tbuckley/cabot-search huggingface dataset:
Women in Labour
Authors: J. Elam
Journal: BMJ (1945)

CD4<sup>+</sup> T cells produce IFN-γ contributing to corneal perforation in C57BL/6 (B6) mice after <i>Pseudomonas aeruginosa</i> infection. To determine the role of NK and NKT cells, infected corneas of B6 mice were dual immunolabeled. Initially, more NKT than NK cells were detected, but as disease progressed, NK cells increased, while NKT cells decreased. Therefore, B6 mice were depleted of NK/NKT cells with anti-asialo GM1 or anti-NK1.1 Ab. Either treatment accelerated time to perforation, increased bacterial load and polymorphonuclear neutrophils, but decreased IFN-γ and IL-12p40 mRNA expression vs controls. Next, RAG-1 knockout (−/−; no T/NKT cells), B6.TCR Jα281<sup>−/−</sup> (NKT cell deficient), α-galactosylceramide (αGalCer) (anergized NKT cells) injected and IL-12p40<sup>−/−</sup> vs B6 controls were tested. IFN-γ mRNA was undetectable in RAG-1<sup>−/−</sup>- and αGalCer-treated mice at 5 h and was significantly reduced vs controls at 1 day postinfection. It also was reduced significantly in B6.TCR Jα281<sup>−/−</sup>, αGalCer-treated, and IL-12p40<sup>−/−</sup> (activated CD4<sup>+</sup> T cells also reduced) vs control mice at 5 days postinfection. In vitro studies tested whether endotoxin (LPS) stimulated Langerhans cells and macrophages (Mφ; from B6 mice) provided signals to activate NKT cells. LPS up-regulated mRNA expression for IL-12p40, costimulatory molecules CD80 and CD86, NF-κB, and CD1d, and addition of rIFN-γ potentiated Mφ CD1d levels. Together, these data suggest that Langerhans cell/Mφ recognition of microbial LPS regulates IL-12p40 (and CD1d) driven IFN-γ production by NKT cells, that IFN-γ is required to optimally activate NK cells to produce IFN-γ, and that depletion of both NKT/NK cells results in earlier corneal perforation.
Influence of External Stent Size on Early Medial and Neointimal Thickening in a Pig Model of Saphenous Vein Bypass Grafting
Authors: Mohammad Bashar Izzat, Dheeraj Mehta, Alan J. Bryan, Barnaby Reeves, Andrew C. Newby, Gianni D. Angelini
Journal: Circulation (1996)

Background Late saphenous vein graft failure results from intimal and medial thickening due to migration and proliferation of vascular smooth muscle cells and superimposed atheroma. These changes may represent an adaptation by the vein to its insertion into the arterial system. Using a porcine model of arteriovenous bypass grafting, we recently demonstrated that supporting the graft with a nonrestrictive external Dacron velour stent significantly reduced intimal hyperplasia and total wall thickness. In the present study, we investigated the influence of different external stent sizes on graft wall dimensions and cell proliferation. Methods and Results Three stent sizes were tested: mildly restrictive, nonrestrictive, and oversized (5, 6, and 8 mm in diameter, respectively). Four weeks after grafting, total wall thickness was decreased 40% by 5-mm stents ( P =.02), 66% by 6-mm stents ( P =.0004), and 81% by 8-mm stents ( P =.02 versus unstented grafts). Neointimal thickness was reduced almost 62% by 6-mm and 72% by 8-mm stents (both P =.01) but not by 5-mm stents. As a result, the encroachment of the intima into the lumen was reduced ≈70% by 6- or 8-mm stents ( P =.02 and P =.01 versus unstented grafts, respectively). Both neointimal and medial cell proliferation were significantly reduced by all three stents compared with unstented grafts. Conclusions External stenting of saphenous vein bypass grafts reduces early intimal and medial hyperplasia. Oversized stents give equally profound suppression of intimal thickening, obviating the need for precise size matching with the graft and greatly simplifying the surgical procedure.
Sustained PI3-kinase activity in myeloid cells enhances osteoclastogenesis and augments local bone destruction
Authors: Stephan Blüml, Gernot Schabbauer, Martin Friedrich, Antonia Puchner, Tobias Lohmeyer, Birgit Niederreiter, George Kollias, Josef Smolen, Kurt Redlich
Journal: Annals of the Rheumatic Diseases (2012)

