tbuckley/cabot-search huggingface dataset:
Abstract 1985: ZNF783, a novel zinc finger protein has tumor suppressor function in prostate cancer.
Authors: Rana Tbaishat, Songping Wang, Bernard Kwabi-Addo
Journal: Cancer Research (2013)

Abstract In the last decade hypermethylation of promoter regions has been accepted to be a prominent feature of human tumorigenesis by silencing tumor suppressor genes and other genes involved in cellular pathways. To study more in depth the involvement of aberrant methylation in prostate cancer tumorigenesis, we used a genome wide methylation array from Illumina (Infunium) to identify novel hypermethylated genes that might contribute to prostate cancer progression. ZNF783 is one such candidate gene. ZNF783 is Zinc-finger transcription factor that maps to human chromosome 7q33, a region implicated in prostate cancer tumorigenesis. We have observed significant hypermethylation of ZNF783 promoter CpG island in prostate cancer cell lines and prostate tumors when compared to match normal prostate tissue samples from radical prostatectomy patients. The treatment of prostate cancer cell lines with pharmacological demethylating agents restored ZNF783 gene expression indicating a role for epigenetic DNA methylation in regulating ZNF783 expression in prostate cancer. The ZNF family of proteins has been identified to play essential roles in gene expression/regulation including inhibition of cell cycle proliferation, differentiation and apoptosis. The current study demonstrates a potential tumor suppressor role for ZNF783 in prostate cancer cells. Citation Format: Rana Tbaishat, Songping Wang, Bernard Kwabi-Addo. ZNF783, a novel zinc finger protein has tumor suppressor function in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1985. doi:10.1158/1538-7445.AM2013-1985
Stimulation of Proximal Tubular Cell Apoptosis by Albumin-Bound Fatty Acids Mediated by Peroxisome Proliferator Activated Receptor-γ
Authors: Mustafa Arici, Ravinder Chana, Andrew Lewington, Jez Brown, Nigel John Brunskill
Journal: Journal of the American Society of Nephrology (2003)

In nephrotic syndrome, large quantities of albumin enter the kidney tubule. This albumin carries with it a heavy load of fatty acids to which the proximal tubule cells are exposed at high concentration. It is postulated that exposure to fatty acids in this way is injurious to proximal tubule cells. This study has examined the ability of fatty acids to interact with peroxisome proliferator-activated receptors (PPAR) in primary cultures of human proximal tubule cells. Luciferase reporter assays in transiently transfected human proximal tubule cells were used to show that albumin bound fatty acids and other agonists activate PPARgamma in a dose-dependent manner. One of the consequences of this activation is apoptosis of the cells as determined by changes in cell morphology, evidence of PARP cleavage, and appearance of DNA laddering. Overexpression of PPARgamma in these cells also results in enhanced apoptosis. Both fatty acid-induced PPAR activation and apoptosis in these cells can be blocked by PPAR response element decoy oligonucleotides. Activation of PPARgamma by the specific agonist PGJ(2) is associated with inhibition of cell proliferation, whereas activation by albumin bound fatty acids is accompanied by increased proliferation. However, the net balance of apoptosis/proliferation favors deletion of cells. These results implicate albumin-bound fatty acids as important mediators of tubular injury in nephrosis and provide fresh impetus for pursuit of lipid-lowering strategies in proteinuric renal disease.
Genetic analysis of the human infective trypanosome Trypanosoma brucei gambiense: chromosomal segregation, crossing over, and the construction of a genetic map
Authors: Anneli Cooper, Andy Tait, Lindsay Sweeney, Alison Tweedie, Liam Morrison, C Michael R Turner, Annette MacLeod
Journal: Genome biology (2008)

