tbuckley/cabot-search huggingface dataset:
KCl co-transport across the basolateral membrane of rabbit renal proximal straight tubules.
Authors: S Sasaki, K Ishibashi, N Yoshiyama, T Shiigai
Journal: Journal of Clinical Investigation (1988)

Mammalian renal proximal tubules reabsorb large amounts of chloride. Mechanisms of the transcellular chloride transport are poorly understood. To determine whether KCl co-transport exists in the basolateral membrane of mammalian renal proximal tubule, isolated rabbit proximal straight tubules (S2 segment) were perfused in vitro, and intracellular activities of potassium and chloride (aKi, aCli) were measured by double-barreled ion-selective microelectrodes. aCli did not change when basolateral membrane voltage was altered by application of a direct current through perfusion pipette. aCli changes in response to bath chloride elimination were not affected by current application as well, indicating that the basolateral chloride transport is electroneutral. An increase in potassium concentration of the bath fluid from 5 to 20 mM reversibly increased aCli by 10 mM. This response of aCli to a change in the bath potassium concentration was also observed when luminal chloride was removed, or ambient sodium was totally removed. aKi significantly decreased by 5 mM when chloride was removed from the bath. These data demonstrate the existence of an electroneutral Na+-independent KCl co-transport in the basolateral membrane of the rabbit proximal tubule. Calculated electrochemical driving force was favorable for the movement of KCl from the cell to the peritubular fluid.
A Malaria Fingerprint in the Human Genome?
Authors: Johanna P. Daily, Pardis Sabeti
Journal: New England Journal of Medicine (2008)

Malaria, a tremendously successful pathogen that is responsible for more than 300 million cases and 1 million deaths annually,1 has had a large impact on the shape of the human genome. Malaria-selected mutations in human genes promote survival in areas where malaria is endemic. The parasite's substantive effect on the human genome is due to its high prevalence in areas where it is endemic and its long history of coevolution with humans. Moreover, its marked genetic diversity, generated by its sexual stage, provides the organism with many opportunities to maximally adapt to host defenses and continue transmission. In this issue . . .
Fra-1 governs cell migration via modulation of CD44 expression in human mesotheliomas
Authors: Maria E Ramos-Nino, Steven R Blumen, Harvey Pass, Brooke T Mossman
Journal: Molecular Cancer (2007)

Silencing of Fra-1, a component of the dimeric transcription factor, activator protein-1 (AP-1), inhibits mRNA expression of c-met and cd44 in rat mesothelioma cells and is causally linked to maintenance of the transformed phenotype. However, the mechanisms of Fra-1 regulation and Fra-1 regulated gene expression in human malignant mesothelioma (MM) are unclear. We first show in a panel of human MM cells that Fra-1 mRNA expression in MM is complex and regulated by extracellular signal-regulated kinase (ERK1, ERK2), Src, and phosphatidyl-inositol-3-kinase (PI3K) pathways in a tumor-specific fashion. Cell lines with PI3K-dependent Fra-1 expression were SV40 positive and expressed the lowest basal Fra-1 levels. Levels of Fra-1 expression correlated with amounts of CD44 expression that were greater in simian virus 40 negative (SV40-) MM cells. Using dominant negative (dn), short hairpin (sh) and small interference (si) RNA constructs, we next demonstrate that expression of CD44, the principal hyaluronic receptor in MMs, correlates with Fra-expression in both simian virus 40 positive (SV40+) and SV40- MMs. Moreover, both Fra-1 and CD44 expression are linked to cell migration in SV40- MM cells. Lastly, in contrast to normal lung tissue, tissue microarrays revealed that Fra-1 was expressed in 33 of 34 human MMs, and that all CD44+ tumors were SV40-. These results suggest that Fra-1 is associated with cell migration in human MMs and that Fra-1 modulation of CD44 may govern migration of selected MMs.
Injuries in judo: a systematic literature review including suggestions for prevention
Authors: Elena Pocecco, Gerhard Ruedl, Nemanja Stankovic, Stanislaw Sterkowicz, Fabricio Boscolo Del Vecchio, Carlos Gutiérrez-García, Romain Rousseau, Mirjam Wolf, Martin Kopp, Bianca Miarka, Verena Menz, Philipp Krüsmann, Michel Calmet, Nikolaos Malliaropoulos, Martin Burtscher
Journal: British Journal of Sports Medicine (2013)

