tbuckley/cabot-search huggingface dataset:
Implicit Cognition and Addiction: A Tool for Explaining Paradoxical Behavior
Authors: Alan W. Stacy, Reinout W. Wiers
Journal: Annual Review of Clinical Psychology (2010)

Research on implicit cognition and addiction has expanded greatly during the past decade. This research area provides new ways to understand why people engage in behaviors that they know are harmful or counterproductive in the long run. Implicit cognition takes a different view from traditional cognitive approaches to addiction by assuming that behavior is often not a result of a reflective decision that takes into account the pros and cons known by the individual. Instead of a cognitive algebra integrating many cognitions relevant to choice, implicit cognition assumes that the influential cognitions are the ones that are spontaneously activated during critical decision points. This selective review highlights many of the consistent findings supporting predictive effects of implicit cognition on substance use and abuse in adolescents and adults; reveals a recent integration with dual-process models; outlines the rapid evolution of different measurement tools; and introduces new routes for intervention.
Gene expression profiles of human glioblastomas are associated with both tumor cytogenetics and histopathology
Authors: Ana Luísa Vital, Maria Dolores Tabernero, Abel Castrillo, Olinda Rebelo, Hermínio Tão, Fernando Gomes, Ana Belen Nieto, Catarina Resende Oliveira, Maria Celeste Lopes, Alberto Orfao
Journal: Neuro-Oncology (2010)

Despite the increasing knowledge about the genetic alterations and molecular pathways involved in gliomas, few studies have investigated the association between the gene expression profiles (GEP) and both cytogenetics and histopathology of gliomas. Here, we analyzed the GEP (U133Plus2.0 chip) of 40 gliomas (35 astrocytic tumors, 3 oligodendrogliomas, and 2 mixed tumors) and their association with tumor cytogenetics and histopathology. Unsupervised and supervised analyses showed significantly different GEP in low- vs high-grade gliomas, the most discriminating genes including genes involved in the regulation of cell proliferation, apoptosis, DNA repair, and signal transduction. In turn, among glioblastoma multiforme (GBM), 3 subgroups of tumors were identified according to their GEP, which were closely associated with the cytogenetic profile of their ancestral tumor cell clones: (i) EGFR amplification, (ii) isolated trisomy 7, and (iii) more complex karyotypes. In summary, our results show a clear association between the GEP of gliomas and tumor histopathology; additionally, among grade IV astrocytoma, GEP are significantly associated with the cytogenetic profile of the ancestral tumor cell clone. Further studies in larger series of patients are necessary to confirm our observations.
On Latency of Symptoms in Acute Abdominal Affections
Authors: E. M. Skerritt
Journal: BMJ (1878)

beladonna extract wAs given every hour; and, after nin-gris's bad 1ei taken, copious alvine evacuation ensued.In two attacks since, the latest being last month, eight grains and nine grains respectively were effectual.No alcohol was prescribed in ay of the above cases, but patient No.x,took about two ounces of port wine before the belladonna treatment was begun.In the after-treatment, and as a preventive' of obstruc- tion, the most effectual remedy I have found has been pulvis glycyi.rhze composita.
<i>Clostridium perfringens</i> Enterotoxin as a Novel-Targeted Therapeutic for Brain Metastasis
Authors: Scott L. Kominsky, Betty Tyler, Jeffrey Sosnowski, Kelly Brady, Michele Doucet, Delissa Nell, James G. Smedley, Bruce McClane, Henry Brem, Saraswati Sukumar
Journal: Cancer Research (2007)

