tbuckley/cabot-search huggingface dataset:
Study Criticisms Unjustified
Authors: IS Chart
Journal: Environmental Health Perspectives (2004)

EvidenceThe National Academy of Sciences (NAS) convened a panel of scientists in early 2003 to advise the U.S. Environmental Protection Agency (EPA) on the scientific and ethical issues surrounding the use of toxicologic studies conducted by third parties on human subjects (NAS 2003).These studies are generally sponsored by chemical manufacturers to provide data for setting regulatory standards or for registering chemicals for commercial use.The test substance is frequently a pesticide or industrial chemical with no medicinal value.Studies of the pesticides dichlorvos (DDVP) and aldicarb are illustrative.The sponsors' intent was to force the U.S. EPA to consider these data for setting exposure standards (Mitka 2003).DDVP, an organophosphate pesticide, exerts its toxicity through inhibition of acetyl cholinesterase.Symptoms of poisoning include diarrhea, vomiting, salivation, convulsions, and-in extreme casesdeath.DDVP is widely used in pesticideimpregnated resin strips
Vascular Signal Transducer and Activator of Transcription-3 Promotes Angiogenesis and Neuroplasticity Long-Term After Stroke
Authors: Christian J. Hoffmann, Ulrike Harms, Andre Rex, Frank Szulzewsky, Susanne A. Wolf, Ulrike Grittner, Gisela Lättig-Tünnemann, Michael Sendtner, Helmut Kettenmann, Ulrich Dirnagl, Matthias Endres, Christoph Harms
Journal: Circulation (2015)

Poststroke angiogenesis contributes to long-term recovery after stroke. Signal transducer and activator of transcription-3 (Stat3) is a key regulator for various inflammatory signals and angiogenesis. It was the aim of this study to determine its function in poststroke outcome.We generated a tamoxifen-inducible and endothelial-specific Stat3 knockout mouse model by crossbreeding Stat3(floxed/KO) and Tie2-Cre(ERT2) mice. Cerebral ischemia was induced by 30 minutes of middle cerebral artery occlusion. We demonstrated that endothelial Stat3 ablation did not alter lesion size 2 days after ischemia but did worsen functional outcome at 14 days and increase lesion size at 28 days. At this late time point vascular Stat3 expression and phosphorylation were still increased in wild-type mice. Gene array analysis of a CD31-enriched cell population of the neurovascular niche showed that endothelial Stat3 ablation led to a shift toward an antiangiogenic and axon growth-inhibiting micromilieu after stroke, with an increased expression of Adamts9. Remodeling and glycosylation of the extracellular matrix and microglia proliferation were increased, whereas angiogenesis was reduced.Endothelial Stat3 regulates angiogenesis, axon growth, and extracellular matrix remodeling and is essential for long-term recovery after stroke. It might serve as a potent target for stroke treatment after the acute phase by fostering angiogenesis and neuroregeneration.
Occupational Asthma Caused by Isocyanates
Authors: JEAN-LUC MALO, HEBERTO GHEZZO, ROBERT ÉLIE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Inhalation challenges to isocyanates are conducted in specialized centers to confirm occupational asthma. The pattern of asthmatic reactions due to consecutively increasing daily doses of isocyanates is unknown. We conducted a study involving 24 subjects who had undergone specific inhalation challenges to isocyanates (toluene diisocyanate [TDI], n = 8; hexamethylene diisocyanate [HDI], n = 10; and methylene diisocyanate [MDI], n = 6) on three or more consecutive days. Challenge tests were given through a closed-circuit apparatus (n = 12) or in small cubicles (n = 12), allowing assessment of the total inhaled dose (concentration x duration). The pattern of asthmatic reactions was described. In addition, dose-response curves were analyzed and tested for their linear and quadratic trends. Four patterns of response were observed: (1) linear (n = 10); (2) minimal effect followed by a brisk change (n = 7); (3) significant change followed by tachyphylaxis or a plateau (n = 4); (4) biphasic (i.e., significant change followed by a reduction in the effect and significant change on the last day of exposure [n = 3]). Subjects with a linear dose-response pattern had been exposed to isocyanates at work for a significantly shorter interval (7.2 +/- 6.7 yr) than subjects with a nonlinear pattern (20.0 +/- 13.1 yr). An analysis of variance covering a 3-d period for all subjects showed a significant linear model for the response (p < 0.0001); there was no quadratic trend. However, when the analysis was done on subjects with four or more days of challenge (n = 10), we found both linear and quadratic significant components. This analysis shows that the most common pattern of asthmatic reactions to inhaled isocyanates generated on consecutive days is linear; however, other patterns are also observed. In some individuals, particularly those in whom more days of challenge are required, we observed in addition to a strong linear component a quadratic component manifested by a brisk change on the last day of exposure.
Studies on the Relations Between Virus Release and Cellular Immunosensitivity in Moloney Lymphomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Eva M. Fenyö, Peter Biberfeld, Eva Klein
Journal: JNCI Journal of the National Cancer Institute (1969)

