tbuckley/cabot-search huggingface dataset:
Mediastinal Cysts of Bronchial Origin
Authors: P. R. Allison
Journal: Thorax (1947)

Congenital cystic disease of the lungs has already been widely studied and described.In 1936 Schenck reviewed the literature up to that date.He says: "That pulmonary cystic disease is due to a developmental error or anomaly is now generally admitted, although many factors in the precise mechanism of its genesis are still unknown.The cyst wall may have the characteristics of bronchi, bronchioles, atria, infundibula, or alveoli.This depends at what intra- uterine age the developmental error or foetal inclusion occurred."The diag- nosis is usually much easier where the cysts are multiple and peripheral than when they are solitary.In each of the cases described in this paper the cyst arose from and had the structure of a large bronchus, and lay in the mediastinum between the two main bronchi behind the pericardium and in front of the oesophagus and descending aorta. CASE REPORTSCase 1.-A man aged 48 years was first seen in December, 1940.His main complaint had been intermittent dyspepsia for twenty years.He had had prolonged treatment for gastric ulcer.There had never been any dysphagia.During 1940 he had had two bad febrile illnesses which had been diagnosed as influenza.With each of these he had had a cough with grey sputum, vague backache, tightness across the front of the chest, a little shortness of breath, and pain in the right loin on exertion.He had lost some weight, had no appetite, and lacked energy.Clinical examination gave no lead to the diagnosis, but radiographic examination by Dr. A. Pollitt showed a large mass occupying the posterior mediastinum (Plate VII, a and b).The shadow was pear-shaped, with the apex between the two main bronchi and its base nearly on the diaphragm.It projected into both sides of the chest, but mainly into the right side, where it displaced the root of the lung upwards and backwards.The mass showed no pulsation and a barium swallow was only momen- tarily delayed.The stomach and duodenum were normal.A provisional diagnosis of simple mediastinal tumour was made, and an operation planned for its removal.Anaesthesia was induced with sodium pentothal and maintained with intratracheal nitrous oxide, oxygen, and cyclopropane.The right pleural cavity was opened after generous resection of parts of the seventh and eighth ribs behind.There was about 4 oz. of clear fluid in the pleural cavity but no adhesions to the chest wall, and the lung was easily displaced forwards.Soft filmy adhesions were found between the lung and the tumour, but these were easily divided without bleeding.The mass had a smooth, on August 31, 2023 by guest.
IMMUNITY IN VOLUNTEERS RECOVERED FROM NON-BACTERIAL GASTROENTERITIS 1
Authors: Irving Gordon, Paul R. Patterson, Elinor Whitney
Journal: Journal of Clinical Investigation (1956)

