tbuckley/cabot-search huggingface dataset:
Release of vasodilator prostaglandin, PGI2, from isolated rat lung during vasoconstriction.
Authors: N F Voelkel, J G Gerber, I F McMurtry, A S Nies, J T Reeves
Journal: Circulation Research (1981)

Prostaglandins are generated by the lungs and released into the circulation. Since inhibitors of prostaglandin synthesis enhance hypoxic pulmonary vasoconstriction, we wondered whether vasodilator prostacyclin was synthesized by the lungs in response to vasoconstriction. To test this hypothesis, we measured vasoconstriction induced by angiotensin II in isolated rat lungs before and after inhibition of prostaglandin synthetase. We found that sodium meclofenamate enhanced and prostacyclin and its precursor arachidonate abolished pulmonary vasoconstriction. In lungs labeled with 14C-arachidonate, effluent radioactivity increased after angiotensin II-induced vasoconstriction. Hypoxic vasoconstriction, but not hypoxia per se, caused an increase in lung effluent radioactivity. Chromatographic analysis of lung effluent showed that 6-keto-prostaglandin F1 alpha was the major arachidonic acid metabolite released during pulmonary vasoconstriction. We concluded that prostacyclin is produced by the lungs in response to vasoconstriction. Hypoxia per se seems not to be the adequate stimulus for enhanced lung prostacyclin formation. Lung prostacyclin may protect the pulmonary circulation against excessive vasoconstriction.
Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines
Authors: S Yokota, H Kiyoi, M Nakao, T Iwai, S Misawa, T Okuda, Y Sonoda, T Abe, K Kahsima, Y Matsuo, T Naoe
Journal: Leukemia (1997)
Breakfast and Crohn's disease.
Authors: A H James
Journal: BMJ (1977)

The breakfast habits in adult life of 34 patients with Crohns disease were compared with those of 68 matched controls. Cornflakes were being eaten at least weekly by 23 of the patients (67--6%) at the time that their symptoms began, compared with 17 (25%) of the controls at the corresponding time. Only one of the 34 patients had not eaten cornflakes at all, compared with half of the controls. A significant but weaker association was found between Crohn's disease and the eating of wheat cereals. However, in both patients and controls the taking of cornflakes and of wheat cereals were correlated, and the observed preponderance of wheat eating among the patients was almost entirely ascribable to this association of habits. Eating of rice cereals and of porridge was not associated with Crohn's disease, though it was correlated with eating cornflakes. There was an excess of bran eaters among the propositi, but this, too, was attributable to their being also cornflake eaters. Other breakfast foods were taken with equal frequency, and omission of breakfast was equally common. Six of the 68 controls, but none of the patients, ate cornflakes later in the day but not at breakfast. The results need confirmation. There was no evidence that bias could have caused the correlation found. The association of Crohn's disease with the eating of cornflakes is strong and unlikely to be indirect. Variable digestive secretory behaviour after waking may play a part in determining susceptibility to Crohn's disease.
Chronic Social Stress and Susceptibility to Concentrated Ambient Fine Particles in Rats
Authors: Jane E. Clougherty, Christina A. Rossi, Joy Lawrence, Mark S. Long, Edgar A. Diaz, Robert H. Lim, Bruce McEwen, Petros Koutrakis, John J. Godleski
Journal: Environmental Health Perspectives (2010)

