tbuckley/cabot-search huggingface dataset:
Prognostic Impact of Pregnancy After Breast Cancer According to Estrogen Receptor Status: A Multicenter Retrospective Study
Authors: Hatem A. Azim, Niels Kroman, Marianne Paesmans, Shari Gelber, Nicole Rotmensz, Lieveke Ameye, Leticia De Mattos-Arruda, Barbara Pistilli, Alvaro Pinto, Maj-Britt Jensen, Octavi Cordoba, Evandro de Azambuja, Aron Goldhirsch, Martine J. Piccart, Fedro A. Peccatori
Journal: Journal of Clinical Oncology (2012)

We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status.A multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC-pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65.A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC-pregnancy interval did not seem to impact the risk of relapse.Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence.
Protein Kinase Cα Negatively Regulates Systolic and Diastolic Function in Pathological Hypertrophy
Authors: Harvey S. Hahn, Yehia Marreez, Amy Odley, Amber Sterbling, Martin G. Yussman, K. Chad Hilty, Ilona Bodi, Stephen B. Liggett, Arnold Schwartz, Gerald W. Dorn
Journal: Circulation Research (2003)

The protein kinase C (PKC) family is implicated in cardiac hypertrophy, contractile failure, and β-adrenergic receptor (βAR) dysfunction. Herein, we describe the effects of gain- and loss-of-PKCα function using transgenic expression of conventional PKC isoform translocation modifiers. In contrast to previously studied PKC isoforms, activation of PKCα failed to induce cardiac hypertrophy, but instead caused βAR insensitivity and ventricular dysfunction. PKCα inhibition had opposite effects. Because PKCα is upregulated in human and experimental cardiac hypertrophy and failure, its effects were also assessed in the context of the Gαq overexpression model (in which PKCα is transcriptionally upregulated). Normalization (inhibition) of PKCα activity in Gαq hearts improved systolic and diastolic function, whereas further activation of PKCα caused a lethal restrictive cardiomyopathy with marked interstitial fibrosis. These results define pathological roles for PKCα as a negative regulator of ventricular systolic and diastolic function.
ATYPICAL ENTERIC INFECTIONS: A REPORT OF FOUR CASES
Authors: J. D. A. Gray
Journal: BMJ (1930)

BAcTERTOLOGICAL illvestigation of ainterial obtained at necrolssies i'n the Royal Infirmiary, Edinburgh, have recenitly demonstrated the Presence of organiisms of the enterica Uroup) int cases which duiringi life hlave presented quite atylpical feattures.TI-me object of-the lIresent coinimunicattion i, to illustrate by means of fouir cases the apparenit fre- quency of such inifections (see Billet an-d others, 1910).In each of the cases the diagnosis of eniteirica i as not made until specimens obtained at the necropsies wer-e exasnineed bacteriologicallv, althoutgh in one case the " step-like " 1-ise of temoiliatlire hladl aroused clin-ical s5ispicionis of en-teric infectioni.Suich atypical cases m(ay 1)0 either p)rimnary infections or acute exacerbations in a chri oniic ctarri-er.Theey are lhable to be.diagnoscd incorrexctly, ant th1e coinseqtuent ab,sence of s,uitable pr1ecaaUtioIns would theni proniote tIme sl)Iead of the inifection1.As emphasized in the report by' Dr. Brincker oni thle outbreak. of pasatvphoid fever in Lonidon1 in 1928, iiifec- tionis witli certaili organismis of the pai atylhoid giroup) ieire coml)paratively rare in Britaini befor e the wvas.Sinice theis, hoN-ever, larc-e num-iilber s of individu.,als,after a sojoUs-ni in areas wx-here such infectiois ar;e en-tdemic, have become
Evidence-Based Breast Cancer Screening Guidelines for Women Who Received Chest Irradiation at a Young Age
Authors: Joachim Yahalom
Journal: Journal of Clinical Oncology (2013)

