tbuckley/cabot-search huggingface dataset:
Extracellular Hypotonicity Increases Na,K-ATPase Cell Surface Expression via Enhanced Na+ Influx in Cultured Renal Collecting Duct Cells
Authors: Manlio Vinciguerra, Serge Arnaudeau, David Mordasini, Martine Rousselot, Marcelle Bens, Alain Vandewalle, Pierre-Yves Martin, Udo Hasler, Eric Feraille
Journal: Journal of the American Society of Nephrology (2004)

In the renal collecting duct (CD), the Na,K-ATPase, which provides the driving force for Na<sup>+</sup> absorption, is under tight multifactorial control. Because CD cells are physiologically exposed to variations of interstitial and tubular fluid osmolarities, the effects of extracellular anisotonicity on Na,K-ATPase cell surface expression were studied. Results show that hypotonic conditions increased, whereas hypertonic conditions had no effect on Na,K-ATPase cell surface expression in confluent mpkCCD<sub>cl4</sub> cells. Incubating cells with amphotericin B, which increases [Na<sup>+</sup>]<sub>i</sub>, under isotonic or anisotonic conditions, revealed that Na,K-ATPase recruitment to the cell surface was not directly related to variations of cell volume and osmolarity. The effects of amphotericin B and extracellular hypotonicity were not additive, and both were prevented by protein kinase A and proteasome inhibitors, suggesting a common mechanism of action. In line with this hypothesis, extracellular hypotonicity induced a sustained stimulation of the amiloride-sensitive short-circuit current, indicating increased Na<sup>+</sup> influx through the apical epithelial Na<sup>+</sup> channel. Moreover, inhibiting apical Na<sup>+</sup> entry by amiloride, a blocker of epithelial Na<sup>+</sup> channel, or incubating cells in Na<sup>+</sup>-free medium prevented the cell surface recruitment of Na,K-ATPase in response to extracellular hypotonicity. Altogether, these findings strongly suggest that extracellular hypotonicity stimulates apical Na<sup>+</sup> influx leading to increased [Na<sup>+</sup>]<sub>i</sub>, protein kinase A activation, and recruitment of Na,K-ATPase units to the cell surface of mpkCCD<sub>cl4</sub> cells.
The association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes
Authors: Roshani N Sanghani, Zarir F Udwadia
Journal: Thorax (2013)

One woe doth tread upon another's heel, So fast they follow. William Shakespeare. Hamlet. Act 1V Scene V11 

We are approaching a day and age where the terms communicable and non-communicable diseases are taking on a new meaning. In the epidemiology and global public health space we track the top five causes of death to measure how well we are doing in combating illness.1 The idea that tuberculosis (TB) and diabetes mellitus (DM) share a synergistic relationship has been creating a growing stir around the world. This is so in the developed world where non-communicable diseases remain the leading cause of death and the developing world where the ‘diabesity’ epidemic is rapidly expanding to possibly overshadow the traditional killers from communicable disease.2 Of what relevance are these classifications in a patient unfortunate enough to have TB and DM? What, if anything, should we do differently in our clinics when a classical non-communicable illness like DM accelerates and amplifies the course of an age-old, communicable infection like TB? As the dreaded Mycobacterium grows deadlier with time, none of us want to see it develop new allies. The study published by Jimenez-Corona et al 3 in this edition of Thorax suggests we have reason to be concerned. It also needs to be lauded upfront for being a major effort at identifying, exploring and characterising the TB-DM connection. They present a 15 year prospective follow-up of this growing area of concern. Indeed in the years since they started collecting data, numerous reports have emerged addressing the same concept in India,4 Brazil5 and the US-Mexico border.6 The study by Jiminez-Corona has several merits worth noting. They followed a large sample size totalling 1262 patients with pulmonary TB (PTB), and found a high prevalence of …
Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats
Authors: Yoshitaka Iwanaga, Masahiko Hoshijima, Yusu Gu, Mitsuo Iwatate, Thomas Dieterle, Yasuhiro Ikeda, Moto-o Date, Jacqueline Chrast, Masunori Matsuzaki, Kirk L Peterson, Kenneth R Chien, John Ross
Journal: Journal of Clinical Investigation (2004)