The afebrile type (1) of acute infectious non- bacterial gastroenteritis seems to be an extremely common diarrhea in the Northeastern United States.It occurs yearly in some families and com- munities (2, 3).Whether the recurrences are due to the early waning of immunity or to the ex- istence of immunologically distinct agents has not been determined.Following an attack of gastro- enteritis evoked by the Marcy strain (4), which is presumably a virus, an effective immunity de- velops in volunteers (1, 4-6), and in an earlier report the opinion was expressed that immunity probably does not persist for long (5).The present study shows that individuals who recov- ered from experimental Marcy gastroenteritis more than a year before were fully resistant to re- infection.It may well be, therefore, that the sec- ond explanation of the recurrences is the correct one and more than one antigenically distinct agent exists. METHODSAfebrile nonbacterial gastroenteritis can be highly con- tagious; numerous large epidemics have been reported (4, 5, 7, 8).Like the experiments previously done with the Marcy strain, therefore, this study was carried out in a closed state correctional institution, where volunteer subjects were individually isolated in well-equipped cells for periods of several weeks.Stringent precautions against accidental spread of the disease were enforced under nursing supervision.Volunteers were healthy male inmates 21 to 30 years old who had no known exposure to gastroenteritis prior to their entry into the study.Their psychological sta-
Catch-up growth in childhood and death from coronary heart disease: longitudinal study
Authors: J G Eriksson, T Forsen, J Tuomilehto, P D Winter, C Osmond, D J P Barker
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To examine whether catch-up growth during childhood modifies the increased risk of death from coronary heart disease that is associated with reduced intrauterine growth. <b>Design:</b> Follow up study of men whose body size at birth was recorded and who had an average of 10 measurements taken of their height and weight through childhood. <b>Setting:</b> Helsinki, Finland. <b>Subjects:</b> 3641 men who were born in Helsinki University Central Hospital during 1924-33 and who went to school in Helsinki. <b>Main outcome measures:</b> Hazard ratios for death from coronary heart disease. <b>Results:</b> Death from coronary heart disease was associated with low birth weight and, more strongly, with a low ponderal index at birth. Men who died from coronary heart disease had an above average body mass index at all ages from 7 to 15 years. In a simultaneous regression the hazard ratio for death from the disease increased by 14% (95% confidence interval 8% to 19%; P&lt;0.0001) for each unit (kg/m3) decrease in ponderal index at birth and by 22% (10% to 36%; P=0.0001) for each unit (kg/m2) increase in body mass index at 11 years of age. Body mass index in childhood was strongly related to maternal body mass index, which in turn was related to coronary heart disease. The extent of crowding in the home during childhood, although related to body mass index in childhood, was not related to later coronary heart disease. <b>Conclusion:</b> The highest death rates from coronary heart disease occurred in boys who were thin at birth but whose weight caught up so that they had an average or above average body mass from the age of 7 years. Death from coronary heart disease may be a consequence of poor prenatal nutrition followed by improved postnatal nutrition.
The grey mouse lemur: A non-human primate model for ageing studies
Authors: S. Languille, S. Blanc, O. Blin, C.I. Canale, A. Dal-Pan, G. Devau, M. Dhenain, O. Dorieux, J. Epelbaum, D. Gomez, I. Hardy, P.-Y. Henry, E.A. Irving, J. Marchal, N. Mestre-Francés, M. Perret, J.-L. Picq, F. Pifferi, A. Rahman, E. Schenker, J. Terrien, M. Théry, J.-M. Verdier, F. Aujard
Journal: Ageing Research Reviews (2011)
Cytomegalovirus Seropositivity and C-Reactive Protein Have Independent and Combined Predictive Value for Mortality in Patients With Angiographically Demonstrated Coronary Artery Disease
Authors: Joseph B. Muhlestein, Benjamin D. Horne, John F. Carlquist, Troy E. Madsen, Tami L. Bair, Robert R. Pearson, Jeffrey L. Anderson
Journal: Circulation (2000)

Background —The role of inflammation in coronary artery disease (CAD) is being increasingly recognized. Markers of inflammation (eg, C-reactive protein [CRP]) and infection (eg, seropositivity to Chlamydia pneumoniae , cytomegalovirus [CMV], and Helicobacter pylori ) have been proposed as risk factors for CAD, but these associations require further evaluation. Methods and Results —We prospectively tested whether CRP levels and IgG seropositivity to C pneumoniae , CMV, and H pylori are predictors of subsequent mortality in 985 consecutive patients with angiographically demonstrated CAD (stenosis ≥70%). Patients were followed for an average of 2.7 years (range 1.5 to 4.0 years). Patients averaged 65 years of age; 77% were men; and 110 (11.2%) died during follow-up. CRP levels were significantly elevated in nonsurvivors compared with survivors (mean CRP 3.1 mg/dL versus 1.5 mg/dL, P =0.003). After controlling for all known baseline variables, the 2nd and 3rd tertiles of CRP compared with the 1st produced a Cox hazard ratio (HR) for mortality of 2.4 ( P =0.001). Of the 3 infectious markers tested, only seropositivity to CMV (HR=1.9, P &lt;0.05) was predictive of mortality. The majority of mortality risk associated with elevated CRP or CMV seropositivity occurred when both risk factors were present ( P for trend &lt;0.0001). Other independent predictors of increased risk of mortality were age (HR=1.07 per year, P &lt;0.0001), left ventricular ejection fraction (HR=0.97 per percent, P &lt;0.0001), and diabetes mellitus (HR=1.7, P =0.02). Conclusions —CMV seropositivity and elevated CRP, especially when in combination, are strong, independent predictors of mortality in patients with CAD. This suggests an interesting hypothesis that a chronic, smoldering infection (CMV) might have the capacity to accelerate the atherothrombotic process.
Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice
Authors: Kojiro Taura, Kouichi Miura, Keiko Iwaisako, Christoph H. Österreicher, Yuzo Kodama, Melitta Penz-Österreicher, David A. Brenner
Journal: Hepatology (2009)

