tbuckley/cabot-search huggingface dataset:
Familial Mortality and Familial Incidence in Cancer
Authors: Kari Hemminki, Jan Sundquist, Andreas Brandt
Journal: Journal of Clinical Oncology (2011)

An overwhelming majority of data on familial risk in cancer is based on incident cancer, whereas familiality in cancer mortality is largely unknown. If fatal form of cancer was a highly familial subtype, then familial risk for mortality may exceed that of incidence, which would be particularly relevant for clinical decision making and counseling.The individuals in the nationwide Swedish Family-Cancer Database were classified according to family history of fatal and nonfatal cancer. Familial risks of incident and fatal concordant cancer were calculated for offspring based on their parental family history using a Cox model with hazard ratio (HR); offspring without family history were the reference.Most HRs for offspring incident cancers were somewhat higher for fatal compared with nonfatal parental family history. For breast (HR, 1.87 fatal v 1.66 nonfatal; P < .001) and prostate (HR, 2.30 fatal v 1.84 nonfatal; P < .001) cancers, 51.0% of patients with familial breast cancer and 56.6% of patients with prostate cancer had fatal family history. HRs for death in offspring according to a fatal compared with nonfatal family history were significantly increased for colorectal (HR, 1.76 v 1.47, respectively; P = .02), breast (HR, 1.97 v 1.51, respectively; P = .002), and prostate (HR, 2.03 v 1.59, respectively; P = .002) cancers. TNM classification did not seem to differ between the family histories. We showed also that an overwhelming proportion of offspring were diagnosed after the parental death.Familial breast, prostate, and colorectal cancers might have a yet unidentified genetic component associated with poorer survival. It may be useful to record survival data in family history records.
Prolyl hydroxylase 3 (PHD3) is essential for hypoxic regulation of neutrophilic inflammation in humans and mice
Authors: Sarah R. Walmsley, Edwin R. Chilvers, Alfred A. Thompson, Kathryn Vaughan, Helen M. Marriott, Lisa C. Parker, Gary Shaw, Selina Parmar, Martin Schneider, Ian Sabroe, David H. Dockrell, Marta Milo, Cormac T. Taylor, Randall S. Johnson, Christopher W. Pugh, Peter J. Ratcliffe, Patrick H. Maxwell, Peter Carmeliet, Moira K.B. Whyte
Journal: Journal of Clinical Investigation (2011)

The regulation of neutrophil lifespan by induction of apoptosis is critical for maintaining an effective host response and preventing excessive inflammation. The hypoxia-inducible factor (HIF) oxygen-sensing pathway has a major effect on the susceptibility of neutrophils to apoptosis, with a marked delay in cell death observed under hypoxic conditions. HIF expression and transcriptional activity are regulated by the oxygen-sensitive prolyl hydroxylases (PHD1–3), but the role of PHDs in neutrophil survival is unclear. We examined PHD expression in human neutrophils and found that PHD3 was strongly induced in response to hypoxia and inflammatory stimuli in vitro and in vivo. Using neutrophils from mice deficient in Phd3, we demonstrated a unique role for Phd3 in prolonging neutrophil survival during hypoxia, distinct from other hypoxia-associated changes in neutrophil function and metabolic activity. Moreover, this selective defect in neutrophil survival occurred in the presence of preserved HIF transcriptional activity but was associated with upregulation of the proapoptotic mediator Siva1 and loss of its binding target Bcl-xL. In vivo, using an acute lung injury model, we observed increased levels of neutrophil apoptosis and clearance in Phd3-deficient mice compared with WT controls. We also observed reduced neutrophilic inflammation in an acute mouse model of colitis. These data support what we believe to be a novel function for PHD3 in regulating neutrophil survival in hypoxia and may enable the development of new therapeutics for inflammatory disease.
Randomized Trial Comparing Iridium Implant Plus External-Beam Radiation Therapy With External-Beam Radiation Therapy Alone in Node-Negative Locally Advanced Cancer of the Prostate
Authors: Jinka R. Sathya, Ian R. Davis, Jim A. Julian, Qing Guo, Dean Daya, Ian S. Dayes, Himu R. Lukka, Mark Levine
Journal: Journal of Clinical Oncology (2005)

