tbuckley/cabot-search huggingface dataset:
Characterisation of adhesion receptors mediating lymphocyte adhesion to bronchial endothelium provides evidence for a distinct lung homing pathway
Authors: M P Ainslie
Journal: Thorax (2002)

<b>Background:</b> The lung is an important tertiary lymphoid organ and many lung diseases are associated with disordered lung immunity. Unlike the gut (α4β7 binding to MAdCAM-1) and skin (CLA+ve T cells binding to E-selectin) where the adhesion receptors involved in organ specific homing of T cells have been identified, the molecular pathways controlling lymphocyte migration to the lung are unclear. Using a modified version of the Stamper-Woodruff assay we have investigated the receptors mediating adhesion of peripheral blood lymphocytes to airway endothelium. <b>Methods:</b> Longitudinal frozen sections of bronchus (8 μm) obtained from lung resection specimens were incubated with T cell enriched peripheral blood mononuclear cells for 30 minutes under shaking conditions in the presence of a fluorescently labelled polyclonal anti-von Willebrand antibody to identify blood vessels. After fixation the percentage of blood vessels supporting adhesion was measured. Blocking monoclonal antibodies were used to determine the role of individual adhesion receptors in lymphocyte binding. <b>Results:</b> Specific cation dependent binding of lymphocytes to bronchial endothelium was observed which was significantly inhibited by antibodies against P-selectin, PSGL-1, L-selectin, LFA-1, ICAM-1 and ICAM-2 but not E-selectin, VLA-4, VCAM-1 or Mac-1. This was consistent with the pattern of endothelial expression of these receptors with strong expression of P-selectin and ICAM-1, but negligible expression of E-selectin on bronchial endothelium. <b>Conclusion:</b> This study suggests an important role for PSGL-1/P-selectin in T cell migration into the bronchi and provides further evidence for a pattern of recirculation for respiratory tract homing T cells distinct from the gut and skin.
Purine-rich foods intake and recurrent gout attacks
Authors: Yuqing Zhang, Clara Chen, Hyon Choi, Christine Chaisson, David Hunter, Jingbo Niu, Tuhina Neogi
Journal: Annals of the Rheumatic Diseases (2012)

To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients.The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods.This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine.The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.
Depletion of epidermal langerhans cells and Ia immunogenicity from tape-stripped mouse skin.
Authors: J W Streilein, L W Lonsberry, P R Bergstresser
Journal: The Journal of Experimental Medicine (1982)

To explore the relationships among Ia antigen expression, epidermal Langerhans cells, and the immunogenicity of skin allografts, cellophane tape-stripping was used in H-2 congenic and recombinant mice of defined immunogenetic disparity. Tape-stripping of murine abdominal wall skin achieved almost complete depletion of epidermal Langerhans cells within a few hours of application, as measured by cell surface ATPase and expression of Ia antigens. Tape-stripping also reduced, to a considerable degree (but not absolutely), the Ia immunogenicity of skin allografts prepared from stripped surfaces. No comparable reduction in immunogenicity of class I major histocompatibility determinants was observed, suggesting that Langerhans cells are relatively unimportant in the presentation of H-2K antigens in skin grafts. Langerhans cells reappear within 24 h of tape-stripping to anatomically intact skin, but are detectable in orthotopically grafted only after the graft has been in residence for 4 d, i.e., shortly after it has acquired a blood supply. Repopulating Langerhans cells at that time and thereafter are exclusively of host origin. These results indicate that the traffic of Langerhans cells to the skin can be extremely dynamic, especially when the epidermal surface has been markedly disturbed, and the data imply that, under normal circumstances, large numbers of Langerhans cells can be mobilized readily from an available pool of precursors.
Development of Epstein-Barr virus-specific memory T cell receptor clonotypes in acute infectious mononucleosis.
Authors: S L Silins, S M Cross, S L Elliott, S J Pye, S R Burrows, J M Burrows, D J Moss, V P Argaet, I S Misko
Journal: The Journal of Experimental Medicine (1996)

