tbuckley/cabot-search huggingface dataset:
Structural Magnetic Resonance Image Averaging in Schizophrenia
Authors: Adam Wolkin, Henry Rusinek, Gita Vaid, Luigi Arena, Todd Lafargue, Michael Sanfilipo, Celia Loneragan, Andrew Lautin, John Rotrosen
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: Intersubject averaging of structural magnetic resonance (MR) images has been infrequently used as a means to study group differences in cerebral structure throughout the brain. In the present study, the authors used linear intersubject averaging of structural MR images to evaluate the validity and utility of this technique and to extend previous research, conducted using a different approach to image averaging, in which reduction in thalamic size and abnormalities in perithalamic white matter tracts in the brains of schizophrenic patients were reported by Andreasen et al. METHOD: A 1.5-T MR scanner was used to obtain high-resolution, whole brain T1-weighted structural MR images for an age-matched sample of 25 schizophrenic patients and 25 normal control subjects. A "bounding box" procedure was used to create a single "averaged" brain for the schizophrenic group and for the control group. Differences in signal intensity between the two average brains were examined on a pixel-wise basis through use of one-tailed effect size maps. RESULTS: Effect size maps revealed widespread patchy signal intensity differences between the two groups in both cortical and periventricular areas, including major white matter tracts. The signal intensity differences were consistent with cortical thinning/sulcal widening and ventricular enlargement. No differences were found within thalamus or in immediately surrounding white matter. Effect size maps for differences (schizophrenic minus normal subjects) had only small values. CONCLUSIONS: These results are consistent with diffuse structural brain abnormalities of both gray and white matter in schizophrenic populations such as the one in this study. (Am J Psychiatry 1998; 155:1064–1073)
Mitochondrial Hsp90s suppress calcium-mediated stress signals propagating from mitochondria to the ER in cancer cells
Authors: Hye-Kyung Park, Ji-Eun Lee, Jaehwa Lim, Byoung Heon Kang
Journal: Molecular Cancer (2014)

Resistance to cell death in the presence of stressful stimuli is one of the hallmarks of cancer cells acquired during multistep tumorigenesis, and knowledge of the molecular mechanism of stress adaptation can be exploited to develop cancer-selective therapeutics. Mitochondria and the endoplasmic reticulum (ER) are physically interconnected organelles that can sense and exchange various stress signals. Although there have been many studies on stress propagation from the ER to mitochondria, reverse stress signals originating from mitochondria have not been well reported. After inactivation of the proteins by pharmacologic and genetic methods, the signal pathways were analyzed by fluorescence microscopy, flow cytometry, MTT assay, and western blotting. A mouse xenograft model was used to examine synergistic anticancer activity and the action mechanism of drugs in vivo. We show in this study that mitochondrial heat shock protein 90 (Hsp90) suppresses mitochondria-initiated calcium-mediated stress signals propagating into the ER in cancer cells. Mitochondrial Hsp90 inhibition triggers the calcium signal by opening the mitochondrial permeability transition pore and, in turn, the ER ryanodine receptor, via calcium-induced calcium release. Subsequent depletion of ER calcium activates unfolded protein responses in the ER lumen, thereby increasing the expression of a pro-apoptotic transcription factor, CEBP homologous protein (CHOP). Combined treatment with the ER stressor thapsigargin and the mitochondrial Hsp90 inhibitor gamitrinib augmented interorganelle stress signaling by elevating CHOP expression, and showed synergistic cytotoxic activity exclusively in cancer cells in vitro and in vivo. Collectively, mitochondrial Hsp90s confer cell death resistance to cancer cells by suppressing the mitochondria-initiated calcium-mediated interorganelle stress response.
Origin of Mammalian Gonadotropin-Releasing Hormones
Authors: NANCY M. SHERWOOD, DAVID A. LOVEJOY, IMOGEN R. COE
Journal: Endocrine Reviews (1993)

GONADOTROPIN-releasing hormone (GnRH) plays a pivotal role in reproduction. The existence of this neuropeptide, also called LHRH, was predicted in the 1950s (1), but the structure of the 10 amino acid peptide for porcine and ovine brains was not reported until the 1970s (2, 3). In the 20 yr since then, only one form of GnRH has been identified in most placental mammals, and this is still considered to be the sole neuropeptide causing the release of LH and FSH. The structure and functions of the mammalian form of GnRH have been reviewed a number of times (4s–8). Meanwhile, both mammalian GnRH and related forms of GnRH are now known to be present in primitive placental mammals, nonplacental mammals, and other vertebrates. Novel functions, in addition to the release of gonadotropins, exist. Studies of GnRH peptides and their genes have altered our views on the origin, function, and regulation of this neuropeptide.
Association of STAT3 and TNFRSF1A with ankylosing spondylitis in Han Chinese
Authors: S. I. Davidson, Y. Liu, P. A. Danoy, X. Wu, G. P. Thomas, L. Jiang, L. Sun, N. Wang, J. Han, H. Han, P. M. Visscher, M. A. Brown, H. Xu
Journal: Annals of the Rheumatic Diseases (2010)

