tbuckley/cabot-search huggingface dataset:
Impact of weather factors on Mycoplasma pneumoniae pneumonia
Authors: D Onozuka, M Hashizume, A Hagihara
Journal: Thorax (2009)

<h3>Background:</h3> Although multiple combinations of weather factors may contribute to an increased incidence of <i>Mycoplasma pneumoniae</i> pneumonia, few studies have investigated the association between weather factors and cases of <i>M pneumoniae</i> pneumonia. <h3>Methods:</h3> Data on cases of <i>M pneumoniae</i> pneumonia and weather factors in Fukuoka, Japan from 1999 to 2007 were obtained and time-series analysis was used to assess the effects of weather variables on <i>M pneumoniae</i> pneumonia cases, adjusting for confounding factors. A total of 13 056 <i>M pneumoniae</i> pneumonia cases were reported during the 9-year study period, of which 12 234 (93.7%) were under 15 years of age. <h3>Results:</h3> The weekly number of <i>M pneumoniae</i> pneumonia cases increased by 16.9% (95% CI 11.3% to 22.8%) for every 1°C increase in the average temperature and by 4.1% (95% CI 2.7% to 5.5%) for every 1% increase in relative humidity. <h3>Conclusions:</h3> From 1999 to 2007, cases of <i>M pneumoniae</i> pneumonia increased significantly with increased average temperature and relative humidity in Fukuoka, Japan.
Analgesic effects of clinically used compounds in novel mouse models of polyneuropathy induced by oxaliplatin and cisplatin
Authors: J. R. Deuis, Y. L. Lim, S. Rodrigues de Sousa, R. J. Lewis, P. F. Alewood, P. J. Cabot, I. Vetter
Journal: Neuro-Oncology (2014)

Peripheral neuropathy is the major dose-limiting side effect of cisplatin and oxaliplatin, and there are currently no effective treatments available. The aim of this study was to assess the pharmacological mechanisms underlying chemotherapy-induced neuropathy in novel animal models based on intraplantar administration of cisplatin and oxaliplatin and to systematically evaluate the analgesic efficacy of a range of therapeutics. Neuropathy was induced by a single intraplantar injection of cisplatin or oxaliplatin in C57BL/6J mice and assessed by quantification of mechanical and thermal allodynia. The pharmacological basis of cisplatin-induced neuropathy was characterized using a range of selective pharmacological inhibitors. The analgesic effects of phenytoin, amitriptyline, oxcarbazepine, mexiletine, topiramate, retigabine, gabapentin, fentanyl, and Ca2+/Mg2+ were assessed 24 hours after induction of neuropathy. Intraplantar administration of cisplatin led to the development of mechanical allodynia, mediated through Nav1.6-expressing sensory neurons. Unlike intraplantar injection of oxaliplatin, cold allodynia was not observed with cisplatin, consistent with clinical observations. Surprisingly, only fentanyl was effective at alleviating cisplatin-induced mechanical allodynia despite a lack of efficacy in oxaliplatin-induced cold allodynia. Conversely, lamotrigine, phenytoin, retigabine, and gabapentin were effective at reversing oxaliplatin-induced cold allodynia but had no effect on cisplatin-induced mechanical allodynia. Oxcarbazepine, amitriptyline, mexiletine, and topiramate lacked efficacy in both models of acute chemotherapy-induced neuropathy. This study established a novel animal model of cisplatin-induced mechanical allodynia consistent with the A-fiber neuropathy seen clinically. Systematic assessment of a range of therapeutics identified several candidates that warrant further clinical investigation.
Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates
Authors: Carrie E. McCurdy, Jacalyn M. Bishop, Sarah M. Williams, Bernadette E. Grayson, M. Susan Smith, Jacob E. Friedman, Kevin L. Grove
Journal: Journal of Clinical Investigation (2009)

