tbuckley/cabot-search huggingface dataset:
Spontaneous Abortion and Aging of Human Ova and Spermatozoa
Authors: Rodrigo Guerrero, Oscar I. Rojas
Journal: New England Journal of Medicine (1975)

To test the hypothesis that aging of human gametes within the genital tract increases the chance of abortion, we measured the probabilities of abortion after insemination on a given day of the menstrual cycle in relation to the day of the shift in the basal body temperature in 965 patients. Cases came from family-planning and sterility clinics where basal body temperature and coital records are kept routinely. The probability of abortion diminished significantly (P less than 0.001) as the shift in temperature was approached and the increased to its highest point (24 per cent) three days later. Animal experiments have shown that aging of both spermatozoa and ova before fertilization is accompanied by higher probabilities of abortion. Present evidence indicates that this higher prevalence is also true for human beings.The basal body temperature in 965 patients were subject to analysis with coital records in order to determine the probability of abortion after insemination on a given day of the menstrual cycle in relation to the shift in basal body temperature. Coital records were examined to assign a responsible insemination, and basal body temperature charts examined to determine a thermal shift. There were 890 term deliveries and 75 spontaneous abortions. The overall probability of abortion was 7 .8%. The lowest corresponded to Day -2 (3.2%) and the highest to Day +3 (24%). The probability of abortion diminished significantly (P less than .001) as the shift in temperature was approached and then increased to its highest point 3 days later. These results strongly suggest that aging of human spermatozoa in the female genital tract is associated with an increased frequency of spontaneous abortions.
Survival and Death Signals Can Predict Tumor Response to Therapy After Oncogene Inactivation
Authors: Phuoc T. Tran, Pavan K. Bendapudi, H. Jill Lin, Peter Choi, Shan Koh, Joy Chen, George Horng, Nicholas P. Hughes, Lawrence H. Schwartz, Vincent A. Miller, Toshiyuki Kawashima, Toshio Kitamura, David Paik, Dean W. Felsher
Journal: Science Translational Medicine (2011)

Cancers can exhibit marked tumor regression after oncogene inhibition through a phenomenon called "oncogene addiction." The ability to predict when a tumor will exhibit oncogene addiction would be useful in the development of targeted therapeutics. Oncogene addiction is likely the consequence of many cellular programs. However, we reasoned that many of these inputs may converge on aggregate survival and death signals. To test this, we examined conditional transgenic models of K-ras(G12D)--or MYC-induced lung tumors and lymphoma combined with quantitative imaging and an in situ analysis of biomarkers of proliferation and apoptotic signaling. We then used computational modeling based on ordinary differential equations (ODEs) to show that oncogene addiction could be modeled as differential changes in survival and death intracellular signals. Our mathematical model could be generalized to different imaging methods (computed tomography and bioluminescence imaging), different oncogenes (K-ras(G12D) and MYC), and several tumor types (lung and lymphoma). Our ODE model could predict the differential dynamics of several putative prosurvival and prodeath signaling factors [phosphorylated extracellular signal-regulated kinase 1 and 2, Akt1, Stat3/5 (signal transducer and activator of transcription 3/5), and p38] that contribute to the aggregate survival and death signals after oncogene inactivation. Furthermore, we could predict the influence of specific genetic lesions (p53⁻/⁻, Stat3-d358L, and myr-Akt1) on tumor regression after oncogene inactivation. Then, using machine learning based on support vector machine, we applied quantitative imaging methods to human patients to predict both their EGFR genotype and their progression-free survival after treatment with the targeted therapeutic erlotinib. Hence, the consequences of oncogene inactivation can be accurately modeled on the basis of a relatively small number of parameters that may predict when targeted therapeutics will elicit oncogene addiction after oncogene inactivation and hence tumor regression.
The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells
Authors: Bettina Grötsch, Sebastian Brachs, Christiane Lang, Julia Luther, Anja Derer, Ursula Schlötzer-Schrehardt, Aline Bozec, Simon Fillatreau, Ingolf Berberich, Elias Hobeika, Michael Reth, Erwin F. Wagner, Georg Schett, Dirk Mielenz, Jean-Pierre David
Journal: The Journal of Experimental Medicine (2014)

