tbuckley/cabot-search huggingface dataset:
The slow miracle.
Authors: P Kent
Journal: BMJ (1981)

1 Pagenelli R, Levinsky RJ, Brostoff J, Wraith DG. Immune complexes containing food proteins in normal and atopic subjects after oral challenge and effect of sodium chromoglycate on antigen absorbtion. Lancet 1979;i:1270-2. 2 Brostoff J, Carini C, Wraith DG, Johns P. Production of IgE complexes by allergen challenge in atopic patients and the effect of sodium chromoglycate. Lancet 1979 ;i: 1268-70. 3 Cunningham-Rundles C, Brandeis WE, Good RA, Day NK. Milk precipitins circulating immune complexes and IgA deficiency. Proc Nati Acad Sei USA 1978;75:3387-9. 4 Cunningham-Rundles C, Brand?is WE, Safai B, O'Reilly R, Day NK, Good RA. Selective IgA deficiency and circulating immune complexes containing bovine proteins in a child with chronic graft versus host disease. Am J Med 1979;67:883-90. 5 Ritchie DM, Boyle JA, Mclnnes JM, et al. Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med 1968;37:393-406. 6 Zubler RH, Lange G, Lambert PH, Miescher PA. Detection of immune complexes in unheated sera by a modified I125 Clq binding test. J Immunol 1976;116:232-5. 7 Elkon KB, Sewell JR, Ryan PFJ, Hughes GRV. Splenic function in non-renal systemic lupus erythematosus. Am J Med 1980;69:80-91. 8 Wide L, Uppsala MD, Bennich H, Johansson SGO. Diagnosis of allergy by an in vitro test for allergen antibodies. Lancet 1967 ;ii: 1105-7. 9 Lessoff MB, Wraith DG, Merrett TG, Merrett J, Buisseret PD. Food allergy and intolerance in 100 patients?local and systemic effects. Q J Med 1980;195:259-71. 10 Kraehenbuhl JP, Campiche MA. Early stages of intestinal absorption of specific antibodies in the new-born. An ultrastructural cytochemical and immunological study in the pig, rat and rabbit. J Cell Biol 1969; 42:345-65. 11 Morris IG. Gamma globulin absorbtion in the newborn. In: Cope CF, ed. Handbook of physiology of the alimentary canal. Vol 2. Washington DC: American Physiological Society, 1968:1491-512. 12 Matthew DJ, Taylor B, Norman AP, Turner MW, Soothill JF. Prevention of eczema. Lancet 1977 ;i:321-4. 13 Korenblat RE, Rothberg RM, Minden P, et al. Immune responses of human adults after oral and parenteral exposure to bovine serum albumin. J Allergy 1968;41:226-35. 14 Walker WA, Isselbacher KJ. Uptake and transport of macromolecules by the intestine. Possible role in clinical disorders. Progress in Gastro enterology 1974;64:531-50. 15 Atherton DJ, Sewell M, Soothill JF, Wells RS, Chilvers CED. A double blind controlled crossover trial of an antigen avoidance diet in atopic eczema. Lancet 1978 ;i:401-3. 16 Elkon KB, Lanham JG, Dash AC, Hughes GRV. The effect of a protein meal on three fluid-phase assays for circulating immune complexes. Clin Exp Immunol (in press).
Oestrogen prevents cardiomyocyte apoptosis by suppressing p38α-mediated activation of p53 and by down-regulating p53 inhibition on p38β
Authors: Han Liu, Ali Pedram, Jin Kyung Kim
Journal: Cardiovascular Research (2010)

We have previously shown that 17-β-estradiol (E2) protects cardiomyocytes exposed to simulated ischaemia–reperfusion (I/R) by differentially regulating pro-apoptotic p38α mitogen-activated protein kinase (p38α MAPK) and pro-survival p38β. However, little is known about how E2 modulation of these kinases alters apoptotic signalling. An attractive downstream target is p53, a well-known mediator of apoptosis and a substrate of p38α MAPK. The aim of this study was to determine whether the cytoprotective actions of oestrogen involve regulation of p53 via cardiac p38 MAPKs. Cultured rat cardiomyocytes underwent hypoxia followed by reoxygenation (H/R) to simulate I/R. We found that inhibiting p53 significantly reduced apoptosis. Phosphorylation of p53 at serine 15 [p-p53(S15)] increased after H/R in a p38α MAPK- and reactive oxygen species (ROS)-dependent manner. E2 at 10 nM effectively inhibited p-p53(S15) and mitochondrial translocation of p53. Blocking p53 led to augmented p38β activity and attenuated ROS, suggesting suppression of this antioxidant kinase by p53. The use of a specific agonist for each oestrogen receptor (ER) isoform, ERα and ERβ, demonstrated that both isoforms participate in preventing cell death by inhibiting p53 in the mitochondria-centred apoptotic processes. Our results demonstrate that during H/R stress, cardiomyocytes undergo p53-dependent apoptosis following phosphorylation of p53 by p38α MAPK, leading to p38β suppression. E2 protects cardiomyocytes by inhibiting p38α-p53 signalling in apoptosis.
PKCβ regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1
Authors: Hisaaki Shinohara, Tomoharu Yasuda, Yuichi Aiba, Hideki Sanjo, Megumi Hamadate, Hiroshi Watarai, Hiroaki Sakurai, Tomohiro Kurosaki
Journal: The Journal of Experimental Medicine (2005)

