tbuckley/cabot-search huggingface dataset:
The functional effect of adenoviral Na+/Ca2+ exchanger overexpression in rabbit myocytes depends on the activity of the Na+/K+-ATPase
Authors: W Schillinger
Journal: Cardiovascular Research (2003)

The functional consequences of Na+/Ca2+ exchanger (NCX) overexpression in heart failure have been controversially discussed. NCX function strongly depends on intracellular sodium which has been shown to be increased in heart failure.We investigated the Na+/K+-ATPase (NKA) inhibitor ouabain (0.5-16 micromol/l) in electrically stimulated, isotonically contracting adult rabbit cardiocytes overexpressing NCX after adenoviral gene transfer (Ad-NCX-GFP, 48 h culture time). Myocytes transfected with adenovirus encoding for green fluorescent protein (Ad-GFP) served as a control. Contractions were analyzed by video-edge detection. In the Ad-NCX-GFP group, the maximum inotropic response was significantly reduced by 50.7% (P<0.05). This was a result of an enhanced susceptibility to contracture after exposure to the drug (median concentration (25-75%): 4 (4-8) vs. 8 (6-16) micromol/l, P<0.05). When analyzing relaxation before contracture, the maximum relaxation velocity was reduced (0.15+/-0.04 vs. 0.27+/-0.04 microm/s, P<0.05) and the time from peak shortening to 90% of relaxation was increased (298+/-39 vs. 185+/-15 ms, P<0.05). No differences in systolic and diastolic parameters were observed with the Na+ channel modulator BDF9198 (1 micromol/l).Inhibition of NKA by ouabain induces a combined diastolic and systolic dysfunction in NCX overexpressing rabbit myocytes. This may be the consequence of cytoplasmic Ca2+ overload due to inhibition of forward mode or induction of reverse mode Na+/Ca2+ exchange. In end-stage failing human myocardium and during digitalis treatment this mechanism may be of major importance.
Inhibition of NF-κB Activation by Pyrrolidine Dithiocarbamate Prevents In Vivo Expression of Proinflammatory Genes
Authors: Shu Fang Liu, Xiaobing Ye, Asrar B. Malik
Journal: Circulation (1999)

Background —The inability to inhibit multiple mediators of septic shock represents a major hurdle in the treatment of septic shock. In vivo inhibition of nuclear factor (NF)-κB activation, a transcription factor regulating expression of many proinflammatory genes, could provide a useful strategy for the treatment of septic shock. Methods and Results —In rats challenged with lipopolysaccharide (LPS) 8 mg/kg IV, we determined the time course of NF-κB activation and expression of multiple inflammatory signals: tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), cytokine-inducible neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1 (ICAM)-1. We studied the effects of in vivo inhibition of NF-κB activation using pyrrolidine dithiocarbamate (PDTC) on the expression of these mediators. NF-κB activation preceded the induction of TNF-α, COX-2, CINC, and ICAM-1 mRNAs. PDTC prevented the LPS-induced NF-κB activation but did not inhibit activation of the transcription factors AP-1, Sp-1, and CREB. PDTC inhibited the LPS-induced expression of TNF-α, COX-2, CINC, and ICAM-1 mRNA and proteins and reduced the LPS-induced increases in plasma TNF-α, 6-keto-prostaglandin F 1α , and CINC concentrations. Inhibition of expression of these mediators prevented the increases in myeloperoxidase activity (a measure of neutrophil sequestration) in the heart, lungs, and liver. Conclusions —NF-κB activation correlates with LPS-induced expression of TNF-α, COX-2, CINC, and ICAM-1 genes in vivo. PDTC inhibits NF-κB activation and expression of these proinflammatory genes and their products. Thus, blocking NF-κB activation may be an effective strategy in the treatment of septic shock.
International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors
Authors: Margarita L. Dubocovich, Philippe Delagrange, Diana N. Krause, David Sugden, Daniel P. Cardinali, James Olcese
Journal: Pharmacological Reviews (2010)

