tbuckley/cabot-search huggingface dataset:
Molecular identification of Knops blood group polymorphisms found in long homologous region D of complement receptor 1
Authors: Joann M. Moulds, Peter A. Zimmerman, Ogobara K. Doumbo, Lalla Kassambara, Issaka Sagara, Dapa A. Diallo, John P. Atkinson, Malgorzata Krych-Goldberg, Richard E. Hauhart, Dennis E. Hourcade, David T. McNamara, Daniel J. Birmingham, J. Alexandra Rowe, John J. Moulds, Louis H. Miller
Journal: Blood (2001)
Transgenic CaMKIIδ <sub>C</sub> Overexpression Uniquely Alters Cardiac Myocyte Ca <sup>2+</sup> Handling
Authors: Lars S. Maier, Tong Zhang, Lu Chen, Jaime DeSantiago, Joan Heller Brown, Donald M. Bers
Journal: Circulation Research (2003)

Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) δ is the predominant cardiac isoform, and the δ C splice variant is cytoplasmic. We overexpressed CaMKIIδ C in mouse heart and observed dilated heart failure and altered myocyte Ca 2+ regulation in 3-month-old CaMKIIδ C transgenic mice (TG) versus wild-type littermates (WT). Heart/body weight ratio and cardiomyocyte size were increased about 2-fold in TG versus WT. At 1 Hz, twitch shortening, [Ca 2+ ] i transient amplitude, and diastolic [Ca 2+ ] i were all reduced by ≈50% in TG versus WT. This is explained by &gt;50% reduction in SR Ca 2+ content in TG versus WT. Peak Ca 2+ current ( I Ca ) was slightly increased, and action potential duration was prolonged in TG versus WT. Despite lower SR Ca 2+ load and diastolic [Ca 2+ ] i , fractional SR Ca 2+ release was increased and resting spontaneous SR Ca 2+ release events (Ca 2+ sparks) were doubled in frequency in TG versus WT (with prolonged width and duration, but lower amplitude). Enhanced Ca 2+ spark frequency was also seen in TG at 4 weeks (before heart failure onset). Acute CaMKII inhibition normalized Ca 2+ spark frequency and I Ca , consistent with direct CaMKII activation of ryanodine receptors (and I Ca ) in TG. The rate of [Ca 2+ ] i decline during caffeine exposure was faster in TG, indicating enhanced Na + -Ca 2+ exchange function (consistent with protein expression measurements). Enhanced diastolic SR Ca 2+ leak (via sparks), reduced SR Ca 2+ -ATPase expression, and increased Na + -Ca 2+ exchanger explain the reduced diastolic [Ca 2+ ] i and SR Ca 2+ content in TG. We conclude that CaMKIIδ C overexpression causes acute modulation of excitation-contraction coupling, which contributes to heart failure.
Head-to-head comparison of accuracy of a rapid point-of-care HIV test with oral versus whole-blood specimens: a systematic review and meta-analysis
Authors: Nitika Pant Pai, Bhairavi Balram, Sushmita Shivkumar, Jorge Luis Martinez-Cajas, Christiane Claessens, Gilles Lambert, Rosanna W Peeling, Lawrence Joseph
Journal: The Lancet Infectious Diseases (2012)
Feasibility of Measuring the Prognostic Factors uPA and PAI-1 in Core Needle Biopsy Breast Cancer Specimens
Authors: Christoph Thomssen, Nadia Harbeck, Juergen Dittmer, Shanti R. Abraha-Spaeth, Nancy Papendick, Angelo Paradiso, Bjoern Lisboa, Fritz Jaenicke, Manfred Schmitt, Martina Vetter
Journal: JNCI Journal of the National Cancer Institute (2009)

References 1. Harris L , Fritsche H , Mennel R , et al . American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer . J Clin Oncol . 2007 ; 25 ( 33 ): 5287 – 5312 . 2. Harbeck N , Thomssen C , Berger U , et al . Invasion marker PAI-1 remains a strong prognostic factor after long-term follow-up both for primary breast cancer and following fi rst relapse . Breast Cancer Res Treat . 1999 ; 54 (2) : 147 – 157 . 3. Annecke K , Schmitt M , Euler U , et al . uPA and PAI-1 in breast cancer: review of their clinical utility and current validation in the prospective NNBC-3 trial . Adv Clin Chem. 2008 ; 45 : 31 – 45 . 4. Janicke F , Prechtl A , Thomssen C , et al . Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identifi ed by urokinase-type plasminogen activator and plasminogen activator Feasibility of Measuring the Prognostic Factors uPA and PAI-1 in Core Needle Biopsy Breast Cancer Specimens
The requirement for two complementing Ir-GLphi immune response genes in the T-lymphocyte proliferative response to poly-(Glu53Lys36Phe11).
Authors: R H Schwartz, M E Dorf, B Benacerraf, W E Paul
Journal: The Journal of Experimental Medicine (1976)