Trypanosoma brucei is the causative agent of human sleeping sickness and animal trypanosomiasis in sub-Saharan Africa, and it has been subdivided into three subspecies: Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, which cause sleeping sickness in humans, and the nonhuman infective Trypanosoma brucei brucei. T. b. gambiense is the most clinically relevant subspecies, being responsible for more than 90% of all trypanosomal disease in humans. The genome sequence is now available, and a Mendelian genetic system has been demonstrated in T. brucei, facilitating genetic analysis in this diploid protozoan parasite. As an essential step toward identifying loci that determine important traits in the human-infective subspecies, we report the construction of a high-resolution genetic map of the STIB 386 strain of T. b. gambiense. The genetic map was determined using 119 microsatellite markers assigned to the 11 megabase chromosomes. The total genetic map length of the linkage groups was 733.1 cM, covering a physical distance of 17.9 megabases with an average map unit size of 24 kilobases/cM. Forty-seven markers in this map were also used in a genetic map of the nonhuman infective T. b. brucei subspecies, permitting comparison of the two maps and showing that synteny is conserved between the two subspecies. The genetic linkage map presented here is the first available for the human-infective trypanosome T. b. gambiense. In combination with the genome sequence, this opens up the possibility of using genetic analysis to identify the loci responsible for T. b. gambiense specific traits such as human infectivity as well as comparative studies of parasite field populations.
Role of T- and B-lymphocytes in pulmonary host defences
Authors: B.B. Moore, T.A. Moore, G.B. Toews
Journal: European Respiratory Journal (2001)

Pulmonary infectious diseases cause significant morbidity and mortality in both industrialized and developing countries. Adaptive immune responses are required to defend the lung against pathogens that survive in normal macrophages and extracellular organisms that evade phagocytosis. Microbes initiate both innate immune responses and specific adaptive immune responses. Innate immune response molecules regulate T-;lymphocyte differentiation. Activated T-;lymphocytes provide cytokines, which activate macrophages and lytic signals that lyse infected antigen-presenting cells. Antibodies produced by plasma cells facilitate microbial clearance through diverse effector mechanisms including opsonization, complement fixation and antibody-dependent cytotoxicity. Lymphocytes determine the specificity of the immune response and orchestrate effector limbs of the immune response.
Peptide Antibiotics and Their Role in Innate Immunity
Authors: Hans G. Boman
Journal: Annual Review of Immunology (1995)

CONTENTS INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 FIVE CHEMICALLY DIFFERENT GROUPS OF PEPTIDE ANTIBIOTICS . . . . . . . . . . .. 63 Linear, Mostly Helical, Peptides Without Cys, With or Without a Hinge . . . . . . . . . . . . . . . 63 Linear Pep tides Without Cys and with a High Proportion of Certain Residues . . . . . . . . . 67 Antibacterial Peptides with One Disulfide Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 Peptides with Two or More S-S Bonds Giving Mainly or Only fJ-Sheet Structures. . . . . . . 69 Antibacterial Peptides Derivedfrom Larger Polypeptides with Other Known Functions . . 72 ANTIBACTERIAL PROTEINS AND ACTIVE FRAGMENTS OF SUCH PROTEINS . . . . 73
The patients' perspective on fertility care: a systematic review
Authors: E. A. F. Dancet, W. L. D. M. Nelen, W. Sermeus, L. De Leeuw, J. A. M. Kremer, T. M. D'Hooghe
Journal: Human Reproduction Update (2010)

Patient-centered reproductive medicine (PCRM) is important for quality of care, and this is increasingly being recognized. However, its scientific basis is unclear. The main research questions addressed in this review are: 'How has the patients' perspective on fertility care been examined (method and quality)?' and 'What is the perspective of patients in developed countries on fertility care?'.A systematic search of electronic databases was conducted and inclusion criteria with respect to eligibility and quality were applied. The methodology of the studies was critically appraised; the findings of the studies were synthesized and organized according to: patients' value clarification and assessment of service quality and dimensions of patient-centeredness. Additionally data on patient preferences and determinants of patients' perspective on care were collected.In 51 selected studies, patients' perspective on fertility care was examined with (few or many item) questionnaires and/or qualitative interviews. Significant methodological problems were observed. Fertility patients attached importance to seven out of eight dimensions of patient-centeredness (Picker institute) and two new dimensions 'fertility clinic staff' and 'skills' were developed. Overall, fertility patients want to be treated like human beings with a need for: medical skills, respect, coordination, accessibility, information, comfort, support, partner involvement and a good attitude of and relationship with fertility clinic staff. Patients' preferences between procedures and demographic, medical and psychological determinants of their perspective were defined.Fertility patients have 'human needs' besides their need for medical care. Evidence on PCRM is available but significant methodological limitations call for the development and validation of a European questionnaire.
Assessing patients' preferences for characteristics associated with homeopathic and conventional treatment of asthma: a conjoint analysis study
Authors: J Ratcliffe
Journal: Thorax (2002)

