tbuckley/cabot-search huggingface dataset:
Processing of Tumor-Associated Antigen by the Proteasomes of Dendritic Cells Controls<i>In vivo</i>T-Cell Responses
Authors: Laurence Chapatte, Maha Ayyoub, Sandra Morel, Anne-Lise Peitrequin, Nicole Lévy, Catherine Servis, Benoît J. Van den Eynde, Danila Valmori, Frédéric Lévy
Journal: Cancer Research (2006)

Abstract Dendritic cells are unique in their capacity to process antigens and prime naive CD8+ T cells. Contrary to most cells, which express the standard proteasomes, dendritic cells express immunoproteasomes constitutively. The melanoma-associated protein Melan-AMART1 contains an HLA-A2-restricted peptide that is poorly processed by melanoma cells expressing immunoproteasomes in vitro. Here, we show that the expression of Melan-A in dendritic cells fails to elicit T-cell responses in vitro and in vivo because it is not processed by the proteasomes of dendritic cells. In contrast, dendritic cells lacking immunoproteasomes induce strong anti-Melan-A T-cell responses in vitro and in vivo. These results suggest that the inefficient processing of self-antigens, such as Melan-A, by the immunoproteasomes of professional antigen-presenting cells prevents the induction of antitumor T-cell responses in vivo. (Cancer Res 2006; 66(10): 5461-8)
Patients with Metabolic Bone Disease
Authors: JULES B. PUSCHETT
Journal: Annals of Internal Medicine (1970)

Letters and Comments1 May 1970Patients with Metabolic Bone DiseaseJULES B. PUSCHETT, M.D.JULES B. PUSCHETT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-762_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Patients who have either vitamin-D-resistant rickets (osteomalacia) or hypoparathyroidism are being sought for metabolic studies to be performed on the Clinical Research Center of the Hospital of the University of Pennsylvania, Philadelphia. Physicians with candidates for study are requested to contact Jules B. Puschett, M.D., at EV 2-2400, ext. 458.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of Pennsylvania Division Veterans Administration Hospital University and Woodland Avenues Philadelphia, Pa. 19104 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 762-762KeywordsBoneHypoparathyroidismMetabolic disorders Issue Published: 1 May 1970 PDF downloadLoading ...
Platelet-activating factor is a weak platelet agonist: Evidence from normal human platelets and platelets with congenital secretion defects
Authors: A. Koneti Rao, Janet Willis, Barbara Hassell, Carol Dangelmaier, Holm Holmsen, J. Bryan Smith
Journal: American Journal of Hematology (1984)

We have examined the effects of a novel platelet agonist, platelet activating factor (PAF), on human platelets. Irreversible aggregation and 14C-serotonin secretion in response to PAF (10(-5) M) was found to be dependent on both thromboxane production and secreted adenosine diphosphate (ADP). Liberation of arachidonic acid (AA) from membrane-bound phospholipids is a prerequisite step in platelet thromboxane production. Studies with 3H-AA-labeled platelets revealed that PAF (10(-5) M) was a weak stimulus for the mobilization of AA. In addition, PAF (10(-5) M) was found to be a weak inducer of thromboxane synthesis (mean = 6 pmol/10(8) platelets) as compared to thrombin 5 U/ml (mean = 177 pmol/10(8) platelets), measured using a radioimmunoassay for thromboxane B2. Formation of phosphatidic acid is an early step in stimulus-response coupling in platelets. Our studies indicate that PAF is a weak stimulus for phosphatidic acid formation as well. To obtain further insights into its action, we examined the effect of PAF on platelets from three groups of patients with congenital secretion defects: patients with the storage pool deficiency, those with impaired thromboxane synthesis due to impaired liberation of AA from phospholipids, and those with impaired secretion despite normal granule stores and thromboxane production. The response to PAF was impaired in all patients, providing further evidence that PAF-induced platelet activation is dependent on secreted ADP and thromboxane A2 synthesis, and occurs by mechanisms common to a number of agonists. Overall, these studies indicate that PAF is a weak platelet agonist.
Acute Inversion of the Urinary Bladder in Labour
Authors: J. C. Sutherland, R. T. Merki
Journal: BMJ (1964)