The B cell antigen receptor (BCR)–mediated activation of IκB kinase (IKK) and nuclear factor–κB require protein kinase C (PKC)β; however, the mechanism by which PKCβ regulates IKK is unclear. Here, we demonstrate that another protein kinase, TGFβ-activated kinase (TAK)1, is essential for IKK activation in response to BCR stimulation. TAK1 interacts with the phosphorylated CARMA1 (also known as caspase recruitment domain [CARD]11, Bimp3) and this interaction is mediated by PKCβ. IKK is also recruited to the CARMA1–Bcl10–mucosal-associated lymphoid tissue 1 adaptor complex in a PKCβ-dependent manner. Hence, our data suggest that phosphorylation of CARMA1, mediated by PKCβ, brings two key protein kinases, TAK1 and IKK, into close proximity, thereby allowing TAK1 to phosphorylate IKK.
Development and validation of a short questionnaire in community acquired pneumonia
Authors: R El Moussaoui, B C Opmeer, P M M Bossuyt, P Speelman, C A J M de Borgie, J M Prins
Journal: Thorax (2004)

A short but sensitive questionnaire evaluating changes in respiratory symptoms and well being during the treatment of community acquired pneumonia (CAP) is needed. We have developed a measurement and evaluated its psychometric properties in 67 patients admitted with CAP.The patients were asked to indicate the presence and severity of dyspnoea, coughing, coughing up sputum, coughing up sputum with ease, the colour of the sputum, fatigue, fitness, and their state of health. The item fatigue showed substantial overlap with fitness and was therefore excluded. The response of the patients to the remaining eight items was used to calculate a CAP score.The percentage of missing data (0.2-1.7%), floor and ceiling effects (0.2/5.5%), internal consistency (Cronbach alpha = 0.87), and the intraclass correlation coefficient for test-retest reproducibility (0.83) met predefined criteria, indicating good acceptability and reliability. Face and clinical validity were satisfactory. Effect sizes under treatment were large, indicating high responsiveness.The newly developed CAP score is a simple, reliable, valid, and highly responsive instrument. This makes it scientifically sound and clinically relevant for measuring outcome when evaluating treatment strategies in CAP.
Community-acquired pneumonia in Europe: causative pathogens and resistance patterns
Authors: M. Woodhead
Journal: European Respiratory Journal (2002)

Community-acquired pneumonia (CAP) is a common condition affecting about 1/1,000 of the adult population per year. It occurs when bacteria enter the alveolar spaces of the lung initiating an inflammatory response which leads to the clinical features of cough, sputum production, breathlessness and sometimes chest pain and haemoptysis. At the end of the last century the causal relationship between bacteria and pneumonia was established and many of the early discoveries about the causes of CAP were made in Europe. Some 41 different prospective studies have established that ∼10 different microbial pathogens regularly cause CAP with occasional cases due to other rarer causes. The frequency of these organisms in Europe is similar in most countries, but there are some geographic differences. Differences in frequency are also apparent according to illness severity. It is generally recognised that Streptococcus pneumoniae is the most important causal bacterium in all countries. A relatively recent development has been the appearance and spread, in some of the common causative bacteria, of resistance to commonly used antibiotics to which they were once sensitive. The frequency of such resistance does vary markedly between European countries. However, published data is often difficult to interpret. The reasons for this are that the frequency of resistance varies according to the age of the patient, the site of the sample, the clinical diagnosis, the use of prior antibiotics and the influence of special groups e.g. those with cystic fibrosis. The impact of in vitro antibiotic resistance on clinical outcome is still poorly understood, but recent studies are helping to clarify this issue and will be discussed.
Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment.
Authors: M del Val, H Hengel, H Häcker, U Hartlaub, T Ruppert, P Lucin, U H Koszinowski
Journal: The Journal of Experimental Medicine (1992)