The immunoresistant subline (YAC-IR) of the immunosensitive Moloney lymphoma YAC is characterized by a tenfold decrease in the Moloney-specific cell-surface antigen concentration. These cells resist the cytotoxic action of Moloney-specific antiserum. Electron microscopic comparison revealed that YAC-IR cells have about one-tenth of the budding and extracellular type-C particles seen in YAC cells. The number of intracisternal type-A particles did not differ significantly. The difference in the number of C particles was reflected in the striking difference of the virus content in the culture media when the cells were incubated for short periods in vitro. However, like previous findings on the two lines, after inoculation of whole, irradiated cells into newborn mice, leukemogenic activity was identical and so was the ability to elicit an antibody response in adult mice. After three passages through hosts neonatally infected with the virus derived from YAC cells, the YAC-IR line became sensitive to the cytotoxic action of specific antiserum. However, when this line was passed in hosts infected with virus derived from YAC-IR cells, resistance to cytotoxicity by specific antiserum did not change.
Reduction in the rate of methicillin-resistant Staphylococcus aureus acquisition in surgical wards by rapid screening for colonization: a prospective, cross-over study
Authors: Katherine Hardy, Charlotte Price, Ala Szczepura, Savita Gossain, Ruth Davies, Nigel Stallard, Sahida Shabir, Claire McMurray, Andrew Bradbury, Peter M Hawkey
Journal: Clinical Microbiology and Infection (2009)
O148 Shiga toxin-producing Escherichia coli outbreak: microbiological investigation as a useful complement to epidemiological investigation
Authors: E. Espié, F. Grimont, V. Vaillant, M.P. Montet, I. Carle, C. Bavai, H. de Valk, C. Vernozy-Rozand
Journal: Clinical Microbiology and Infection (2006)
Assessment of pulmonary hypertension in patients over 70
Authors: Christopher Valerio, Benjamin Schreiber, Clive Handler, Christopher Denton, John Coghlan
Journal: European Respiratory Journal (2012)

Background  Recent registry data suggests that the average age of patients with PAH is rising. Pulmonary hypertension affects elderly people and there is increasing prevalence of cardiac and respiratory disease with age.  Methods  We report the findings for 120 consecutive patients aged over 70 referred to a tertiary service during 2008-09 for invasive haemodynamic studies to confirm or exclude a diagnosis of pulmonary hypertension.  Results  Four patients died within 30 days of referral and before being assessed, 15 patients did not undergo cardiac catheterisation. 50% of those assessed had an associated connective tissue disease. 36 patients had resting pulmonary artery pressures   Conclusion  Pulmonary hypertension of all types may be present in older patients. Thorough assessment may provide insight into the drivers of symptoms in older patients and help to guide treatment, which can be successful.
Overview of Current Knowledge of Metabolism of Vitamin A and Carotenoids&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Dewitt S. Goodman
Journal: JNCI Journal of the National Cancer Institute (1984)