Follow-upguidelinesareimportantforthelong-termhealthcare of cancer survivors, particularly those treated at a young age. Appropriate guidelines are powerful tools to improve quality of care, reduce variability in clinical practice, and contain cost. Instituting clear and evidence-based standards is essential for compliance of both patients and providers. Hence, it is encouraging that guidelines on routine imaging of cancer survivors for early detection of treatment-related breastcancer(BC)arefinallysupportedbydirectevidenceforefficacy. Inthearticlethataccompaniesthiseditorial,aprospectivestudybyNg et al 1 addressed the contribution of both mammography and breast magnetic resonance imaging (MRI) in the early detection of BC in femalesurvivorsofHodgkinlymphoma(HL)whoreceivedradiation to the chest at a young age. The Ng et al study supports recent retrospective data on this topic 2 and further solidifies a consensus that several groups have reached on imaging of women who had received chestradiotherapy(RT). 3-5 TheNgetalstudyexemplifieshowappropriately designed research can strengthen and clarify survivorship guidelinesthatpreviouslywerebasedmerelyoninferencefromimaging of familial/genetic high-risk groups. The increased risk for BC of women cured of Hodgkin lymphoma (HL) who had significant radiation exposure of the breast at a youngage(30years)hasbeenacentralissueinsurvivorshipscreening programs for almost 20 years. 6-8 Although the treatment practice
STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors
Authors: Seng-Ryong Woo, Mercedes B. Fuertes, Leticia Corrales, Stefani Spranger, Michael J. Furdyna, Michael Y.K. Leung, Ryan Duggan, Ying Wang, Glen N. Barber, Katherine A. Fitzgerald, Maria-Luisa Alegre, Thomas F. Gajewski
Journal: Immunity (2014)
Dynamics of leukotriene C production by macrophages.
Authors: C A Rouzer, W A Scott, A L Hamill, Z A Cohn
Journal: The Journal of Experimental Medicine (1980)

A method for the radiochemical assay of LTC production by mouse peritoneal macrophages in vitro is presented. The method involves labeling macrophages in culture with [5,6,8,9,11,12,14,15-3H]20:4 followed by stimulation of arachidonic acid (20:4) release under the experimental conditions desired. Radiolabeled leukotriene C (LTC) is recovered from the culture medium by extraction and silicic acid chromatography in 40% yield with full retention of biological activity. Because this LTC is radiochemically pure, the quantity of LTC release may be estimated from the amount of radioactivity in the sample. Use of the radioassay to study parameters affecting LTC synthesis by macrophages indicated that the time course of LTC synthesis and its relationship to the dose of a phagocytic stimulus (zymosan) were very similar to those of prostaglandin (PG) release. LTC release was also similar to that of PG in that lower levels of both metabolites were produced by Corynebacterium parvum-elicited macrophages than by resident cells. Finally, LTC release was stimulated in response to a challenge with antigen-antibody complexes, but lower maximal levels were attained than those with zymosan. The data presented here are consistent with the hypothesis that challenge of macrophages with a phagocytic stimulus leads to the release of 20:4 by an inducible phospholipase. Cyclooxygenase and lipoxygenase then compete for the released 20:4, leading to the production of PG, hydroxyeicosatetraenoic acids, and LTC.
Origin and Spread of Photosynthesis Based upon Conserved Sequence Features in Key Bacteriochlorophyll Biosynthesis Proteins
Authors: Radhey S. Gupta
Journal: Molecular Biology and Evolution (2012)

The origin of photosynthesis and how this capability has spread to other bacterial phyla remain important unresolved questions. I describe here a number of conserved signature indels (CSIs) in key proteins involved in bacteriochlorophyll (Bchl) biosynthesis that provide important insights in these regards. The proteins BchL and BchX, which are essential for Bchl biosynthesis, are derived by gene duplication in a common ancestor of all phototrophs. More ancient gene duplication gave rise to the BchX-BchL proteins and the NifH protein of the nitrogenase complex. The sequence alignment of NifH-BchX-BchL proteins contain two CSIs that are uniquely shared by all NifH and BchX homologs, but not by any BchL homologs. These CSIs and phylogenetic analysis of NifH-BchX-BchL protein sequences strongly suggest that the BchX homologs are ancestral to BchL and that the Bchl-based anoxygenic photosynthesis originated prior to the chlorophyll (Chl)-based photosynthesis in cyanobacteria. Another CSI in the BchX-BchL sequence alignment that is uniquely shared by all BchX homologs and the BchL sequences from Heliobacteriaceae, but absent in all other BchL homologs, suggests that the BchL homologs from Heliobacteriaceae are primitive in comparison to all other photosynthetic lineages. Several other identified CSIs in the BchN homologs are commonly shared by all proteobacterial homologs and a clade consisting of the marine unicellular Cyanobacteria (Clade C). These CSIs in conjunction with the results of phylogenetic analyses and pair-wise sequence similarity on the BchL, BchN, and BchB proteins, where the homologs from Clade C Cyanobacteria and Proteobacteria exhibited close relationship, provide strong evidence that these two groups have incurred lateral gene transfers. Additionally, phylogenetic analyses and several CSIs in the BchL-N-B proteins that are uniquely shared by all Chlorobi and Chloroflexi homologs provide evidence that the genes for these proteins have also been laterally transferred between these groups. Other results and observations reported here indicate that the genes for the BchL-N-B proteins in Proteobacteria are derived from the Clade C Cyanobacteria, whereas those in Chlorobi were acquired from Chloroflexus or related bacteria by means of LGTs. Some implications of these observations regarding the origin and spread of photosynthesis are discussed.
Aberrant integrin expression during epidermal wound healing and in psoriatic epidermis.
Authors: M D Hertle, M D Kubler, I M Leigh, F M Watt
Journal: Journal of Clinical Investigation (1992)

