tbuckley/cabot-search huggingface dataset:
Radical surgical approach now indicated
Authors: L P Fielding
Journal: BMJ (1995)

IL-31, a member of the IL-6 protein family, is one of the latest additions to the list of T cell–derived cytokines. Th2 cells are regarded as a main source of IL-31, which is produced in response to stimulation by IL-4. Because the development of Th9 cells also requires IL-4 as a polarizing cytokine, the current study investigates IL-31 production in human Th9 cells compared with Th2 cells. We found that, although Th9 cells were able to release IL-31 during the first weeks of in vitro polarization, no IL-31 was detected in Th9 cultures after a final restimulation in the absence of polarizing cytokines. We further show that TGF-β, which is required to obtain Th9 cells in vitro, potently inhibits the release of IL-31 from Th2 cells, whereas IL-33, a cytokine associated with Th2-mediated inflammation, synergizes with IL-4 in inducing IL-31 secretion. To analyze the molecular mechanisms underlying the induction of IL-31, EMSAs, reporter gene assays, and small interfering RNA-based silencing experiments were carried out. We show that STAT6 and NF-κB are central players in mediating IL-31 expression induced by IL-4/IL-33. In addition, we identified a novel NF-κB–binding element within the <i>Il31</i> promoter that mediates the enhancing effects of IL-33 on IL-4/STAT6–induced IL-31 expression in human Th2 cells. Taken together, this study shows that IL-4 is essential for the production of IL-31, whereas TGF-β significantly suppresses IL-31 expression at the mRNA and protein levels. As a consequence, in vitro polarized Th2 cells, but not Th9 cells, are able to release IL-31.
Respiratory and circulatory analysis of CO2 output during exercise in chronic heart failure.
Authors: R Hachamovitch, H V Brown, S A Rubin
Journal: Circulation (1991)

The output of carbon dioxide (VCO2) is controlled by both hemodynamics and ventilation. To understand VCO2 in patients who have chronic heart failure (CHF), we studied 14 patients who had New York Heart Association functional class III failure by measurements of hemodynamics, ventilation, and arterial and venous blood gases at rest and at 50 W of cycle ergometry exercise.Fick principle analysis of VCO2 showed that because of a limited increase in cardiac output, CHF patients widened their venoarterial CO2 content difference from 4.9 +/- 3.5 ml/dl at rest to 11.1 +/- 4.0 ml/dl with exercise (p less than 0.05). This increase in CO2 content difference was achieved with no change in venous CO2 content (from 54.3 +/- 3.3 ml/dl at rest to 54.5 +/- 4.8 ml/dl at exercise, p = NS); however, there was a decrease of arterial CO2 content (from 49.4 +/- 3.7 ml/dl at rest to 43.4 +/- 2.3 ml/dl with exercise, p less than 0.05). Modeling of the CO2 tension-content relation showed that there would have been a small, nonproportional increase of venous CO2 content as venous CO2 tension increased from 43.2 +/- 1.8 mm Hg at rest to 55.3 +/- 4.2 mm Hg during exercise (p less than 0.05); however, the development of metabolic acidosis during exercise entirely blunted the increase of CO2 content. In contrast, both the shape of the tension-content relation and the acidosis of exercise further influenced the decrease of arterial CO2 content as arterial CO2 tension decreased from 37.0 +/- 2.9 mm Hg at rest to 32.0 +/- 3.4 mm Hg during exercise (p less than 0.05) as a result of excess ventilation.In CHF patients during exercise, the circulatory limitations imposed by a low cardiac output on VCO2 are compensated by a widened venoarterial CO2 content difference. The content difference is not widened through an increase of venous CO2 content but rather by a decrease of arterial CO2 content caused by arterial hypocapnia and metabolic acidosis.
A healthy home environment?
Authors: J Manuel
Journal: Environmental Health Perspectives (1999)