The antibody response to poly-(Glu53Lys36Phe11) (GLphi) has been shown to be under the control of two independent, major histocompatibility-linked immune response genes, designated alpha and beta. In the present work we demonstrate that the T-lymphocyte proliferative response is also under the control of these two immune response genes. Thus, mice of the H-2a, H-2b, H-2k, and H-2s haplotypes were all nonresponders to GLphi. In contrast F1 hybrids between these strains, such as (B10 X B10.A)F1 and (C3H X SJL)F1, as well as several recombinant mice derived from the nonresponder haplotypes, such as B10.1(5R), B10.HTT, and B10.S(9R), were all responders to GLphi. The complementation between nonresponder genomes appeared to be stronger in the cis position than in the trans position for some strain combinations. The failure of strains bearing only one of the two responder alleles to show a T-lymphocyte proliferative response to GLphi, argues strongly that neither gene can be expressed exclusively in B lymphocytes. This conclusion is discussed in relation to another two gene model which has recently been proposed.
Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer
Authors: Sami Sarfaraz, Farrukh Afaq, Vaqar M. Adhami, Hasan Mukhtar
Journal: Cancer Research (2005)

Abstract Cannabinoids, the active components of Cannabis sativa Linnaeus (marijuana) and their derivatives have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects and tumor regression. Here we show that expression levels of both cannabinoid receptors, CB1 and CB2, are significantly higher in CA-human papillomavirus-10 (virally transformed cells derived from adenocarcinoma of human prostate tissue), and other human prostate cells LNCaP, DUI45, PC3, and CWR22Rν1 than in human prostate epithelial and PZ-HPV-7 (virally transformed cells derived from normal human prostate tissue) cells. WIN-55,212-2 (mixed CB1/CB2 agonist) treatment with androgen-responsive LNCaP cells resulted in a dose- (1-10 μmol/L) and time-dependent (24-48 hours) inhibition of cell growth, blocking of CB1 and CB2 receptors by their antagonists SR141716 (CB1) and SR144528 (CB2) significantly prevented this effect. Extending this observation, we found that WIN-55,212-2 treatment with LNCaP resulted in a dose- (1-10 μmol/L) and time-dependent (24-72 hours) induction of apoptosis (a), decrease in protein and mRNA expression of androgen receptor (b), decrease in intracellular protein and mRNA expression of prostate-specific antigen (c), decrease in secreted prostate-specific antigen levels (d), and decrease in protein expression of proliferation cell nuclear antigen and vascular endothelial growth factor (e). Our results suggest that WIN-55,212-2 or other non–habit-forming cannabinoid receptor agonists could be developed as novel therapeutic agents for the treatment of prostate cancer.
Is the cyclic AMP in psoriatic epidermis low?*
Authors: K. YOSHIKAWA, K. ADACHI, K.M. HALPRIN, V. LEVINE
Journal: British Journal of Dermatology (1975)

A deficiency of epidermal cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) has been implicated as the cause of the incomplete differentiation, increased mitosis and increased glycogen concentration which characterize the psoriatic lesion. This communication contains our data on the epidermal concentration of cyclic AMP in the lesional and ‘normal’ (non‐involved) skin of patients with psoriasis. In these studies we have introduced the following improvement in methodology: (1) Local ischaemia in the biopsy specimens was prevented by not giving any injections prior to removal of the tissues and by freezing the tissues prior to removal. (2) The epidermis was microdissected from the dermis prior to cyclic AMP assay so as to give as pure an epidermal specimen as possible. Epidermal cyclic AMP was found to be 20–25% higher in the skin lesion than in the uninvolved skin when compared on a dry weight or protein basis but essentially the same when compared on the basis of DNA content. Our conclusion is that the cyclic AMP level in the psoriatic lesion is not lower than that in the ‘normal’ skin and thus these characteristics in psoriatic lesions cannot be related simply to a cyclic AMP deficiency.
The Autonomic Nervous System and Hypertension
Authors: Giuseppe Mancia, Guido Grassi
Journal: Circulation Research (2014)

