tbuckley/cabot-search huggingface dataset:
A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease.
Authors: J Wu, J C Edberg, P B Redecha, V Bansal, P M Guyre, K Coleman, J E Salmon, R P Kimberly
Journal: Journal of Clinical Investigation (1997)

A novel polymorphism in the extracellular domain 2 (EC2) of FcgammaRIIIA affects ligand binding by natural killer (NK) cells and monocytes from genotyped homozygous normal donors independently of receptor expression. The nonconservative T to G substitution at nucleotide 559 predicts a change of phenylalanine (F) to valine (V) at amino acid position 176. Compared with F/F homozygotes, FcgammaRIIIa expressed on NK cells and monocytes in V/V homozygotes bound more IgG1 and IgG3 despite identical levels of receptor expression. In response to a standard aggregated human IgG stimulus, FcgammaRIIIa engagement on NK cells from V/V (high-binding) homozygotes led to a larger rise in [Ca2+]i, a greater level of NK cell activation, and a more rapid induction of activation-induced cell death (by apoptosis). Investigation of an independently phenotyped normal cohort revealed that all donors with a low binding phenotype are F/F homozygotes, while all phenotypic high binding donors have at least one V allele. Initial analysis of 200 patients with SLE indicates a strong association of the low binding phenotype with disease, especially in patients with nephritis who have an underrepresentation of the homozygous high binding phenotype. Thus, the FcgammaRIIIa polymorphism at residue 176 appears to impact directly on human biology, an effect which may extend beyond autoimmune disease characterized by immune complexes to host defense mechanisms.
Expression of Notch-1 and Its Ligands, Delta-Like-1 and Jagged-1, Is Critical for Glioma Cell Survival and Proliferation
Authors: Benjamin W. Purow, Raqeeb M. Haque, Martha W. Noel, Qin Su, Michael J. Burdick, Jeongwu Lee, Tilak Sundaresan, Sandra Pastorino, John K. Park, Irina Mikolaenko, Dragan Maric, Charles G. Eberhart, Howard A. Fine
Journal: Cancer Research (2005)

The Notch family of proteins plays an integral role in determining cell fates, such as proliferation, differentiation, and apoptosis. We show that Notch-1 and its ligands, Delta-like-1 and Jagged-1, are overexpressed in many glioma cell lines and primary human gliomas. Immunohistochemistry of a primary human glioma tissue array shows the presence in the nucleus of the Notch-1 intracellular domain, indicating Notch-1 activation in situ. Down-regulation of Notch-1, Delta-like-1, or Jagged-1 by RNA interference induces apoptosis and inhibits proliferation in multiple glioma cell lines. In addition, pretreatment of glioma cells with Notch-1 or Delta-like-1 small interfering RNA significantly prolongs survival in a murine orthotopic brain tumor model. These results show, for the first time, the dependence of cancer cells on a single Notch ligand; they also suggest a potential Notch juxtacrine/autocrine loop in gliomas. Notch-1 and its ligands may present novel therapeutic targets in the treatment of glioma.
Intra-arterial Prourokinase for Acute Ischemic Stroke
Authors: Anthony Furlan, Randall Higashida, Lawrence Wechsler, Michael Gent, Howard Rowley, Carlos Kase, Michael Pessin, Arvind Ahuja, Fred Callahan, Wayne M. Clark, Frank Silver, Frank Rivera, None for the PROACT Investigators
Journal: JAMA (1999)

ContextIntravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset, but many patients present later after stroke onset and alternative treatments are needed.ObjectiveTo determine the clinical efficacy and safety of intra-arterial (IA) recombinant prourokinase (r-proUK) in patients with acute stroke of less than 6 hours' duration caused by middle cerebral artery (MCA) occlusion.DesignPROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized, controlled, multicenter, open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998.SettingFifty-four centers in the United States and Canada.PatientsA total of 180 patients with acute ischemic stroke of less than 6 hours' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infarction signs on computed tomographic scan.InterventionPatients were randomized to receive 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59).Main Outcome MeasuresThe primary outcome, analyzed by intention-to-treat, was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less. Secondary outcomes included MCA recanalization, the frequency of intracranial hemorrhage with neurological deterioration, and mortality.ResultsFor the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = .04). Mortality was 25% for the r-proUK group and 27% for the control group. The recanalization rate was 66% for the r-proUK group and 18% for the control group (P&lt;.001). Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of control patients (P = .06).ConclusionDespite an increased frequency of early symptomatic intracranial hemorrhage, treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days.
Guidelines of care for the management of psoriasis and psoriatic arthritis
Authors: Alice Gottlieb, Neil J. Korman, Kenneth B. Gordon, Steven R. Feldman, Mark Lebwohl, John Y.M. Koo, Abby S. Van Voorhees, Craig A. Elmets, Craig L. Leonardi, Karl R. Beutner, Reva Bhushan, Alan Menter
Journal: Journal of the American Academy of Dermatology (2008)
Arrhythmogenicity of IgG and Anti-52-kD SSA/Ro Affinity-Purified Antibodies From Mothers of Children With Congenital Heart Block
Authors: Mohamed Boutjdir, Long Chen, Zhi-Hao Zhang, Chung-E Tseng, Francis DiDonato, William Rashbaum, Alan Morris, Nabil El-Sherif, Jill P. Buyon
Journal: Circulation Research (1997)

An important advance in the description and understanding of congenital heart block (CHB) came in the 1970s with the observation that mothers of affected infants frequently had autoimmune diseases and, in particular, that many maternal sera contained antibodies to SSA/Ro and SSB/La ribonucleoproteins. Although the molecular biology of the candidate antigens has been extensively defined, the arrhythmogenic and electrophysiological effects of their cognate antibodies on the human fetal heart are unknown. In the present study, we provide evidence that IgG-enriched fractions and anti-52-kD SSA/Ro antibodies affinity-purified from sera of mothers whose children have CHB induce complete atrioventricular (AV) block in the human fetal heart perfused by the Langendorff technique and inhibit L-type Ca2+ currents at the whole-cell and single-channel level. Immunization of female BALB/c mice with recombinant 52-kD SSA/Ro protein generated high-titer antibodies that crossed the placenta during pregnancy and were associated with varying degrees of AV conduction abnormalities, including complete AV block, in the pups. These findings strongly suggest that anti-52-kD SSA/Ro antibodies are causally related to the development of CHB.
Magnetic Resonance Imaging Measurements of the Response of Murine and Human Tumors to the Vascular-Targeting Agent ZD6126
Authors: Jeffrey L. Evelhoch, Patricia M. LoRusso, Zhanquan He, Zachary DelProposto, Lisa Polin, Thomas H. Corbett, Peter Langmuir, Catherine Wheeler, Andrew Stone, Joanna Leadbetter, Anderson J. Ryan, David C. Blakey, John C. Waterton
Journal: Clinical Cancer Research (2004)

Abstract Purpose: ZD6126 is a novel vascular targeting agent currently undergoing clinical evaluation. It acts by destabilizing the microtubulin of fragile and proliferating neoendothelial cells in tumors. The drug leads to blood vessel congestion, the selective destruction of the vasculature, and extensive necrosis in experimental tumors. The aim of the study reported here was to assess the ability of dynamic contrast enhanced magnetic resonance imaging (MRI) to measure the antivascular effects of ZD6126 in tumors. Experimental Design: The work was carried out in mice bearing C38 colon adenocarcinoma and in patients with advanced cancers. MRI was performed before and 6 h (human tumors) or 24 h (C38 tumors) after i.v. drug administration. Contrast agent (gadolinium diethylenetriaminepentaacetate) enhancement was characterized by the initial area under the gadolinium diethylenetriaminepentaacetate uptake versus time curve (IAUC). IAUC reflects blood flow, vascular permeability, and the fraction of interstitial space. Results: The median IAUC was reduced in all C38 tumors after ZD6126 administration [by 6–48% at 50 mg/kg (n = 3)], 58–91% at 100 mg/kg (n = 4), and 11–93% at 200 mg/kg (n = 6). In contrast, the administration of vehicle only led to no consistent change in median IAUC (n = 4). The ZD6126-induced changes in median IAUC appeared to be dose dependent (P = 0.045). No ZD6126-induced changes were apparent in murine muscle. Similar effects were seen in preliminary data from human tumors (11 tumors studied, 9 patients). At doses of 80 mg/m2 and higher, the median IAUC post-ZD6126 treatment was reduced in all of the tumors studied (8 tumors, 6 patients) to 36–72% from the baseline value. There was a significant trend of increasing reductions with increasing exposure (P &amp;lt; 0.01). No drug-induced changes in human muscle or spleen IAUC were apparent. The reproducibility of the median IAUC parameter was investigated in patients. In 19 human tumors (measured in 19 patients) inter- and intratumor coefficients of variation were 64 and 18%. Conclusions: The contrast enhanced-MRI measured median IAUC is a useful end point for quantifying ZD6126 antivascular effects in human tumors.
The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized mice
Authors: Wenwei Tu, Jian Zheng, Yinping Liu, Sin Fun Sia, Ming Liu, Gang Qin, Iris H.Y. Ng, Zheng Xiang, Kwok-Tai Lam, J.S. Malik Peiris, Yu-Lung Lau
Journal: The Journal of Experimental Medicine (2011)

