tbuckley/cabot-search huggingface dataset:
Magnetic Resonance Studies of Brain Function and Neurochemistry
Authors: Kâmil Uğurbil, Gregor Adriany, Peter Andersen, Wei Chen, Rolf Gruetter, Xiaoping Hu, Hellmut Merkle, Dae-Shik Kim, Seong-Gi Kim, John Strupp, Xiao Hong Zhu, Seiji Ogawa
Journal: Annual Review of Biomedical Engineering (2000)

▪ Abstract In the short time since its introduction, magnetic resonance imaging (MRI) has rapidly evolved to become an indispensable tool for clinical diagnosis and biomedical research. Recently, this methodology has been successfully used for the acquisition of functional, physiological, and biochemical information in intact systems, particularly in the human body. The ability to map areas of altered neuronal activity in the brain, often referred to as functional magnetic resonance imaging (fMRI), is probably one of the most significant recent achievements that rely on this methodology. This development has permitted the examination of functional specialization in human and animal brains with unprecedented spatial resolution, as demonstrated by mapping at the level of orientation and ocular dominance columns in the visual cortex. These functional imaging studies are complemented by the ability to study neurochemistry using magnetic resonance spectroscopy, allowing the determination of metabolic processes that support neurotransmission and neurotransmission rates themselves.
Non‐invasive measurement of cardiac output by whole‐body bio‐impedance during dobutamine stress echocardiography: Clinical implications in patients with left ventricular dysfunction and ischaemia
Authors: Marina Leitman, Edgar Sucher, Edo Kaluski, Ruth Wolf, Eli Peleg, Yaron Moshkovitz, Olga Milo‐Cotter, Zvi Vered, Gad Cotter
Journal: European Journal of Heart Failure (2005)
Bladder Cancer: Narrowing the Gap Between Evidence and Practice
Authors: Maha H.A. Hussain, David P. Wood, Dean F. Bajorin, Bernard H. Bochner, Robert Dreicer, Donald L. Lamm, Michael A. O'Donnell, Arlene O. Siefker-Radtke, Dan Theodorescu, Colin P. Dinney
Journal: Journal of Clinical Oncology (2009)

The American Cancer Society estimates that bladder cancer (BC) accounted for more than 14,000 deaths in 2008. At only 14 months, the median survival for patients with metastatic BC has not significantly changed during the last two decades. No new agents have been approved for BC treatment for more than a decade, few new therapies are being tested in this area, and research in BC has historically been underfunded. In addition, several therapeutic interventions known to influence survival have not been widely adopted into practice.

Cystectomy is often delayed in patients with high-risk non–muscle-invasive BC. In muscle-invasive disease, mounting evidence supports the importance of a more extensive surgical approach and the beneficial role of neoadjuvant chemotherapy on survival; however, a wide gap remains between evidence and practice. Even in academic centers, only a few patients with muscle-invasive disease undergo a more extended lymph node dissection and receive neoadjuvant chemotherapy. A recent study1 evaluating the integration of chemotherapy for BC in the United States using the National Cancer Database revealed that only 11.6% of patients received any perioperative chemotherapy, most of those in the adjuvant setting.

Given these challenges, two imperatives are before us: (1) improving patient outcomes by defining and implementing optimal standards of care, and (2) identifying and prioritizing specific strategies to advance development of more effective therapies for patients with BC.
Heparin-Binding Epidermal Growth Factor-Like Growth Factor Regulates Fibroblast Growth Factor-2 Expression in Aortic Smooth Muscle Cells
Authors: Kimberly A. Peifley, Gregory F. Alberts, Debbie K.W. Hsu, Sheau-Line Y. Feng, Jeffrey A. Winkles
Journal: Circulation Research (1996)