Physiological studies have long documented the key role played by the autonomic nervous system in modulating cardiovascular functions and in controlling blood pressure values, both at rest and in response to environmental stimuli. Experimental and clinical investigations have tested the hypothesis that the origin, progression, and outcome of human hypertension are related to dysfunctional autonomic cardiovascular control and especially to abnormal activation of the sympathetic division. Here, we review the recent literature on the adrenergic and vagal abnormalities that have been reported in essential hypertension, with emphasis on their role as promoters and as amplifiers of the high blood pressure state. We also discuss the possible mechanisms underlying these abnormalities and their importance in the development and progression of the structural and functional cardiovascular damage that characterizes hypertension. Finally, we examine the modifications of sympathetic and vagal cardiovascular influences induced by current nonpharmacological and pharmacological interventions aimed at correcting elevations in blood pressure and restoring the normotensive state.
Influenza – the need to stay ahead of the virus
Authors: S van der Werf, D Lévy-Bruhl
Journal: Eurosurveillance (2015)

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The Relationship Between Delusions and Violence
Authors: Jeremy W. Coid, Simone Ullrich, Constantinos Kallis, Robert Keers, Dave Barker, Fiona Cowden, Rebekah Stamps
Journal: JAMA Psychiatry (2013)

Psychotic persons who are violent often explain their violence as being due to delusions. However, research has failed to confirm associations between delusions and violent behavior.To investigate which delusional beliefs and characteristics are associated with violent behavior during a first episode of psychosis and whether these associations are mediated by affect due to delusions.Population-based epidemiological survey of first-episode psychosis during a 2-year study period.Three inner-city boroughs in East London, England.A total of 458 patients with first-episode psychosis who were 18 to 64 years of age.Patients were clinically assessed (using the Schedules for Clinical Assessment in Neuropsychiatry and the Maudsley Assessment of Delusions Schedule) and interviewed about their displaying violent behavior while experiencing psychotic symptoms during the 12-month period prior to interview.Violence was classified at 2 levels of severity: minor and serious violence.The prevalence of violence was 38% during the 12-month period, and 12% of the sample engaged in serious violence. Distinct sets of demographic and comorbid risk factors were associated with minor and serious violence. These were adjusted for in subsequent analyses. Anger was the only affect due to delusions that was positively associated with violence. The population-attributable risk percentage was 30.8% for minor violence and 55.9% for serious violence. A small number of uncommon delusional beliefs demonstrated direct pathways leading to minor violence. Three highly prevalent delusions demonstrated pathways to serious violence mediated by anger due to delusional beliefs: persecution (z = 3.09, P = .002), being spied on (z = 3.03, P = .002), and conspiracy (z = 2.98, P = .002).Anger due to delusions is a key factor that explains the relationship between violence and acute psychosis. A subset of delusional beliefs may be causally linked to violence, and certain uncommon beliefs demonstrated a direct association with minor violence. Highly prevalent delusional beliefs implying threat were associated with serious violence, but they were mediated by anger.
A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease
Authors: I. Dotan, D. Rachmilewitz, S. Schreiber, R. Eliakim, C. J. van der Woude, A. Kornbluth, A. L. Buchman, S. Bar-Meir, B. Bokemeyer, E. Goldin, C. Maaser, U. Mahadevan, U. Seidler, J. C. Hoffman, D. Homoky, T. Plasse, B. Powers, P. Rutgeerts, D. Hommes
Journal: Gut (2010)

<h3>Objective</h3> Semapimod, a small molecule known to inhibit proinflammatory cytokine activity, was studied to determine the optimal dose necessary to achieve a response in patients with moderate to severe Crohn9s disease (CD). <h3>Methods</h3> A randomised, double-blind, placebo-controlled trial (CD04) was carried out followed by an open-label extension study (CD05). The trial was conducted in international multicentre outpatient clinics and included patients with moderate to severe CD (Crohn9s Disease Activity Index (CDAI) 250–400). Placebo was administered for 3 days; 60 mg semapimod intravenously for 1 day with placebo for 2 days; or 60 mg semapimod intravenously for 3 days. Participants who completed CD04 could participate in the open-label extension study, CD05, to receive up to five additional semapimod HCl 60 mg daily doses three times every 6–8 weeks. The main outcome measures were CDAI, Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn9s Disease Endoscopic Inflammation Score (CDEIS) and serum C-reactive protein (CRP) concentration. <h3>Results</h3> 152 patients were randomised in CD04. Responses for 1 and 3 day regimens were similar to placebo for CDAI (p=0.82), IBDQ (p=0.85), CDEIS (p=0.57) and CRP (p=0.40). The only noteworthy treatment-related safety finding was infusion reaction (phlebitis): 7.3, 34.8 and 62.7% for the placebo and 1 and 3 day semapimod treatment groups, respectively (p&lt;0.001). In the open-label CD05 study (included=119 patients) a posthoc analysis showed that the mean CDAI improved in patients receiving 6 compared with ≤3 cumulative doses (204.1±83 vs 251.4±103.05, p=0.006). <h3>Conclusions</h3> Single and 3 day dosing of semapimod (≤180 mg) was ineffective for the treatment of moderate to severe CD. However, cumulative dosing ≥360 mg was associated with decreased CDAI in a limited number of patients.
Role of a 10-Gy boost in the conservative treatment of early breast cancer: results of a randomized clinical trial in Lyon, France.
Authors: P Romestaing, Y Lehingue, C Carrie, R Coquard, X Montbarbon, J M Ardiet, N Mamelle, J P Gérard
Journal: Journal of Clinical Oncology (1997)