Maternal obesity is thought to increase the offspring's risk of juvenile obesity and metabolic diseases; however, the mechanism(s) whereby excess maternal nutrition affects fetal development remain poorly understood. Here, we investigated in nonhuman primates the effect of chronic high-fat diet (HFD) on the development of fetal metabolic systems. We found that fetal offspring from both lean and obese mothers chronically consuming a HFD had a 3-fold increase in liver triglycerides (TGs). In addition, fetal offspring from HFD-fed mothers (O-HFD) showed increased evidence of hepatic oxidative stress early in the third trimester, consistent with the development of nonalcoholic fatty liver disease (NAFLD). O-HFD animals also exhibited elevated hepatic expression of gluconeogenic enzymes and transcription factors. Furthermore, fetal glycerol levels were 2-fold higher in O-HFD animals than in control fetal offspring and correlated with maternal levels. The increased fetal hepatic TG levels persisted at P180, concurrent with a 2-fold increase in percent body fat. Importantly, reversing the maternal HFD to a low-fat diet during a subsequent pregnancy improved fetal hepatic TG levels and partially normalized gluconeogenic enzyme expression, without changing maternal body weight. These results suggest that a developing fetus is highly vulnerable to excess lipids, independent of maternal diabetes and/or obesity, and that exposure to this may increase the risk of pediatric NAFLD.
Consciousness, memory, and the hippocampal system: What kind of connections can we make?
Authors: Howard Eichenbaum, Neal J. Cohen
Journal: Behavioral and Brain Sciences (1995)

Abstract Gray's account is remarkable in its depth and scope but too little attention is paid to poor correspondences with the literature on hippocampal/subicular damage, the theta rhythm, and novelty detection. An alternative account, focusing on hippocampal involvement in organizing memories in a way that makes them accessible to conscious recollection but not in access to consciousness per se, avoids each of these limitations.
BCR-ABL rearrangement is not detectable in essential thrombocythemia
Authors: Giovanni Emilia, Roberto Marasca, Patrizia Zucchini, Paola Temperani, Mario Luppi, Giuseppe Torelli, Francesco Lanza, Cristiano De Angelis, Domenica Gandini, GianLuigi Castoldi, Daniele Vallisa, Luigi Cavanna, Laura del Senno
Journal: Blood (2001)
Molecular Dissection of Hyperdiploid Multiple Myeloma by Gene Expression Profiling
Authors: Wee J. Chng, Shaji Kumar, Scott VanWier, Greg Ahmann, Tammy Price-Troska, Kim Henderson, Tae-Hoon Chung, Seungchan Kim, George Mulligan, Barbara Bryant, John Carpten, Morie Gertz, S. Vincent Rajkumar, Martha Lacy, Angela Dispenzieri, Robert Kyle, Philip Greipp, P. Leif Bergsagel, Rafael Fonseca
Journal: Cancer Research (2007)

Abstract Hyperdiploid multiple myeloma (H-MM) is the most common form of myeloma. In this gene expression profiling study, we show that H-MM is defined by a protein biosynthesis signature that is primarily driven by a gene dosage mechanism as a result of trisomic chromosomes. Within H-MM, four independently validated patient clusters overexpressing nonoverlapping sets of genes that form cognate pathways/networks that have potential biological importance in multiple myeloma were identified. One prominent cluster, cluster 1, is characterized by high expression of cancer testis antigen and proliferation-associated genes. Tumors from these patients were more proliferative than tumors in other clusters (median plasma cell labeling index, 3.8; P &amp;lt; 0.05). Another cluster, cluster 3, is characterized by genes involved in tumor necrosis factor/nuclear factor-κB signaling and antiapoptosis. These patients have better response to bortezomib as compared with patients within other clusters (70% versus 29%; P = 0.02). Furthermore, for a group of patients generally thought to have better prognosis, a cluster of patients with short survival (cluster 1; median survival, 27 months) could be identified. This analysis illustrates the heterogeneity within H-MM and the importance of defining specific cytogenetic prognostic factors. Furthermore, the signatures that defined these clusters may provide a basis for tailoring treatment to individual patients. [Cancer Res 2007;67(7):2982–9]
Anaplastic, Plasmablastic, and Plasmacytic Plasmacytomas of Mice: Relationships to Human Plasma Cell Neoplasms and Late-Stage Differentiation of Normal B Cells
Authors: Chen-Feng Qi, Jeff X. Zhou, Chang Hoon Lee, Zohreh Naghashfar, Shao Xiang, Alexander L. Kovalchuk, Torgny N. Fredrickson, Janet W. Hartley, Derry C. Roopenian, Wendy F. Davidson, Siegfried Janz, Herbert C. Morse
Journal: Cancer Research (2007)