Heparin-binding epidermal growth factor–like growth factor (HB-EGF) is a vascular smooth muscle cell (SMC) mitogen and chemotactic factor that is expressed by endothelial cells, SMCs, monocytes/macrophages, and T lymphocytes. Both the membrane-anchored HB-EGF precursor and the secreted mature HB-EGF protein are biologically active; thus, HB-EGF may stimulate SMC growth via autocrine, paracrine, and juxtacrine mechanisms. In the present study, we report that HB-EGF treatment of serum-starved rat aortic SMCs can induce fibroblast growth factor (FGF)-2 (basic FGF) gene expression but not FGF-1 (acidic FGF) gene expression. Increased FGF-2 mRNA expression is first detectable at 1 hour after HB-EGF addition, and maximal FGF-2 mRNA levels, corresponding to an ≈46-fold level of induction, are present at 4 hours. The effect of HB-EGF on FGF-2 mRNA levels appears to be mediated primarily by a transcriptional mechanism and requires de novo synthesized proteins. HB-EGF induction of FGF-2 mRNA levels can be inhibited by treating cells with the anti-inflammatory glucocorticoid dexamethasone or the glycosaminoglycan heparin. Finally, Western blot analyses indicate that HB-EGF–treated SMCs also produce an increased amount of FGF-2 protein. These results indicate that HB-EGF expressed at sites of vascular injury or inflammation in vivo may upregulate FGF-2 production by SMCs.
Phase I Study of Tirapazamine Plus Cisplatin/Etoposide and Concurrent Thoracic Radiotherapy in Limited-Stage Small Cell Lung Cancer (S0004)
Authors: Quynh-Thu Le, Jason McCoy, Stephen Williamson, Janice Ryu, Laurie E. Gaspar, Martin J. Edelman, Shaker R. Dakhil, Stanley D. Sides, John J. Crowley, David R. Gandara
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To determine the feasibility and a recommended phase II dose of tirapazamine when combined with chemoradiotherapy in limited-stage small cell lung cancer (LSCLC). Experimental Design: Concurrent chemoradiotherapy consisted of two cycles of cisplatin, etoposide, and once-daily radiation to 61 Gy. Tirapazamine (260 mg/m2) was given 1 h before cisplatin with planned dose escalation to 330 mg/m2 in the absence of dose-limiting toxicity, defined as ≥33% esophagitis (grade 3 or above). Consolidation therapy consisted of two cycles of tirapazamine (330 mg/m2), cisplatin, and etoposide. Complete responders received prophylactic cranial irradiation. Results: Thirty patients were enrolled at the 260 mg/m2 tirapazamine dose. All had performance status of 0–1. By comparison with S9713, a predecessor Southwest Oncology Group study in LSCLC that used the same concurrent chemoradiotherapy without tirapazamine, the present trial showed a higher rate of grade 3–4 esophagitis (34% versus 22%), vomiting (34% versus 23%), and febrile neutropenia (7% versus 2%). The consolidation phase was relatively well tolerated, with grade 4 neutropenia in 44% and febrile neutropenia in 5% of patients. There were two treatment-related deaths: one from neutropenic fever and one from respiratory infection. The overall response rate was 80%, and the median survival was 22 months. Conclusions: Protocol-defined dose-limiting toxicity was observed at the initial tirapazamine dose, precluding dose escalation. Compared with S9713, the addition of tirapazamine increased the incidence of vomiting, neutropenia, and febrile neutropenia, although the overall toxicity profile remained acceptable. In view of the observed favorable survival, further study of tirapazamine in LSCLC is warranted.
Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome
Authors: K. S. Boparai, J. B. Reitsma, V. Lemmens, T. A. M. van Os, E. M. H. Mathus-Vliegen, J. J. Koornstra, F. M. Nagengast, L. P. van Hest, J. J. Keller, E. Dekker
Journal: Gut (2010)

Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable evidence concerning the magnitude of a possible excess risk is necessary to determine whether preventive measures, like screening colonoscopies, in FDRs are justified.We analysed the incidence rate of CRC in FDRs and compared this with the general population through person-year analysis after adjustment for demographic characteristics. Population-based incidence data from the Eindhoven Cancer Registry during the period 1970-2006 were used to compare observed numbers of CRC cases in FDRs with expected numbers based on the incidence in the general population.A total of 347 FDRs (41% male) from 57 pedigrees were included, contributing 11 053 person-years of follow-up. During the study period, a total of 27 CRC cases occurred among FDRs compared to five expected CRC cases (p<0.001). The RR of CRC in FDRs compared to the general population was 5.4 (95% CI 3.7 to 7.8). Four FDRs satisfied the criteria for HPS. Based on the estimated HPS prevalence of 1:3000 in the general population the projected RR of HPS in FDRs was 39 (95% CI 13 to 121).FDRs of HPS patients have an increased risk for both CRC and HPS compared to the general population. Hence, as long as no genetic substrate has been identified, screening colonoscopies for FDRs seem justified but this needs to be prospectively evaluated.
Systematic review of antistaphylococcal antibiotic therapy in cystic fibrosis
Authors: K. McCaffery, R. E Olver, M. Franklin, S. Mukhopadhyay
Journal: Thorax (1999)

