tbuckley/cabot-search huggingface dataset:
Decreased Regional Brain Metabolism After ECT
Authors: Mitchell S. Nobler, Maria A. Oquendo, Lawrence S. Kegeles, Kevin M. Malone, Carl Campbell, Harold A. Sackeim, J. John Mann
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The antidepressant action of ECT may be related to its anticonvulsant properties. Positron emission tomography (PET) studies of regional cerebral metabolic rate for glucose were used to test this hypothesis. METHOD: Ten patients with major depression were studied with PET before and approximately 5 days after a course of bilateral ECT. Statistical parametric mapping was used to identify regions of decreased cerebral glucose metabolism. RESULTS: Widespread regions of decreased regional cerebral glucose metabolism were identified after ECT, especially in the frontal and parietal cortex, anterior and posterior cingulate gyrus, and left temporal cortex. A region-of-interest analysis similarly indicated post-ECT reductions in regional cerebral glucose metabolism. CONCLUSIONS: ECT reduces neuronal activity in selected cortical regions, a potential anticonvulsant and antidepressant effect.
Autoimmune hepatitis associated with infliximab in a patient with psoriatic arthritis
Authors: V Germano, A Picchianti Diamanti, G Baccano, E Natale, A Onetti Muda, R Priori, G Valesini
Journal: Annals of the Rheumatic Diseases (2005)

We read with interest the debate about liver toxicity of infliximab in psoriatic arthritis (PsA).1,2 We describe the case of a 53 year old woman with a 4 year history of refractory PsA who developed transaminasitis during infliximab treatment.

Despite combination treatment (ciclosporin 300 mg/day, fluocortolone 10 mg/day, and methotrexate (MTX)15 mg/week intramuscularly), disease activity was still high, and intravenous infliximab at 3 mg/kg was administered initially at weeks 0, 2, 6, 14 and then every 6 weeks. Ciclosporin was withdrawn.

Within 3 weeks she improved, fluocortolone was gradually stopped while methotrexate (MTX) 20 mg/week intramuscularly, was continued. After the sixth infusion, she developed a mild transaminasitis and MTX, initially tapered, was stopped. After the eighth infusion transaminases continued to rise and in the absence of any other plausible cause, infliximab was withdrawn.

She was admitted to our department with persistently high values of aspartate aminotransferase and alanine aminotransferase and a flare of PsA. …
Identification and Epitope Enhancement of a PAX-FKHR Fusion Protein Breakpoint Epitope in Alveolar Rhabdomyosarcoma Cells Created by a Tumorigenic Chromosomal Translocation Inducing CTL Capable of Lysing Human Tumors
Authors: Leon T. van den Broeke, C. David Pendleton, Crystal Mackall, Lee J. Helman, Jay A. Berzofsky
Journal: Cancer Research (2006)

Abstract Fusion proteins created by chromosomal translocations in tumors can create neoantigenic determinants at the breakpoint, which are unique to the tumor cells but shared by the vast majority of tumors of that histologic type. If the fusion protein is responsible for the malignant transformation, its expression cannot be lost by the tumor to escape immune responses against this tumor antigen. Here, we identify such a fusion protein breakpoint epitope in the PAX-FKHR fusion protein created by the t(2;13) translocation present in 80% of cases of alveolar rhabdomyosarcoma, a highly aggressive pediatric soft-tissue sarcoma. We use autologous dendritic cells pulsed with the RS10 breakpoint fusion peptide to raise a human CTL line from a normal healthy HLA-B7+ blood donor specific for this peptide. These CTLs are CD8+ (CD4−CD56−) and restricted by HLA-B7. These human peptide-specific CTL lyse human HLA-B7+ rhabdomyosarcoma tumor cells. Therefore, the fusion protein is endogenously processed to produce this natural epitope presented by HLA-B7 and thus this peptide is a bone fide human tumor antigen. We also define a substitution that increases the affinity for HLA-B7 without loss of antigenicity. This epitope-enhanced peptide may serve as a candidate cancer vaccine for HLA-B7+ patients with alveolar rhabdomyosarcoma. (Cancer Res 2006; 66(3): 1818-23)
An Experimental Study on the Origin of T-Waves Based on Determinations of Effective Refractory Period from Epicardial and Endocardial Aspects of the Ventricle
Authors: ERNEST W. REYNOLDS, CONDON R. VANDER ARK
Journal: Circulation Research (1959)