The importance of cytotoxic T lymphocytes (CTLs) in the immunosurveillance of Epstein-Barr virus (EBV)-infected B cells is firmly established, and the viral antigens of CTL recognition in latent infection are well defined. The epitopes targeted by CTLs during primary infection have not been identified, however, and there is only limited information about T cell receptor (TCR) selection. In the present report, we have monitored the development of memory TCR-beta clonotypes selected in response to natural EBV infection in a longitudinal study of an HLA-B8+ individual with acute infectious mononucleosis (IM). By stimulating peripheral blood lymphocytes with HLA-B8+ EBV-transformed B lymphoblastoid cells, the primary virus-specific CTL response was shown to include specificities for two HLA-B8-restricted antigenic determinants, FLRGRAYGL and QAKWRLQTL, which are encoded within the latent EBV nuclear antigen EBNA-3. TCR-beta sequence analysis of CTL clones specific for each epitope showed polyclonal TCR-beta repertoire selection, with structural restrictions on recognition that indicated antigen-driven selection. Furthermore, longitudinal repertoire analysis revealed long-term preservation of a multiclonal effector response throughout convalescence, with the reemergence of distinct memory T cell clonotypes sharing similar structural restrictions. Tracking the progression of specific TCR-beta clonotypes and antigen-specific TCR-V beta family gene expression in the peripheral repertoire ex vivo using semiquantitative PCR strongly suggested that selective TCR-beta expansions were present at the clonotype level, but not at the TCR-V beta family level. Overall, in this first analysis of antigen-specific TCR development in IM, a picture of polyclonal TCR stimulation is apparent. This diversity may be especially important in the establishment of an effective CTL control during acute EBV infection and in recovery from disease.
US university psychiatrist loses chairmanship over drug company payments
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

Charles Nemeroff, a psychiatrist and expert in depression and mood and anxiety disorders, has lost his post as chairman of the department of psychiatry and behavioural sciences at Emory University in Atlanta, Georgia, because of payments from drug companies that he had not disclosed.

In October, Dr Nemeroff, who had chaired the department for 17 years, temporarily stepped down after the Senate finance committee found that he had received payments from GlaxoSmithKline and other companies but had not reported them to the university or to the National Institutes of Health as required. Emory then set up a new conflict of interest office ( BMJ 2008;337:a2200).

In a statement on 23 December, Emory said that Dr Nemeroff “will remain in the department …
TNF blockade requires 1,25(OH)2D3 to control human Th17-mediated synovial inflammation
Authors: Jan Piet van Hamburg, Patrick S Asmawidjaja, Nadine Davelaar, Adriana M C Mus, Ferry Cornelissen, Johannes P T M van Leeuwen, Johanna M W Hazes, Radboud J E M Dolhain, Pieter A G M Bakx, Edgar M Colin, Erik Lubberts
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> T helper 17 (Th17) cells from patients with early rheumatoid arthritis (RA) induce a proinflammatory feedback loop upon RA synovial fibroblast (RASF) interaction, including autocrine interleukin (IL)-17A production. A major challenge in medicine is how to control the pathogenic Th17 cell activity in human inflammatory autoimmune diseases. The objective of this study was to examine whether tumour necrosis factor (TNF) blockade and/or 1,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>) controls Th17-mediated synovial inflammation. <h3>Methods</h3> Peripheral CD4+CD45RO+CCR6+ Th17 cells of patients with early RA, Th17–RASF cocultures and synovial biopsy specimens were cultured with or without 1,25(OH)<sub>2</sub>D<sub>3</sub> and/or TNFα blockade. Intracellular cytokine expression was detected by flow cytometry. Cytokine and matrix metalloprotease (MMP) production was determined by ELISA. <h3>Results</h3> The authors show that the 1,25(OH)<sub>2</sub>D<sub>3</sub>, but not TNFα blockade, significantly suppressed autocrine IL-17A production in Th17–RASF and synovial biopsy cultures. Combining 1,25(OH)<sub>2</sub>D<sub>3</sub> and TNFα blockade had a significant additive effect compared with single treatment in controlling synovial inflammation, indicated by a further reduction in IL-6, IL-8, MMP-1 and MMP-3 in Th17–RASF cocultures and IL-6 and IL-8 expression in cultures of RA synovial tissue. <h3>Conclusions</h3> These data show that TNF blockade does not suppress IL-17A and IL-22, which can be overcome by 1,25(OH)<sub>2</sub>D<sub>3</sub>. The combination of neutralising TNF activity and 1,25(OH)<sub>2</sub>D<sub>3</sub> controls human Th17 activity and additively inhibits synovial inflammation. This indicates more valuable therapeutic potential of activation of Vitamin D receptorsignalling over current TNF neutralisation strategies in patients with RA and potentially other Th17-mediated inflammatory diseases.
Tuberculosis in National Health Service hospital staff in the west Midlands region of England, 1992-5
Authors: A. Hill, A. Burge, C. Skinner
Journal: Thorax (1997)

