tbuckley/cabot-search huggingface dataset:
Neuropeptide Y
Authors: Zofia Zukowska-Grojec, Ewa Karwatowska-Prokopczuk, Wesley Rose, Janice Rone, Sharareh Movafagh, Hong Ji, Yunyun Yeh, Wen-Tien Chen, Hynda K. Kleinman, Eric Grouzmann, Derrick S. Grant
Journal: Circulation Research (1998)

Sympathetic nerves have long been suspected of trophic activity, but the nature of their angiogenic factor has not been determined. Neuropeptide Y (NPY), a sympathetic cotransmitter, is the most abundant peptide in the heart and the brain. It is released during nerve activation and ischemia and causes vasoconstriction and smooth muscle cell proliferation. Here we report the first evidence that NPY is angiogenic. At low physiological concentrations, in vitro, it promotes vessel sprouting and adhesion, migration, proliferation, and capillary tube formation by human endothelial cells. In vivo, in a murine angiogenic assay, NPY is angiogenic and is as potent as a basic fibroblast growth factor. The NPY action is specific and is mediated by Y1 and Y2 receptors. The expression of both receptors is upregulated during cell growth; however, Y2 appears to be the main NPY angiogenic receptor. Its upregulation parallels the NPY-induced capillary tube formation on reconstituted basement membrane (Matrigel); the Y2 agonist mimics the tube-forming activity of NPY, whereas the Y2 antagonist blocks it. Endothelium contains not only NPY receptors but also peptide itself, its mRNA, and the "NPY-converting enzyme" dipeptidyl peptidase IV (both protein and mRNA), which terminates the Y1 activity of NPY and cleaves the Tyr1-Pro2 from NPY to form an angiogenic Y2 agonist, NPY3-36. Endothelium is thus not only the site of action of NPY but also the origin of the autocrine NPY system, which, together with the sympathetic nerves, may be important in angiogenesis during tissue development and repair.
Varicella-Zoster Virus Transfer to Skin by T Cells and Modulation of Viral Replication by Epidermal Cell Interferon-α
Authors: Chia-Chi Ku, Leigh Zerboni, Hideki Ito, Brad S. Graham, Mark Wallace, Ann M. Arvin
Journal: The Journal of Experimental Medicine (2004)

Primary infection with varicella-zoster virus (VZV) causes the characteristic syndrome of varicella, or chickenpox. Experiments in severe combined immunodeficiency mice with human skin grafts (SCIDhu mice) indicate that VZV infection of T cells can mediate transfer of infectious virus to skin. VZV-infected T cells reached epithelial sites of replication within 24 h after entering the circulation. Memory CD4+ T cells were the predominant population recovered from skin in SCIDhu mice given uninfected or infected mononuclear cells, suggesting that immune surveillance by memory T cells may facilitate VZV transfer. The increased susceptibility of memory T cells to VZV infection may further enhance their role in VZV pathogenesis. During VZV skin infection, viral gene products down-regulated interferon-α to permit focal replication, whereas adjacent epidermal cells mounted a potent interferon-α response against cell–cell spread. Interleukin-1α, although activated in VZV-infected cells, did not trigger expression of endothelial adhesion molecules, thereby avoiding early recruitment of inflammatory cells. The prolonged varicella incubation period appears to represent the time required for VZV to overcome antiviral responses of epidermal cells and generate vesicles at the skin surface. Modulation of VZV replication by cutaneous innate immunity may avoid an incapacitating infection of the host that would limit opportunities for VZV transmission.
Therapy of Experimental Pulmonary Edema in the Dog
Authors: DOMINGO M. AVIADO, JOHN R. DUFFY
Journal: Circulation Research (1959)

The results of analysis of edema fluid and excised lungs show that there is leakage of protein-rich fluid into the lung tissue and ultimately into the respiratory passages. This leakage cannot be explained by the reduction in oxygen uptake as observed in lung tissue slices. The ultimate cause of pulmonary edema is not known. The survival time of anesthetized dogs suffering from thermal edema, can be prolonged by inhalation of oxygen and by administration of antihistaminic drugs and pulmonary vasodilators.
Idiopathic chronic pancreatitis in India
Authors: H. Ramesh
Journal: Gut (2010)

I read with interest the paper by Midha et al 1 which brings a new perspective on non-alcoholic chronic pancreatitis in India which raises some concerns.