Abstract Brain metastasis is the most commonly occurring intracranial tumor whose incidence seems to be increasing. With standard therapy, the average survival time of patients is ∼8 months, and treatment often leads to neurologic dysfunction in long-term survivors, emphasizing the need for novel therapeutics. Clostridium perfringens enterotoxin (CPE) has recently been shown to rapidly and specifically destroy cancer cells expressing CPE receptors claudin-3 and claudin-4. Unfortunately, the utility of CPE is precluded by systemic toxicity because its receptors are expressed in numerous organs. Here, we provide the first preclinical evidence that CPE may be uniquely suited to the local treatment of brain metastasis. By immunohistochemical analysis, claudin-3 and claudin-4 were expressed frequently in metastases from breast (15 of 18), lung (15 of 20), and colon (12 of 14) carcinoma, and infrequently in metastases from renal cell carcinoma (2 of 16) and melanoma (2 of 16). In contrast, expression of claudin-3 and claudin-4 was absent in adjacent normal brain tissue. Further examination of the central nervous system (CNS) revealed low or undetectable levels of claudin-3 and claudin-4 in all regions tested by Western and immunohistochemical analysis. Treatment of breast cancer cell lines (MCF-7, MDA-MB-468, NT2.5-luc) and normal human astrocytes with CPE in vitro resulted in rapid and dose-dependent cytolysis exclusively in breast cancer cells, correlating with claudin-3 and claudin-4 expression. Moreover, intracranial CPE treatment significantly inhibited tumor growth and increased survival in two murine models of breast cancer brain metastasis, without any apparent local or systemic toxicity. These data suggest that CPE therapy may have efficacy against a wide variety of brain metastases without CNS toxicity. [Cancer Res 2007;67(17):7977–82]
New (alternative) temozolomide regimens for the treatment of glioma
Authors: Wolfgang Wick, Michael Platten, Michael Weller
Journal: Neuro-Oncology (2008)

One barrier to successful treatment of malignant glioma is resistance to alkylating agents such as temozolomide. The cytotoxic activity of temozolomide and other alkylating agents is believed to manifest largely by the formation of O(6)-methylguanine DNA adducts. Consequently, the primary mechanism of resistance to temozolomide is a function of the activity of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT). Fortuitously, MGMT is inactivated after each reaction (i.e., suicide enzyme). Therefore, if the rate of DNA alkylation were to outpace the rate of MGMT protein synthesis, the enzyme could, in theory, be depleted. Several studies have shown that prolonged exposure to temozolomide can deplete MGMT activity in blood cells, a process that could potentially increase the antitumor activity of the drug. To date, however, there are limited data demonstrating the depletion of MGMT activity in tumor tissue exposed to temozolomide. A variety of dosing schedules that increase the duration of exposure and the cumulative dose of temozolomide are currently being investigated for the treatment of glioma, with the goal of improving antitumor activity and overcoming resistance. These alternative dosing regimens have been shown to deplete MGMT activity in peripheral blood mononuclear cells, but the regimen that provides the best balance between enhanced antitumor activity and acceptable hematologic toxicity has yet to be determined.
Increased Stress-Induced Inflammatory Responses in Male Patients With Major Depression and Increased Early Life Stress
Authors: Thaddeus W.W. Pace, Tanja C. Mletzko, Oyetunde Alagbe, Dominique L. Musselman, Charles B. Nemeroff, Andrew H. Miller, Christine M. Heim
Journal: American Journal of Psychiatry (2006)

The authors sought to determine innate immune system activation following psychosocial stress in patients with major depression and increased early life stress.Plasma interleukin (IL)-6, lymphocyte subsets, and DNA binding of nuclear factor (NF)-kB in peripheral blood mononuclear cells were compared in medically healthy male subjects with current major depression and increased early life stress (N=14) versus nondepressed male comparison subjects (N=14) before and after completion of the Trier Social Stress Test.Trier Social Stress Test-induced increases in IL-6 and NF-kappaB DNA-binding were greater in major depression patients with increased early life stress and independently correlated with depression severity, but not early life stress. Natural killer (NK) cell percentages also increased following stress. However, there were no differences between groups and no correlation between NK cell percentage and stress-induced NF-kappaB DNA-binding or IL-6.Male major depression patients with increased early life stress exhibit enhanced inflammatory responsiveness to psychosocial stress, providing preliminary indication of a link between major depression, early life stress and adverse health outcomes in diseases associated with inflammation.
Demonstration of a geode by magnetic resonance imaging: a new light on the cause of juxta-articular bone cysts in rheumatoid arthritis.
Authors: E A Moore, R K Jacoby, R E Ellis, M E Fry, S Pittard, W Vennart
Journal: Annals of the Rheumatic Diseases (1990)

The magnetic resonance imaging (MRI) features of a rheumatoid arthritic geode are presented. Development of such a cyst from before x ray diagnosis to its coalescence with the wrist joint is described. The evidence suggests that these juxta-articular cysts are not merely an intrusion of the synovial cavity into the bone marrow but start as isolated structures beneath the subchondral bone.
The Role of Telomere Biology in Cancer
Authors: Lifeng Xu, Shang Li, Bradley A. Stohr
Journal: Annual Review of Pathology Mechanisms of Disease (2012)