<b>Background:</b> A study was undertaken to investigate the preferences of patients with asthma for attributes or characteristics associated with treatment for their asthma and to investigate the extent to which such preferences may differ between patient subgroups. <b>Methods:</b> The economic technique of conjoint analysis (CA) was used to investigate patients9 strength of preference for several key attributes associated with services for the treatment of asthma. A CA questionnaire was administered to two groups of asthma outpatients aged 18 years or older, 150 receiving conventional treatment at Whipps Cross Hospital (WC) and 150 receiving homeopathic treatment at the Royal London Homoeopathic Hospital (RL). <b>Results:</b> An overall response rate of 47% (n=142) was achieved. Statistically significant attributes in influencing preferences for both the WC and RL respondents were (1) the extent to which the doctor gave sufficient time to listen to what the patient has to say, (2) the extent to which the treatment seemed to relieve symptoms, and (3) the travel costs of attending for an asthma consultation. The extent to which the doctor treated the patient as a whole person was also a statistically significant attribute for the RL respondents. <b>Conclusions:</b> This study has shown that aspects associated with the process of delivery of asthma services are important to patients in addition to treatment outcomes. The homeopathic respondents expressed stronger preferences for the doctor to treat them as a whole person than the patients receiving conventional treatment. Overall, the preferences for the attributes included in the study were similar for both groups.
Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties
Authors: Tetsuhiro Chiba, Kaoru Kita, Yun-Wen Zheng, Osamu Yokosuka, Hiromitsu Saisho, Atsushi Iwama, Hiromitsu Nakauchi, Hideki Taniguchi
Journal: Hepatology (2006)

Recent advances in stem cell biology enable us to identify cancer stem cells in solid tumors as well as putative stem cells in normal solid organs. In this study, we applied side population (SP) cell analysis and sorting to established hepatocellular carcinoma (HCC) cell lines to detect subpopulations that function as cancer stem cells and to elucidate their roles in tumorigenesis. Among four cell lines analyzed, SP cells were detected in Huh7 (0.25%) and PLC/PRF/5 cells (0.80%), but not in HepG2 and Huh6 cells. SP cells demonstrated high proliferative potential and anti-apoptotic properties compared with those of non-SP cells. Immunocytochemistry examination showed that SP fractions contain a large number of cells presenting characteristics of both hepatocyte and cholangiocyte lineages. Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) xenograft transplant experiments showed that only 1 x 10(3) SP cells were sufficient for tumor formation, whereas an injection of 1 x 10(6) non-SP cells did not initiate tumors. Re-analysis of SP cell-derived tumors showed that SP cells generated both SP and non-SP cells and tumor-initiating potential was maintained only in SP cells in serial transplantation. Microarray analysis discriminated a differential gene expression profile between SP and non-SP cells, and several so-called "stemness genes" were upregulated in SP cells in HCC cells. In conclusion, we propose that a minority population, detected as SP cells in HCC cells, possess extreme tumorigenic potential and provide heterogeneity to the cancer stem cell system characterized by distinct hierarchy.
Stigma as Related to Mental Disorders
Authors: Stephen P. Hinshaw, Andrea Stier
Journal: Annual Review of Clinical Psychology (2008)

Individuals with mental illness receive harsh stigmatization, resulting in decreased life opportunities and a loss of independent functioning over and above the impairments related to mental disorders themselves. We begin our review with a multidisciplinary discussion of mechanisms underlying the strong propensity to devalue individuals displaying both deviant behavior and the label of mental illness. Featured is the high potential for internalization of negative perceptions on the part of those with mental disorders-i.e., self-stigmatization. We next focus on several issues of conceptual and practical relevance: (a) stigma against less severe forms of mental disorder; (b) the role of perceptions of dangerousness related to mental illness; (c) reconciliation of behavioral research with investigations of explicit and implicit attitudes; (d) evolutionary models and their testability; (e) attributional accounts of the causes of mental illness, especially to personal control versus biogenetic factors; and (f) developmental trends regarding stigma processes. We conclude with a brief review of multilevel efforts to overcome mental illness stigma, spanning policy and legislation, alterations in media depictions, changed attitudes and practices among mental health professionals, contact and empathy enhancement, and family and individual treatment.
Association of years of occupational quartz exposure with spirometric airflow limitation in Norwegian men aged 30-46 years
Authors: S. Humerfelt, G. E Eide, A. Gulsvik
Journal: Thorax (1998)