The term ‘tropical pancreatitis’ was used to denote a form of chronic pancreatitis unassociated with alcohol abuse which occurred in the tropics and subtropics. The subtropics, by definition, denote geographic areas adjacent to the tropical zone (usually 20–40° latitude) where daytime temperatures remain above 10°C for >8 months of the year. India's geographic latitudinal extent is 6.74678°N to 37.09681°N and daytime temperatures do exceed 10°C for >8 months, and hence qualifies as being ‘tropical’.

In the study, the definition for chronic pancreatitis is vague. Our own preference is to use four criteria: …
Treatment recommendations for cystic fibrosis-related diabetes: too little, too late?
Authors: B. Nathan, A. Moran
Journal: Thorax (2011)

In the general population, altered glucose metabolism is associated with deleterious microvascular changes, inflammatory cardiovascular disease and death. Large population studies have established clinically relevant glucose threshold levels associated with these risks. These have led to the currently accepted definitions of diabetes and oral glucose tolerance abnormalities as well as recommendations for treatment. While these same definitions and treatment recommendations may be appropriate to prevent microvascular disease in those with cystic fibrosis (CF), they may be inadequate when it comes to preventing the major complications of diabetes in CF—namely, respiratory failure and death.

CF-related diabetes (CFRD) is primarily caused by insulin insufficiency as a result of pancreatic fibrosis and islet destruction. In addition, there is a variable component of insulin resistance related to underlying chronic inflammation superimposed with bouts of acute infection. Patients with CFRD are at risk of typical diabetic microvascular complications which, although they occur less frequently and may be less severe than in other diabetes populations, are similarly related to duration of diabetes and the level of glycaemic control.1 In contrast, macrovascular disease—the primary cause of mortality in the general diabetes population—is not known to occur in CFRD, perhaps at least in part because cholesterol levels are low. However, CFRD is associated with its own unique morbidity and mortality profile which has been explored in detail in a recent technical review.2

A number of studies have documented worse …
Intratumoral Heterogeneity: From Diversity Comes Resistance
Authors: Ariel Pribluda, Cecile C. de la Cruz, Erica L. Jackson
Journal: Clinical Cancer Research (2015)

Tumors consist of a heterogeneous mixture of functionally distinct cancer cells. These functional differences can be caused by varying levels of receptor activity, differentiation, and distinct metabolic and epigenetic states. Intratumoral heterogeneity can lead to interdependence among different subpopulations of cells for sustained tumor growth. In addition, subpopulations can vary widely in their responses to therapeutic agents. As such, it is believed that intratumoral heterogeneity may underlie incomplete treatment responses, acquired and innate resistance, and disease relapse observed in the clinic in response to conventional chemotherapy and targeted agents.
Ovarian Hormone Fluctuation, Neurosteroids, and HPA Axis Dysregulation in Perimenopausal Depression: A Novel Heuristic Model
Authors: Jennifer L. Gordon, Susan S. Girdler, Samantha E. Meltzer-Brody, Catherine S. Stika, Rebecca C. Thurston, Crystal T. Clark, Beth A. Prairie, Eydie Moses-Kolko, Hadine Joffe, Katherine L. Wisner
Journal: American Journal of Psychiatry (2015)

In this conceptual review, the authors propose a novel mechanistic candidate in the etiology of depression with onset in the menopause transition ("perimenopausal depression") involving alterations in stress-responsive pathways, induced by ovarian hormone fluctuation.The relevant literature in perimenopausal depression, including prevalence, predictors, and treatment with estrogen therapy, was reviewed. Subsequently, the growing evidence from animal models and clinical research in other reproductive mood disorders was synthesized to describe a heuristic model of perimenopausal depression development.The rate of major depressive disorder and clinically meaningful elevations in depressive symptoms increases two- to threefold during the menopause transition. While the mechanisms by which ovarian hormone fluctuation might impact mood are poorly understood, growing evidence from basic and clinical research suggests that fluctuations in ovarian hormones and derived neurosteroids result in alterations in regulation of the HPA axis by γ-aminobutyric acid (GABA). The authors' heuristic model suggests that for some women, failure of the GABAA receptor to regulate overall GABA-ergic tone in the face of shifting levels of these neurosteroids may induce HPA axis dysfunction, thereby increasing sensitivity to stress and generating greater vulnerability to depression.The proposed model provides a basis for understanding the mechanisms by which the changing hormonal environment of the menopause transition may interact with the psychosocial environment of midlife to contribute to perimenopausal depression risk. Future research investigating this model may inform the development of novel pharmacological treatments for perimenopausal depression and related disorders, such as postpartum depression and premenstrual dysphoric disorder.
Hereditary chondrocalcinosis in an Ashkenazi Jewish family.
Authors: G Eshel, A Gulik, N Halperin, E Avrahami, H R Schumacher, D J McCarty, D Caspi
Journal: Annals of the Rheumatic Diseases (1990)