<h3>BACKGROUND</h3> The respiratory tract in patients with cystic fibrosis is frequently colonised with <i>Staphylococcus aureus</i>. There is great diversity of clinical practice in this area of cystic fibrosis. A systematic review was conducted to study the evidence relating antistaphylococcal therapy to clinical outcome in patients with cystic fibrosis. <h3>METHODS</h3> A search strategy already evaluated for the study of the epidemiology of cystic fibrosis clinical trials was used. This yielded 3188 references from which 13 clinical trials of antistaphylococcal therapy were identified. <h3>RESULTS</h3> Substantial heterogeneity was observed between trials. In the 13 clinical trials a total of 19 antibiotics were used to assess a wide variety of outcome measures (11 clinical, six laboratory). Both intermittent and continuous treatment strategies were used. Sputum clearance of<i>S aureus</i> was more frequently achieved than any other beneficial outcome. A beneficial effect on pulmonary function was rarely measured or observed. Although five randomised clinical trials were identified, the extent of heterogeneity precluded the use of meta-analysis for further synthesis of information. <h3>CONCLUSIONS</h3> Antistaphylococcal treatment achieves sputum clearance of <i>S aureus</i> in patients with cystic fibrosis. Prophylactic antistaphylococcal treatment in young children with cystic fibrosis is likely to be of clinical benefit. It remains to be determined whether the use of "prophylactic" versus "intermittent" antistaphylococcal therapy in cystic fibrosis is associated with improved lung function and/or chest radiographic scores, an increase in bacterial resistance, or earlier acquisition of<i>Pseudomonas aeruginosa</i>. A large randomised clinical trial lasting approximately two years is urgently required to address this problem.
Coupling of Cardiac Electrical Activity Over Extended Distances by Fibroblasts of Cardiac Origin
Authors: Giedrius Gaudesius, Michele Miragoli, Stuart P. Thomas, Stephan Rohr
Journal: Circulation Research (2003)

Roughly half of the cells of the heart consist of nonmyocardial cells, with fibroblasts representing the predominant cell type. It is well established that individual cardiomyocytes and fibroblasts in culture establish gap junctional communication at the single cell level (short-range interaction). However, it is not known whether such coupling permits activation of cardiac tissue over extended distances (long-range interaction). Long-range interactions may be responsible for electrical synchronization of donor and recipient tissue after heart transplantation and may play a role in arrhythmogenesis. This question was investigated using a novel heterocellular culture model with strands of cardiomyocytes interrupted by cardiac fibroblasts over defined distances. With use of optical recording techniques, it could be shown that impulse propagation along fibroblast inserts was successful over distances up to 300 μm and was characterized by length-dependent local propagation delays ranging from 11 to 68 ms (apparent local “conduction velocities” 4.6±1.8 mm/s, n=23). Involvement of mechanical stretch in this phenomenon was excluded by showing that inserts consisting of communication-deficient HeLa cells were incapable of supporting propagation. In contrast, HeLa cells expressing connexin43 permitted impulse conduction over distances as long as 600 μm. Immunocytochemistry showed that fibroblasts and cardiomyocytes expressed connexin43 and connexin45, whereas connexin40 was absent. These results illustrate that fibroblasts of cardiac origin are capable of synchronizing electrical activity of multicellular cardiac tissue over extended distances through electrotonic interactions. This synchronization is accompanied by extremely large local conduction delays, which might contribute to the generation of arrhythmias in fibrotic hearts.
Bioaerosol lung damage in a worker with repeated exposure to fungi in a water-damaged building.
Authors: D Trout, J Bernstein, K Martinez, R Biagini, K Wallingford
Journal: Environmental Health Perspectives (2001)

There has been increased concern over health effects related to potential exposure of building occupants to bioaerosols. We report the case of a worker with a respiratory illness related to bioaerosol exposure in a water-damaged building with extensive fungal contamination. We performed environmental tests to evaluate potential exposure to fungi, and we used mycotoxin-specific IgG antibody in serologic studies in the attempt to evaluate exposure to mycotoxins. Extensive fungal contamination was documented in many areas of the building. Penicillium, Aspergillus, and Stachybotrys species were the most predominant fungi found in air sampling. Our serologic test was not useful in differentiating workers who were probably occupationally exposed to mycotoxins from those who were not; however, it did yield evidence that individuals may make specific IgG antibodies to macrocyclic tricothecene mycotoxins. Further research is needed concerning health effects related to bioaerosol exposures, particularly regarding markers of exposure to specific fungi that may produce mycotoxins. In the absence of clinical tools specific for evaluation of mycotoxin-related illness, a systematic clinical approach for evaluating persons with suspected building-related respiratory illness is warranted.
Elevated Rates of Nonsynonymous Substitution in Island Birds
Authors: Kevin P. Johnson, Jon Seger
Journal: Molecular Biology and Evolution (2001)

