tbuckley/cabot-search huggingface dataset:
Inhibition of leucocyte motility and prevention of immune-complex experimental colitis by hydroxychloroquine.
Authors: J M Rhodes, J E McLaughlin, D J Brown, L A Nuttall, D P Jewell
Journal: Gut (1982)

The inhibitory effects of hydroxychloroquine on leucocyte motility have been compared with those of prednisolone. It has been shown to have similar potency to prednisolone as an inhibitor of human neutrophil and monocyte motility. Hydroxychloroquine has then been compared with placebo in the prevention of an immune-complex experimental colitis in rabbits. Rectal biopsies were taken from rabbits 24 hours after initiation of colitis, coded, and graded histologically. The summated gradings for acute inflammation and goblet cell depletion had worsened more in the control rabbits (mean grade +6.7) than in the treated rabbits (mean grade +1.8) P less than 0.05. There was no difference in the mononuclear cell infiltrate between the two groups. Hydroxychloroquine, which is a potent inhibitor of leucocyte motility, effectively prevents the acute inflammatory infiltrate in this experimental colitis model and therefore merits trial in human ulcerative colitis.
Aorto-atrial fistula in rheumatoid arthritis
Authors: P. A. Crean, D. S. Reid, J. Buchanan
Journal: Annals of the Rheumatic Diseases (1983)

A patient with severe deforming rheumatoid arthritis presented with a short history of chest pain. The clinical signs were of an unusual diastolic murmur and profound shock unresponsive to therapy. Post-mortem examination disclosed the unexpected finding of a large aorto-atrial fistula.
The Stromal Cell–Derived Factor-1 Chemokine Is a Potent Platelet Agonist Highly Expressed in Atherosclerotic Plaques
Authors: S. Abi-Younes, A. Sauty, F. Mach, G. K. Sukhova, P. Libby, A. D. Luster
Journal: Circulation Research (2000)

Abstract —Chemokines are chemotactic cytokines that activate and direct the migration of leukocytes. However, their role in modulating platelet function has not been shown. We studied the direct effect of chemokines on human platelets and found that of the 16 tested only stromal cell–derived factor (SDF)-1 induced platelet aggregation, accompanied by a rise in intracellular calcium. Platelets expressed the SDF-1 receptor, CXCR4, and an antibody to CXCR4 and pertussis toxin inhibited SDF-1–induced platelet aggregation, confirming that this effect is mediated through CXCR4, a Gαi-coupled receptor. SDF-1–induced platelet aggregation was also inhibited by wortmannin, LY294002, and genistein, suggesting that phosphatidylinositol 3–kinase and tyrosine kinase are likely involved in SDF-1–induced platelet aggregation. Because chemokines are produced from multiple vascular cells and atherosclerotic vessels are prone to develop platelet-rich thrombi, we examined the expression of SDF-1 in human atheroma. SDF-1 protein was highly expressed in smooth muscle cells, endothelial cells, and macrophages in human atherosclerotic plaques but not in normal vessels. Our studies demonstrate a direct effect of a chemokine in inducing platelet activation and suggest a role for SDF-1 in the pathogenesis of atherosclerosis and thrombo-occlusive diseases.
The spatial organisation of joint surface chondrocytes: review of its potential roles in tissue functioning, disease and early, preclinical diagnosis of osteoarthritis
Authors: Wilhelm K Aicher, Bernd Rolauffs
Journal: Annals of the Rheumatic Diseases (2013)

Chondrocytes display within the articular cartilage depth-dependent variations of their many properties that are comparable to the depth-dependent changes of the properties of the surrounding extracellular matrix. However, not much is known about the spatial organisation of the chondrocytes throughout the tissue. Recent studies revealed that human chondrocytes display distinct spatial patterns of organisation within the articular surface, and each joint surface is dominated in a typical way by one of four basic spatial patterns. The resulting complex spatial organisations correlate with the specific diarthrodial joint type, suggesting an association of the chondrocyte organisation within the joint surface with the occurring biomechanical forces. In response to focal osteoarthritis (OA), the superficial chondrocytes experience a destruction of their spatial organisation <i>within</i> the OA lesion, but they also undergo a defined remodelling process <i>distant</i> from the OA lesion in the remaining, intact cartilage surface. One of the biological insights that can be derived from this spatial remodelling process is that the chondrocytes are able to respond in a generalised and coordinated fashion to distant focal OA. The spatial characteristics of this process are tremendously different from the cellular aggregations typical for OA lesions, suggesting differences in the underlying mechanisms. Here we summarise the available information on the spatial organisation of chondrocytes and its potential roles in cartilage functioning. The spatial organisation could be used to diagnose early OA onset before manifest OA results in tissue destruction and clinical symptoms. With further development, this concept may become clinically suitable for the diagnosis of preclinical OA.
Single Cell Analysis Reveals Regulated Hierarchical T Cell Antigen Receptor Signaling Thresholds and Intraclonal Heterogeneity for Individual Cytokine Responses of CD4+ T Cells
Authors: Yasushi Itoh, Ronald N. Germain
Journal: The Journal of Experimental Medicine (1997)

