tbuckley/cabot-search huggingface dataset:
Overview of reproductive and developmental toxicity studies of 1,3-butadiene in rodents.
Authors: R E Morrissey, B A Schwetz, P L Hackett, M R Sikov, B D Hardin, B J McClanahan, J R Decker, T J Mast
Journal: Environmental Health Perspectives (1990)

A series of studies to further evaluate the developmental and reproductive toxicity of inhaled 1,3-butadiene was sponsored by the National Toxicology Program. Pregnant Sprague-Dawley rats (24-28/group) and Swiss (CD-1) mice (18-22/group) were exposed to atmospheric concentrations of 0, 40, 200, or 1000 ppm 1,3-butadiene for 6 hr/day on days 6 through 15 of gestation (dg) and killed on dg 18 (mice) or dg 20 (rats). Subsequently, the uterine contents were evaluated; individual fetal body weights were recorded; and external, visceral, and skeletal examinations were performed. In rats, maternal toxicity was observed in the 1000-ppm group in the form of reduced extragestational weight gain and, during the first week of treatment, decreased body weight gain. Under these conditions, there was no evidence of developmental toxicity in rats. In contrast, results of the mouse developmental toxicity study indicated that the fetus may be more susceptible than the dam to inhaled 1,3-butadiene. Maternal toxicity was observed in mice at the 200- and 1000-ppm 1,3-butadiene exposure levels, whereas 40 ppm and higher concentrations of 1,3-butadiene caused significant exposure-related reductions in the mean body weights of male fetuses. Mean body weights of female fetuses were also reduced at the 200- and 1000-ppm exposure levels. No increased incidence of malformations was observed in either study. Other studies addressing male reproductive and mutagenesis end points were performed with B6C3F1 mice (sperm-head morphology) and Swiss (CD-1) mice (dominant lethal study).(ABSTRACT TRUNCATED AT 250 WORDS)
Lack of Tissue Inhibitor of Metalloproteinases 2 Leads to Exacerbated Left Ventricular Dysfunction and Adverse Extracellular Matrix Remodeling in Response to Biomechanical Stress
Authors: Vijay Kandalam, Ratnadeep Basu, Linn Moore, Dong Fan, Xiuhua Wang, Diane M. Jaworski, Gavin Y. Oudit, Zamaneh Kassiri
Journal: Circulation (2011)

Remodeling of the extracellular matrix (ECM) is a key aspect of myocardial response to biomechanical stress and heart failure. Tissue inhibitors of metalloproteinases (TIMPs) regulate the ECM turnover through negative regulation of matrix metalloproteinases (MMPs), which degrade the ECM structural proteins. Tissue inhibitor of metalloproteinases 2 is unique among TIMPs in activating pro-MMP2 in addition to inhibiting a number of MMPs. Given this dual role of TIMP2, we investigated whether TIMP2 serves a critical role in heart disease.Pressure overload by transverse aortic constriction (TAC) in 8-week-old male mice resulted in greater left ventricular hypertrophy, fibrosis, dilation, and dysfunction in TIMP2-deficient (TIMP2(-/-)) compared with wild-type mice at 2 weeks and 5 weeks post-TAC. Despite lack of MMP2 activation, total collagenase activity and specific membrane type MMP activity were greater in TIMP2(-/-)-TAC hearts. Loss of TIMP2 resulted in a marked reduction of integrin β1D levels and compromised focal adhesion kinase phosphorylation, resulting in impaired adhesion of cardiomyocytes to ECM proteins, laminin, and fibronectin. Nonuniform ECM remodeling in TIMP2(-/-)-TAC hearts revealed degraded network structure as well as excess fibrillar deposition. Greater fibrosis in TIMP2(-/-)-TAC compared with wild-type TAC hearts was due to higher levels of SPARC (secreted protein acidic and rich in cysteine) and posttranslational stabilization of collagen fibers rather than increased collagen synthesis. Inhibition of MMPs including membrane type MMP significantly reduced left ventricular dilation and dysfunction, hypertrophy, and fibrosis in TIMP2(-/-)-TAC mice.Lack of TIMP2 leads to exacerbated cardiac dysfunction and remodeling after pressure overload because of excess activity of membrane type MMP and loss of integrin β1D, leading to nonuniform ECM remodeling and impaired myocyte-ECM interaction.
Predictors of Indoor Radon Concentrations in Pennsylvania, 1989–2013
Authors: Joan A. Casey, Elizabeth L. Ogburn, Sara G. Rasmussen, Jennifer K. Irving, Jonathan Pollak, Paul A. Locke, Brian S. Schwartz
Journal: Environmental Health Perspectives (2015)