Over the past seven years, the U.S. Environmental Protection Agency has consistently ranked indoor air pollution among the top five risks to public health. One of the most dangerous indoor air pollutants is carbon monoxide (CO). CO can be lethal, but perhaps more important, many people suffer ill health from chronic, often undetected exposure to low levels of this gas, resulting in fatigue, headache, dizziness, nausea, and vomiting. Another dangerous pollutant is volatile organic compounds (VOCs), which come from sources including building products, cleaning agents, and paints. One VOC, formaldehyde, can act as an irritant to the conjunctiva and upper and lower respiratory tract. Formaldehyde is also known to cause nasal cancer in test animals.
p21Cip1 modulates arterial wound repair through the stromal cell–derived factor-1/CXCR4 axis in mice
Authors: Michelle Olive, Jason A. Mellad, Leilani E. Beltran, Mingchao Ma, Thomas Cimato, Audrey C. Noguchi, Hong San, Richard Childs, Jason C. Kovacic, Manfred Boehm
Journal: Journal of Clinical Investigation (2008)

Cyclin-dependent kinase inhibitors, including p21Cip1, are implicated in cell turnover and are active players in cardiovascular wound repair. Here, we show that p21Cip1 orchestrates the complex interactions between local vascular and circulating immune cells during vascular wound repair. In response to femoral artery mechanical injury, mice with homozygous deletion of p21Cip1 displayed accelerated proliferation of VSMCs and increased immune cell infiltration. BM transplantation experiments indicated that local p21Cip1 plays a pivotal role in restraining excessive proliferation during vascular wound repair. Increased local vascular stromal cell-derived factor-1 (SDF-1) levels were observed after femoral artery injury in p21+/+ and p21-/- mice, although this was significantly greater in p21-/- animals. In addition, disruption of SDF-1/CXCR4 signaling inhibited the proliferative response during vascular remodeling in both p21+/+ and p21-/- mice. We provide evidence that the JAK/STAT signaling pathway is an important regulator of vascular SDF-1 levels and that p21Cip1 inhibits STAT3 binding to the STAT-binding site within the murine SDF-1 promoter. Collectively, these results suggest that p21Cip1 activity is essential for the regulation of cell proliferation and inflammation after arterial injury in local vascular cells and that the SDF-1/CXCR4 signaling system is a key mediator of vascular proliferation in response to injury.
What Is Medical Sociology?
Authors: Florence A. Ruderman
Journal: JAMA (1981)

AS WE have seen, medical sociology has found some place in medical schools. But clearly, its status there is not high. In medicine's core department, internal medicine, it receives quite a low rating: most responding chairmen consider it unimportant, and many are strongly negative. True, in departments of pediatrics, and still more, in family medicine, its rating is better. Also, one might question the degree to which department chairmen are representative even of their own fields: perhaps age or other variables introduce a bias. But despite whatever questions might legitimately be raised about the results of the study, I believe the picture Petersdorf and Feinstein give us is essentially accurate. It would be a mistake to dismiss the evidence that many, if not most, medical educators—who, after all, have more contact with medical sociology than physicians generally do—have a view of the field that is not particularly flattering. I should
Related individuals with different androgen receptor gene deletions.
Authors: H E MacLean, S Chu, G L Warne, J D Zajac
Journal: Journal of Clinical Investigation (1993)

We have identified different members of one family affected by androgen insensitivity syndrome who have deletions of different exons of the X-linked androgen receptor (AR) gene. Two affected (XY) siblings have a deletion of exon E of the AR gene and their affected (XY) aunt has a normal exon E, but a deletion of exons F and G of the same gene. The mother and maternal grandmother of the children both carry the exon E deletion, but not the exon F, G deletion. Both deletions are 5 kb in length and have one breakpoint within a 200-bp region in intron 5; however, they extend in opposite directions. The probability that these two different deletions have arisen at random is extremely low, but the cause of this intriguing phenomenon remains to be found.
Slide Immunological Pregnancy Test
Authors: William A. Little, Charles D. Christian, John B. Henry
Journal: JAMA (1964)