To determine if iridium implant (IM) and external-beam radiation therapy (EBRT) is better than standard EBRT in locally advanced prostate cancer.Patients with T2 and T3 prostate cancer with no evidence of metastatic disease were randomly assigned to EBRT of 66 Gy in 33 fractions during 6.5 weeks or to IM of 35 Gy delivered to the prostate during 48 hours plus EBRT of 40 Gy in 20 fractions during 4 weeks. The primary outcome consisted of biochemical or clinical failure (BCF). BCF was defined by biochemical failure, clinical failure, or death as a result of prostate cancer. Secondary outcomes included 2-year postradiation biopsy positivity, toxicity, and survival.Between 1992 and 1997, 51 patients were randomly assigned to receive IM plus EBRT, and 53 patients were randomly assigned to receive EBRT alone. The median follow-up was 8.2 years. In the IM plus EBRT arm, 17 patients (29%) experienced BCF compared with 33 patients (61%) in the EBRT arm (hazard ratio, 0.42; P = .0024). Eighty-seven patients (84%) had a postradiation biopsy; 10 (24%) of 42 in the IM plus EBRT arm had biopsy positivity compared with 23 (51%) of 45 in the EBRT arm (odds ratio, 0.30; P = .015). Overall survival was 94% in the IM plus EBRT arm versus 92% in the EBRT arm.The combination of IM plus EBRT was superior to EBRT alone for BCF and postradiation biopsy. This trial provides evidence that higher doses of radiation delivered in a shorter duration result in better local as well as biochemical control in locally advanced prostrate cancer.
Subclinical activation of coagulation and fibrinolysis in laparoscopic cholecystectomy: Do risk factors exist?
Authors: Dimitris Ntourakis, Thodoris N. Sergentanis, Ioannis Georgiopoulos, Eleni Papadopoulou, Lambros Liasis, Emmanuel Kritikos, Periklis Tzardis, Vasilios Laopodis
Journal: International Journal of Surgery (2011)
Mitochondrial proteome remodelling in pressure overload-induced heart failure: the role of mitochondrial oxidative stress
Authors: Dao-Fu Dai, Edward J. Hsieh, Yonggang Liu, Tony Chen, Richard P. Beyer, Michael T. Chin, Michael J. MacCoss, Peter S. Rabinovitch
Journal: Cardiovascular Research (2011)

We investigate the role of mitochondrial oxidative stress in mitochondrial proteome remodelling using mouse models of heart failure induced by pressure overload. We demonstrate that mice overexpressing catalase targeted to mitochondria (mCAT) attenuate pressure overload-induced heart failure. An improved method of label-free unbiased analysis of the mitochondrial proteome was applied to the mouse model of heart failure induced by transverse aortic constriction (TAC). A total of 425 mitochondrial proteins were compared between wild-type and mCAT mice receiving TAC or sham surgery. The changes in the mitochondrial proteome in heart failure included decreased abundance of proteins involved in fatty acid metabolism, an increased abundance of proteins in glycolysis, apoptosis, mitochondrial unfolded protein response and proteolysis, transcription and translational control, and developmental processes as well as responses to stimuli. Overexpression of mCAT better preserved proteins involved in fatty acid metabolism and attenuated the increases in apoptotic and proteolytic enzymes. Interestingly, gene ontology analysis also showed that monosaccharide metabolic processes and protein folding/proteolysis were only overrepresented in mCAT but not in wild-type mice in response to TAC. This is the first study to demonstrate that scavenging mitochondrial reactive oxygen species (ROS) by mCAT not only attenuates most of the mitochondrial proteome changes in heart failure, but also induces a subset of unique alterations. These changes represent processes that are adaptive to the increased work and metabolic requirements of pressure overload, but which are normally inhibited by overproduction of mitochondrial ROS.
Differential effects of transforming growth factor-beta 1 and phorbol myristate acetate on cardiac fibroblasts. Regulation of fibrillar collagen mRNAs and expression of early transcription factors.
Authors: M Eghbali, R Tomek, V P Sukhatme, C Woods, B Bhambi
Journal: Circulation Research (1991)

