tbuckley/cabot-search huggingface dataset:
Endothelin-1 receptor antagonists prevent the development of pulmonary emphysema in rats
Authors: Y. Chen, M. Hanaoka, Y. Droma, P. Chen, N. F. Voelkel, K. Kubo
Journal: European Respiratory Journal (2009)

We hypothesised that endothelin (ET)-1 plays an important role in the pathogenesis of emphysema. We attempted to apply ET-1 receptor antagonists to demonstrate and further elucidate the molecular pathogenesis pathways through which ET-1 may cause emphysematous changes. Sprague-Dawley rats were divided into four groups: control, cigarette smoke extract (CSE), CSE+BQ-123 (a selective endothelin receptor type A (ET A ) antagonist) and CSE+bosentan (a mixed ET A /ET B receptor antagonist). The CSE was injected intraperitoneally once a week for 3 weeks, and BQ-123 or bosentan was administered daily for the same duration. The expression of ET A receptor, apoptosis index, caspase-3 activity, matrix metalloproteinase (MMP)-2 and MMP-9 activity, and tumour necrosis factor (TNF)-α and interleukin (IL)-1β concentrations were measured in the lung tissue. The ET-1 levels and antioxidant activity were measured in the serum. Both BQ-123 and bosentan prevented the development of CSE-induced emphysema, blocked the expression of ET A receptor, inhibited pulmonary apoptosis, inactivated MMP-2 and MMP-9 activities in the lung tissues, reduced the concentrations of inflammatory cytokines TNF-α and IL-1β, and improved the biological antioxidant activity in the serum. Emphysema development is suppressed by ET-1 receptor antagonists. ET-1 may cause emphysematous changes through molecular pathogenesis pathways involving apoptosis, proteinase and antiproteinase imbalance, inflammation and oxidative stress.
Serum Ferritin Is Associated With Visceral Fat Area and Subcutaneous Fat Area
Authors: Tomoyuki Iwasaki, Atsushi Nakajima, Masato Yoneda, Yoshihiko Yamada, Koji Mukasa, Koji Fujita, Nobutaka Fujisawa, Koichiro Wada, Yasuo Terauchi
Journal: Diabetes Care (2005)

OBJECTIVE—Until now, few clinical studies have reported on the association between the indexes of body fat distribution and serum ferritin, an indicator of body iron stores and a putative risk factor for insulin resistance. We investigated the association between serum ferritin concentrations and the indexes of distribution of adipose tissues in the body, such as the visceral fat area (VFA), the subcutaneous fat area (SFA), and the hepatic fat content in Japanese subjects. RESEARCH DESIGN AND METHODS—A total of 248 Japanese subjects (127 men and 121 postmenopausal women aged 57.8 ± 13.9 years, BMI 25.7 ± 4.6 kg/m2; 140 subjects with type 2 diabetes and 108 nondiabetic subjects) were evaluated. Subjects with a history of alcohol intake were excluded from the study. We measured body height, body weight, and serum ferritin, as well as fasting plasma glucose and plasma insulin concentrations. We estimated insulin resistance by homeostasis model assessment. The fat distribution was evaluated by measuring the VFA and SFA by abdominal computed tomography at the umbilical level. To assess the hepatic fat content, the ratio of the computed tomography attenuation value of the liver to that of the spleen was calculated. RESULTS—Serum ferritin was significantly correlated with the various indexes of adiposity examined, such as the hepatic fat content (r = −0.280, P &amp;lt; 0.0001), VFA (r = 0.254, P &amp;lt; 0.0001), SFA (r = 0.231, P = 0.0005), and homeostasis model assessment (r = 0.286, P = 0.0008). CONCLUSIONS—This is the first report to directly demonstrate an association between serum ferritin and VFA and SFA. The results of this study suggest that the serum ferritin concentration may be a useful indicator of systemic fat content and degree of insulin resistance.
MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION OF WHITE MICE
Authors: Ida W. Pritchett
Journal: The Journal of Experimental Medicine (1925)