LATEX agglutination-inhibition is one of the recently reported methods for the immunological detection of chorionic gonadotropin in body fluids. The relatively high accuracy of a test-tube test of this type in our laboratory<sup>1</sup>has also been reported by many other authors.<sup>2-6</sup>Still others<sup>7-10</sup>have found this test to be less reliable than biological tests. Inconsistency in reports is probably partially due to lack of uniformity in methodology and reagents. Modification of the test-tube test into an extremely rapid, low-cost, easily-read slide agglutination test has resulted in a procedure worthy of a brief description, as well as a report of current findings. <h3>Procedure and Results</h3> Freshly voided urine specimens obtained from patients at the J. Hillis Miller Health Center were centrifuged at high speed for three minutes. Clear supernatant urine was separated by decantation and used for testing. The test was performed on a clean glass slide placed
Abstract 5514: Metformin sensitizes anticancer effect of dasatinib through AMPK-dependent ER stress in head and neck squamous cell carcinoma cells
Authors: Yu-Chin Lin, Meng-Hsuan Wu, Tzu-Tang Wei, Yun-Chieh Lin, Ching-Chow Chen
Journal: Cancer Research (2014)

Abstract Purpose: Head and neck squamous cell carcinoma (HNSCC) is an important endemic disease in Taiwan with aggressive course and dismal outcome. Dasatinib is a Bcr-bl and Src kinase inhibitor that has potential against HNSCC. We recently disclosed that EGFR degradation is critical for dasatinib-induced apoptosis. Here, we further demonstrate that AMPK-dependent ER stress is responsible for this effect. Experimental design: Dasatinib-induced ER stress and AMPK activation was investigated in HNSCC cells including Ca9-22, HSC3, and SAS. The anti-cancer activity of dasatinib in combination with AMPK activator was examined in vitro and in vivo. EGFR expression and AMPK activation were correlated in human specimens. Results: Dasatinib-induced ER stress was involved in dasatinib-induced EGFR degradation and apoptosis, and ER stress mediated EGFR degradation in a c-cbl-dependent manner. In addition, dasatinib-induced AMPK activation led to dasatinib-induced ER stress and EGFR degradation, and activation of AMPK might be due to ATP decrease through the up-regulation of pyruvate dehydrogenase kinase 4 (PDK4) induced by dasatinib. Furthermore, activation of AMPK by metformin potentiated dasatinib-induced anti-cancer effect in vitro and in vivo. The correlation of AMPK activation and EGFR expression was seen in HNSCC cells and human tumor specimens. Conclusions: Our results disclose that AMPK-dependent ER stress plays a crucial role in anti-cancer effect of dasatinib on HNSCC and activation of AMPK might enhance dasatinib efficacy. Note: This abstract was not presented at the meeting. Citation Format: Yu-Chin Lin, Meng-Hsuan Wu, Tzu-Tang Wei, Yun-Chieh Lin, Ching-Chow Chen. Metformin sensitizes anticancer effect of dasatinib through AMPK-dependent ER stress in head and neck squamous cell carcinoma cells. [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 5514. doi:10.1158/1538-7445.AM2014-5514
Adult Respiratory Distress Syndrome and Trimethoprim-Sulfamethoxazole
Authors: ROGER M. CASS
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 February 1987Adult Respiratory Distress Syndrome and Trimethoprim-SulfamethoxazoleROGER M. CASS, M.D.ROGER M. CASS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-106-2-331_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The adult respiratory distress syndrome has been associated with various diseases, injuries, and several drugs (1, 2). Our patient experienced three episodes of this syndrome, each occurring 5 to 6 hours after the ingestion of a single trimethoprim-sulfamethoxazole tablet.An 81-year-old woman awoke with the sudden onset of chills, cough, and rapidly worsening dyspnea 5 hours after ingesting one 160/800-mg trimethoprim-sulfamethoxazole tablet. She had a cigarette smoking history of 20 pack-years. Her temperature was 38.5 °C, and she was in severe respiratory distress with bilateral crackles. Her leukocyte count was 23 500/mm3; her arterial blood pH was...References1. RINALDO J and ROGERS R. Adult respiratory distress syndrome: changing concepts of lung injury and repair. N Engl J Med. 1982;306:900-9. CrossrefMedlineGoogle Scholar2. BEDROSSIAN C. Pathology of drug-induced lung diseases. Semin Respir Med. 1982;4:103-4. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROGER M. CASS, M.D.Affiliations: Strong Memorial Hospital University of Rochester School of Medicine and Dentistry Rochester, NY 14642 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySuspected Case of Drug-Induced Acute Respiratory Distress Syndrome following Trimethoprim-Sulfamethoxazole TreatmentTrimethoprim-sulfamethoxazole induced eosinophilic pneumonia: A case reportSevere Acute Respiratory Failure in Healthy Adolescents Exposed to Trimethoprim-Sulfamethoxazole 1 February 1987Volume 106, Issue 2 Page: 331-331 Keywords Acute respiratory distress syndrome Blood Drugs Dyspnea Ingestion Pulmonary diseases Temperature ePublished: 1 December 2008 Issue Published: 1 February 1987 PDF downloadLoading ...
Assisted Circulation by Pump-oxygenator During Operative Dilatation of the Aortic Valve in Man
Authors: I. Aird, D. G. Melrose, W. P. Cleland, R. B. Lynn
Journal: BMJ (1954)

