tbuckley/cabot-search huggingface dataset:
Energized endocytosis in human erythrocyte ghosts.
Authors: S L Schriei, K G Bensch, M Johnson, I Junga
Journal: Journal of Clinical Investigation (1975)

The mechanism of endocytosis in resealed human erythrocyte ghosts was studied. The energy for endocytosis or micropinocytosis appears to be derived from Mg-ATP, and membrane internalization is preceded by activation of a membrane-associated Ca,Mg-ATPase and by the active efflux of Ca. Endocytosis, Ca,Mg-ATPase activity, and active Ca efflux all require the presence of Mg. Furthermore, these three phenomena, endocytosis, Ca,Mg-ATPase activity, and active Ca extrusion, all have a concentration dependence on Ca such that low concentrations stimulate and higher concentrations inhibit the phenomena. The optimal concentration of Ca is identical for endocytosis, active Ca efflux, and Ca,Mg-ATPase. Morphologic studies indicated that while active Ca efflux and activation of the Ca,Mg-ATPase activity occurred promptly upon onset of incubation, there was a significant time delay before endocytosis occurred, which suggests that endocytosis additionally involved a more slowly functioning mechanicochemical mechanism. Ruthenium red, a specific inhibitor of Ca,Mg-ATPase and Ca transport, inhibited endocytosis in a concentration-related manner. Prostaglandins E1 and E2 had no measurable effect on ghost endocytosis, active Ca efflux, or Ca,Mg-ATPase activity.
Methotrexate revisited: effects of long-term treatment in psoriasis
Authors: R.J. DOOREN-GREEBE, A.L.A. KUIJPERS, J. MULDER, TH. BOO, P.C.M. KERKHOF
Journal: British Journal of Dermatology (1994)

In the past 22 years, 113 patients with severe psoriasis have been treated with low-dose methotrexate (MTX) in our department. The maximum weekly dosage was 15 mg (Weinstein schedule), the estimated mean cumulative dose was 4803 mg, and the estimated mean duration of therapy was 8 years and 11 months. In 81% of the patients, prolonged clearance or near clearance was achieved, indicating the potent and sustained potential of MTX in the treatment of both the pustular and erythematosquamous variants of psoriasis. Eighty-three patients (73%) had side-effects, most frequently abnormal liver function tests, nausea and gastric complaints. Apart from hair loss in seven patients, there were no mucocutaneous side-effects, probably because of the low-dose treatment schedule. In 71 patients MTX therapy was discontinued; in 33 patients because of side-effects. In 55 patients one or more liver biopsies were performed. Fibrosis was seen in seven of these patients (13%) and cirrhosis in two (4%). There was no relation between liver biopsy classification and cumulative dosage or duration of MTX therapy, nor was there any relation between liver histology and abnormal liver function tests. During this 22-year period, there were no deaths or life-threatening side-effects attributable to MTX treatment. We conclude that low-dose MTX (< or = 15 mg/week) is a relatively safe therapy for severe psoriasis, if patients are carefully selected beforehand, and regular monitoring for side-effects and drug interactions is performed during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Forced Alignment of Mesenchymal Stem Cells Undergoing Cardiomyogenic Differentiation Affects Functional Integration With Cardiomyocyte Cultures
Authors: Daniël A. Pijnappels, Martin J. Schalij, Arti A. Ramkisoensing, John van Tuyn, Antoine A.F. de Vries, Arnoud van der Laarse, Dirk L. Ypey, Douwe E. Atsma
Journal: Circulation Research (2008)