The hormone melatonin (5-methoxy-<i>N</i>-acetyltryptamine) is synthesized primarily in the pineal gland and retina, and in several peripheral tissues and organs. In the circulation, the concentration of melatonin follows a circadian rhythm, with high levels at night providing timing cues to target tissues endowed with melatonin receptors. Melatonin receptors receive and translate melatonin9s message to influence daily and seasonal rhythms of physiology and behavior. The melatonin message is translated through activation of two G protein-coupled receptors, MT<sub>1</sub> and MT<sub>2</sub>, that are potential therapeutic targets in disorders ranging from insomnia and circadian sleep disorders to depression, cardiovascular diseases, and cancer. This review summarizes the steps taken since melatonin9s discovery by Aaron Lerner in 1958 to functionally characterize, clone, and localize receptors in mammalian tissues. The pharmacological and molecular properties of the receptors are described as well as current efforts to discover and develop ligands for treatment of a number of illnesses, including sleep disorders, depression, and cancer.
The Clinical Assessment Interview for Negative Symptoms (CAINS): Final Development and Validation
Authors: Ann M. Kring, Raquel E. Gur, Jack J. Blanchard, William P. Horan, Steven P. Reise
Journal: American Journal of Psychiatry (2013)

A major barrier to developing treatments for negative symptoms has been measurement concerns with existing assessment tools. Fulfilling the top recommendation of the National Institute of Mental Health's Consensus Development Conference on Negative Symptoms, the Clinical Assessment Interview for Negative Symptoms (CAINS) was developed using an iterative, empirical approach, and includes items assessing motivation, pleasure, and emotion expression. The authors employed multiple analytic techniques to develop the CAINS and here provide final development and validation results.The CAINS structure, interrater agreement, test-retest reliability, and convergent and discriminant validity were assessed in a large and diverse sample of 162 outpatients with schizophrenia or schizoaffective disorder recruited from four sites.Three items with poor psychometric properties were removed, resulting in a 13-item CAINS. The CAINS factor structure was replicated, demonstrating two modestly correlated scales: expression (four items) and motivation/pleasure (nine items). The scales demonstrated good internal consistency, test-retest stability, and interrater agreement. Strong convergent validity was demonstrated by linkages with other negative symptom measures, self-report scales of sociality, pleasure, and motivation, and coded facial expressions. Discriminant validity was shown by independence from depression, medication side effects, and cognition. Notably, the CAINS scales were related to real-world vocational, independent living, and social/familial functioning.The CAINS is an empirically developed and evaluated measure of negative symptoms. Findings indicate that the CAINS is brief yet comprehensive and employable across a wide range of research and clinical contexts.
Renal Energy Metabolism and Sodium Reabsorption
Authors: P R Lewy, A Quintanilla, N W Levin, R H Kessler
Journal: Annual Review of Medicine (1973)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Salicylate-NSAID interactions.
Authors: D M Grennan, L Aarons
Journal: Annals of the Rheumatic Diseases (1984)

<h3>Introduction</h3> Despite extensive prevention campaigns and scale-up of antiretroviral therapy, HIV incidence among young women in southern Africa remains high. While the development of an efficacious vaccine remains a challenge, the discovery of broadly neutralising monoclonal antibodies (mAbs) has created the opportunity to explore passive immunisation as a long-acting injectable HIV prevention strategy. The purpose of this trial is to provide safety, pharmacokinetic (PK) and functional activity data of VRC07-523LS and PGT121 when administered subcutaneously (SC) to young South African women. Going forward, the aim is to select the ideal dose and/or monoclonal antibody for co-formulation and testing with CAP256-VRC26.25LS, a potent monoclonal antibody against subtype C virus, in an efficacy trial. <h3>Methods and analysis</h3> CAPRISA 012A is a randomised, double blinded, placebo-controlled phase I trial to assess the safety and PK profile of two mAbs, VRC07-523LS and PGT121 administered SC to 35 young HIV negative women at low risk for HIV infection. Women will be randomised into seven groups of five participants each. In each group, women will be randomised (4:1) to the active intervention, VRC07-523LS and/or PGT121, or placebo. Participants will be followed up for 24 weeks after the administration of the last dose of study product with a total study duration of 72 weeks. Safety in the study will be assessed by the number and percentage of reactogenicity and adverse events experienced by participants and the relatedness to study product. The PK study design was based on preliminary PK data for VRC07-523LS and PGT121. <h3>Ethics and dissemination</h3> Ethical approval has been granted by the South African Health Products Regulatory Authority and by the University of KwaZulu-Natal Biomedical Research Ethics Committee. Results will be presented at international conferences and published in academic peer-reviewed journals. Trial results will be uploaded on the clinical trial registry. <h3>Trial registration number</h3> PACTR201808919297244; Pre-results.
Faecal phytic acid and its relation to other putative markers of risk for colorectal cancer.
Authors: R W Owen, U M Weisgerber, B Spiegelhalder, H Bartsch
Journal: Gut (1996)