The effective refractory period was determined at the surface and in the deeper layers of the dog heart and was correlated with the surface T-waves. A small delay in recovery of cardiac excitability appeared at the surface when T-waves were negative and in the deeper layers when T-waves were positive. Acute injury produced by ligation of the coronary artery caused a marked acceleration of recovery in the deeper layers, sometimes extending to the surface.
Noninvasive, In Utero Imaging of Mouse Embryonic Heart Development With 40-MHz Echocardiography
Authors: Shardha Srinivasan, H. Scott Baldwin, Orlando Aristizabal, Lia Kwee, Mark Labow, Michael Artman, Daniel H. Turnbull
Journal: Circulation (1998)

Background —The increasing number of transgenic and targeted mutant mice with embryonic cardiac defects has resulted in the need for noninvasive techniques to examine cardiac structure and function in early mouse embryos. We report the first use of a novel 40-MHz ultrasound imaging system in the study of mouse cardiac development in utero. Methods and Results —Transabdominal scans of mouse embryos staged between 8.5 and 13.5 days of gestation (E8.5 to E13.5) were obtained in anesthetized mice. Atrial and ventricular contractions could be discerned from E9.5, and changes in cardiac morphology were observed from E9.5 to E13.5. Hyperechoic streaming patterns delineated flow through the umbilical, vitelline, and other major blood vessels. Diastolic and systolic ventricular areas were determined by planimetry of the epicardial borders, and fractional area change was measured as an index of contractile function. Significant increases in ventricular size were documented at each stage between E10.5 and E13.5, and the ability to perform serial imaging studies over 3 days of embryonic development is described. Finally, the detection of vascular cell adhesion molecule 1 (VCAM-1) homozygous null mutant embryos demonstrates the first example of noninvasive, in utero analysis of cardiac structure and function in a targeted mouse mutant. Conclusions —We used 40-MHz echocardiography to identify key elements of the early mouse embryonic cardiovascular system and for noninvasive dimensional analysis of developing cardiac ventricles. The ability to perform serial measurements and to detect mutant embryos with cardiac defects highlights the usefulness of the technique for investigating normal and abnormal cardiovascular development.
The Von Hippel-Lindau Tumor Suppressor Gene and Kidney Cancer
Authors: William G. Kaelin
Journal: Clinical Cancer Research (2004)

Abstract The von Hippel-Lindau tumor suppressor gene (VHL), which resides on chromosome 3p25, is mutated or silenced in &amp;gt;50% of sporadic clear cell renal cell carcinomas. Germ-line VHL mutations give rise to VHL disease, which is characterized by an increased risk of blood vessel tumors (hemangioblastomas) and renal cell carcinomas. In this setting, VHL inactivation gives rise to premalignant renal cysts. Additional genetic alterations are presumably required for conversion of these cysts to renal cell carcinomas. Restoration of VHL function in VHL−/− renal cell carcinomas is sufficient to inhibit tumorigenesis in vivo. On the basis of these and other data, VHL appears to be a critical gatekeeper with respect to the development of renal cell carcinoma. The VHL gene product, pVHL, is the substrate recognition module of an E3 ubiquitin ligase that targets the hypoxia-inducible factor (HIF) for destruction in the presence of oxygen. Hypoxic cells, or cells lacking pVHL, accumulate high levels of HIF, which activates the transcription of a variety of genes, including vascular endothelial growth factor, platelet-derived growth factor B, and transforming growth factor α. We have demonstrated that inhibition of HIF is necessary and sufficient for tumor suppression by pVHL in renal cell carcinoma nude mouse xenograft assays. This provides a rationale for treating VHL−/− renal cell carcinoma with inhibitors of HIF or its downstream targets. Genotype-phenotype correlations in VHL disease suggest, however, that pVHL has targets in addition to HIF. Elucidating these targets should provide a more complete picture of how pVHL suppresses tumor growth.
Lung diffusing capacity and exercise in subjects with previous high altitude pulmonary oedema
Authors: JM Steinacker, P Tobias, E Menold, S Reissnecker, E Hohenhaus, Y Liu, M Lehmann, P Bartsch, ER Swenson
Journal: European Respiratory Journal (1998)