Alignment of cardiomyocytes (CMCs) contributes to the anisotropic (direction-related) tissue structure of the heart, thereby facilitating efficient electrical and mechanical activation of the ventricles. This study aimed to investigate the effects of forced alignment of stem cells during cardiomyogenic differentiation on their functional integration with CMC cultures. Labeled neonatal rat (nr) mesenchymal stem cells (nrMSCs) were allowed to differentiate into functional heart muscle cells in different cell-alignment patterns during 10 days of coculture with nrCMCs. Development of functional cellular properties was assessed by measuring impulse transmission across these stem cells between 2 adjacent nrCMC fields, cultured onto microelectrode arrays and previously separated by a laser-dissected channel (230+/-10 microm) for nrMSC transplantation. Coatings in these channels were microabraded in a direction (1) parallel or (2) perpendicular to the channel or were (3) left unabraded to establish different cell patterns. Application of cells onto microabraded coatings resulted in anisotropic cell alignment within the channel. Application on unabraded coatings resulted in isotropic (random) alignment. After coculture, conduction across seeded nrMSCs occurred from day 1 (perpendicular and isotropic) or day 6 (parallel) onward. Conduction velocity across nrMSCs at day 10 was highest in the perpendicular (11+/-0.9 cm/sec; n=12), intermediate in the isotropic (7.1+/-1 cm/sec; n=11) and lowest in the parallel configuration (4.9+/-1 cm/sec; n=11) (P<0.01). nrCMCs and fibroblasts served as positive and negative control, respectively. Also, immunocytochemical analysis showed alignment-dependent increases in connexin 43 expression. In conclusion, forced alignment of nrMSCs undergoing cardiomyogenic differentiation affects the time course and degree of functional integration with surrounding cardiac tissue.
The Immunogenicity of a New Human Minor Histocompatibility Antigen Results from Differential Antigen Processing
Authors: Anthony G. Brickner, Edus H. Warren, Jennifer A. Caldwell, Yoshiki Akatsuka, Tatiana N. Golovina, Angela L. Zarling, Jeffrey Shabanowitz, Laurence C. Eisenlohr, Donald F. Hunt, Victor H. Engelhard, Stanley R. Riddell
Journal: The Journal of Experimental Medicine (2001)

Minor histocompatibility antigens (mHAgs) present a significant impediment to organ and bone marrow transplantation between HLA-identical donor and recipient pairs. Here we report the identification of a new HLA-A*0201-restricted mHAg, HA-8. Designation of this mHAg as HA-8 is based on the nomenclature of Goulmy (Goulmy, E. 1996. Curr. Opin. Immunol. 8:75-81). This peptide, RTLDKVLEV, is derived from KIAA0020, a gene of unknown function located on chromosome 9. Polymorphic alleles of KIAA0020 encode the alternative sequences PTLDKVLEV and PTLDKVLEL. Genotypic analysis demonstrated that the HA-8-specific cytotoxic T lymphocyte (CTL) clone SKH-13 recognized only cells that expressed the allele encoding R at P1. However, when PTLDKVLEV was pulsed onto cells, or when a minigene encoding this sequence was used to artificially translocate this peptide into the endoplasmic reticulum, it was recognized by CTLs nearly as well as RTLDKVLEV. This indicates that the failure of CTLs to recognize cells expressing the PTLDKVLEV-encoding allele of KIAA0020 is due to a failure of this peptide to be appropriately proteolyzed or transported. Consistent with the latter possibility, PTLDKVLEV and its longer precursors were transported poorly compared with RTLDKVLEV by transporter associated with antigen processing (TAP). These studies identify a new human mHAg and provide the first evidence that minor histocompatibility differences can result from the altered processing of potential antigens rather than differences in interaction with the relevant major histocompatibility complex molecule or T cell receptor.
INTERFERON PRODUCTION BY MOUSE LEUKOCYTES IN VITRO AND IN VIVO
Authors: Lowell A. Glasgow, Karl Habel
Journal: The Journal of Experimental Medicine (1963)

Vaccinia virus penetrates, or is phagocytosed by, mouse leukocytes in vitro. A cytotoxic effect is observed, but no new infectious virus is produced. Vaccinia virus, as infectious particles, is eliminated from a culture of leukocytes at a more rapid rate than can be accounted for by thermal inactivation. Leukocytes infected with vaccinia virus produce a substance with the properties of interferon. The evidence presented suggests that leukocytes also produce interferon in vivo and that this interferon is related to the observed protective effect on the outcome of intracerebral vesicular stomatitis virus challenge in mice. It is postulated that leukocytes, in this manner, may make a positive contribution to the host's defense mechanism and to the process of recovery from viral infections.
SHORT COMMUNICATIONPhotodynamic therapy with delta-aminolaevulinic acid for nodular basal cell carcinomas using a prior debulking technique
Authors: M.R.T.M. Thissen, C.A. Schroeter, H.A.M. Neumann
Journal: British Journal of Dermatology (2000)

