tbuckley/cabot-search huggingface dataset:
Tissue concentration and urinary excretion pattern of sulfofluorescein by the rat kidney.
Authors: U Ammer, Y u Natochin, K J Ullrich
Journal: Journal of the American Society of Nephrology (1993)

In order to find a fluorescein analog that is excreted in a way similar to p-aminohippurate (PAH) and is suitable to register excretion into the urine and also to monitor continuously the concentration within cortical tissue, the interference of fluorescein, sulfofluorescein (SF), and fluorescein-5(6)-sulfonate with the contraluminal transport systems of PAH, succinate, and sulfate and with the luminal transport system of sulfate and lactate was evaluated. All three substances exerted a strong inhibitory potency against contraluminal PAH uptake (apparent Ki, 0.06 to 0.1 mmol/L) and also showed a moderate to small inhibitory potency against contraluminal sulfate transport (apparent Ki, 0.7 to 5.3 mmol/L). None of the three substrates interacted with the contraluminal dicarboxylate transport. Luminally, fluorescein and SF interacted with the lactate transporter (apparent Ki, approximately 3.0 mmol/L), whereas SF and fluorescein-5(6)-sulfonate had a very weak inhibitory potency against luminal sulfate transport (apparent Ki, 30 to 40 mmol/L). Because of its relatively low interference with the contraluminal sulfate transport, we preferred SF in the following study (protein binding, 88%) over fluorescein-5(6)-sulfonate (protein binding, 43.3%) and fluorescein (protein binding, 77.3%). A bolus injection of SF was given together with [14C]inulin into the jugular vein to rats in mannitol diuresis. Excretion of both substances in the urine was measured in 5-min samples. Fluorescence of the kidney surface was monitored at the exposed kidney with a photocell (excitation light, 470 nm; emission light, 530 nm). The effect of interfering substances was evaluated by their application 1 min before, simultaneously, or 1 min after SF bolus injection. PAH < probenecid < apalcillin inhibited SF excretion in the urine and, to a similar degree, SF fluorescence in cortical tissue. Inhibition was strongest when the substances were given simultaneously with SF. With the injection of alpha-ketoglutarate, glutarate, and succinate, an increase of SF excretion in the urine and, partially also, of SF content in tissue was seen. Tetrafluorosuccinate and mercaptosuccinate inhibited urinary SF excretion and tissue fluorescence strongly. Therefore, SF secretion is completely inhibited whereas filtration remained unaffected. The injection of acetate, lactate, and pyruvate as well as of 2-chloropropionate and thiosulfate did not change urinary excretion and tissue fluorescence of SF significantly. In SF-preloaded animals, the injection of probenecid, apalcillin, tetrafluorosuccinate, and mercaptosuccinate caused an immediate decrease of cellular SF content, whereas the injection of glutarate caused an increase. SF fluorescence in tissue was linearly related to urinary excretion of SF, whereas urinary excretion of inulin was barely affected.(ABSTRACT TRUNCATED AT 400 WORDS)
GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis
Authors: J J LoTurco, D F Owens, M J Heath, M B Davis, A R Kriegstein
Journal: Neuron (1995)

We have found that, during the early stages of cortical neurogenesis, both GABA and glutamate depolarize cells in the ventricular zone of rat embryonic neocortex. In the ventricular zone, glutamate acts on AMPA/kainate receptors, while GABA acts on GABAA receptors. GABA induces an inward current at resting membrane potentials, presumably owing to a high intracellular Cl- concentration maintained by furosemide-sensitive Cl- transport. GABA and glutamate also produce increases in intracellular Ca2+ in ventricular zone cells, in part through activation of voltage-gated Ca2+ channels. Furthermore, GABA and glutamate decrease the number of embryonic cortical cells synthesizing DNA. Depolarization with K+ similarly decreases DNA synthesis, suggesting that the neurotransmitters act via membrane depolarization. Applied alone, GABAA and AMPA/kainate receptor antagonists increase DNA synthesis, indicating that endogenously released amino acids influence neocortical progenitors in the cell cycle. These results demonstrate a novel role for amino acid neurotransmitters in regulating neocortical neurogenesis.
Gender modulates cardiac phenotype development in genetically modified mice
Authors: X DU
Journal: Cardiovascular Research (2004)