Subjects with a history of high-altitude pulmonary oedema (HAPE) have increased pulmonary artery pressure and more ventilation-perfusion (V'A/Q') inhomogeneity with hypoxia and exercise. We used noninvasive methods to determine whether there are differences in the pulmonary diffusing capacity for carbon monoxide (DL,CO) and cardiac output (Q') during exercise, indicative of a more restricted pulmonary vascular bed in subjects with a history of HAPE. Eight subjects with radiographically documented HAPE and five controls with good altitude tolerance had standard pulmonary function testing and were studied during exercise at 30 and 50% of normoxic maximal oxygen consumption (V'O2) at an inspiratory oxygen fraction of 0.14 and 0.21. DL,CO and Q' were measured by CO and acetylene rebreathing techniques. HAPE-resistant subjects had 35% greater functional residual capacity than HAPE-susceptible subjects. Vital capacity and total lung capacity were also 7-10% greater. There were no differences in airflow rates or resting diffusing capacity. However, DL,CO in HAPE-susceptible subjects was lower in hypoxia and with exercise, and showed less increase (32 versus 49%) with the combined stimulus of hypoxic exercise. HAPE-susceptible subjects had smaller increases in stroke volume, Q', and ventilation during exercise. The findings are consistent with lower pulmonary vasoconstriction, greater vascular capacitance and greater ventilatory responsiveness during exercise in subjects who are resistant to high-altitude pulmonary oedema. Their larger lung volumes suggest a constitutional difference in pulmonary parenchyma or vasculature, which may be a determinant of high-altitude pulmonary oedema resistance.
Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases
Authors: Ana V. Miletic, Amy N. Anzelon-Mills, David M. Mills, Sidne A. Omori, Irene M. Pedersen, Dong-Mi Shin, Jeffrey V. Ravetch, Silvia Bolland, Herbert C. Morse, Robert C. Rickert
Journal: The Journal of Experimental Medicine (2010)

The inositol phosphatases phosphatase and tensin homologue (PTEN) and Src homology 2 domain–containing inositol phosphatase (SHIP) negatively regulate phosphatidylinositol-3-kinase (PI3K)–mediated growth, survival, and proliferation of hematopoietic cells. Although deletion of PTEN in mouse T cells results in lethal T cell lymphomas, we find that animals lacking PTEN or SHIP in B cells show no evidence of malignancy. However, concomitant deletion of PTEN and SHIP (bPTEN/SHIP−/−) results in spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma or, less frequently, follicular or centroblastic lymphoma. bPTEN/SHIP−/− B cells exhibit enhanced survival and express more MCL1 and less Bim. These cells also express low amounts of p27kip1 and high amounts of cyclin D3 and thus appear poised to undergo proliferative expansion. Unlike normal B cells, bPTEN/SHIP−/− B cells proliferate to the prosurvival factor B cell activating factor (BAFF). Interestingly, although BAFF availability may promote lymphoma progression, we demonstrate that BAFF is not required for the expansion of transferred bPTEN/SHIP−/− B cells. This study reveals that PTEN and SHIP act cooperatively to suppress B cell lymphoma and provides the first direct evidence that SHIP is a tumor suppressor. As such, assessment of both PTEN and SHIP function are relevant to understanding the etiology of human B cell malignancies that exhibit augmented activation of the PI3K pathway.
Paralimbic and Medial Prefrontal Cortical Involvement in Neuroendocrine Responses to Traumatic Stimuli
Authors: Israel Liberzon, Anthony P. King, Jennifer C. Britton, K. Luan Phan, James L. Abelson, Stephan F. Taylor
Journal: American Journal of Psychiatry (2007)