Five separate strains of mice have been tested for their relative susceptibility to per os infection with the Type II bacillus of mouse typhoid (Bacillus pestis caviae), more than 500 individuals of each strain having been employed in the course of 12 months. Clear-cut differences in the susceptibility of these strains to the infection have been shown to exist.
MicroRNA Detection in Cervical Exfoliated Cells as a Triage for Human Papillomavirus–Positive Women
Authors: Qifang Tian, Yang Li, Fenfen Wang, Ying Li, Junfen Xu, Yuanming Shen, Feng Ye, Xinyu Wang, Xiaodong Cheng, Yaxia Chen, Xiaoyun Wan, Weiguo Lu, Xing Xie
Journal: JNCI Journal of the National Cancer Institute (2014)

BackgroundPapanicolaou (Pap) triage, with high specificity, has been recommended for primary Human papillomavirus (HPV) testing but is flawed by poor sensitivity and cytologist dependence. We evaluated the potential role of microRNA (miRNA) detection in cervical exfoliated cells in HPV-positive women from a clinic-based population.
Mutant Tamm-Horsfall Glycoprotein Accumulation in Endoplasmic Reticulum Induces Apoptosis Reversed by Colchicine and Sodium 4-Phenylbutyrate
Authors: Sung Won Choi, Ok Hee Ryu, Sun Jin Choi, In Sun Song, Anthony J. Bleyer, Thomas C. Hart
Journal: Journal of the American Society of Nephrology (2005)

As a consequence of uromodulin gene mutations, individuals develop precocious hyperuricemia, gout, and progressive renal failure. In vitro studies suggest that pathologic accumulation of uromodulin/Tamm-Horsfall glycoprotein (THP) occurs in the endoplasmic reticulum (ER), but the pathophysiology of renal damage is unclear. It was hypothesized that programmed cell death triggered by accumulation of misfolded THP in the ER causes progressive renal disease. Stably transfected human embryonic kidney 293 cells and immortalized thick ascending limb of Henle's loop cells with wild-type and mutated uromodulin cDNA were evaluated to test this hypothesis. Immunocytochemistry, ELISA, and deglycosylation studies indicated that accumulation of mutant THP occurred in the ER. FACS analyses showed a significant increase in early apoptosis signal in human embryonic kidney 293 and thick ascending limb of Henle's loop cells that were transfected with mutant uromodulin constructs. Colchicine and sodium 4-phenylbutyrate treatment increased secretion of THP from the ER to the cell membrane and into the culture media and significantly improved cell viability. These findings indicate that intracellular accumulation of THP facilitates apoptosis and that this may provide the pathologic mechanism responsible for the progressive renal damage associated with uromodulin gene mutations. Colchicine and sodium 4-phenylbutyrate reverse these processes and could potentially be beneficial in ameliorating the progressive renal damage in uromodulin-associated kidney diseases.
Synergy between <i>In situ</i> Cryoablation and TLR9 Stimulation Results in a Highly Effective <i>In vivo</i> Dendritic Cell Vaccine
Authors: Martijn H.M.G.M. den Brok, Roger P.M. Sutmuller, Stefan Nierkens, Erik J. Bennink, Liza W.J. Toonen, Carl G. Figdor, Theo J.M. Ruers, Gosse J. Adema
Journal: Cancer Research (2006)

Abstract Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo–generated, tumor antigen–loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitate the application of DC-based vaccines. We have previously shown that in situ tumor destruction by ablative treatments efficiently delivers antigens for the in vivo induction of antitumor immunity. In this article, we show that although 20% of the draining lymph node DCs acquire intratumorally injected model antigens after in situ cryoablation, only partial protection against a subsequent tumor rechallenge is observed. However, we also show that a combination treatment of cryoablation plus TLR9 stimulation via CpG-oligodeoxynucleotides is far more effective in the eradication of local and systemic tumors than either treatment modality alone. Analysis of the underlying mechanism revealed that in situ tumor ablation synergizes with TLR9 stimulation to induce DC maturation and efficient cross-presentation in tumor-bearing mice, leading to superior DC function in vivo. Therefore, in situ tumor destruction in combination with CpG-oligodeoxynucleotide administration creates a unique “in situ DC vaccine” that is readily applicable in the clinic. (Cancer Res 2006; 66(14): 7285-92)
Analysis of coronary flow fields in thoracotomized dogs.
Authors: H B Atabek, S C Ling, D J Patel
Journal: Circulation Research (1975)