Recent research using genetically modified mice has revealed significant sex differences in cardiac phenotypes. In the majority of strains, females display a lower mortality, less severe hypertrophy, better preserved function and mitigated cardiac pathology compared with male counterparts. Thus, gender is an independent determinant for the development of cardiac phenotype in murine models. While there is strong evidence for estrogen as a cardiac protector, emerging evidence indicates adverse actions of testicular hormones that might be responsible in part for the sex differences. Studies using mouse models have also revealed novel information on signalling mechanisms mediating the sex difference.
Isolation of plasma membrane from human neutrophils and determination of cytochrome b and quinone content
Authors: EP Sloan, DR Crawford, DL Schneider
Journal: The Journal of Experimental Medicine (1981)

Analyses of plasma membrane and other subcellular fractions indicate that the primary location of cytochrome b in human neutrophils is not the plasma membrane. The procedure developed for the purification of plasma membrane from fresh human neutrophils yielded a 14-fold enrichment in the marker enzyme 5'-nucleotidase and a 10-fold enrichment in ouabain-sensitive ATPase. On sucrose density gradients, the peak density of 5'-nucleotidase activity was 1.12 g/ml, and was shifted after digitonin addition to 1.15 g/ml. Protein in the plasma membrane equalled approximately 8 percent of the whole cell protein. A b-type cytochrome was found to be present in the plasma membrane fraction at a concentration of 205 pmol/mg of protein, which is three times greater than that in the neutrophil overall. Although this cytochrome has been reported previously in the neutrophil, this is the first determination for purified plasma membrane and may indicate that b-type cytochrome has a dual localization in the human neutrophil. Differential centrifugation results suggest that the primary location is in the granules, probably specific granules. Quinone content in the plasma membrane was found to be 740 pmol/mg of protein, a concentration two times greater than in the whole cell. Such a small enhancement of quinone indicates that quinone also is not primarily located in the plasma membrane.
Follicular Homing T Helper (Th) Cells and the Th1/Th2 Paradigm
Authors: Charles R. Mackay
Journal: The Journal of Experimental Medicine (2000)

The Th1/Th2 paradigm is a cornerstone for our understanding of T cell responses ([1][1]). It conveniently subdivides T cell immune responses into those specialized for defense against intracellular pathogens including viruses and some bacteria (Th1), and a second for defense against large
Inhibitors of XIAP sensitize CD40-activated chronic lymphocytic leukemia cells to CD95-mediated apoptosis
Authors: Arnon P. Kater, Frank Dicker, Massimo Mangiola, Kate Welsh, Richard Houghten, John Ostresh, Adel Nefzi, John C. Reed, Clemencia Pinilla, Thomas J. Kipps
Journal: Blood (2005)
CCL3 Restores Bacterial Clearance in Nontypeable Haemophilus Influenzae (NTHi)-induced Otitis Media in TNF−/− mice
Authors: S.I. Wasserman, A. Leichtle, M. Hernandez, K. Yamasaki, K. Pak, A. Ryan
Journal: Journal of Allergy and Clinical Immunology (2009)
An Optimized Telomerase-Specific Lentivirus for Optical Imaging of Tumors
Authors: Song-Tao Yu, Yin-Bing Yang, Guang-Ping Liang, Chuan Li, Ling Chen, Chun-Meng Shi, Xu-Dong Tang, Chang-Zhu Li, Ling Li, Guo-Zheng Wang, Yu-Yun Wu, Shi-Ming Yang, Dian-Chun Fang
Journal: Cancer Research (2010)

Abstract Advances in medical imaging techniques, such as ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography, have made great progress in detecting tumors. However, these imaging techniques are unable to differentiate malignant tumors from benign ones. Recently developed optical imaging of tumors in small animals provides a useful method to distinguish malignant tumors from their surrounding normal tissues. Human telomerase reverse transcriptase (hTERT) is normally inactivated in most somatic cells, whereas it is commonly reactivated in many cancer cells. In this study, we constructed a lentiviral vector that expresses green fluorescent protein (GFP) driven by an optimized hTERT promoter to create a noninvasive tumor-specific imaging methodology. The activity of this optimized hTERT promoter was found to be equal to the activity of SV40 and cytomegalovirus promoters. In vitro experiments showed that GFP was only expressed in telomerase-positive tumor cells infected with this lentivirus, whereas there was no GFP expression in telomerase-negative tumor cells or normal somatic cells. We also found that subcutaneous telomerase-positive tumors could be visualized 24 hours after an intratumoral injection with this lentivirus by using a charge-coupled device (CCD) camera. In contrast, telomerase-negative tumors could not be imaged after an intratumoral injection even for 30 days. These results suggest that infection with lentivirus containing this optimized hTERT promoter might be a useful diagnostic tool for the real-time visualization of macroscopically invisible tumor tissues using a highly sensitive CCD imaging system. Cancer Res; 70(7); 2585–94
Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease
Authors: Bertalan Mesko, Szilard Poliska, Andrea Váncsa, Zoltan Szekanecz, Karoly Palatka, Zsolt Hollo, Attila Horvath, Laszlo Steiner, Gabor Zahuczky, Janos Podani, and Laszlo Nagy
Journal: Genome Medicine (2013)

