tbuckley/cabot-search huggingface dataset:
Bet v 1 homologues in strawberry identified as IgE‐binding proteins and presumptive allergens
Authors: A. L. Karlsson, R. Alm, B. Ekstrand, S. Fjelkner‐Modig, Å. Schiött, U. Bengtsson, L. Björk, K. Hjernø, P. Roepstorff, C. S. Emanuelsson
Journal: Allergy (2004)

Background: No strawberry allergen has so far been identified and characterized. Methods: Serum samples were collected from patients with a suggestive case history of adverse reactions to strawberry and other fruits. Extracts from fresh and frozen strawberries were analysed by sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE), Western blotting and mass spectrometry. Patient blood samples were analysed for inhibition of IgE binding and basophil degranulation. Results: Several IgE‐binding proteins could be detected. In more than half of the patient sera, a 20/18‐kDa doublet band was observed in Western blotting. These two bands were excised and analysed by mass spectrometry showing the presence of proteins belonging to the Bet v 1 family of allergens. Inhibition of the IgE binding to the 20/18‐kDa doublet was obtained by addition of two recombinantly expressed allergens belonging to the Bet v 1 family (Bet v 1 and Mal d 1) and strawberry protein extract. In a cell‐based assay of patient blood samples, basophil degranulation could be induced by strawberry protein extract and by Bet v 1 and Mal d 1. Conclusions: We conclude that strawberry homologues to Bet v 1 may be allergens of importance for adverse reactions to strawberry.
Lysosomal activation by neutral saccharides in cell cultures of synovium.
Authors: J L Marshall, J R Fraser, K D Muirden
Journal: Annals of the Rheumatic Diseases (1977)

On exposure to sucrose or neutral polysaccharides, cell cultures from human synovium showed cytoplasmic vacuolation, increased numbers of lysosomes, and ultrastructural changes simulating those described in rheumatoid synovial intima and similarly treated embryonic caritlage and bone. These changes were accompanied by raised intracellular lysosomal enzyme activity without corresponding increases in the extracellular level of these enzymes. Structural changes and enzymic responses were less intense during exposure to the neutral polysaccharides. The secretion of large polymers of hyaluronic acid was consistently decreased during sucrose treatment. Evidence of heightened hyaluronidase-like activity was found in cellular extracts of sucrose-treated cultures, but not in the culture medium.
Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells
Authors: Stefan Schoenfelder, Tom Sexton, Lyubomira Chakalova, Nathan F Cope, Alice Horton, Simon Andrews, Sreenivasulu Kurukuti, Jennifer A Mitchell, David Umlauf, Daniela S Dimitrova, Christopher H Eskiw, Yanquan Luo, Chia-Lin Wei, Yijun Ruan, James J Bieker, Peter Fraser
Journal: Nature Genetics (2009)
Clindamycin versus Trimethoprim–Sulfamethoxazole for Uncomplicated Skin Infections
Authors: Loren G. Miller, Robert S. Daum, C. Buddy Creech, David Young, Michele D. Downing, Samantha J. Eells, Stephanie Pettibone, Rebecca J. Hoagland, Henry F. Chambers
Journal: New England Journal of Medicine (2015)