Epidemiologic evidence suggests that chronic stress may alter susceptibility to air pollution. However, persistent spatial confounding between these exposures may limit the utility of epidemiologic methods to disentangle these effects and cannot identify physiologic mechanisms for potential differential susceptibilities.Using a rat model of social stress, we compared respiratory responses to fine concentrated ambient particles (CAPs) and examined biological markers of inflammation.Twenty-four 12-week-old male Sprague-Dawley rats were randomly assigned to four groups [stress/CAPs, stress/filtered air (FA), nonstress/CAPs, nonstress/FA]. Stress-group animals were individually introduced into the home cage of a dominant male twice weekly. Blood drawn at sacrifice was analyzed for immune and inflammatory markers. CAPs were generated using the Harvard ambient particle concentrator, which draws real-time urban ambient fine particles, enriching concentrations approximately 30 times. CAPs/FA exposures were delivered in single-animal plethysmographs, 5 hr/day for 10 days, and respiratory function was continuously monitored using a Buxco system.Stressed animals displayed higher average C-reactive protein, tumor necrosis factor-alpha, and white blood cell counts than did nonstressed animals. Only among stressed animals were CAPs exposures associated with increased respiratory frequency, lower flows, and lower volumes, suggesting a rapid, shallow breathing pattern. Conversely, in animals with elevated CAPs exposures alone, we observed increased inspiratory flows and greater minute volumes (volume of air inhaled or exhaled per minute).CAPs effects on respiratory measures differed significantly, and substantively, by stress group. Higher CAPs exposures were associated with a rapid, shallow breathing pattern only under chronic stress. Blood measures provided evidence of inflammatory responses. Results support epidemiologic findings that chronic stress may alter respiratory response to air pollution and may help elucidate pathways for differential susceptibility.
Respiratory Syncytial Virus Bronchiolitis in Infancy Is an Important Risk Factor for Asthma and Allergy at Age 7
Authors: NELE SIGURS, RAGNAR BJARNASON, FRIDRIK SIGURBERGSSON, BENGT KJELLMAN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We previously reported an increased risk for bronchial obstructive disease and allergic sensitization up to age 3 in 47 children hospitalized with a respiratory syncytial virus (RSV) bronchiolitis in infancy compared with 93 matched control subjects recruited during infancy. The aims of the present study were to evaluate the occurrences of bronchial obstructive disease and allergic sensitization in these children at age 7(1)/ (2). All 140 children reported for the follow-up, which included physical examination, skin prick tests, and serum IgE tests for common food and inhaled allergens. The cumulative prevalence of asthma was 30% in the RSV group and 3% in the control group (p < 0.001), and the cumulative prevalence of "any wheezing" was 68% and 34%, respectively (p < 0.001). Asthma during the year prior to follow-up was seen in 23% of the RSV children and 2% in the control subjects (p < 0.001). Allergic sensitization was found in 41% of the RSV children and 22% of the control subjects (p = 0.039). Multivariate evaluation of possible risk factors for asthma and sensitization using a stepwise logistic statistical procedure for all 140 children showed that RSV bronchiolitis had the highest independent risk ratio for asthma (OR: 12.7, 95% CI 3.4 to 47.1) and a significantly elevated independent risk ratio for allergic sensitization (OR: 2.4, 95% CI 1.1 to 5.5). In conclusion, RSV bronchiolitis in infancy severe enough to cause hospitalization was highly associatied with the development of asthma and allergic sensitization up to age 7(1)/ (2). The results support the theory that the RSV influences the mechanisms involved in the development of asthma and allergy in children.
Abstract LB-488: Induction of autophagy by heat shock factor 1 promotes breast cancer resistance to chemotherapy
Authors: Shruti Desai, Zixing Liu, Oystein Fodstad, Ming Tan
Journal: Cancer Research (2012)