A hereditary chondrocalcinosis is described for the first time in an Ashkenazi Jewish kindred. Of 34 family members in five generations, seven had medical history suggesting the disease. Five of 25 members of generations III-V had direct evidence for their disease. Characteristically, symptoms started at a fairly early age (third decade) while radiological evidence of chondrocalcinosis was delayed to the fourth decade. Joints commonly affected were knees, wrists, and elbows. The course was chronic with acute, exercise induced exacerbations.
Interferon- release assays do not identify more children with active tuberculosis than the tuberculin skin test
Authors: B. Kampmann, E. Whittaker, A. Williams, S. Walters, A. Gordon, N. Martinez-Alier, B. Williams, A. M. Crook, A-M. Hutton, S. T. Anderson
Journal: European Respiratory Journal (2009)

Data are lacking on the performance of interferon-gamma release assays (IGRAs) in children. Although IGRAs are recommended for screening for latent tuberculosis infection (LTBI), many clinicians wish to employ them as a diagnostic test for active tuberculosis (TB). The objective of the present study was to compare the performance of the two commercially available IGRAs and the tuberculin skin test (TST) side-by-side in children with active TB and LTBI. In a prospective study, 209 children were investigated for active (n = 91) or latent TB (n = 118). TST, QuantiFERON-TB Gold In-tube (QFG-IT; Cellestis, Carnegie, Australia) and T-SPOT.TB (Oxford Immunotec, Abingdon, UK) assays were simultaneously used. For culture-confirmed active TB, the sensitivity of the TST was 83%, compared with 80% for QFG-IT and 58% for T-SPOT.TB. IGRAs did not perform significantly better than TST, although QFG-IT was significantly better than T-SPOT.TB. The agreement between QFG-IT and T-SPOT.TB in culture-confirmed TB was poor at 66.7%. In LTBI, the agreement between QFG-IT and T-SPOT.TB was very good (92%) with moderate agreement between TST and T-SPOT.TB (75%) and QFG-IT and TST (77%). A negative interferon-gamma release assay should not dissuade paediatricians from diagnosing and treating presumed active tuberculosis. If used for diagnosis of latent tuberculosis infection, interferon-gamma release assays could significantly reduce the numbers of children receiving chemoprophylaxis. Very good concordance between both tests was found.
Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults
Authors: Elizabeth Selvin, Michael W. Steffes, Hong Zhu, Kunihiro Matsushita, Lynne Wagenknecht, James Pankow, Josef Coresh, Frederick L. Brancati
Journal: New England Journal of Medicine (2010)

Fasting glucose is the standard measure used to diagnose diabetes in the United States. Recently, glycated hemoglobin was also recommended for this purpose.
<i>Legionella</i> Subvert the Functions of Rab1 and Sec22b to Create a Replicative Organelle
Authors: Jonathan C. Kagan, Mary-Pat Stein, Marc Pypaert, Craig R. Roy
Journal: The Journal of Experimental Medicine (2004)

Legionella pneumophila is a bacterial pathogen that infects eukaryotic host cells and replicates inside a specialized organelle that is morphologically similar to the endoplasmic reticulum (ER). To better understand the molecular mechanisms governing transport of the Legionella-containing vacuole (LCV), we have identified host proteins that participate in the conversion of the LCV into a replicative organelle. Our data show that Rab1 is recruited to the LCV within minutes of uptake. Rab1 recruitment to the LCV precedes remodeling of this compartment by ER-derived vesicles. Genetic inhibition studies demonstrate that Rab1 is important for the recruitment of ER-derived vesicles to the LCV and that inhibiting Rab1 function abrogates intracellular growth of Legionella. Morphological studies indicate that the Sec22b protein is located on ER-derived vesicles recruited to the LCV and that Sec22b is delivered to the LCV membrane. Sec22b function was found to be important for biogenesis of the specialized organelle that supports Legionella replication. These studies demonstrate that Legionella has the ability to subvert Rab1 and Sec22b function to facilitate the transport and fusion of ER-derived vesicles with the LCV, resulting in the formation of a specialized organelle that can support bacterial replication.
COMPLEMENT FIXATION BY A TWO-COMPONENT ANTIBODY SYSTEM: IMMUNOGLOBULIN G AND IMMUNOGLOBULIN M ANTI-GLOBULIN (RHEUMATOID FACTOR)
Authors: Frank R. Schmid, Ivan M. Roitt, Maria J. Rocha
Journal: The Journal of Experimental Medicine (1970)