PURPOSE To define the role of a 10-Gy boost to the primary tumor in the conservative treatment of early infiltrating breast carcinoma treated by limited surgery and radiotherapy. PATIENTS AND METHODS Between 1986 and 1992, 1,024 women with early breast carcinoma (&lt; or = 3 cm in diameter) were treated by local excision, axillary dissection, and conventional 50-Gy irradiation given in 20 fractions over 5 weeks and then randomly assigned to receive either no further treatment or a boost of 10 Gy by electrons to the tumor bed. The median follow-up time was 3.3 years as of September 1994. The occurrence of telangiectasia was reported, and the patients were asked to evaluate the cosmetic result. RESULTS At 5 years, 10 patients of 521 who had received the boost (Kaplan-Meier estimate of local relapse rate, 3.6%) and 20 of 503 who had received no further treatment (Kaplan-Meier estimate of local relapse rate, 4.5%) had developed a local recurrence (P = .044). After adjustment for the main prognostic variables, the relative risk was still significantly lower for the boost group (0.3; range, 0.12 to 0.95). The boost group had a higher rate of grade 1 and 2 telangiectasia (12.4% v 5.9%), but no difference was seen between the two treatment arms in the self-assessment score for the cosmetic result. CONCLUSION Delivery of a boost of 10 Gy to the tumor bed after 50 Gy to the whole breast following limited surgery significantly reduces the risk of early local recurrence, with no serious deterioration in the cosmetic result. Additional follow-up evaluation will be required to assess the long-term results.
Increased Oxidative Stress and Platelet Activation in Patients With Hypertension and Renovascular Disease
Authors: Pietro Minuz, Paola Patrignani, Stefania Gaino, Maurizio Degan, Laura Menapace, Rosamaria Tommasoli, Francesca Seta, Marta L. Capone, Stefania Tacconelli, Simone Palatresi, Chiara Bencini, Cecilia Del Vecchio, Giancarlo Mansueto, Enrico Arosio, Clara Lechi Santonastaso, Alessandro Lechi, Alberto Morganti, Carlo Patrono
Journal: Circulation (2002)

Hypertensive patients with renovascular disease (RVD) may be exposed to increased oxidative stress, possibly related to activation of the renin-angiotensin system.We measured the urinary excretion of 8-iso-prostaglandin (PG) F2alpha and 11-dehydro-thromboxane (TX) B2 as indexes of in vivo lipid peroxidation and platelet activation, respectively, in 25 patients with RVD, 25 patients with essential hypertension, and 25 healthy subjects. Plasma renin activity in peripheral and renal veins, angiotensin II in renal veins, cholesterol, glucose, triglycerides, homocysteine, and antioxidant vitamins A, C, and E were also determined. Patients were also studied 6 months after a technically successful angioplasty of the stenotic renal arteries. Urinary 8-iso-PGF2alpha was significantly higher in patients with RVD (median, 305 pg/mg creatinine; range, 124 to 1224 pg/mg creatinine) than in patients with essential hypertension (median, 176 pg/mg creatinine; range, 48 to 384 pg/mg creatinine) or in healthy subjects (median, 123 pg/mg creatinine; range, 58 to 385 pg/mg creatinine). Urinary 11-dehydro-TXB2 was also significantly higher in RVD patients compared with healthy subjects. In RVD patients, urinary 8-iso-PGF2alpha correlated with 11-dehydro-TXB2 (r(s)=0.48; P<0.05) and renal vein renin (r(s)=0.67; P<0.005) and angiotensin II (r(s)=0.65; P=0.005) ratios. A reduction in 8-iso-PGF2alpha after angioplasty was observed in RVD patients with high baseline levels of lipid peroxidation. Changes in 8-iso-PGF2alpha were related to baseline lipid peroxidation (r(s)=-0.73; P<0.001), renal vein angiotensin II (r(s)=-0.70; P<0.01) and renin (r(s)=-0.63; P<0.05) ratios.Lipid peroxidation is markedly enhanced in hypertensive patients with RVD and is related to activation of the renin-angiotensin system. Moreover, persistent platelet activation triggered or amplified by bioactive isoprostanes may contribute to the progression of cardiovascular and renal damage in this setting.
Recombinant Soluble CD4 Therapy in Patients with the Acquired Immunodeficiency Syndrome (AIDS) and AIDS-Related Complex
Authors: Robert T. Schooley
Journal: Annals of Internal Medicine (1990)