Ablation or inhibition of phospholamban (PLN) has favorable effects in several genetic murine dilated cardiomyopathies, and we showed previously that a pseudophosphorylated form of PLN mutant (S16EPLN) successfully prevented progressive heart failure in cardiomyopathic hamsters. In this study, the effects of PLN inhibition were examined in rats with heart failure after myocardial infarction (MI), a model of acquired disease. S16EPLN was delivered into failing hearts 5 weeks after MI by transcoronary gene transfer using a recombinant adeno-associated virus (rAAV) vector. In treated (MI-S16EPLN, n = 16) and control (MI-saline, n = 18) groups, infarct sizes were closely matched and the left ventricle was similarly depressed and dilated before gene transfer. At 2 and 6 months after gene transfer, MI-S16EPLN rats showed an increase in left ventricular (LV) ejection fraction and a much smaller rise in LV end-diastolic volume, compared with progressive deterioration of LV size and function in MI-saline rats. Hemodynamic measurements at 6 months showed lower LV end-diastolic pressures, with enhanced LV function (contractility and relaxation), lowered LV mass and myocyte size, and less fibrosis in MI-S16EPLN rats. Thus, PLN inhibition by in vivo rAAV gene transfer is an effective strategy for the chronic treatment of an acquired form of established heart failure.
Pharmacological blockade of group II metabotropic glutamate receptors reduces the growth of glioma cells in vivo
Authors: Antonietta Arcella, Giulia Carpinelli, Giuseppe Battaglia, Mara D'Onofrio, Filippo Santoro, Richard Teke Ngomba, Valeria Bruno, Paola Casolini, Felice Giangaspero, Ferdinando Nicoletti
Journal: Neuro-Oncology (2005)

U87MG human glioma cells in cultures expressed metabotropic glutamate (mGlu) receptors mGlu2 and mGlu3. Addition of the mGlu2/3 receptor antagonist LY341495 to the cultures reduced cell growth, expression of cyclin D1/2, and activation of the MAP kinase and phosphatidylinositol-3-kinase pathways. This is in line with the evidence that activation of mGlu2/3 receptors sustains glioma cell proliferation. U87MG cells were either implanted under the skin (1× 106 cells/0.5 ml) or infused into the caudate nucleus (0.5× 106 cells/5 μl) of nude mice. Animals were treated for 28 days with mGlu receptor antagonists by means of subcutaneous osmotic minipumps. Treatments with LY341495 or (2S)-α-ethylglutamate (both infused at a rate of 1 mg/kg per day) reduced the size of tumors growing under the skin. Infusion of LY341495 (10 mg/kg per day) also reduced the growth of brain tumors, as assessed by magnetic resonance imaging analysis carried out every seven days. The effect of drug treatment was particularly evident during the exponential phase of tumor growth, that is, between the third and the fourth week following cell implantation. Immunohistochemical analysis showed that U87MG cells retained the expression of mGlu2/3 receptors when implanted into the brain of nude mice. These data suggest that mGlu2/3 receptor antagonists are of potential use in the experimental treatment of malignant gliomas.
CLINICAL EVALUATION OF CARPHENAZINE AND PIPERACETAZINE IN PREVIOUSLY PLACEBO-TREATED CHRONIC SCHIZOPHRENICS
Authors: BESSIE CLAFFEY, LESTER H. MARGOLIS, WILLIAM MANDEL
Journal: American Journal of Psychiatry (1962)

Carphenazine and piperacetazine, two new phenothiazines, were given to 80 chronic schizophrenic patients for 4 to 9 months. These patients had previously served as control subjects in a controlled drug evaluation and had not improved. A global rating of moderate or marked improvement over their pre-study status was observed in 73% of the patients. There were no statistically significant differences between the drugs in degree of improvement or incidence of extrapyramidal reactions. Both drugs were considered effective phenothiazines for the chronic schizophrenic patient.
The Fc receptor on thymus-derived lymphocytes. IV. Inhibition of binding of antigen-antibody complexes to Fc receptor-positive T cells by anti-Ia sera.
Authors: R D Stout, D B Murphy, H O McDevitt, L A Herzenberg
Journal: The Journal of Experimental Medicine (1977)