Systemic bone loss in diseases such as osteoporosis or local bone destruction in rheumatoid arthritis, proriasis arthritis or ankylosing spondylitis often leads to disability and severely reduced quality of life. This damage to the bony structures is almost exclusively mediated by a special cell type, the osteoclasts. Therefore, it is important to understand factors and pathways regulating the generation of osteoclasts. In this study, the authors analysed the impact of the PI3-Kinase/PTEN axis on osteoclast generation and bone biology under basal and inflammatory conditions. PTEN is a lipid phosphatase and one of the main antagonists of the PI3-kinase. The authors show that mice with a monocyte/macrophage-specific deletion of PTEN (myeloid specific PTEN<sup>−/−</sup>) display increased osteoclastogenesis in vitro and in vivo compared to wild-type mice. However, under homeostatic conditions, enhanced osteoclastogenesis did not result in systemic bone loss. This was most likely due to a significantly increased bone formation evidenced by an enhanced mineral apposition rate in myeloid specific PTEN<sup>−/−</sup> mice, whereas osteoblast numbers were not different. In contrast, under inflammatory conditions in the hTNFtg mouse model of arthritis, myeloid specific PTEN<sup>−/−</sup> displayed enhanced local bone destruction as well as osteoclast formation in the inflamed joints. The extent of synovial inflammation, however, was not different between wt and myeloid specific PTEN<sup>−/−</sup> mice. These data demonstrate that enhanced PI3-Kinase activity in myeloid cells leads to increased osteoclastogenesis. Under homeostatic conditions, increased osteoclastogenesis is compensated by enhanced osteoblast activity. However, under inflammatory conditions, loss of control of PI3-Kinase activity by PTEN in myeloid cells leads to enhanced local bone destruction.
Helper T-cell responses elicited by Der p 1–pulsed dendritic cells and recombinant IL-12 in atopic and healthy subjects
Authors: Dominique De Wit, Zoulikha Amraoui, Benoît Vincart, Olivier Michel, Alain Michils, Laurence Van Overvelt, Fabienne Willems, Michel Goldman
Journal: Journal of Allergy and Clinical Immunology (2000)
Hyperventilation Syndrome With Unilateral Somatic Symptoms
Authors: Morton E. Tavel
Journal: JAMA (1964)

OVERBREATHING produces a symptom-complex which is commonly encountered by the medical profession: Published data<sup>1,2</sup>would lead one to conclude that 5% to 11% of all general-medical patients have complaints resulting directly or indirectly from hyperventilation. The symptom-complex has been well described during the past quarter-century<sup>1-8</sup>and ordinarily presents no diagnostic challenge. However, considerable confusion can arise when somatic symptoms resulting from the overbreathing occur unilaterally, for these symptoms possess certain similarities to serious organic disease. This peculiar localization of symptoms has been mentioned briefly by other writers<sup>3,5-8</sup>and is believed to be rare. Hysteria has been postulated as its cause,<sup>8</sup>but this theory remains hypothetical. During an 18-month period, this writer has seen seven cases manifesting this curious phenomenon. The purpose herein is to give two cases as examples and summarize briefly the clinical findings, to point out the approximate frequency of unilateral symptoms, and to
Activation of endothelial cells to pathological status by down-regulation of connexin43
Authors: Hsueh-Hsiao Wang, Chang-I Kung, Yuen-Yi Tseng, Yi-Chun Lin, Chi-Hau Chen, Cheng-Ho Tsai, Hung-I Yeh
Journal: Cardiovascular Research (2008)

We investigated the effects of connexin43 (Cx43) down-regulation on endothelial function.We used two different sequences of Cx43-specific small interference RNA (siRNA) to reduce de novo synthesis of Cx43 in human aortic endothelial cells and then examined the expression profiles, proliferation activity and viability, and angiogenic potential. The involvement of mitogen-activated protein kinase signalling pathways was analysed. In parallel, the effect of inhibition of gap-junctional communication by connexin-mimetic peptides was evaluated. During the down-regulation of Cx43 by the siRNA, the cells exhibited impaired gap-junctional communication, proliferation, viability, and angiogenic potential. In addition, plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor were up-regulated. Furthermore, c-jun N-terminal kinase (JNK) and its downstream target c-jun were activated, while caspase-3, p38, and extracellular signal-regulated kinase remained unchanged. Inhibition of JNK by SP600125 blocked the siRNA-induced increased expression of PAI-1 and partially recovered the impaired angiogenic potential. Short-term inhibition of Cx43 channels by connexin-mimetic peptides did not activate JNK.Down-regulation of Cx43 inhibits gap-junctional communication and activates endothelial cells to pathological status, as characterized by up-regulation of coagulatory molecules and impairment of proliferation, viability, and angiogenesis. The processes are associated with activation of JNK signalling pathways and rectified by inhibition of the activation. These results suggest that inadequate expression of Cx43 per se impairs endothelial function by the activation of stress-activated protein kinase.
Hepatitis B Virus Infection among Children Born in the United States to Southeast Asian Refugees
Authors: Adele L. Franks, Cynthia J. Berg, Mark A. Kane, Barbara B. Browne, R. Keith Sikes, William R. Elsea, Anthony H. Burton
Journal: New England Journal of Medicine (1989)