Medical MemorandaMEDIBuR 991was 429 mg./100 ml., with no serum turbidity.The patient was placed on a low-cholesterol diet together with maize-oil supplements, and a month later was started on Atromid 0.5 g. t.d.s.The lesions began to regress, and by January 1964 had almost disappeared (Fig. 4).Cholesterol values during this time, however, remained elevated (260-358 mg./100 ml.).Once again, no side-effects were observed.COMMENT Disappearance of xanthomatous deposits from the skin makes one hopeful that similar deposits in the arterial wall may regress and that atheroma may be prevented or postponed.Up to the present the best therapy has probably been the replacement of the normal dietary fats by an unsaturated fat, corn oil (Jepson, 1961).In his series regression of xanthoma tuberosum was seen in six of nine patients, and of xanthoma tendinosum in seven of 12 patients.Significant depression of blood cholesterol, phospholipids, and plasma turbidity was also obtained.Corn-oil foods are, however, expensive and there is a danger that this regimen, which m'ust presumably be lifelong, may be abandoned.It is possible that therapy with Atromid is equally or more effective; it can be carried out without dietary restric- tion and is simple and safe.Xanthomata underwent remarkable regression in our two patients, and in Harrison and Goldberg's patient (1963), but were unaffected in the seven patients treated by Jepson and James (1963).It is clear, therefore, that further trials are needed.
Endogenous prostaglandins in peptic ulcer disease.
Authors: R Baker, B M Jaffe, C W Venables
Journal: Gut (1979)

Plasma concentrations of prostaglandins E and F have been measured by radioimmunoassay in patients undergoing diagnostic upper intestinal endoscopy. The results fail to support a previously reported deficiency of plasma PGE in duodenal ulcer patients. Plasma prostaglandin concentrations failed to correlate with the parameters of gastric secretion studied; and were unaffected by histamine H2-receptor blockade or the activity of duodenal ulceration. During combined pentagastrin and insulin secretory studies there was a significant correlation between the outputs of PGE and acid into gastric juice.
Comparison of chaotic and sinusoidal vasomotion in the regulation of microvascular flow
Authors: D. Parthimos, D.H. Edwards, T.M. Griffith
Journal: Cardiovascular Research (1996)

Objective: In order to elucidate the physiological consequences of irregular vasomotion on microvascular flow we have compared the theoretical hydrodynamic consequences of sinusoidal and chaotic fluctuations in the diameter of a single resistance,vessel.Methods: In initial experimental studies vasomotion was induced by histamine in isolated rabbit ear resistance arteries (m 150 pm diameter) perfused with physiological buffer under both controlled-flow and controlled-pressure conditions.The phase relationships between the observed oscillations in flow and pressure were used to validate a theoretical electrical circuit in which vasomotion was simulated as sinusoidal or as chaotic fluctuations in distal resistance, with compliance incorporated as a parallel capacitance.Results: In both the experimental and theoretical situation, oscillations in flow led those in pressure by * 90" in controlled-flow mode, whereas they were -180" out of phase in controlled-pressure mode.In the theoretical model an increase in the amplitude of sinusoidal or chaotic diameter fluctuations enhanced flow, but "paradoxically" increased both time-averaged resistance and conductance.The model showed that with sinusoidal fluctuations the "efficiency" of perfusion (i.e., flow/viscous work expended in perfusing the vessel undergoing vasomotion) exhibited a peak whose magnitude was a function of vasomotion amplitude and the proximal capacitance in the circuit, and was attributable to transient release of charge from this capacitance.This phenomenon was not observed in simulations with chaotic vasomotion.Hydrodynamic effects specific to the presence of chaotic dynamics (e.g., abrupt increases or decreases in flow under the variation of a single parameter) were also evident when the intrinsic complexity of the vasomotion, rather than its amplitude, was varied.Conclusions: The model suggests (i) that vasomotion may serve to increase flow, (ii) that conductance provides a more accurate physiological measure of the functional consequences of active vasomotion than resistance, (iii) that chaotic vasomotion dissipates transients more readily than sinusoidal vasomotion, thereby conferring greater stability to microcirculatory perfusion and (iv) that specific modes of chaotic vasomotion may influence flow independently of their amplitude.
Evidence for the association of unexplained pulmonary hypertension in children with the major histocompatibility complex.
Authors: R J Barst, E R Flaster, A Menon, M Fotino, J H Morse
Journal: Circulation (1992)