There are few antiviral drugs for treating influenza, and the emergence of antiviral resistance has further limited the available therapeutic options. Furthermore, antivirals are not invariably effective in severe influenza, such as that caused by H5N1 viruses. Thus, there is an urgent need to develop alternative therapeutic strategies. Here, we show that human Vγ9Vδ2 T cells expanded by the aminobisphosphonate pamidronate (PAM) kill influenza virus–infected cells and inhibit viral replication in vitro. In Rag2−/−γc−/− immunodeficient mice reconstituted with human peripheral mononuclear cells (huPBMCs), PAM reduces disease severity and mortality caused by human seasonal H1N1 and avian H5N1 influenza virus, and controls the lung inflammation and viral replication. PAM has no such effects in influenza virus–infected Rag2−/−γc−/− mice reconstituted with Vγ9Vδ2 T cell–depleted huPBMCs. Our study provides proof-of-concept of a novel therapeutic strategy for treating influenza by targeting the host rather than the virus, thereby reducing the opportunity for the emergence of drug-resistant viruses. As PAM has been commonly used to treat osteoporosis and Paget’s disease, this new application of an old drug potentially offers a safe and readily available option for treating influenza.
A General Textbook of Entomology. Including the Anatomy, Physiology, Development and Classification of Insects.
Authors: A. D. Imms
Journal: JAMA (1926)

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Ocular Complications of Drugs
Authors: W. Morton Grant
Journal: JAMA (1969)

Glaucoma, whether spontaneous or drug-induced, is caused in nearly all instances by abnormal resistance to outflow of aqueous humor to the veins on the outer surface of the eye. Three types of glaucoma can affect adults: angle-closure glaucoma, open-angle glaucoma, and the secondary glaucomas that result from preexisting ocular diseases. The adverse effects on intraocular pressure produced by systemic drugs principally involve the first two types of glaucoma. An acute attack of angle-closure glaucoma, which may be precipitated by drugs that dilate the pupil, is caused by the periphery of the iris bulging forward to obstruct the trabecular meshwork and, thus, prevent the aqueous from reaching the outflow channels. In open-angle glaucoma, which may be aggravated by anticholinergic and corticosteroid drugs, excessive resistance to outflow is caused by changes within the outflow channels themselves, mainly within the trabecular meshwork, independent of the size of the pupil. The intraocular pressure usually
Effect of a Risk-stratified Grade of Nerve-sparing Technique on Early Return of Continence After Robot-assisted Laparoscopic Radical Prostatectomy
Authors: Abhishek Srivastava, Sameer Chopra, Anthony Pham, Prasanna Sooriakumaran, Matthieu Durand, Bilal Chughtai, Siobhan Gruschow, Alexandra Peyser, Niyati Harneja, Robert Leung, Richard Lee, Michael Herman, Brian Robinson, Maria Shevchuk, Ashutosh Tewari
Journal: European Urology (2012)
Role of β1 and β3 Integrins in Human Smooth Muscle Cell Adhesion to and Contraction of Fibrin Clots In Vitro
Authors: Karen O Yee, Michael M. Rooney, Cecilia M. Giachelli, Susan T. Lord, Stephen M. Schwartz
Journal: Circulation Research (1998)