A nonlinear theory of pulsatile flow was used to investigate the detailed flow field in the left circumflex coronary artery of anesthetized open-chest dogs. Studies were carried out under a wide range of blood pressures and flow rates induced by intravenous infusions of dipyridamole. The results indicated that (1) the flow profiles, although less blunt than those in the descending aorta, are still nonparabolic, (2) the wall shear in the coronary arteries maintains a high value through diastole, and (3) during intravenous infusions of dipyridamole both coronary flow and wall shear increase. The peak value of the shear stress during these infusions, which reached 360 dynes/cm2, can approach the yield stress value of 400 dynes/cm2 reported by Fry for endothelial cells.
Interpersonal Intensity, Competition, and Synergy: Determinants of Achievement, Aggression, and Mental Illness
Authors: RODERIC GORNEY
Journal: American Journal of Psychiatry (1971)

On the basis of his investigations of some aspects of interpersonal bonding in several widely different species and human cultures, the author suggests that high-intensity interpersonal bonding may be a prerequisite for various human behaviors, including cultural achievement, aggression, and mental illness. He further suggests that by increasing the degree of synergy in our society we may be able to reduce aggression and mental illness while maintaining a high level of cultural achievement.
Review: parent-child relationships and child development in donor insemination families
Authors: A. Brewaeys
Journal: Human Reproduction Update (2001)

The present article reviews the empirical research regarding the parent–child relationships and the development of children in donor insemination (DI) families. Over the years, follow-up studies have appeared sporadically and, despite the varying quality of the research methods, preliminary findings have emerged. Heterosexual DI parents were psychologically well adjusted and had stable marital relationships. DI parents showed a similar or higher quality of parent–child interaction and a greater emotional involvement with their children compared with naturally conceived families. The majority of studies which investigated several aspects of child development found that, overall, DI children were doing well. Findings with regard to emotional/behavioural development, however, were divergent in that some studies identified an increase of such problems while others did not. A steadily growing group within the DI population is lesbian mother families. More recently, follow-up studies have been carried out among DI children who were raised from birth by two mothers. Despite many concerns about the well-being of these children, no adverse effects of this alternative family structure on child development could be identified. As the DI children in all investigations were still young, our knowledge about the long-term effects of DI remains incomplete.
Unscientific practice flourishes in science
Authors: R. Smith
Journal: BMJ (1998)

Education and debate p 1079 

All around the world the scientific performance of individuals and research groups is being assessed using the impact factors of the journals in which they publish.1 Unfortunately the indisputable evidence that this method is scientifically meaningless is being ignored. Those who assess the performance of researchers seem to be bewitched by the spurious precision of a number that is available to several decimal places.

Most researchers accept that research funds should be concentrated on those who perform well. Performance …
c-sis is translocated from chromosome 22 to chromosome 9 in chronic myelocytic leukemia.
Authors: J Groffen, N Heisterkamp, J R Stephenson, A G van Kessel, A de Klein, G Grosveld, D Bootsma
Journal: The Journal of Experimental Medicine (1983)

By analysis of a series of somatic cell hybrids derived by fusion of either mouse or Chinese hamster cells with leukocytes from different chronic myelocytic leukemia (CML) patients or from normal donors, we have localized the human oncogene, c-sis, on the q11 to qter segment of chromosome 22 and demonstrated its translocation from chromosome 22 to chromosome 9 (q34) in CML.
TCT- 145 RADIATION PROTECT: A randomized trial to assess the effectiveness of a novel pelvic lead shield and a novel, non-lead surgical cap to reduce operator radiation exposure during coronary angiography or intervention
Authors: Ashraf Alazzoni, Darar Al Khdair, Amparo Casanova, Brandi Meeks, Mike Rokoss, Jon-David Schwalm, Pandie Shaheen, Tej Sheth, Michael B. Tsang, Nicholas Valettas, Ed Waller, Madhu K. Natarajan, Shamir Mehta, Sanjit Jolly
Journal: Journal of the American College of Cardiology (2014)
Raised troponin T and echocardiographic abnormalities after prolonged strenuous exercise—the Australian Ironman Triathlon
Authors: L Tulloh, D Robinson, A Patel, A Ware, C Prendergast, D Sullivan, L Pressley
Journal: British Journal of Sports Medicine (2006)