Telomere biology plays a critical and complex role in the initiation and progression of cancer. Although telomere dysfunction resulting from replicative attrition constrains tumor growth by engaging DNA-damage signaling pathways, it can also promote tumorigenesis by causing oncogenic chromosomal rearrangements. Expression of the telomerase enzyme enables telomere-length homeostasis and allows tumor cells to escape the antiproliferative barrier posed by short telomeres. Telomeres and telomerase also function independently of one another. Recent work has suggested that telomerase promotes cell growth through pathways unrelated to telomere maintenance, and a subset of tumors elongate telomeres through telomerase-independent mechanisms. In an effort to exploit the integral link between telomere biology and cancer growth, investigators have developed several telomerase-based therapeutic strategies, which are currently in clinical trials. Here, we broadly review the state of the field with a particular focus on recent developments of interest.
IL-18 Induces Emphysema and Airway and Vascular Remodeling via IFN-γ, IL-17A, and IL-13
Authors: Min-Jong Kang, Je-Min Choi, Bo Hye Kim, Chang-Min Lee, Won-Kyung Cho, Gina Choe, Do-Hyun Kim, Chun Geun Lee, Jack A. Elias
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation, alveolar destruction, and airway and vascular remodeling. However, the mechanisms that lead to these diverse alterations have not been defined.Objectives: We hypothesized that IL-18 plays a central role in the pathogenesis of these lesions.Methods: We generated and characterized lung-specific, inducible IL-18 transgenic mice.Measurements and Main Results: Here we demonstrate that the expression of IL-18 in the mature murine lung induces inflammation that is associated with the accumulation of CD4+, CD8+, CD19+, and NK1.1+ cells; emphysema; mucus metaplasia; airway fibrosis; vascular remodeling; and right ventricle cardiac hypertrophy. We also demonstrate that IL-18 induces type 1, type 2, and type 17 cytokines with IFN-γ–inhibiting macrophage, lymphocyte, and eosinophil accumulation while stimulating alveolar destruction and genes associated with cell cytotoxicity and IL-13 and IL-17A inducing mucus metaplasia, airway fibrosis, and vascular remodeling. We also highlight interactions between these responses with IL-18 inducing IL-13 via an IL-17A–dependent mechanism and the type 1 and type17/type 2 responses counterregulating each another.Conclusions: These studies define the spectrum of inflammatory, parenchymal, airway, and vascular alterations that are induced by pulmonary IL-18; highlight the similarities between these responses and the lesions in COPD; and define the selective roles that type 1, type 2, and type 17 responses play in the generation of IL-18–induced pathologies.
Macrophage Inhibitory Cytokine 1: A New Prognostic Marker in Prostate Cancer
Authors: David A. Brown, Fredrik Lindmark, Pär Stattin, Katarina Bälter, Hans-Olov Adami, Sigun L. Zheng, Jianfeng Xu, William B. Isaacs, Henrik Grönberg, Samuel N. Breit, Fredrik E. Wiklund
Journal: Clinical Cancer Research (2009)