We have examined integrin expression during the remodeling of the epidermis that takes place during wound healing, using a suction blister model in which the epidermis is detached from the dermis, leaving the basement membrane intact. By immunofluorescence microscopy, we found that the same integrin subunits were expressed during wound healing as in normal epidermis with very little change in the relative intensity or distribution of staining at the leading edge of the migrating epidermis. However, at the time of wound closure, when the epidermis is still hyperproliferative, alpha 2, alpha 3, alpha 6, and beta 1 were no longer confined to the basal layer, as in normal epidermis, but were also found in all the living suprabasal cell layers, coexpressed with the terminal differentiation markers involucrin, keratin 10, and keratin 16. Strong suprabasal staining for alpha v was also found in one specimen. beta 4, which normally forms a heterodimer with alpha 6, and alpha 5 remained predominantly basal. Three of the integrin ligands, fibronectin, type IV collagen, and laminin, remained largely confined to the basement membrane zone and dermis. By 14 d after wounding, the integrins were once more restricted to the basal layer. Suprabasal integrin expression was also observed in involved psoriatic lesions. Thus, in two situations in which the epidermis is hyperproliferative, there is a failure to downregulate integrin expression on initiation of terminal differentiation. The functional consequences of this aberrant integrin expression remain to be explored.
Quantitative histological study of enteropathy associated with HIV infection.
Authors: A G Cummins, J T LaBrooy, D P Stanley, R Rowland, D J Shearman
Journal: Gut (1990)

A quantitative histological study was performed on small intestinal biopsies from eight ambulatory patients with HIV infection (AIDS/AIDS-related complex, ARC) and compared with those from 16 normal subjects. Enteropathy was assessed by measurement of villus area, crypt length and mitotic count, as well as duodenal counts of intraepithelial lymphocytes, mucosal mast cells and goblet cells. Enteropathy in subjects with AIDS/ARC was shown by reduced mean villus area of 0.363 (SD 0.081) compared with 0.500 (SD 0.064) mm2 in control subjects (p less than 0.0001), while intestinal crypts were of similar length with 239 (SD 36) compared with 225 (SD 28 microns, but mitotic count was increased to 3.8 (SD 1.2) compared with 2.4 (SD 0.8) (p = 0.01) in the same control subjects. These results indicate villous atrophy with impaired crypt hyperplasia. Duodenal cell counts showed similar numbers of mucosal mast cells, intraepithelial lymphocytes and goblet cells in AIDS/ARC patients and fifteen control subjects.
Diabetic-induced endothelial dysfunction in rat aorta: role of hydroxyl radicals
Authors: Galen M Pieper, Peter Langenstroer, Wolfgang Siebeneich
Journal: Cardiovascular Research (1997)