The origin of fibrogenic cells in liver fibrosis remains controversial. We assessed the emerging concept that hepatocytes contribute to production of extracellular matrix (ECM) in liver fibrosis through epithelial-mesenchymal transition (EMT). We bred triple transgenic mice expressing ROSA26 stop β-galactosidase (β-gal), albumin Cre, and collagen α1(I) green fluorescent protein (GFP), in which hepatocyte-derived cells are permanently labeled by β-gal and type I collagen-expressing cells are labeled by GFP. We induced liver fibrosis by repetitive carbon tetrachloride (CCl4) injections. Liver sections and isolated cells were evaluated for GFP and β-gal as well as expression of α-smooth muscle actin (α-SMA) and fibroblast-specific protein 1 (FSP-1). Upon stimulation with transforming growth factor β-1, cultured hepatocytes isolated from untreated liver expressed both GFP and β-gal with a fibroblast-like morphological change but lacked expression of other mesenchymal markers. Cells from CCl4-treated livers never showed double-positivity for GFP and β-gal. All β-gal-positive cells exhibited abundant cytoplasm, a typical morphology of hepatocytes, and expressed none of the mesenchymal markers including α-SMA, FSP-1, desmin, and vimentin. In liver sections of CCl4-treated mice, GFP-positive areas were coincident with fibrotic septa and never overlapped X-gal-positive areas. Conclusion: Type I collagen-producing cells do not originate from hepatocytes. Hepatocytes in vivo neither acquire mesenchymal marker expression nor exhibit a morphological change clearly distinguishable from normal hepatocytes. Our results strongly challenge the concept that hepatocytes in vivo acquire a mesenchymal phenotype through EMT to produce the ECM in liver fibrosis. (Hepatology 2009.)
Prenatal exposure to allergen, <scp>DNA</scp> methylation, and allergy in grandoffspring mice
Authors: M. Niedzwiecki, H. Zhu, L. Corson, G. Grunig, P. H. Factor, S. Chu, H. Jiang, R. L. Miller
Journal: Allergy (2012)

Abstract Background Prenatal allergen exposure has been linked to both induction and protection of allergic sensitization in offspring. We hypothesized that prenatal exposure of mice ( F 0) to A spergillus fumigatus ( A . fumigatus ) would be associated with decreased immunoglobulin (Ig) E and airway eosinophilia and alterations in CpG methylation of T ‐helper genes in third‐generation mice ( F 2). Methods Female BALB /c mice were sensitized to A . fumigatus (62.5, 125, 1250 μg, or saline) and re‐exposed to the same dose on days 7 and 14 (early) or days 12 and 17 (late) gestation. Grandoffspring were treated with A . fumigatus (62.5 μg) at 9 weeks. IgE, IgG 1 , and IgG 2a levels and cell counts from bronchoalveolar lavage fluid were determined. Lung DNA was pyrosequenced at multiple sites in the interferon ( IFN )‐γ and interleukin ( IL )‐4 promoters. Results Grandoffspring of mothers dosed with 1250 μg early during pregnancy developed increased airway eosinophilia ( P &lt; 0.05). Grandoffspring of mothers dosed late in pregnancy developed lower IgE ( P &lt; 0.05) and airway eosinophilia ( P &lt; 0.05). Grandoffspring of mothers dosed early had lower methylation at IL ‐4 CpG −408 and CpG −393 compared to late dosed mice ( P &lt; 0.005 across all doses). Few correlations were found between methylation levels and airway eosinophilia and IgE. Conclusion Prenatal exposure to A . fumigatus late during pregnancy, but not early, was associated with lower IgE and airway eosinophilia in grandoffspring. Prenatal exposure to A . fumigatus was associated with changes in CpG methylation in the IFN ‐γ and IL ‐4 promoters that did not correlate consistently with indicators of allergic sensitization.
When "Minimal Risk" Research Yields Clinically-Significant Data, Maybe the Risks Aren't So Minimal
Authors: Helen M. Sharp, Robert D. Orr
Journal: The American Journal of Bioethics (2004)

Surveys and routine clinical procedures applied in research protocols are typically considered only minimally risky to participants. The apparent benign nature of "minimal risk" tasks increases the chance that investigators and Institutional Review Boards (IRBs) will overlook the probability that clinical tools will identify signs, symptoms, or definitive test results that are clinically-relevant to subjects' welfare. "Minimal risk" procedures may also pose a particular hazard to participants in clinical research by increasing the therapeutic misconception because the tasks mimic clinical care and are often conducted in clinical settings. Investigators should anticipate which measures could yield clinically-important findings and should describe explicit plans for data monitoring, disclosure, and follow-up. Protocols that include reliable and valid clinical measures should prompt a more detailed risk assessment by the IRB, even when the tasks meet the regulatory criteria for minimal physical, psychological, or emotional risk.
THE ROUTINE TREATMENT OF DIABETES WITH INSULIN
Authors: ELLIOTT P. JOSLIN
Journal: JAMA (1923)

