tbuckley/cabot-search huggingface dataset:
Tissue Prostate-Specific Antigen Facilitates Refractory Prostate Tumor Progression via Enhancing ARA70-Regulated Androgen Receptor Transactivation
Authors: Yuanjie Niu, Shuyuan Yeh, Hiroshi Miyamoto, Gonghui Li, Saleh Altuwaijri, Jianqun Yuan, Ruifa Han, Tengxiang Ma, Hann-Chorng Kuo, Chawnshang Chang
Journal: Cancer Research (2008)

Abstract Despite being well recognized as the best biomarker for prostate cancer, pathophysiologic roles of prostate-specific antigen (PSA) remain unclear. We report here that tissue PSA may be involved in the hormone-refractory prostate cancer progression. Histologic analyses show that the increased tissue PSA levels are correlated with lower cell apoptosis index and higher cell proliferation rate in hormone-refractory tumor specimens. By stably transfecting PSA cDNA into various prostate cancer cell lines, we found that PSA could promote the growth of androgen receptor (AR)-positive CWR22rv1 and high-passage LNCaP (hormone-refractory prostate cancer cells) but not that of AR-negative PC-3 and DU145 cells. Surprisingly, the protease activity of PSA is not crucial for PSA to stimulate growth and promote AR transactivation. We further showed that increased PSA could enhance ARA70-induced AR transactivation via modulating the p53 pathway that results in the decreased apoptosis and increased cell proliferation in prostate cancer cells. Knockdown of PSA in LNCaP and CWR22rv1 cells causes cell apoptosis and cell growth arrest at the G1 phase. In vitro colony formation assay and in vivo xenografted tumor results showed the suppression of prostate cancer growth via targeting PSA expression. Collectively, our findings suggest that, in addition to being a biomarker, PSA may also become a new potential therapeutic target for prostate cancer. PSA small interfering RNA or smaller molecules that can degrade PSA protein may be developed as alternative approaches to treat the prostate cancer. [Cancer Res 2008;68(17):7110–9]
WEIRD societies may be more compatible with human nature
Authors: Alexandra Maryanski
Journal: Behavioral and Brain Sciences (2010)

Abstract Are WEIRD societies unrepresentative of humanity? According to Henrich et al., they are not useful for generalizing about humans because they are at the extreme end of the distribution for societal formations. In their vision, it is best to stick with the “tried and true” traditional societies for speculations about human nature. This commentary offers a more realistic starting point, and, oddly enough, concludes that WEIRD populations may be more compatible with humans' evolved nature than are most traditional societies.
Chemical composition of gallstones resistant to dissolution therapy with chenodeoxycholic acid.
Authors: M J Whiting, V Jarvinen, J M Watts
Journal: Gut (1980)

The gallstones of 14 patients, who had been treated unsuccessfully with chenodeoxycholic acid (15 mg/kg/day) for at lest six months, were obtained at cholecystectomy. The stones were then analysed for their cholesterol and calcium content. Two patients' stones were black in colour and low in cholesterol content, and were classified as pigment stones. Of the remaining 12 patients' stones, which all contained more than 70% cholesterol, 10 contained at lest 1% calcium on the stone surface. In two patients, the surface contained sufficient calcium to form a radio-opaque layer, although the stones had been radiolucent at the start of dissolution therapy. Overall, the results suggest that deposition of calcium salts inhibits the dissolution treatment of gallstones with chenodeoxycholic acid, irrespective of the radiolucency of the stones.
Screening Asymptomatic Adults With Resting or Exercise Electrocardiography: A Review of the Evidence for the U.S. Preventive Services Task Force
Authors: Roger Chou, Bhaskar Arora, Tracy Dana, Rongwei Fu, Miranda Walker, Linda Humphrey
Journal: Annals of Internal Medicine (2011)