The cornerstone of humoral immunity is the differentiation of B cells into antibody-secreting plasma cells. This process is tightly controlled by a regulatory gene network centered on the transcriptional repressor B lymphocyte–induced maturation protein 1 (Blimp1). Proliferation of activated B cells is required to foster Blimp1 expression but needs to be terminated to avoid overshooting immune reactions. Activator protein 1 (AP-1) transcription factors become quickly up-regulated upon B cell activation. We demonstrate that Fra1, a Fos member of AP-1, enhances activation-induced cell death upon induction in activated B cells. Moreover, mice with B cell–specific deletion of Fra1 show enhanced plasma cell differentiation and exacerbated antibody responses. In contrast, transgenic overexpression of Fra1 blocks plasma cell differentiation and immunoglobulin production, which cannot be rescued by Bcl2. On the molecular level, Fra1 represses Blimp1 expression and interferes with binding of the activating AP-1 member c-Fos to the Blimp1 promoter. Conversely, overexpression of c-Fos in Fra1 transgenic B cells releases Blimp1 repression. As Fra1 lacks transcriptional transactivation domains, we propose that Fra1 inhibits Blimp1 expression and negatively controls plasma cell differentiation through binding to the Blimp1 promoter. In summary, we demonstrate that Fra1 negatively controls plasma cell differentiation by repressing Blimp1 expression.
AHP1. QUALITY OF LIFE IN PEDIATRIC RHEUMATOLOGY - METHODOLOGICAL AND CLINICAL ASPECTSAHP2. RELEVANCE OF PHYSICAL ACTIVITY TO THE CHILD WITH A MUSCULO-SKELETAL DISEASEAHP3. PROMOTION OF ACTIVE LIFE- AND COPING STYLES BY BEHAVIOURAL SKILLS TRAINING PROGRAMSAHP4. CHANGING PARADIGMS IN DEVELOPMENTAL PEDIATRICS: THEIR EFFECTS ON THE TREATMENT OF CHILDREN WITH JIA
Authors: B. Andersson Gäre, O. Bar-Or, G. Sinnema, P. J. M. Helders, J. van der Net, W. Kuis
Journal: Annals of the Rheumatic Diseases (2001)

During the past two decades, quality of life (QOL) has been increasingly recognised as one of the most important parts in patient outcomes and in the evaluation of therapeutic interventions - especially in chronic disease. However, the area is complicated by unclear terminology, where there is confusion over the meanings of the terms overall QOL, health related QUL (HRQOL) and health status which are frequently used without clear definitions (1,2,3). One definition of QOL in children states that it is a multidimensional subjective concept that includes social, emotional, and physical functioning of the child and family, while HRQOL incorporates measures of physical symptoms, functional status and disease impact on psychological and social functioning. Traditional health status measures, on the other hand, are more focused on, for example, physical function or disease severity and do not reflect the patient's own values. In clinical studies and clinical care all 3 measures are of value since …
Central Role for Interferon-γ Receptor in the Regulation of Renal MHC Expression
Authors: YUTAKA TAKEI, TASHA N. SIMS, JOAN URMSON, PHILIP F. HALLORAN
Journal: Journal of the American Society of Nephrology (2000)