Since 1975 nearly 1 million persons have entered the United States from Southeast Asia, where infection with hepatitis B virus (HBV) is hyperendemic. To evaluate the prevalence and patterns of transmission of HBV infection among the children of refugees from Southeast Asia, we studied 196 refugee families with 257 children born in the United States. Of 31 children born in the United States to mothers with infectious disease, 17 (55 percent) had been infected with HBV. Of 226 children whose mothers did not have infectious disease, 15 had HBV infection — a prevalence of 6.6 percent (95 percent confidence interval, 4.1 to 10.7). The risk of infection was greatest (26 percent) among children living in households with children with infectious disease (relative risk, 5.5; confidence interval, 2.3 to 13.4). Exposure to fathers or other adults with infectious disease was not significantly associated with infection. Of children from households with no persons with infectious disease, 3.9 percent (confidence interval, 1.7 to 8.8) were infected. Nearly half (46 percent) the cases of HBV infection among the U.S.-born children of refugees were not attributable to perinatal transmission from a mother with infectious disease. We conclude that child-to-child transmission may be occurring within and between households. Current recommendations to immunize the newborns of mothers with infectious disease are not sufficient to protect all U.S.-born children of Southeast Asian refugees from HBV infection early in life, when the risk of chronic sequelae and premature death is highest. We recommend that the HBV vaccination policy be expanded to include all newborns of Southeast Asian immigrants. (N Engl J Med 1989; 321: 1301–5.)
Belgium gives terminally ill people the right to die
Authors: Rory Watson
Journal: BMJ (2001)

Belgium is set to become the second country in the world to decriminalise euthanasia. The draft legislation was overwhelmingly approved by its upper house, the Senate, last week and is expected to be approved by its lower chamber before the end of the year.

Strict criteria will have to be met before a patient's wish to end his or her life can be honoured. Patients will have to be aged over 18 years, be …
Theta-Gamma-Modulated Synaptic Currents in Hippocampal Granule Cells In Vivo Define a Mechanism for Network Oscillations
Authors: Alejandro Javier Pernía-Andrade, Peter Jonas
Journal: Neuron (2013)

Theta-gamma network oscillations are thought to represent key reference signals for information processing in neuronal ensembles, but the underlying synaptic mechanisms remain unclear. To address this question, we performed whole-cell (WC) patch-clamp recordings from mature hippocampal granule cells (GCs) in vivo in the dentate gyrus of anesthetized and awake rats. GCs in vivo fired action potentials at low frequency, consistent with sparse coding in the dentate gyrus. GCs were exposed to barrages of fast AMPAR-mediated excitatory postsynaptic currents (EPSCs), primarily relayed from the entorhinal cortex, and inhibitory postsynaptic currents (IPSCs), presumably generated by local interneurons. EPSCs exhibited coherence with the field potential predominantly in the theta frequency band, whereas IPSCs showed coherence primarily in the gamma range. Action potentials in GCs were phase locked to network oscillations. Thus, theta-gamma-modulated synaptic currents may provide a framework for sparse temporal coding of information in the dentate gyrus.
MACROPHAGE-MELANOCYTE HETEROKARYONS
Authors: Saimon Gordon, Zanvil Cohn
Journal: The Journal of Experimental Medicine (1971)