BACKGROUND: This study was designed to assess the current incidence of tuberculosis (TB) in National Health Service hospital staff in the West Midlands region of England and to evaluate the effectiveness of occupational health screening and surveillance procedures. METHODS: A four year prospective study (1992-5) was carried out with case ascertainment through occupational health departments and the Midlands Thoracic Society registry of rare respiratory diseases. RESULTS: No case was known to an occupational health department that was not notified by the registry and, in addition, the registry yielded a further six cases. There were 26 cases of active TB, of which 24 presented with symptoms and 12 had no pre-employment screening. All except one doctor were foreign born--mainly from the Indian subcontinent (ISC)--and of recent UK entry, whilst all except one nurse were white females. The following are annual TB incidences per 10(4) (95% confidence interval): ISC and non-white doctors 17.0 (7.8 to 26.2), not significantly greater than in the local ISC and non-white social class 1 working age population (11.8 (8.5 to 15.1)); white nurses 0.6 (0.2 to 1.0), significantly greater (p &lt; 0.05) than that of white women in the local social class 2 working age population (0.2 (0.1 to 0.3)); others (mortuary attendant, physiotherapist, radiographer and theatre technician) 1.0 (0.02 to 2.0), not significantly greater than in the local social class 2 working age population (0.6 (0.5 to 0.7)). CONCLUSIONS: Case ascertainment via the registry was complete. Most cases of TB were in nurses and doctors, more commonly in doctors. However, all but one of the doctors were foreign born and probably had reactivation of infection acquired abroad rather than infection occupationally acquired in the UK. All but one of the nurses, however, were UK born and may have had occupationally acquired disease, their incidence being higher than in the community. As most cases present with symptoms, there needs to be continued emphasis on prompt reporting of suspicious symptoms both before and during employment, and pre-employment BCG vaccination where appropriate.
Wage Losses in the Year After Breast Cancer: Extent and Determinants Among Canadian Women
Authors: S. Lauzier, E. Maunsell, M. Drolet, D. Coyle, N. Hebert-Croteau, J. Brisson, B. Masse, B. Abdous, A. Robidoux, J. Robert
Journal: JNCI Journal of the National Cancer Institute (2008)

Wage losses after breast cancer may result in considerable financial burden. Their assessment is made more urgent because more women now participate in the workforce and because breast cancer is managed using multiple treatment modalities that could lead to long work absences. We evaluated wage losses, their determinants, and the associations between wage losses and changes for the worse in the family's financial situation among Canadian women over the first 12 months after diagnosis of early breast cancer. We conducted a prospective cohort study among women with breast cancer from eight hospitals throughout the province of Quebec. Information that permitted the calculation of wage losses and information on potential determinants of wage losses were collected by three pretested telephone interviews conducted over the year following the start of treatment. Information on medical characteristics was obtained from medical records. The main outcome was the proportion of annual wages lost because of breast cancer. Multivariable analysis of variance using the general linear model was used to identify personal, medical, and employment characteristics associated with the proportion of wages lost. All statistical tests were two-sided. Among 962 eligible breast cancer patients, 800 completed all three interviews. Of these, 459 had a paying job during the month before diagnosis. On average, these working women lost 27% of their projected usual annual wages (median = 19%) after compensation received had been taken into account. Multivariable analysis showed that a higher percentage of lost wages was statistically significantly associated with a lower level of education ( Ptrend = .0018), living 50 km or more from the hospital where surgery was performed ( P = .070), lower social support ( P = .012), having invasive disease ( P = .086), receipt of chemotherapy ( P < .001), self-employment ( P < .001), shorter tenure in the job ( Ptrend < .001), and part-time work ( P < .001). Wage losses and their effects on financial situation constitute an important adverse consequence of breast cancer in Canada.
Presidential Address on Traps and Pitfalls in Special and General Practice: Delivered before the Hunterian Society of London
Authors: J. D. Grant
Journal: BMJ (1901)

Neurotrophins, as target-derived factors, are essential for neuronal survival during development, but during adulthood, their scope of actions widens to become also mediators of synaptic and morphological plasticity. Target disconnection by axotomy produces an initial synaptic stripping ensued by synaptic rearrangement upon target reinnervation. Using abducens motoneurons of the oculomotor system as a model for axotomy, we report that trophic support by brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) or a mixture of both, delivered to the stump of severed axons, results in either the prevention of synaptic stripping when administered immediately after lesion or in a promotion of reinnervation of afferents to abducens motoneurons once synaptic stripping had occurred, in concert with the recovery of synaptic potentials evoked from the vestibular nerve. Synaptotrophic effects, however, were larger when both neurotrophins were applied together. The axotomy-induced reduction in firing sensitivities related to eye movements were also restored to normal values when BDNF and NT-3 were administered, but discharge characteristics recovered in a complementary manner when only one neurotrophin was used. This is the first report to show selective retrograde trophic dependence of circuit-driven firing properties <i>in vivo</i> indicating that NT-3 restored the phasic firing, whereas BDNF supported the tonic firing of motoneurons during eye movement performance. Therefore, our data report a link between the synaptotrophic actions of neurotrophins, retrogradely delivered, and the alterations of neuronal firing patterns during motor behaviors. These trophic actions could be responsible, in part, for synaptic rearrangements that alter circuit stability and synaptic balance during plastic events of the brain.
Failure of postnatal adaptation of the pulmonary circulation after chronic intrauterine pulmonary hypertension in fetal lambs.
Authors: S H Abman, P F Shanley, F J Accurso
Journal: Journal of Clinical Investigation (1989)