Abstract We have compared histologic features and gene expression profiles of newly identified plasmacytomas from NFS.V+ congenic mice with plasmacytomas of IL6 transgenic, Fasl mutant, and SJL-β2M−/− mice. NFS.V+ tumors comprised an overlapping morphologic spectrum of high-grade/anaplastic, intermediate-grade/plasmablastic, and low-grade/plasmacytic cases with similarities to subsets of human multiple myeloma and plasmacytoma. Microarray and immunohistochemical analyses of genes expressed by the most prevalent tumors, plasmablastic plasmacytomas, showed them to be most closely related to immunoblastic lymphomas, less so to plasmacytomas of Fasl mutant and SJL mice, and least to plasmacytic plasmacytomas of IL6 transgenic mice. Plasmablastic tumors seemed to develop in an inflammatory environment associated with gene signatures of T cells, natural killer cells, and macrophages not seen with plasmacytic plasmacytomas. Plasmablastic plasmacytomas from NFS.V+ and SJL-β2M−/− mice did not have structural alterations in Myc or T(12;15) translocations and did not express Myc at high levels, regular features of transgenic and pristane-induced plasmacytomas. These findings imply that, as for human multiple myeloma, Myc-independent routes of transformation contribute to the pathogenesis of these tumors. These findings suggest that plasma cell neoplasms of mice and humans exhibit similar degrees of complexity. Mouse plasmacytomas, previously considered to be homogeneous, may thus be as diverse as their human counterparts with respect to oncogenic mechanisms of plasma cell transformation. Selecting specific types of mouse plasmacytomas that relate most closely to subtypes of human multiple myeloma may provide new opportunities for preclinical testing of drugs for treatment of the human disease. [Cancer Res 2007;67(6):2439–47]
Is Posttraumatic Stress in Youth a Culture-Bound Phenomenon? A Comparison of Symptom Trends in Selected U.S. and Russian Communities
Authors: Vladislav Ruchkin, Mary Schwab-Stone, Stephanie Jones, Domenic V Cicchetti, Roman Koposov, Robert Vermeiren
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The cross-cultural applicability of the concept of posttraumatic stress was investigated by assessing symptom frequency and levels of comorbid psychopathology in adolescents from the United States and Russia. METHOD: A self-report survey was conducted in representative samples of 2,157 adolescents 14 to 17 years old from urban communities of the United States (N=1,212) and Russia (N=945). RESULTS: In both countries, the levels of all three major clusters of posttraumatic symptoms (reexperiencing, avoidance, and arousal), as well as of internalizing psychopathology, increased along with the level of posttraumatic stress. Expectations about the future had a tendency to decrease with increasing posttraumatic stress. No differences between countries in significant interaction effects for symptom levels were found. CONCLUSIONS: The current findings suggest that posttraumatic symptoms and their associations with other adolescent mental health problems are not culture bound and that the psychological consequences of trauma follow similar dynamics cross-culturally.
Genetic Components of the Circadian Clock Regulate Thrombogenesis In Vivo
Authors: Elizabeth J. Westgate, Yan Cheng, Dermot F. Reilly, Tom S. Price, Jacqueline A. Walisser, Christopher A. Bradfield, Garret A. FitzGerald
Journal: Circulation (2008)