Slightly deleterious mutations are expected to fix at relatively higher rates in small populations than in large populations. Support for this prediction of the nearly-neutral theory of molecular evolution comes from many cases in which lineages inferred to differ in long-term average population size have different rates of nonsynonymous substitution. However, in most of these cases, the lineages differ in many other ways as well, leaving open the possibility that some factor other than population size might have caused the difference in substitution rates. We compared synonymous and nonsynonymous substitutions in the mitochondrial cyt b and ND2 genes of nine closely related island and mainland lineages of ducks and doves. We assumed that island taxa had smaller average population sizes than those of their mainland sister taxa for most of the time since they were established. In all nine cases, more nonsynonymous substitutions occurred on the island branch, but synonymous substitutions showed no significant bias. As in previous comparisons of this kind, the lineages with smaller populations might differ in other respects that tend to increase rates of nonsynonymous substitution, but here such differences are expected to be slight owing to the relatively recent origins of the island taxa. An examination of changes to apparently "preferred" and "unpreferred" synonymous codons revealed no consistent difference between island and mainland lineages
QUANTITATIVE STUDIES OF PHYTOHEMAGGLUTININ-INDUCED DNA AND RNA SYNTHESIS IN NORMAL AND AGAMMAGLOBULINEMIC LEUKOCYTES
Authors: Douglass C. Tormey, Roberta Kamin, H. Hugh Fudenberg
Journal: The Journal of Experimental Medicine (1967)

Leukocytes from nine patients with acquired agammaglobulinemia were studied in vitro. Synthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) induced by phytohemagglutinin was measured by determination of the degree of incorporation of labeled precursor. Synthesis of both DNA and RNA was decreased in the agammaglobulinemic cells. The presence of an inhibitor in the patients' sera could not be demonstrated. These results suggest that the basic defect in agammaglobulinemia is cellular rather than humoral.
Molecular Basis of Cardioprotection
Authors: Gerd Heusch
Journal: Circulation Research (2015)

Reperfusion is mandatory to salvage ischemic myocardium from infarction, but reperfusion per se contributes to injury and ultimate infarct size. Therefore, cardioprotection beyond that by timely reperfusion is needed to reduce infarct size and improve the prognosis of patients with acute myocardial infarction. The conditioning phenomena provide such cardioprotection, insofar as brief episodes of coronary occlusion/reperfusion preceding (ischemic preconditioning) or following (ischemic postconditioning) sustained myocardial ischemia with reperfusion reduce infarct size. Even ischemia/reperfusion in organs remote from the heart provides cardioprotection (remote ischemic conditioning). The present review characterizes the signal transduction underlying the conditioning phenomena, including their physical and chemical triggers, intracellular signal transduction, and effector mechanisms, notably in the mitochondria. Cardioprotective signal transduction appears as a highly concerted spatiotemporal program. Although the translation of ischemic postconditioning and remote ischemic conditioning protocols to patients with acute myocardial infarction has been fairly successful, the pharmacological recruitment of cardioprotective signaling has been largely disappointing to date.
A Spleen Tyrosine Kinase Inhibitor Reduces the Severity of Established Glomerulonephritis
Authors: Jennifer Smith, John P. McDaid, Gurjeet Bhangal, Ratana Chawanasuntorapoj, Esteban S. Masuda, H. Terence Cook, Charles D. Pusey, Frederick W.K. Tam
Journal: Journal of the American Society of Nephrology (2009)