There is concern about whether cardiac damage occurs as a result of prolonged strenuous exercise.To investigate whether competing in a triathlon is associated with cardiac damage based on a sustained increase in cardiac troponin T (cTnT), and whether such an increase correlates with echocardiographic changescTnT and echocardiographic measurements were made in 38 participants in the 2001 Australian ironman triathlon. cTnT was measured the day before, immediately after, and the day following the race. Echocardiography was done the day before, immediately after, and two to six weeks later for measurement of ejection fraction, stroke volume, cardiac output, wall motion analysis, and global left ventricular function (LVF).No subject had detectable cTnT in the pre-race sample. Following the race, 32 subjects (86.5%) had detectable levels of cTnT (>0.01 ng/ml), with six (16.2%) having >0.10 ng/ml. The day after the race, nine subjects (23.7%) still had detectable cTnT, with two recording a level >0.10 ng/ml. Previously described echocardiographic changes of "cardiac fatigue" were observed in the whole cohort. There was a modest but significant correlation between change in ejection fraction and peak cTnT level (p = 0.02, r = 0.39). Athletes with a post-race cTnT >0.10 ng/ml had a greater decrease in global LVF (p = 0.02) and a trend toward a greater fall in ejection fraction and stroke volume than athletes with cTnT levels <0.10 ng/ml. Cardiac output fell in the group with cTnT >0.10 ng/ml (p>0.05).Participation in ironman triathlon often resulted in persistently raised cTnT levels, and the troponin rise was associated with echocardiographic evidence of abnormal left ventricular function. The clinical significance and long term sequelae of such damage remains to be determined.
RAP80 Is Critical in Maintaining Genomic Stability and Suppressing Tumor Development
Authors: Zhengyu Yin, Daniel Menendez, Michael A. Resnick, John E. French, Kyathanahalli S. Janardhan, Anton M. Jetten
Journal: Cancer Research (2012)

Abstract The ubiquitin interaction motif-containing protein RAP80 was recently found to play a key role in DNA damage response (DDR) signaling by facilitating the translocation of several DDR mediators, including BRCA1, to ionizing irradiation (IR)-induced foci. In this study, we examine the effect of the loss of RAP80 on genomic stability and the susceptibility to cancer development in RAP80 null (RAP80−/−) mice. RAP80−/− mice are viable and did not exhibit any apparent developmental defects. Mouse embryonic fibroblasts (MEF) derived from RAP80−/− mice underwent premature senescence compared with wild-type (WT) MEFs, were more sensitive to IR, and exhibited a higher level of spontaneous and IR-induced genomic instability. RAP80−/− thymocytes were more sensitive to IR-induced cell death than WT thymocytes. RAP80−/− mice were more susceptible to spontaneous lymphoma development and the development of 7,12-dimethylbenz(a)anthracene-induced mammary gland tumors. Moreover, the loss of RAP80 accelerated tumor formation in both p53−/− and p53+/− mice. Our data indicate that RAP80-deficiency promotes genomic instability and causes an increase in cancer risk consistent with the concept that RAP80 exhibits a tumor suppressor function. Cancer Res; 72(19); 5080–90. ©2012 AACR.
The effects of propranolol on acute hypertension of anesthetized dogs and on the carotid sinus reflex responses of anesthetized and awake dogs.
Authors: W M Booker, A Hyde, A Fletcher, D Hawthorne
Journal: Circulation Research (1977)