Radon is the second-leading cause of lung cancer worldwide. Most indoor exposure occurs by diffusion of soil gas. Radon is also found in well water, natural gas, and ambient air. Pennsylvania has high indoor radon concentrations; buildings are often tested during real estate transactions, with results reported to the Department of Environmental Protection (PADEP).We evaluated predictors of indoor radon concentrations.Using first-floor and basement indoor radon results reported to the PADEP between 1987 and 2013, we evaluated associations of radon concentrations (natural log transformed) with geology, water source, building characteristics, season, weather, community socioeconomic status, community type, and unconventional natural gas development measures based on drilled and producing wells.Primary analysis included 866,735 first measurements by building, with the large majority from homes. The geologic rock layer on which the building sat was strongly associated with radon concentration (e.g., Axemann Formation, median = 365 Bq/m3, IQR = 167-679 vs. Stockton Formation, median = 93 Bq/m3, IQR = 52-178). In adjusted analysis, buildings using well water had 21% higher concentrations (β = 0.191, 95% CI: 0.184, 0.198). Buildings in cities (vs. townships) had lower concentrations (β = -0.323, 95% CI: -0.333, -0.314). When we included multiple tests per building, concentrations declined with repeated measurements over time. Between 2005 and 2013, 7,469 unconventional wells were drilled in Pennsylvania. Basement radon concentrations fluctuated between 1987 and 2003, but began an upward trend from 2004 to 2012 in all county categories (p < 0.001), with higher levels in counties having ≥ 100 drilled wells versus counties with none, and with highest levels in the Reading Prong.Geologic unit, well water, community, weather, and unconventional natural gas development were associated with indoor radon concentrations. Future studies should include direct environmental measurement of radon, as well as building features unavailable for this analysis.Casey JA, Ogburn EL, Rasmussen SG, Irving JK, Pollak J, Locke PA, Schwartz BS. 2015. Predictors of indoor radon concentrations in Pennsylvania, 1989-2013. Environ Health Perspect 123:1130-1137; http://dx.doi.org/10.1289/ehp.1409014.
Poor one year prognosis in acute myocardial infarction patients with saphenous vein grafts as the infarct related vessel treated by primary balloon angioplasty
Authors: Thanh T. Nguyen, William W. O'Neill, Simon R. Dixon, Judith A. Boura, Lorelei Grines, David A. Cox, Gregg W. Stone, Bruce Brodie, Cindy L. Grines
Journal: Journal of the American College of Cardiology (2002)
The right kind of content for a physicalist about color
Authors: Paul Skokowski
Journal: Behavioral and Brain Sciences (2003)

Color experiences have representational content. But this content need not include a propositional component, particularly for reflectance physicalists such as Byrne &amp; Hilbert (B&amp;H). Insisting on such content gives primacy to language where it is not required, and makes the extension of the argument to nonhuman animals suspect.
Prospective assessment of quality of life in patient with congestive heart failure receiving dual chamber pacing: bradycardia related impact
Authors: A. Natale, K. Newby, L. Zimerman, S. Beheiry, A. Wolverton, E. Pisano, R. Fanelli, H. Barold, G. Tomassoni
Journal: Journal of the American College of Cardiology (1998)
Abstract 1119: Utilization of the TGFβ signaling pathway and cell substrate interaction in a novel anti-cancer drug screen
Authors: Wontak Kim, Jacob P. Hoj, Nicholas E. Saguibo, Kendra E. Fullmer
Journal: Cancer Research (2014)