BACKGROUND A link between primary pulmonary hypertension (PPH) and autoimmune disorders has been postulated. To investigate this relation, we performed immunofluorescent antinuclear antibody tests (ANA) and serological human leukocyte antigen (HLA)-A, B, C, DR, and DQ typing on two groups of Caucasian children with unexplained pulmonary hypertension (PHT) and their parents. METHODS AND RESULTS Group 1 consisted of 17 children with PPH including two patients with familial PPH and three patients with trivial congenital pulmonary to systemic communications. Group 2 consisted of 13 children with advanced PHT and anatomically large congenital pulmonary to systemic communications (PHT + shunt). Both groups had comparably severe pulmonary vascular disease documented by cardiac catheterization. The following statistically significant data (p less than 0.05) were obtained when the study groups were compared with those published for normal controls. Although positive ANAs and varying titers of autoantibodies were found in both groups of children and mothers (not fathers), +ANAs were only significant for the maternal groups. The PPH (group 1) children had increased frequencies of HLA-DR3, DRw52, and DQw2 and decreased DR5, whereas the group 2 (PHT + shunt) children (also their parents) had no statistically significant alterations in any of the DR or DQ alleles. The PPH mothers had decreased DQw3, an allele in linkage disequilibrium with DR5. CONCLUSIONS These immunogenetic data suggest that childhood PPH appears to be associated with the major histocompatibility complex alleles HLA-DR3, DRw52, and DQw2. This newly found correlation of juvenile PPH with these alleles adds this disease to the DR3+ group of autoimmune diseases. Further studies are needed to determine whether there is also an immunological or autoimmune component in some children with PHT + shunt lesions because this group lacked an HLA association.
Metal particulate matter components affect gene expression and beat frequency of neonatal rat ventricular myocytes.
Authors: Donald W Graff, Wayne E Cascio, Joseph A Brackhan, Robert B Devlin
Journal: Environmental Health Perspectives (2004)

Soluble particulate matter (PM) components (e.g., metals) have the potential to be absorbed into the bloodstream and transported to the heart where they might induce the expression of inflammatory cytokines and remodel electrical properties. We exposed cultured rat ventricular myocytes to similar concentrations of two metals [zinc (Zn) and vanadium (V)] found commonly in PM and measured changes in spontaneous beat rate. We found statistically significant reductions in spontaneous beat rate after both short-term (4-hr) and long-term (24-hr) exposures, with a more substantial effect seen with Zn. We also measured the expression of genes associated with inflammation and a number of sarcolemmal proteins associated with electrical impulse conduction. Exposure to Zn or V (6.25-50 microM) for 6 hr produced significant increases in IL-6, IL-1 alpha, heat shock protein 70, and connexin 43 (Cx43). After 24 hr exposure, Zn induced significant changes in the gene expression of Kv4.2 and KvLQt (potassium channel proteins), the alpha 1 subunit of the L-type calcium channel, and Cx43, as well as IL-6 and IL-1 alpha. In contrast, V produced a greater effect on Cx43 and affected only one ion channel (KvLQT1). These results show that exposure of rat cardiac myocytes to noncytotoxic concentrations of Zn and V alter spontaneous beat rate as well as the expression of ion channels and sarcolemmal proteins relevant to electrical remodeling and slowing of spontaneous beat rate, with Zn producing a more profound effect. As such, these data suggest that the cardiac effects of PM are largely determined by the relative metal composition of particles.
Higher Levels of the Anti-inflammatory Protein CC10 Are Associated with Improvement in Bronchial Dysplasia and Sputum Cytometric Assessment in Individuals at High Risk for Lung Cancer
Authors: Jiping Chen, Stephen Lam, Aprile Pilon, Annette McWilliams, Calum MacAulay, Eva Szabo
Journal: Clinical Cancer Research (2008)