Background: Coronary heart disease is the leading cause of death in adults. Screening for abnormalities by using resting or exercise electrocardiography (ECG) might help identify persons who would benefit from interventions to reduce cardiovascular risk. Purpose: To update the 2004 U.S. Preventive Services Task Force evidence review on screening for resting or exercise ECG abnormalities in asymptomatic adults. Data Sources: MEDLINE (2002 through January 2011), the Cochrane Library database (through the fourth quarter of 2010), and reference lists. Study Selection: Randomized, controlled trials and prospective cohort studies. Data Extraction: Investigators abstracted details about the study population, study design, data analysis, follow-up, and results and assessed quality by using predefined criteria. Data Synthesis: No study evaluated clinical outcomes or use of risk-reducing therapies after screening versus no screening. No study estimated how accurately resting or exercise electrocardiography classified participants into high-, intermediate-, or low-risk groups, compared with traditional risk factor assessment alone. Sixty-three prospective cohort studies evaluated abnormalities on resting or exercise ECG as predictors of cardiovascular events after adjustment for traditional risk factors. Abnormalities on resting ECG (ST-segment or T-wave abnormalities, left ventricular hypertrophy, bundle branch block, or left-axis deviation) or exercise ECG (ST-segment depression with exercise, chronotropic incompetence, abnormal heart rate recovery, or decreased exercise capacity) were associated with increased risk (pooled hazard ratio estimates, 1.4 to 2.1). Evidence on harms was limited, but direct harms seemed minimal (for resting ECG) or small (for exercise ECG). No study estimated harms from subsequent testing or interventions, although rates of angiography after exercise ECG ranged from 0.6% to 2.9%. Limitations: Only English-language studies were included. Statistical heterogeneity was present in several of the pooled analyses. Conclusion: Abnormalities on resting or exercise ECG are associated with an increased risk for subsequent cardiovascular events after adjustment for traditional risk factors, but the clinical implications of these findings are unclear. Primary Funding Source: Agency for Healthcare Research and Quality.
Improvement of left ventricular function and cardiovascular neural control after endoventriculoplasty and myocardial revascularization
Authors: Laura Dalla Vecchia, Andrea Mangini, Pietro Di Biasi, Carmine Santoli, Alberto Malliani
Journal: Cardiovascular Research (1998)

To investigate the effects of endoventriculoplasty (EVP) and myocardial revascularization on left ventricular function and on sympathovagal balance modulating sinus node and vasomotor activity, we studied patients with left anterior, septal or anteroseptal ventricular aneurysm, before and after surgery. It has been demonstrated that, compared to the standard aneurismectomy, EVP associated with coronary grafting has a lower operative mortality and improves ventricular function, clinical status and prognosis.We collected pre- and post-operative echocardiographic and angiographic data to determine morphological and hemodynamic changes. The pre- and post-operative neural cardiovascular control was assessed by power spectrum analysis of heart rate and systolic arterial pressure (SAP) variabilities during rest and tilt.As expected, post-operative ventricular function improved significantly: ejection fraction increased from 33 +/- 2 to 46 +/- 3% (p < 0.01) when assessed by echocardiography and from 40 +/- 4 to 55 +/- 5% (p < 0.01) when assessed by angiography; left ventricular end-diastolic pressure fell from 22 +/- 3 to 13 +/- 2 mmHg (p < 0.05). Pre-operatively sympathovagal balance responsiveness was blunted: tilt test did not induce, in respect to resting values, any significant change in low frequency (LFRR) and high frequency (HFRR) components of RR variability (in normalized units, n.u.) and in LFSAP. Post-operatively, tilt induced significant changes in LFRR and HFRR (in n.u.), in LF/HF ratio and LFSAP in respect to resting values. The pre- and post-operative percent differences--delta%--, from rest to tilt, of LFRR, HFRR, LF/HF and LFSAP were also significantly different (p < 0.01, p < 0.05, p < 0.05, p < 0.05). In addition, we compared data obtained from survivors and non-survivors (6 out of 19 patients died within 4 months because of heart failure). Non-survivors were characterized by significantly lower RR variance (184 +/- 80 vs. 1193 +/- 309 ms2 at rest, 196 +/- 87 vs. 546 +/- 104 ms2 during tilt, p < 0.05) and lower LFRR (15 +/- 7 vs. 61 +/- 6 at rest, 23 +/- 10 vs. 58 +/- 6 during tilt, in n.u., p < 0.01).(1) The improvement of ventricular function induced by EVP and myocardial revascularization is accompanied by a restored capability to oscillate of cardiovascular neural regulatory mechanisms; (2) the drastic reduction of variance and LF component from RR variability seems to be associated with an ominous outcome.
Attenuation of propranolol-induced bronchoconstriction by frusemide.
Authors: J D Myers, M A Higham, B H Shakur, M Wickremasinghe, P W Ind
Journal: Thorax (1997)