Study Objective:To study the safety and pharmacokinetics and to derive preliminary evidence on surrogate indicators of efficacy of recombinant soluble CD4 (rsCD4) in patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex. Design:Open label, escalating dosage, phase I-II tolerance trial. Setting:Massachusetts General Hospital, Cedars-Sinai Medical Center, and Stanford University Medical School, three tertiary care institutions and members of the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. Instructions:Cohorts of 3 to 11 patients received rsCD4 by intravenous infusion or intramuscular injection in dosages of up to 30 mg per day for 28 days. Measurements and Main Results:Recombinant soluble CD4 was tolerated by these patients with no significant clinical or immunologic toxicities. Serum levels of rsCD4 in patients receiving doses of 9 or 30 mg per day administered intramuscularly were in the range of rsCD4 concentrations required to inhibit replication of human immunodeficiency virus 1 (HIV-1) in vitro. A decline in serum HIV-1 p24 antigen was seen in patients receiving 30 mg of rsCD4 daily, but no such changes were noted at lower dosages. Conclusions:Recombinant soluble CD4 is well tolerated by patients with AIDS or advanced AIDS-related complex. Our study has also provided preliminary evidence of antiviral activity of rsCD4 in vivo. Our data suggest that further trials of receptor-based therapies against HIV-1 are warranted.
Sociality and self interest
Authors: Vernon L. Smith
Journal: Behavioral and Brain Sciences (2005)

Selfishness narrowly defined as choosing dominant outcomes independent of context is widely rejected by experimentalists. Humans live in two worlds of personal and impersonal exchange; both are manifestations of human sociality, but the emphasis on preferences rather than cultural norms of personal exchange across time too much reflects a limited economic modeling, and fails to capitalize on the fresher experimental economics message of culture and diversity.
Altered Transcript Expression of NMDA Receptor-Associated Postsynaptic Proteins in the Thalamus of Subjects With Schizophrenia
Authors: Sarah M. Clinton, Vahram Haroutunian, Kenneth L. Davis, James H. Meador-Woodruff
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: NMDA receptor dysfunction has been implicated in the pathophysiology of schizophrenia. The NMDA receptor is a multimeric ligand-gated ion channel, and the obligate NR1 subunit is expressed as one of eight isoforms due to the alternative splicing of exons 5, 21, and 22. Alternative splicing of NR1 subunits modulates receptor function by influencing the association of NR1 with other NMDA receptor subunits and myriad intracellular molecules, such as the postsynaptic density family of proteins that target NMDA receptors to the synaptic membrane and couple it to numerous signal transduction enzymes. Recently, the authors reported that the NMDA receptor subunits NR1 and NR2C are abnormally expressed in the thalamus in schizophrenia. They hypothesized that this reduction is associated with specific NR1 isoforms and that NMDA receptor-related postsynaptic density proteins are abnormally expressed. METHOD: Using in situ hybridization, the authors examined expression of the transcripts encoding NR1 isoforms containing exons 5, 21, or 22, and the NMDA receptor-related postsynaptic density proteins NF-L, PSD93, PSD95, and SAP102. RESULTS: Reduced NR1 subunit transcript expression was restricted to exon 22-containing isoforms. Increased expression of the NMDA receptor-associated postsynaptic density proteins NF-L, PSD95, and SAP102 was also detected in the thalamus of subjects with schizophrenia. CONCLUSIONS: These data support the hypothesis of glutamatergic abnormalities in schizophrenia and suggest that glutamatergic dysfunction may occur not only at the level of receptor expression but also within intracellular pathways associated with glutamate receptor-associated signal transduction.