T cell receptor (TCR) recognition of peptide-major histocompatibility complex antigens can elicit a diverse array of effector activities. Here we simultaneously analyze TCR engagement and the production of multiple cytokines by individual cells in a clonal Th1 CD4(+) cell population. Low concentrations of TCR ligand elicit only interferon-gamma (IFN-gamma) production. Increasing ligand recruits more cells into the IFN-gamma+ pool, increases IFN-gamma produced per cell, and also elicits IL-2, but only from cells already making IFN-gamma. Most cells producing only IFN-gamma show less TCR downmodulation than cells producing both cytokines, consistent with a requirement for more TCR signaling to elicit IL-2 than to evoke IFN-gamma synthesis. These studies emphasize the hierarchical organization of TCR signaling thresholds for induction of distinct cytokine responses, and demonstrate that this threshold phenomenon applies to individual cells. The existence of such thresholds suggests that antigen dose may dictate not only the extent, but also the quality of an immune response, by altering the ratios of the cytokines produced by activated T cells. The quantitative relationships in this response hierarchy change in response to costimulation through CD28 or LFA-1, as well as the differentiation state of the lymphocyte, explaining how variations in these parameters in the face of a fixed antigen load can qualitatively influence immune outcomes. Finally, although the IFN-gamma/IL-2 hierarchy is seen with most cells, among cells with the greatest TCR downmodulation, some produce only IFN-gamma and not IL-2, and the amount of IFN-gamma exceeds that in double producers. Thus, these single cell analyses also provide clear evidence of nonquantitative intraclonal heterogeneity in cytokine production by long-term Th1 cells, indicating additional complexity of T cell function during immune responses.
Hyperglycemia and Diabetes in Patients With Schizophrenia or Schizoaffective Disorders
Authors: Dan Cohen, Ronald P. Stolk, Diederick E. Grobbee, Christine C. Gispen-de Wied
Journal: Diabetes Care (2006)

OBJECTIVE—Pharmacoepidemiological studies have shown an increased prevalence of diabetes in patients with schizophrenia. To address this issue, we decided to assess glucose metabolism in a population of patients with schizophrenia or schizoaffective disorder. RESEARCH DESIGN AND METHODS—Oral glucose tolerance tests (OGTTs) were performed in 200 unselected in- and outpatients. Insulin sensitivity and β-cell function were assessed using the homeostasis model assessment (HOMA) indexes and 30-min glucose and insulin levels. RESULTS—The mainly Western European (87.7%) study population had a mean age of 40.8 years, was 70% male, and had a mean fasting glucose of 5.1 mmol/l and a mean fasting insulin of 14.8 mU/l. Hyperglycemia was present in 7% of the population: 1.5% with impaired fasting glucose and 5.5% with impaired glucose tolerance. The prevalence of diabetes was 14.5%, of which 8% was previously known and 6.5% was newly diagnosed. Compared with a 1.5% prevalence of diabetes in the age-matched general Dutch population, the prevalence of identified cases was significantly increased in the study population. Comparable figures on the prevalence of hyperglycemia in the general population are not available. Insulin resistance was increased in the study population as a whole (HOMA of insulin resistance: 3.1–3.5), irrespective of the use of antipsychotic medication and, if used, irrespective of its type (typical or atypical). No indication of β-cell defect was found, whereas a nonsignificant increased insulin resistance was found with antipsychotic medication. CONCLUSIONS—OGTTs in 200 mainly Caucasian patients with schizophrenia or schizoaffective disorder, mean age 41 years, showed that 7% suffered from hyperglycemia and 14.5% from diabetes. The prevalence of diabetes was significantly increased compared with the general population. No differential effect of antipsychotic monotherapy in diabetogenic effects was found. Therefore, a modification of the consensus statement on antipsychotic drugs, obesity, and diabetes is proposed, i.e., measurement of fasting glucose in all patients with schizophrenia, irrespective of prescribed antipsychotic drug.
Histone Methyltransferase Gene <i>SETD2</i> Is a Novel Tumor Suppressor Gene in Clear Cell Renal Cell Carcinoma
Authors: Gerben Duns, Eva van den Berg, Inge van Duivenbode, Jan Osinga, Harry Hollema, Robert M.W. Hofstra, Klaas Kok
Journal: Cancer Research (2010)