Complement-mediated lysis of sheep erythrocytes coated with optimal concentrations of rabbit IgG hemolysin was inhibited by euglobulin fractions from the sera of patients with seropositive rheumatoid arthritis. That this was due to direct interaction with the IgG coat on the red cell rather than a nonspecific reaction with complement in the fluid phase was confirmed by controls using cells coated with IgM hemolysin. The inhibitory activity was recovered in purified IgM rheumatoid factor preparations and could be absorbed out with insoluble aggregated human IgG. The inhibitory potency of the rheumatoid factors correlated well with their sheep cell agglutination titers. Inhibition was not the result of physical aggregation of the erythrocytes by rheumatoid factor. Kinetic studies were consistent with the view that rheumatoid factor displaces C1q from its binding to IgG. Paradoxically, at suboptimal sensitizing concentrations of IgG hemolysin, rheumatoid factor enhances the fixation of complement. These results can be interpreted on the basis of the blockage of complement fixation by IgG and its replacement by a relatively weak direct fixation by the IgM rheumatoid factor. Thus, the interaction of RF with IgG generates only a limited ability to fix complement which, when contrasted with the fixation at suboptimal concentrations of IgG hemolysin alone, appears as net enhancement; when this is contrasted with fixation occurring with optimal concentrations of IgG, it appears as net inhibition.
A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease
Authors: Cailin H Sibley, Andrea Chioato, Sandra Felix, Laurence Colin, Abhijit Chakraborty, Nikki Plass, Jackeline Rodriguez-Smith, Carmen Brewer, Kelly King, Christopher Zalewski, H Jeffrey Kim, Rachel Bishop, Ken Abrams, Deborah Stone, Dawn Chapelle, Bahar Kost, Christopher Snyder, John A Butman, Robert Wesley, Raphaela Goldbach-Mansky
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To study efficacy and safety of escalating doses of canakinumab, a fully human anti-IL-1β monoclonal antibody in the severe cryopyrin-associated periodic syndrome, neonatal-onset multisystem inflammatory disease (NOMID). <h3>Methods</h3> 6 patients were enrolled in this 24-month, open-label phase I/II study. All underwent anakinra withdrawal. The initial subcutaneous canakinumab dose was 150 mg (or 2 mg/kg in patients ≤40 kg) or 300 mg (or 4 mg/kg) with escalation up to 600 mg (or 8 mg/kg) every 4 weeks. Full remission was remission of patient-reported clinical components <i>and</i> measures of systemic inflammation <i>and</i> CNS inflammation. Hearing, vision and safety were assessed. Primary endpoint was full remission at month 6. <h3>Results</h3> All patients flared after anakinra withdrawal, and symptoms and serum inflammatory markers improved with canakinumab. All patients required dose escalation to the maximum dose. At month 6, none had full remission, although 4/6 achieved inflammatory remission, based on disease activity diary scores and normal C-reactive proteins. None had CNS remission; 5/6 due to persistent CNS leucocytosis. At the last study visit, 5/6 patients achieved inflammatory remission and 4/6 had continued CNS leucocytosis. Visual acuity and field were stable in all patients, progressive hearing loss occurred in 1/10 ears. Adverse events (AEs) were rare. One serious AE (abscess due to a methicillin-resistant <i>Staphylococcus aureus</i> infection) occurred. <h3>Conclusions</h3> Canakinumab at the studied doses improves symptoms and serum inflammatory features of NOMID, although low-grade CNS leukocytosis in four patients and headaches in one additional patient persisted. Whether further dose intensifications are beneficial in these cases remains to be assessed. <h3>ClinicalTrials.gov identifier</h3> NCT00770601.
American Medical Association approves stem cell research
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

Doctors' participation in cloning stem cells for research and treatment—but not for making babies—is consistent with medical ethics and was approved by the American Medical Association's House of Delegates at its annual meeting in Chicago last week.