BiuC ISHMEDICAL JOJURNAL the normal subject, as well as in the haemorrhagic anaemias, even though hatmoglobin synthesis in the latter is retarded by lack of iron.In leukaemia, leucocytes accumulate a high concentration of ribosenucleic acids in the cytoplasm and nucleoli which does' not rapidly decline, as in the case of normal cells.Desoxyribosenucleic acids are an important constituent of chromosomes, being apparently attached at specific loci in the polypeptide chain which goes to make up the chromo- some fibre; the amount differs at the different phases of chromosome division, and is noticeably abnormal in certain pathological states.Under normal conditions there is more desoxyribosenucleic acid in the chromosomes of the proerythroblast than the promyelocyte at the metaphase.In pernicious anaemia, however, the promyelocyte chromosomes contain very little desoxyribosenucleic acid, and this leads to incomplete spiralization; the proerythroblasts and early megaloblasts.on the other hand, show an excess which consequently leads to over-spiralization.Over-spiralized chromosomes are associated with irregular division, multipolar spindles, and chromatoid bridges at the anaphase.In short, it would seem that mitotic abnormalities are closely associated with different distributions of desoxyribosenucleic acid.
Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.
Authors: K S Nair, G C Ford, K Ekberg, E Fernqvist-Forbes, J Wahren
Journal: Journal of Clinical Investigation (1995)

To elucidate the mechanism of insulin's anticatabolic effect in humans, protein dynamics were evaluated in the whole-body, splanchnic, and leg tissues in six C-peptide-negative type I diabetic male patients in the insulin-deprived and insulin-treated states using two separate amino acid models (leucine and phenylalanine). L-(1-13C,15N)leucine, L-(ring-2H5)phenylalanine, and L-(ring-2H2) tyrosine were infused intravenously, and isotopic enrichments of [1-13C,15N]-leucine, (13C)leucine, (13C)ketoisocaproate, (2H5)phenylalanine, [2H4]tyrosine, (2H2)tyrosine, and 13CO2 were measured in arterial, hepatic vein, and femoral vein samples. Whole-body leucine flux, phenylalanine flux, and tyrosine flux were decreased (< 0.01) by insulin treatment, indicating an inhibition of protein breakdown. Moreover, insulin decreased (< 0.05) the rates of leucine oxidation and leucine transamination (P < 0.01), but the percent rate of ketoisocaproate oxidation was increased by insulin (P < 0.01). Insulin also reduced (< 0.01) whole-body protein synthesis estimated from both the leucine model (nonoxidative leucine disposal) and the phenylalanine model (disposal of phenylalanine not accounted by its conversion to tyrosine). Regional studies demonstrated that changes in whole body protein breakdown are accounted for by changes in both splanchnic and leg tissues. The changes in whole-body protein synthesis were not associated with changes in skeletal muscle (leg) protein synthesis but could be accounted for by the splanchnic region. We conclude that though insulin decreases whole-body protein breakdown in patients with type I diabetes by inhibition of protein breakdown in splanchnic and leg tissues, it selectively decreases protein synthesis in splanchnic tissues, which accounted for the observed decrease in whole-body protein synthesis. Insulin also augmented anabolism by decreasing leucine transamination.
Bites by puff-adder (Bitis arietans) in Nigeria, and value of antivenom.
Authors: D A Warrell, L D Ormerod, N M Davidson
Journal: BMJ (1975)