The role of the interferon-gamma (IFN-gamma) receptor 1 (IFN-gammaR1) was investigated in the regulation of MHC expression in kidney in the basal state, in response to potent inflammatory stimuli, and after renal injury. In this study, MHC regulation in mice lacking IFN-gammaR due to targeted disruption of the IFN-gammaR1 gene (GRKO mice) was compared with regulation in 129Sv/J mice with wild-type IFN-gammaR1 genes. Basal class I expression was reduced by approximately 45% in kidneys of GRKO mice, while basal class II expression was confined to interstitial cells and was not reduced in GRKO kidneys. Recombinant IFN-gamma administration induced widespread expression of class I and II in renal tubules, arterial endothelium, and glomeruli of 129Sv/J mice, but produced no change in kidneys of GRKO mice. Potent systemic inflammatory stimuli (injections of allogeneic cells, skin sensitization with oxazolone, and injection of bacterial lipopolysaccharide) significantly induced both class I and class II expression in 129Sv/J mice, but not in GRKO mice. Acute renal injury increased local expression of class I and II in both 129Sv/J and GRKO mice, but the induction in GRKO mice was reduced compared with 129Sv/J mice. Thus, the IFN-gamma receptor plays a unique and nonredundant role in the regulation of renal MHC in the response to inflammation, in the response to renal injury, and in the basal state.
Methylation of Serum DNA Is an Independent Prognostic Marker in Colorectal Cancer
Authors: Maike Wallner, Andreas Herbst, Andrea Behrens, Alexander Crispin, Petra Stieber, Burkhard Göke, Rolf Lamerz, Frank T. Kolligs
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Aberrant CpG island hypermethylation is a feature of a subgroup of colorectal cancers, which can be detected in the serum of affected patients. This study was designed to identify methylation targets with prognostic significance in the serum of patients with colorectal cancer. Experimental Design: In a gene evaluation set consisting of sera from 24 patients with local colorectal cancers, 14 with metastasized disease, and 20 healthy controls, the genes HPP1/TPEF, HLTF, and hMLH1 were identified as potential serum DNA methylation markers. These genes were further analyzed in a test set of sera of 104 patients with colorectal cancer. Results: Methylation of HLTF, HPP1/TPEF, and hMLH1 was found to be significantly correlated with tumor size, and methylation of HLTF and HPP1/TPEF was significantly associated with metastatic disease and tumor stage. Moreover, methylation of HPP1/TPEF was also associated with serum carcinoembryonic antigen. The prognostic relevance of methylation of these genes was tested in pretherapeutic sera of 77 patients with known follow-up. Patients with methylation of HPP1/TPEF or HLTF were found to have unfavorable prognosis (P = 0.001 and 0.008). In contrast, serum methylation of hMLH1 was not associated with a higher risk of death. Multivariate analysis showed methylated HPP1 and/or HLTF serum DNA to be independently associated with poor outcome and a relative risk of death of 3.4 (95% confidence interval, 1.4-8.1; P = 0.007). Conclusions: These data show that the methylation status of specific genes in the serum of patients with colorectal cancer has the potential to become a pretherapeutic predictor of outcome.
Syndecan-4 regulates cartilage degradation in osteoarthritis
Authors: F Echtermeyer, J Betrand, I Meinecke, K Neugebauer, C Herzog, Y J Lee, Y W Song, R Dreier, T Pap
Journal: Annals of the Rheumatic Diseases (2010)

Cartilage breakdown by loss of proteoglycans is one of the hallmarks of osteoarthritis (OA).The aggrecanase ADAMTS-5 has been shown to be responsible for proteoglycan loss in arthritic mouse cartilage.However, the mechanisms that lead on July 9,
The Metabolic Syndrome in the West Bank Population
Authors: Hanan F. Abdul-Rahim, Abdullatif Husseini, Espen Bjertness, Rita Giacaman, Nahida H. Gordon, Jak Jervell
Journal: Diabetes Care (2001)

To compare the prevalence of components of the metabolic syndrome, including hypertension, abnormal glucose metabolism, dyslipidemia, central obesity, and overall obesity, between a rural and an urban Palestinian West Bank community.A total of 500 rural and 492 urban men and women aged 30-65 years participated in a community-based cross-sectional survey Diabetes and impaired glucose tolerance were diagnosed using the oral glucose tolerance test. BMI, waist-to-hip ratio, and blood pressure were measured, and blood samples were taken from each subject. Sociodemographic characteristics were investigated using a questionnaire.Hypertriglyceridemia, low HDL cholesterol, overall obesity, and smoking were significantly more prevalent in the urban population, whereas central obesity was more prevalent in the rural population. Prevalence of hypertension was not significantly different between the rural and urban populations (25.4 and 21.5%, respectively; P = 0.15). The age-adjusted prevalences of diabetes were high: 11.3% (8.5-14.1 95% CI) and 13.9% (10.8-17.0) in the rural and urban populations, respectively, but not significantly different. In each community, the age-adjusted prevalence of the metabolic syndrome as defined by the World Health Organization was 17%.Although no significant differences were found in the prevalences of hypertension and diabetes between the two populations, other components of the metabolic syndrome, namely elevated triglycerides, low HDL cholesterol, and overall obesity, were more prevalent in the urban population. Given the rapid urbanization of the Palestinian population, the implications for a rise in noncommunicable diseases should be a major public health concern.
Growth Hormone–Mediated Janus Associated Kinase–Signal Transducers and Activators of Transcription Signaling in the Growth Hormone–Resistant Potassium-Deficient Rat
Authors: Franz Schaefer, Sun-Ae Yoon, Pouneh Nouri, Tanny Tsao, Padmaja Tummala, Ellen Deng, Ralph Rabkin
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Potassium deficiency (KD) is associated with severe growth failure, in part caused by growth hormone (GH) resistance. This study set out to determine whether the resistance could be caused by a defect in GH-mediated janus associated kinase–signal transducers and activators of transcription (STAT) signaling as occurs in uremia. To this end, rats were fed a K-deficient diet for 8 d and pair-fed controls received a K-replete diet. Animals from each group received GH or vehicle, and during this period, KD rats were GH resistant; GH induced body and liver weight gain and linear body growth were severely attenuated in these rats. In addition, signal transduction was studied in the liver of rats that were killed 10 or 15 min after an intravenous GH bolus or vehicle. When the rats were killed, GH receptor mRNA and protein levels were similar in the two groups. The abundance of STAT5, STAT3, and STAT1, proteins that mediate GH signaling, was significantly increased by 40 to 130% in KD. Furthermore, GH induced a far greater increase in STAT5 and STAT3 phosphorylation in this group. STAT5 phosphorylation was enhanced fourfold even when normalized for total STAT5 content. Phosphorylated STAT5 and STAT3 proteins were also increased in nuclear extracts, suggesting normal nuclear translocation of the activated signaling proteins. DNA binding of nuclear STAT5 was unaltered. Thus, in KD, there is resistance to the growth-promoting action of GH despite hyperactivation of the janus associated kinase–STAT signaling pathway. This suggests the presence of a defect distal to the nuclear binding of STAT or, alternatively, a defect in a STAT-independent GH-activated signaling pathway.
Lipid Lowering by Simvastatin Induces Regression of Human Atherosclerotic Lesions
Authors: Roberto Corti, Valentin Fuster, Zahi A. Fayad, Stephen G. Worthley, Gerard Helft, Donald Smith, Jesse Weinberger, Jolanda Wentzel, Gabor Mizsei, Michele Mercuri, Juan J. Badimon
Journal: Circulation (2002)