Background There is limited knowledge on epidemiological injury data in judo. Objective To systematically review scientific literature on the frequency and characteristics of injuries in judo. Methods The available literature up to June 2013 was searched for prospective as well as retrospective studies on injuries in judo. Data extraction and presentation focused on the incidence rate, injury risk, types, location and causes of injuries. Results During the Olympic Games in 2008 and 2012, an average injury risk of about 11–12% has been observed. Sprains, strains and contusions, usually of the knee, shoulder and fingers, were the most frequently reported injuries, whereas being thrown was the most common injury mechanism. Severe injuries were quite rare and usually affected the brain and spine, whereas chronic injuries typically affected the finger joints, lower back and ears. The most common types of injuries in young judo athletes were contusions/abrasions, fractures and sprains/strains. Sex-differences data on judo injuries were mostly inconsistent. Some studies suggested a relationship between nutrition, hydration and/or weight cycling and judo injuries. Also, psychological factors may increase the risk of judo injuries. Conclusions The present review provides the latest knowledge on the frequency and characteristics of injuries in judo. Comprehensive knowledge about the risk of injury during sport activity and related risk factors represents an essential basis to develop effective strategies for injury prevention. Thus, the introduction of an ongoing injury surveillance system in judo is of utmost importance.
Induced sputum cell and fluid-phase indices of inflammation: comparison of treatment with dithiothreitol vs phosphate-buffered saline
Authors: A Efthimiadis, MM Pizzichini, E Pizzichini, J Dolovich, FE Hargreave
Journal: European Respiratory Journal (1997)

Treatment of sputum with dithiothreitol (DTT) gives reliable measurements of cellular and fluid-phase markers of airway inflammation. We investigated the extent to which DTT treatment influences these measurements as compared with phosphate-buffered saline (PBS). Hypertonic saline-induced sputum, collected from 20 asthmatic subjects, was examined within 2 h. All portions which looked more solid (less fluid) than saliva were collected from the expectorate. The selected sputum was then divided into two portions: one treated with one volume of DTT and one volume of PBS, the other with two volumes of PBS. The filtrates were assessed blind for total and differential cell count, viability, and fluid-phase eosinophil cationic protein (ECP), fibrinogen, interleukin (IL)-5 and IL-8. Sputum treated with DTT compared with PBS had lower proportions of viable cells (median 66 versus 74%; p=0.003). In contrast, DTT-treated sputum had higher total cell counts (median 8.8 vs 2.8 x 10(6) mL(-1); p&lt;0.001) and levels of ECP (median 1340 vs 584 mg x L(-1); p&lt;0.001) The measurements were similar with respect to the proportion of eosinophils, neutrophils, lymphocytes, macrophages, and fluid-phase fibrinogen, IL-5 and IL-8. We conclude that dithiothreitol disperses cells more effectively and that this might account for the higher levels of eosinophil cationic protein. Dithiothreitol may affect cell viability, but the changes are not relevant with respect to cell counts. Additionally, dithiothreitol does not seem to influence the other measurements performed.
Proximal coronary vasomotor reactivity after exercise training in dogs.
Authors: A A Bove, J D Dewey
Journal: Circulation (1985)

The effects of exercise on large coronary vasoreactivity were determined in eight dogs trained by treadmill running for 8 weeks. Six nontrained dogs comprised the control group. The trained group showed a significant reduction in heart rate during graded submaximal exercise testing when compared with the controls, and resting plasma levels of norepinephrine (nontrained group, 331 +/- 99 pg/ml; trained group, 142 +/- 30 pg/ml; p less than .05) and epinephrine (nontrained, 424 +/- 105; trained, 258 +/- 45 pg/ml; p less than .05) were reduced significantly in the trained group. Epicardial coronary responses to intracoronary infusion of serotonin and phenylephrine were evaluated by quantitative coronary angiography, and myocardial blood flow was measured with 15 microns radioactive microspheres. Left ventricular/body weight ratio was similar in the trained (4.81 +/- 0.24 g/kg) and nontrained groups (4.79 +/- 0.17), and no differences were noted in resting myocardial oxygen consumption or coronary arteriovenous oxygen difference. The constriction of the proximal left anterior descending artery (LAD) in response to serotonin infusion was not different in the two groups, but the LAD and circumflex artery constrictor responses to phenylephrine were attenuated in the trained when compared with the nontrained dogs. The data indicate that endurance exercise diminishes the large epicardial coronary vasoconstrictor response to alpha-adrenergic stimulation, but not to serotonin. The blunted constrictor response in the trained animals suggests that exercise may be useful in reducing epicardial coronary vasoconstriction, which is thought to be important in some patients with coronary artery disease.
Distribution of type VI collagen expression in synovial tissue and cultured synoviocytes: relation to fibronectin expression.
Authors: J Wolf, S E Carsons
Journal: Annals of the Rheumatic Diseases (1991)