Myocardial infarction, stroke, and sudden death undergo diurnal variation. Although genes relevant to hemostasis and vascular integrity undergo circadian oscillation, the role of the molecular clock in thrombotic events remains to be established.A diurnal variation in the time to thrombotic vascular occlusion (TTVO) subsequent to a photochemical injury was observed in wild-type mice: TTVO varied from 24.6+/-2.7 minutes at zeitgeber time (ZT) 2 to 40.3+/-4.3 minutes at ZT8, 24.3+/-2.3 minutes at ZT14, and 31.0+/-4.4 minutes at ZT20. This pattern was disrupted or altered when core clock genes-BMAL1, CLOCK, and NPAS2-were mutated or deleted. Mutation of CLOCK abolished the diurnal variation in TTVO, whereas deletion of NPAS2 altered its temporal pattern. NPAS2 deletion prolonged TTVO and reduced blood pressure irrespective of clock time. Global BMAL1 deletion shortened TTVO at ZT8, and the diurnal variation in TTVO, but not in systemic blood pressure, was disrupted in mice in which BMAL1 had been selectively deleted in endothelium.Key components of the molecular clock regulate the response to a thrombogenic stimulus in vivo. Such a phenomenon may interact with environmental variables, and together with the influence of these genes on blood pressure may contribute to the diurnal variation in cardiovascular events observed in humans.
Functional Polymorphisms of<i>Matrix Metalloproteinase-9</i>Are Associated with Risk of Occurrence and Metastasis of Lung Cancer
Authors: Zhibin Hu, Xiang Huo, Daru Lu, Ji Qian, Jiannong Zhou, Yijiang Chen, Lin Xu, Hongxia Ma, Jingfu Zhu, Qingyi Wei, Hongbing Shen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Matrix metalloproteinase 9 (MMP-9) plays critical roles in cancer development and aggression. Nonsynonymous single-nucleotide polymorphisms (SNP) in the functional domain of the MMP-9 gene may influence substrate and inhibitor binding and contribute to cancer predisposition and aggression. Patients and Methods: To test our hypothesis that common nonsynonymous SNPs, R279Q, P574R, and R668Q, in MMP-9 are associated with lung cancer development and metastasis, we conducted a case-control study of 744 patients with incident lung cancer and 747 cancer-free controls in Southeast China. Multivariate logistic regression analysis was used to calculate adjusted odds ratio (OR) and 95% confidence interval (95% CI). Results: We found that compared with the 279QQ genotype, the 279RR genotype was associated with significant elevated risk of lung cancer with metastasis (adjusted OR, 1.79; 95% CI, 1.03-3.08), whereas the 574PR heterozygote and 574PP homozygote had 1.46-fold (95% CI, 0.94-2.26) and 1.69-fold elevated risk (95% CI, 1.10-2.60), respectively, compared with the 574RR genotype. When we examined the combined effect of R279Q and P574R and used the 279R and 574P as the risk alleles, a significantly increased risk of lung cancer was associated with both the genotypes containing “1 to 2 risk alleles” (adjusted OR, 2.16; 95% CI, 1.30-3.59) and containing “&amp;gt;2 risk alleles” (adjusted OR, 2.44; 95% CI, 1.48-4.03), and it was more pronounced in 290 lung cancer cases with metastasis [adjusted OR, 2.30 (95% CI, 1.09-4.85) for the 1 to 2 risk alleles subgroup and adjusted OR, 2.82 (95% CI, 1.35-5.88) for the &amp;gt;2 risk alleles subgroup], compared with those without any risk alleles. However, no overall significant associations were observed between R668Q and lung cancer risk in this study population. Conclusion: These findings indicate that the potentially functional polymorphisms, MMP-9 P574R and R279Q, may confer the biomarker in the occurrence and metastasis of primary lung cancer. Further functional studies including these two genetic variants are warranted to confirm our findings.
Dopamine tightens, not loosens
Authors: Don M. Tucker
Journal: Behavioral and Brain Sciences (1999)

Depue &amp; Collins propose that extraversion should be separated from the impulsivity-constraint dimension of personality, and that the VTA dopamine system is the primary engine of extraversion. Although their focus is on personality traits, it may be useful to consider the evidence on psychological state changes, related both to affective arousal and to drug effects. This evidence shows that there are inherent relations between extraversion and impulsivity-constraint, and that there are influences of dopamine on impulsivity-constraint that are not consistent with the Depue &amp; Collins model. Increased positive affect leads to increased extraversion, and this is associated with more impulsivity and less constraint. The evidence on drug effects shows that greater dopaminergic control is associated with more constraint, and with anxiety and vigilance rather than positive affect.
MicroRNA miR-302 Inhibits the Tumorigenecity of Human Pluripotent Stem Cells by Coordinate Suppression of the CDK2 and CDK4/6 Cell Cycle Pathways
Authors: Shi-Lung Lin, Donald C. Chang, Shao-Yao Ying, Davey Leu, David T.S. Wu
Journal: Cancer Research (2010)