Statins are widely used to treat hypercholesterolemia and atherosclerotic disease. Noninvasive MRI allows serial monitoring of atherosclerotic plaque size changes. Our aim was to investigate the effects of lipid lowering with simvastatin on atherosclerotic lesions.A total of 44 aortic and 32 carotid artery plaques were detected in 21 asymptomatic hypercholesterolemic patients at baseline. The effects of statin on these atherosclerotic lesions were evaluated as changes versus baseline in lumen area (LA), vessel wall thickness (VWT), and vessel wall area (VWA) by MRI. Maximal reduction of plasma total and LDL cholesterol by simvastatin (23% and 38% respectively; P<0.01 versus baseline) was achieved after approximately 6 weeks of therapy and maintained thereafter throughout the study. Significant (P<0.01) reductions in maximal VWT and VWA at 12 months (10% and 11% for aortic and 8% and 11% for carotid plaques, respectively), without changes in LA, have been reported. Further decreases in VWT and VWA ranging from 12% to 20% were observed at 18 and 24 months. A slight but significant increase (ranging from 4% to 6%) in LA was seen in both carotid and aortic lesions at these later time points.The present study demonstrates that maintained lipid-lowering therapy with simvastatin is associated with significant regression of established atherosclerotic lesions in humans. Our observations indicate that lipid-lowering therapy is associated with sustained vascular remodeling and emphasize the need for longer-term treatment.
The effects of gonadectomy on left ventricular function and cardiac contractile proteins in male and female rats.
Authors: T F Schaible, A Malhotra, G Ciambrone, J Scheuer
Journal: Circulation Research (1984)