Biological therapies have been introduced for the treatment of chronic inflammatory diseases including rheumatoid arthritis (RA) and Crohn's disease (CD). The efficacy of biologics differs from patient to patient. Moreover these therapies are rather expensive, therefore treatment of primary non-responders should be avoided.We addressed this issue by combining gene expression profiling and biostatistical approaches. We performed peripheral blood global gene expression profiling in order to filter the genome for target genes in cohorts of 20 CD and 19 RA patients. Then RT-quantitative PCR validation was performed, followed by multivariate analyses of genes in independent cohorts of 20 CD and 15 RA patients, in order to identify sets ofinterrelated genes that can separate responders from non-responders to the humanized chimeric anti-TNFalpha antibody infliximab at baseline.Gene panels separating responders from non-responders were identified using leave-one-out cross-validation test, and a pool of genes that should be tested on larger cohorts was created in both conditions.Our data show that peripheral blood gene expression profiles are suitable for determining gene panels with high discriminatory power to differentiate responders from non-responders in infliximab therapy at baseline in CD and RA, which could be cross-validated successfully. Biostatistical analysis of peripheral blood gene expression data leads to the identification of gene panels that can help predict responsiveness of therapy and support the clinical decision-making process.
Impact of theophylline/corticosteroid combination therapy on sputum hydrogen sulfide levels in patients with COPD
Authors: P. A. Kirkham, M. Whiteman, P. G. Winyard, G. Caramori, F. Gordon, P. A. Ford, P. J. Barnes, I. M. Adcock, K. F. Chung
Journal: European Respiratory Journal (2014)

To the Editor: 

Hydrogen sulfide (H2S) has emerged as a new and important endogenous regulator of inflammation in recent years [1] and may also protect from emphysema induced by cigarette smoke exposure [2]. We have also recently shown that H2S can inhibit airway smooth muscle cell proliferation and inflammatory mediator release in vitro [3]. Serum levels of H2S positively correlate with the decline in lung function in chronic obstructive pulmonary disease (COPD) and were significantly lower in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients compared with those in GOLD I [4]. Existing therapies for COPD, such as corticosteroids or long-acting anticholinergic agents, may reduce the exacerbation rate but do not significantly slow disease progression. A previous study has shown that theophylline alone had no impact on serum H2S levels and is of limited value in the management of stable COPD [5]. Interestingly, sputum H2S measured in patients with asthma correlated with sputum neutrophil counts and the degree of airflow obstruction measured by forced expiratory volume in 1 s (FEV1) % predicted [6]. Moreover, combination therapy of an inhaled glucocorticoid with low-dose theophylline has been shown to attenuate airway inflammation in patients with COPD and reverse glucocorticoid resistance [7]. We therefore investigated whether the combination of inhaled corticosteroid and low-dose theophylline, as opposed to …
Evidence for two-stage binding by the 175-kD erythrocyte binding antigen of Plasmodium falciparum.
Authors: K C Kain, P A Orlandi, J D Haynes, K L Sim, D E Lanar
Journal: The Journal of Experimental Medicine (1993)