Successful treatment of diabetes with insulin depends on the utilization of all those measures that have proved of the greatest value in the treatment of diabetes without insulin. These are: adherence to a diet which will keep the urine sugar-free; avoidance of over nutrition or extreme undernutrition, and a method of life compatible with the strength such a diet affords. A knowledge of the fundamental principles of the diet and of the food values of a few foods is essential; otherwise the insulin will be squandered and the patient placed in jeopardy. Insulin does not cure diabetes. Insulin does not allow a diabetic to eat anything he desires. It is cruel for prominent individuals to make such statements and arouse false hopes. It is true that heretofore there has never been anything discovered as valuable for the diabetic as insulin; but diabetes, though subdued, is not yet conquered. Insulin is
FoxM1 Drives a Feed-Forward STAT3-Activation Signaling Loop That Promotes the Self-Renewal and Tumorigenicity of Glioblastoma Stem-like Cells
Authors: Ai-hua Gong, Ping Wei, Sicong Zhang, Jun Yao, Ying Yuan, Ai-dong Zhou, Frederick F. Lang, Amy B. Heimberger, Ganesh Rao, Suyun Huang
Journal: Cancer Research (2015)

The growth factor PDGF controls the development of glioblastoma (GBM), but its contribution to the function of GBM stem-like cells (GSC) has been little studied. Here, we report that the transcription factor FoxM1 promotes PDGFA-STAT3 signaling to drive GSC self-renewal and tumorigenicity. In GBM, we found a positive correlation between expression of FoxM1 and PDGF-A. In GSC and mouse neural stem cells, FoxM1 bound to the PDGF-A promoter to upregulate PDGF-A expression, acting to maintain the stem-like qualities of GSC in part through this mechanism. Analysis of the human cancer genomic database The Cancer Genome Atlas revealed that GBM expresses higher levels of STAT3, a PDGF-A effector signaling molecule, as compared with normal brain. FoxM1 regulated STAT3 transcription through interactions with the β-catenin/TCF4 complex. FoxM1 deficiency inhibited PDGF-A and STAT3 expression in neural stem cells and GSC, abolishing their stem-like and tumorigenic properties. Further mechanistic investigations defined a FoxM1-PDGFA-STAT3 feed-forward pathway that was sufficient to confer stem-like properties to glioma cells. Collectively, our findings showed how FoxM1 activates expression of PDGF-A and STAT3 in a pathway required to maintain the self-renewal and tumorigenicity of glioma stem-like cells.
Expansion of Circulating Toll-Like Receptor 4–Positive Monocytes in Patients With Acute Coronary Syndrome
Authors: Heiko Methe, Jong-Oh Kim, Sieglinde Kofler, Michael Weis, Michael Nabauer, Joerg Koglin
Journal: Circulation (2005)

Atherosclerosis is an inflammatory disease in which monocytes and macrophages have been suggested to play an essential role. The underlying signaling mechanisms are unknown thus far. We hypothesized that the human isoform of Toll-like receptor (hTLR)-4 is involved in monocyte activation of patients with accelerated forms of atherosclerosis.Expression of hTLR4 on circulating monocytes from 30 controls, 20 patients with stable angina (SA), 40 patients with unstable angina (UA), and 28 patients with acute myocardial infarction (AMI) was compared with the use of flow-cytometry and reverse transcription-polymerase chain reaction. Regulation of interleukin (IL)-12 and B7-1 as downstream events of TLR4 activation was analyzed after lipopolysaccharide stimulation of monocytes. TLR4-transfected Chinese hamster ovary (CHO) cells were used to identify potential hTLR4 ligands in the serum of patients with UA or AMI. Circulating hTLR4+/CD14+ monocytes were approximately 2.5-fold increased above controls and patients with SA in the UA and AMI groups (P<0.0001). This was paralleled by enhanced transcript levels of TLR4 and Myd88 in patients with UA and AMI (P<0.0001) and increased expression of IL-12 (UA 35.5+/-7.8, AMI 31.8+/-7.7 versus SA 2.2+/-0.5, controls 2.1+/-0.3 pg/mL; P<0.0002) and B7-1 (UA 27.3+/-14.4, AMI 22.6+/-11.1 versus SA 3.4+/-2.5, controls 2.4+/-2.3%; P<0.0001). Compared with serum from patients with UA and AMI, challenging TLR4-transfected CHO cells with serum from SA patients yielded only a weak response (P<0.0001). Coincubation with anti-heat shock protein 60 inhibited CHO cell activation.UA and AMI are associated with enhanced expression and signaling events downstream of hTLR4 in circulating monocytes. These observations suggest hTLR4 activation as a signaling mechanism in immune-mediated progression of atherosclerosis.
Naevi in schoolchildren in Scotland and Australia
Authors: L. FRITSCHI, P. McHENRY, A. GREEN, R. MACKIE, L. GREEN, V. SISKIND
Journal: British Journal of Dermatology (1994)