Abstract —The degree of lumen narrowing in advanced lesions correlates poorly with the amount of intimal mass accumulated in the atherosclerotic plaque. As an alternate mechanism of stenosis, we propose that human smooth muscle cells bind to fibrin deposited in the matrix and exert contractile forces to cause a narrowing of the lumen. In the present study we demonstrated in vitro that human newborn aortic smooth muscle cell lines can contract and adhere to fibrin clots composed of either fibronectin-depleted plasma (“plasma”) or recombinant fibrin. By using neutralizing antibodies and RGD peptides, we showed that members of the integrin family mediated the interaction between human newborn smooth muscle cells and fibrin. Neutralizing antibodies against the integrin αvβ3 (c7E3 Fab and LM609) did not inhibit either plasma clot contraction or recombinant fibrin clot contraction by human newborn smooth muscle cells. In contrast, antibodies against α5, β1, and α5β1 inhibited contraction of clots composed of either plasma or recombinant fibrin. Anti-αvβ3, anti-αv, anti-α5, anti-β1, and anti-α5β1 antibodies inhibited human newborn smooth muscle cell adhesion to plasma clots; however, only anti-α5, anti-β1, and anti-α5β1 antibodies significantly inhibited adhesion to recombinant fibrin. While the linear RGD peptides had no effect, the cyclic peptide penRGD inhibited adhesion to plasma clots and recombinant fibrin. However, it did not block contraction of recombinant fibrin clots. These results suggest that during the interaction of human newborn smooth muscle cell lines with fibrin, α5β1 plays a significant role. This interaction is of potential interest as a target for efforts to block vascular contraction.
Hematological aspect of Rh deficiency syndrome: A case report and a review of the literature
Authors: R. Nash, A. M. Shojania
Journal: American Journal of Hematology (1987)

The hematological aspects of the original case of Rhmod are reported. The subject, as in other reported cases, had a chronic hemolytic anemia characterized by stomatocytosis, reduced osmotic fragility, and abnormal autohemolysis correctable with the addition of glucose. The 51Cr red cell survival studies showed the spleen to be the preferential site of red cell destruction and splenectomy produced a dramatic improvement in red cell survival. The topic of Rh deficiency syndrome (Rhnull and Rhmod) is briefly reviewed with regard to the number of cases reported, to genetic aspects, to the hematological findings, and to the results of splenectomy.
Cystic fibrosis, a Burkholderia cenocepacia chest wall abscess and rapid clinical deterioration
Authors: Nj Simmonds, Km Gyi
Journal: Journal of the Royal Society of Medicine (2008)

The Burkholderia cepacia complex (Bcc) is a group of Gram-negative, non-spore-forming bacilli representing at least nine closely related bacterial species, of which Burkholderia cenocepacia and Burkholderia multivorans are the most prevalent in cystic fibrosis (CF). Outcome with Bcc infection can be difficult to predict for an individual CF patient, but generally it has been shown to correlate with a worse prognosis, longer hospital stays and an increased risk of death.1–3 ‘Cepacia syndrome’ is a term used to describe an important subgroup of Bcc-infected patients who develop a rapidly progressive pneumonic process associated with high fevers, positive blood cultures, respiratory failure and high mortality.4

The present case report describes a CF patient who, despite having B. cenocepacia for 13 years, had an excellent state of health with stable disease until he developed a large chest wall B. cenocepacia abscess and – despite aggressive medical and surgical management – deteriorated rapidly with sepsis, multiorgan failure and eventual death.
The relationship between IgE-mediated and cell-mediated hypersensitivities in an unselected Danish population: The Glostrup Allergy Study, Denmark
Authors: N.H. NIELSEN, T. MENNÉ
Journal: British Journal of Dermatology (1996)

In this study, we have assessed the relationship between IgE‐mediated and cell‐mediated hypersensitivities in an unselected population living in western Copenhagen, Denmark. A total of 793 subjects, aged 15–69 years, were studied. Measurements of total serum IgE prick tests with aeroallergens and patch tests with environmental haptens were performed in 561 (70·7% of 793) subjects. One or more positive prick tests were present in 28·4%, and contact sensitization occurred in 15·2%. When adjusted for the effects of sex and age, the probability of contact sensitization to one or more hapten was independent of serum IgE level (the odds ratio value (OR) = 1.0; 95% confidence interval (CI) = 0·7–1·4), and the probability of contact sensitization was independent of the number of positive prick tests (0R = 1·0; CI = 0·8–1·2). Contact sensitization appeared to be independent of enhanced IgE responsiveness in an unselected adult population.
Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis
Authors: Yoshitaka Morita, Jianmin Yang, Raj Gupta, Koichi Shimizu, Eric A. Shelden, Judith Endres, James J. Mulé, Kevin T. McDonagh, David A. Fox
Journal: Journal of Clinical Investigation (2001)