Plasmodium falciparum malaria merozoites invade human erythrocytes bearing sialic acid in a multistage process involving the sialic acid-dependent binding of a malaria molecule, the 175-kD erythrocyte binding antigen (EBA-175). We show here that after the initial interaction of EBA-175 with its sialic acid-containing erythrocyte determinant, endogenous proteases can cleave EBA-175 to 65-kD fragment(s), whose binding to erythrocytes is sialic acid independent. A 65-kD fragment was immunoprecipitated by antibodies against peptides between residues 354 and 1061 but not beyond residue 1062. Binding experiments utilizing combinations of native protein, expression-PCR-synthesized EBA-175 polypeptides, peptide synthesis, and antibodies, demonstrated that sialic acid-independent binding could be further mapped to a small (about 40-amino acid) homologous part of the dimorphic allelic region of EBA-175, residues 898-938 (Camp strain numbering). These data support a two-step binding hypothesis and are discussed in relation to the formation of a junction between the merozoite and the erythrocyte, and the finding that after the interaction of some viruses with specific cellular receptors, they undergo conformational changes or cleavage permitting membrane fusion with the host cell.
Hippocampal sparing radiotherapy for pediatric medulloblastoma: impact of treatment margins and treatment technique
Authors: N. Patrik Brodin, Per Munck af Rosenschöld, Malin Blomstrand, Anne Kiil-Berthlesen, Christian Hollensen, Ivan R. Vogelius, Birgitta Lannering, Søren M. Bentzen, Thomas Björk-Eriksson
Journal: Neuro-Oncology (2013)

We investigated how varying the treatment margin and applying hippocampal sparing and proton therapy impact the risk of neurocognitive impairment in pediatric medulloblastoma patients compared with current standard 3D conformal radiotherapy.We included 17 pediatric medulloblastoma patients to represent the variability in tumor location relative to the hippocampal region. Treatment plans were generated using 3D conformal radiotherapy, hippocampal sparing intensity-modulated radiotherapy, and spot-scanned proton therapy, using 3 different treatment margins for the conformal tumor boost. Neurocognitive impairment risk was estimated based on dose-response models from pediatric CNS malignancy survivors and compared among different margins and treatment techniques.Mean hippocampal dose and corresponding risk of cognitive impairment were decreased with decreasing treatment margins (P < .05). The largest risk reduction, however, was seen when applying hippocampal sparing proton therapy-the estimated risk of impaired task efficiency (95% confidence interval) was 92% (66%-98%), 81% (51%-95%), and 50% (30%-70%) for 3D conformal radiotherapy, intensity-modulated radiotherapy, and proton therapy, respectively, for the smallest boost margin and 98% (78%-100%), 90% (60%-98%), and 70% (39%-90%) if boosting the whole posterior fossa. Also, the distance between the closest point of the planning target volume and the center of the hippocampus can be used to predict mean hippocampal dose for a given treatment technique.We estimate a considerable clinical benefit of hippocampal sparing radiotherapy. In choosing treatment margins, the tradeoff between margin size and risk of neurocognitive impairment quantified here should be considered.
Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids.
Authors: E M Lafer, J Rauch, C Andrzejewski, D Mudd, B Furie, B Furie, R S Schwartz, B D Stollar
Journal: The Journal of Experimental Medicine (1981)

Hybridomas the produce anti-DNA autoantibodies were prepared from spleen cells of unimmunized MRL/1 mice, a strain that spontaneously develops severe systemic lupus erythematous (SLE). Reactivities of these monoclonal antibodies with a wide range of polynucleotides prompted tests of their reactions with phospholipids which, like polynucleotides, contain diester-linked phosphate groups in their backbones. In competitive radioimmunoassays, cardiolipin, phosphatidic acid, and phosphatidyl glycerol blocked the binding of these hybridoma antibodies to denatured DNA. These phospholipids also specifically inhibited the reaction between a hybridoma antibody and a site-specific anti-idiotypic antibody. The antinuclear reaction of one of these antibodies was specifically inhibited by cardiolipin. This same antibody prolonged the activated partial thromboplastin time in a manner characteristic of a lupus anticoagulant, presumably by binding to phospholipid in the test system. The polyspecific reactivity of a single molecular species of lupus autoantibody suggests that some of the diverse serological abnormalities of SLE may be a result of the binding of certain autoantibodies to a phosphodiester-containing epitope that is present in diverse biological molecules.
Role of Thymic Stromal Lymphopoietin (TSLP) in Chronic Rhinosinusitis
Authors: A. Kato, J.A. Poposki, D.R. Nagarkar, B.K. Tan, M.R. Comeau, A.L. Budelsky, L. Suh, J. Norton, K.E. Harris, A.T. Peters, L.C. Grammer, R.K. Chandra, D.B. Conley, R.C. Kern, R.P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2012)
Age related changes in gut physiology and nutritional status.
Authors: L B Lovat
Journal: Gut (1996)