Abstract Breast cancer is the most common type of cancer as well as one of the leading causes of cancer-related deaths in women. The increasing emergence of drug resistance to commonly used chemotherapeutic agents has warranted the development of novel and robust treatment options for cancer patients. Carboplatin, a DNA damaging agent, is one of the therapeutic agents which has shown promising results in breast cancer clinical trials. Carboplatin is a second generation platinum drug, increasingly used in clinic to treat cancer patients because of its reduced toxicity and side effects when compared to Cisplatin. Heat Shock Factor 1 (HSF1) is the master regulator of heat shock responses which has also been shown to regulate certain non-heat shock reponse genes. As a transcription factor HSF1 can function as both an activator and repressor of its target genes, resulting in regulation of critical cellular processes invovled in managing cellular stress. The focus of this study is to identify the role of HSF1 in Carboplatin mediated-sensitivity in breast cancer cells, to provide novel insights to improve treatment strategies for cancer patients. Carboplatin treatment in multiple breast cancer cell lines induced growth inhibition which was significantly enhanced upon HSF1 knockdown. Interestingly, the treatment also induced autophagy in these cells. Autophagy is a type II programmed cell death, which is induced in response to metabolic stress and has been demonstrated to mediate drug resistance, since it can play a protective role and allow cells to survive under stressful conditions. Knockdown of HSF1 along with inhibition of autophagy by 3-Methyladenine (3-MA) led to increase in apoptosis in these cells. Furthermore, HSF1 was required for the induction of autophagy in Carboplatin treated cells. Knockdown of HSF1 by siRNA (transient) and shRNA (stable), inhibited induction of autophagy in the presence of Carboplatin, as measured by the punctate EGFP-LC3 structures as well as acridine orange staining. Chromatin immunoprecipitation (ChIP) assay along with Real time- PCR analysis revealed that HSF1 can regulate autophagy by directly regulating the expression of autophagy related genes in the presence of Carboplatin. These findings indicate that HSF1 activates autophagy in response to the Carboplatin induced cellular stress thus leading to cell survival and reducing sensitivity to Carboplatin. Our data strongly support a critical role for HSF1 in promoting chemoresistance through induction of autophgy. This finding has important implications in the development of targeted therapeutics for overcoming Carboplatin resistance in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-488. doi:1538-7445.AM2012-LB-488
Tumor Embolism to Coronary Artery After Pneumonectomy
Authors: Gabriel Haiby
Journal: JAMA (1965)

EMBOLISM of the coronary arteries is a rather rare cause of coronary occlusion. Almost all of these cases reported have been spontaneous embolism. The occurrence of embolism as a complication of pulmonary resection is very rare. In the only other previously noted case that we know of, the embolus originated in a thrombus at the ligated stump of the pulmonary vein.' In our patient, the embolus was composed of tumor, and occurred after pulmonary resection of adenocarcinoma. <h3>Report of a Case</h3> A 60-year-old white man noted shortness of breath in October 1962. The chest x-ray at that time showed a lesion in the apex of the left lung. The patient did not return for follow-up studies. In August 1963 hemoptysis developed, and the patient was admitted to this hospital. On physical examination, the left upper part of the chest was dull to percussion, and breath sounds were absent. The heart
Abstract 1330: Immunotherapy targeting folate receptor induces autophagy in ovarian cancer
Authors: Yun-Fei Wen, Whitney Spannuth Graybill, Anil Sood
Journal: Cancer Research (2014)

Abstract Objective Cancer cells are highly dependent on folate metabolism for replication of DNA, making these cells susceptible to drugs that inhibit folate metabolism. Herein, we investigated the functional mechanism underlying blockade of folate receptor (FR) in human ovarian cancer with MORAb-003 antibody, a humanized monoclonal antibody directly against folate receptor 1 (FRα). Methods We first used FACS analysis and real-time PCR to compare the expression of FRα in several human ovarian cancer cells. We then examined the tumor growth in the orthotopic models of human ovarian cancer cells SKOV3 and A2780. Consequently, we performed in vitro genomic and proteomic profiling in these cells to identify the functional mechanism of MORAb-003. Results Among 7 human ovarian cancer cell lines, SKOV3ip1 cells have the highest levels of FRα and A2780 cells have the lowest. In vivo, MORAb-003 monotherapy led to significantly decreased tumor growth in the SKOV3ip1 model, but not in the A2780 model. Combination of MORAb-003 and docetaxel resulted in significantly greater reduction in tumor growth in the SKOV3ip1 model, but not in the A2780 model. MORAb-003 reduced proliferation but had no significant effect on apoptosis. Reverse-phase array analysis in SKOV3 cells revealed MORAb-003 up-regulated autophagic factors including PEA-15, Beclin-1, and ATG3 and down-regulated mTOR. cDNA microarray further showed that MORAb-003 up-regulated the expression of BECN1, ATG8, ATG3 and LC3B. Levels of Beclin-1 and LC3B were substantially increased in SKOV3 tumors treated with MORAb-003 alone or in combination with docetaxel, but not in A2780 tumors. Using FACS analysis with acridine orange (AO) staining, we observed significantly more AO positive population in SKOV3 cells treated with MORAb-003 alone (16.9%) or MORAb-003+docetaxel (21.2%) than in cells treated with control IgG (5.24%). Such differences were not observed in A2780 cells. Finally, we measured conversion of LC3 from isoform I to isoform II in cells treated with MORAb-003, and observed the significantly increased LC3II in SKOV3 cells but not in A2780 cells. Conclusion Taken together, our results indicate that MORAb-003 results in prominent anti-tumor activity through inducing sustained autophagy in ovarian cancer cells. Citation Format: Yun-Fei Wen, Whitney Spannuth Graybill, Department of Gyneocologic Oncology, Anil Sood. Immunotherapy targeting folate receptor induces autophagy in ovarian cancer. [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 1330. doi:10.1158/1538-7445.AM2014-1330
Case of chronic fatigue syndrome after Crimean war and Indian mutiny
Authors: E. Jones, S. Wessely
Journal: BMJ (1999)