Abstract The TGF-β signaling pathway has been demonstrated to play a multifunctional and complicated role in cancer progression, making it an intriguing target for anti-cancer therapeutics. TGF-β signaling drives proliferation of cancer cells, invasion at the tumor periphery, and is associated with metastatic potential in a number of cancer types. Tumors expressing TGF-β activity are positively correlated with poorer prognosis in patients. Complicating the role of TGF-β signaling in cancer progression is that TGF-β signaling leads to distinct cellular responses at different stages of cancer progression. How the same signal transduction pathway drives distinct cellular responses is a critical question. One likely possibility is that TGF-β signaling is highly context dependent. Changes in the tumor microenvironment, as occur during cancer progression, alter the outcome of TGF-β signaling. As an extreme example of how TGF-β signaling is affected by micro-environmental stimuli, we and others previously reported that certain non-cancerous cells on rigid collagen I substrates become sensitized to HGF-induced epithelial scattering in response to TGF-β, while cells on pliant collagen I substrates undergo apoptosis in response to TGF-β. Given that tumors are typically rigid tissues, we sought to define whether cancer cells would respond to TGF-β by undergoing apoptosis when cultured on pliant substrates. We plated a wide variety of cancer cell lines on highly pliant substrates, treated then with TGF-β, and observed cell viability over time. While a number of cells showed no apoptotic response to TGF-β signaling under any condition, we find that a significant number of cancer cells derived from solid tumors respond to TGF-β signaling on pliant substrates by undergoing apoptosis. Another group of cell lines undergo apoptosis on pliant substrates in the absence of any TGF-β stimulation. Reasoning that perturbation of cellular signaling that communicated substrate rigidity to cells might sensitize them to apoptosis in response to TGF-β, we designed a high-content high throughput screen to look for molecules that would induce cells to undergo apoptosis in response to TGF-β signaling. This chemical genetics approach will yield cues into the mechanism of tumor microenvironment sensing, as well as provide lead compounds for development of novel therapeutics Note: This abstract was not presented at the meeting. Citation Format: Wontak Kim, Jacob P. Hoj, Nicholas E. Saguibo, Kendra E. Fullmer. Utilization of the TGFβ signaling pathway and cell substrate interaction in a novel anti-cancer drug screen. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1119. doi:10.1158/1538-7445.AM2014-1119
Activation and inhibition of lymphocytes by costimulation
Authors: Kenneth A. Frauwirth, Craig B. Thompson
Journal: Journal of Clinical Investigation (2002)

Mounting an appropriate immune response depends on the careful regulation of lymphocyte activation. To this end, lymphocytes require two independent signals to become fully activated. The first, an antigen-specific signal is sent via the unique antigen receptor: T cell receptor (TCR) on T cells or surface Ig on B cells. The second signal, termed costimulation, is independent of the antigen receptor and is critical to allow full activation, sustain cell proliferation, prevent anergy and/or apoptosis, induce differentiation to effector and memory status, and allow cell-cell cooperation. Costimulation is in turn regulated by the expression of inhibitory receptors upon lymphocyte activation. Here we will consider the growing list of costimulatory and inhibitory molecules, with emphasis on signaling events they initiate. Potentially complex patterns of regulation implied by the variety of receptor/ligand pairs and their differential expression patterns will also be discussed.
Emergency Medical Therapy
Authors: John C. Johnson
Journal: JAMA (1983)

<b>Emergency Medicine: A Quick Reference for Primary Care,</b>by John E. Hocutt, Jr, 439 pp, with illus, paper, $12, New York, Arco Publishing Co Inc, 1982. <i>Emergency Medical Therapy</i>is a therapeutic index for the evaluation and initial treatment of the major emergent medical problems. Safe and effective use of this text, however, requires prior medical knowledge and experience. Each section defines the medical problem, listing salient historical, physical, and ancillary findings that confirm the diagnosis. The therapeutic discussion that follows clearly lists the appropriate drug(s), dosage(s), and additional considerations germane to the diagnosed problem. While all problems discussed are not life threatening, all are discernibly relevant to a discussion of emergency medical care. Surgical, gynecologic, and pediatric problems, for the most part, are excluded from this handbook. The appendices provide additional useful prescribing information on 334 drugs in 48 different categories in an abbreviated format and a listing of
Estimated Effect of Climatic Variables on the Transmission of <i>Plasmodium vivax</i> Malaria in the Republic of Korea
Authors: Young-Min Kim, Jae-Won Park, Hae-Kwan Cheong
Journal: Environmental Health Perspectives (2012)