Dendritic cells (DCs) are specialized antigen-presenting cells that migrate from the periphery to lymphoid tissues, where they activate and regulate T cells. Genetic modification of DCs to express immunoregulatory molecules would provide a new immunotherapeutic strategy for autoimmune and other diseases. We have engineered bone marrow–derived DCs that express IL-4 and tested the ability of these cells to control murine collagen-induced arthritis (CIA), a model for rheumatoid arthritis in which Th1 cells play a critical role. IL-4–transduced DCs inhibited Th1 responses to collagen type II in vitro. A single injection of IL-4–transduced DCs reduced the incidence and severity of CIA and suppressed established Th1 responses and associated humoral responses, despite only transient persistence of injected DCs in the spleen. In contrast, control DCs and IL-4–transduced T cells or fibroblastic cells failed to alter the course of the disease. The functional effects correlated well with the differential efficiency of DC migration from various sites of injection to lymphoid organs, especially the spleen. The ability of splenic T cells to produce IL-4 in response to anti-CD3 was enhanced after the administration of IL-4–transduced DCs. These results support the feasibility of using genetically modified DCs for the treatment of autoimmune disease.
Effect of sodium chenodeoxycholate on oxalate absorption from the excluded human colon--a mechanism for 'enteric' hyperoxaluria.
Authors: P D Fairclough, T G Feest, V S Chadwick, M L Clark
Journal: Gut (1977)

A perfusion technique has been used to study the effect of sodium chenodeoxycholate (5 mmol 1-1) on absorption of oxalate (2 mmol 1-1) from the surgically excluded colon in two patients with chronic liver disease.Colonic absorption of oxalate increased at least fivefold when sodium chenodeoxycholate was incorporated in the perfusion solutions.This observation may explain enteric hyperoxaluria after ileal resection and in some other gastrointestinal disorders.
Temsirolimus in combination with carboplatin and paclitaxel in patients with advanced solid tumors: a NCIC-CTG, phase I, open-label dose-escalation study (IND 179)
Authors: C Kollmannsberger, H Hirte, L L Siu, J Mazurka, K Chi, L Elit, W Walsh, J Sederias, A Doyle, E A Eisenhauer, A M Oza
Journal: Annals of Oncology (2011)
Optimistic Bias in the Perception of Personal Risk: Patterns in Schizophrenia
Authors: Kristen J. Prentice, James M. Gold, William T. Carpenter
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Biases in the perception of personal vulnerability to risk could influence how individuals make decisions in many contexts. Schizophrenia patients, because of neurocognitive deficits and psychiatric symptoms, are often seen as compromised in their ability to appreciate risk information and in their decision-making capacity. The authors investigated whether schizophrenia patients share the same optimistic biases frequently demonstrated by non-ill adults in their perceptions of personal risk. METHOD: Twenty-five schizophrenic outpatients and 23 healthy comparison subjects completed a risk perception questionnaire on which they compared their own likelihood of experiencing adverse events to that of other adults. Questionnaire items were adverse events of three types: controllable, uncontrollable, and neutral. The degree to which subjects rated their own likelihood of experiencing adverse events as lower than others' was an index of optimistic bias. RESULTS: Although both groups showed an optimistic bias in general, healthy comparison subjects demonstrated a greater level of optimism than did schizophrenia patients, especially for events typically perceived as controllable. Psychiatric symptoms rated with the Brief Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms bore little relationship to patients' ratings on the risk questionnaire. CONCLUSIONS: Results showed that an unrealistically optimistic bias in the perception of personal risk was at least as evident in a healthy comparison group as in a schizophrenia group. Such a bias could influence decision making. By identifying and responding to such biases, clinicians and researchers can promote more fully informed and rational decisions in patients and healthy adults.