Treatment of splenic T lymphocytes with anti-Ia antiserum inhibits the binding of antigen-antibody (AgAb) complexes to the majority (less than 50%) of Fc receptor-positive (FcR+) T cells. A similar inhibition was observed with anti-H-2D and anti-H-2K sera but not with anti-Thy 1.2. Despite the presence of Ia determinants on peripheral T cells, as established by the inhibition of AgAb binding, Ia could not be detected on peripheral T cells by immunofluorescence assays. Data obtained with the AgAb-binding inhibition assay indicate that determinants controlled by loci mapping in the I-A and I-C, S, or G regions are present on the FcR+ T cells. Evidence is presented that subpopulations of T cells within the FcR+ T-cell population may be distinguishable on the basis of which I-region-controlled determinant is expressed. The data are discussed in terms of phenotypic and functional heterogeneity of T lymphocytes.
AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements
Authors: Alexander L. Kovalchuk, Wendy duBois, Elizabeth Mushinski, Nicole E. McNeil, Carsten Hirt, Chen-Feng Qi, Zhaoyang Li, Siegfried Janz, Tasuku Honjo, Masamichi Muramatsu, Thomas Ried, Timothy Behrens, Michael Potter
Journal: The Journal of Experimental Medicine (2007)

Activation-induced cytidine deaminase (AID) is required for immunoglobulin (Ig) class switch recombination and somatic hypermutation, and has also been implicated in translocations between Ig switch regions and c-Myc in plasma cell tumors in mice. We asked if AID is required for accelerated tumor development in pristane-treated Bcl-xL transgenic BALB/c mice deficient in AID (pBxAicda−/−). pBxAicda−/− mice developed tumors with a lower frequency (24 vs. 62%) and a longer mean latency (108 vs. 36 d) than AID-sufficient mice. The tumors appeared in oil granuloma tissue and did not form ascites. By interphase fluorescence in situ hybridization, six out of nine pBxAicda−/− primary tumors had T(12;15) and one had T(6;15) chromosomal translocations. Two tumors were transplantable and established as stable cell lines. Molecular and cytogenetic analyses showed that one had an unusual unbalanced T(12;15) translocation, with IgH Cμ and Pvt-1 oriented head to tail at the breakpoint, resulting in an elevated expression of c-Myc. In contrast, the second was T(12;15) negative, but had an elevated N-Myc expression caused by a paracentric inversion of chromosome 12. Thus, novel mechanisms juxtapose Ig and Myc-family genes in AID-deficient plasma cell tumors.
Microengineering in cardiovascular research: new developments and translational applications
Authors: Juliana M. Chan, Keith H.K. Wong, Arthur Mark Richards, Chester L. Drum
Journal: Cardiovascular Research (2015)

Microfluidic, cellular co-cultures that approximate macro-scale biology are important tools for refining the in vitro study of organ-level function and disease. In recent years, advances in technical fabrication and biological integration have provided new insights into biological phenomena, improved diagnostic measurements, and made major steps towards de novo tissue creation. Here we review applications of these technologies specific to the cardiovascular field, emphasizing three general categories of use: reductionist vascular models, tissue-engineered vascular models, and point-of-care diagnostics. With continued progress in the ability to purposefully control microscale environments, the detailed study of both primary and cultured cells may find new relevance in the general cardiovascular research community.
Molecular Basis for the Critical Role of Suppressor of Cytokine Signaling-1 in Melanoma Brain Metastasis
Authors: Feng-Ju Huang, Patricia S. Steeg, Janet E. Price, Wen-Tai Chiu, Ping-Chieh Chou, Keping Xie, Raymond Sawaya, Suyun Huang
Journal: Cancer Research (2008)