Mouse peritoneal macrophages, which do not synthesize DNA in vitro, were fused with melanocytes, a mouse cell strain which proliferates rapidly in vitro. DNA synthesis was induced in macrophage nuclei 2-3 hr after fusion and occurred irrespective of the number of macrophage nuclei present per melanocyte nucleus in each heterokaryon. 50-80% of macrophage nuclei initiated DNA synthesis in the 3-7 hr period after fusion. The activation of most 11-12-day chick red cell nuclei in melanocyte cytoplasm took longer than 10 hr. The lag before DNA synthesis may reflect the heterochromatin content of each nucleus. Studies with actinomycin showed that heterokaryon RNA synthesis was essential for subsequent macrophage DNA synthesis. This RNA was synthesized 1-4 hr before the DNA and was unlikely to be ribosomal RNA, since it was insensitive to <0.1 microg/ml actinomycin. Melanocytes and macrophages were treated before fusion with actinomycin and bromotubercidin to bring about a more selective inhibition of RNA synthesis. Macrophages pretreated for 1 hr with 5 microg/ml of actinomycin showed less than 20% of control RNA synthesis in the first 4 hr after fusion, but a normal activation of macrophage DNA synthesis. Pretreatment of melanocytes for 3-7 hr with 5 microg/ml bromotubercidin, a reversible inhibitor of RNA synthesis, prevented macrophage DNA synthesis without affecting macrophage RNA synthesis in the heterokaryons (81% of control). These studies showed that only melanocyte RNA synthesis was essential for the production of macrophage DNA. The exposure of one cell partner to actinomycin before fusion caused cross-toxicity of the untreated nucleus after fusion. Bromotubercidin, an adenosine analogue which is incorporated into RNA, did not give rise to such cross-toxicity after fusion. Once the macrophage nucleus becomes activated in the heterokaryon it becomes less sensitive to the action of actinomycin.
A CASE OF TORSION OF THE GALL BLADDER
Authors: H. C. Jonas
Journal: BMJ (1923)

MEDICAL JOURNAl absorbed, instead of being thus excreted, they exercise the typical effect of protein bodies on metabolism-that is, they stimulate metabolism to a degree considerably in excess of their mere calorific value.The same fate also overtakes the fatty amino-acids.The second factor to be nioted is this: that if we can assume that the source of adrelnaline is to be found among the amino-acids in the intestine produced by the digestive ferments, the failure of the putrefactive organisms still further to split up this precursor into an excretable substaince again has a specific bearing upon the increase in the basal metabolic rate, for it is now generally conceded that adrenaline is the sensitizer of the sympathetic nervous systen, " the katabolic nerve of the body."
Memory T cells represent the predominant lymphocyte subset in acute and chronic liver inflammation
Authors: Riccardo Volpes, Joost J. van den Oord, Valeer J. Desmet
Journal: Hepatology (1991)

T cells can be divided into two main phenotypic subpopulations-i.e., the CD45RA-positive (2H4-positive) "naive" subset and the CD45RO-positive (UCHL1-positive) "memory" subset. In light of this recent functional reinterpretation of T-lymphocyte subpopulations, we reinvestigated the composition of the inflammatory infiltrate in liver biopsy specimens from patients with acute and chronic hepatitis. In normal liver, the few scattered mononuclear cells present in portal tracts and in the intralobular parenchyma consisted of both CD45RA-positive (2H4-positive) naive and CD45RO-positive (UCHL1-positive) memory T cells. In inflammatory liver diseases, portal tract and periportal and intralobular areas of inflammation consisted virtually only of CD45RO-positive (UCHL1-positive) memory T cells, which strongly expressed the CDw29 (4B4) antigen, and the adhesion molecules LFA-1, CD2, LFA-3, CD44 and VLA-4 and the activation marker human leukocyte antigen-DR. These results indicate that activated memory T cells represent the predominant subpopulation of lymphocytes in areas of liver inflammation. Memory T cells strongly express various homing receptors and adhesion molecules, which probably allow them to accumulate at inflammatory sites and to strengthen interaction with target cells. Furthermore, the increased number of memory T cells with enhanced interferon-gamma production in areas of liver inflammation may contribute to the maintenance and up-regulation of immune responses occurring in inflammatory liver diseases.
O1.03 * DENSITY OF TUMOR INFILTRATING LYMPHOCYTES CORRELATES WITH BRAIN EDEMA AND OVERALL SURVIVAL IN BRAIN METASTASES
Authors: A. S. Berghoff, A. Wohrer, M. Hackl, J. Pichler, M. Hutterer, G. Widhalm, K. Dieckmann, D. Prayer, J. A. Hainfellner, M. Preusser
Journal: Neuro-Oncology (2014)