Current knowledge about the metabolism of naturally occurring retinoids and carotenoids was summarized. Dietary provitamin A carotenoids are largely converted to retinol (vitamin A) during intestinal absorption in the mucosal cell. In humans, a limited amount of carotenoids can be absorbed intact, along with retinyl esters (newly synthesized or from dietary vitamin A), mainly via lymph chylomicrons. Carotenoids are stored in several tissues, particularly liver and fat. They are transported in plasma by lipoproteins (density less than 1.21 g/ml), particularly by the low-density lipoproteins. Plasma carotenoids are usually a mixture of compounds with and without provitamin A activity; beta-carotene is about 20-25% of the total. Newly absorbed vitamin A is stored in the liver as retinyl esters. Storage involves both the hepatic parenchymal cells and the nonparenchymal stellate cells. Vitamin A is mobilized from liver stores and transported in plasma as retinol bound to a specific transport protein, retinol-binding protein (RBP). Retinol mobilization is highly regulated by factors that control the rates of RBP synthesis and secretion. Much is known now about the chemical structure, metabolism, and biologic roles of RBP, RBP delivers retinol to peripheral target tissues; delivery may involve cell surface receptors for RBP. Tissues of rats, humans, and other species contain soluble binding proteins with specificity for either retinol (cellular retinol-binding protein) or retinoic acid (cellular retinoic acid-binding protein). These intracellular proteins have been purified from several tissues and partly characterized. From both immunoassay and immunocytochemical studies, information is available about their tissue distribution and levels. Retinoic acid is mainly absorbed through the portal system and transported in plasma as the anion bound to serum albumin. Nonspecific and unregulated delivery of retinoids to biologic membranes apparently leads to vitamin A (retinoid) toxicity.
Reduced grip strength is related to frequency of exacerbations and lower health status in COPD
Authors: Khalid Ansari, Joan Munby, Graham Burn, Ian Taylor, Andrea Kay, Malcolm Farrow, Niall Keaney
Journal: European Respiratory Journal (2011)

Muscle weakness is a feature of COPD that affects quality of life. Systemic inflammation, an accompaniment of acute exacerbations, has been implicated in its aetiology. Recurrent exacerbations are also associated with lowered health status. This study examines the relationship between muscle weakness, health status and exacerbation frequency in a cohort of patients with COPD.  This is an observational study of 188 (95 female) COPD patients attending two hospital clinics in the North –East of England. We recorded spirometry, health status (SGRQ), grip strength (Jamar), MRC dyspnoea score and the reported frequency of exacerbations in the previous year.  Patients were aged 72.5±8.3 years with MRC score of 3.6±0.8, FEV1 of 49.2±21.5 percent predicted and a total SGRQ score of 72.2±15.5. Grip strength, expressed as percent predicted, was 72.0±21.8 in men and 81.0±18.2 in women (mean ± SD). Exacerbations ranged from zero to five in the previous year and there were associations of reduced grip strength with exacerbation frequency (χ2 = 9.63; p = 0.0019) and lower health status (χ2 = 34.0; p   Conclusion: Our data clearly demonstrate that reduction in grip strength is greater in patients with a history of frequent exacerbations and is associated with reduced health status.
Hormone-Dependent Accumulation of Rough Endoplasmic Reticulum in Mouse Mammary Epithelial Cells &lt;italic&gt;In Vitro&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: Takami Oka, Yale J. Topper
Journal: JNCI Journal of the National Cancer Institute (1972)

The accumulation of rough endoplasmic reticulum (RER) in hormone-dependent differentiation of mammary glands was studied in vitro. The minimal hormone requirements for RER accumulation were insulin and corticosteroid. Several lines of evidence strongly suggested that casein formation by mammary epithelial cells depended on the presence of insulin- hydrocortisone-induced RER.
Abstract 4225: Periadventitial Adipose Tissue Inflammation Assessed By 64-slice Computed Tomography Is Associated With Coronary Artery Atherosclerosis
Authors: masaaki konishi, Seigo Sugiyama, Takeshi Nakaura, Kazuo Awai, Yasuyuki Yamashita, Yasuo Nagayoshi, Hitoshi Sumida, Yasushi Matsuzawa, Shinichi Hirota, Keisuke Ohba, Jun-ichi Matsubara, Kouichi Sugamura, Toshimitsu Nozaki, Kazuo Kimura, Satoshi Umemura, Hisao Ogawa
Journal: Circulation (2008)