Few gastrointestinal functions decline to an important extent as a result of old age alone and there is little clinical evidence that significant malnutrition occurs in any normal elderly person as a result of the aging process itself. Nevertheless, decreased gastrointestinal reserve makes older people highly sensitive to minor insults and decompensation can rapidly occur. Drugs appreciably affect taste sensation, which is already blunted and psychological as well as physical disability can have a major impact on appetite. Malabsorption can be caused by gastric hypochlorhydria with small bowel bacterial overgrowth and while gastrointestinal dysmotility can be caused by subclinical hypothyroidism, it can improve in response to physical exercise. Evidence is now mounting that thorough investigation of gastrointestinal disturbances in elderly patients coupled with intensive nutritional support can make a very real impact on their outcome. Gastroenterologists should therefore seek out and actively treat gastrointestinal disorders in the elderly and not just ascribe them to old age.
The Generalist/Cardiovascular Specialist: A Proposal for a New Training Track
Authors: Valentin Fuster
Journal: Annals of Internal Medicine (1997)

The economic forces that are reshaping the delivery of health care in the United States have led to intense examination of the appropriate roles for specialists and generalists. Resolving this issue has profound implications for the future of U.S. health care and for the economic health of academic training centers and individual physicians. The issues are particularly intense in cardiovascular care, a field that has had dramatic success in the application of new diagnostic and therapeutic technology and rapid growth in specialist practitioners but is now under pressure to shrink its ranks. A new generalist/cardiovascular specialist training track and a parallel reduction in the number of standard fellowship training positions in cardiovascular disease may be a partial solution. The first 2 years of the proposed 5-year program would consist of training in internal medicine, the final 2 would consist of training in cardiovascular disease, and the middle year would be a flexible combination of the two. Graduates would be Board eligible in internal medicine but would have enhanced competency in cardiovascular disease. This plan may improve the balance between generalists and specialists, improve the quality of primary and specialized cardiovascular care, and strengthen departments of medicine and academic training centers while facing new economic realities.
The ‘anatomic shunt test’ in clinical practice; contemporary description of test and in-service evaluation
Authors: Damien K Y Ming, Mehul S Patel, Nicholas S Hopkinson, Simon Ward, Michael I Polkey
Journal: Thorax (2013)

The 100% oxygen shunt test for detecting right-to-left anatomical shunting was originally described 70 years ago. However, its clinical value is not yet established. We conducted an audit in 80 patients undergoing the test between 1996 and 2012 in a tertiary referral centre. A significant difference (p=0.02) existed between the median shunt percentages where anatomical shunting was identified (10.2%) and absent (5.0%). The area under the curve for a ROC plot was 0.70. A shunt percentage of 8.3 had a sensitivity of 80% and specificity of 75% for detection of an anatomic shunt. We conclude the test is satisfactory for the first-line investigation for anatomic shunting.
Making music in the operating theatre
Authors: D. C. Bosanquet, J. C. Glasbey, R. Chavez
Journal: BMJ (2014)

Wake me up before you go-go

One hundred years ago, Pennsylvanian surgeon Evan Kane penned a brief letter to JAMA in which he declared himself a rigorous proponent of the “benefic [sic] effects of the phonograph within the operating room.” To Kane, it was an optimal means of “calming and distracting the patient from the horror of their situation.” Perhaps it was by harnessing these distracting properties that he was able to face the operating room as both patient and surgeon, becoming the first person to perform an auto-appendicectomy in 1920. A century later, although we have more in our anaesthetic armamentarium than distraction, music can still bring a calming effect to the operating team and surgical patient.

Music and healing share an intertwined history. As early as 4000 BC the Codex haburami (hallelujah to the healer), delivered by harp playing priests and musicians, served as part payment for medicinal services. Aristotle recognised the innate ability of melodies to surpass “feelings such as pity and fear, or enthusiasm,” and thus “heal and purify the soul.” The Greeks identified Apollo as the father of both healing and music, alongside his many other accolades (as God of light, sun, truth, prophecy, plague and poetry). Two physicians famed for using their musical abilities to implement medical achievements described chest percussion (Leopold Joseph Auenbrugger, 1722-1809) and invented the …