tbuckley/cabot-search huggingface dataset:
Deletion of LCE3C and LCE3B genes at PSORS4 does not contribute to susceptibility to psoriatic arthritis in German patients
Authors: U. Huffmeier, X. Estivill, E. Riveira-Munoz, H. Traupe, J. Wendler, J. Lohmann, B. Bohm, H. Burkhardt, A. Reis
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Introduction</h3> Psoriasis susceptibility locus 4 (PSORS4) is a susceptibility locus for psoriasis vulgaris (PsV), a common inflammatory, hyperproliferative skin disorder. Recently, a deletion of 2 late cornified envelope (<i>LCE</i>) genes within epidermal differentiation complex on chromosome 1 was shown to be enriched in 1426 patients with PsV, suggesting compromised barrier function in deletion carriers. This genetic association was subsequently confirmed in a German cohort. <h3>Methods</h3> In order to investigate whether this variant also predisposes to psoriatic arthritis (PsA), this deletion and 3 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium with it were genotyped in a case-control cohort of 650 patients and 937 control individuals of German origin. <h3>Results</h3> <i>LCE</i> deletion frequency did not significantly differ between patients with PsA and controls (65.0% vs 65.5%). Similarly, no evidence for association to the three SNPs was observed. <h3>Discussion</h3> This is the first non-human leucocyte antigen (HLA) risk factor predisposing only to skin type of psoriasis, supporting the concept of partially overlapping but different aetiological factors underlying skin and joint manifestations.
British Society of Gastroenterology guidelines for the management of the irritable bowel syndrome
Authors: J Jones
Journal: Gut (2000)

Prepulse inhibition (PPI) of startle is the suppression of the startle reflex when a weaker sensory stimulus (the prepulse) shortly precedes the startling stimulus. PPI can be attentionally enhanced in both humans and laboratory animals. This study investigated whether the following three forebrain structures, which are critical for initial cortical processing of auditory signals, auditory fear conditioning/memories, and spatial attention, respectively, play a role in the top-down modulation of PPI in rats: the primary auditory cortex (A1), lateral nucleus of the amygdala (LA), and posterior parietal cortex (PPC). The results show that, under the noise-masking condition, PPI was enhanced by fear conditioning of the prepulse in a prepulse-specific manner, and the conditioning-induced PPI enhancement was further increased by perceptual separation between the conditioned prepulse and the noise masker. Reversibly blocking glutamate receptors in the A1 with 2 mm kynurenic acid eliminated both the conditioning-induced and perceptual separation-induced PPI enhancements. Blocking the LA eliminated the conditioning-induced but not the perceptual separation-induced PPI enhancement, and blocking the PPC specifically eliminated the perceptual separation-induced PPI enhancement. The two types of PPI enhancements were also eliminated by the extinction manipulation. Thus, the top-down modulation of PPI is differentially organized and depends on operations of various forebrain structures. Due to the fine-tuned modulation by higher-order cognitive processes, functions of PPI can be more flexible to complex environments. The top-down enhancements of PPI in rats are also useful for modeling some mental disorders, such as schizophrenia, attention deficit/hyperactivity disorder, and posttraumatic stress disorder.
Will new Indian growth charts help stem the rise in childhood obesity?
Authors: None Manupriya
Journal: BMJ (2015)

New body mass index charts for children in India have the same overweight and obesity cut-off points as for adults, but not everyone agrees that they will help, writes Manupriya 

The growth charts committee of the Indian Academy of Paediatrics (IAP) has recently recommended revised growth charts for height, weight, and body mass index for Indian children aged 5-18. As well as reflecting changes in average height and weight over the past decade, the new charts aim to better identify children with overweight and obesity.

The charts were last revised in 2007, using data that had been collected as long ago as 1989. The new charts are based on the academy’s study of 33 991 children living in 14 cities of India, which was published in 2015.1

Improvements in financial security and availability of adequate nourishing food have affected dietary patterns in India, helping children—especially those from richer socioeconomic groups—to grow. While poorer children remain undernourished, some children from richer families are experiencing obesity. Accurate estimates for childhood obesity in India are not available, but studies have pegged its prevalence between 5% and 14%.2 Obese children are more likely to become obese adults, with a greater burden of lifestyle related non-communicable diseases such as diabetes, cardiovascular problems, and arthritis.