miR-302 is the major microRNA found in human embryonic stem cells and induced pluripotent stem cells, but its function has been unclear. In mice, there is evidence that miR-302 may silence p21Cip1 (CDKN1A) to promote cell proliferation, whereas studies in human reprogrammed pluripotent stem cells suggested that elevated miR-302 expression inhibited cell cycle transit. Here, we clarify this difference, reporting that in human cells, miR-302 simultaneously suppressed both the cyclin E-CDK2 and cyclin D-CDK4/6 pathways to block>70% of the G1-S cell cycle transition. Concurrent silencing of BMI-1, a cancer stem cell marker targeted by miR-302, further promoted tumor suppressor functions of p16Ink4a and p14/p19Arf directed against CDK4/6-mediated cell proliferation. Among all G1 phase checkpoint regulators, human p21Cip1 was found not to be a valid target of miR-302. Overall, our findings indicate that miR-302 inhibits human pluripotent stem cell tumorigenicity by enhancing multiple G1 phase arrest pathways rather than by silencing p21Cip1.
Peritoneal and Subperitoneal Stroma May Facilitate Regional Spread of Ovarian Cancer
Authors: Ena Wang, Yvonne Ngalame, Monica C. Panelli, Hoainam Nguyen-Jackson, Michael Deavers, Peter Mueller, Wei Hu, Cherylyn A. Savary, Ryuji Kobayashi, Ralph S. Freedman, Francesco M. Marincola
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Epithelial ovarian cancer (EOC) is characterized by early peritoneal involvement ultimately contributing to morbidity and mortality. To study the role of the peritoneum in fostering tumor invasion, we analyzed differences between the transcriptional repertoires of peritoneal tissue lacking detectable cancer in patients with EOC versus benign gynecologic disease. Experimental Design: Specimens were collected at laparotomy from patients with benign disease (b) or malignant (m) ovarian pathology and comprised primary ovarian tumors, paired bilateral specimens from adjacent peritoneum and attached stroma (PE), subjacent stroma (ST), peritoneal washes, ascites, and peripheral blood mononuclear cells. Specimens were immediately frozen. RNA was amplified by in vitro transcription and cohybridized with reference RNA to a custom-made 17.5k cDNA microarray. Results: Principal component analysis and unsupervised clustering did not segregate specimens from patients with benign or malignant pathology. Class comparison identified differences between benign and malignant PE and ST specimens deemed significant by permutation test (P = 0.027 and 0.012, respectively). A two-tailed Student's t test identified 402 (bPE versus mPE) and 663 (mST versus bST) genes differentially expressed at a significance level of P2 ≤ 0.005 when all available paired samples from each patient were analyzed. The same comparison using one sample per patient reduced the pool of differentially expressed genes but retained permutation test significance for bST versus mST (P = 0.031) and borderline significance for bPE versus mPE (P = 0.056) differences. Conclusions: The presence of EOC may foster peritoneal implantation and growth of cancer cells by inducing factors that may represent molecular targets for disease control.
Cinnamon Improves Glucose and Lipids of People With Type 2 Diabetes
Authors: Alam Khan, Mahpara Safdar, Mohammad Muzaffar Ali Khan, Khan Nawaz Khattak, Richard A. Anderson
Journal: Diabetes Care (2003)

The objective of this study was to determine whether cinnamon improves blood glucose, triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol levels in people with type 2 diabetes.A total of 60 people with type 2 diabetes, 30 men and 30 women aged 52.2 +/- 6.32 years, were divided randomly into six groups. Groups 1, 2, and 3 consumed 1, 3, or 6 g of cinnamon daily, respectively, and groups 4, 5, and 6 were given placebo capsules corresponding to the number of capsules consumed for the three levels of cinnamon. The cinnamon was consumed for 40 days followed by a 20-day washout period.After 40 days, all three levels of cinnamon reduced the mean fasting serum glucose (18-29%), triglyceride (23-30%), LDL cholesterol (7-27%), and total cholesterol (12-26%) levels; no significant changes were noted in the placebo groups. Changes in HDL cholesterol were not significant.The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.
458 FINAL RESULTS OF THE PHARMACOKINETICS, EFFICACY, AND SAFETY/TOLERABILITY OF 400 AND 600 MG ONCE-DAILY DOSING OF ACH-1625 (HCV NS3 PROTEASE INHIBITOR) IN HCV GENOTYPE 1
Authors: V. Detishin, W. Haazen, R. Hooijmaijers, M. Ruppert, K. Bol, H. Robison, L. Robarge, A. Agarwal, M. Deshpande, E. Olek
Journal: Journal of Hepatology (2011)
Presence of rheumatoid factor and antibodies to citrullinated peptides in systemic lupus erythematosus
Authors: I E A Hoffman
Journal: Annals of the Rheumatic Diseases (2005)

Rheumatoid factor (RF) is found commonly in patients with systemic lupus erythematosus (SLE), and has been associated with a more benign disease course.1,2 Anti-citrullinated peptide antibodies (ACPA) are more specific for rheumatoid arthritis (RA).3–5 Several assays for ACPA detection have been developed: among others, an enzyme linked immunosorbent assay (ELISA) for anti-cyclic citrullinated peptide (anti-CCP) antibodies3 and a line immunoassay (LIA) for antibodies to peptide A (pepA) and peptide B (pepB), two synthetic citrullinated peptides.4 Few reports exist about the presence of ACPA in SLE. Although patients with SLE are often part of the control group when determining the specificity of ACPA for RA, SLE alone is seldom studied. Mediwake et al found that 3/66 …