Recent association studies by the Australo-Anglo-American Spondyloarthritis Consortium (TASC) in Caucasian European populations from Australia, North America and the UK have identified a number of genes as being associated with ankylosing spondylitis (AS). A candidate gene study in a Han Chinese population was performed based on these findings to identify associated genes in this population.A case-control study was performed in a Han Chinese population of patients with AS (n = 775) and controls (n = 1587) from Shanghai and Nanjing. All patients met the modified New York criteria for AS. The cases and controls were genotyped for 115 single nucleotide polymorphisms (SNPs) tagging IL23R, ERAP1, STAT3, JAK2, TNFRSF1A and TRADD, as well as other confirmation SNPs from the TASC study, using the Sequenom iPlex and the ABI OpenArray platforms. Statistical analysis of genotyped SNPs was performed using the Cochran-Armitage test for trend and meta-analysis was performed using METAL. SNPs in AS-associated genes in this study were then imputed using MaCH, and association with AS tested by logistic regression.SNPs in TNFRSF1A (rs4149577, p = 8.2 × 10⁻⁴), STAT3 (rs2293152, p = 0.0015; rs1053005, p = 0.017) and ERAP1 (rs27038, p = 0.0091; rs27037, p = 0.0092) were significantly associated with AS in Han Chinese. Association was also observed between AS and the intergenic region 2p15 (rs10865331, p = 0.023). The lack of association between AS and IL23R in Han Chinese was confirmed (all SNPs p > 0.1).The study results demonstrate for the first time that genetic polymorphisms in STAT3, TNFRSF1A and 2p15 are associated with AS in Han Chinese, suggesting common pathogenic mechanisms for the disease in Chinese and Caucasian European populations. Furthermore, previous findings demonstrating that ERAP1, but not IL23R, is associated with AS in Chinese patients were confirmed.
Watchdog set to reject four drugs for kidney cancer on the NHS
Authors: A. O'Dowd
Journal: BMJ (2008)

The UK clinical watchdog has proposed rejecting four drugs for use on the NHS for advanced renal cancer, saying they are clinically effective but not good value for money.

The National Institute for Health and Clinical Excellence (NICE) issued draft guidance this week that rejects the drugs sunitinib (Sutent), bevacizumab (Avastin), sorafenib (Nexavar), and temsirolimus (Torisel). The guidance is out for consultation until 29 August, with the final guidance due in early 2009.

The recommendation, which applies in England, Wales, and Northern Ireland, has provoked an angry response from charities that claimed that NICE’s appraisal system was not appropriate for all types of drugs.

NICE’s draft guidance says that it does not recommend these drugs for advanced or metastatic …
Luciferase expression and bioluminescence does not affect tumor cell growth in vitro or in vivo
Authors: Jessamy C Tiffen, Charles G Bailey, Cynthia Ng, John EJ Rasko, Jeff Holst
Journal: Molecular Cancer (2010)

Live animal imaging is becoming an increasingly common technique for accurate and quantitative assessment of tumor burden over time. Bioluminescence imaging systems rely on a bioluminescent signal from tumor cells, typically generated from expression of the firefly luciferase gene. However, previous reports have suggested that either a high level of luciferase or the resultant light reaction produced upon addition of D-luciferin substrate can have a negative influence on tumor cell growth. To address this issue, we designed an expression vector that allows simultaneous fluorescence and luminescence imaging. Using fluorescence activated cell sorting (FACS), we generated clonal cell populations from a human breast cancer (MCF-7) and a mouse melanoma (B16-F10) cell line that stably expressed different levels of luciferase. We then compared the growth capabilities of these clones in vitro by MTT proliferation assay and in vivo by bioluminescence imaging of tumor growth in live mice. Surprisingly, we found that neither the amount of luciferase nor biophotonic activity was sufficient to inhibit tumor cell growth, in vitro or in vivo. These results suggest that luciferase toxicity is not a necessary consideration when designing bioluminescence experiments, and therefore our approach can be used to rapidly generate high levels of luciferase expression for sensitive imaging experiments.
Bone Morphogenetic Protein (BMP)-6 Signaling and BMP Antagonist Noggin in Prostate Cancer
Authors: Dominik R. Haudenschild, Sabrina M. Palmer, Timothy A. Moseley, Zongbing You, A. Hari Reddi
Journal: Cancer Research (2004)

