100 % and a specificity of 100 % (<i>P</i> < 0.05). Assuming that an EC3b classification was diagnostic of SMm or worse, we were able to differentiate "SMm or worse" from other neoplastic lesions (dysplasias and slightly invasive submucosal cancers) with a sensitivity of 90.1 % and a specificity of 99.2 % (<i>P</i> < 0.05). <b>Conclusions:</b> The endocytoscopic classification was particularly useful for differentiating between neoplastic and nonneoplastic lesions and between "SMm or worse" and other neoplastic lesions, which in the case of colorectal neoplasms would help to determine treatment.
Activity of dasatinib in human osteosarcoma
Authors: Pooja Gidwani, Wendong Zhang, Richard Gorlick, Edward Kolb
Journal: Cancer Research (2007)

3255  Osteosarcoma, the most common primary malignant bone tumor in children and young adults has overall mortality rates that have changed little in the past 20 years. The overall survival remains around 60-70%. Pulmonary metastasis remains the major cause of mortality in osteosarcoma with the 5-year survival rate in such patients at 25-30%. Novel agents are needed to decrease the risk of metastases and improve survival rates.  Recent literature has implicated the Src family of kinases in key oncogenic mechanisms including proliferation, resistance to apoptosis, decreased adhesion, increased motility and invasion capabilities in a variety of human cancers, making it a rational target for novel drug development. Dasatinib is a novel dual src-abl kinase inhibitor. It inhibits c-src mediated downstream pathways in a variety of malignant cell lines such as prostate cancer cells, head and neck cancer cells and lung cancer cells thus affecting their proliferation, adhesion and migration capabilities. In this study c-src expression and activity of dasatinib was tested in osteosarcoma.  c-Src expression was assessed in both patient samples and osteosarcoma cell lines (U2OS, HOS, SaOS). Using the Affymetrix U95Av2 oligonucleotide microarray c-src expression was evaluated in forty primary osteosarcoma patient samples. All forty samples expressed c-src tyrosine kinase. The average expression level was 2912, with a 1.42 fold difference (p=0.03) between 15 tumors with a good response to chemotherapy (Huvos Grade III/IV) and those with a poor response to chemotherapy  (Huvos Grade I/II).  Using Western blot analysis, three cell lines (U2OS, HOS, and SaOS) were shown to express c-src protein. Additional experiments are underway to evaluate the effects of dasatinib on downstream signaling pathways as well as cell motility and invasion.  In-vitro dasatinib has cytotoxic activity against three osteosarcoma cell lines (U2OS, HOS, SaOS). The IC50 ranged from 0.1 nmol /l to 6.25 nmol /l.  In summary, c-src is expressed in both osteosarcoma patient samples and cell lines. Dasatinib is a potent inhibitor of cell proliferation in osteosarcoma cell lines. Taken together these data suggest that c-src is a potential therapeutic target in osteosarcoma.
Hypogammaglobulinemia: Adverse Effect of Systemic Corticosteroid in Severe Asthma Patients
Authors: M.V. Aun, C. Bisaccioni, A. Castro-Coelho, F.G. Montenegro, J. Kalil, R. Agondi, P. Giavina-Bianchi
Journal: Journal of Allergy and Clinical Immunology (2010)
The predictive model for perinatal asphyxia risk evaluation in the neonates
Authors: Natalia Gorovenko, Svetlana Kyryachenko, Zoya Rossokha
Journal: European Respiratory Journal (2012)

Background: Perinatal asphyxia (PA) is often associated with nonreversible adverse neurological outcome. Modern tests for PA diagnostic have low predictive values.  The aim of this study was to define the genetical based predictive model for early preventive diagnostic of PA.  Methods: We performed a case-control study of 201 neonates PA cases and 110 from control group. The I/D, A1166C, G308A, C677T polymorphism of ACE, AT2R1, TNF-a, MTHFR genes were detected using PCR and RFLP analysis. Statistical analysis was performed to assess the effects of all analyzed genes and their combinations (logistic regression (SPSS_17.0) and MDR model (MDR_2.0)).  Results: The frequency of all investigated genotypes with mutant alelle was significantly higher among PA cases.  The statistical model including all investigated genes had the higher predictive value (Percentage Correct=76,5). We have found positive entropy which determined synergy interaction between ACE and AT2R1 genes.  Conclusion: We suggest that using predictive model baised on I/D, A1166C, G308A, C677T polymorphism of ACE, AT2R1, TNF-a, MTHFR genes and their combination may increase early diagnostic of PA.
Implantation failure: molecular mechanisms and clinical treatment
Authors: Hakan Cakmak, Hugh S. Taylor
Journal: Human Reproduction Update (2010)

methods: This review summarizes the current knowledge about the proposed mechanisms of implantation failure in gynecological diseases, the evaluation of endometrial receptivity and the treatment methods to improve implantation. results:The absence or suppression of molecules essential for endometrial receptivity results in decreased implantation rates in animal models and gynecological diseases, including endometriosis, hydrosalpinx, leiomyoma and polycystic ovarian syndrome.The mechanisms are diverse and include abnormal cytokine and hormonal signaling as well as epigenetic alterations.conclusions: Optimizing endometrial receptivity in fertility treatment will improve success rates.Evaluation of implantation markers may help to predict pregnancy outcome and detect occult implantation deficiency.Treating the underlying gynecological disease with medical or surgical interventions is the optimal current therapy.Manipulating the expression of key endometrial genes with gene or stem cell-based therapies may some day be used to further improve implantation rates.
Signaling Mechanism of TGF-β1 in Prevention of Renal Inflammation
Authors: Wansheng Wang, Xiao R Huang, Allen G Li, Fang Liu, Jin-Hua Li, Luan D Truong, Xiao J Wang, Hui Y Lan
Journal: Journal of the American Society of Nephrology (2005)

TGF-beta has been shown to play a critical role in anti-inflammation; however, the signaling mechanisms of TGF-beta in anti-inflammatory response remains largely unclear. This study reported that mice that overexpress latent TGF-beta1 on skin are protected against renal inflammation in a model of obstructive kidney disease and investigated the signaling mechanism of TGF-beta1 in inhibition of renal inflammation in vivo and in vitro. Seven days after urinary obstruction, wild-type mice developed severe renal inflammation, including massive T cell and macrophage infiltration and marked upregulation of IL-1beta, TNF-alpha, and intercellular adhesion molecule-1 (all P < 0.001). Surprising, renal inflammation was prevented in transgenic mice. This was associated with an increase in latent TGF-beta1 in circulation (a 10-fold increase) and renal tissues (a 2.5-fold increase). Further studies showed that inhibition of renal inflammation in TGF-beta1 transgenic mice was also associated with a marked upregulation of renal Smad7 and IkappaBalpha and a suppression of NF-kappaB activation in the diseased kidney (all P < 0.01). These in vivo findings suggested the importance of TGF-beta-NF-kappaB cross-talk signaling pathway in regulating renal inflammation. This was tested in vitro in a doxycycline-regulated Smad7-expressing renal tubular cell line. Overexpression of Smad7 was able to upregulate IkappaBalpha directly in a time- and dose-dependent manner, thereby inhibiting NF-kappaB activation and NF-kappaB-driven inflammatory response. In conclusion, latent TGF-beta may have protective roles in renal inflammation. Smad7-mediated inhibition of NF-kappaB activation via the induction of IkBalpha may be the central mechanism by which latent TGF-beta prevents renal inflammation.