The new recommendations will be submitted to a medical journal for publication; meanwhile a summary is posted on the news section of the association's website (www.ama-assn.org).

There is no conflict between the recommendations and the Bush administration's opposition to all research involving cloning, said Dr Michael Goldrich, chairman elect of the association's council on ethical and judicial affairs. He said that President Bush's stance related to federal funding for stem cell research, whereas the association's report “gives guidance to …
Persuading Natural Killer Cells to Eliminate Bad B Cells
Authors: Laurence J.N. Cooper
Journal: Clinical Cancer Research (2009)

Abstract Clinical trials are underway infusing T cells genetically modified to be specific for B-cell malignancies using a chimeric antigen receptor (CAR) to redirect specificity for CD19. However, issues remain about whether the CAR can provide a fully competent application signal and whether other lymphocytes with lytic capacity can target CD19+ tumors.
Vectorcardiographic Changes During Intracoronary Injections
Authors: RAPHAEL F. SMITH, J. WARREN HARTHORNE, CHARLES A. SANDERS
Journal: Circulation (1967)

To determine mechanisms of myocardial toxicity of radiopaque media and to correlate specifically induced changes in the composition of coronary artery blood with changes in the surface electrocardiogram, simultaneous recordings were made from Frank leads X, Y, and Z during intracoronary injections of radiopaque media and special test solutions. The study group consisted of 19 patients, 29 to 64 years of age, with either abnormal or normal-appearing coronary vessels on cineangiography. Recordings were analyzed with an electronic integrator, an oscilloscope, and directly from photographic tracings. With injections of sodium-containing radiopaque media into the right coronary system, the spatial mean T vector increased in magnitude and deviated to the left and superiorly. With injections into the left coronary system, the T vector increased in magnitude and shifted to the right, downward, and anteriorly. Changes in the QRS complex were less constant but, when present, consisted of slight prolongation of the QRS duration and shift of the QRS vector toward the area of myocardium perfused by the coronary system injected. Similar T-vector changes could be produced by intracoronary injections of saline solutions, but minimal or no changes were observed with injections of hypertonic mannitol, Ringer's solution, hypoxic blood, plasma, and 5% dextrose in water. It is concluded that the T-wave changes are caused by regional prolongation of the repolarization process, presumably due to extracellular sodium excess or sodium-calcium antagonism. Delay of the repolarization process and the resulting potential difference may be responsible for re-entrant excitation and the ventricular arrhythmias observed during coronary angiography.
Serum Selenium and Diabetes in U.S. Adults
Authors: Joachim Bleys, Ana Navas-Acien, Eliseo Guallar
Journal: Diabetes Care (2007)

The purpose of this study was to examine the relationship between serum selenium levels and the prevalence of diabetes among U.S. adults.We conducted a cross-sectional analysis of 8,876 adults > or =20 years of age who participated in the Third National Health and Nutrition Examination Survey. Diabetes was defined as the presence of a fasting plasma glucose > or =126 mg/dl, a self-report of a physician diagnosis of diabetes, or current use of insulin or oral hypoglycemic medication. Serum selenium was measured by atomic absorption spectrometry.Mean serum selenium levels in participants with and without diabetes were 126.5 and 125.7 ng/ml, respectively. Age-, sex-, race-, and BMI-adjusted mean selenium levels were 126.8 ng/ml in participants with diabetes and 124.7 ng/ml in participants without diabetes (adjusted difference 2.1 ng/ml [95% CI 0.4-3.8]; P = 0.02). The multivariable adjusted odds ratio for diabetes comparing the highest to the lowest quintile of serum selenium was 1.57 [1.16-2.13]. However, the association between high serum selenium and the prevalence of diabetes was nonlinear, with no clear trend in quintiles 2-4.In a probability sample of the U.S. population, high serum selenium levels were positively associated with the prevalence of diabetes. Until findings from prospective studies and randomized controlled trials are available, selenium intake, including selenium supplementation, should not be recommended for primary or secondary diabetes prevention in populations with adequate selenium status such as the U.S. population.