Selective expression of murine cytomegalovirus (MCMV) immediate-early (IE) genes leads to the presentation by the major histocompatibility complex (MHC) class I molecule Ld of a peptide derived from MCMV IE protein pp89 (Reddehase, M.J., J. B. Rothbard, and U.H. Koszinowski. 1989. Nature (Lond.). 337:651). Characterization of endogenous antigenic peptides identified the pp89 peptide as the nonapeptide 168YPHFMPTNL176 (del Val, M., H.-J. Schlicht, T. Ruppert, M.J. Reddehase, and U.H. Koszinowski. 1991. Cell. 66:1145). Subsequent expression of MCMV early genes prevents presentation of pp89 (del Val, M., K. Münch, M.J. Reddehase, and U.H. Koszinowski. 1989. Cell. 58:305). We report on the mechanism by which MCMV early genes interfere with antigen presentation. Expression of the IE promoter-driven bacterial gene lacZ by recombinant MCMV subjected antigen presentation of beta-galactosidase to the same control and excluded antigen specificity. The Ld-dependent presence of naturally processed antigenic peptides also in nonpresenting cells located the inhibitory function subsequent to the step of antigen processing. The finding that during the E phase of MCMV gene expression the MHC class I heavy chain glycosylation remained in an Endo H-sensitive form suggested a block within the endoplasmic reticulum/cis-Golgi compartment. The failure to present antigenic peptides was explained by a general retention of nascent assembled trimolecular MHC class I complexes. Accordingly, at later stages of infection a significant decrease of surface MHC class I expression was seen, whereas other membrane glycoproteins remained unaffected. Thus, MCMV E genes endow this virus with an effective immune evasion potential. These results also indicate that the formation of the trimolecular complex of MHC class I heavy chain, beta 2-microglobulin, and the finally trimmed peptide is completed before entering the medial-Golgi compartment.
A 3p26-3p25 Genetic Linkage Finding for DSM-IV Major Depression in Heavy Smoking Families
Authors: Michele L. Pergadia, Anne L. Glowinski, Naomi R. Wray, Arpana Agrawal, Scott F. Saccone, Anu Loukola, Ulla Broms, Tellervo Korhonen, Brenda W.J.H. Penninx, Julia D. Grant, Elliot C. Nelson, Anjali K. Henders, Andrew J. Schrage, Yi-Ling Chou, Kaisu Keskitalo-Vuokko, Qin Zhu, Scott D. Gordon, Jacqueline M. Vink, Eco J.C. de Geus, Stuart MacGregor, Jimmy Z. Liu, Gonneke Willemsen, Sarah E. Medland, Dorret I. Boomsma, Grant W. Montgomery, John P. Rice, Alison M. Goate, Andrew C. Heath, Jaakko Kaprio, Nicholas G. Martin, Pamela A.F. Madden
Journal: American Journal of Psychiatry (2011)

The authors tested for genetic linkage of DSM-IV-diagnosed major depressive disorder in families that were ascertained for cigarette smoking.Within a study that targeted families characterized by a history of smoking, analyses derived a subset of 91 Australian families with two or more offspring with a history of DSM-IV major depressive disorder (affected sibling pairs, N=187) and 25 Finnish families (affected sibling pairs, N=33). Within this affected sibling pairs design, the authors conducted nonparametric linkage analysis.In the Australian heavy smoking families, the authors found a genome-wide significant multipoint LOD score of 4.14 for major depressive disorder on chromosome 3 at 24.9 cM (3p26-3p25).Genome-wide significant linkage was detected for major depressive disorder on chromosome 3p in a sample ascertained for smoking. A linkage peak at this location was also observed in an independent study of major depressive disorder.
Plyometric training programmes improve motor performance in prepubertal children
Authors: Damien McKay, Nicholas Henschke
Journal: British Journal of Sports Medicine (2012)

▸  Johnson BA , Salzberg CL, Stevenson DA. A systematic review: plyometric training programs for young children. J Strength Cond Res 2011; 25 :2623–33.

Children with low motor competence have lower levels of physical fitness, perform less physical activity and participate in fewer organised recreational and play activities.1 Plyometric exercise can potentially enhance a child's speed of movement, running speed, power production and jumping ability. However, it is unclear whether plyometric training can be a safe and effective way to progress exercise load in young children.

To evaluate the efficacy and safety of plyometric training for improving motor performance in young children and to determine whether plyometric training could be used to improve the strength, running speed, agility and jumping ability of children with low motor competence.