Cardiac fibroblasts are responsible for synthesis and deposition of fibrillar collagen types I and III. Transforming growth factor-beta 1 (TGF-beta 1) has been proved to increase collagen biosynthesis in various systems, both in vivo and in vitro. We have investigated the effect of TGF-beta 1 on collagen gene expression in cultured cardiac fibroblasts and have compared this effect with that of a mitogenic agent, phorbol myristate acetate (PMA). The regulation of collagen types I and III gene expression was examined by using cDNA probes to rat alpha 2 (I) and mouse alpha 1 (III) procollagens. Quiescent cultured cardiac fibroblasts from rabbit heart were treated with TGF-beta 1 (10-15 ng/ml) and PMA (200 ng/ml). After 24 hours of treatment with TGF-beta 1, the abundance of mRNA for pro-alpha 2 (I) and pro-alpha 1 (III) collagens was increased by 112% (p less than 0.001) and 97% (p = 0.05), respectively, in treated fibroblasts compared with untreated cells. However, PMA-treated cells showed an opposite response: a 42% (p = 0.01) decrease in mRNA levels for pro-alpha 2 (I) collagen was observed. Immunofluorescent staining of cardiac fibroblasts in culture with anti-type I collagen antibody showed that alterations in mRNA levels led to altered collagen synthesis: cellular collagen was relatively increased in TGF-beta 1-treated cells and significantly diminished in PMA-treated cells. The abundance of mRNA for pro-alpha 1 (III) collagen was not affected by PMA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Separation of the gut hormone endocrine-cell storage granules of human jejunum using analytical subcellular fractionation.
Authors: M G Bryant, J Dawson, S R Bloom, T J Peters
Journal: Gut (1980)

Analytical subcellular fractionation techniques in combination with specific radioimmunoassays have been used to investigate the properties of the hormone-containing granules in human jejunal biopsy specimens. After gentle homogenisation, for all hormones except VIP, over 90% of the immunoreactivity was released in intact granules into the post-nuclear supernatant. Approximately 50% of the VIP immunoreactivity sedimented with the low speed pellet, probably reflecting the presence of this peptide in nerve fibres. The following hormone granules (equilibrium densities between parentheses) were separated by isopycnic centrifugation on the sucrose density gradients: VIP (1 x 17), motilin (1 x 20), and secretin (1 x 24). Gastrin and GIP granules were not resolved, both having the same modal density of 1 x 22 g/cm3. This combination of procedures thus provides a new quantitative technique for studying the properties of the gastrointestinal hormone-containing granules, and should therefore be of value in investigating pathophysiological problems in a variety of gastrointestinal diseases.
Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel with planned crossover to the alternate single agent in metastatic breast cancer
Authors: A.D. Seidman, A. Brufsky, R.H. Ansari, L.L. Hart, R.S. Stein, L.S. Schwartzberg, J.F. Stewart, C.A. Russell, S.-C. Chen, L.E. Fein, J.A. De La Cruz Vargas, S.-B. Kim, J. Cavalheiro, L. Zhao, J.F. Gill, C.K. Obasaju, M. Orlando, D.F. Tai
Journal: Annals of Oncology (2010)
Phosphorylated Peptides Are Naturally Processed and Presented by Major Histocompatibility Complex Class I Molecules in Vivo
Authors: Angela L. Zarling, Scott B. Ficarro, Forest M. White, Jeffrey Shabanowitz, Donald F. Hunt, Victor H. Engelhard
Journal: The Journal of Experimental Medicine (2000)

Posttranslational modification of peptide antigens has been shown to alter the ability of T cells to recognize major histocompatibility complex (MHC) class I–restricted peptides. However, the existence and origin of naturally processed phosphorylated peptides presented by MHC class I molecules have not been explored. By using mass spectrometry, significant numbers of naturally processed phosphorylated peptides were detected in association with several human MHC class I molecules. In addition, CD8+ T cells could be generated that specifically recognized a phosphorylated epitope. Thus, phosphorylated peptides are part of the repertoire of antigens available for recognition by T cells in vivo.
Population Biology of Lymphocytes: The Flight for Survival
Authors: Antonio A. Freitas, Benedita Rocha
Journal: Annual Review of Immunology (2000)