Abstract It has been proposed that the osteoblastic nature of prostate cancer skeletal metastases is due in part to elevated activity of bone morphogenetic proteins (BMPs). BMPs are osteoinductive morphogens, and elevated expression of BMP-6 correlates with skeletal metastases of prostate cancer. In this study, we investigated the expression levels of BMPs and their modulators in prostate, using microarray analysis of cell cultures and gene expression. Addition of exogenous BMP-6 to DU-145 prostate cancer cell cultures inhibited their growth by up-regulation of several cyclin-dependent kinase inhibitors such as p21/CIP, p18, and p19. Expression of noggin, a BMP antagonist, was significantly up-regulated by BMP-6 by microarray analysis and was confirmed by quantitative reverse transcription-polymerase chain reaction and at the protein level. Noggin protein was present in prostate biopsies and localized to the epithelial components of prostate by immunohistochemistry. Recombinant noggin inhibited the function of BMP-6, suggesting a negative feedback regulation of BMP activity and indicating a strategy for the development of a novel therapeutic target in the treatment of painful osteosclerotic bone metastases of prostate cancer.
Medically unexplained symptoms: the biopsychosocial model found wanting
Authors: C. C Butler, M. Evans, D. Greaves, S. Simpson
Journal: Journal of the Royal Society of Medicine (2004)

The recognition that all illnesses have both mental and physical components and that there is a dynamic relationship between components of systems (general systems theory) led to criticisms of the biomedical model and to the development of the biopsychosocial model of Western medicine.1,2 From this model emerged the concept of triple diagnosis, whereby clinicians make diagnoses at three levels, the biological or physical, the personal or psychological and the social and contextual.2,3 By understanding relevant factors at all three levels and their interactions, clinicians are better able to treat the whole person—the patient-centred clinical method.4
April and Baff Connect Autoimmunity and Cancer
Authors: Carl F. Ware
Journal: The Journal of Experimental Medicine (2000)

Recent studies of two newcomers to the TNF cytokine family have revealed an unsuspected link between autoimmunity and cancer. In this issue, Rennert et. al. ([1][1]) define the specific receptors for the orphan ligand known as APRIL (a proliferation-inducing ligand), which was previously recognized
Solid-Phase Radioimmunoelectrophoresis: An Assay for Carcinoembryonic Antigen2
Authors: Calvin A. Saravis, Norman Zamcheck, Herbert Z. Kupchik, Richard P. McCabe, Munjal Devidayal
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Solid-Phase Radioimmunoelectrophoresis: An Assay for Carcinoembryonic Antigen Get access Calvin A. Saravis, Calvin A. Saravis 3Mallory Gastrointestinal Laboratory and Sears Surgical Unit, Harvard Surgical Unit, Boston City Hospital, Boston, Mass. 02118. Search for other works by this author on: Oxford Academic PubMed Google Scholar Norman Zamcheck, Norman Zamcheck 4Mallory Gastrointestinal Laboratory, Boston City Hospital, Department of Medicine, Harvard Medical School and Department of Pathology, Boston University Medical School, Boston, Mass. 02115. Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert Z. Kupchik, Herbert Z. Kupchik 4Mallory Gastrointestinal Laboratory, Boston City Hospital, Department of Medicine, Harvard Medical School and Department of Pathology, Boston University Medical School, Boston, Mass. 02115. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard P. McCabe, Richard P. McCabe 5Mallory Gastrointestinal Laboratory, Boston City Hospital, Boston, Mass. 02115. Search for other works by this author on: Oxford Academic PubMed Google Scholar Munjal Devidayal Munjal Devidayal 4Mallory Gastrointestinal Laboratory, Boston City Hospital, Department of Medicine, Harvard Medical School and Department of Pathology, Boston University Medical School, Boston, Mass. 02115. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 4, October 1974, Pages 921–926, https://doi.org/10.1093/jnci/53.4.921 Published: 01 October 1974 Article history Received: 14 March 1974 Accepted: 18 June 1974 Published: 01 October 1974
Karyotypic Evolution Associated With Loss of Tumorigenicity2
Authors: June S. Shepard, Olive S. Pettengill, Doris H. Wurster Hill, George D. Sorenson
Journal: JNCI Journal of the National Cancer Institute (1979)