Type VI collagen has recently been shown to be an important component of connective tissue. Double label immunofluorescence procedures were used to immunolocalize type VI collagen in normal and rheumatoid synovium and its distribution was compared with that of fibronectin. In normal synovium type VI collagen is expressed in the synovial membrane but not in the interstitium of the villus. In rheumatoid synovium, however, type VI collagen is extensively deposited in both the interstitial connective tissue and along the lining of the synovial membrane. Cultured rheumatoid and normal synoviocytes produce type VI collagen and fibronectin and incorporate them into their extracellular matrix. These data suggest that type VI collagen may play a part in matrix remodelling of the inflamed joint.
Transmission of tuberculosis in British centre for patients infected with HIV
Authors: R J Kent, A H C Uttley, N G Stoker, R Miller, A L Pozniak
Journal: BMJ (1994)

Patients infected with HIV are at particular risk of tuberculosis, because of both the reactivation of latent infection and the rapid development of disease after exposure to any new source of infection. Many outbreaks of tuberculosis in patients infected with HIV and in the carers of those patients have occurred in hospitals and other institutions in the United States and Europe.1, 2 Those with tuberculosis caused by multiple drug resistant strains have been associated with a high mortality.

Study of the epidemiology of tuberculosis has been helped by restriction fragment length polymorphism analysis with the insertion sequence IS6110. This repetitive element is randomly inserted, usually in multiple copies, in the genomic DNA of members of the Mycobacterium tuberculosis complex. A standardised methodology for this technique has been proposed.3 We used this methodology to investigate a cluster …
L-Kynurenine/Aryl Hydrocarbon Receptor Pathway Mediates Brain Damage After Experimental Stroke
Authors: María I. Cuartero, Iván Ballesteros, Juan de la Parra, Andrew L. Harkin, Aine Abautret-Daly, Eoin Sherwin, Pedro Fernández-Salguero, Ángel L. Corbí, Ignacio Lizasoain, María A. Moro
Journal: Circulation (2014)

Background— Aryl hydrocarbon receptor (AhR) is a transcription factor that belongs to the basic helix-loop-helix PAS (Per-Arnt-Sim homology domain) family known to mediate the toxic and carcinogenic effects of xenobiotics. Interestingly, AhR is widely expressed in the central nervous system, but its physiological and pathological roles are still unclear. Methods and Results— To define the role of AhR in stroke, we used middle cerebral artery occlusion in mice and oxygen-glucose deprivation in rat cortical neurons. The results presented here show that the ischemic insult increases total and nuclear AhR levels and AhR transcriptional activity in neurons in vivo and in vitro. We also show that AhR has a causal role in acute ischemic damage because pharmacological or genetic loss-of-function approaches result in neuroprotection. Inhibition of cAMP response element-binding protein–dependent signaling may participate in the deleterious actions of AhR. Finally, we have also found that L-kynurenine, a tryptophan metabolite with AhR agonistic properties, is an endogenous ligand that mediates AhR activation in the brain after middle cerebral artery occlusion. Conclusions— Our data demonstrate that an L-kynurenine/AhR pathway mediates acute brain damage after stroke and open new possibilities for the diagnosis and treatment of this pathology.
Plasminogen activator inhibitor-1 synthesis in the human hepatoma cell line Hep G2. Metformin inhibits the stimulating effect of insulin.
Authors: F Anfosso, N Chomiki, M C Alessi, P Vague, I Juhan-Vague
Journal: Journal of Clinical Investigation (1993)