The incidence of basal cell carcinomas (BCCs) is still increasing, and there is a demand for an easy, effective and selective non-invasive treatment such as topical photodynamic therapy (PDT). Twenty-three patients with 24 nodular BCCs were treated once with delta-aminolaevulinic acid (δ-ALA) PDT (100 mW cm−2, 120 J/cm2) 3 weeks after prior debulking of the BCCs. Three months after PDT, all lesions were surgically excised and histopathologically evaluated for residual tumour. Twenty-two (92%) of the 24 nodular BCCs showed a complete response on clinical and histopathological examination. PDT for superficially abraded nodular BCCs with topically applied δ-ALA and the VersaLight® as light source is an easy, effective and safe therapy, with excellent cosmetic results and no serious side-effects, in cases where non-surgical treatment of BCCs is indicated.
Gross Hematuria as a Complication in the Combination Use of Psychotrophic Drugs
Authors: ERNEST C. MILLER, E. L. HARRELL, J. B. STOKES
Journal: American Journal of Psychiatry (1967)

A case of gross hematuria complicating the combined use of chlorpromazine, trifluoperazine, amitriptyline, and benztropine mesylate is reported. The mechanism involved is felt to be secondary to mechanical stresses on bladder vasculature following bladder atony produced by the anticholinergic side effects of the drugs. Advantages of the combination use of psychoactive drugs are cited; however, an increased awareness of the side effects and complications attendant to such use is to be encouraged.
Immortal time bias and infliximab-related mortality and malignancy incidence
Authors: L. E. Targownik
Journal: Gut (2010)

In this intriguing article, Fidder et al report on the long-term follow-up of a cohort of subjects with inflammatory bowel disease (IBD) managed at a tertiary care institution.1 The authors conclude that IBD patients exposed to infliximab are at no higher risk for mortality or being diagnosed as having malignancy than controls with no prior infliximab exposure. These results would appear to confirm the safety of this drug in the treatment of IBD, as suggested by other studies of IBD cohorts followed over the long-term. However, it appears that this study may contain significant biases which …
Functional Analysis of Epidermal Growth Factor Receptor (EGFR) Mutations and Potential Implications for EGFR Targeted Therapy
Authors: Rama Krishna Kancha, Nikolas von Bubnoff, Christian Peschel, Justus Duyster
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) might be predictive for clinical response to EGFR inhibitor treatment. However, retrospective analyses of EGFR mutations in clinical trials have shown inconclusive results and the effect of EGFR sequencing in NSCLC is still controversial. Because the vast majority of EGFR mutations described have not been functionally characterized, simple correlation of mutational status and treatment response may not provide reliable information about the predictive value of EGFR mutations. Thus, we aimed to characterize a comprehensive panel of clinically observed EGFR mutations. Experimental Design and Results: A panel of 30 EGFR mutations was cloned and characterized for kinase activity and the ability to confer growth factor independence. Interestingly, 4 of 30 EGFR mutations showed no kinase activity even after ligand stimulation and were not able to confer growth factor independence. Ba/F3 cells expressing activating EGFR mutants were then used to test the efficacy of EGFR inhibitors in a cell proliferation assay. IC50 values were calculated for gefitinib, erlotinib, and AEE788. We show that the sensitivity of EGFR mutations toward different inhibitors varies significantly, thus establishing a comprehensive sensitivity profile for each inhibitor. Conclusions: EGFR mutations identified in NSCLC patients display distinct biological features. The variability in kinase activity, transforming potential, and sensitivity to EGFR inhibitors has to be considered in clinical studies aiming to correlate mutational status and drug response. The identification of comprehensive drug resistance profiles opens the opportunity to test alternative EGFR inhibitors in vitro.
Enhanced cardiac preconditioning in the isolated heart of the transgenic ((mREN-2)27) hypertensive rat
Authors: M Randall
Journal: Cardiovascular Research (1997)