High serum levels of macrophage inhibitory cytokine 1 (MIC-1) are strongly associated with metastatic prostate cancer, suggesting MIC-1 is a biomarker for prostate cancer prognosis.We conducted a prospective cohort study of 1,442 Swedish men with a pathologically verified diagnosis of prostate cancer between 2001 and 2003. Blood was drawn either pretreatment (n = 431) or posttreatment (n = 1,011) and cases were followed for a mean time of 4.9 years (range, 0.1-6.8 years).MIC-1 serum levels independently predicted poor cancer-specific survival with an almost 3-fold higher cancer death rate in patients with serum levels in the highest quartile compared with men with serum levels in the lowest quartile (adjusted hazard ratio, 2.98; 95% confidence interval, 1.82-4.68). Pretreatment MIC-1 levels revealed an even stronger association with disease outcome with an 8-fold higher death rate in the highest compared with the lowest category (adjusted hazard ratio, 7.98; 95% confidence interval, 1.73-36.86). Among patients considered to have localized disease, MIC-1 significantly increased the discriminative capacity between indolent and lethal prostate cancer compared with the established prognostic markers clinical stage, pathologic grade, and prostate-specific antigen level (P = 0.016). A sequence variant in the MIC-1 gene was associated with decreased MIC-1 serum levels (P = 0.002) and decreased prostate cancer mortality (P = 0.003), suggesting a causative role of MIC-1 in prostate cancer prognosis.Serum MIC-1 concentration is a novel biomarker capable of predicting prostate cancer prognosis.
Association of Common <i>PALB2</i> Polymorphisms with Breast Cancer Risk: A Case-Control Study
Authors: Peizhan Chen, Jie Liang, Zhanwei Wang, Xiaoyi Zhou, Lu Chen, Mian Li, Dong Xie, Zhibin Hu, Hongbing Shen, Hui Wang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The PALB2 gene has an essential role in BRCA2-mediated DNA double-strand break repair and intra–S phase DNA damage checkpoint control, and its mutations are moderately associated with breast cancer susceptibility. This study was designed to investigate the common variants of PALB2 and their association with breast cancer risk. Experimental Design: Four single nucleotide polymorphisms (SNP; rs249954, rs249935, rs120963, and rs16940342) which tagged all 19 of the reported SNPs (minor allele frequency &amp;gt;0.05) covering PALB2 were selected and genotyped in 1,049 patients with breast cancer and 1,073 cancer-free controls in a female Chinese population. Results: Based on the multiple hypothesis testing with the Benjamini-Hochberg method, tagging SNPs (tSNP) rs249954, rs120963, and rs16940342 were found to be associated with an increase of breast cancer risk (false discovery rate–adjusted P values of 0.004, 0.028, and 0.049, respectively) under the dominant model. tSNP rs249954 was associated with a 36% increase of breast cancer risk [adjusted odds ratio (OR), 1.36; 95% confidence intervals (CI), 1.13-1.64; P = 0.001; TT/TC versus CC genotypes]. The adjusted OR for rs120963 was 1.25 (95% CI, 1.04-1.49; P = 0.014; CC/CT versus TT genotypes). For rs16940342, the adjusted OR was 1.21 (95% CI, 1.02-1.45; P = 0.037; GG/GA versus AA genotypes). Based on an additive model, tSNPs rs249954 and rs120963 were associated with an increase of breast cancer risk (P = 0.005 and 0.019; respectively), with the false discovery rate–adjusted P values being 0.020 and 0.038, respectively. Conclusions: Our data suggest that the variants of PALB2 confer low-penetrance breast cancer susceptibility in a Chinese population.
STUDIES ON THE VIRULENCE OF TUBERCLE BACILLI
Authors: Hubert Bloch
Journal: The Journal of Experimental Medicine (1950)

The bacillary cords characteristic for virulent tubercle bacilli are readily disrupted when wet bacilli are suspended in hydrocarbons such as paraffin oil or petroleum ether. The disruption of cords is due to the removal of a material coating the surface of the bacilli and causing them to adhere to each other. This material can be obtained from virulent bacilli by extracting them with petroleum ether. It is a lipid. Avirulent variants of tubercle bacilli do not yield a similar material after extraction in the same manner; only little of it is obtained from BCG bacilli. The following properties of the fraction obtained by petroleum ether extraction are described: (a) It inhibits the migration of leukocytes in vitro. (b) If repeatedly injected in small doses into mice, it is toxic, whereas a single high dose does not give rise to toxic manifestations. (c) The susceptibility of mice to the toxic action of repeated injections parallels to some extent their degree of susceptibility to infection with the strain of tubercle bacilli from which the fraction was obtained. (d) The injection of the extracted material into guinea pigs does not induce a state of allergic reactivity toward tuberculin. Likewise, tuberculin-positive guinea pigs do not show hypersensitivity against injections of the extracted substance. Bacilli extracted with petroleum ether do not lose their viability. They grow out normally in vitro, and they are still pathogenic. However, the removal of the petroleum ether-soluble lipid from the bacilli results in a loss of the ability of the organisms to inhibit the migration of polymorphonuclear leukocytes. Moreover, mice and guinea pigs infected with extracted bacilli may develop tuberculosis considerably slower than animals injected with comparable amounts of unextracted organisms. The significance of these findings is discussed in relation to the problem of the virulence of tubercle bacilli.
Association of Acculturation Levels and Prevalence of Diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Namratha R. Kandula, Ana V. Diez-Roux, Cheeling Chan, Martha L. Daviglus, Sharon A. Jackson, Hanyu Ni, Pamela J. Schreiner
Journal: Diabetes Care (2008)