Objective: Previous studies suggest a role of superoxide anion radicals (·O2−) in impaired endothelium-dependent relaxation of diabetic blood vessels; however, the role of secondary reactive oxygen species remains unclear. In the present study, we investigated a role of various potential reactive oxygen species in diabetic endothelial dysfunction. Methods: Thoracic aortic rings from 8-week streptozotocin-induced diabetic and age-matched control rats were mounted in isolated tissue baths. Endothelium-dependent relaxation to acetylcholine (ACH) and endothelium-independent relaxation to nitroglycerin (NTG) were assessed in precontracted rings. Results: ACH-induced relaxation was impaired in diabetic compared to control rings and was not improved with either indomethacin or daltroban. ACH-induced relaxation in both control and diabetic rings was completely blocked with the nitric oxide synthase inhibitors, l-nitroarginine methyl ester or l-nitroarginine (l-NA). NTG-induced relaxation was insensitive to l-NA and was unaltered by diabetes. Pretreatment with superoxide dismutase (SOD) at activities which did not alter contractile tone failed to alter responses to ACH in diabetic rings. Similar results were obtained using either catalase or mannitol. In contrast, the combination of SOD plus catalase or DETAPAC, an inhibitor of metal-facilitated hydroxyl radical (·OH) formation, markedly enhanced relaxation to ACH in diabetic but not in control rings. Neither the combination of SOD plus catalase nor DETAPAC altered the sensitivity or relaxation to NTG in control rings with or without endothelium. In diabetic rings with endothelium, both DETAPAC or SOD plus catalase increased sensitivity but not maximum relaxation to NTG. In diabetic rings without endothelium, relaxation and sensitivity to NTG were unaltered by either treatment. In l-NA-treated diabetic rings with endothelium, sensitivity and relaxation to NTG was unaltered by either DETAPAC or SOD plus catalase. Conclusion: Diabetic endothelium produces increases in both ·O2− and H2O2 leading to enhanced intracellular production of ·OH. Thus, ·OH are implicated in diabetes-induced endothelial dysfunction.
THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC JAUNDICE
Authors: J. Harold Austin, Richard M. Pearce
Journal: The Journal of Experimental Medicine (1914)

Our studies give evidence of increase in the iron elimination in three of five dogs during a period of two weeks following splenectomy, but not in two other dogs. The occasional increased output of iron may have some relation to the anemia which occurs in the early weeks after splenectomy and which varies in degree in different animals. No evidence was secured of an increase in the iron output at 1, 9, and 20 months after splenectomy. From our own studies and from examination of the literature of the subject, we conclude that the spleen does not exercise a constant and important influence upon the iron metabolism of the body.
Interleukin 10: a novel stimulatory factor for mast cells and their progenitors.
Authors: L Thompson-Snipes, V Dhar, M W Bond, T R Mosmann, K W Moore, D M Rennick
Journal: The Journal of Experimental Medicine (1991)

We have characterized the mast cell stimulating activity of murine cytokine synthesis inhibitory factor, referred to as interleukin 10 (IL-10). It was found that IL-10 alone failed to support the growth of mast cell lines and mast cell progenitors. Nevertheless, it dramatically enhanced their growth when combined with IL-3 or IL-4. Moreover, IL-4 plus IL-10 supported the proliferation of mast cells as well as IL-3, suggesting that these two factors may provide a pathway for their development independent of IL-3. However, optimal mast cell growth was stimulated by the combination of IL-10, IL-4, and IL-3. This particular set of cytokines are coordinately produced by activated T cells and may constitute an effective network regulating early and late stages of mast cell development during certain immune responses.
NEUROPSYCHIATRIC PROBLEMS AT AN ALEUTIAN POST
Authors: GEORGE CRESWELL BURNS
Journal: American Journal of Psychiatry (1945)

1. A series of 325 neuropsychiatric disorders studied at an Aleutian post is presented and discussed from the standpoint of etiology, incidence, reaction types and treatment. 2. Though combat was not a factor in precipitating or reactivating neurotic syndromes in this particular locality, other less tangible external factors played a decisive role in the production of neuropsychiatric disability. 3. Of the psychoneurotic patients, 80% gave a history of clear-cut symptoms before entering the service. 4. Psychoneuroses made up over 50% of the cases. 5. Some of the psychoneurotic reactions in these men who were not in combat were similar to cases reported in the literature as "battle neurosis" and "combat fatigue." 6. Psychoneurosis, dementia precox and miscellaneous disorders are illustrated by case histories. Certain problems in dealing with these disorders are discussed. 7. The general problem of disposition and treatment is presented, emphasis being laid on mental hygiene. Roughly 75% of the psychoneurotic soldiers were kept on duty status. One-third of the total neuropsychiatric cases were evacuated.
NecroX-5 prevents hypoxia/reoxygenation injury by inhibiting the mitochondrial calcium uniporter
Authors: Vu Thi Thu, Hyoung-Kyu Kim, Le Thanh Long, Sung-Ryul Lee, Tran My Hanh, Tae Hee Ko, Hye-Jin Heo, Nari Kim, Soon Ha Kim, Kyung Soo Ko, Byoung Doo Rhee, Jin Han
Journal: Cardiovascular Research (2012)