A reproducible association between loss of tumorigenicity and specific karyotypic changes was described in cell culture lines SLU-5 and DMS-402 established from mouse plasmacytoma MOPC-21 carried in BALB/c mice. The defect in chromosome no. 15, which has been specifically associated with mouse myelomas, was neither corrected nor eliminated in the karyotypic evolution that occurred simultaneously and progressively with the grandual loss of oncogenicity.
<i>In vivo</i> Assessment of RAS-Dependent Maintenance of Tumor Angiogenesis by Real-time Magnetic Resonance Imaging
Authors: Yi Tang, Minjung Kim, Daniel Carrasco, Andrew L. Kung, Lynda Chin, Ralph Weissleder
Journal: Cancer Research (2005)

Abstract New blood vessel formation is a prominent feature of human cancers and tumor progression and is frequently accompanied by the acquisition of an angiogenic phenotype associated with a switch in the balance of proangiogenic and antiangiogenic molecules. This study was designed to investigate the role of activated H-RAS on the angiogenic phenotype of melanoma that arises in the inducible Tyr/Tet-RAS Ink4a/Arf−/− model using in vivo imaging with histopathologic correlation. We show that loss of RAS activity in fully established melanomas led to a reduction in tumor volume, which was preceded by impairment of vascular function as determined by in vivo magnetic resonance imaging. This correlated with activation of apoptosis in host-derived endothelial cells as well as in tumor cells. Thus, real-time in vivo imaging provided evidence that maintenance of tumor angiogenesis requires activated RAS in this model system, and that loss of vascular integrity upon inactivation of RAS is an active process rather than a consequence of loss of tumor cell viability.
Titrated sedation with propofol or midazolam for flexible bronchoscopy: a randomised trial
Authors: G. Clark, M. Licker, A. B. Younossian, P. M. Soccal, J-G. Frey, T. Rochat, J. Diaper, P-O. Bridevaux, J-M. Tschopp
Journal: European Respiratory Journal (2009)

In this study, we questioned whether propofol provided clinical benefits compared with midazolam in terms of neuropsychometric recovery, safety profile and patient tolerance. Patients, aged &gt;18 yrs, were randomised to receive midazolam or propofol, given by non-anaesthetist physicians to achieve moderate levels of sedation as assessed by the electroencephalographic bispectral index (BIS; between 70 and 85). The primary end-point was the time delay until recovery of the BIS above 90. Other end-points included a neuropsychometric continuous performance test (CPT), serious respiratory adverse events, patient tolerance and physician satisfaction. Neuropsychometric recovery was improved in the propofol compared to the midazolam group as evidenced by faster normalisation of BIS index (5.4±4.7 min versus 11.7±10.2 min; p = 0.001) and better results at the CPT. In the midazolam group, 15% of patients presented profound sedation precluding CPT completion and one patient required mechanical ventilatory support. Patient tolerance was significantly better in the propofol group, whereas the operator’s assessment was comparable in both groups. Compared with midazolam, propofol provided a higher quality of sedation in terms of neuropsychometric recovery and patient tolerance. BIS-guided propofol administration represents a safe sedation technique that can be performed by the non-anaesthesiologist.
Lung function at one month of age as a risk factor for infant respiratory symptoms in a high risk population
Authors: C S Murray
Journal: Thorax (2002)

Background: Abnormal premorbid lung function is a risk factor for subsequent wheezing in children with one or no atopic parent. This study was undertaken to establish whether early lung function in high risk infants (both parents atopic) was a risk factor for respiratory symptoms in infancy and to examine the influence of maternal asthma, smoking, and allergen exposure during pregnancy on any association. Methods: Infants were recruited from the NAC Manchester Asthma and Allergy Study cohort at birth. Partial forced expiratory flow volume technique under sedation was carried out to determine maximal flow at FRC (V′maxFRC). Children were followed prospectively and parents completed a standard respiratory questionnaire at one year of age. Results: Sixty nine term infants (34 boys; 88% mothers non-smokers; no household pets) underwent respiratory function testing. Size adjusted V′maxFRC was significantly lower in infants who had recurrent wheeze during the first year of life (mean 1.3 ml/s/cm, 95% CI 0.99 to 1.60) than in those who did not (mean 2.03 ml/s/cm, 95% CI 1.71 to 2.36; p=0.01). V′maxFRC was also significantly lower in infants who had recurrent cough symptoms. In multivariate regression analysis, when adjusted for age at test, sex, maternal asthma, smoking and maternal mattress Der 1 levels, a lower size adjusted V′maxFRC score remained strongly associated with wheezing (OR 0.37, 95% CI 0.18 to 0.77, p=0.007). Maternal smoking also remained an independent risk factor (OR 29.85, 95% CI 2.46 to 362.5, p=0.008). Conclusion: Significantly diminished lung function was present in high risk infants who subsequently wheezed and coughed. This was independent of maternal exposure to mite allergen, asthma, and smoking during pregnancy.
Chronic ulcerative colitis: incidence and prevalence in a community.
Authors: C M Stonnington, S F Phillips, L J Melton, A R Zinsmeister
Journal: Gut (1987)