Background: Climate change may affect Plasmodium vivax malaria transmission in a wide region including both subtropical and temperate areas.Objectives: We aimed to estimate the effects of climatic variables on the transmission of P. vivax in temperate regions.Methods: We estimated the effects of climatic factors on P. vivax malaria transmission using data on weekly numbers of malaria cases for the years 2001–2009 in the Republic of Korea. Generalized linear Poisson models and distributed lag nonlinear models (DLNM) were adopted to estimate the effects of temperature, relative humidity, temperature fluctuation, duration of sunshine, and rainfall on malaria transmission while adjusting for seasonal variation, between-year variation, and other climatic factors.Results: A 1°C increase in temperature was associated with a 17.7% [95% confidence interval (CI): 16.9, 18.6%] increase in malaria incidence after a 3-week lag, a 10% rise in relative humidity was associated with 40.7% (95% CI: –44.3, –36.9%) decrease in malaria after a 7-week lag, a 1°C increase in the diurnal temperature range was associated with a 24.1% (95% CI: –26.7, –21.4%) decrease in malaria after a 7-week lag, and a 10-hr increase in sunshine per week was associated with a 5.1% (95% CI: –8.4, –1.7%) decrease in malaria after a 2-week lag. The cumulative relative risk for a 10-mm increase in rainfall (≤ 350 mm) on P. vivax malaria was 3.61 (95% CI: 1.69, 7.72) based on a DLNM with a 10-week maximum lag.Conclusions: Our findings suggest that malaria transmission in temperate areas is highly dependent on climate factors. In addition, lagged estimates of the effect of rainfall on malaria are consistent with the time necessary for mosquito development and P. vivax incubation.
The Motorcycle Helmet Law in Taiwan
Authors: Wen-Ta Chiu
Journal: JAMA (1995)

<h3>To the Editor.</h3> —In his Editorial,<sup>1</sup>Dr Martinez provides significant information on injury prevention measures for reducing head injuries caused by the use of motorcycles and bicycles. Actually, most countries, especially developing countries, are still in the dark era of injury prevention. These articles provide excellent injury prevention approaches and suggestions to the world. In the United States, motorcycles account for less than 2% of all motor vehicles, yet they are responsible for 7.8% of motor vehicle—related deaths. In contrast, in Taiwan the number of motorcycles has reached 11 million in a population of 22 million. Motorcycles account for 74% of all motor vehicles, while motorcycle-related deaths have reached 48% of all motor vehicle—related deaths. Therefore, the main concerns of traffic injury prevention in Taiwan are significantly different from those in the United States, with the prevention of motorcycle injury and the implementation of helmet use law being the
DETECTING ACUTE STRESS DISORDERS IN PATIENTS WITH CORONARY ARTERY DISEASE: A PROGNOSTIC EVALUATION OF THE PHQ-9 IN ACUTE CORONARY CARE: FINDINGS FROM THE ISACS-TC STUDY
Authors: Edina Cenko, Zorana Vasiljevic, Jelena Stepanovic, Natasa Mickovski, Olivia Manfrini, Raffaele Bugiardini
Journal: Journal of the American College of Cardiology (2015)
Bilateral Pulsating Exophthalmos Due to Metastases from Carcinoma of Prostate
Authors: P. C. Gautier-Smith
Journal: BMJ (1960)

Bilateral Pulsating Exophthalmos Due to Metastases from Carcinoma of ProstateThe orbit is a rare situation for blood-borne metastases.Only four cases of secondary deposits in the orbit from carcinoma of the prostate have been found in a search of the literature.There is not a single recorded example of pulsating exophthalmos due to metastases from this or any other primary site. CASE REPORTIn November, 1957, the patient, a man of 73, noticed one morning that he was seeing double.The two objects were one above the other when he looked up and side by side when he looked to the right.At about the same time he noticed a humming in both ears, which gradually increased until he said that he could hear a noise like marching feet, which appeared to come from the left side of his head.Shortly afterwards he began to get a deep aching pain in his right leg, left arm, and back, and noticed that his hearing was less good than formerly.He felt perfectly fit in him- self, was eating and sleeping well, and said that he felt like a man of 40.At this time he had no abnormal urinary symptoms at all, but apparently in 1955, following a partial gastrectomy for a peptic ulcer, he developed retention of urine, requiring suprapubic drainage for a short period.At that time his prostate was felt to be enlarged, but there was no evidence of malignancy.He had no recurrence of this trouble subsequently.
Interrelations among children, parents, premedication, and anaesthetists in paediatric day stay surgery.
Authors: N. M. Schofield, J. B. White
Journal: BMJ (1989)