Sporadic clear cell renal cell carcinoma (cRCC) is genetically characterized by the recurrent loss of the short arm of chromosome 3, with a hotspot for copy number loss in the 3p21 region. We applied a method called "gene identification by nonsense-mediated mRNA decay inhibition" to a panel of 10 cRCC cell lines with 3p21 copy number loss to identify biallelic inactivated genes located at 3p21. This revealed inactivation of the histone methyltransferase gene SETD2, located on 3p21.31, as a common event in cRCC cells. SETD2 is nonredundantly responsible for trimethylation of the histone mark H3K36. Consistent with this function, we observed loss or a decrease of H3K36me3 in 7 out of the 10 cRCC cell lines. Identification of missense mutations in 2 out of 10 primary cRCC tumor samples added support to the involvement of loss of SETD2 function in the development of cRCC tumors.
Reciprocity: Weak or strong? What punishment experiments do (and do not) demonstrate
Authors: Francesco Guala
Journal: Behavioral and Brain Sciences (2012)

Abstract Economists and biologists have proposed a distinction between two mechanisms – “strong” and “weak” reciprocity – that may explain the evolution of human sociality. Weak reciprocity theorists emphasize the benefits of long-term cooperation and the use of low-cost strategies to deter free-riders. Strong reciprocity theorists, in contrast, claim that cooperation in social dilemma games can be sustained by costly punishment mechanisms, even in one-shot and finitely repeated games. To support this claim, they have generated a large body of evidence concerning the willingness of experimental subjects to punish uncooperative free-riders at a cost to themselves. In this article, I distinguish between a “narrow” and a “wide” reading of the experimental evidence. Under the narrow reading, punishment experiments are just useful devices to measure psychological propensities in controlled laboratory conditions. Under the wide reading, they replicate a mechanism that supports cooperation also in “real-world” situations outside the laboratory. I argue that the wide interpretation must be tested using a combination of laboratory data and evidence about cooperation “in the wild.” In spite of some often-repeated claims, there is no evidence that cooperation in the small egalitarian societies studied by anthropologists is enforced by means of costly punishment. Moreover, studies by economic and social historians show that social dilemmas in the wild are typically solved by institutions that coordinate punishment, reduce its cost, and extend the horizon of cooperation. The lack of field evidence for costly punishment suggests important constraints about what forms of cooperation can or cannot be sustained by means of decentralised policing.
The effects of recombinant human DNase on neutrophil elastase activity and interleukin-8 levels in the sputum of patients with cystic fibrosis
Authors: PL Shah, SF Scott, RA Knight, ME Hodson
Journal: European Respiratory Journal (1996)

In cystic fibrosis (CF), neutrophil-dominated airway inflammation results in high levels of neutrophil elastase (NE). Some of these proteases are sequestered by the large amounts of deoxyribonucleic acid (DNA) present in purulent sputum. Recombinant human deoxyribonuclease (rhDNase), a new treatment in CF, depolymerizes DNA. Our concerns were that this might release proteases bound to DNA, which could be potentially harmful. The in vitro and in vivo effects of rhDNase on NE and interleukin-8 (IL-8) were evaluated. The acute effects of rhDNase were evaluated in CF patients during the first 6 days of treatment. Medium-term effects were evaluated in stable CF patients observed in rhDNase over 6 months. Sputum samples were collected at regular intervals and NE activity was measured by a fluorimetric assay and IL-8 with a radioimmunoassay. In vitro addition of rhDNase resulted in a twofold increase in protease activity and this was reflected in an acute transient rise on initiation of treatment with rhDNase. Medium-term treatment was associated with a decline in NE activity and IL-8. These in vivo results are encouraging, since the increase in protease activity was transient and the trend over 6 months was a reduction in both inflammatory markers.
Age-adjusted high-sensitivity troponin T cut-off value for risk stratification of pulmonary embolism
Authors: Anja Kaeberich, Valerie Seeber, David Jiménez, Maciej Kostrubiec, Claudia Dellas, Gerd Hasenfuß, Evangelos Giannitsis, Piotr Pruszczyk, Stavros Konstantinides, Mareike Lankeit
Journal: European Respiratory Journal (2015)

