tbuckley/cabot-search huggingface dataset:
Tinea versicolor: Epidemiologic, clinical, and therapeutic aspects
Authors: Dante Borelli, Paul H. Jacobs, Lexie Nall
Journal: Journal of the American Academy of Dermatology (1991)

Age of the patient, climate, season, and local environmental factors influence the onset and course of tinea versicolor (pityriasis versicolor).A number of effective topical therapies are available.In addition, a single dose of 400 mg oforal ketoconazole eliminates the disease and can be used prophylactically in some cases to prevent recurrence.(J AM ACAD DERMATOL 1991;25:300-5.)Tinea versicolor is a common superficial fungus infection that most frequently affects the trunk, neck, and/or upper arms.Lesions are slightly scaly, papular, and nummular, or they may be confluent and involve large portions of the body.[3][4][5][6][7] EPIDEMIOLOGIC ASPECTS Prevalence Although tinea versicolor occurs worldwide, it is especially common in hot, humid tropical climates; for example, in Samoa and Liberia, almost half the adult population may be affected.An overall prevalence rate of 30% or more probably occurs in tropical zones. 6 , 7 The actual frequency of the disease in temperate climates is not known. 8 In the U.S. National Health Survey (1971 to 1974) 28,000 persons from 1 to 74 years of age, tinea versicolor was found in 0.8%.9, 10 Faergemann and FredrikssonII surveyed 20,962 patients and identified 232 (1.1 %) with tinea versicolor.
Molecular Imaging of Tumor-Infiltrating Macrophages in a Preclinical Mouse Model of Breast Cancer
Authors: Xianlei Sun, Duo Gao, Liquan Gao, Chenran Zhang, Xinhe Yu, Bing Jia, Fan Wang, Zhaofei Liu
Journal: Theranostics (2015)

Significant evidence has indicated that tumor-associated macrophages (TAMs) play a critical role in the proliferation, invasion, angiogenesis, and metastasis of a variety of human carcinomas.In this study, we investigated whether near-infrared fluorescence (NIRF) imaging using a macrophage mannose receptor (MMR; CD206)-targeting agent could be used to noninvasively visualize and quantify changes in TAMs in vivo.The CD206-targeting NIRF agent, Dye-anti-CD206, was prepared and characterized in vitro and in vivo.By using NIRF imaging, we were able to noninvasively image tumor-infiltrating macrophages in the 4T1 mouse breast cancer model.Importantly, longitudinal NIRF imaging revealed the depletion of macrophages in response to zoledronic acid (ZA) treatment.However, ZA alone did not lead to the inhibition of 4T1 tumor growth.We therefore combined anti-macrophage ZA therapy and tumor cytotoxic docetaxel (DTX) therapy in the mouse model.The results demonstrated that this combination strategy could significantly inhibit tumor growth as well as tumor metastasis to the lungs.Based on these findings, we concluded that CD206-targeted molecular imaging can sensitively detect the dynamic changes in tumor-infiltrating macrophages, and that the combination of macrophage depletion and cytotoxic therapy is a promising strategy for the effective treatment of solid tumors.
Biomechanical analysis of the single-leg decline squat
Authors: J Zwerver, S W Bredeweg, A L Hof
Journal: British Journal of Sports Medicine (2007)

Background: The single-leg squat on a 25° decline board has been described as a clinical assessment tool and as a rehabilitation exercise for patients with patellar tendinopathy. Several assumptions have been made about its working mechanism on patellar load and patellofemoral forces, but these are not substantiated by biomechanical evaluations. Aim: To investigate knee moment and patellofemoral contact force as a function of decline angle in the single-leg squat. Methods: Five subjects performed single-leg eccentric squats at decline angles of 0°, 5°, 10°, 15°, 20° and 25° (with/without a backpack of 10 kg), and 30° on a board that was placed over a forceplate. Kinematic and forceplate data were recorded by the Optotrak system. Joint moments of ankle, knee and hip were calculated by two-dimensional inverse dynamics. Results: Knee moment increased by 40% at decline angles of 15° and higher, whereas hip and ankle moment decreased. Maximum knee and ankle angles increased with steeper decline. With a 10 kg backpack at 25° decline, the knee moment was 23% higher than unloaded. Both patellar tendon and patellofemoral forces increased with higher decline angles, but beyond 60°, the patellofemoral force rose steeper than the tendon force. Conclusions: All single-leg squats at decline angles &gt;15° result in 40% increase in maximum patellar tendon force. In knee flexions &gt;60°, patellofemoral forces increase more than patellar tendon forces. Higher tendon load can be achieved by the use of a backpack with extra weight.
NHS Health Check programme wastes £450m a year, report says
Authors: Jacqui Wise
Journal: BMJ (2015)

The NHS Health Check programme is ineffective and wastes £450m (€620m; $700m) a year, a highly critical report has said.