In this essay we suggest that the primary goal of the cells of the immune system is to ensure their own growth and survival. In adults, in steady-state conditions, the number and distribution of lymphocyte populations is under homeostatic control. New lymphocytes that are continuously produced in primary and secondary lymphoid organs must compete with resident cells for survival. We discuss recent findings supporting lymphocyte survival as a continuous active process and implicating cognate receptor engagement as fundamental survival signals for both T and B lymphocytes. The conflict of survival interests between different cell types gives rise to a pattern of interactions that mimics the behavior of complex ecological systems. In their flight for survival and in response to competition, lymphocytes use different survival signals within different ecological niches during cell differentiation. This is the case for T and B lymphocytes and also for naive and memory/activated T and B cells. We discuss how niche differentiation allows the co-existence of different cell types and guarantees both repertoire diversity and efficient immune responses.
Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
Authors: Vivianna M Van Deerlin, Patrick M A Sleiman, Maria Martinez-Lage, Alice Chen-Plotkin, Li-San Wang, Neill R Graff-Radford, Dennis W Dickson, Rosa Rademakers, Bradley F Boeve, Murray Grossman, Steven E Arnold, David M A Mann, Stuart M Pickering-Brown, Harro Seelaar, Peter Heutink, John C van Swieten, Jill R Murrell, Bernardino Ghetti, Salvatore Spina, Jordan Grafman, John Hodges, Maria Grazia Spillantini, Sid Gilman, Andrew P Lieberman, Jeffrey A Kaye, Randall L Woltjer, Eileen H Bigio, Marsel Mesulam, Safa al-Sarraj, Claire Troakes, Roger N Rosenberg, Charles L White, Isidro Ferrer, Albert Lladó, Manuela Neumann, Hans A Kretzschmar, Christine Marie Hulette, Kathleen A Welsh-Bohmer, Bruce L Miller, Ainhoa Alzualde, Adolfo Lopez de Munain, Ann C McKee, Marla Gearing, Allan I Levey, James J Lah, John Hardy, Jonathan D Rohrer, Tammaryn Lashley, Ian R A Mackenzie, Howard H Feldman, Ronald L Hamilton, Steven T Dekosky, Julie van der Zee, Samir Kumar-Singh, Christine Van Broeckhoven, Richard Mayeux, Jean Paul G Vonsattel, Juan C Troncoso, Jillian J Kril, John B J Kwok, Glenda M Halliday, Thomas D Bird, Paul G Ince, Pamela J Shaw, Nigel J Cairns, John C Morris, Catriona Ann McLean, Charles DeCarli, William G Ellis, Stefanie H Freeman, Matthew P Frosch, John H Growdon, Daniel P Perl, Mary Sano, David A Bennett, Julie A Schneider, Thomas G Beach, Eric M Reiman, Bryan K Woodruff, Jeffrey Cummings, Harry V Vinters, Carol A Miller, Helena C Chui, Irina Alafuzoff, Päivi Hartikainen, Danielle Seilhean, Douglas Galasko, Eliezer Masliah, Carl W Cotman, M Teresa Tuñón, M Cristina Caballero Martínez, David G Munoz, Steven L Carroll, Daniel Marson, Peter F Riederer, Nenad Bogdanovic, Gerard D Schellenberg, Hakon Hakonarson, John Q Trojanowski, Virginia M-Y Lee
Journal: Nature Genetics (2010)
Pathways of Self-Reported Problem Behaviors From Adolescence Into Adulthood
Authors: Marijke B. Hofstra, Jan Van der Ende, Frank C. Verhulst
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The authors determined the impact of different pathways of psychopathological development on adult outcome in subjects followed from ages 11–18 to ages 21–28. METHOD: Problem behaviors of subjects from a general population sample were assessed through the Youth Self-Report and the Young Adult Self-Report given at four time points (1987, 1989, 1991, and 1997). In addition, DSM-IV diagnoses, information pertaining to signs of maladjustment, and measures of social functioning were obtained at the last assessment. On the basis of the self-report ratings, four contrasting developmental pathways of psychopathology were determined: persistent, decreasing, increasing, and consistently normal. RESULTS: Subjects whose overall level of psychopathology was persistent over time had a higher lifetime prevalence of DSM-IV diagnoses and a poorer general outcome in adulthood than did subjects whose level of psychopathology increased. Subjects whose level of psychopathology returned to normal after high levels of problems in adolescence were only slightly different in terms of outcome from subjects with consistently normal ratings. CONCLUSIONS: 1) People who showed high levels of problems in early adolescence but whose level of psychopathology diminished by adulthood seemed to be as healthy as people who never attained a serious level of psychopathology. 2) An ongoing devious pathway into adulthood had negative effects on many domains of functioning. These two findings are both powerful arguments for early intervention in adolescence.
<sup>23</sup> Na and <sup>31</sup> P Nuclear Magnetic Resonance Studies of Ischemia-Induced Ventricular Fibrillation
Authors: M. M. Pike, C. S. Luo, S. Yanagida, G. R. Hageman, P. G. Anderson
Journal: Circulation Research (1995)