Utilising the population based data resources of the Rochester Epidemiology Project, we determined the incidence and prevalence of chronic ulcerative colitis among Rochester, Minnesota, residents over the 20 year period, 1960-79. One hundred and thirty eight cases met diagnostic and residency criteria, for an overall age, and sex adjusted chronic ulcerative colitis incidence rate of 15.0 per 100,000 person years. The male:female ratio of age adjusted rates was 1.5:1. Age specific incidence was roughly bimodal in appearance but was not consistent in different patient subgroups. On 1-1-80, there were 120 Rochester residents with a history of chronic ulcerative colitis, corresponding to a prevalence rate of 225.2 per 100,000 population. Fifty three per cent of chronic ulcerative colitis incidence cases were 9definite9 and 47% were 9probable9, the former requiring consistent observations for at least six months. The definite group had proportionately more men and disease of greater extent and severity. Pancolitis comprised about one-third of all cases (4.6 per 100,000 person years). Proctitis and distal disease (7.1 and 2.0 per 100,000 person years) made up most of the rest. One-fourth of all patients had 9severe9 or 9moderate9 disease (3.8 per 100,000 person years), while the remainder had either 9mild9 or 9transient9 chronic ulcerative colitis (11.2 per 100,000 person years). In residents of Rochester, Minnesota, chronic ulcerative colitis is most often a mild disease. The over-representation of severe or complicated examples that results from selected referral to major centres probably distorts the natural clinical spectrum of the disease.
Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease
Authors: Luciana Teofili, Anna Laura Di Febo, Francesco Pierconti, Nicola Maggiano, Maurizio Bendandi, Sergio Rutella, Antonella Cingolani, Nicola Di Renzo, Pellegrino Musto, Stefano Pileri, Giuseppe Leone, Luigi Maria Larocca
Journal: Blood (2001)
THE NUCLEIC ACIDS OF T2, T4, AND T<scp>6</scp> BACTERIOPHAGES
Authors: Margeris A. Jesaitis
Journal: The Journal of Experimental Medicine (1957)

The deoxyribonucleic acids of the wild type strains of the T(2), T(4), and T(6) bacteriophages have been shown to contain glucose as an integral part of the molecule; the amount of hexose present in each nucleic acid differs. A study of the acid degradation products of the three nucleic acids has revealed that in each instance glucose is linked to the apurinic acid component. In the case of the T(6) nucleic acid it was found that two molecules of glucose are linked to hydroxymethylcytidylic acid. The other mononucleotides contained no glucose. From the results which have been presented here, and from data presented by others, it can be concluded that the three viral nucleic acids differ in that they contain different proportions of free and glucose-substituted hydroxymethylcytidylic acids.
AMPK and mTOR in Cellular Energy Homeostasis and Drug Targets
Authors: Ken Inoki, Joungmok Kim, Kun-Liang Guan
Journal: The Annual Review of Pharmacology and Toxicology (2011)

The mammalian target of rapamycin (mTOR) is a central controller of cell growth and proliferation. mTOR forms two distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC1 is regulated by multiple signals such as growth factors, amino acids, and cellular energy and regulates numerous essential cellular processes including translation, transcription, and autophagy. The AMP-activated protein kinase (AMPK) is a cellular energy sensor and signal transducer that is regulated by a wide array of metabolic stresses. These two pathways serve as a signaling nexus for regulating cellular metabolism, energy homeostasis, and cell growth, and dysregulation of each pathway may contribute to the development of metabolic disorders such as obesity, type 2 diabetes, and cancer. This review focuses on our current understanding of the relationship between AMPK and mTORC1 signaling and discusses their roles in cellular and organismal energy homeostasis.