To examine the influence of the sex hormones on mechanical properties and biochemistry of the adult heart, we studied left ventricular function and cardiac contractile proteins in hearts from 20-week-old male and female rats that had been gonadectomized at 18 days of age, compared with hearts from sham-operated animals. Testosterone and estradiol were not detectable in serum from male and female gonadectomized rats, respectively. The male rats had lower body and heart weights than male sham operated rats, whereas these values were higher in female gonadectomized than in female sham-operated rats. Left ventricular function was studied in a working heart apparatus at similar heart rate and at controlled levels of aortic diastolic pressure and left atrial pressure. At moderate left atrial pressure, end-diastolic pressure and volume per gram dry left ventricle were the same in all groups, but at high left atrial pressure, end-diastolic pressure, and volume per gram dry left ventricle were lower in male and female gonadectomized than in the respective sham-operated rats. Further increases in left atrial pressure were associated with mechanical alternans in male and female gonadectomized rats. Significantly (P less than 0.05) lower values for cardiac output, peak systolic pressure, ejection fraction, and myocardial oxygen consumption occurred in male gonadectomized compared with sham-operated rats at moderate and high left atrial pressure at higher levels of aortic diastolic pressure. Decreases in these values for female gonadectomized compared with sham-operated rats occurred only at high left atrial pressure. A significant downward shift in the mean force-velocity relationship was observed in all gonadectomized rats at both moderate and high left atrial pressure. In a follow-up study, when end-diastolic pressure was kept the same at both moderate and high left atrial pressure in female sham-operated and gonadectomized rats by reducing heart rate, decreases in contractile function in gonadectomized rats were observed at all preloads. Ca++-myosin ATPase activity was significantly reduced by 34% in male and by 19% in female gonadectomized rats when compared to respective sham-operated control hearts. These alterations in myosin ATPase activity were associated with a reduction in the V1 myosin isoenzyme and an increase in the V3 isoenzyme. Thus, left ventricular filling and left ventricular function were impaired in hearts of gonadectomized rats. Alterations in function were associated with depressed cardiac myosin ATPase activity in male and female gonadectomized rats.(ABSTRACT TRUNCATED AT 400 WORDS)
The Role of Nutrition in Neural Tube Defects
Authors: J. M. Scott, P. N. Kirke, D. G. Weir
Journal: Annual Review of Nutrition (1990)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Phase III Comparison of Prophylactic Cranial Irradiation Versus Observation in Patients With Locally Advanced Non–Small-Cell Lung Cancer: Primary Analysis of Radiation Therapy Oncology Group Study RTOG 0214
Authors: Elizabeth M. Gore, Kyounghwa Bae, Stuart J. Wong, Alexander Sun, James A. Bonner, Steven E. Schild, Laurie E. Gaspar, Jeffery A. Bogart, Maria Werner-Wasik, Hak Choy
Journal: Journal of Clinical Oncology (2010)

This study was conducted to determine if prophylactic cranial irradiation (PCI) improves survival in locally advanced non-small-cell lung cancer (LA-NSCLC).Patients with stage III NSCLC without disease progression after treatment with surgery and/or radiation therapy (RT) with or without chemotherapy were eligible. Participants were stratified by stage (IIIA v IIIB), histology (nonsquamous v squamous), and therapy (surgery v none) and were randomly assigned to PCI or observation. PCI was delivered to 30 Gy in 15 fractions. The primary end point of the study was overall survival (OS). Secondary end points were disease-free survival (DFS), neurocognitive function (NCF), and quality of life. Kaplan-Meier and log-rank analyses were used for OS and DFS. The incidence of brain metastasis (BM) was evaluated with the logistic regression model.Overall, 356 patients were accrued of the targeted 1,058. The study was closed early because of slow accrual; 340 of the 356 patients were eligible. The 1-year OS (P = .86; 75.6% v 76.9% for PCI v observation) and 1-year DFS (P = .11; 56.4% v 51.2% for PCI v observation) were not significantly different. The hazard ratio for observation versus PCI was 1.03 (95% CI, 0.77 to 1.36). The 1-year rates of BM were significantly different (P = .004; 7.7% v 18.0% for PCI v observation). Patients in the observation arm were 2.52 times more likely to develop BM than those in the PCI arm (unadjusted odds ratio, 2.52; 95% CI, 1.32 to 4.80).In patients with stage III disease without progression of disease after therapy, PCI decreased the rate of BM but did not improve OS or DFS.
A Controlled Trial of Long-Term Inhaled Hypertonic Saline in Patients with Cystic Fibrosis
Authors: Mark R. Elkins, Michael Robinson, Barbara R. Rose, Colin Harbour, Carmel P. Moriarty, Guy B. Marks, Elena G. Belousova, Wei Xuan, Peter T.P. Bye
Journal: New England Journal of Medicine (2006)

Inhaled hypertonic saline acutely increases mucociliary clearance and, in short-term trials, improves lung function in people with cystic fibrosis. We tested the safety and efficacy of inhaled hypertonic saline in a long-term trial.
Authors' response to assessment of intraparenchymal lung collateral ventilation
Authors: Helen Marshall, Rod Lawson, Jim M Wild
Journal: Thorax (2012)

We thank the writers of the letter1 for their interest and agree that the potential placement of this novel imaging method in the planning of patient treatment, such as bronchoscopic and surgical lung volume reduction, is not yet determined.

The example of collateral ventilation shown in figure …
5-Fluorouracil versus 5-fluorouracil plus α-interferon as treatment of metastatic colorectal carcinoma. A randomized study
Authors: P. Dufour, F. Husseini, B. Dreyfus, H. Cure, C. Martin, G. Prevost, J.-P. Olivier, F. Dumas, B. Duclos, R. Olivares, A. Leszler, J.-P. Bergerat, B. Audhuy, L. Thill, F. Oberling
Journal: Annals of Oncology (1996)