BACKGROUND: Inhaled propranolol causes bronchoconstriction in asthmatic subjects by an indirect mechanism which remains unclear. Inhaled frusemide has been shown to attenuate a number of indirectly acting bronchoconstrictor challenges. The aim of this study was to investigate whether frusemide could protect against propranolol-induced bronchoconstriction in patients with stable mild asthma. METHODS: Twelve asthmatic subjects were studied on three separate days. At the first visit subjects inhaled increasing doubling concentrations of propranolol (0.25-32 mg/ml), breathing tidally from a jet nebuliser. The provocative concentration of propranolol causing a 20% reduction in FEV1 (PC20FEV1 propranolol) was determined from the log concentration-response curve for each subject. At the following visits nebulised frusemide (4 ml x 10 mg/ml) or placebo (isotonic saline) was administered in a randomised, double blind, crossover fashion. FEV1 was measured immediately before and five minutes after drug administration. Individual PC20FEV1 propranolol was then administered and FEV1 was recorded at five minute intervals for 15 minutes. Residual bronchoconstriction was reversed with nebulised salbutamol. RESULTS: Frusemide had no acute bronchodilator effect but significantly reduced the maximum fall in FEV1 due to propranolol: mean fall 18.2% after placebo and 11.8% after frusemide. The median difference in maximum % fall in FEV1 within individuals between study days was 3.6% (95% CI 1.2 to 11.7). CONCLUSIONS: Frusemide attenuates propranolol-induced bronchoconstriction, a property shared with sodium cromoglycate. Both drugs block other indirect challenges and the present study lends further support to the suggestion that frusemide and cromoglycate share a similar mechanism of action in the airways.
Local production of corticotropin releasing hormone is increased in experimental intestinal inflammation in rats.
Authors: E A van Tol, P Petrusz, P K Lund, M Yamauchi, R B Sartor
Journal: Gut (1996)

BACKGROUND/AIMS: Corticotropin releasing hormone (CRH) suppresses immunological functions via stimulation of the pituitary-adrenal axis, but is also found in peripheral tissues. Peripheral proinflammatory activity of CRH is suggested by increased tissue concentrations in arthritis and in vitro immunostimulatory effects. This study evaluated intestinal CRH concentrations, immunolocalisation, and synthesis in chronic enterocolitis and investigated in vitro responsiveness of lamina propria mononuclear cells to CRH. METHODS: Chronic granulomatous enterocolitis was induced by intramural injection of peptidoglycan-polysaccharide polymers in the ileocaecal region of Lewis rats. CRH protein was measured in caecal specimens by immunohistochemistry and radioimmunoassay and caecal CRH mRNA expression was analysed by reverse transcriptase polymerase chain reaction. RESULTS: In the chronically inflamed caecum abundant immunoreactive CRH was found in inflammatory cells, mesenchymal cells, as well as in myenteric plexi. In contrast, only a few CRH containing cells were detected in normal and HSA injected control caecums. Moreover, caecal CRH protein levels were increased during chronic enterocolitis. Local CRH synthesis as indicated by mRNA expression was considerably increased in chronic enterocolitis whereas it was undetectable or low in uninflamed caecum. In addition, CRH stimulated in vitro proliferation of lamina propria mononuclear cells and inhibited mitogen induced proliferation. CONCLUSION: Increased CRH protein and mRNA expression in chronic enterocolitis and responsiveness of intestinal mononuclear cells to CRH indicate an immunomodulatory role for locally produced CRH in intestinal inflammation.
Selective Responsiveness of Human Breast Cancer Cells to Indole-3-carbinol, a Chemopreventive Agent
Authors: R. K. Tiwari, L. Guo, H. L. Bradlow, N. T. Telang, M. P. Osborne
Journal: JNCI Journal of the National Cancer Institute (1994)

Background: Indole-3-carbinol (13C), a compound found in cabbage, broccoli, and brussels sprouts, inhibits the growth of mammary tumors when fed to certain strains of mice. The chemopreventive and antitumor effects of 13C depend on the species and tissue type. The mechanism of action and specific human cell types that respond to 13C are not known. Purpose: Our purpose was to study the mechanism of action of I3C in estrogen-responsive (MCF-7) and estrogen-nonresponsive(MDAMB-231) human breast cancer cell lines. Methods: Estrogen responsiveness was determined by the ability of estradiol to stimulate the growth of breast cancer cells deprived of estrogen. The effect of I3C was measured on cell growth, estradiol metabolism, and level of cytochrome P-4501A1. Growth was measured by cell counts and soft-ager assay, estrogen metabolism was examined by a radiometric assay, and the level of cytochrome P-4501A1 was measured by Western blots with a poly-clonal antibody. Results: I3C inhibits the growth of estrogen-responsive cell line MCF-7 but has little effect on estrogen-nonresponsive cell line MDA-MB-231. Specific C-2 hydrox-ylation of estrogen and induction of cytochrome P-4501A1 was enhanced by I3C in the MCF-7 but not in the MDA-MB-231 cells. Conclusion: I3C has specific antigrowth effects in human breast cancer cells. The inhibitory effects of I3C may involve selective induction of estradiol metabolism and the related cytochrome P-450 system that may be limited to estrogen-sensitive cells. [J Natl Cancer Inst 86: 126–131, 1994].
GATM Polymorphism Associated with the Risk for Statin-Induced Myopathy Does Not Replicate in Case-Control Analysis of 715 Dyslipidemic Individuals
Authors: Jasmine A. Luzum, Joseph P. Kitzmiller, Paul J. Isackson, Changxing Ma, Marisa W. Medina, Anees M. Dauki, Eduard B. Mikulik, Heather M. Ochs-Balcom, Georgirene D. Vladutiu
Journal: Cell Metabolism (2015)
Molecular Architecture of Smell and Taste in<i>Drosophila</i>
Authors: Leslie B. Vosshall, Reinhard F. Stocker
Journal: Annual Review of Neuroscience (2007)