Doctors have long called for revised growth charts to reflect the changing growth patterns in India and to provide better …
Liver-directed gene therapy of chronic hepadnavirus infection using interferon alpha tethered to apolipoprotein A-I
Authors: Pedro Berraondo, Marianna Di Scala, Kyle Korolowicz, Linta M. Thampi, Itziar Otano, Lester Suarez, Jessica Fioravanti, Fernando Aranda, Nuria Ardaiz, Junming Yang, Bhaskar V. Kallakury, Robin D. Tucker, Marcos Vasquez, Stephan Menne, Jesús Prieto, Gloria González-Aseguinolaza
Journal: Journal of Hepatology (2015)
Effects of epoprostenol infusion on myocardial inflammation in acute afterload-induced right ventricular failure
Authors: Céline Dewachter, Laurence Dewachter, Marie Vercruyssen, Benoit Rondelet, Dean Schraufnagel, Isabelle Roland, Serge Brimioulle, François Kerbaul, Robert Naeije
Journal: European Respiratory Journal (2013)

Background:  Acute transient pulmonary hypertension may induce a state of persistent right ventricular (RV) failure.  Aims and objectives:  We hypothesized that this could be related to an activation of inflammatory pathways, and reduced by prostacyclin therapy.  Methods:  Twenty-three dogs were randomized to a sham- (n=8) or to a 90-min pulmonary artery constriction-operation followed by 30-min banding release (n=15). In 7 dogs with persistent RV failure, epoprostenol infusion was performed 30-min after banding release. Myocardial tissue was finally sampled.  Results:  Persistent RV failure was associated with increased myocardial expressions of interleukin(IL)-1β, IL-6, monocyte chemoattractant protein(MCP)-1, pro-inflammatory IL-6/IL-10 ratio, and infiltration of neutrophils and macrophages, while heme oxygenase(HO)-1 expression was decreased. These changes were observed in the RV and, to a lesser extent, in the LV. In the RV only, expressions of prostacyclin synthase (PGI2S), IL-10 and IL-33 decreased and expression of vascular cell adhesion molecule(VCAM)1 increased. Epoprostenol decreased RV and LV expressions of IL-1β, VCAM1 and increased IL-10 expression, while MCP-1 decreased only in the RV. Epoprostenol decreased RV IL-6/IL-10 and pro-apoptotic Bax/Bcl-2 ratios, together with decreased neutrophil and macrophage infiltrations. RV ratio of end-systolic to arterial elastances was inversely correlated to RV IL-6/IL-10 ratio, macrophage and neutrophil infiltrations, and correlated to RV expressions of HO-1 and IL-33.  Conclusion:  Acute afterload-induced persistent RV failure is associated with an activation of inflammation which is limited by an epoprostenol infusion.
(55) Birt-Hogg-Dube syndrome and lichen sclerosus et atrophicus
Authors: C.I. Harrington, A.G. Messenger
Journal: British Journal of Dermatology (1986)

Journal Article (55) Birt‐Hogg‐Dubé syndrome and lichen sclerosus et atrophicus Get access C.I. Harrington, Drs, C.I. Harrington, Drs Search for other works by this author on: Oxford Academic Google Scholar A.G. Messenger A.G. Messenger Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s30, 1 July 1986, Pages 97–98, https://doi.org/10.1111/j.1365-2133.1986.tb07750.x Published: 01 July 1986
Overdispersion of the Molecular Clock: Temporal Variation of Gene-Specific Substitution Rates in Drosophila
Authors: T. Bedford, D. L. Hartl
Journal: Molecular Biology and Evolution (2008)

Simple models of molecular evolution assume that sequences evolve by a Poisson process in which nucleotide or amino acid substitutions occur as rare independent events. In these models, the expected ratio of the variance to the mean of substitution counts equals 1, and substitution processes with a ratio greater than 1 are called overdispersed. Comparing the genomes of 10 closely related species of Drosophila, we extend earlier evidence for overdispersion in amino acid replacements as well as in four-fold synonymous substitutions. The observed deviation from the Poisson expectation can be described as a linear function of the rate at which substitutions occur on a phylogeny, which implies that deviations from the Poisson expectation arise from gene-specific temporal variation in substitution rates. Amino acid sequences show greater temporal variation in substitution rates than do four-fold synonymous sequences. Our findings provide a general phenomenological framework for understanding overdispersion in the molecular clock. Also, the presence of substantial variation in gene-specific substitution rates has broad implications for work in phylogeny reconstruction and evolutionary rate estimation.
Cross-priming of minor histocompatibility antigen-specific cytotoxic T cells upon immunization with the heat shock protein gp96.
Authors: D Arnold, S Faath, H Rammensee, H Schild
Journal: The Journal of Experimental Medicine (1995)