High plasma plasminogen activator inhibitor-1 (PAI-1) activity is associated with insulin resistance and is correlated with hyperinsulinemia. The cellular origin of plasma PAI-1 in insulin resistance is not known. The hepatoma cell line Hep G2 has been shown to synthesize PAI-1 in response to insulin. The aim of this study was to analyze the insulin-mediated response of PAI-1 and lipid synthesis in Hep G2 cells after producing an insulin-resistant state by decreasing insulin receptor numbers. The effect of metformin, a dimethyl-substituted biguanide, known to lower plasma insulin and PAI-1 levels in vivo was concomitantly evaluated. Preincubation by an 18-h exposure of Hep G2 cells to 10(-7) M insulin aimed at reducing the number of insulin receptors, was followed by a subsequent 24-h stimulation with 10(-9) M insulin. The decrease in insulin receptors was accompanied as expected, by a reduction in [14C]acetate incorporation, an index of lipid synthesis, whereas PAI-1 secretion and PAI-1 mRNA expression were enhanced. The addition of metformin did not modify the effect of insulin on insulin receptors or [14C]acetate incorporation. In contrast, the drug (10(-4) M) inhibited insulin-mediated PAI-1 synthesis. The results indicate that PAI-1 synthesis in presence of insulin is markedly increased in down-regulated cells, and that metformin inhibits this effect by acting at the cellular level. These in vitro data are relevant with those found in vivo in insulin-resistant patients. Hep G2 cells may be a suitable model to study PAI-1 regulation in response to hyperinsulinemia.
Cyclooxygenase-2 Expression during Immortalization and Breast Cancer Progression
Authors: Xiangshan Zhao, Monica Goswami, Nidhi Pokhriyal, Hui Ma, Hongyan Du, Jun Yao, Thomas A. Victor, Kornelia Polyak, Charles D. Sturgis, Hamid Band, Vimla Band
Journal: Cancer Research (2008)

Abstract Identification of molecular aberrations in premalignant human mammary epithelial cells (hMEC), the precursors for breast cancers, is a central goal in breast cancer biology. Recent studies implicated expression of cyclooxygenase 2 (COX-2) as a marker to identify precursor cells for breast cancer. In this study, we analyzed COX-2 expression in preselection and postselection hMEC cells and observed similar COX-2 levels in both cells. Interestingly, immortalization of postselection cells using various methods leads to a dramatic decrease in COX-2 expression. Similar to immortal cells, the majority of breast cancer cell lines expressed low levels of COX-2 protein. Finally, analyses of COX-2 expression in a series of specimens from reduction mammoplasty, adenosis, ductal carcinoma in situ, and infiltrating ductal carcinoma showed down-regulation of COX-2 expression during tumor progression. Importantly, down-regulation of COX-2 using small interfering RNA in cells showed no effect on cell proliferation, anchorage-independent growth, migration, or invasion. These results show that (a) COX-2 overexpression does not seem to predict a breast cancer precursor cell and does not provide advantage for the cell to be transformed; (b) inhibition of COX-2 does not affect hMEC growth and oncogenic behavior in the conditions analyzed; and (c) COX-2 expression is decreased in breast cancer cell lines and cancer specimens as compared with normal mammary epithelial cells. [Cancer Res 2008;68(2):467–75]
Phase III Randomized Study of Rituximab/Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) Compared With Iodine-131 Tositumomab/BEAM With Autologous Hematopoietic Cell Transplantation for Relapsed Diffuse Large B-Cell Lymphoma: Results From the BMT CTN 0401 Trial
Authors: Julie M. Vose, Shelly Carter, Linda J. Burns, Ernesto Ayala, Oliver W. Press, Craig H. Moskowitz, Edward A. Stadtmauer, Shin Mineshi, Richard Ambinder, Timothy Fenske, Mary Horowitz, Richard Fisher, Marcie Tomblyn
Journal: Journal of Clinical Oncology (2013)