The chemical senses-smell and taste-allow animals to evaluate and distinguish valuable food resources from dangerous substances in the environment. The central mechanisms by which the brain recognizes and discriminates attractive and repulsive odorants and tastants, and makes behavioral decisions accordingly, are not well understood in any organism. Recent molecular and neuroanatomical advances in Drosophila have produced a nearly complete picture of the peripheral neuroanatomy and function of smell and taste in this insect. Neurophysiological experiments have begun to provide insight into the mechanisms by which these animals process chemosensory cues. Given the considerable anatomical and functional homology in smell and taste pathways in all higher animals, experimental approaches in Drosophila will likely provide broad insights into the problem of sensory coding. Here we provide a critical review of the recent literature in this field and comment on likely future directions.
Frequencies in Pulsatile Flow and Response of Magnetic Meter
Authors: DONALD J. FERGUSON, HERBERT S. WELLS
Journal: Circulation Research (1959)

An electromagnetic meter has been calibrated for pulsatile flow with use of a sinusoidal driver operating up to 45 c.p.s. Accurate recording of alternating flow at this frequency was possible under specified conditions. Pulsatile flow measurements from animals were directly calibrated by fractional collection of blood after it passed through the meter. Harmonic analyses of flow curves indicated that full response to 20 c.p.s. permitted adequate recording of femoral artery flow in an anesthetized dog.
Chronic gastrointestinal ischaemia: shifting paradigms
Authors: P. B. F. Mensink, L. M. G. Moons, E. J. Kuipers
Journal: Gut (2010)

Chronic gastrointestinal ischaemia (CGI) is generally considered to be a rare disease entity. The majority of patients with CGI are only diagnosed after a long period of slowly progressive abdominal symptoms, in some cases with impressive weight loss. These patients may have a broad range of clinical signs and quite often undergo repeated extensive evaluation of their symptoms with negative outcome. The classical triad of symptoms, also known as 'abdominal angina', is defined as the combination of postprandial pain, weight loss due to fear of pain after eating, and an abdominal bruit during physical examination. Recent studies have shed new lights on these long unchallenged concepts. These studies first showed that CGI is more prevalent than previously thought and can occur in patients with both single- and multi-vessel disease. Second, the disease presents with a much wider range in symptoms, and only a minority of patients present with the classical triad. Third, long-term positive outcomes can be achieved after endovascular or surgical revascularisation therapy in large proportion of patients. This knowledge results from a combination of clinical research by dedicated focus groups, the current widespread availability of new imaging techniques such as CT-angiography, the development of new functional tests for assessment of mucosal perfusion, and the evolution of endovascular stenting options. Clinicians diagnosing and treating patients with acute and chronic abdominal conditions have to be aware of these new developments. We therefore here review the new insights on CGI with a focus on epidemiology, pathophysiology, current diagnostics and treatment.
Metalloprotease-Mediated Tumor Cell Shedding of B7-H6, the Ligand of the Natural Killer Cell–Activating Receptor NKp30
Authors: Eva Schlecker, Nathalie Fiegler, Annette Arnold, Peter Altevogt, Stefan Rose-John, Gerhard Moldenhauer, Antje Sucker, Annette Paschen, Elke Pogge von Strandmann, Sonja Textor, Adelheid Cerwenka
Journal: Cancer Research (2014)