Abstract Our recent study found that activation of signal transducer and activator of transcription 3 (Stat3) is up-regulated in human brain metastatic cells and contributes to brain metastasis of melanoma. However, the molecular mechanisms underlying this increased Stat3 activation and effect on brain metastasis are unknown. In this report, we showed that the expression of Janus-activated kinase 2 (JAK2), a Stat3 activator, was increased, whereas the expression of a negative regulator of Stat3, suppressor of cytokine signaling-1 (SOCS-1), was reduced in the brain metastatic melanoma cell line A375Br, relative to that in the parental A375P cell line. Consistently, SOCS-1 expression was also lower in the human brain metastatic tissues than in the primary melanoma tissues. Mechanistically, increased JAK2 expression in the A375Br cells was due to, at least in part, its decreased degradation, which was directly correlated with low expression of SOCS-1. Moreover, restoration of SOCS-1 expression resulted in the inhibition of Stat3 activation, whereas depletion of SOCS-1 up-regulated Stat3 activation. These clinical, experimental, and mechanistic findings strongly suggest that increased activation of Stat3 in brain metastatic melanoma cells might be due to decreased SOCS-1 expression. Furthermore, restoration of SOCS-1 expression in brain metastatic A375Br cells significantly inhibited brain metastasis in animal models (P &amp;lt; 0.001). Additionally, alterations of SOCS-1 expression profoundly affected the expression of matrix metalloproteinase-2 (MMP-2), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) and the melanoma cell invasion and angiogenesis. Collectively, these data suggest that the loss of SOCS-1 expression is a critical event, leading to elevated Stat3 signaling and overexpression of MMP-2, bFGF, and VEGF, as well as enhanced invasion and angiogenesis of melanoma cells, consequently promoting brain metastasis. [Cancer Res 2008;68(23):9634–42]
Screening for Chlamydial Infection: An Evidence Update for the U.S. Preventive Services Task Force
Authors: David S. Meyers, Heather Halvorson, Sara Luckhaupt
Journal: Annals of Internal Medicine (2007)

Background: Chlamydial infection is the most common sexually transmitted bacterial infection in the United States, with an estimated 3 million new cases annually. In 2001, the U.S. Preventive Services Task Force (USPSTF) recommended that clinicians screen all sexually active women at increased risk for infection for Chlamydia trachomatis. Purpose: To summarize a systematic evidence review commissioned by the USPSTF in preparation for an update of its 2001 recommendation. Data Sources: English-language articles identified in PubMed between July 2000 and July 2005. Additional articles were identified by bibliographic reviews and discussions with experts. A total of 452 articles were identified. Study Selection: Explicit inclusion and exclusion criteria were used for each of 3 key questions. For studies of screening in nonpregnant women at increased risk, review was limited to randomized, controlled trials. For other groups, both randomized, controlled studies and nonrandomized, prospective, controlled studies were included. Data Abstraction: Using standardized forms, staff of the Agency for Healthcare Research and Quality abstracted data on study design, setting, sample, randomization, blinding, results, and harms. Data Synthesis: Only 1 new study met inclusion criteria. This poor-quality study of the effectiveness of screening for chlamydial infection among nonpregnant women at increased risk found that screening was associated with a lower prevalence of chlamydial infection and fewer reported cases of pelvic inflammatory disease at 1-year follow-up. Limitations: No new evidence was found on screening in pregnant women, nonpregnant women not at increased risk, or men. Conclusions: A systematic review found a small amount of new evidence to inform the USPSTF as it updates its recommendations regarding screening for chlamydial infection. There are large gaps in the evidence about screening men to improve health outcomes in women.
Alveolar concentration of nitric oxide predicts pulmonary function deterioration in scleroderma
Authors: Kiet Phong Tiev, Thong Hua-Huy, Adrien Kettaneh, Yannick Allanore, Nhat-Nam Le-Dong, Sy Duong-Quy, Jean Cabane, Anh Tuan Dinh-Xuan
Journal: Thorax (2011)