Objective: Cardiac preconditioning represents an important cardioprotective mechanism which limits myocardial ischaemic damage. The aim of this investigation was to assess the impact of preconditioning in hypertension, which is a major risk factor for ischaemic heart disease. Methods: Hearts isolated from male transgenic ((mREN-2)27) hypertensive (TGH) rats, and their normotensive controls (Hannover Sprague-Dawley; SD rats), were perfused at constant flow using the Langendorff technique, and were subjected to either ischaemic preconditioning (3×4 min ischaemia) or continuous perfusion. Global ischaemia was then induced for 30 min, followed by 60 min of reperfusion, during which time mechanical performance was assessed (left ventricular developed pressure (LVDP), heart rate, and end-diastolic pressure). Results: In the absence of preconditioning, mechanical performance was substantially depressed on reperfusion, and there was no difference between TGH hearts and SD hearts (area under the curve (AUC) for the LVDP (LVDP0–60) plot against time for reperfusion = 356±115 and 296±206 mmHg·min, respectively). Cardiac preconditioning caused significant protection in both groups, but this was significantly (P<0.05) greater (3-fold) in the TGH hearts (AUC for LVDP0–60 = 3349±610 mmHg·min) compared to the SD hearts (AUC for LVDP0–60 = 1153±527 mmHg·min). In both groups, preconditioning induced significant protection of diastolic function. The enhanced effects of preconditioning on mechanical performance in the TGH hearts were unaffected by the angiotensin AT1-receptor antagonist, losartan (3 μM). However, losartan did partially reverse the beneficial effects of preconditioning on post-ischaemic diastolic function in the TGH hearts. Conclusions: The results of the present investigation clearly show that cardiac preconditioning is substantially enhanced in hearts from TGH rats. Furthermore, the beneficial effects of preconditioning on diastolic function, but not mechanical performance, in TGH hearts is partially mediated by AT1-receptors.
Graphic Representation of Electrocardiographic Leads by Means of Fluid Mappers
Authors: RICHARD MCFEE, ROBERT M. STOW, FRANKLIN D. JOHNSTON
Journal: Circulation (1952)

A new method for the study of electrocardiographic leads is described. It makes use of plaster models having the same shape as the body in the frontal (or other) planes through which water flows in sheets. The flow of water is approximately analogous to the flow of electric currents through the body, and the flow lines are made visible by small crystals of soluble dye. If fluid passes in and out of the flow space from points that correspond to the location of electrodes of the electrocardiographic leads, the flow lines may be used to study the effects that electromotive forces arising in the heart have on these leads. With these models it is possible to study many different kinds of leads and the effects of variations of body shape, position of the heart, and electric conductivity of the tissues on them. Preliminary observations largely concerned with standard, unipolar extremity and chest leads are reported.
Lithium Prophylaxis in Recurrent Affective Illness
Authors: ROBERT F. PRIEN, C. JAMES KLETT, EUGENE M. CAFFEY
Journal: American Journal of Psychiatry (1974)

The authors report on two recent two-year studies that attempted to determine the effectiveness of lithium carbonate in treating recurrent affective illness. In study I, 205 bipolar (manic-depressive) patients were randomly assigned to lithium or placebo; in study 2, 44 bipolar and 78 unipolar (depressive) patients were randomly assigned lithium, imipramine, or placebo. The results showed lithium to be effective in treating both manic and depressive episodes and imipramine to be effective in treating depressive episodes. The findings emphasize the importance of considering the patient's previous course of illness in selecting a program of maintenance treatment.
Mechanotransduction at Cell-Matrix and Cell-Cell Contacts
Authors: Christopher S. Chen, John Tan, Joe Tien
Journal: Annual Review of Biomedical Engineering (2004)

Mechanical forces play an important role in the organization, growth, maturation, and function of living tissues. At the cellular level, many of the biological responses to external forces originate at two types of specialized microscale structures: focal adhesions that link cells to their surrounding extracellular matrix and adherens junctions that link adjacent cells. Transmission of forces from outside the cell through cell-matrix and cell-cell contacts appears to control the maturation or disassembly of these adhesions and initiates intracellular signaling cascades that ultimately alter many cellular behaviors. In response to externally applied forces, cells actively rearrange the organization and contractile activity of the cytoskeleton and redistribute their intracellular forces. Recent studies suggest that the localized concentration of these cytoskeletal tensions at adhesions is also a major mediator of mechanical signaling. This review summarizes the role of mechanical forces in the formation, stabilization, and dissociation of focal adhesions and adherens junctions and outlines how integration of signals from these adhesions over the entire cell body affects how a cell responds to its mechanical environment. This review also describes advanced optical, lithographic, and computational techniques for the study of mechanotransduction.
Chronic pneumonia caused by Rhodococcus equi in a patient without impaired immunity
Authors: MJ Linares, A Lopez-Encuentra, S Perea
Journal: European Respiratory Journal (1997)