Background It has become increasingly evident that adipose tissue is a multifunctional organ that produces and secretes various paracrine and endocrine factors. Periadventitial cardiac adipose tissue (PCAT), which exists closely around coronary arteries, is now recognized as a rich source of a number of bioactive molecules. There have been some reports that highlight local chronic inflammation of PCAT as a potential contributing factor to the pathogenesis of coronary artery disease (CAD) and adipose tissue with inflammation is known to have high density in computed tomography (CT). We assessed CT density of adipose tissues to evaluate the inflammatory activity and investigated the association between PCAT inflammation and CAD. Methods and results We assessed the CT density of periadventitial adipose tissues in consecutive 69 patients suspected of CAD ( 51% men, 65 ± 11 years) using 64-slice CT. By using the image scanned for coronary CT angiography, adipose tissue and presence of CAD (&gt;75% organic stenosis) were confirmed in the same scan. We measured CT density of PCAT around the proximal right coronary artery (Coronary-PCAT), pericardial fat apart from coronary arteries (between ascending and descending aorta as the control site; Cont-PCAT), and thoracic subcutaneous fat. In each of these sites, the CT density measurements in two or more regions of interest were randomly performed and the mean value was recorded. The mean of CT density was −81 ± 11 Hounsfield Unit (HU) in Coronary-PCAT, −99±11HU in Cont-PCAT, −103±7HU in the subcutaneous fat, which were significantly different values (p &lt; 0.01). The difference of CT density between Coronary-PCAT and the Cont-PCAT was significantly greater in patients with CAD (n = 30) than those without CAD (n=39) (22±16 versus 16±10 HU, p &lt; 0.05) but the difference between Cont-PCAT and subcutaneous fat was not related to the presence of CAD (6 ± 12 versus 3 ± 14 HU, p = 0.22). Conclusions Coronary-PCAT had significantly higher CT density than the Cont-PCAT and subcutaneous fat. The difference of CT density between Coronary-PCAT and Cont-PCAT was significantly greater in patients with CAD than non-CAD patients. The inflammatory actively of local PCAT rather than whole pericardial fat may implicate in the development of CAD.
Reduced expression of plakoglobin indicates an unfavorable prognosis in subsets of patients with non-small-cell lung cancer.
Authors: K Pantel, B Passlick, J Vogt, P Stosiek, M Angstwurm, R Seen-Hibler, K Häussinger, O Thetter, J R Izbicki, G Riethmüller
Journal: Journal of Clinical Oncology (1998)

PURPOSE Plakoglobin is thought to play a key role in cadherin-mediated epithelial cell adhesion, because it is a common component of desmosomal and nondesmosomal adherens junctions. Because loss of homotypic cell adhesion is an important early step in invasion and metastasis of solid tumors, we evaluated the frequency and prognostic significance of a deficient expression of plakoglobin in human lung cancer. PATIENTS AND METHODS At primary surgery, representative specimens of the primary tumor were obtained from 96 consecutive patients with completely resected non-small-cell lung carcinoma (NSCLC) without overt distant metastases. Cryostat sections of these specimens and metastatic lymph nodes were stained with monoclonal antibody (mAb) PG 5.1 against plakoglobin, using an immunoperoxidase technique. Patients were monitored for a median of 39 months (range, 12 to 56) after surgery. RESULTS Absent or severely reduced expression of plakoglobin (ie, &lt; 30% positive tumor cells) was observed in 39 patients (40.6%). There was no significant correlation to established risk factors, such as the histology, extension, and histologic grade of the primary tumor and metastatic lymph node involvement, or expression of alpha-catenin. Expression of plakoglobin in lymph node metastases ranged from 0% to greater than 60% positive tumor cells. Deficient plakoglobin expression on the primary tumor was significantly correlated to a shortened disease-free and overall survival in patients with adenocarcinomas, pT1-2 tumors, or negative lymph nodes (pN0). In patients with pT1-2 tumors, the independence of this prognostic influence from established risk factors was demonstrated by Cox regression analyses (disease-free survival, P = .002; overall survival, P = .038). CONCLUSION Deficient expression of plakoglobin appears to be an important event in the progression of NSCLC.
Pancreatic pseudocyst drainage by endoscopic sphincterotomy
Authors: Mokthar Uheba, Sukhpal Singh, Lain M Paterson
Journal: Journal of the Royal Society of Medicine (1999)