Skin and skin-structure infections are common in ambulatory settings. However, the efficacy of various antibiotic regimens in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is unclear.We enrolled outpatients with uncomplicated skin infections who had cellulitis, abscesses larger than 5 cm in diameter (smaller for younger children), or both. Patients were enrolled at four study sites. All abscesses underwent incision and drainage. Patients were randomly assigned in a 1:1 ratio to receive either clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) for 10 days. Patients and investigators were unaware of the treatment assignments and microbiologic test results. The primary outcome was clinical cure 7 to 10 days after the end of treatment.A total of 524 patients were enrolled (264 in the clindamycin group and 260 in the TMP-SMX group), including 155 children (29.6%). One hundred sixty patients (30.5%) had an abscess, 280 (53.4%) had cellulitis, and 82 (15.6%) had mixed infection, defined as at least one abscess lesion and one cellulitis lesion. S. aureus was isolated from the lesions of 217 patients (41.4%); the isolates in 167 (77.0%) of these patients were MRSA. The proportion of patients cured was similar in the two treatment groups in the intention-to-treat population (80.3% in the clindamycin group and 77.7% in the TMP-SMX group; difference, -2.6 percentage points; 95% confidence interval [CI], -10.2 to 4.9; P=0.52) and in the populations of patients who could be evaluated (466 patients; 89.5% in the clindamycin group and 88.2% in the TMP-SMX group; difference, -1.2 percentage points; 95% CI, -7.6 to 5.1; P=0.77). Cure rates did not differ significantly between the two treatments in the subgroups of children, adults, and patients with abscess versus cellulitis. The proportion of patients with adverse events was similar in the two groups.We found no significant difference between clindamycin and TMP-SMX, with respect to either efficacy or side-effect profile, for the treatment of uncomplicated skin infections, including both cellulitis and abscesses. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health; ClinicalTrials.gov number, NCT00730028.).
Economic evaluation of a general practitioner with special interests led dermatology service in primary care
Authors: Joanna Coast, Sian Noble, Alison Noble, Sue Horrocks, Oya Asim, Tim J Peters, Chris Salisbury
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To carry out an economic evaluation of a general practitioner with special interest service for non-urgent skin problems compared with hospital outpatient care. <b>Design</b> Cost effectiveness analysis and cost consequences analysis alongside a randomised controlled trial. <b>Setting</b> General practitioner with special interest dermatology service covering 29 general practices in Bristol. <b>Participants</b> Adults referred to a hospital dermatology clinic who were potentially suitable for management by a general practitioner with special interest. <b>Interventions</b> Participants were randomised 2:1 to receive either care by general practitioner with special interest service or usual hospital outpatient care. <b>Main outcome measures</b> Costs to NHS, patients, and companions, and costs of lost production. Cost effectiveness, using the two primary outcomes of dermatology life quality index scores and improved patient perceived access, was assessed by incremental cost effectiveness ratios and cost effectiveness acceptability curves. Cost consequences are presented in relation to all costs and both primary and secondary outcomes from the trial. <b>Results</b> Costs to the NHS for patients attending the general practitioner with special interest service were £208 ($361; euro 308) compared with £118 for hospital outpatient care. Based on analysis with imputation of missing data, costs to patients and companions were £48 and £51, respectively; costs of lost production were £27 and £34, respectively. The incremental cost effectiveness ratios for general practitioner with special interest care over outpatient care were £540 per one point gain in the dermatology life quality index and £66 per 10 point change in the access scale. <b>Conclusions</b> The general practitioner with special interest service for dermatology is more costly than hospital outpatient care, but this additional cost needs to be weighed against improved access and broadly similar health outcomes.
Immunological crossreactivity between the human immunodeficiency virus type 1 virion infectivity factor and a 170-kD surface antigen of Schistosoma mansoni.
Authors: J Khalife, J M Grzych, R Pierce, J C Ameisen, A M Schacht, H Gras-Masse, A Tartar, J P Lecocq, A Capron
Journal: The Journal of Experimental Medicine (1990)

A monoclonal antibody (mAb) directed against a synthetic peptide derived from the sequence of the human immunodeficiency virus type 1 (HIV-1) regulatory protein virion infectivity factor (vif) labeled the surface of Schistosoma mansoni schistosomula by indirect immunofluorescence. Western blotting showed that two S. mansoni proteins of 170 and 65 kD were recognized by the mAb. Sera from 20% of S. mansoni-infected HIV-seronegative individuals tested recognized the PS4 peptide in an ELISA as did sera from S. mansoni-infected rats. Sera from individuals seropositive for HIV-1, but without schistosomiasis, that reacted with the vif peptide also recognized a 170-kD S. mansoni protein. This crossreactive S. mansoni antigen appears to be a target of immunity in vivo since passive transfer of the mAb VIF-CD3 to naive rats had a protective effect against a challenge infection with S. mansoni cercariae.
Nicotine Enhances Presynaptic and Postsynaptic Glutamatergic Neurotransmission to Activate Cardiac Parasympathetic Neurons
Authors: Robert A. Neff, John Humphrey, Mark Mihalevich, David Mendelowitz
Journal: Circulation Research (1998)