Vaccination of mice with heat shock proteins isolated from tumor cells induces immunity to subsequent challenge with those tumor cells the heat shock protein was isolated from but not with other tumor cells (Udono, H., and P.K. Srivastava. 1994. J. Immunol. 152:5398-5403). The specificity of this immune response is caused by tumor-derived peptides bound to the heat shock proteins (Udono., H., and P.K. Srivastava. 1993. J. Exp. Med. 178:1391-1396). Our experiments show that a single immunization with the heat shock protein gp96 isolated from beta-galactosidase (beta-gal) expressing P815 cells (of DBA/2 origin) induces cytotoxic T lymphocytes (CTLs) specific for beta-gal, in addition to minor H antigens expressed by these cells. CTLs can be induced in mice that are major histocompatibility complex (MHC) identical to the gp96 donor cells (H-2d) as well as in mice with a different MHC (H-2b). Thus gp96 is able to induce "cross priming" (Matzinger, P., and M.J. Bevan. 1977. Cell. Immunol. 33:92-100), indicating that gp96-associated peptides are not limited to the MHC class I ligands of the gp96 donor cell. Our data confirm the notion that samples of all cellular antigens presentable by MHC class I molecules are represented by peptides associated with gp96 molecules of that cell, even if the fitting MHC molecule is not expressed. In addition, we extend previous reports on the in vivo immunogenicity of peptides associated gp96 molecules to two new groups of antigens, minor H antigens, and proteins expressed in the cytosol.
Docosahexaenoic Acid Signalolipidomics in Nutrition: Significance in Aging, Neuroinflammation, Macular Degeneration, Alzheimer's, and Other Neurodegenerative Diseases
Authors: Nicolas G. Bazan, Miguel F. Molina, William C. Gordon
Journal: Annual Review of Nutrition (2011)

Essential polyunsaturated fatty acids (PUFAs) are critical nutritional lipids that must be obtained from the diet to sustain homeostasis. Omega-3 and -6 PUFAs are key components of biomembranes and play important roles in cell integrity, development, maintenance, and function. The essential omega-3 fatty acid family member docosahexaenoic acid (DHA) is avidly retained and uniquely concentrated in the nervous system, particularly in photoreceptors and synaptic membranes. DHA plays a key role in vision, neuroprotection, successful aging, memory, and other functions. In addition, DHA displays anti-inflammatory and inflammatory resolving properties in contrast to the proinflammatory actions of several members of the omega-6 PUFAs family. This review discusses DHA signalolipidomics, comprising the cellular/tissue organization of DHA uptake, its distribution among cellular compartments, the organization and function of membrane domains rich in DHA-containing phospholipids, and the cellular and molecular events revealed by the uncovering of signaling pathways regulated by DHA and docosanoids, the DHA-derived bioactive lipids, which include neuroprotectin D1 (NPD1), a novel DHA-derived stereoselective mediator. NPD1 synthesis agonists include neurotrophins and oxidative stress; NPD1 elicits potent anti-inflammatory actions and prohomeostatic bioactivity, is anti-angiogenic, promotes corneal nerve regeneration, and induces cell survival. In the context of DHA signalolipidomics, this review highlights aging and the evolving studies on the significance of DHA in Alzheimer's disease, macular degeneration, Parkinson's disease, and other brain disorders. DHA signalolipidomics in the nervous system offers emerging targets for pharmaceutical intervention and clinical translation.
Case report: Allergic reaction with immune hemolytic anemia resulting from chlorambucil
Authors: Luis Thompson‐Moya, Thomas Martin, Hans‐Gert Heuft, Andreas Neubauer, Richard Herrmann
Journal: American Journal of Hematology (1989)

In a 73-year-old female with chronic lymphocytic leukemia we observed an acute illness with shivering, high fever, and hemolytic anemia following chlorambucil administration. Reexposure in a controlled clinical situation suggested an allergic drug reaction. In an in vitro assay, we were able to demonstrate chlorambucil as the causative agent of immune hemolysis.
Objectivity, intentionality, and levels of explanation
Authors: Ulrich Müller, Jeremy I. M. Carpendale
Journal: Behavioral and Brain Sciences (2001)

Notwithstanding many similarities between Thelen et al.'s and Piaget's accounts of the A-not-B error, we argue that, in contrast to Piaget, they do not explicitly address the issue of objectivity. We suggest that this omission is partly due to the fact that Thelen et al. and Piaget's accounts are pitched at different levels of explanation.
Wound Botulism Associated With Black Tar Heroin Among Injecting Drug Users
Authors: Douglas J. Passaro
Journal: JAMA (1998)