High-sensitivity troponin T (hsTnT) helps in identifying pulmonary embolism patients at low risk of an adverse outcome. In 682 normotensive pulmonary embolism patients we investigate whether an optimised hsTnT cut-off value and adjustment for age improve the identification of patients at elevated risk. Overall, 25 (3.7%) patients had an adverse 30-day outcome. The established hsTnT cut-off value of 14 pg·mL −1 retained its high prognostic value (OR (95% CI) 16.64 (2.24–123.74); p=0.006) compared with the cut-off value of 33 pg·mL −1 calculated by receiver operating characteristic analysis (7.14 (2.64–19.26); p&lt;0.001). In elderly (aged ≥75 years) patients, an age-optimised hsTnT cut-off value of 45 pg·mL −1 but not the established cut-off value of 14 pg·mL −1 predicted an adverse outcome. An age-adjusted hsTnT cut-off value (≥14 pg·mL −1 for patients aged &lt;75 years and ≥45 pg·mL −1 for patients aged ≥75 years) provided additive and independent prognostic information on top of the simplified pulmonary embolism severity index (sPESI) and echocardiography (OR 4.56 (1.30–16.01); p=0.018, C-index=0.77). A three-step approach based on the sPESI, hsTnT and echocardiography identified 16.6% of all patients as being at higher risk (12.4% adverse outcome). Risk assessment of normotensive pulmonary embolism patients was improved by the introduction of an age-adjusted hsTnT cut-off value. A three-step approach helped identify patients at higher risk of an adverse outcome who might benefit from advanced therapy.
Immunogens consisting of oligosaccharides from the capsule of Haemophilus influenzae type b coupled to diphtheria toxoid or the toxin protein CRM197.
Authors: P Anderson, M E Pichichero, R A Insel
Journal: Journal of Clinical Investigation (1985)

Haemophilus influenzae type b (Hib) capsular polysaccharide (PRP) was selectively hydrolyzed to reducing oligosaccharides, and the fraction containing 3-10 ribosylribitolphosphate repeating units (VS) was conjugated by reductive amination to diphtheria toxin (DTx), its nontoxic derivative CRM197 (Dcr), or diphtheria toxoid (DTd). Conjugate DTx-VS retained approximately 1% of native toxicity, which was eliminated by treatment with formalin. Immunization of rabbits with the conjugates elicited antibody (Ab) to PRP and to DTx but not to a model for the linkage determinant. Human adults given single subcutaneous injections had rises in serum Ab to PRP and in bactericidal activity in vitro; the Ab protected infant rats challenged with Hib. Adults had rises also in Ab to DTd, and these Ab protected rabbits against DTx. A series of two injections of the conjugates Dcr-VS and DTd-VS was tested in infants beginning at 19-23 mo of age. Rises in anti-PRP Ab after the primary resembled the rises after PRP vaccine. In contrast to PRP, the conjugates elicited large rises after the secondary vaccinations and a substantial IgG component. Development of bactericidal activity paralleled the rises in anti-PRP Ab. Secondary rises after Dcr-VS were higher than after DTd-VS. In infants 12-16 mo of age, Dcr-VS (but not DTd-VS) elicited strong primary and secondary Ab responses that included IgG and bactericidal activity. Both conjugates produced consistent rises in Ab to DTd.
Persistent Organochlorine Pesticides and Risk of Testicular Germ Cell Tumors
Authors: Katherine A. McGlynn, Sabah M. Quraishi, Barry I. Graubard, Jean-Philippe Weber, Mark V. Rubertone, Ralph L. Erickson
Journal: JNCI Journal of the National Cancer Institute (2008)