Preservation of mitochondrial function is essential to limit myocardial damage in ischaemic heart disease. We examined the protective effects and mechanism of a new compound, NecroX-5, on rat heart mitochondria in a hypoxia/reoxygenation (HR) model.NecroX-5 reduced mitochondrial oxidative stress, prevented the collapse in mitochondrial membrane potential, improved mitochondrial oxygen consumption, and suppressed mitochondrial Ca(2+) overload during reoxygenation in an in vitro rat heart HR model. Furthermore, NecroX-5 reduced the ouabain- or histamine-induced increase in mitochondrial Ca(2+).These findings suggest that NecroX-5 may act as a mitochondrial Ca(2+) uniporter inhibitor to protect cardiac mitochondria against HR damage.
Effects of gas and other fume emitting heaters on the development of asthma during childhood
Authors: L L Phoa
Journal: Thorax (2004)

<b>Background:</b> Several studies have shown adverse effects of gas cookers and heaters on respiratory health. The long term effects of early life exposure to these appliances are not known. This study investigated the effect of exposure to fume emitting heaters, currently and during the first year of life, on the risk of asthma outcomes. <b>Methods:</b> A cross sectional study of schoolchildren (n = 627) aged 8–11 years was conducted in Belmont, Australia. Information on symptoms and heating types was collected by parent completed questionnaire. Atopy was assessed by skin prick tests and airway hyperresponsiveness (AHR) was assessed by histamine challenge test. <b>Results:</b> There was no association between the current use of fume emitting heaters and any of the asthma outcomes. However, having been exposed to fume emitting heaters during the first year of life was associated with an increased risk of having AHR (relative risk (RR) 1.47, 95% confidence interval (CI) 1.06 to 2.03), recent wheeze (RR 1.44, 95% CI 1.11 to 1.86), and recent wheeze + AHR (RR 2.08, 95% CI 1.31 to 3.31). <b>Conclusion:</b> If confirmed in other settings, this finding would require a review of the range of heating types that are appropriate for use in households in which young children live.
Role of caveolae in shear stress-mediated endothelium-dependent dilation in coronary arteries
Authors: Qiang Chai, Xiao-Li Wang, Darryl C. Zeldin, Hon-Chi Lee
Journal: Cardiovascular Research (2013)

Caveolae are membrane microdomains where important signalling pathways are assembled and molecular effects transduced.In this study, we hypothesized that shear stress-mediated vasodilation (SSD) of mouse small coronary arteries (MCA) is caveolae-dependent. Methods and resultsMCA (80 -150 mm) isolated from wild-type (WT) and caveolin-1 null (Cav-1 2/2 ) mice were subjected to physiological levels of shear stress (1-25 dynes/cm 2 ) with and without pre-incubation of inhibitors of nitric oxide synthase (L-NAME), cyclooxygenase (indomethacin, INDO), or cytochrome P450 epoxygenase (SKF 525A).SSD was endothelium-dependent in WT and Cav-1 2/2 coronaries but that in Cav-1 2/2 was significantly diminished compared with WT.Pre-incubation with L-NAME, INDO, or SKF 525A significantly reduced SSD in WT but not in Cav-1 2/2 mice.Vessels from the soluble epoxide hydrolase null (Ephx2 2/2 ) mice showed enhanced SSD, which was further augmented by the presence of arachidonic acid.In donor -detector-coupled vessel experiments, Cav-1 2/2 donor vessels produced diminished dilation in WT endothelium-denuded detector vessels compared with WT donor vessels.Shear stress elicited a robust intracellular Ca 2+ increase in vascular endothelial cells isolated from WT but not those from Cav-1 2/2 mice. ConclusionIntegrity of caveolae is critical for endothelium-dependent SSD in MCA.Cav-1 2/2 endothelium is deficient in shear stress-mediated generation of vasodilators including NO, prostaglandins, and epoxyeicosatrienoic acids.Caveolae plays a critical role in endothelial signal transduction from shear stress to vasodilator production and release.