Objective: Hypothalamic-pituitary-adrenal axis activity and cortisol release are consequences of central stress system activation, but they may also influence cognitive and emotional processes within the brain. Despite the importance of central stress response systems, little is known about the specific brain circuits through which psychosocial stimuli activate the hypothalamic-pituitary-adrenal axis and through which cortisol feedback modulates central processing. The authors used [ 15 O]H 2 O positron emission tomography (PET) on subjects with posttraumatic stress disorder (PTSD) to study these circuits. Method: Participants were combat-PTSD patients, combat-exposed healthy comparison subjects, and noncombat-exposed healthy comparison subjects. Participants were scanned using [ 15 O]H 2 O PET while they experienced a series of emotional-induction conditions, which included aversive pictures and autobiographic narratives. Blood samples were obtained 2 minutes before and 5 minutes after each activation scan in order to measure the subjects’ plasma adrenocorticotropic hormone and cortisol levels. Results: In voxel-wise analyses, the authors found that adrenocorticotropic hormone responses were covaried with regional cerebral blood flow (rCBF) in the dorsal medial prefrontal cortex, rostral anterior cingulate cortex, and right insula, with some differences between PTSD patients and comparison subjects. Prestimulus cortisol levels covaried with rCBF responses in the rostral anterior cingulate cortex. In combat-PTSD patients only, prestimulus cortisol levels covaried with rCBF in the subgenual anterior cingulate cortex. Conclusions: These findings provide evidence of cortical involvement in hypothalamic-pituitary-adrenal responses to psychological stimuli, specifically implicating the insula, dorsal medial prefrontal cortex, and rostral anterior cingulate cortex. These findings also show, for the first time, that cortisol may modulate activity in specific brain areas such as the rostral and subgenual anterior cingulate cortices. Differential patterns of covariation between combat veterans with and without PTSD potentially implicate the dorsal medial prefrontal cortex and subgenual anterior cingulate cortex as areas of dysregulation in PTSD.
The Growth Hormone/Insulin-Like Growth Factor-I Axis in Exercise and Sport
Authors: James Gibney, Marie-Louise Healy, Peter H. Sönksen
Journal: Endocrine Reviews (2007)

The syndrome of adult GH deficiency and the effects of GH replacement therapy provide a useful model with which to study the effects of the GH/IGF-I axis on exercise physiology. Measures of exercise performance including maximal oxygen uptake and ventilatory threshold are impaired in adult GH deficiency and improved by GH replacement, probably through some combination of increased oxygen delivery to exercising muscle, increased fatty acid availability with glycogen sparing, increased muscle strength, improved body composition, and improved thermoregulation. In normal subjects, in addition to the long-term effects of GH/IGF-I status, there is evidence that the acute GH response to exercise is important in regulating substrate metabolism after exercise. Administration of supraphysiological doses of GH to athletes increases fatty acid availability and reduces oxidative protein loss, particularly during exercise, and increases lean body mass. Despite a lack of evidence that these metabolic effects translate to improved performance, GH abuse by athletes is widespread. Tests to detect GH abuse have been developed based on measurement in serum of 1) indirect markers of GH action, and 2) the relative proportions of the two major naturally occurring isoforms (20 and 22kDa) of GH. There is evidence that exercise performance and strength are improved by administration of GH and testosterone in combination to elderly subjects. The potential benefits of GH in these situations must be weighed against potential adverse effects.
EXPERIMENTAL SYPHILIS IN THE RABBIT
Authors: Wade H. Brown, Louise Pearce
Journal: The Journal of Experimental Medicine (1920)

In a series of more than 200 rabbits in which generalized lesions were observed following local inoculation with Treponema pallidum, there were a number of animals in which characteristic lesions were noted upon mucous membranes or along mucocutaneous borders. These lesions were distributed with about equal frequency between the nose or nasolacrimal system and the eyelids on the one hand, and the genital and anal regions on the other. The lips and buccal mucosa appeared to be less subject to localized infections unless the papillomatous growths noted on the lips and under side of the tongue should prove to be in some way connected with such an infection. In many instances, the local reaction was initiated by an acute inflammatory process, and in the case of nasal and genital infections, a definite exudate was formed. The succeeding stages of the reaction consisted in an infiltration of the parts involved, together with a variable degree of proliferation of fixed tissue cells, leading eventually to necrosis and ulceration. The resulting lesions differed according to their location and the character of the reaction in the individual case. Localized infections of the nose occurred in several forms, first, as a rather diffuse affection of the nasal mucosa characterized by the presence of a mucopurulent exudate, second, as a more or less circumscribed process of infiltration with an especial predilection for the region of the anterior nares, and third, as a granulomatous process involving the alae in particular. Involvement of the nasal mucosa was very commonly associated with lacrimal overflow and with some degree of conjunctivitis. The lesions of the eyelids were usually small, elevated papules or lesions of an ulcerative character some of which were surrounded by a zone of infiltration. In exceptional instances, large granulomatous lesions occurred along the margins of the lower lids. Infection of the penis and sheath gave rise to conditions analogous to those of the nose. In one group of animals, there was a diffuse affection characterized by redness and swelling of the parts with a mucopurulent exudate, in another there were circumscribed or diffuse infiltrations, while in a third the lesions formed were indurated granulomatous masses. Secondary necrosis with erosion or ulceration was a common feature of all these conditions. Localized infections in the region of the anus differed from those in other localities chiefly in the absence of an exudative group of affections and in the frequency with which lesions of a papillomatous type occurred. Lesions of mucous membranes and mucocutaneous borders developed at periods of time varying from a few weeks to several months after inoculation. Most of them were rather enduring and in several instances persisted in an active condition for considerably more than a year.
Weekend treatment with 20 and 40 mg omeprazole: effect on intragastric pH, fasting and postprandial serum gastrin, and serum pepsinogens.
Authors: L C Baak, J B Jansen, I Biemond, C B Lamers
Journal: Gut (1991)