The programme is advertised as a free “midlife MOT” for everyone in England aged 40-74 without a pre-existing condition. The check, offered every five years, assesses a patient’s risk of heart disease, diabetes, kidney disease, stroke, and dementia and provides support and advice to help them manage and reduce their risk of future disease.

But the report, published in the Journal …
Bovine tracheal responsiveness in vitro: role of the epithelium and nitric oxide
Authors: G Sadeghi-Hashjin, PA Henricks, G Folkerts, AK Verheyen, HJ van der Linde, FP Nijkamp
Journal: European Respiratory Journal (1996)

Airway epithelium releases inhibitory factors, such as nitric oxide (NO) and prostaglandin E2 (PGE2), which may counteract bronchoconstriction. We investigated whether epithelium-derived inhibitory substances exert a crucial influence on bovine tracheal responsiveness in vitro. Isotonic and isometric contractions in response to histamine of intact and epithelium-denuded tracheal smooth muscle strips were compared. In addition, the effects of L-arginine (L-arg), N(G)-nitro-L-arginine methyl esther (L-NAME), and N(G)-monomethyl L-arginine (L-NMMA) on histamine responsiveness were investigated. The release of NO and PGE2 from tracheal epithelium was measured. Removal of the epithelium from tracheal smooth muscle strips did not change the negative log of the concentration of histamine producing half the maximal effect (pD2) or the maximal effect (Emax). Incubation of the tissues for 25 min with L-arg or L-NAME did not influence basal tone or the contractions induced by histamine. However, incubation with L-NMMA increased the basal tone and caused a slight hyporesponsiveness to histamine. S-nitroso-N-acetyl-penicillamine (SNAP, a direct NO donor) reversed the contraction induced by histamine in a concentration-dependent manner. Stimulation of the epithelial layer by 0.1 microM histamine increased the release of NO 3-4 fold compared to basal levels; this effect was completely inhibited in the presence of L-NMMA. In addition, 1 mM histamine caused a significant increase in the release of PGE2 from the epithelial tissue. In conclusion, no functional inhibitory influence of the epithelium can be identified in bovine airways. The S-nitroso-N-acetyl-penicillamine-induced relaxation demonstrates the presence of a nitric oxide sensitive pathway in bovine airways. However, the amounts of nitric oxide and prostaglandin E2 released from bovine tracheal epithelium are probably too low to exert a significant effect on the histamine-induced contractions.
Vascular Endothelial Growth Factor Receptor-1 Signaling Promotes Mobilization of Macrophage Lineage Cells from Bone Marrow and Stimulates Solid Tumor Growth
Authors: Masashi Muramatsu, Seiji Yamamoto, Tsuyoshi Osawa, Masabumi Shibuya
Journal: Cancer Research (2010)

Abstract Vascular endothelial growth factor and its receptors, including Flt-1 and Flk-1, are involved in angiogenesis under physiologic and pathologic conditions. Recently, Flt-1–expressing cells were reported to contribute to the intracranial growth of glioma cells. However, the role of Flt-1 signaling in solid tumor growth in s.c. tissue has not been elucidated. To investigate how Flt-1 signaling is involved in the proliferation of solid tumors, we implanted tumor cells into wild-type (Wt) and Flt-1 tyrosine kinase (TK)–deficient (Flt-1 TK−/−) mice. Growth of HSML and B16 but not Lewis lung carcinoma cell in s.c. tissue was significantly decreased in Flt-1 TK−/− mice. Angiogenesis in HSML and B16 tumors was remarkably reduced in Flt-1 TK−/− mice. Moreover, the infiltration of macrophage lineage cells into HSML and B16 tumors was clearly suppressed in Flt-1 TK−/− mice. Pericyte marker+ cells were also reduced in Flt-1 TK−/− mice. However, in the border area of tumor, angiogenesis and the infiltration of macrophage lineage cell were basically similar between Wt and Flt-1 TK−/− mice. In bone marrow (BM) transplantation experiments, tumor angiogenesis, infiltration of macrophage lineage cells, and tumor growth were significantly suppressed in Wt/Flt-1 TK−/− mice implanted with Flt-1 TK−/− BM cells compared with those implanted with Wt BM cells. We conclude that Flt-1 signaling is involved in the function of BM-derived cell, such as the migration of macrophages into cancerous tissues, and significantly contributes to angiogenesis and tumor progression. Cancer Res; 70(20); 8211–21. ©2010 AACR.
Endocytosis and uptake of lucifer yellow by cultured atrial myocytes and isolated intact atria from adult rats. Regulation and subcellular localization.
Authors: E Page, G E Goings, J Upshaw-Earley, D A Hanck
Journal: Circulation Research (1994)