Abstract To clarify the role of Na + i , pH i , and high-energy phosphate (HEP) levels in the initiation and maintenance of ischemia-induced ventricular fibrillation (VF), interleaved 23 Na and 31 P nuclear magnetic resonance spectra were collected on perfused rat hearts during low-flow ischemia (51 minutes, 1.2 mL/g wet wt). When untreated, 50% of the hearts from normal (sham) rats and 89% of the hypertrophied hearts from aortic-banded (band) rats ( P &lt;.01 versus sham) exhibited VF. Phosphocreatine content was significantly higher in sham than band hearts during control perfusion (53.3±1.6 versus 39.8±2.0 μmol/g dry wt). Before VF at 20 minutes of ischemia, Na + i accumulation was greater in hearts that eventually developed VF than in hearts that did not develop VF for both band and sham groups (144% versus 128% of control in sham; P &lt;.005) and was the strongest metabolic predictor of VF; ATP depletion was also greater for VF hearts in the sham group. Infusion of the Na + -H + exchange inhibitor 5-( N , N -hexamethylene)-amiloride prevented VF in sham and band hearts; reduced Na + i accumulation but similar HEP depletion were observed compared with VF hearts before the onset of VF. Rapid changes in Na + i , pH i , and HEP began with VF, resulting in intracellular Na + i overload (≈300% of control) and increased HEP depletion. A delayed postischemic functional recovery occurred in VF hearts, which correlated temporally with the recovery of Na + i . In conclusion, alterations in Na + i were associated with spontaneous VF transitions, consistent with involvement of excess Na + i accumulation in VF initiation and maintenance and with previously reported alterations in Ca 2+ i with VF. Hypertrophied band hearts exhibited enhanced susceptibility to ischemia-induced VF, possibly linked to a lower HEP reserve.
A CD4/Foxp3/OX40 triple immunofluorescence assay determines association between T cell immune subsets and outcome in colorectal cancer
Authors: James Ziai, Mahrukh Huseni, Oded Foreman, Jeffrey Eastham-Anderson, Yuanyuan Xiao, Felix Chu, Marcin Kowanetz, Priti S Hegde, Jeong Kim
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Increased numbers of OX40+ T cells in the tumor microenvironment of colorectal cancer (CRC) patients have been associated with improved outcome. However, the OX40+ T cell population is heterogeneous and includes, among others, CD4+Foxp3+ regulatory T cells (Treg) as well as CD4+
RXRα overexpression in cardiomyocytes causes dilated cardiomyopathy but fails to rescue myocardial hypoplasia in RXRα-null fetuses
Authors: Vemparala Subbarayan, Manuel Mark, Nadia Messadeq, Pierre Rustin, Pierre Chambon, Philippe Kastner
Journal: Journal of Clinical Investigation (2000)

Retinoid X receptor α–null (RXRα-null) mutants exhibit hypoplasia of their ventricular myocardium and die at the fetal stage. In the present study, we wished to determine whether transgenic re-expression of RXRα in mutant cardiac myocytes could rescue these defects. Two transgenic mouse lines specifically overexpressing an RXRα protein in cardiomyocytes were generated, using the cardiac α-myosin heavy chain (α-MHC) promoter. Breeding the high copy number transgenic line onto an RXRα-null genetic background did not prevent the myocardial hypoplasia and fetal lethality associated with the RXRα–/– genotype, even though the transgene was expressed in the ventricles as early as 10.5 days post-coitum. These data suggest that the RXRα function involved in myocardial growth may correspond to a non–cell-autonomous requirement forsignal orchestrating the growth and differentiation of myocytes. Interestingly, the adult transgenic mice developed a dilated cardiomyopathy, associated with myofibrillar abnormalities and specific deficiencies in respiratory chain complexes I and II, thus providing an additional model for this genetically complex disease.
Use of No-Suicide Contracts by Psychiatrists in Minnesota
Authors: J Kroll
Journal: American Journal of Psychiatry (2000)

The no-suicide contract is widely recommended as an important intervention in the care of suicidal patients; however, there are no data demonstrating its effectiveness or its acceptance in the professional community. This study examines the use of no-suicide contracts by psychiatrists in Minnesota.A postcard questionnaire was mailed to 514 psychiatrists in Minnesota inquiring about their practices and experiences with no-suicide contracts.There were 267 responses, yielding a response rate of 52%. No-suicide contracts were used by 152 (57%) of the respondents. Within this group, 62 (41%) of the psychiatrists had patients who committed suicide or made serious attempts after entering into a no-suicide contract.Among the respondents to the questionnaire, slightly more than half used no-suicide contracts, indicating that such contracts are not universally accepted as standard practice among these psychiatrists. More data are needed to determine the effectiveness of no-suicide contracts in preventing suicide.