AIMS--Phytic acid, a major constituent of cereals, pulses, and seeds has been advocated as an important antioxidant component of dietary fibre that affords possible protection against colorectal cancer. This is supported by experimental studies showing it has antineoplastic activity in animal models of both colon and breast cancer. To date the concentration of faecal phytic acid in human clinical groups has not been evaluated. Therefore the faecal phytic acid content of adenoma patients drawn from a placebo controlled calcium intervention trial was evaluated. METHODS--Phytic acid was measured in faecal extracts by an improved ion-pair high performance liquid chromatography method. RESULTS--Phytic acid was detected in the range 0.68-4.00 mumol/g wet faeces and 55-2038 mumol/day. Linear regression analyses showed no association between stool phytic acid and lipid content. Strong correlations were seen, however, between phytic acid and iron content, both on a concentration (r = 0.52; p = 0.00004) and daily excretion (r = 0.76; p = 5.5 x 10(-12) basis. Phytic acid was also strongly correlated with the daily excretion of calcium (r = 0.59; p = 1.36 x 10(-6) and magnesium (r = 0.42; p = 0.001). Cell proliferation in the sigmoid colon, an intermediate biomarker of colorectal cancer was not significantly associated with faecal phytic acid, minerals or lipid content in this compromised clinical group. CONCLUSIONS--This improved method, developed for the determination of phytic acid in faeces should allow further studies on the role of phytic acid in the aetiology of colorectal cancer to be conducted on a population or case control basis.
Progesterone for the reduction of cocaine use in post-partum women with a cocaine use disorder: a randomised, double-blind, placebo-controlled, pilot study
Authors: Kimberly Ann Yonkers, Ariadna Forray, Charla Nich, Kathleen M Carroll, Cristine Hine, Brian C Merry, Howard Shaw, Julia Shaw, Mehmet Sofuoglu
Journal: The Lancet Psychiatry (2014)
Expansion of donor hepatocytes after recombinant adenovirus-induced liver regeneration in mice
Authors: Vrancken M T F Peeters, G A Patijn, A Lieber, J Perkins, M A Kay
Journal: Hepatology (1997)

Hepatocyte transplantation is a potential form of therapy for patients with genetic hepatodeficiency disorders. Unfortunately, hepatocellular transplantation has been limited because of the relatively low numbers of donor cells that can ultimately take up residence in the host liver. To give the donor cells a proliferative stimulus, a recombinant adenovirus vector that expresses a nonsecreted urokinase (urokinase-type plasminogen activator) was transduced into the livers of recipient animals before transplantation. Because urokinase production in hepatocytes causes the slow turnover of hepatocytes, 2 days after adenovirus-mediated gene transfer into the livers of recipient mice, 2 × 10 6 congenic donor cells tagged with β-galactosidase (β-Gal) reporter were implanted via the portal vein. As a result, on average, 8.6% of the recipient hepatocytes in the livers were derived from donor cells-a 20-fold increase compared with control animals in which no proliferative stimulus was present.
Spanish surgeons perform country's first renal transplant chain involving altruistic donor
Authors: A. Garcia Rada
Journal: BMJ (2011)

Surgeons from Barcelona and Granada have just carried out Spain’s first renal transplant chain. This was innovative not just because it was a chain operation involving six people but because it involved an altruistic “good Samaritan” donor, who offered a kidney not knowing who the recipient would be. The other people were two married couples and one recipient who was on the transplant waiting list.

The successful series of transplantations was announced in Madrid on 27 April by Leire Pajin, the health minister. Spain is the third …
Regional and overall inequality of ventilation and blood flow in patients with chronic airflow obstruction
Authors: M. C. F. Pain, J. B. Glazier, H. Simon, J. B. West
Journal: Thorax (1967)