Chronic fatigue syndrome was first proposed as a diagnostic label in 1988 to classify a disorder characterised by severe fatigue and exhaustion after minimal physical and mental effort accompanied by other unexplained somatic symptoms.1 It was introduced partly as an acceptable clinical alternative to the term myalgic encephalomyelitis, which described a similar presentation and had been coined in 1956 in the aftermath of an outbreak of illness among the nursing and medical staff of the Royal Free Hospital.2 The condition was widely assumed to be a new addition to the medical scene. In the popular press, and occasionally in the professional publications, attempts have been made to explain chronic fatigue syndrome as a product of the unwelcome features of modern life, such as pollution, stress, working practices, and new infections.

Attention has recently been drawn to the often striking similarities between chronic fatigue syndrome and myalgic encephalomyelitis and the condition formerly known as neurasthenia, a term first coined independently in 1869 by the neurologist George Beard and psychiatrist E Van Deusen.3 Like its modern variants, neurasthenia was believed to be a physical disorder, largely caused or aggravated by “the selfishness and luxury of modern life, the restlessness and the craving for excitement, the frantic speeding about in motors” and other features of industrial society.4 In this article, we suggest that conditions resembling either chronic fatigue syndrome or neurasthenia have an even older provenance, and draw attention to the cases of two British soldiers who served in the Crimean war and in India at the time of the mutiny.

#### Summary points

Chronic fatigue syndromes existed before the description of neurasthenia in 1869

These syndromes are not limited to the civilian population but occur in the military as well

Soldiers awarded a pension as a result of fatigue syndromes continued …
Postoperative Changes in the Electrocardiogram in Congenital Heart Disease
Authors: BERNHARD LANDTMAN
Journal: Circulation (1954)

Electrocardiograms of 41 cases of coarctation and of 73 cases of patent ductus arteriosus were analyzed before and after surgical correction of the defect. The changes in the electrocardiogram which occurred after surgical repair of the coarctation were considered to be due to the diminished load on the left ventricle. In 65 of the cases of patent ductus arteriosus, electrocardiographic signs of left ventricular hypertrophy were recorded. Eight patients, seven of whom presented atypical murmurs, showed evidence of right ventricular or combined ventricular hypertrophy. Following ligation of the ductus, the electrocardiogram became normal in the majority of the cases.
Medical Education in Facilities for the Elderly
Authors: James O. Woolliscroft, Judith G. Calhoun, Bruce R. Maxim, Fredric M. Wolf
Journal: JAMA (1984)

The development of positive attitudes toward elderly patients has been identified as being an important factor in providing quality geriatric care. Medical students (N = 234) interviewed elderly individuals in three types of facilities, ranging from independent apartment living to nursing homes, as part of a required medical interviewing course. The students' attitudes were measured by an Attitudes Toward the Elderly scale before and after this course. Analyses disclosed significant posttest improvement in students' attitudes concerning the functioning, integrity, and personal acceptability of the elderly at all sites, except for attitudes toward functioning at nursing home sites. Staff and residents of participating facilities rated the experience favorably. This study shows that students' attitudes toward the elderly can be positively changed through incorporation of training at appropriate community facilities for the elderly into existing curricula.
Survival in patients undergoing transjugular intrahepatic portosystemic shunt: ePTFE-covered stentgrafts versus bare stents
Authors: Bernhard Angermayr, Manfred Cejna, Franz Koenig, Franz Karnel, Franz Hackl, Alfred Gangl, Markus Peck-Radosavljevic
Journal: Hepatology (2003)