Purpose This clinical trial evaluated standard-dose radioimmunotherapy with a chemotherapy-based transplantation regimen followed by autologous hematopoietic cell transplantation versus rituximab with the same regimen in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients with chemotherapy-sensitive persistent or relapsed DLBCL were randomly assigned to receive iodine-131 tositumomab (dosimetric dose of 5 mCi on day −19 and therapeutic dose of 0.75 Gy on day −12), carmustine 300 mg/m 2 (day −6), etoposide 100 mg/m 2 twice daily (days −5 to −2), cytarabine 100 mg/m 2 twice daily (days −5 to −2), and melphalan 140 mg/m 2 (day −1; B-BEAM) or rituximab 375 mg/m 2 on days −19 and −12 and the same chemotherapy regimen (R-BEAM). Results Two hundred twenty-four patients were enrolled, with 113 patients randomly assigned to R-BEAM and 111 patients assigned to B-BEAM. Two-year progression-free survival (PFS) rates, the primary end point, were 48.6% (95% CI, 38.6% to 57.8%) for R-BEAM and 47.9% (95% CI, 38.2% to 57%; P = .94) for B-BEAM, and the 2-year overall survival (OS) rates were 65.6% (95% CI, 55.3% to 74.1%) for R-BEAM and 61% (95% CI, 50.9% to 69.9%; P = .38) for B-BEAM. The 100-day treatment-related mortality rates were 4.1% (95% CI, 0.2% to 8.0%) for R-BEAM and 4.9% (95% CI, 0.8% to 9.0%; P = .97) for B-BEAM. The maximum mucositis score was higher in the B-BEAM arm (0.72) compared with the R-BEAM arm (0.31; P &lt; .001). Conclusion The B-BEAM and R-BEAM regimens produced similar 2-year PFS and OS rates for patients with chemotherapy-sensitive relapsed DLBCL. No differences in toxicities other than mucositis were noted.
Reduction of Glucose Metabolic Activity Is More Accurate than Change in Size at Predicting Histopathologic Response to Neoadjuvant Therapy in High-Grade Soft-Tissue Sarcomas
Authors: Vladimir Evilevitch, Wolfgang A. Weber, William D. Tap, Martin Allen-Auerbach, Kira Chow, Scott D. Nelson, Fredrick R. Eilber, Jeffery J. Eckardt, Robert M. Elashoff, Michael E. Phelps, Johannes Czernin, Fritz C. Eilber
Journal: Clinical Cancer Research (2008)

Change in tumor size as classified by Response Evaluation Criteria in Solid Tumors poorly correlates with histopathologic response to neoadjuvant therapy in patients with soft-tissue sarcomas. The aim of this study was to prospectively evaluate whether positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) allows for a more accurate evaluation of histopathologic response.From January 2005 to January 2007, 42 patients with resectable biopsy-proven high-grade soft-tissue sarcoma underwent a FDG-PET/computed tomography scan before and after neoadjuvant treatment. Relative changes in tumor FDG uptake and size from the baseline to the follow-up scan were calculated, and their accuracy for assessment of histopathologic response was compared by receiver operating characteristic curve analysis. Histopathologic response was defined as > or =95% tumor necrosis.In histopathologic responders (n = 8; 19%), reduction in tumor FDG uptake was significantly greater than in nonresponders (P < 0.001), whereas no significant differences were found for tumor size (P = 0.24). The area under the receiver operating characteristic curve for metabolic changes was 0.93, but only 0.60 for size changes (P = 0.004). Using a 60% decrease in tumor FDG uptake as a threshold resulted in a sensitivity of 100% and a specificity of 71% for assessment of histopathologic response, whereas Response Evaluation Criteria in Solid Tumors showed a sensitivity of 25% and a specificity of 100%.Quantitative FDG-PET was significantly more accurate than size-based criteria at assessing histopathologic response to neoadjuvant therapy. FDG-PET should be considered as a modality to monitor treatment response in patients with high-grade soft-tissue sarcoma.
Intrathoracic tuberculous lymphadenopathy: clinical and bronchoscopic features in 17 adults without parenchymal lesions.
Authors: R. Baran, M. Tor, K. Tahaoglu, K. Ozvaran, A. Kir, O. Kizkin, H. Turker
Journal: Thorax (1996)

BACKGROUND: Whilst intrathoracic lymphadenitis is a characteristic sign of primary tuberculosis in children, its presence without parenchymal lesions in adults is unusual and makes the diagnosis using noninvasive techniques difficult. The diagnostic role of bronchoscopy in adults with intrathoracic tuberculous lymphadenitis is reported. METHODS: Seventeen patients with intrathoracic lymphadenopathy seen during 1993 who had all undergone bronchoscopy and had been found to have tuberculosis in the absence of any parenchymal lung lesions were evaluated retrospectively. RESULTS: Right paratracheal lymphadenopathy was observed on the plain chest radiograph in all the patients. Fifteen of the 17 patients had an endobronchial abnormality and samples taken at bronchoscopy gave a definitive diagnosis in nine (53%) of the 17. Four patients had ulcerating endobronchial granuloma and all had biopsy samples positive for tuberculosis. Transbronchial or transcarinal needle aspiration samples were diagnostic in five of 11 patients (45%) subjected to the procedure. Peripheral lymph node biopsy diagnosed tuberculosis in two cases and in the remaining six patients the diagnosis wa achieved by mediastinoscopy or thoracotomy. CONCLUSIONS: Bronchoscopy has an important role in the diagnosis of intrathoracic tuberculous lymphadenopathy in adults and should be considered before other invasive procedures.