To determine the effects of chronic intrauterine pulmonary hypertension on the perinatal pulmonary circulation, we induced chronic elevations of pulmonary artery pressure in 24 late-gestation fetal lambs by maintaining partial compression of the ductus arteriosus with an inflatable vascular occluder. Pulmonary artery pressure was increased from 44 +/- 1 to 62 +/- 3 mmHg for 3-14 d. Although left pulmonary artery blood flow initially increased during acute partial ductus compression, the increase in flow was not sustained during chronic ductus compression despite persistent elevations of pulmonary artery pressure (P less than 0.01). Chronic hypertension decreased the slope of the pressure-flow relationship from 3.4 +/- 0.3 (initial) to 0.9 +/- 0.1 ml/min per mmHg, and blunted the fetal pulmonary vascular response to small increases in PO2 (P less than 0.0001). Pulmonary hypertension for greater than 8 d increased the wall thickness of small pulmonary arteries (P less than 0.001). Compared with controls, hypertensive animals had higher pulmonary artery pressure, lower pulmonary blood flow, and predominant right-to-left ductus shunting after cesarean-section delivery (P less than 0.0001). We conclude that chronic pulmonary hypertension in utero, in the absence of hypoxemia or sustained increases in blood flow, causes abnormal fetal pulmonary vasoreactivity, structural remodeling, and the failure to achieve the normal decline in pulmonary resistance at birth.
Leukotriene B4, a mediator of inflammation present in synovial fluid in rheumatoid arthritis.
Authors: E M Davidson, S A Rae, M J Smith
Journal: Annals of the Rheumatic Diseases (1983)

Leukotriene B4 (LTB4), generated from arachidonic acid following lipoxygenase activity by a variety of inflammatory leucocytes, has been shown to be present in synovial fluid from patients with active rheumatoid arthritis. It does not persist as such, being converted to less active metabolites. The role of LTB4 as one of the natural mediators of inflammation is discussed.
Wilson's disease and hepatocellular carcinoma: possible protective role of copper.
Authors: M L Wilkinson, B Portmann, R Williams
Journal: Gut (1983)

A male patient with Wilson9s disease developed a hepatocellular carcinoma after treatment for nine years with D-penicillamine. Examination at necropsy showed that excess liver copper had been effectively removed. As copper has been shown to protect against chemically induced hepatocellular carcinoma in rats, this may be the reason for the extreme rarity of hepatocellular carcinoma in patients with Wilson9s disease and possibly in other liver diseases with hepatic copper overload.
Paneth cells: their role in innate immunity and inflammatory disease
Authors: D A Elphick
Journal: Gut (2005)

The size and density of stomatal pores limit the maximum rate of leaf carbon gain and water loss (<i>g</i><sub>max</sub>) in land plants. Stomatal size and density are negatively correlated at broad phylogenetic scales, such that species with small stomata tend to have greater stomatal density, but the consequences of this relationship for leaf function has been controversial. The prevailing hypothesis posits that the negative scaling of size and density arises because species that evolved higher <i>g</i><sub>max</sub> also achieved reduced allocation of epidermal area to stomata (stomatal-area minimization). Alternatively, the negative scaling of size and density might reflect the maintenance of a stable mean and variance in <i>g</i><sub>max</sub> despite variation in stomatal size and density, which would result in a higher allocation of epidermal area to achieve high <i>g</i><sub>max</sub> (stomatal-area increase). Here, we tested these hypotheses by comparing their predictions for the structure of the covariance of stomatal size and density across species, applying macroevolutionary models and phylogenetic regression to data for 2408 species of angiosperms, gymnosperms, and ferns from forests worldwide. The observed stomatal size-density scaling and covariance supported the stomatal area increase hypothesis for high <i>g</i><sub>max</sub>. Thus, contrary to the prevailing view, higher <i>g</i><sub>max</sub> is not achieved while minimizing stomatal area allocation but requires increasing epidermal area allocated to stomata. Understanding of optimal stomatal conductance, photosynthesis, and plant water-use efficiency used in Earth System and crop productivity models will thus be improved by including the cost of higher <i>g</i><sub>max</sub> both in construction cost of stomata and opportunity cost in epidermal space.