OBJECTIVE--To investigate the incidence of difficulties associated with parental presence during the induction of anaesthesia in children and the influence of premedication with special reference to vomiting after papaveretum. DESIGN--Mixed factual and multiple choice questionnaire completed by medical and nursing staff and parents during and after admission. SETTING--Teaching hospital with regional paediatric general surgical unit where parental presence during induction of anaesthesia is long established. PATIENTS--151 Children aged 1-14 years who had not previously undergone surgery attending with parents for day stay general surgical procedures. INTERVENTION--Children were randomly allocated to receive no premedication (group 1), oral diazepam elixir (0.3 mg/kg) (group 2), or intramuscular papaveretum with hyoscine (0.3 mg/kg with 0.006 mg/kg) (group 3). No other modification to established day stay routine was made. RESULTS--No major problems were associated with the presence of parents during the induction of anaesthesia. Only 10 of the 141 parents who accompanied their child caused some difficulty, and five became distressed. Premedication with both diazepam and papaveretum resulted in sedation but did not ease induction of anaesthesia. Papaveretum greatly reduced pain and distress immediately after the operation, pain and discomfort being observed in only 15% of children (7/48) compared with 66% (27/41) in group 1 and 49% (22/45) in group 2. Papaveretum, however, must be given intramuscularly, and nurses observed that the children preferred being given premedication orally to intramuscularly. In addition, the incidences of nausea and vomiting were significantly higher in the postoperative ward and at home with papaveretum, although no patient who had been given the drug was nauseous or vomited in the recovery area. The incidences of nausea in group 3 were 62% (31/50) and 57% (27/47) in the postoperative ward and at home, respectively, v 21% (7/33) and 14% (4/29) in group 1 and 13% (5/38) and 14% (5/37) in group 2; the incidences of vomiting in group 3 were 60% and 43% in the postoperative ward and at home, respectively, v 18% and 7% in group 1 and 11% and 11% in group 2. Finally, neither the administration or otherwise of premedication nor the drug given affected the children9s or parents9 perception of day care surgery. CONCLUSIONS--Difficulties with parents in anaesthetic rooms were not common or severe. Premedication provides preoperative sedation and papaveretum improves the immediate postoperative course but the incidences of nausea and vomiting after operation are higher with its use than without.
Fulminant hepatic failure in rats: Survival and effect on blood chemistry and liver regeneration
Authors: S Eguchi, A Kamlot, J Ljubimova, W R Hewitt, L T Lebow, A A Demetriou, J Rozga
Journal: Hepatology (1996)

A reproducible experimental animal model of fulminant hepatic failure (FHF) resembling the clinical condition is needed. We have developed such a model in the rat by combining resection of the two anterior liver lobes (68% liver mass) with ligation of the right lobes pedicle (24% liver mass), resulting in liver necrosis; the remaining two omental lobes (8% liver mass) are left intact. Adult Sprague-Dawley rats (250-300 g) were used. Survival time was determined in 60 rats. Because maintenance of body temperature at 37 degrees C shortened survival time by half, FHF rats were not warmed during the postinduction period and were allowed to gradually enter a state of mild to moderate hypothermia (29-32 degrees C). Additionally, 42 FHF rats were killed in batches of six rats each 2, 6, 12, 18, 24, 30, and 36 hours postoperatively to evaluate changes in blood chemistry (glucose, lactate, liver function tests, prothrombin time) and to assess liver regenerative response in the residual omental liver lobes (weight, protein content, incorporation of bromodeoxyuridine [BrdU], expression of proliferation cell nuclear antigen [PCNA], mitotic activity), plasma levels of hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1), and tissue expression of the HGF and it's receptor c-met. Rats undergoing partial hepatectomy of 68% (PH; n = 42) and a sham operation (SO; n = 42) served as controls. All SO and PH controls survived. PH rats showed only transient decreases in body temperature, signs of modest early hepatic dysfunction (hyperlactemia, hyperammonemia, prolonged PT time), and normal restitution of liver mass. All FHF rats became comatose by 24 hours postoperatively. Most animals (90%) died within 24-48 hours postoperatively (mean, 39 +/- 11 hours). Changes in blood chemistry reflected rapid development of liver failure. Plasma HGF levels were markedly elevated and at all time points were higher than in PH controls (P < .05). At the same time, expression of HGF and c-met messenger RNA in the remnant liver was delayed. Plasma TGF-beta1 levels increased early (18 hours) and remained twofold to threefold higher than that of PH and SO controls (P < .05). There was only a 20% increase in the weight of the remnant liver lobes due to swelling. No hepatocytes stained positively for BrdU and PCNA, and none showed mitotic figures. In contrast, all PH controls showed vigorous liver regeneration. In conclusion, we have developed and characterized a novel model of FHF in rats that has a number of physiological and biochemical features seen clinically in FHF, including severely impaired ability of the residual liver tissue to regenerate.