tbuckley/cabot-search huggingface dataset:
Potential Liability for Transfusion-Associated AIDS
Authors: Patti J. Miller
Journal: JAMA (1985)

THE CENTERS for Disease Control (CDC) defines a case of the acquired immunodeficiency syndrome (AIDS) as "a disease, at least moderately predictive of a defect in cell-mediated immunity, occurring in a person with no known cause for diminished resistance to that disease."<sup>1</sup>As of Jan 8, 1985, there were 7,788 reported cases of AIDS in the United States, with 3,687 deaths (John Ward, MD, oral communication, CDC, AIDS Activity, Jan 8, 1985). Eighty percent of cases reported to date have been concentrated in six metropolitan areas.<sup>2</sup>In addition, reports of AIDS have emanated from 47 states, Puerto Rico, Washington, DC, and 36 countries.<sup>3,4</sup> First identified in homosexual and bisexual men with multiple sexual partners,<sup>5-11</sup>AIDS has subsequently afflicted intravenous (IV) drug users,<sup>1</sup>female sexual partners of IV drug users,<sup>12,13</sup>hemophiliacs,<sup>2,3,14-32</sup>Haitians,<sup>33</sup>and infants born to mothers from high-risk groups—raising concerns about in
Weaving Klotho into bile acid metabolism
Authors: A. Moschetta
Journal: Journal of Clinical Investigation (2005)

Bile acids are natural detergents that assist in the absorption and digestion of fats in the intestine. In liver, the synthesis of bile acids from cholesterol is regulated by multiple signaling cascades that repress transcription of the gene encoding cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in the classic bile acid synthesis pathway. In this issue of the JCI, Ito and coworkers demonstrate that mice lacking βKlotho, a membrane protein with 2 putative glycosidase domains, have increased Cyp7a1 mRNA levels and bile acid concentrations. βKlotho-KO mice also have small gallbladders and are resistant to cholesterol gallstone formation. These findings highlight the central role of βKlotho in bile acid homeostasis and raise the possibility that this protein could be a pharmacologic target for the treatment of gallstones.
Long-Term Prognosis and the Response of Schizophrenic Children to Drug Therapy : A Controlled Study of Trifluoperazine
Authors: BARBARA FISH, THEODORE SHAPIRO, MAGDA CAMPBELL
Journal: American Journal of Psychiatry (1966)

Previous studies have demonstrated that severity of language impairment is a critical determinant of long-term outcome for schizophrenic children in the age group of two to six years. Language impairment was therefore used as the major measure of severity in this study, designed to test whether subgroups of schizophrenic children, divided according to prognostic criteria, would respond differently to drugs as well as to placebo. Responses to both nonpharmacologic aspects of treatment and to the drug itself were found to be related to the initial severity of language impairment. Thus the major developmental defect determining long-term outcome for schizophrenic children in this age group also predicted the immediate responsiveness to treatment.
The effect of bradykinin on proximal tubular sodium reabsorption in the dog: evidence for functional nephron heterogeneity
Authors: Jay H. Stein, Rolando C. Congbalay, Dennis L. Karsh, Richard W. Osgood, Thomas F. Ferris
Journal: Journal of Clinical Investigation (1972)