Weekend treatment with 20 mg omeprazole reduces ulcer relapse rates but the results may improve with a higher dose regimen. We have evaluated three day weekend treatment with 20 and 40 mg doses of omeprazole in eight healthy subjects in a double blind crossover study. Twenty four hour ambulatory intragastric pH and basal and meal stimulated serum gastrin and serum pepsinogens A and C values were studied. The investigations began on the Friday before the third weekend course of omeprazole and were repeated on alternate days, except Sundays, for two weeks. When compared with values before the study, median 24 hour intragastric pH and basal and meal stimulated gastrin concentrations were significantly (p less than 0.01-0.05), but transiently, raised with both doses of omeprazole. Basal pepsinogen A and C values were significantly (p less than 0.01) increased on all study days, but did not return to their pre-study values before the next weekend dose, except for pepsinogen C in subjects treated with 20 mg omeprazole. A dose dependent effect was found for all parameters studied (p less than 0.05). In conclusion, weekend treatment with 20 and 40 mg omeprazole produces pronounced and dose dependent increases in intragastric pH, basal and meal stimulated serum gastrin, and basal serum pepsinogen A and C without inducing prolonged hypoacidity or hypergastrinaemia. Weekend treatment with 40 mg omeprazole merits further study in the prevention of peptic ulcer relapse.
IMMUNOCHEMICAL STUDIES OF ANTITOXIN PRODUCED IN NORMAL AND ALLERGIC INDIVIDUALS HYPERIMMUNIZED WITH DIPHTHERIA TOXOID
Authors: William J. Kuhns
Journal: The Journal of Experimental Medicine (1954)

Electrophoresis on a starch-supporting medium was used to fractionate sera containing human diphtheria antitoxin of the following varieties (a) precipitating antitoxin, (b) non-precipitating skin-sensitizing antitoxin, and (c) mixtures containing precipitating and skin-sensitizing antitoxins. Aliquots of the protein fractions thus separated were tested for activity using the rabbit toxin neutralization test, precipitin techniques, and passive transfer tests in human skin. Non-precipitating, skin-sensitizing diphtheria antitoxin migrated largely as a fast moving gamma (γ1) globulin. Passive transfer studies of isolated antitoxic fractions showed that they were as potent as whole serum in the ability to cause immediate wheal reactions. These fractions were not precipitable using appropriate quantities of purified toxoid. Precipitating diphtheria antitoxin migrated largely as a slow moving gamma (γ2) globulin. Isolated antitoxic fractions of appropriate strength obtained from representative sera were precipitable by toxin and were unable to cause immediate wheal reactions upon toxoid challenge in human recipients. Mixtures of skin-sensitizing and precipitating antitoxins were separable by the technique of starch electrophoresis. The individual components removed from mixtures by this method retained the properties by which they could be characterized in whole serum.
Intermediate filaments: primary determinants of cell architecture and plasticity
Authors: Harald Herrmann, Sergei V. Strelkov, Peter Burkhard, Ueli Aebi
Journal: Journal of Clinical Investigation (2009)

Intermediate filaments (IFs) are major constituents of the cytoskeleton and nuclear boundary in animal cells. They are of prime importance for the functional organization of structural elements. Depending on the cell type, morphologically similar but biochemically distinct proteins form highly viscoelastic filament networks with multiple nanomechanical functions. Besides their primary role in cell plasticity and their established function as cellular stress absorbers, recently discovered gene defects have elucidated that structural alterations of IFs can affect their involvement both in signaling and in controlling gene regulatory networks. Here, we highlight the basic structural and functional properties of IFs and derive a concept of how mutations may affect cellular architecture and thereby tissue construction and physiology.