Abstract —Although peripheral cholinergic neurotransmission has long been known to play a pivotal role in the control of heart rate and blood pressure, recent evidence has suggested that central cholinergic mechanisms may be involved in the genesis of hypertension, anxiety, cardiorespiratory control, and, in particular, the respiratory modulation of heart rate. Yet, the sites, mechanisms, and receptor subtypes involved in the action of nicotine within the central nervous system are controversial. The present study demonstrates that nicotine has at least 3 sites of action to increase the activity of vagal cardiac neurons. Nicotine, but not muscarinic agonists, activates postsynaptic receptors and a depolarizing inward current in vagal cardiac neurons studied with the perforated patch-clamp technique in a visualized brain stem slice. In addition, nicotine acts at different presynaptic and postsynaptic sites to facilitate glutamatergic neurotransmission. Presynaptic nicotinic receptors increase the frequency of transmitter release and are sensitive to block by α-bungarotoxin. Nicotine also elicits a previously undescribed augmentation of postsynaptic non-NMDA currents. The presynaptic and postsynaptic receptors may prove to be future targets in the search for agonists to increase vagal cardiac activity and reduce the fatality associated with cardiac hyperexcitability and for antagonists to reduce cardiac vagal activity in pathological conditions associated with abnormally low heart rates and cardiac function such as sudden infant death syndrome.
Risk of Dementia Among White and African American Relatives of Patients With Alzheimer Disease
Authors: Robert C. Green
Journal: JAMA (2002)

Evidence exists that the incidence of Alzheimer disease (AD), as well as risk attributable to specific genetic factors such as apolipoprotein E (APOE) genotype, may vary considerably among ethnic groups. Family studies of probands with AD offer an opportunity to evaluate lifetime risk of dementia among relatives of these probands.To compare lifetime dementia risk estimates among relatives of white and African American probands with probable or definite AD.Risk analysis using data collected by questionnaire and supplemental records between May 1991 and March 2001 at 17 medical centers contributing to the Multi-Institutional Research in Alzheimer's Genetic Epidemiology Study.A total of 17 639 first-degree biological relatives and 2474 spouses of 2339 white AD probands, and 2281 first-degree biological relatives and 257 spouses of 255 African American AD probands.Cumulative risk of dementia by age 85 years, stratified by ethnicity and sex of relatives and by APOE genotype of probands.Cumulative risk of dementia in first-degree biological relatives of African American AD probands by age 85 years was 43.7% (SE, 3.1%), and the corresponding risk in first-degree biological relatives of white AD probands was 26.9% (SE, 0.8%), yielding a relative risk (RR) of 1.6 (95% confidence interval [CI], 1.4-1.9; P<.001). The risk in spouses of African American AD probands of 18.5% (SE, 8.4%) was also higher than the risk in white spouses of 10.4% (SE, 1.7%) but did not reach statistical significance (RR, 1.8; 95% CI, 0.5-6.0; P =.34), likely due to the smaller sample size of African Americans. The proportional increase in risk of dementia among white first-degree biological relatives compared with white spouses of 2.6 (95% CI, 2.1-3.2) was similar to that of 2.4 (95% CI, 1.3-4.4) in African American first-degree biological relatives compared with African American spouses. Female first-degree biological relatives of probands had a higher risk of developing dementia than did their male counterparts, among whites (31.2% vs 20.4%; RR, 1.5; 95% CI, 1.3-1.7; P<.001) as well as among African Americans, although this was not significant among African Americans (46.7% vs 40.1%; RR, 1.2; 95% CI, 0.9-1.7, P =.30). The patterns of risk among first-degree biological relatives stratified by APOE genotype of the probands were similar in white families and African American families.First-degree relatives of African Americans with AD have a higher cumulative risk of dementia than do those of whites with AD. However, in this study, the additional risk of dementia conferred by being a first-degree relative, by being female, or by the probability of having an APOE epsilon4 allele appeared similar in African American and white families. These data provide estimates of dementia risk that can be used to offer counseling to family members of patients with AD.
Switched at birth: a new family for PECAM-1
Authors: Peter J. Newman
Journal: Journal of Clinical Investigation (1999)