Experiments are presented to show the effects of (1) propranolol on tbe response of systolic blood pressure and diastolic blood pressure to bilateral carotid artery occlusion in choralose-anesthetized dogs; (2) the effects of propranolol on acute hypertensive states in chloralose-anesthetized dogs; and (3) the effects of propranolol on the response of trained awake dogs to bilateral carotid artery occlusion.Acutely, propranolol in successive doses administered intravenously lowered the systolic and diastolic blood pressure response to 35% and 27%, respectively, of the original response during bilateral carotid artery occlusion.There was no significant change in the systolic and diastolic blood pressure of controls.Systolic blood pressure, diastolic blood pressure, ventricular contractile force, dp/ dt, and heart rate, which were elevated by double vagotomy and carotid sinus denervation, were returned to control levels by doses of propranolol.Hypertensive blood pressures of dogs infused with angiotensin and norepinephrine were made normotensive by simultaneous infusion or bolus injection of propranolol.Administered centrally in "isolated head" experiments (dogs) and ventromedial nucleus (in cats), propranolol had no effect on acute hypertension or on carotid sinus reflex response or ventromedial nucleus stimulation.The systolic and diastolic blood pressure responses to bilateral carotid artery occlusion in awake dogs were not significantly altered after the 1st week of daily treatment with propranolol (2.5 mg/kg).The responses of both the systolic and diastolic blood pressure to bilateral carotid artery occlusion decreased, however, after 1 week of daily propranolol administration at 5.0 mg/kg and there was a further decrease in heart rate, and in systolic and diastolic blood pressure responses to bilateral carotid artery occlusion when propranolol was raised to 7.5 mg/kg in daily doses for 1 week.
Studies of FBJ Osteosarcoma Virus in Tissue Culture. II. Autoinhibition of Focus Formation
Authors: J A Levy, J W Hartley, W P Rowe, R J Huebner
Journal: JNCI Journal of the National Cancer Institute (1975)

A high-titered non-focus-forming virus, FBJ-MuLV (murine leukemia virus), present in FBJ tumor preparations, inhibited significantly the expression and production of FBJ-MuSV (murine sarcoma virus) in tissue culture. This "autoinhibition" was comparable to that observed when a 3- to 4-log excess of infectious MuLV was added to standard MuSV. The degree of inhibition was influenced by the tropism of the MuLV (or the ease of spread and propagation of MuLV in certain cells), multiplicity of infection by MuLV, amount of excess MuLV, and ability of the MuSV-transformed cells to replicate independently. The FBJ MuLV-MuSV complex may be a model system for the detection of sarcoma viruses in spontaneous tumors in various animals where inhibition by excess nontransforming virus could be an important biologic phenomenon.
Effectiveness of Olanzapine, Quetiapine, Risperidone, and Ziprasidone in Patients With Chronic Schizophrenia Following Discontinuation of a Previous Atypical Antipsychotic
Authors: T. Scott Stroup, Jeffrey A. Lieberman, Joseph P. McEvoy, Marvin S. Swartz, Sonia M. Davis, A. Rosenheck, Diana O. Perkins, Clarence E. Davis, John K. Hsiao
Journal: American Journal of Psychiatry (2006)

Background: In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic. Method: Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5–30 mg/day [N=66]; quetiapine, 200–800 mg/day [N=63]; risperidone, 1.5–6.0 mg/day [N=69]; or ziprasidone, 40–160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason. Results: The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168). Conclusions: Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.
TREM2-Transduced Myeloid Precursors Mediate Nervous Tissue Debris Clearance and Facilitate Recovery in an Animal Model of Multiple Sclerosis
Authors: Kazuya Takahashi, Marco Prinz, Massimiliano Stagi, Olga Chechneva, Harald Neumann
Journal: PLoS Medicine (2007)

In multiple sclerosis, inflammation can successfully be prevented, while promoting repair is still a major challenge. Microglial cells, the resident phagocytes of the central nervous system (CNS), are hematopoietic-derived myeloid cells and express the triggering receptor expressed on myeloid cells 2 (TREM2), an innate immune receptor. Myeloid cells are an accessible source for ex vivo gene therapy. We investigated whether myeloid precursor cells genetically modified to express TREM2 affect the disease course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis.EAE was induced in mice by immunization with a myelin autoantigen. Intravenous application of TREM2-transduced bone marrow-derived myeloid precursor cells at the EAE peak led to an amelioration of clinical symptoms, reduction in axonal damage, and prevention of further demyelination. TREM2-transduced myeloid cells applied intravenously migrated into the inflammatory spinal cord lesions of EAE-diseased mice, showed increased lysosomal and phagocytic activity, cleared degenerated myelin, and created an anti-inflammatory cytokine milieu within the CNS.Intravenously applied bone marrow-derived and TREM2-tranduced myeloid precursor cells limit tissue destruction and facilitate repair within the murine CNS by clearance of cellular debris during EAE. TREM2 is a new attractive target for promotion of repair and resolution of inflammation in multiple sclerosis and other neuroinflammatory diseases.