Measurements of the topographical distribution of pulmonary blood flow and ventilation have been made in 26 subjects with chronic irreversible obstructive lung disease using a radioactive xenon scanning technique. The distribution of blood flow was found to range between a normal gradient and the reverse of normal. Differences between left and right lungs were present in patients with associated bronchiectasis, previous lobectomy, and obvious radiological emphysema but not in most of those subjects with no obvious destructive changes. Ventilation was commonly decreased towards the base of the lung, that is the reverse of the normal pattern. Acetylcholine altered the blood flow distribution pattern in three out of nine subjects and this may represent vasodilatation in hypoxic regions of the lung. Repeatability of the scanning technique was found to be 10% (one standard deviation) for blood flow measurements and 11% for single-breath ventilation measurements. Examination of the expired xenon plateaux following a single inhalation of xenon in air consistently revealed a fall in count rate with expired volume, indicating the presence of poorly ventilated alveoli. However, there was a poor correlation between the degree of ventilatory inequality revealed by external counting on the one hand and the slope of the expired plateau on the other. The shape of the expired xenon plateau following xenon injection was usually horizontal and correlated poorly with the topographical distribution of blood flow. This is evidence that the extent of the inequality of ventilation-perfusion ratios at the alveolar level in patients with chronic lung disease cannot be obtained by external counters.
Stevens-Johnson Syndrome
Authors: Harry I. Katz
Journal: JAMA (1967)

THE CLINICAL manifestations of Stevens-Johnson syndrome (erythema multiforme exudativum) were frequently observed in the dermatology and dental services at the US Naval Hospital, Great Lakes, Ill, during the late summer and fall of 1965. The apparently increased incidence of this syndrome prompted clinical as well as laboratory investigations. The serological evidence of associated<i>Mycoplasma pneumoniae</i>infection in Stevens-Johnson syndrome presented by Ludlam et al<sup>1</sup>suggested<i>Mycoplasma</i>studies. This communication is a case report of a patient with Stevens-Johnson syndrome in which an associated infection by<i>M pneumoniae</i>was documented by serological and cultural techniques. <h3>Report of a Case</h3> This 19-year-old white man was admitted to the US Naval Hospital, Great Lakes, on Oct 16, 1965, complaining of a widespread rash and sores in his mouth and on his penis. <h3>History.—</h3> He had been in a state of good health when he arrived at the Great Lakes Naval Station on
A Randomized Trial Comparing Perioperative Chemotherapy and Surgery With Surgery Alone in Resectable Stage IIIA Non-Small-Cell Lung Cancer
Authors: J. A. Roth, F. Fossella, R. Komaki, M. B. Ryan, J. B. Putnam, J. S. Lee, H. Dhingra, L. De Caro, M. Chasen, M. McGavran, E. N. Atkinson, W. K. Hong
Journal: JNCI Journal of the National Cancer Institute (1994)