In patients with liver cirrhosis, implantation of a transjugular intrahepatic shunt (TIPS) leads to reduction of portal pressure, but not of mortality compared with other therapies. The high stenosis rates of conventional bare stents causes high reintervention rates and costs and may be correlated with poor survival. ePTFE–covered stentgrafts provide much improved patency rates, but their impact on survival is unclear. All suitable patients receiving either bare TIPS (419/466) or undergoing implantation of ePTFE endoprostheses (89/100) in several centers in Austria up to 2002 were included in this retrospective analysis. Both patient groups were compared regarding survival with Kaplan–Meier and Cox regression analysis. Unmatched and 1:1–matched survival analyses were performed. Patients undergoing ePTFE stentgraft implantation had significantly higher survival rates in all analyses. The 3–month, 1–year, and 2–year survival rates were 93%, 88%, and 76% for the ePTFE–group and 83%, 73%, and 62% for conventional TIPS patients, respectively. The matched survival analyses validated these findings. The model of the stent, patient age, and Child–Pugh Class (CPC) were independent predictors of survival. In conclusion, patients undergoing ePTFE–endoprosthesis implantation had higher survival rates within 2 years after TIPS–implantation. This may be the result of improved patency rates after correct placement (up to the inferior caval vein [ICV]) of the ePTFE stentgraft. These data should be validated in a prospective series. (Hepatology 2003;38:1043-1050).
Toxicology of octabromobiphenyl and decabromodiphenyl oxide.
Authors: J M Norris, R J Kociba, B A Schwetz, J Q Rose, C G Humiston, G L Jewett, P J Gehring, J B Mailhes
Journal: Environmental Health Perspectives (1975)

Decabromodiphenyl oxide (DBDPO) and octabromobiphenyl (OBBP) perform well as fire-retardant additives for thermoplastics. Both compounds have low acute oral toxicity and low skin absorption toxicity. They are neither primary skin irritants or skin sensitizers and are only mildly irritating to the eyes. A 30-day dietary feeding study in rats established 8 mg DBDPO/kg-day as an unequivocal no-effect level and 80 mg/kg-day as a marginal effect level. A no-effect level was not established for OBBP in a comparative study. A 2-yr rat study providing 0.1 mg DBDPO/kg-day in the diet revealed the bromine concentration reached a plateau in the liver within 30 days, while the concentration in adipose tissue slowly increased. A comparable OBBP study revealed bromine concentration in the liver and adipose tissue increased steadily and rapidly with no attainment of a plateau during 180 days of the study. Neither compound produced an accumulation of bromine in other tissues. After administration of 14C DBDPO, all 14C activity was eliminated via the feces within 2 days. After administration of 14C OBBP, 62% was eliminated with a half-life of less than 24 hr; the half-life for the remainder was greater than 16 days. In a teratology study, 10, 100, or 1000 mg DBDPO/kg-day had no effect in rats. Reproductive capacity of rats was not effected at 3, 30, or 100 mg DBDPO/kg-day. No effects were observed on cytogenetic examination of bone marrow cells of parents and weanlings from the reproduction study.
News embargoes--in whose interest?
Authors: J. Roberts
Journal: BMJ (1994)

In the US viewers know that it is Wednesday when they turn on the television evening news: Wednesday is New England Journal of Medicine day, and virtually no week passes without some news being reported from that publication.

The Journal is seen by reporters a few days before its Thursday cover date, but its contents are embargoed from public reporting until 6 pm Eastern time Wednesday. Many viewers were therefore confused on 12 April, a Tuesday, when ABC News chief medical correspondent Timothy Johnson, a doctor, reported on a 10 year Finnish study from the Journal that suggested that vitamin A might …