Four electronic databases (CINAHL, HealthSource, MEDLINE and SportDisc) were searched up to March 2010 for articles describing plyometrics training programmes for children. An initial search for literature using plyometric training in children with low motor proficiency, low motor …
A CASE OF PERTHES'S DISEASE OF THE HIP
Authors: T. G. Evans
Journal: BMJ (1928)

side it can be seeii that-the outline of the acetabulumln on the affected side is distinctly irregular.There is definite increase in the vertical depth of the neck of the femnur.General rarefactioni of the nleck can also be seen.The N'liole of the shaft of the femur shows rarefactioni.Treatmiient.-Mr.J. B. Haycraft, xwho also exaiiiined the patient, was of opinion that coimiplete fixatioln of the hip) in.plaster was nlot necessary; he advised that a walking calliper 5s)liflt w-ould give all the necessary rest to the joint and protection from weight-bearing.Conclulsion .
How to compare color sensations in different brains
Authors: Werner Backhaus
Journal: Behavioral and Brain Sciences (1999)

The qualitative and quantitative properties of color sensations and neuronal color coding are discussed in relation to physiological color exchanges and their evolutionary constraints. Based on the identity mind/matter thesis, additional physical measurements on color sensations are described that will allow us, at least in principle, to compare the qualitative properties of color sensations in different brains.
CD13/aminopeptidase N, a Novel Chemoattractant for T Lymphocytes in Pulmonary Sarcoidosis
Authors: KENJI TANI, FUMITAKA OGUSHI, LUPING HUANG, TETSUYA KAWANO, HIROYA TADA, NORIMITSU HARIGUCHI, SABURO SONE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

CD13/aminopeptidase N (E.C.3.4.11.2) is an ectoenzyme located in the outer membrane of a variety of cells. Because aminopeptidase expression was shown to be upregulated by a Th1-related cytokine, IFN- γ , we examined here the significance of CD13/aminopeptidase N in pulmonary sarcoidosis. The activity of aminopeptidase in bronchoalveolar lavage fluid (BALF) was significantly higher in patients with sarcoidosis than in normal volunteers (NV) and control patients (CP). The activity significantly correlated with lymphocyte percentages and the ratio of CD4 + to CD8 + T lymphocytes in the BALF, and was higher in patients with sarcoidosis with parenchymal involvement than in those without the involvement. CD13/aminopeptidase N protein, which has a molecular mass of approximately 150 kD, was detectable in alveolar macrophages (AM) from patients with sarcoidosis at higher levels than in those from NV. CD13/aminopeptidase N induced in vitro chemotactic migration of human lymphocytes in a concentration range of 10− 5 to 10− 1 U/ml. The chemotactic activity was greater for CD4 + T lymphocytes than for CD8 + T lymphocytes. The enzymatic activity of CD13/aminopeptidase N was responsible for the chemotactic activity because bestatin, an inhibitor of CD13/aminopeptidase N, abolished the chemotactic activity. Higher chemotactic activity for lymphocytes was detected in the BALF from patients with sarcoidosis than in that from NV, and the activity was significantly decreased by treatment with bestatin. This study indicates that CD13/ aminopeptidase N expressed in AM may have a role in T-lymphocyte involvement in the sarcoid lung and the pathogenesis of alveolitis in this disorder.
The Nm23 gene and colorectal cancer.
Authors: S C Whitelaw, J M Northover
Journal: Gut (1994)

EDITOR,-We are glad that Dr Jolobe agreed with the importance of considering coeliac disease in patients with iron deficiency anaemia, even when symptomatology is atypical.The precaution of taking endoscopic biopsy specimens prevents oversight of the diagnosis.We also note his comment on the abnormal appearance of duodenal folds in coeliac disease.We indeed routinely comment on such abnormalities having previously pub- lished evidence' supporting the data of Brocchi et al.'
Eosinophilic Esophagitis: A 10-Year Experience in 381 Children
Authors: Chris A. Liacouras, Jonathan M. Spergel, Eduardo Ruchelli, Ritu Verma, Maria Mascarenhas, Edisio Semeao, Jonathan Flick, Janice Kelly, Terry Brown–Whitehorn, Petar Mamula, Jonathan E. Markowitz
Journal: Clinical Gastroenterology and Hepatology (2005)
CD40-deficient, Influenza-specific CD8 Memory T Cells Develop and Function Normally in a CD40-sufficient Environment
Authors: Byung O. Lee, Louise Hartson, Troy D. Randall
Journal: The Journal of Experimental Medicine (2003)