Antibody-mediated glomerulonephritis, including that resulting from immune complexes, is an important cause of renal failure and is in need of more specific and effective treatment. Binding of antibody or immune complexes to Fc receptors activates intracellular signal transduction pathways, including spleen tyrosine kinase (Syk), leading to the production of inflammatory cytokines. We examined the effect of R788 (fostamatinib disodium), an oral prodrug of the selective Syk inhibitor R406, in nephrotoxic nephritis in Wistar-Kyoto rats. Treatment with R788 reduced proteinuria, tissue injury, glomerular macrophage and CD8+ cell numbers, and renal monocyte chemoattractant protein-1 (MCP-1) and IL-1beta, even when we started treatment after the onset of glomerulonephritis. When we administered R788 from days 4 to 10, glomerular crescents reduced by 100% (P < 0.01) compared with the vehicle group. When we administered R788 treatment from days 7 to 14, established glomerular crescents reversed (reduced by 21%, P < 0.001), and renal function was better than the vehicle group (P < 0.001). In vitro, R406 downregulated MCP-1 production from mesangial cells and macrophages stimulated with aggregated IgG. These results suggest that Syk is an important therapeutic target for the treatment of glomerulonephritis.
Analysis Of Severe Asthma Phenotypes By Using High-Resolution Computed Tomography: Relation To Clinical Assessment
Authors: Sujeong Kim, Kwang-Nam Jin, Chang Hyun Lee, So-Hee Lee, Jae-Won Jung, Woo-Jung Song, Hye-Ryun Kang, Kyung-Up Min, Sang Heon Cho
Journal: Journal of Allergy and Clinical Immunology (2014)
Effect of sulphasalazine and its metabolites on the generation of reactive oxygen species.
Authors: Y Miyachi, A Yoshioka, S Imamura, Y Niwa
Journal: Gut (1987)

The relative in vitro anti-oxidant efficacy of sulphasalazine (salicylazosulphapyridine, SASP) and its metabolites (5-aminosalicylic acid, 5-ASA; sulphapyridine, SP) was examined by studying their effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leucocytes (PMNs) and a cell free, xanthine-xanthine oxidase system. Salicylazosulphapyridine, 5-ASA, and SP showed anti-oxidant effects to the various degrees. In particular, production of OH, which is one of the most potent reactive oxygen species, was remarkably suppressed by 5-ASA dose relatedly. These findings suggest that SASP and its metabolites play an important role in the inhibition of respiratory bursts. As the potent products of the respiratory burst by polymorphonuclear leucocytes are thought to be important inflammatory mediators, suppression of toxic reactive oxygen species generation by these agents may partly explain the therapeutic efficacy of SASP in ulcerative colitis, which is characterised by an acute mucosal inflammation dominated by polymorphonuclear leucocytes accumulation.
Anti-tuberculosis therapy as a reason for ejaculatory disorders
Authors: Ekaterina Kulchavenya, Elena Brizhatyuk, Denis Kholtobin, Alexander Osadchyi
Journal: European Respiratory Journal (2012)

Introduction. The sexual life is an integral part full and happy life. Patient with pulmonary tuberculosis (TB) suffers from his disease itself as well as from different complications. The aim was to estimate the frequency of ejaculatory disorders in men suffering from tuberculosis and to determine the effect of TB treatment on the ejaculation.  Material and Methods. 98 pulmonary TB patients were enrolled in study. The intravaginal latency time before onset of TB was estimated retrospectively and in 3 months of anti-TB therapy.  Results. Before anti-TB therapy 14.3% of pulmonary TB patients had ejaculatory disorders: 10.2% had premature ejaculation, and 4.1% delayed ejaculation. The rest 85.7% of patients had normal ejaculation.  After three months of the therapy with 4 anti-TB drugs (isonazid, rifampicin, pyrazinamid and streptomycin) the proportion was changed significantly. The share of patients with normal ejaculation decreased to 61.2%. On contrary, frequency of premature ejaculation increased twice (20.4%), and delayed ejaculation – in 4.5 times (18.4%).  Conclusion. Proportion of ejaculatory disorders in patients with pulmonary TB before a start of anti-TB therapy was the same as in population as whole. So, tuberculosis as a disease doesn9t damage an ejaculatory function. Three months of standard anti-TB therapy with four drugs significantly worsened the ejaculatory function of patients. The high growth of delayed ejaculation may be explained by neurotoxicity of anti-TB drugs. So, tuberculosis as a disease doesn9t damage an ejaculatory function, but the treatment of tuberculosis does it. There is necessary a special pathogenetic therapy to prevent this complication.
Evidence That CD31, CD49b, and CD62L Are Immunodominant Minor Histocompatibility Antigens in HLA Identical Sibling Bone Marrow Transplants
Authors: Etsuko Maruya, Hiroh Saji, Shigeki Seki, Yasuhiko Fujii, Koji Kato, Syunro Kai, Akira Hiraoka, Keisei Kawa, Yasutaka Hoshi, Kazuhiko Ito, Shigeki Yokoyama, Takeo Juji
Journal: Blood (1998)