Abstract Purpose: CC10, a 10-kDa anti-inflammatory protein secreted by bronchiolar Clara cells, is infrequently expressed in non–small cell lung cancer and its overexpression in non–small cell lung cancer cell lines results in a less malignant phenotype. Several lines of evidence have shown that bronchial dysplasia and sputum atypia are predictors of lung cancer. We investigated whether changes in CC10 expression correlate with regression of bronchial dysplasia and/or improvement in sputum abnormalities as measured by image cytometry. Experimental Design: High-risk smokers enrolled in a chemoprevention trial underwent serial bronchoscopies with biopsies and bronchoalveolar lavage (BAL) collection, sputum assessment by image cytometry, and blood collection. CC10 was measured by competitive ELISA in BAL and plasma. Logistic regression analyses were done to determine the associations between CC10 levels and the improvement in bronchial dysplasia and sputum cytometric assessment. Results: The net change in the BAL CC10 levels in subjects with improved bronchial lesions or improved sputum cytometry assessment was significantly higher than in those without improvement (P &amp;lt; 0.05). The odds ratio (95% confidence interval) associated with 1-unit increase in CC10 was 2.72 (1.31-5.64) for regression of dysplastic lesions and 2.94 (1.22-7.05) for improvement in sputum cytometry assessment after multivariate adjustment. Plasma CC10 was not significantly associated with either outcome. Conclusions: Higher BAL CC10 levels are significantly correlated with regression of bronchial dysplasia and improvement in sputum cytometry assessment in smokers with high lung cancer risk. Whether CC10 levels can predict clinical outcomes among high-risk populations warrants further investigation.
Realistic neurons can compute the operations needed by quantum probability theory and other vector symbolic architectures
Authors: Terrence C. Stewart, Chris Eliasmith
Journal: Behavioral and Brain Sciences (2013)

Abstract Quantum probability (QP) theory can be seen as a type of vector symbolic architecture (VSA): mental states are vectors storing structured information and manipulated using algebraic operations. Furthermore, the operations needed by QP match those in other VSAs. This allows existing biologically realistic neural models to be adapted to provide a mechanistic explanation of the cognitive phenomena described in the target article by Pothos &amp; Busemeyer (P&amp;B).
Effect of chloroacetic acids on the kidneys.
Authors: M E Davis
Journal: Environmental Health Perspectives (1986)

The effects of dichloroacetate (DCA) and trichloroacetate (TCA) administered in drinking water were studied. At high concentrations of either compound, weight loss, or failure to gain weight, was observed. Food consumption was also decreased; both effects were attributed to decreased water consumption. Renal phosphate-dependent glutaminase activity was increased at the highest concentration, and urinary ammonia was also increased. These changes indicated renal adaptation to an acid load. DCA, in pharmacological doses, impairs glucoenogenesis from lactate in part by decreasing lactate availability. Similar tendencies were observed in the present studies; however, female rats showed a biphasic response. At lower DCA concentrations, tissue lactate and plasma glucose concentrations were increased, whereas at higher concentrations of DCA, the expected decreases were observed.
Mushroom‐shaped red blood cells in protein band‐3 deficiency
Authors: Jean‐François Lesesve
Journal: American Journal of Hematology (2010)

A 12-year-old boy was hospitalized for a chronic compensated hemolytic anemia, with asthenia as the major complaint. No particular familial history was present and there was no exposure to toxic substances. Scleral icterus and mild splenomegaly were noted. Laboratory tests indicated Hb: 11.1 g/dL; mean cell volume: 90.2 fL; mean corpuscular hemoglobin concentration: 35.1 g/dL; red cell distribution width: 18.1%; reticulocytes: 121 × 109/L. White blood cells and platelets were in reference range (RR). Haptoglobin was below the level of detection, lactic dehydrogenase: 310 UI/L (RR < 210), bilirubin: 35 μmol/L (RR < 18). Direct Coombs test was negative. Hemoglobin electrophoresis revealed HbA1: 96% and HbA2: 4%. No anomalies were detected in the erythrocyte activities of either glucose-6-phosphate dehydrogenase or pyruvate kinase. Flow cytometric testing (CD55 and CD59 determination on erythrocytes and polymorphonuclears) for paroxysmal nocturnal hemoglobinuria was negative. May-Grunwald-Giemsa staining of the peripheral blood smear highlighted some peculiar erythrocyte shapes with numerous “mushrooms” (more than 2 per field at high power magnification) and some spherocytes among moderate aniso-poïkilocytosis (mosaic figure; Image 1). A SDS-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated decrease of protein band-3. Unfortunately, neither osmotic gradient ektacytometry nor molecular testing could be performed. Mosaic image of bizarre erythrocytes (mushroom-/fish-/whale-shaped); May-Grunwald-Giemsa, ×1000. Mutations in the SLC-A1 gene encoding the band-3 protein are frequently reported as the cause of hereditary spherocytosis [1-3]. When numerous, “mushroom” but also “puzzle” “fish”/“whale,” or “yeast”-shaped erythrocytes are associated with band-3 deficiency. Such bizarre erythrocytes can be also observed after bone marrow myelofibrosis and, occasionally, in non specific dyserythropoïesis, but, in such contexts, mushroom cells are only scattered in the middle of a marked poïkilocytosis.
The Effect of Bisacodyl on Whole-Gut Irrigation in Preparation for Colonoscopy
Authors: E. H. H. M. Rings, C. J. J. Mulder, G. N. J. Tytgat
Journal: Endoscopy (1989)