Two models have been proposed to explain the requirement for CD40 signaling in CD8 T cell responses. The first model suggests that CD4 T cells activate antigen-presenting cells (APCs) through CD40 signaling (APC licensing). In turn, licensed APCs are able to prime naive CD8 T cells. The second model suggests that CD154-expressing CD4 T cells activate CD40-bearing CD8 T cells directly. Although the requirement for CD40 in APC licensing can be bypassed by inflammatory responses to pathogens that activate APCs directly, the second model predicts that CD8 responses to all antigens will be dependent on CD40 signaling. Here we determined which model applies to CD8 responses to influenza. We demonstrate that optimal CD8 T cell responses to influenza are dependent on CD40 signaling, however both primary and secondary responses to influenza require CD40 expression on non–T cells. Furthermore, CD40−/− CD8 T cells proliferate and differentiate to the same extent as CD40+/+ CD8 T cells in response to influenza, as long as they have equal access to CD40+/+ APCs. Thus, CD4 T cells do not activate influenza-specific CD8 cells directly through CD40 signaling. Instead, these data support the classical model, in which CD4 T cells provide help to CD8 T cells indirectly by activating APCs through CD40.
Chemotherapy for cervical carcinoma: factors determining response and implications for clinical trial design.
Authors: K R Brader, M Morris, C Levenback, L Levy, K R Lucas, D M Gershenson
Journal: Journal of Clinical Oncology (1998)

To identify characteristics that predict response to chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix.Between January 1986 and May 1996, 190 chemotherapy-naive patients with advanced or recurrent squamous cell carcinoma of the cervix not amenable to curative radiation therapy or surgery were treated on 14 different chemotherapy protocols at M.D. Anderson Cancer Center. Patient's charts were retrospectively reviewed for patient demographics, tumor and treatment characteristics, and patterns of response and survival.Of 190 patients, 22 had advanced or persistent disease and 168 had recurrent disease. Patients were treated with platinum-based (n=95) and non-platinum-based (n=95) regimens. The overall response rate was 20.0% (4.2% complete response; 15.8% partial response), with a median response duration of 4.8 months. Race, socioeconomic class, tumor stage and grade, mode of primary treatment, time from primary diagnosis to disease recurrence, initial performance status, and use of platinum-based therapy were not significant predictors of response. Age at time of chemotherapy (P=.001) and site of recurrence (P=.044) were significant determinants by multivariate analysis. Patients who were older were more likely to respond to therapy, and the response rate for patients in whom disease recurred outside the irradiated field was 25.2%, compared with a 5.3% response rate for patients with recurrent disease limited to a previously irradiated field.The site of disease recurrence and patient age should be taken into account when designing chemotherapy trials and also when considering chemotherapy in the patient with recurrent cervix cancer.
RAGE-Induced Cytosolic ROS Promote Mitochondrial Superoxide Generation in Diabetes
Authors: Melinda T. Coughlan, David R. Thorburn, Sally A. Penfold, Adrienne Laskowski, Brooke E. Harcourt, Karly C. Sourris, Adeline L.Y. Tan, Kei Fukami, Vicki Thallas-Bonke, Peter P. Nawroth, Michael Brownlee, Angelika Bierhaus, Mark E. Cooper, Josephine M. Forbes
Journal: Journal of the American Society of Nephrology (2009)

Damaged mitochondria generate an excess of superoxide, which may mediate tissue injury in diabetes. We hypothesized that in diabetic nephropathy, advanced glycation end-products (AGEs) lead to increases in cytosolic reactive oxygen species (ROS), which facilitate the production of mitochondrial superoxide. In normoglycemic conditions, exposure of primary renal cells to AGEs, transient overexpression of the receptor for AGEs (RAGE) with an adenoviral vector, and infusion of AGEs to healthy rodents each induced renal cytosolic oxidative stress, which led to mitochondrial permeability transition and deficiency of mitochondrial complex I. Because of a lack of glucose-derived NADH, which is the substrate for complex I, these changes did not lead to excess production of mitochondrial superoxide; however, when we performed these experiments in hyperglycemic conditions in vitro or in diabetic rats, we observed significant generation of mitochondrial superoxide at the level of complex I, fueled by a sustained supply of NADH. Pharmacologic inhibition of AGE-RAGE–induced mitochondrial permeability transition in vitro abrogated production of mitochondrial superoxide; we observed a similar effect in vivo after inhibiting cytosolic ROS production with apocynin or lowering AGEs with alagebrium. Furthermore, RAGE deficiency prevented diabetes-induced increases in renal mitochondrial superoxide and renal cortical apoptosis in mice. Taken together, these studies suggest that AGE-RAGE–induced cytosolic ROS production facilitates mitochondrial superoxide production in hyperglycemic environments, providing further evidence of a role for the advanced glycation pathway in the development and progression of diabetic nephropathy.