The prevalence of type 2 diabetes among Hispanic and Asian Americans is increasing. These groups are largely comprised of immigrants who may be undergoing behavioral and lifestyle changes associated with development of diabetes. We studied the association between acculturation and diabetes in a population sample of 708 Mexican-origin Hispanics, 547 non-Mexican-origin Hispanics, and 737 Chinese participants in the Multi-Ethnic Study of Atherosclerosis (MESA).Diabetes was defined as fasting glucose >/=126 mg/dl and/or use of antidiabetic medications. An acculturation score was calculated for all participants using nativity, years living in the U.S., and language spoken at home. The score ranged from 0 to 5 (0 = least acculturated and 5 = most acculturated). Relative risk regression was used to estimate the association between acculturation and diabetes.For non-Mexican-origin Hispanics, the prevalence of diabetes was positively associated with acculturation score, after adjustment for sociodemographics. The prevalence of diabetes was significantly higher among the most acculturated versus the least acculturated non-Mexican-origin Hispanics (prevalence ratio 2.49 [95% CI 1.14-5.44]); the higher the acculturation score is, the higher the prevalence of diabetes (P for trend 0.059). This relationship between acculturation and diabetes was partly attenuated after adjustment for BMI or diet. Diabetes prevalence was not related to acculturation among Chinese or Mexican-origin Hispanics.Among non-Mexican-origin Hispanics in MESA, greater acculturation is associated with higher diabetes prevalence. The relation is at least partly mediated by BMI and diet. Acculturation is a factor that should be considered when predictors of diabetes in racial/ethnic groups are examined.
Upper respiratory tract infections and exercise.
Authors: D C Nieman
Journal: Thorax (1995)

The epidemiological data suggest that endurance athletes are at increased risk for upper respiratory tract infections during periods of heavy training and the 1-2 week period following a marathon or similar event. At present there is no clear indication that chronic alterations in immune function explain this increased risk. Following acute bouts of prolonged heavy endurance exercise, several components of the immune system are suppressed for several hours. This has led to the concept of the "open window" theory described as the 1-9 hour period following prolonged endurance exercise when host defense is decreased and the risk of upper respiratory tract infection is increased.
Acute Regulation of Fatty Acid Oxidation and AMP-Activated Protein Kinase in Human Umbilical Vein Endothelial Cells
Authors: Zeina Dagher, Neil Ruderman, Keith Tornheim, Yasuo Ido
Journal: Circulation Research (2001)

It is generally accepted that endothelial cells generate most of their ATP by anaerobic glycolysis and that very little ATP is derived from the oxidation of fatty acids or glucose. Previously, we have reported that, in cultured human umbilical vein endothelial cells (HUVECs), activation of AMP-activated protein kinase (AMPK) by the cell-permeable activator 5-aminoimidazole-4-carboximide riboside (AICAR) is associated with an increase in the oxidation of (3)H-palmitate. In the present study, experiments carried out with cultured HUVECs revealed the following: (1) AICAR-induced increases in palmitate oxidation during a 2-hour incubation are associated with a decrease in the concentration of malonyl coenzyme A (CoA) (an inhibitor of carnitine palmitoyl transferase 1), which temporally parallels the increase in AMPK activity and a decrease in the activity of acetyl CoA carboxylase (ACC). (2) AICAR does not stimulate either palmitate oxidation when carnitine is omitted from the medium or oxidation of the medium-chain fatty acid octanoate. (3) When intracellular lipid pools are prelabeled with (3)H-palmitate, the measured rate of palmitate oxidation is 3-fold higher, and in the presence of AICAR, it accounts for nearly 40% of calculated ATP generation. (4) Incubation of HUVECs in a glucose-free medium for 2 hours causes the same changes in AMPK, ACC, malonyl CoA, and palmitate oxidation as does AICAR. (5) Under all conditions studied, the contribution of glucose oxidation to ATP production is minimal. The results indicate that the AMPK-ACC-malonyl CoA-carnitine palmitoyl transferase 1 mechanism plays a key role in the physiological regulation of fatty acid oxidation in HUVECs. They also indicate that HUVECs oxidize fatty acids from both intracellular and extracellular sources, and that when this is taken into account, fatty acids can be a major substrate for ATP generation. Finally, they suggest that AMPK is likely to be a major factor in modulating the response of the endothelium to stresses that alter its energy state.