To test the hypothesis that children living in subtropical and tropical environments have more naevi than those of similar ethnicity living in temperate countries, a comparative study of melanocytic naevi in 111 schoolchildren from Brisbane, Australia, and 222 from Glasgow, Scotland, was carried out. All children were aged 13–15 years, of European ancestry, and had spent most of their lives at latitudes of less than 30°S (Australia) or greater than 30°N (Scotland), Using an identical protocol, all naevi of 2 mm or more in diameter occurring on the right arm were counted by either a highly experienced research nurse in Brisbane, or a dermatologist in Glasgow, Hair and eye colour, and facial freckling, were assessed by the examiner, and axillary skin colour of children in both cities was measured using the same reflectance spectrophotometer. Children in Brisbane had significantly more naevi than those in Glasgow (P<0–05), after adjusting for complexion variables. The difference in the geometric mean number of naevi on the arm was much greater among boys (7.7 vs, 4.4, in Brisbane and Glasgow, respectively) than among girls (7.3 vs, 6.7). This has parallels with the sex differences in melanoma at later ages in the two countries. Besides country of residence, freckles and innate skin colour were the most significant predictors of large numbers of naevi, whereas red hair had a significant protective effect. Overall, these data on prevalence of naevi in children from contrasting environments provide some evidence in support of the theory that naevus development is related to the level of sun exposure in childhood and adolescence.
Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes. A new approach to platelet activation and recruitment.
Authors: M T Santos, J Valles, A J Marcus, L B Safier, M J Broekman, N Islam, H L Ullman, A M Eiroa, J Aznar
Journal: Journal of Clinical Investigation (1991)

Erythrocytes are known to influence hemostasis. Bleeding times are prolonged in anemia and corrected by normalizing the hematocrit. We now demonstrate that intact erythrocytes modulate biochemical and functional responsiveness of activated platelets. A two-stage procedure, permitting studies of cell-cell interactions and independently evaluating platelet activation and recruitment within 1 min of stimulation, was developed. Erythrocytes increased platelet serotonin release despite aspirin treatment, enzymatic adenosine diphosphate removal, protease inhibition, or combinations thereof. The data suggested that erythrocyte enhancement of platelet reactivity can reduce the therapeutic effectiveness of aspirin. Erythrocytes metabolically modified platelet arachidonate or eicosapentaenoate release and eicosanoid formation. They promoted significant increases in cyclooxygenase and lipoxygenase metabolites upon platelet stimulation with collagen or thrombin. However, with ionophore, erythrocytes strongly reduced platelet lipoxygenation. These erythrocyte modulatory effects were stimulus-specific. Activated platelet-erythrocyte mixtures, with or without aspirin, promoted 3-10-fold increases in extracellular free fatty acid, which would be available for transcellular metabolism. Erythrocyte-induced increases in free eicosapentaenoate may contribute to antithrombotic and anti-inflammatory effects of this fish oil derivative. These results provide biochemical insight into erythrocyte contributions to thrombosis and hemostasis, and support the concept of thrombus formation as a multicellular event.
The Emerging Concept of Vascular Remodeling
Authors: Franklin H. Epstein, Gary H. Gibbons, Victor J. Dzau
Journal: New England Journal of Medicine (1994)

The vessel wall is an active, integrated organ composed of endothelial, smooth-muscle, and fibroblast cells coupled to each other in a complex autocrine-paracrine set of interactions. The vasculature is capable of sensing changes within its milieu, integrating these signals by intercellular communication, and changing itself through the local production of mediators that influence structure as well as function. Vascular remodeling is an active process of structural alteration that involves changes in at least four cellular processes -- cell growth, cell death, cell migration, and production or degradation of extracellular matrix -- and is dependent on a dynamic interaction between locally . . .