In a previous study we have found that acetylcholine, a renal vasodilator, inhibits fractional and absolute reabsorption of sodium in the proximal tubule of the dog. To delineate whether this effect on proximal tubular sodium reabsorption was related to alterations in renal hemodynamics or to a direct tubular action of the drug, free-flow micropuncture studies were performed in the dog in which the tubular fluid to plasma inulin ratio and nephron filtration rate were determined before and during the administration of a structurally different renal vasodilator, bradykinin. This agent increased sodium excretion from 12 to 96 muEq/min and decreased total kidney filtration fraction from 0.35 to 0.25. However, sodium reabsorption in the proximal tubule of the superficial nephrons was unchanged during bradykinin administration. Since it has been shown that a decrease in filtration fraction and presumably peritubular capillary protein concentration will decrease proximal tubular sodium reabsorption, studies were performed to determine whether the fall in total kidney filtration fraction seen with both vasodilators is paralleled by a similar change in the circulation of superficial nephrons. The results of these studies indicate that neither agent altered superficial nephron capillary protein concentration, hematocrit, or filtration fraction. In contrast, a decrease in capillary protein concentration, hematocrit, and filtration fraction was consistently demonstrated during the intrarenal infusion of 7.5-15 ml/min of Ringer's solution while an increase in these parameters occurred during the i.v. administration of norepinephrine, 60 mug/min. In the Ringer's infusion studies, both fractional and absolute sodium reabsorption in the proximal tubule were decreased concomitant with the fall in capillary protein concentration and hematocrit. THIS DATA SUGGESTS THAT: (a) the hemodynamic effect of renal vasodilatation is not the same in the circulation of all nephrons; (b) the inhibitory effect of acetylcholine on proximal tubular sodium reabsorption is due to a direct tubular action; (c) a decrease in capillary protein concentration and/or hematocrit does decrease proximal tubular sodium reabsorption; (d) although proximal reabsorption of sodium is unchanged in the superficial nephrons during bradykinin administration, a decrease in reabsorption may be present in deeper nephrons in which filtration fraction is decreased.
CROSS-STIMULATION OF MONOCLONAL ANTIBODIES IN ANAMNESTIC RESPONSES
Authors: Matthias Cramer, Dietmar G. Braun
Journal: The Journal of Experimental Medicine (1973)

Immunization of BALB/c mice with Group A streptococcal vaccines leads to the induction of high levels of monoclonal antibody populations. Subsequent immunization of these mice with Group A-variant streptococcal vaccines induces a significant level of monoclonal antibody of A-variant antigen specificity revealed by labeled group A-variant polysaccharide. During these course Av and Av' immunizations, the monoclonal Group A-specific antibodies were also restimulated to levels usually higher than the variant-specific antibodies. With two exceptions, these homogeneous antibody populations were not cross-reactive in vitro with the related antigen. Such cross-stimulation of monoclonal antibodies was interpreted as a function of particular membrane properties of the Ig receptor-bearing memory cells which, for restimulation, would only require the structurally closely related antigen which serves as a backbone to the original antigen, and not necessarily the exact fit of the homologous immunodominant group.
A fat chance for hepatocyte transplantation?
Authors: J. A Thomas, S. J Forbes
Journal: Gut (2009)

A virtually unlimited supply of hepatocytes for transplantation, bio-artificial livers and drug testing would be highly desirable. If stem cell biology is to fulfil its potential and deliver this dream, then certain requirements must be met. Stem cell-derived “hepatocytes” should be readily available from an ethically acceptable source, tolerate cryopreservation allowing “off the shelf” use, demonstrate adequate metabolic and synthetic activity and, if transplanted should functionally integrate with non-parenchymal cells in the liver. Most importantly, cell transplantation must be safe. Derivation from an autologous source, thereby overcoming immunological barriers would further increase the applicability of this potential therapy.

There is a growing number of potential starting cell populations from which one may potentially derive hepatocyte-like cells (for a comprehensive review, see Oertel and Shafritz1). Broadly speaking the starting cell populations may be developmentally “primitive” such as the embryonic stem cells or be more differentiated such as foetal hepatocytes. Generally, the more primitive the starting cell population, then the greater is the potential to expand in culture the numbers of cells available for use. The challenge with such cells is to accurately control their differentiation into mature cells types such as hepatocytes and control their subsequent proliferation so that unwanted tumours do not form. Embryonic stem cells have an almost unlimited capacity for proliferation and have the ability to form all cell types – so-called pluripotentiality. However, the current use of embryonic stem cell derived tissues for transplantation is hampered by the potential of these cells to form tumours. Induced pluripotent stem cells have been an extremely exciting innovation from the Yamanaka laboratory.2 By over-expressing certain transcription factors …
Membrane cofactor protein of complement is present on human fibroblast, epithelial, and endothelial cells.
Authors: T McNearney, L Ballard, T Seya, J P Atkinson
Journal: Journal of Clinical Investigation (1989)