Context.-Wound botulism (WB) is a potentially lethal, descending, flaccid, paralysis that results when spores of Clostridium botulinum germinate in a wound and elaborate neurotoxin.Since 1988, California has experienced a dramatic increase in WB associated with injecting "black tar" heroin (BTH), a dark, tarry form of the drug.Objective.-Toidentify risk factors for WB among injecting drug users (IDUs).Design.-Case-control study based on data from in-person and telephone interviews.Participants.-Casepatients (n=26) were IDUs who developed WB from January 1994 through February 1996.Controls (n=110) were IDUs newly enrolled in methadone detoxification programs in 4 counties.Main Outcome Measures.-Factorsassociated with the development of WB.Results.-Among the 26 patients, the median age was 41.5 years, 15 (58%) were women, 14 (54%) were non-Hispanic white, 11 (42%) were Hispanic, and none were positive for the human immunodeficiency virus.Nearly all participants (96% of patients and 97% of controls) injected BTH, and the mean cumulative dose of BTH used per month was similar for patients and controls (27 g and 31 g, respectively; P=.6).Patients were more likely than controls to inject drugs subcutaneously or intramuscularly (92% vs 44%, PϽ.001) and used this route of drug administration more times per month (mean, 67 vs 24, PϽ.001), with a greater cumulative monthly dose of BTH (22.3 g vs 6.3 g, PϽ.001).A dose-response relationship was observed between the monthly cumulative dose of BTH injected subcutaneously or intramuscularly and the development of WB ( 2 for linear trend, 26.5; PϽ.001).In the final regression model, subcutaneous or intramuscular injection of BTH was the only behavior associated with WB among IDUs (odds ratio, 13.7; 95% confidence interval, 3.0-63.0).The risk for development of WB was not affected by cleaning the skin, cleaning injection paraphernalia, or sharing needles.Conclusions.-Injection of BTH intramuscularly or subcutaneously is the primary risk factor for the development of WB.Physicians in the western United States, where BTH is widely used, should be aware of the potential for WB to occur among IDUs.
Insulin Analogs—Are They Worth It? Yes!
Authors: George Grunberger
Journal: Diabetes Care (2014)

The availability of insulin analogs has offered insulin replacement strategies that are proposed to more closely mimic normal human physiology. Specifically, there are a considerable number of reports demonstrating that prandial insulin analogs (lispro, aspart, glulisine) have pharmacokinetic and pharmacodynamic profiles closer to normal, with resulting faster onset and offset of insulin effect when compared with regular human insulin. In addition, basal insulin analogs (glargine, detemir) have been reported to offer longer duration of action, less variability, more predictability, less hypoglycemia (especially nocturnal), and a favorable effect on weight. However, an argument against use of analog insulins as compared with use of regular or NPH insulin is one that states that the effectiveness and risk of hypoglycemia are the only two valid clinical outcomes that should be used to compare the analog and human insulins. Thus, there remains a debate in some circles that analog insulins are no more effective than human insulins, yet at a much higher financial cost. To provide an in-depth understanding of both sides of the argument, we provide a discussion of this topic as part of this two-part point-counterpoint narrative. In the counterpoint narrative, Dr. Davidson provides his argument and defends his opinion that outside of a few exceptions, analog insulins provide no clinical benefit compared with human insulins but cost much more. In the point narrative presented here, Dr. Grunberger provides a defense of analog insulins and their value in clinical management and suggests that when evaluating the “cost” of therapy, a much more global assessment is needed. —William T. Cefalu Editor in Chief, Diabetes Care
ALTERNATING PSYCHOSES IN TWINS: REPORT OF 4 CASES
Authors: E. GARDNER JACOBS, ALVIN M. MESNIKOFF
Journal: American Journal of Psychiatry (1961)

In this series, a psychotic reaction in one twin disturbed the twin relationship. When attempts of the other twin to compensate for this disturbance were not successful, an alternating psychotic reaction developed. Most often the psychoses were of paranoid or depressive type, thus emphasizing the frequent attributing of cause for the illness to the other twin and the acceptance of responsibility by that twin with subsequent guilt and depression. There was evidence of strong rivalry between the twins during illness as well as during relatively well periods; this rivalry led to a sharing of medical and family care. The second twin was able unconsciously to exact as much help from his environment as the first. The unusually strong identification observed in normal twins appeared to carry over into illness. Ego integrity of one twin may depend on the integrity of the ego of the other.
Frequency of Chromosomal Aberrations Involving <b> <i>MALT1</i> </b> in Mucosa-Associated Lymphoid Tissue Lymphoma in Patients with Sjögren’s Syndrome
Authors: Berthold Streubel, Daniela Huber, Stefan Wöhrer, Andreas Chott, Markus Raderer
Journal: Clinical Cancer Research (2004)