A 48 year old, human immunodeficiency virus (HIV)-negative, immunocompetent male patient had a chronic progressive pulmonary infiltrate, without radiological cavitation, in the middle lobe of the right lung produced by Rhodococcus equi. He reported direct contact with a diseased dog. The patient was diagnosed by thoracotomy and treated by lobectomy. After 16 months of follow-up, the patient was asymptomatic and had neither recurrence nor immunological disturbances.
Differences in Brain Glucose Metabolism Between Responders to CBT and Venlafaxine in a 16-Week Randomized Controlled Trial
Authors: Sidney H Kennedy, Jakub Z Konarski, Zindel V Segal, Mark A Lau, Peter J Bieling, Roger S McIntyre, Helen S Mayberg
Journal: American Journal of Psychiatry (2007)

Objective: Neuroimaging investigations reveal changes in glucose metabolism (fluorine-18-fluorodeoxyglucose positron emission tomography [PET]) associated with response to disparate antidepressant treatment modalities, including cognitive behavior therapy (CBT), antidepressant pharmacotherapies, and deep brain stimulation. Using a nonrandomized design, the authors previously compared changes following CBT or paroxetine in depressed patients. In this study, the authors report changes in fluorine-18-fluorodeoxyglucose PET in responders to CBT or venlafaxine during a randomized controlled trial. Methods Subjects meeting DSM-IV-TR criteria for a major depressive episode and a diagnosis of a major depressive disorder received a fluorine-18-fluorodeoxyglucose PET scan before randomization and after 16 weeks of antidepressant treatment with either CBT (N=12) or venlafaxine (N=12). Modality-specific and modality-independent regional brain metabolic changes associated with response status were analyzed. Results: Response rates were comparable between the CBT (7/12) and venlafaxine (9/12) groups. Response to either treatment modality was associated with decreased glucose metabolism bilaterally in the orbitofrontal cortex and left medial prefrontal cortex, along with increased metabolism in the right occipital-temporal cortex. Changes in metabolism in the anterior and posterior parts of the subgenual cingulate cortex and the caudate differentiated CBT and venlafaxine responders. Conclusions: Responders to either treatment modality demonstrated reduced metabolism in several prefrontal regions. Consistent with earlier reports, response to CBT was associated with a reciprocal modulation of cortical-limbic connectivity, while venlafaxine engaged additional cortical and striatal regions previously unreported in neuroimaging investigations.
A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project
Authors: F. Navarro-Sarabia, P. Coronel, E. Collantes, F. J. Navarro, A. R. de la Serna, A. Naranjo, M. Gimeno, G. Herrero-Beaumont
Journal: Annals of the Rheumatic Diseases (2011)

Bacterial flagellin has recently been identified as a ligand for Toll-like receptor 5 (TLR5). Human sites known to specifically express TLR5 include macrophages and gastric and intestinal epithelium. Because infection of intestinal epithelial cells with <i>Salmonella</i> leads to an active transport of flagellin to the subepithelial compartment in proximity to microvessels, we hypothesized that human intestinal endothelial cells functionally express TLR5, thus enabling an active inflammatory response upon binding of translocated flagellin. Endothelial expression of TLR5 in human macro- and microvascular endothelial cells was examined by RT-PCR, immunoblot analysis, and immunofluorescence. Endothelial expression of TLR5 in vivo was verified by immunohistochemistry. Endothelial modulation of ICAM-1 expression was quantitated using flow cytometry, and leukocyte transmigration in vitro was assessed by an endothelial transmigration assay. Epithelial-endothelial cellular interactions upon infection with viable <i>Salmonella</i> were investigated using a coculture system in vitro. We found that <i>Salmonella</i>-infected intestinal epithelial cells induce endothelial ICAM-1 expression in cocultured human endothelial cells. Both macro- (HUVEC) and microvascular endothelial cells derived from human skin (human dermal microvascular endothelial cell 1) and human colon (human intestinal microvascular endothelial cells) were found to express high constitutive amounts of TLR5 mRNA and protein. These findings were paralleled by strong immunoreactivity for TLR5 of normal human colonic microvessels in vivo. Furthermore, incubation of human dermal microvascular endothelial cells with flagellin from clinical isolates of <i>Escherichia</i> and <i>Salmonella</i> strains led to a marked up-regulation of ICAM-1, as well as to an enhanced leukocyte transendothelial cell migration. These results suggest that endothelially expressed TLR5 might play a previously unrecognized role in the innate immune response toward bacterial Ags.