Platelet endothelial cell adhesion molecule-1 (PECAM-1, or CD31) is a 130-kDa member of the immunoglobulin (Ig) superfamily that is expressed on the surface of circulating platelets, monocytes, neutrophils, and particular T-cell subsets. It is also a major constituent of the endothelial cell intercellular junction, where up to an estimated one million molecules are concentrated. Because of this cellular expression pattern, PECAM-1 is implicated in several functions, including transendothelial migration of leukocytes, angiogenesis, and integrin activation (for a review of the biology of PECAM-1, see ref. 1). When the cDNA sequence for PECAM-1 was determined more than eight years ago (2), it was originally assigned to the growing family of Ig-like cell adhesion molecules (Ig-CAMs). This classification was the result of the sequence similarity of PECAM-1's extracellular Ig domains to those of other Ig-CAMs characterized at that time, including carcinoembryonic antigen (CEA), intercellular adhesion molecule-1 (ICAM-1), and neural cell adhesion molecule (NCAM). Recent observations however, suggest that we may have been following the wrong half of the molecule and that PECAM-1 may not be a member of the Ig-CAM family after all.
Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations
Authors: Jochen Hampe, Andrew Cuthbert, Peter JP Croucher, Muddassar M Mirza, Silvia Mascheretti, Sheila Fisher, Henning Frenzel, Kathy King, Anja Hasselmeyer, Andrew JS MacPherson, Stephen Bridger, Sander van Deventer, Alastair Forbes, Susanna Nikolaus, John E Lennard-Jones, Ulrich R Foelsch, Michael Krawczak, Cathryn Lewis, Stefan Schreiber, Christopher G Mathew
Journal: The Lancet (2001)
Hypoglycemia in a Diabetes Nurse Care Coordinator
Authors: William A Bauman, Larry N Merkle, Raymond A Rachman, Sumi M Mitsuto
Journal: Diabetes Care (1984)

A 26-yr-old registered nurse who is employed as a diabetes nurse care coordinator had episodes of symptomatic fasting hypoglycemia associated with hyperinsulinemia and a relatively suppressed plasma C-peptide concentration, arousing the suspicion of self-induced illness. However, using a species-specific radioimmunoassay, the species of insulin during an episode of hypoglycemia was determined to be human in origin. Once the patient's illness was attributed to endogenous insulin hypersecretion, prompt surgical intervention and the diagnosis of nesidioblastosis in an adult was made.
Median survival of cancer patients has risen from one to 10 years over past 40 years
Authors: I. Torjesen
Journal: BMJ (2014)

Half of patients who are given a diagnosis of cancer today will survive at least 10 years, whereas only a quarter would have done so 40 years ago, show figures published today by Cancer Research UK.

The charity unveiled the figures as it launched an ambitious 10 year strategy to accelerate progress against cancer still further and set a goal which, in 20 years’ time, would see at least three quarters of all patients with cancer surviving at least10 years after their diagnosis.

In 1971-72 only half of patients with a cancer diagnosis survived for one year. By 2005-06 survival among 50% of patients had risen to five years, and in the next five years it doubled. Predicted survival is 10 years for 50% of patients whose cancer was diagnosed in 2010-11.

To demonstrate this trend, Cancer Research UK analysed details of more than seven million patients …
The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection
Authors: Nilu Goonetilleke, Michael K.P. Liu, Jesus F. Salazar-Gonzalez, Guido Ferrari, Elena Giorgi, Vitaly V. Ganusov, Brandon F. Keele, Gerald H. Learn, Emma L. Turnbull, Maria G. Salazar, Kent J. Weinhold, Stephen Moore, Norman Letvin, Barton F. Haynes, Myron S. Cohen, Peter Hraber, Tanmoy Bhattacharya, Persephone Borrow, Alan S. Perelson, Beatrice H. Hahn, George M. Shaw, Bette T. Korber, Andrew J. McMichael
Journal: The Journal of Experimental Medicine (2009)