Patients with resectable stage IIIA non-small-cell lung cancer have a low survival rate following standard surgical treatment. Nonrandomized trials in which induction chemotherapy or a combination of chemotherapy and radiation prior to surgery were used to treat patients with regionally advanced primary cancers have suggested that survival is improved when compared with treatment by surgery alone.We performed a prospective, randomized study of patients with previously untreated, potentially resectable clinical stage IIIA non-small-cell lung cancer to compare the results of perioperative chemotherapy and surgery with those of surgery alone.This trial was designed to test the null hypothesis that the proportion of patients surviving 3 years is 12% for either treatment group against the alternate hypothesis that the 3-year survival rate would be 12% in the surgery alone group and 32% in the perioperative chemotherapy group. The estimated required sample size was 65 patients in each group. The trial was terminated at an early time according to the method of O'Brien and Fleming following a single unplanned interim analysis. The decision to terminate the trial was based on ethical considerations, the magnitude of the treatment effect, and the high degree of statistical significance attained. In total, 60 patients were randomly assigned between 1987 and 1993 to receive either six cycles of perioperative chemotherapy (cyclophosphamide, etoposide, and cisplatin) and surgery (28 patients) or surgery alone (32 patients). For patients in the former group, tumor measurements were made before each course of chemotherapy and the clinical tumor response was evaluated after three cycles of chemotherapy; they then underwent surgical resection. Patients who had documented tumor regression after preoperative chemotherapy received three additional cycles of chemotherapy after surgery.After three cycles of preoperative chemotherapy, the rate of clinical major response was 35%. Patients treated with perioperative chemotherapy and surgery had an estimated median survival of 64 months compared with 11 months for patients who had surgery alone (P < .008 by log-rank test; P < .018 by Wilcoxon test). The estimated 2- and 3-year survival rates were 60% and 56% for the perioperative chemotherapy patients and 25% and 15% for those who had surgery alone, respectively.In this trial, the treatment strategy using perioperative chemotherapy and surgery was more effective than surgery alone.This clinical trial strengthens the validity of using perioperative chemotherapy in the management of patients with resectable stage IIIA non-small-cell lung cancer. Further investigation of the perioperative chemotherapy strategy in earlier stage lung cancer is warranted.
Peanut Oral Immunotherapy (OIT) Confers Long-Term Tolerance Mediated by Decreased T-helper Type 2 (TH2) Cytokines and Cytokines Generated by Regulatory T cells (Tregs)
Authors: M. Breslin, L. Pons, X. Yue, M. Kulis, S.M. Jones, B. Vickery, A.W. Burks
Journal: Journal of Allergy and Clinical Immunology (2010)
The<i>rs1143679</i>(R77H) lupus associated variant of<i>ITGAM</i>(CD11b) impairs complement receptor 3 mediated functions in human monocytes
Authors: Benjamin Rhodes, Barbara G Fürnrohr, Amy L Roberts, George Tzircotis, Georg Schett, Tim D Spector, Timothy J Vyse
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> The <i>rs1143679</i> variant of <i>ITGAM</i>, encoding the R77H variant of CD11b (part of complement receptor 3; CR3), is among the strongest genetic susceptibility effects in human systemic lupus erythematosus (SLE). The authors aimed to demonstrate R77H function in ex-vivo human cells. <h3>Methods</h3> Monocytes/monocyte-derived macrophages from healthy volunteers homozygous for either wild type (WT) or 77H CD11b were studied. The genotype-specific expression of CD11b, and CD11b activation using conformation-specific antibodies were measured. Genotype-specific differences in iC3b-mediated phagocytosis, adhesion to a range of ligands and the secretion of cytokines following CR3 ligation were studied. The functionality of R77H was confirmed by replicating findings in COS7 cells expressing variant-specific CD11b. <h3>Results</h3> No genotype-specific difference in CD11b expression or in the expression of CD11b activation epitopes was observed. A 31% reduction was observed in the phagocytosis of iC3b opsonised sheep erythrocytes (sRBC<sub>iC3b</sub>) by 77H cells (p=0.003) and reduced adhesion to a range of ligands: notably a 24% reduction in adhesion to iC3b (p=0.014). In transfected COS7 cells, a 42% reduction was observed in phagocytosis by CD11b (77H)-expressing cells (p=0.004). A significant inhibition was seen in the release of Toll-like receptor 7/8-induced pro-inflammatory cytokines from WT monocytes when CR3 was pre-engaged using sRBC<sub>iC3b</sub>, but no inhibition in 77H monocytes resulting in a significant difference between genotypes (interleukin (IL)-1β p=0.030; IL-6 p=0.029; tumour necrosis factor alpha p=0.027). <h3>Conclusions</h3> The R77H variant impairs a broad range of CR3 effector functions in human monocytes. This study discusses how perturbation of this pathway may predispose to SLE.
Fish consumption during the first year of life and development of allergic diseases during childhood
Authors: I. Kull, A. Bergström, G. Lilja, G. Pershagen, M. Wickman
Journal: Allergy (2006)

Background: Fish consumption during infancy has been regarded as a risk factor for allergic disease but later evidence suggests a protective role. However, methodological limitations in the studies make conclusions uncertain. The aim of this study was to assess the association between fish consumption during the first year of life and development of allergic diseases by age 4. Methods: A prospective birth cohort of 4089 new‐born infants was followed for 4 years using parental questionnaires at ages 2 months, 1, 2 and 4 years to collect information on exposure and health effects. The response rate at 4 years was 90%. A clinical investigation was performed at age 4 years, which included blood sampling for analysis of specific IgE to common food and airborne allergens. Results: Parental allergic disease and onset of eczema or wheeze during the first year of life delayed introduction of fish in the child's diet. After exclusion of such children to avoid disease‐related modification of exposure, regular fish consumption during the first year of life was associated with a reduced risk for allergic disease by age 4, OR adj 0.76 (95% CI 0.61–0.94) and sensitization, OR adj 0.76 (0.58–1.0). The reduced risk appeared most pronounced for multiple disease, OR adj 0.56 (0.35–0.89). IgE‐sensitization to fish was only present among 18 of the 2614 children. Conclusion: Regular fish consumption before age 1 appears to be associated with a reduced risk of allergic disease and sensitization to food and inhalant allergens during the first 4 years of life.