Ten patients bitten by the puff-adder (Bitis arietans) were studied in the North of Nigeria. Six showed severe local signs, and four also had evidence of systemic envenoming, including spontaneous bleeding with thrombocytopenia, hypotension, and bradycardia. Two patients died after developing circulatory collapse and renal failure. Antivenom and intravenous fluid restored blood pressure in two hypotensive patients, and antivenom probably prevented the development of local necrosis in four others with massive local swelling. Victims of B arietans who have swelling of more than half the bitten limb or show signs of systemic envenoming should be given at least 80 ml of specific polyvalent antivenom and watched carefully for signs of circulatory collapse. Debridement of necrotic tissue may be necessary.
pH-dependent Perforation of Macrophage Phagosomes by Listeriolysin O from <i>Listeria monocytogenes </i>
Authors: Kathryn E. Beauregard, Kyung-Dall Lee, R. John Collier, Joel A. Swanson
Journal: The Journal of Experimental Medicine (1997)

The pore-forming toxin listeriolysin O (LLO) is a major virulence factor implicated in escape of Listeria monocytogenes from phagocytic vacuoles. Here we describe the pH-dependence of vacuolar perforation by LLO, using the membrane-impermeant fluorophore 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) to monitor the pH and integrity of vacuoles in mouse bone marrow–derived macrophages. Perforation was observed when acidic vacuoles containing wild-type L. monocytogenes displayed sudden increases in pH and release of HPTS into the cytosol. These changes were not seen with LLO-deficient mutants. Perforation occurred at acidic vacuolar pH (4.9–6.7) and was reduced in frequency or prevented completely when macrophages were treated with the lysosomotropic agents ammonium chloride or bafilomycin A1. We conclude that acidic pH facilitates LLO activity in vivo.
ELEVATED HIGH-SENSITIVITY TROPONIN LEVELS ON PRESENTATION PREDICT INCREASED MORTALITY AMONG PATIENTS WITH NORMAL CONVENTIONAL TROPONIN LEVELS: INSIGHTS FROM A META-ANALYSIS
Authors: Saurav Chatterjee, Jiwon Kim, Ali Dahhan, Gaurav Choudhary, Satish Sharma, Wen-Chih Wu
Journal: Journal of the American College of Cardiology (2013)
Sperm Quality and Tap Water: Disinfection By-Product Effects Not Supported
Authors: Valerie J. Brown
Journal: Environmental Health Perspectives (2007)

Chronic physical or emotional stress is known to impair the immune system, a link that may explain some of the health disparities found among different socioeconomic groups.Researchers have also found that living in poor, urban communities or near highways is linked to a greater risk of developing childhood asthma and other breathing problems.A new study now reveals that psychosocial stressors may increase children's vulnerability to the effects of traffic-related air pollution [EHP 115:1140-1146; Clougherty et al.].The researchers examined data from the Maternal-Infant Smoking Study of East Boston, which began in 1987 to establish a cohort of pregnant women.In 1997, parents or guardians of 417 children of the cohort, then aged 4 to 11.5, answered questions about the children's exposure to violence.Respondents were asked about the frequency with which the children had ever seen hitting, a shooting, or a stabbing, or heard domestic verbal abuse or gunshots.Other studies have suggested that residual trauma from witnessing episodic violence is a source of chronic stress for urban residents.About 45% of the children had witnessed at least one violent act, and almost 20% had witnessed at least two.Responses were generalized to account for variables that can affect the severity of such acts, including whether the child knew the victim or perpetrator.The researchers then acquired data collected between 1987 and 2004 on Boston levels of nitrogen dioxide (NO 2 ), a constituent of vehicular exhaust with a known link to asthma.They used computerized mapping tools to estimate NO 2 exposure at the children's residences in East Boston, a working-class urban neighborhood with highways running through it.About 25% of the children in the study had asthma.However, residential exposure to NO 2 was linked to asthma only among children who were above the median for exposure to violence.The association between asthma and NO 2 exposure disappeared when the researchers looked at the group as a whole.The authors conclude that their findings "indicate ancillary effects of violence on children in addition to direct injury and post-traumatic stress."Larger studies are needed to investigate other possible interactions among risk factors for asthma.It is also important to study the effects of other pollutants, including indoor air pollution.The authors observe that accurate reports about violence are difficult to obtain, and that violence exposures may be a sign of other problems with family stability that affect stress levels and health.-Tina Adler Added burden.Stress can compound the physiological effects of environmental pollutants such as nitrogen dioxide.