Exposure to endocrine-disrupting chemicals, such as persistent organochlorine pesticides, has been suggested to increase the risk of testicular germ cell tumors (TGCTs).To study the relationship of POP exposure to TGCT risk, prediagnostic serum samples from 754 case subjects and 928 control subjects enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study were analyzed for cis-nonachlor, trans-nonachlor, oxychlordane, total chlordanes, beta-hexachlorocyclohexane, mirex, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and p,p'-dichlorodiphenyltrichloroethane. Adjusted odds ratios (ORs) and their associated 95% confidence intervals (CIs) for the risk of TGCT overall and for the histological subgroups, seminoma and nonseminoma, were estimated using multivariable logistic regression. All statistical tests were two-sided.TGCT risk was statistically significantly associated with higher plasma levels of p,p'-DDE (for highest quartile [Q4] vs lowest quartile [Q1], OR = 1.71, 95% CI = 1.23 to 2.38, P(trend) = .0002) and of two chlordane components, cis-nonachlor (Q4 vs Q1, OR = 1.56, 95% CI = 1.11 to 2.18, P(trend) = .009) and trans-nonachlor (Q4 vs Q1, OR = 1.46, 95% CI = 1.07 to 2.00, P(trend) = .026). Seminoma risk was statistically significantly associated with p,p'-DDE (Q4 vs Q1, OR = 1.91, 95% CI = 1.22 to 2.99, P(trend) = .0008), cis-nonachlor (Q4 vs Q1, OR = 1.93, 95% CI = 1.27 to 2.93, P(trend) = .0045), trans-nonachlor (Q4 vs Q1, OR = 1.72, 95% CI = 1.11 to 2.67, P(trend) = .033), and a chlordane metabolite, oxychlordane (Q4 vs Q1, OR = 1.64, 95% CI = 1.04 to 2.60, P(trend) = .048), whereas nonseminoma risk showed a statistically significant association with p,p'-DDE only (Q4 vs Q1, OR = 1.63, 95% CI = 1.10 to 2.42, P(trend) = .0044).Increased exposure to p,p'-DDE may be associated with the risk of both seminomatous and nonseminomatous TGCTs, whereas exposure to chlordane compounds and metabolites may be associated with the risk of seminoma. Because evidence suggests that TGCT is initiated in very early life, it is possible that exposure to these persistent organic pesticides during fetal life or via breast feeding may increase the risk of TGCT in young men.
Custom Therapeutic Insoles Based on Both Foot Shape and Plantar Pressure Measurement Provide Enhanced Pressure Relief
Authors: Tammy M. Owings, Julie L. Woerner, Jason D. Frampton, Peter R. Cavanagh, Georgeanne Botek
Journal: Diabetes Care (2008)

The purpose of this study was to determine whether custom insoles tailored to contours of the barefoot pressure distribution and shape of a patient's foot can reduce plantar pressures in the metatarsal head (MTH) region to a greater extent than conventional custom insoles.Seventy regions of elevated barefoot pressures (mean peak 834 kPa under MTHs) were identified in 20 subjects with diabetes. Foam box impressions of their feet were sent to three different orthotic supply companies for fabrication of custom insoles. One company was also given plantar pressure data, which were incorporated into the insole design. Measurements of in-shoe plantar pressures were recorded during gait for the three custom insoles in a flexible and a rocker-bottom shoe. Peak pressure and force-time integral were extracted for analysis.In 64 of 70 regions, the shape-plus-pressure-based insole in the flexible shoe achieved superior unloading compared with the two shape-based insoles. On average, peak pressure was reduced by 32 and 21% (both P <or= 0.0001) and force-time integral by 40 and 34% (both P < 0.0001) compared with the shape-based insoles. At the midfoot, force-time integral was increased by 51 and 33% (both P < 0.01). Similar trends were found using the rocker-bottom shoe.Compared with insoles based only on shape, the use of foot shape with barefoot plantar pressure measurements in designing custom insoles results in enhanced offloading of high-pressure areas under the forefoot. This offloading was achieved by a greater transfer of load to the midfoot without additional loading of other forefoot structures.
Filaggrin loss-of-function mutations do not predict food allergy over and above the risk of food sensitization among infants
Authors: Hern-Tze Tina Tan, Justine A. Ellis, Jennifer J. Koplin, Melanie C. Matheson, Lyle C. Gurrin, Adrian J. Lowe, Pamela E. Martin, Thanh D. Dang, Melissa Wake, Mimi L.K. Tang, Anne-Louise Ponsonby, Shyamali C. Dharmage, Katrina J. Allen
Journal: Journal of Allergy and Clinical Immunology (2012)
Points from Letters: Tests of Acupuncture
Authors: F. S. Rickards
Journal: BMJ (1973)

relevant to the choice of treatment and might explain why the pseudomonas in the sputum of one patient "showed no sign of suppression by colistin aerosol."Also, many pseudomonas (60%) are sensitive to tetra- cydline and this might explain the finding that tetracycline is "less likely to be interfered with by pseudomonas" in the treatment of underlying infection.I would question the presumption that pseudomonas can reach the pharynx by ascending the oesophagus.Though I have cultured many different organisms from the small intestine, I have never found pseudomonas as high as the duodenum in the gastrointestinal tract.There are many other more likely sources of infection, as pseudomonas conmnonly contaminates hospital equipment (especially ventilators, humidifiers, and suction apparatus), contaminates hos- pital food,' and is carried on the hands of staff, contaminated by an infected patient.-I
Transient Occlusion of the Middle Cerebral Artery by Macroembolism During Carotid Stenting for Traumatic Dissection of the Common Carotid Artery
Authors: Eisuke Furui, Yoshikazu Okamoto, Shinya Kida, Junkoh Yamashita, Osamu Matsui, Masahito Yamada
Journal: Circulation (2005)