The association between occupational quartz exposure and ventilatory function was investigated in men in a general population after adjusting for other potential determinants of outcome.All eligible men aged 30-46 years living in western Norway (n = 45,380) were invited to a cross sectional community survey. This included a self administered questionnaire (with respiratory symptoms, smoking habits and occupational exposures), spirometric recordings (using dry wedge below spirometers), and a chest radiograph (65% attendance). Measurements of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were obtained in 91% (n = 26,803) of those who participated, 26,106 of whom performed successful spirometric tests and had normal chest radiographs and remained for further analysis. Age, body mass index, and technician standardised residuals ((observed minus predicted value)/residual standard error) of maximum FEV1/height2 and FVC/height2 were used as outcome variables for adjusted lung function levels, respectively.Occupational quartz exposure was reported by 13% (n = 3445) of those who participated in the survey, with a mean duration of seven years. Among those exposed to quartz, significant inverse linear relationships were observed between years of exposure and FEV1 level and the ratio of FEV1/FVC, independent of host characteristics. Multiple linear regression analyses showed that the difference in FEV1 associated with each year of quartz exposure was -4.3 ml (95% CI -1.1 to -7.5 ml; p = 0.01) compared with -6.9 ml (95% CI -4.7 to -9.1 ml; p < 0.01) from smoking 20 cigarettes/day for one year after adjusting for age, atopy, asthma, wheezing, marital status, and other occupational exposures.In men aged 30-46 years with occupational quartz exposure and normal chest radiographs the duration of occupational quartz exposure was an independent predictor for spirometric airflow limitation.
A randomized phase III study comparing pegylated liposomal doxorubicin with capecitabine as first-line chemotherapy in elderly patients with metastatic breast cancer: results of the OMEGA study of the Dutch Breast Cancer Research Group BOOG
Authors: C.H. Smorenburg, S.M. de Groot, A.E. van Leeuwen-Stok, M.E. Hamaker, A.N. Wymenga, H. de Graaf, F.E. de Jongh, J.J. Braun, M. Los, E. Maartense, H. van Tinteren, J.W.R. Nortier, C. Seynaeve
Journal: Annals of Oncology (2014)
Drug Combinations
Authors: F. Gilbert McMahon
Journal: JAMA (1971)

The<i>Federal Register</i>of Feb 18, 1971, contained the new Food and Drug Administration (FDA) policy statement on fixed drug combinations. Physicians were solicited for comments within 30 days. The principal effect of the proposed new regulations is to threaten removal from the market of hundreds of prescription drug combinations and most of the socalled over-the-counter (OTC) drugs, ie, nonprescription drugs. Unless each active ingredient can be shown to<i>enhance drug efficacy</i>or<i>diminish side effects</i>, the combination will be removed. Whether one agrees with the proposed regulations or not, the removal of these drugs will have a profound effect on American medicine as now practiced. There are some obviously irrational combination drugs still on the market, such as Ritonic (containing androgen, estrogen, vitamins, minerals, and methylphenidate hydrochloride), which simply represent bad medicine. The avaricious marketing of such nostrums in the 1960's has helped create the present problem for the
Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial
Authors: Hoosen M Coovadia, Elizabeth R Brown, Mary Glenn Fowler, Tsungai Chipato, Dhayendre Moodley, Karim Manji, Philippa Musoke, Lynda Stranix-Chibanda, Vani Chetty, Wafaie Fawzi, Clemensia Nakabiito, Lindiwe Msweli, Roderick Kisenge, Laura Guay, Anthony Mwatha, Diana J Lynn, Susan H Eshleman, Paul Richardson, Kathleen George, Philip Andrew, Lynne M Mofenson, Sheryl Zwerski, Yvonne Maldonado
Journal: The Lancet (2011)
Too Blunt a Tool: A Case for Subsuming Analyses of Exploitation in Transnational Gestational Surrogacy Under a Justice or Human Rights Framework
Authors: G. K. D. Crozier
Journal: The American Journal of Bioethics (2014)