A man aged 50 was admitted with acute pancreatitis. Ultrasound examination revealed no gallstones or duct dilatation but suggested polyps in the gallbladder. He improved with conservative management. Sixteen days after discharge he was readmitted with further abdominal pain and a raised serum amylase. On this admission a computed tomographic (CT) scan showed a 2 cm fluid collection in the lesser sac. Again the symptoms resolved with conservative treatment and he was discharged, but required readmission three days later. On this occasion the serum amylase was only slightly raised, and there were signs of generalized peritonitis. At laparotomy he was found to have a ruptured pseudocyst. Cholecystectomy was performed because the gallbladder wall was thickened and there was a suspicion of stones, and a drain was inserted into the cyst cavity. On the eighth postoperative day a sinogram revealed a residual 2 x 2 cm cavity. The drain was removed and he was discharged home symptom-free, but four days later he was again readmitted with severe abdominal pain. A CT scan showed an 8 x 8 cm unilocular pseudocyst, and endoscopic retrograde pancreatography revealed a normal duct communicating with the pseudocyst. A sphincterotomy was performed, since we reasoned that a reduction in pressure in the ductal system might allow the cyst to decompress; and immediately afterwards the patient's symptoms dramatically resolved. A subsequent CT scan indicated complete resolution of the pseudocyst and the patient has been painfree and well for 48 months since the sphincterotomy. COMMENT
Altered Immunologic Responsiveness in Mastocytoma-Bearing Mice2
Authors: Isao Kamo, Chandu Patel, Herman Friedman
Journal: JNCI Journal of the National Cancer Institute (1976)

Immune responses to sheep erythrocytes were enhanced in mice bearing small mastocytomas soon after injection of a few tumor cells. In contrast, mice with larger tumors after transfer of a greater number of mastocytoma cells and those in the later stages of tumor development after transfer of small numbers of tumor cells showed moderately suppressed immune responses. Transfer of spleen cells from mastocytoma-bearing mice to irradiated recipients resulted in more antibody-forming cells as compared to transfer of splenocytes from normal donor mice. The addition of graded numbers of mastocytoma cells to a constant amount of normal spleen cells transferred to irradiated mice also resulted in enhanced responses and increased spleen weights in the recipients. This increase, in direct proportion to the number of mastocytoma cells transferred, also occurred when Escherichia coli lipopolysaccharide (a T-cell independent antigen) was used to immunize animals given spleen cells from normal mice and mastocytoma cells. Mastocytoma cell-free homogenates or X-irradiated tumor cells also heightened immune responses in recipient mice, which indicated that viable cells were not needed for the effect. Such homogenates, as well as the tumor cells per se, stimulated increased lactate dehydrogenase (LDH) activity in the sera of recipient mice. However, tumor cells passaged in tissue culture for several months, those derived from mice bearing a mastocytoma cell line with a low LDH-stimulatory activity, or UV-irradiated mastocytoma cells with a high LDH-stimulatory activity did not induce enhanced plaque-forming cell responses.
Looking back over 20 years of sports medicine prevention and treatment: progress, but still a lot to achieve
Authors: Mats Börjesson, Magnus Forssblad, Jón Karlsson
Journal: British Journal of Sports Medicine (2015)

Looking back over the past 20–25 years of taking care of athletes at all levels, we can appreciate substantial improvements. In most cases during this period, the injured athlete returned to sports activity; previously, sports-related injuries were often career-ending.

Credit is due in part to the work of sports traumatologists, pioneers within modern orthopaedics. Mini-invasive surgery, especially arthroscopic techniques, have considerably reduced surgical morbidity. From what previously required an open wound 10–25 cm long, ACL reconstruction is now performed through 2 or 3 stab wounds, 5 mm in size. This means shorter surgical times, shorter hospital stay and improved patient-rated outcomes.

Similarly, sports cardiology has developed and now offers team physicians and athletes preventive measures (cardiac screening, superior ECG interpretation recommendations1) as well as improved safety at sports events (automated external defibrillators).

Despite the above achievements, we see room for further improvement in at least four areas.

1.  Prevention programmes need better implementation.
        Ten to 15 years ago, prevention …