Membrane cofactor protein (MCP) of the complement system is a iC3/C3b binding molecule with cofactor activity that has been identified on all human peripheral blood cells except erythrocytes. Human mononuclear and platelet MCP is dimeric with molecular weights of 68,000 and 63,000 and is expressed in three phenotypic patterns. To further determine its tissue distribution, surface-labeled human fibroblast, epithelial, and endothelial cells and cell lines were assessed for the presence of MCP by iC3 affinity chromatography and by immunoprecipitation with a monospecific anti-MCP rabbit polyclonal antibody. All sources of adult and fetal fibroblast and epithelial cells and cell lines examined and umbilical vein endothelial cells expressed MCP. The molecular weight and phenotypic patterns of MCP were similar to those of peripheral blood cells. MCP was synthesized by fibroblast and epithelial cell lines. Solubilized extracts of these cell lines expressed factor I-dependent cofactor activity for the first cleavage of iC3/C3b which was abrogated by removal of MCP. Expression of MCP was modulated by SV40 transformation of two fetal fibroblast lines. There was a 5- to 10-fold increase in expression of MCP and a preferential expression of the lower species such that the phenotypic designation was changed. The wide tissue distribution and activity profile of MCP suggest that it is likely to play an important role in the regulation of the complement cascade.
Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis
Authors: L Xu
Journal: Gut (2004)

<b>Background:</b> Hepatic stellate cells (HSCs) are a major fibrogenic cell type that contributes to collagen accumulation during chronic liver disease. With increasing interest in developing antifibrotic therapies, there is a need for cell lines that preserve the in vivo phenotype of human HSCs to elucidate pathways of human hepatic fibrosis. We established and characterised two human HSC cell lines termed LX-1 and LX-2, and compared their features with those of primary human stellate cells. <b>Methods and results:</b> LX-1 and LX-2 were generated by either SV40 T antigen immortalisation (LX-1) or spontaneous immortalisation in low serum conditions (LX-2). Both lines express α smooth muscle actin, vimentin, and glial fibrillary acid protein, as visualised by immunocytochemistry. Similar to primary HSCs, both lines express key receptors regulating hepatic fibrosis, including platelet derived growth factor receptor β (βPDGF-R), obese receptor long form (Ob-R<sub>L</sub>), and discoidin domain receptor 2 (DDR2), and also proteins involved in matrix remodelling; matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinase (TIMP)-2, and MT1-MMP, as determined by western analyses. LX-2 have reduced expression of TIMP-1. LX-2, but not LX-1, proliferate in response to PDGF. Both lines express mRNAs for α1(I) procollagen and HSP47. Transforming growth factor β1 stimulation increased their α1(I) procollagen mRNA expression, as determined by quantitative reverse transcription-polymerase chain reaction. LX-2, but not LX-1, cells are highly transfectable. Both lines had a retinoid phenotype typical of stellate cells. Microarray analyses showed strong similarity in gene expression between primary HSCs and either LX-1 (98.4%) or LX-2 (98.7%), with expression of multiple neuronal genes. <b>Conclusions:</b> LX-1 and LX-2 human HSC lines provide valuable new tools in the study of liver disease. Both lines retain key features of HSCs. Two unique advantages of LX-2 are their viability in serum free media and high transfectability.
DIFFERENCES IN THE SENSITIZING CAPACITY OF NEOMYCIN IN CREAMS AND IN OINTMENTS
Authors: NIELS HJORTH, KRISTIAN THOMSEN
Journal: British Journal of Dermatology (1968)

SUMMARY. In 1963–4, 10% of patients with dermatitis gave positive patch test reactions to neomycin. Of 115 patients 89 (79%) had used neomycin in ointment bases, while only 14 (12%) had used creams or lotions, and 7 (6%) powders.



In order to establish the extent to which different preparations were prescribed a market analysis was performed. The sale in 1964 of neomycin for topical use was found to be 137,000 units (tubes or other containers). A small number of proprietary preparations dominated the market.



In proportion to their sale creams, lotions and powders containing neomycin were rarely connected with sensitization. This investigation suggests that neomycin ointments are the major cause of sensitization to this antibiotic.



The possible significance of these findings and the influence of the vehicle on sensitizing capacity are discussed.