Mucosa-associated lymphoid tissue (MALT) lymphoma develops in the context of longstanding antigenic stimulation such as infection with Helicobacter pylori or autoimmune disease, including Sjögren's syndrome (SS). Recently, two chromosomal aberrations involving the MALT1 gene, i.e., t(11;18)(q21;q21) and t(14;18)(q32;q21) have been reported as genetic events specific for MALT lymphoma. In view of the association between SS and the development of MALT lymphoma, we have analyzed the frequency of t(11;18)(q21;q21) and t(14;18)(q32;q21) in patients with MALT lymphomas arising in the background of SS.A retrospective analysis of patients diagnosed with MALT lymphoma and SS was performed. The t(11;18)(q21;q21) was analyzed using reverse transcriptase-PCR, whereas t(14;18)(q32;q21) was assessed by two-color interphase fluorescence in situ hybridization.Twenty-six patients (20 female and 6 male) with MALT lymphoma and SS could be identified. The lymphoma was located in the parotid (n = 14), orbit (n = 2), and submandibular gland (n = 1), whereas 9 patients had gastric MALT lymphoma. Seven of 26 patients (27%) harbored t(11;18)(q21;q21). Interestingly, only 1 of 17 patients (6%) with extragastrointestinal lymphoma was positive, as opposed to 6 of 9 patients (67%) with gastric MALT lymphoma. Four of 26 patients were positive for t(14;18)(q32;q21): 3 of 17 extragastrointestinal (18%) and 1 of 9 gastric lymphomas (11%).The overall frequency of MALT1 rearrangement appears to be low in patients with extragastrointestinal MALT lymphoma associated with SS. By contrast, MALT1 rearrangement was demonstrated in 7 of 9 patients (78%) with gastric MALT lymphoma and SS. This finding may explain at least in part why gastric MALT lymphomas in patients with SS are refractory to H. pylori eradication therapy.
Atelectasis Causes Vascular Leak and Lethal Right Ventricular Failure in Uninjured Rat Lungs
Authors: Michelle Duggan, Conán L. McCaul, Patrick J. McNamara, Doreen Engelberts, Cameron Ackerley, Brian P. Kavanagh
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

During mechanical ventilation, lung recruitment attenuates injury caused by high VT, improves oxygenation, and may optimize pulmonary vascular resistance (PVR). We hypothesized that ventilation without recruitment would induce injury in otherwise healthy lungs. Anesthetized rats were ventilated with conventional mechanical ventilation (VT 8 ml/kg; respiratory frequency 40 per minute) and 21% inspired oxygen, with or without a recruitment strategy consisting of recruitment maneuvers plus positive end-expiratory pressure, in the presence or absence of a laparotomy. Additional experiments examined the impact of atelectasis on right ventricular function using echocardiography, as well as functional residual capacity and PVR. Lack of recruitment resulted in reduced overall survival (59% nonrecruited vs. 100% recruited, p < 0.05), increased microvascular leak, greater impairment of oxygenation and lung compliance, increased PVR, and elevated plasma lactate. Echocardiography demonstrated that right ventricular dysfunction occurred in the absence of recruitment. Finally, samples from nonrecruited lungs demonstrated ultrastructural evidence of microvascular endothelial disruption. Although such effects clearly do not occur with comparable magnitude in the clinical context, the current data suggest novel mechanisms (microvascular leak, right ventricular dysfunction) whereby derecruitment may contribute to development of lung injury and adverse systemic outcome.
Patients with Refractory Seizures
Authors: O Devinsky
Journal: New England Journal of Medicine (1999)

In the United States, epilepsy affects approximately 0.6 percent of the population (1.6 million persons) and has a lifetime prevalence of approximately 3 percent (and will thus affect 7.2 million persons).1 For the majority of patients, epileptic seizures are controlled with a single antiepileptic drug, which may be withdrawn when the patient has been without seizures for two years.2 Some patients, however, do not become completely free of seizures even though they comply scrupulously with the prescribed regimen. Aside from having deleterious effects on health, persistent epileptic seizures have psychosocial, behavioral, and cognitive consequences and often impose a financial burden. . . .