The cleansing effect of whole-gut irrigation with a balanced electrolyte solution (BES), with or without pretreatment with bisacodyl, was compared, in order to establish whether bisacodyl reduces the duration and side effects of whole-gut irrigation. Bisacodyl at a dose of 20 mg in 2 days reduced the duration of the whole-gut irrigation procedure. No side-effects related to bisacodyl were demonstrated. We therefore consider bisacodyl to be a useful and inexpensive adjunt for colonic preparation of patients receiving whole-gut irrigation.
TV: Driving Mum Crazy
Authors: I. McClure
Journal: BMJ (2000)

Channel 5, Fridays at 8 30 pm, 11 to 25 January

Can the media do justice to mental health issues? Channel 4's recent series Psychos was strongly condemned by the Royal College of Psychiatrists' Public Education Committee and other interest groups for its inflammatory title and insensitive content. Media coverage of mental health topics is increasing, with particular focus on child and adolescent issues. But what constitutes abnormal behaviour?

At the extreme end of the spectrum, the “Bulger case” has raised debate about what levels of disturbance children are capable of. Milder, but much more common, hyperkinetic disorder (or attention deficit hyperactivity disorder) and its treatment options are also of concern. With this in mind, I was intrigued to see how this complex subject was tackled by Channel 5's recent documentary series Driving Mum Crazy .

I was struck by the explicitness of the violence shown. For example, …
TREATMENT OF GONOCOCCAL INFECTION BY DIATHERMY
Authors: E. P. Cumberbatch, C. A. Robinson
Journal: BMJ (1923)

THE clinical investigation of the treatment of gonococcal infection by diathermy was commenced in the electrical- department of St. Bartholomew's Hospital in 1913.An indication of the value of diathermy for this purpose was furnished by the results obtained in two cases of gonococcal arthritis.These cases had resisted long courses of treat- ment in the wards by other methods and were then sent
A reform too late and a "redisorganisation" too far
Authors: K. Abbasi
Journal: BMJ (2014)

The World Health Organization is at the forefront of our efforts to defeat Ebola virus disease. Preventing and treating communicable diseases were the making of WHO as an international organisation capable of delivering successful health campaigns. Historically, Africa has preoccupied WHO more than any other continent. Recent pandemic threats, from avian flu to Middle East respiratory syndrome, readied WHO for the current crisis that now threatens 15 countries (doi:10.1136/bmj.g6305).

Ebola, on the face of it, plays to WHO’s strengths. WHO might demonstrate the benefits of its focus on health information and strengthening of health systems. Instead, Ebola is firming up the case for the organisation’s critics, who argue that WHO …
Expression of arthritis-causing HLA-B27 on Hela cells promotes induction of c-fos in response to in vitro invasion by Salmonella typhimurium.
Authors: T Ikawa, M Ikeda, A Yamaguchi, W C Tsai, N Tamura, N Seta, M Trucksess, R B Raybourne, D T Yu
Journal: Journal of Clinical Investigation (1998)

HLA-B27 confers a very strong genetic predisposition to development of a reactive arthritis after infection by bacteria such as Salmonella typhimurium. This study examines the role of HLA-B27 in the initiation of the earliest host activities after exposure to Salmonella, namely activation of the immediate early genes in the epithelial cells. Our major finding is that in Hela cells, the expression of c-fos was induced by Salmonella invasion only when the cells expressed the transfected HLA-B27 gene, but not the HLA-A1 gene or a truncated HLA-B27 gene lacking the exons encoding the cytoplasmic domain. C-fos is potentially capable of complexing with members of the c-jun family to become the AP-1 transcription complex. Parallel to c-fos expression, we found that only with the HLA-B27 transfectant was there expression of AP-1. AP-1 potentially controls the expression of a large number of genes. On screening a panel of proinflammatory molecules, we found that Salmonella invasion induced expression of monocyte chemoattractant protein-1 in the HLA-B27 cells. Since each of these separate positive findings belong to the same cascade of events after cell activation, together they reinforce the hypothesis that HLA-B27 plays a modulatory role in the early signal transduction events induced by Salmonella invasion. This hypothesis adds another item to the list of allele-specific activities carried out by HLA class I molecules. If similar activation also occurs in the joints, it may play a major role in arthritis.