It is recommended that neomycin should not be prescribed in ointments. The risk of inducing sensitization with neomycin in creams, lotions or powders appears to be significantly less.
A deletion at<i>ADAMTS9-MAGI1</i>locus is associated with psoriatic arthritis risk
Authors: Antonio Julià, José Antonio Pinto, Jordi Gratacós, Rubén Queiró, Carlos Ferrándiz, Eduardo Fonseca, Carlos Montilla, Juan Carlos Torre-Alonso, Lluís Puig, José Javier Pérez Venegas, Antonio Fernández Nebro, Emilia Fernández, Santiago Muñoz-Fernández, Esteban Daudén, Carlos González, Daniel Roig, José Luís Sánchez Carazo, Pedro Zarco, Alba Erra, José Luís López Estebaranz, Jesús Rodríguez, David Moreno Ramírez, Pablo de la Cueva, Francisco Vanaclocha, Enrique Herrera, Santos Castañeda, Esteban Rubio, Georgina Salvador, César Díaz-Torné, Ricardo Blanco, Alfredo Willisch Domínguez, José Antonio Mosquera, Paloma Vela, Jesús Tornero, Simón Sánchez-Fernández, Héctor Corominas, Julio Ramírez, María López-Lasanta, Raül Tortosa, Nuria Palau, Arnald Alonso, Andrés C García-Montero, Josep Lluís Gelpí, Laia Codó, Kenneth Day, Devin Absher, Richard M Myers, Juan D Cañete, Sara Marsal
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objective</h3> Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. <h3>Methods</h3> A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ<sup>2</sup> test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). <h3>Results</h3> A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between <i>ADAMTS9</i> and <i>MAGI1</i> genes on chromosome <i>3p14.1</i> (p=0.00014). Using the independent patient and control cohort, we validated the association between <i>ADAMTS9-MAGI1</i> deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p&gt;0.3). <h3>Conclusions</h3> The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk.
Emotional status does not alter exercise tolerance in patients with chronic obstructive pulmonary disease
Authors: J Borak, E Chodosowska, A Matuszewski, J Zielinski
Journal: European Respiratory Journal (1998)

Exercise tolerance in chronic obstructive pulmonary disease (COPD) patients has been shown to be related to airway limitation and dyspnoea, but little is known about the effects of an emotional status on physical performance. We examined 49 COPD patients with a wide spectrum of airway limitation severity and hypoxaemia. Exercise tolerance was evaluated using the Six-minute Walking Distance Test (6MWD), dyspnoea at rest and on exercise was measured using the visual analogue scale, and the emotional status was evaluated using the battery of psychological tests. The average 6MWD (mean+/-SD) was 355+/-112 m. In the majority of patients a fall in arterial blood oxygen saturation (Sa,O2) on exercise of >3% was found. The mean dyspnoea score of 21+/-19 at rest increased to 66+/-19 on exercise. All subjects demonstrated an increased level of anxiety. The majority also demonstrated elevated emotional tension, and half of the study group showed signs of depression. Step-wise multiple regression analysis with results of 6MWD as dependent and other studied variables as independent variables showed that exercise tolerance depended mainly on airway limitation. The forced expiratory volume in one second (FEV1) explained 24% of the variance. The forced vital capacity added a further 10%, and arterial blood carbon dioxide tension contributed 7%. The dyspnoea level on exercise added only 0.9%. All four variables explained 42% of the variance. There was no correlation between 6MWD and any of the variables characterizing the emotional status. We conclude that the emotional status of chronic obstructive pulmonary disease patients is characterized by an increased level of psychological tension, anxiety and depression, but these do not affect exercise tolerance as assessed by the six-minute walking distance test.
Cortexolone 17α-propionate 1% cream, a new potent antiandrogen for topical treatment of acne vulgaris. A pilot randomized, double-blind comparative study vs. placebo and tretinoin 0·05% cream
Authors: V. Trifu, G.-S. Tiplica, E. Naumescu, L. Zalupca, L. Moro, G. Celasco
Journal: British Journal of Dermatology (2011)