Jeffrey Kirby's article “Transnational Gestational Surrogacy: Does It Have to Be Exploitative?” (2014) is representative of a trend in the bioethics literature whereby transnational gestational sur...
Tauroursodeoxycholic acid protects hepatocytes from ethanol-fed rats against tumor necrosis factor-induced cell death by replenishing mitochondrial glutathione
Authors: Anna Colell, Olga Coll, Carmen García-Ruiz, Raquel París, Claudio Tiribelli, Neil Kaplowitz, José C. Fernández-Checa
Journal: Hepatology (2001)

Mitochondrial glutathione (GSH) plays a key role against tumor necrosis factor α (TNF)-induced apoptosis because its depletion is known to sensitize hepatocytes to TNF. The present study examined the role of tauroursodeoxycholic acid (TUDCA) administration to chronic ethanol-fed rats on mitochondrial GSH levels and kinetics, mitochondrial membrane physical properties, TNF-induced peroxide formation, and subsequent hepatocyte survival. TUDCA selectively increased the levels of GSH in mitochondria without an effect on cytosolic GSH. This outcome was accompanied by improved initial rate of GSH transport examined at low (1 mmol/L) and high (10 mmol/L) GSH concentrations both in intact mitochondria and mitoplasts prepared from ethanol-fed livers. Assessment of membrane fluidity revealed an increased order parameter in mitochondria and mitoplasts from ethanol-fed rats compared with pair-fed controls, which was prevented by TUDCA administration. Compared with hepatocytes from pair-fed rats, TNF stimulated peroxide generation in hepatocytes from ethanol-fed rats, preceding TNF-induced cell death. Administration of TUDCA to ethanol-fed rats prevented TNF-induced peroxide formation and cell death, an effect that was reversed on depletion of the recovered mitochondrial GSH levels by (R,S)-3-hydroxy-4-pentenoate before TNF treatment. The protective effect of TUDCA against TNF was not because of activation of phosphatidylinositol 3-kinase, discarding a role for a survival-dependent pathway. Thus, these findings reveal a novel role of TUDCA in protecting hepatocytes in long-term ethanol-fed rats through modulation of mitochondrial membrane fluidity and subsequent normalization of mitochondrial GSH levels.
Doctors accused of keeping their heads down at Mid Staffs trust
Authors: A. O'Dowd
Journal: BMJ (2013)

Too many doctors kept their heads down when things went wrong at Mid Staffordshire NHS Foundation Trust, according to the prime minister, who has promised action to prevent the “horrific abuse” that took place there from happening again.

David Cameron made a statement in the House of Commons on 6 February, shortly after the Francis report was published, and expressed his anger at what transpired at the trust between 2005 and 2009.

He announced that he had asked the NHS’s main regulator, the Care Quality Commission, to create a new post of chief inspector of hospitals by the autumn.

The prime minister apologised to the families of patients who suffered “horrific …
<i>LIN28B</i> Promotes Colon Cancer Progression and Metastasis
Authors: Catrina E. King, Miriam Cuatrecasas, Antoni Castells, Antonia R. Sepulveda, Ju-Seog Lee, Anil K. Rustgi
Journal: Cancer Research (2011)

LIN28B is a homologue of LIN28 that induces pluripotency when expressed in conjunction with OCT4, SOX2, and KLF4 in somatic fibroblasts. LIN28B represses biogenesis of let-7 microRNAs and is implicated in both development and tumorigenesis. Recently, we have determined that LIN28B overexpression occurs in colon tumors. We conducted a comprehensive analysis of LIN28B protein expression in human colon adenocarcinomas. We found that LIN28B overexpression correlates with reduced patient survival and increased probability of tumor recurrence. To elucidate tumorigenic functions of LIN28B, we constitutively expressed LIN28B in colon cancer cells and evaluated tumor formation in vivo. Tumors with constitutive LIN28B expression exhibit increased expression of colonic stem cell markers LGR5 and PROM1, mucinous differentiation, and metastasis. Together, our findings point to a function for LIN28B in promoting colon tumor pathogenesis, especially metastasis.