Identification of the transmitted/founder virus makes possible, for the first time, a genome-wide analysis of host immune responses against the infecting HIV-1 proteome. A complete dissection was made of the primary HIV-1–specific T cell response induced in three acutely infected patients. Cellular assays, together with new algorithms which identify sites of positive selection in the virus genome, showed that primary HIV-1–specific T cells rapidly select escape mutations concurrent with falling virus load in acute infection. Kinetic analysis and mathematical modeling of virus immune escape showed that the contribution of CD8 T cell–mediated killing of productively infected cells was earlier and much greater than previously recognized and that it contributed to the initial decline of plasma virus in acute infection. After virus escape, these first T cell responses often rapidly waned, leaving or being succeeded by T cell responses to epitopes which escaped more slowly or were invariant. These latter responses are likely to be important in maintaining the already established virus set point. In addition to mutations selected by T cells, there were other selected regions that accrued mutations more gradually but were not associated with a T cell response. These included clusters of mutations in envelope that were targeted by NAbs, a few isolated sites that reverted to the consensus sequence, and bystander mutations in linkage with T cell–driven escape.
Novel amiloride-sensitive sodium-dependent proton secretion in the mouse proximal convoluted tubule
Authors: Joo Young Choi, Mehul Shah, Min Goo Lee, Patrick J. Schultheis, Gary E. Shull, Shmuel Muallem, Michel Baum
Journal: Journal of Clinical Investigation (2000)

The proximal convoluted tubule (PCT) reabsorbs most of the filtered bicarbonate. Proton secretion is believed to be mediated predominantly by an apical membrane Na+/H+ exchanger (NHE). Several NHE isoforms have been cloned, but only NHE3 and NHE2 are known to be present on the apical membrane of the PCT. Here we examined apical membrane PCT sodium-dependent proton secretion of wild-type (NHE3+/+/NHE2+/+), NHE3–/–, NHE2–/–, and double-knockout NHE3–/–/NHE2–/– mice to determine their relative contribution to luminal proton secretion. NHE2–/– and wild-type mice had comparable rates of sodium-dependent proton secretion. Sodium-dependent proton secretion in NHE3–/– mice was approximately 50% that of wild-type mice. The residual sodium-dependent proton secretion was inhibited by 100 μM 5-(N-ethyl-N-isopropyl) amiloride (EIPA). Luminal sodium-dependent proton secretion was the same in NHE3–/–/NHE2–/– as in NHE3–/– mice. These data point to a previously unrecognized Na+-dependent EIPA-sensitive proton secretory mechanism in the proximal tubule that may play an important role in acid-base homeostasis.
Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells
Authors: Alessandra Biffi, Michele De Palma, Angelo Quattrini, Ubaldo Del Carro, Stefano Amadio, Ilaria Visigalli, Maria Sessa, Stefania Fasano, Riccardo Brambilla, Sergio Marchesini, Claudio Bordignon, Luigi Naldini
Journal: Journal of Clinical Investigation (2004)

Gene-based delivery can establish a sustained supply of therapeutic proteins within the nervous system. For diseases characterized by extensive CNS and peripheral nervous system (PNS) involvement, widespread distribution of the exogenous gene may be required, a challenge to in vivo gene transfer strategies. Here, using lentiviral vectors (LVs), we efficiently transduced hematopoietic stem cells (HSCs) ex vivo and evaluated the potential of their progeny to target therapeutic genes to the CNS and PNS of transplanted mice and correct a neurodegenerative disorder, metachromatic leukodystrophy (MLD). We proved extensive repopulation of CNS microglia and PNS endoneurial macrophages by transgene-expressing cells. Intriguingly, recruitment of these HSC-derived cells was faster and more robust in MLD mice. By transplanting HSCs transduced with the arylsulfatase A gene, we fully reconstituted enzyme activity in the hematopoietic system of MLD mice and prevented the development of motor conduction impairment, learning and coordination deficits, and neuropathological abnormalities typical of the disease. Remarkably, ex vivo gene therapy had a significantly higher therapeutic impact than WT HSC transplantation, indicating a critical role for enzyme overexpression in the HSC progeny. These results indicate that transplantation of LV-transduced autologous HSCs represents a potentially efficacious therapeutic strategy for MLD and possibly other neurodegenerative disorders.