BACKGROUND: Density of tumor-infiltrating lymphocytes (TILs) has a prognostic impact in various extracranial solid tumors. While a favorable correlation of CD3+ effector TIL, CD8+ cytotoxic TIL and CD45RO+ memory TIL density was observed, high density of FOXP3+ regulatory TILs is associated with impaired survival prognosis in previous studies of primary extracranial solid tumors. So far, TILs have not been analyzed in brain metastases (BM) from solid tumors. METHODS: 118 BM specimens (primary tumor: lung cancer (62/118; 52%); breast cancer (17/118; 14%); melanoma (6/118; 5%); kidney cancer (10/118; 8%); another primary tumor (23/118; 19%)) were available. All patients had one single BM and received neurosurgical resection as first treatment for BM. Preoperative MRT was available in all patients. Clinical data was retrieved by chart review. Overall survival (OS) was defined as time from first diagnosis of BM to last follow up or death. Analysis of for CD3, CD8, CD45RO and FOXP3 was performed by immunohistochemical methods on full section slides and analyzed using previously published semiquantitative evaluation criteria. RESULTS: Dense infiltration with CD3+ TILs was observed in 64/118 (54%) specimens, with CD8+ TILs in 70/118 (59%), with CD45R0+ TILs in 72/118 (61%) and with FOXP3+ TILs in 26/118 (22%) specimens. Dense CD3+ TILs infiltration was more frequently observed in lung cancer, melanoma and kidney cancer BM than in breast cancer BM (p = 0.024; Chi square test). Melanoma BM had more frequently dense infiltration with FOXP3+ TILs (p = 0.003; Chi square test). Density of CD3 + , CD8 + , CD45RO + , or FOXP3+ TILs did not correlate with preoperative steroid application (p > 0.05; Chi Square test). Patients with dense infiltration of CD3+ TIL had significantly improved OS (27 vs. 12 months; p = 0.002; log rank test). Further, dense infiltration with CD8+ TILs was associated with improved OS (16 vs. 12 months; p = 0.048; log rank test) and large peritumoral edema on the preoperative MRI (p = 0.03; Chi Square test). Dense infiltration with CD45RO+ TILs was correlated with improved survival prognosis (18 vs. 8 months; p = 0.01; log rank test). Patients with dense infiltration of FOXP3+ TILs had an impaired survival prognosis (6 vs. 16 months; p = 0.05; log rank test). A composite "immuno score" showed a strong association with median OS (27 months for cases CD8 + /CD45RO + /FOXP3- infiltrates and 6 for cases with CD8-/CD45RO-/FOXP3+ infiltrates; p = 0.001 log-rank test). CONCLUSION: Dense TILs infiltrates are common in BM and correlate with the amount of peritumoral brain edema and improved survival prognosis. Further studies should investigate the therapeutic impact of immunomodulatory agents in patients with BM.
Prevention of the Development and Progression of Renal Disease
Authors: Thomas H. Hostetter
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Prevention of the major causes of ESRD, hypertension, and diabetes, is possible. Careful glycemic control can prevent diabetes nephropathy. BP control can likely prevent the large majority of hypertensive renal disease. Testing for diabetic renal disease is well founded. In contrast, screening for hypertensive kidney disease is less well defined. Most established renal disease can be treated with glycemic control in the case of diabetes, BP treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and dietary protein restriction. Other therapeutic targets have been proposed, but are not well established. Future research should focus on defining the high risk patients, developing better markers of risk, and designing additional therapies. E-mail: [email protected]
Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation
Authors: Guoliang Cui, Xia Qin, Lili Wu, Yuebo Zhang, Xiaoyan Sheng, Qiwen Yu, Hongguang Sheng, Beili Xi, Jingwu Z. Zhang, Ying Qin Zang
Journal: Journal of Clinical Investigation (2011)

Th17 cells are a subset of CD4+ T cells with an important role in clearing certain bacterial and fungal pathogens. However, they have also been implicated in autoimmune diseases such as multiple sclerosis. Exposure of naive CD4+ T cells to IL-6 and TGF-β leads to Th17 cell differentiation through a process in which many proteins have been implicated. We report here that ectopic expression of liver X receptor (LXR) inhibits Th17 polarization of mouse CD4+ T cells, while LXR deficiency promotes Th17 differentiation in vitro. LXR activation in mice ameliorated disease in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, whereas LXR deficiency exacerbated disease. Further analysis revealed that Srebp-1, which is encoded by an LXR target gene, mediated the suppression of Th17 differentiation by binding to the E-box element on the Il17 promoter, physically interacting with aryl hydrocarbon receptor (Ahr) and inhibiting Ahr-controlled Il17 transcription. The putative active site (PAS) domain of Ahr and the N-terminal acidic region of Srebp-1 were essential for this interaction. Additional analyses suggested that similar LXR-dependent mechanisms were operational during human Th17 differentiation in vitro. This study reports what we believe to be a novel signaling pathway underlying LXR-mediated regulation of Th17 cell differentiation and autoimmunity.
TCT-535 5 year experience with the Absorb bioresorbable vascular scaffold: The Maasstad Absorb Registry
Authors: Georgios J. Vlachojannis, Kees-Jan Royaards, Marielle A. Koper, Bianca M. Boxma-de Klerk, Victor van den Berg, Jochem Wassing, Pieter C. Smits
Journal: Journal of the American College of Cardiology (2015)