Acne vulgaris is a disorder of the pilosebaceous unit in which the androgens contribute to its onset and persistence. The use of antiandrogens is therefore potentially effective; however, antiandrogens for topical use are not available on the market. Cortexolone 17α-propionate (CB-03-01; Cosmo S.p.A, Lainate, Italy) is a new potent topical antiandrogen potentially useful in acne vulgaris.To evaluate the safety and the topical efficacy of CB-03-01 1% cream in acne vulgaris as compared with placebo and with tretinoin 0·05% cream (Retin-A® ; Janssen-Cilag).Seventy-seven men with facial acne scored 2-3 according to Investigator's Global Assessment (IGA) were randomized to receive placebo cream (n = 15), or CB-03-01 1% cream (n = 30), or tretinoin 0·05% cream (n = 32) once a day at bedtime for 8 weeks. Clinical efficacy was evaluated every 2 weeks including total lesion count (TLC), inflammatory lesion count (ILC), acne severity index (ASI) and IGA. Safety assessment included local irritancy score, laboratory tests, physical examination, vital signs and recording of adverse events.CB-03-01 1% cream was very well tolerated, and was significantly better than placebo regarding TLC (P = 0·0017), ILC (P = 0·0134) and ASI (P = 0·0090), and also clinically more effective than comparator. The product also induced a faster attainment of 50% improvement in all the above parameters.This pilot study supports the rationale for the use of topical antiandrogens in the treatment of acne vulgaris. CB-03-01 1% cream seems to fit with the profile of an ideal antiandrogen for topical use.
ALLERGIC PURPURA IN A PATIENT TREATED WITH CABPHENAZINE
Authors: HANS J. CORNEILLE
Journal: American Journal of Psychiatry (1965)

We have presented a rare case of allergic purpura, accompanied by a life-endangering mental picture of catatonia in connection with carphenazine treatment in a chronic schizophrenic female, historically stigmatized by an allergic response to the combination of chlorpromazine and imipramine.
Transtracheal oxygen therapy: an effective and safe alternative to nasal oxygen administration
Authors: MJ Kampelmacher, M Deenstra, RG van Kesteren, CF Melissant, JM Douze, JW Lammers
Journal: European Respiratory Journal (1997)

Transtracheal oxygen therapy (TTOT) improves the efficiency of oxygen delivery and overcomes the discomfort associated with nasal oxygen delivery in patients on long-term oxygen therapy (LTOT). In addition, TTOT improves compliance and quality of life, and may reduce morbidity. Experience with TTOT in Europe is, however, scarce and the safety of TTOT has not yet been completely determined. These were reasons for testing the acceptance, efficacy and safety of TTOT. Patients were selected on the basis of the accepted indications and contraindications for TTOT. In 75 patients (48 males and 27 females) the mean follow-up time was 16 (range 0.5-51.5) months. Compared to nasal cannulae, TTOT caused a reduction in the oxygen flow rate of 47 (33-60)% at rest and a significant increase in the number of hours that oxygen was used. All patients on TTOT used oxygen for at least 20 h x day(-1). Most patients saw the procedure as a minor intervention. It was usually performed on an out-patient basis. In 34 patients, 51 mainly minor complications were seen, and most of these occurred in the first 10 patients. After precautions had been taken, complications occurred less frequently. No patient needed to be hospitalized because of a complication. TTOT had to be stopped in two patients; nevertheless, all patients preferred TTOT to the nasal cannulae. We conclude that transtracheal oxygen therapy is an effective and safe alternative to nasal oxygen administration, provided that it is restricted to a well-defined group of patients and applied by a motivated and experienced group of physicians.
BMK1 Kinase Suppresses Epithelial–Mesenchymal Transition through the Akt/GSK3β Signaling Pathway
Authors: Runqiang Chen, Qingkai Yang, Jiing-Dwan Lee
Journal: Cancer Research (2012)

Abstract Epithelial–mesenchymal transition (EMT) plays a crucial role in the development of cancer metastasis. The mitogen-activated protein (MAP) kinases extracellular signal–regulated kinase, c-jun-NH2-kinase, and p38 have been implicated in promoting EMT, but a role for the MAP kinase BMK1 has not been studied. Here, we report that BMK1 signaling suppresses EMT. BMK1 elevation augmented E-cadherin–mediated cell–cell adhesion, downregulated mesenchymal markers, and decreased cell motility. Conversely, BMK1 silencing attenuated E-cadherin–mediated cell–cell adhesion, upregulated mesenchymal markers, and stimulated cell motility. BMK1 depletion dramatically increased the accumulation of endogenous Snail in the nuclear compartment. Snail accumulation was mediated by Akt/GSK3β signaling, which was activated by a modulation in the expression of the mTOR inhibitor DEPTOR. In support of these observations, BMK1 depletion promoted metastasis in vivo. Together, our findings reveal a novel mechanism of EMT control via mTOR/Akt inhibition that suppresses cancer metastasis. Cancer Res; 72(6); 1579–87. ©2012 AACR.