<h3>Background</h3> Respiratory failure is a life-threatening and unpredictable complication of systemic sclerosis (SSc). A study was undertaken to assess the value of alveolar nitric oxide (NO) in predicting the risk of lung function deterioration leading to respiratory failure or death in patients with SSc. <h3>Methods</h3> 105 patients with SSc were enrolled in this prospective cohort and were followed longitudinally over a 3-year period during which the risk of occurrence of deleterious events was analysed according to alveolar concentration (C<sub>A</sub>no), conducting airway output (J′<sub>aw</sub>no) and fractional concentration (F<sub>E</sub>no<sub>0.05</sub>) of exhaled NO measured at inclusion. Comparison was made between each NO parameter to predict the occurrence of deleterious events, defined as a 10% decrease in total lung capacity or forced vital capacity from baseline, or death. <h3>Results</h3> The area under the receiver operating characteristic curve of C<sub>A</sub>no to predict the occurrence of the combined events was 0.84 (95% CI 0.76 to 0.92; p&lt;0.001), which was significantly higher than those of J′<sub>aw</sub>no and F<sub>E</sub>no<sub>0.05</sub> (p&lt;0.001). A cut-off of C<sub>A</sub>no of 5.3 ppb had a sensitivity of 88% and a specificity of 62% for the prediction of the occurrence of combined events during follow-up, and was validated in an independent cohort of patients with SSc. Combined events occurred more frequently in patients whose C<sub>A</sub>no was &gt;5.3 ppb. The adjusted HR for patients with C<sub>A</sub>no &gt;5.3 ppb was 6.06 (95% CI 2.36 to 15.53; p&lt;0.001). C<sub>A</sub>no accurately predicted the occurrence of combined events irrespective of forced vital capacity values or the presence of interstitial lung disease at baseline. <h3>Conclusions</h3> Increased C<sub>A</sub>no accurately identifies patients with SSc with a high risk of developing lung function deterioration and may help to initiate early appropriate treatment.
Effects of α-Synuclein Immunization in a Mouse Model of Parkinson’s Disease
Authors: Eliezer Masliah, Edward Rockenstein, Anthony Adame, Michael Alford, Leslie Crews, Makoto Hashimoto, Peter Seubert, Michael Lee, Jason Goldstein, Tamie Chilcote, Dora Games, Dale Schenk
Journal: Neuron (2005)
Comprehensive Molecular Diagnostics in Autosomal Dominant Polycystic Kidney Disease
Authors: Sandro Rossetti, Mark B. Consugar, Arlene B. Chapman, Vicente E. Torres, Lisa M. Guay-Woodford, Jared J. Grantham, William M. Bennett, Catherine M. Meyers, Denise L. Walker, Kyongtae Bae, Qin (Jean) Zhang, Paul A. Thompson, J. Philip Miller, Peter C. Harris
Journal: Journal of the American Society of Nephrology (2007)

Mutation-based molecular diagnostics of autosomal dominant polycystic kidney disease (ADPKD) is complicated by genetic and allelic heterogeneity, large multi-exon genes, duplication of PKD1, and a high level of unclassified variants (UCV). Present mutation detection levels are 60 to 70%, and PKD1 and PKD2 UCV have not been systematically classified. This study analyzed the uniquely characterized Consortium for Radiologic Imaging Study of PKD (CRISP) ADPKD population by molecular analysis. A cohort of 202 probands was screened by denaturing HPLC, followed by direct sequencing using a clinical test of 121 with no definite mutation (plus controls). A subset was also screened for larger deletions, and reverse transcription-PCR was used to test abnormal splicing. Definite mutations were identified in 127 (62.9%) probands, and all UCV were assessed for their potential pathogenicity. The Grantham Matrix Score was used to score the significance of the substitution and the conservation of the residue in orthologs and defined domains. The likelihood for aberrant splicing and contextual information about the UCV within the patient (including segregation analysis) was used in combination to define a variant score. From this analysis, 44 missense plus two atypical splicing and seven small in-frame changes were defined as probably pathogenic and assigned to a mutation group. Mutations were thus defined in 180 (89.1%) probands: 153 (85.0%) PKD1 and 27 (15.0%) PKD2. The majority were unique to a single family, but recurrent mutations accounted for 30.0% of the total. A total of 190 polymorphic variants were identified in PKD1 (average of 10.1 per patient) and eight in PKD2. Although nondefinite mutation data must be treated with care in the clinical setting, this study shows the potential for molecular diagnostics in ADPKD that is likely to become increasingly important as therapies become available.
Expression of Myeloid-Related Protein-8 and -14 in Patients With Acute Kawasaki Disease
Authors: Keiich Hirono, Dirk Foell, Yanlin Xing, Sachiko Miyagawa-Tomita, Fei Ye, Martina Ahlmann, Thomas Vogl, Takeshi Futatani, Chen Rui, Xianyi Yu, Kazuhiro Watanabe, Sayaka Wanatabe, Shinichi Tsubata, Keiichiro Uese, Ikuo Hashimoto, Fukiko Ichida, Makoto Nakazawa, Johannes Roth, Toshio Miyawaki
Journal: Journal of the American College of Cardiology (2006)