Abstract Natural killer (NK) cells are potent immune effector cells capable of mediating antitumor responses. Thus, during immunoediting, tumor cell populations evolve strategies to escape NK-cell–mediated recognition. In this study, we report a novel mechanism of immune escape involving tumor cell shedding of B7-H6, a ligand for the activating receptor NKp30 that mediates NK-cell binding and NK-cell–mediated killing. Tumor cells from different cancer entities released B7-H6 by ectodomain shedding mediated by the cell surface proteases “a disintegrin and metalloproteases” (ADAM)-10 and ADAM-17, as demonstrated through the use of pharmacologic inhibitors or siRNA-mediated gene attenuation. Inhibiting this proteolytic shedding process increased the levels of B7-H6 expressed on the surface of tumor cells, enhancing NKp30-mediated activation of NK cells. Notably, we documented elevated levels of soluble B7-H6 levels in blood sera obtained from a subset of patients with malignant melanoma, compared with healthy control individuals, along with evidence of elevated B7-H6 expression in melanoma specimens in situ. Taken together, our results illustrated a novel mechanism of immune escape in which tumor cells impede NK-mediated recognition by metalloprotease-mediated shedding of B7-H6. One implication of our findings is that therapeutic inhibition of specific metalloproteases may help support NK-cell–based cancer therapy. Cancer Res; 74(13); 3429–40. ©2014 AACR.
Disodium octaborate tetrahydrate (DOT) application and vacuum cleaning, a combined strategy to control house dust mites
Authors: R. Codina, R. F. Lockey, R. Diwadkar, L. L. Mobly, S. Godfrey
Journal: Allergy (2003)

Background: The effectiveness of acaricides in homes is controversial. Objective: To determine whether disodium octaborate tetrahydrate (DOT) combined with vacuuming lowers dust mite numbers and their allergens in carpets and sofas. Methods: A 6‐month study was carried out with 93 homes, which were randomized into three groups: (i) active, received DOT; (ii) placebo, received water; and (iii) control, received no application. Active and placebo homes were vacuumed weekly. Dust was collected from carpets and sofas at the start of the study and every 2 months thereafter and quantified for live, total mites, and mite allergen levels. Results: At 2 months, live mite numbers in active carpets were 3 ± 1, in placebo carpets 129 ± 48, and in control carpets 177 ± 39 mites/g. The corresponding numbers in sofas were 3 ± 2, 81 ± 31, and 134 ± 45 mites/g, respectively ( P &lt; 0.001 active vs placebo and vs. control). Live mites in carpets and sofas remained lower in the active group at 6 months ( P &lt; 0.001). Total mites in active carpets decreased from 555 ± 69 at baseline to 223 ± 32 mites/g at 6 months ( P &lt; 0.001) and mite allergen levels from 1.36 ± 0.13 to 0.85 ± 0.16 μ g/g ( P &lt; 0.001). Total mites in active sofas remained unchanged, but mite allergen levels decreased from 1.48 ± 0.25 at baseline to 0.7 ± 0.15 μ g/g at month 6 (P &lt; 0.05). Conclusion: DOT kills mites in carpets and sofas, and, combined with vacuuming, effectively reduces total mites in carpets and mite allergen levels in carpets and sofas.
Role of Interleukin-1β in Acute Inflammation and Graft Death After Cell Transplantation to the Heart
Authors: Ken Suzuki, Bari Murtuza, Jonathan R. Beauchamp, Nigel J. Brand, Paul J. R. Barton, Anabel Varela-Carver, Satsuki Fukushima, Steven R. Coppen, Terence A. Partridge, Magdi H. Yacoub
Journal: Circulation (2004)

Poor survival of grafted cells is a major factor hindering the therapeutic effect of cell transplantation; however, the causes of cell death remain unclear. We hypothesized that interleukin-1beta (IL-1beta) might play a role in the acute inflammatory response and graft death after cell transplantation and that inhibition of IL-1beta might improve graft survival.14C-labeled male skeletal muscle precursor cells were implanted into female mouse hearts by direct intramuscular injection. The amount of 14C-label provides an estimate of the surviving cell number, whereas the amount of male-specific Smcy gene measured by polymerase chain reaction indicates the total (surviving+proliferated) number of donor-derived cells. At 10 minutes after implantation, 44.8+/-2.4% of the grafted cells survived and this steadily decreased to 14.6+/-1.1% by 24 hours, and to 7.9+/-0.6% by 72 hours (n=6 in each point). Proliferation of the surviving cells, which began after 24 hours, resulted in an increase in the total cell number from 15.5+/-0.8% at 24 hours to 24.4+/-1.6% at 72 hours. Acute inflammation was prominent at 24 hours and was reduced by 72 hours, in parallel with IL-1beta expression. Administration of anti-IL-1beta antibody improved graft survival at both 24 (25.6+/-1.6%) and 72 hours (14.8+/-1.1%) and resulted in a 2-fold increase in the total cell number at 72 hours (45.8+/-2.4%). The effects of IL-1beta inhibition corresponded with a reduced inflammatory response.IL-1beta is involved in acute inflammation and graft death after direct intramyocardial cell transplantation. Targeted inhibition of IL-1beta may be a useful strategy to improve graft survival.