The time course of endocytic uptake of Lucifer yellow (LY) was followed by fluorescence and electron microscopy after exposure of primary cultures of atrial myocytes from adult rats to LY under conditions that prevented transplasmalemmal LY entry via channels or carriers. After a 2-minute exposure to LY at 37 degrees C, electron microscopy revealed classic clathrin-coated vesicles fused to endosomes, which were absent in LY-free medium or at 2 degrees C, suggesting that LY turns on endocytosis or accelerates a slow constitutive endocytosis. Fluorescence microscopy, which detected no LY entry at 2 minutes in LY, showed punctate cytoplasmic fluorescent densities after 10 minutes, which were readily distinguishable from intrinsic perinuclear fluorescence. Fluorescence microscopy after immunostaining with antibodies against clathrin, vacuolar H(+)-ATPase, atrial peptide, or a marker for acidified compartments suggested LY sorting into an acidified prelysosomal pathway. Using absence of punctate fluorescence after 10 minutes in LY as a criterion for inhibition of endocytosis, we showed that endocytosis was inhibited by inhibitors of protein phosphatases 1 and 2A or inhibitors of cAMP-dependent protein kinases 1 and 2, by effects of caffeine on sarcoplasmic reticulum Ca2+ release, and by temperatures below 18 degrees C, but not by staurosporine, phorbol esters, pertussis toxin, thapsigargin, preventing contractions with nifedipine, ryanodine and low [Ca2+]o, or raising cytosolic cAMP concentrations. Both phosphatase inhibitors and caffeine also inhibited a fraction of LY uptake by intact rat atria. We conclude that endocytic uptake of LY is an energy-dependent, specifically regulated process, whose understanding and control are potentially important for the medically relevant problem of introducing drugs and macromolecules into atrial heart muscle cells.
Short Communication: Subcellular Motion Compensation for Minimally Invasive Microscopy, In Vivo
Authors: James L. Schroeder, Merav Luger-Hamer, Randall Pursley, Tom Pohida, Chris Chefd'Hotel, Peter Kellman, Robert S. Balaban
Journal: Circulation Research (2010)

In vivo microscopy seeks to observe dynamic subcellular processes in a physiologically relevant context. A primary limitation of optical microscopy in vivo is tissue motion, which prevents physiological time course observations or image averaging.To develop and demonstrate motion compensation methods that can automatically track image planes within biological tissues, including the tissue displacements associated with large changes in blood flow, and to evaluate the effect of global hypoxia on the regional kinetics and steady state levels of mitochondrial NAD(P)H.A dynamic optical microscope, with real-time prospective tracking and retrospective image processing, was used collect high-resolution images through cellular responses to various perturbations. The subcellular metabolic response to hypoxia was examined in vivo. Mitochondria closest to the capillaries were significantly more oxidized at rest (67+/-3%) than the intrafibrillar mitochondria (83+/-3%; P<0.0001) in the same cell.These data are consistent with the hypothesis that a significant oxygen gradient from capillary to muscle core exists at rest, thereby reducing the oxidative load on the muscle cell.
Associations between Hemodialysis Access Type and Clinical Outcomes
Authors: Pietro Ravani, Suetonia C. Palmer, Matthew J. Oliver, Robert R. Quinn, Jennifer M. MacRae, Davina J. Tai, Neesh I. Pannu, Chandra Thomas, Brenda R. Hemmelgarn, Jonathan C. Craig, Braden Manns, Marcello Tonelli, Giovanni F.M. Strippoli, Matthew T. James
Journal: Journal of the American Society of Nephrology (2013)

Clinical practice guidelines recommend an arteriovenous fistula as the preferred vascular access for hemodialysis, but quantitative associations between vascular access type and various clinical outcomes remain controversial. We performed a systematic review of cohort studies to evaluate the associations between type of vascular access (arteriovenous fistula, arteriovenous graft, and central venous catheter) and risk for death, infection, and major cardiovascular events. We searched MEDLINE, EMBASE, and article reference lists and extracted data describing study design, participants, vascular access type, clinical outcomes, and risk for bias. We identified 3965 citations, of which 67 (62 cohort studies comprising 586,337 participants) met our inclusion criteria. In a random effects meta-analysis, compared with persons with fistulas, those individuals using catheters had higher risks for all-cause mortality (risk ratio=1.53, 95% CI=1.41–1.67), fatal infections (2.12, 1.79–2.52), and cardiovascular events (1.38, 1.24–1.54). Similarly, compared with persons with grafts, those individuals using catheters had higher risks for mortality (1.38, 1.25–1.52), fatal infections (1.49, 1.15–1.93), and cardiovascular events (1.26, 1.11–1.43). Compared with persons with fistulas, those individuals with grafts had increased all-cause mortality (1.18, 1.09–1.27) and fatal infection (1.36, 1.17–1.58), but we did not detect a difference in the risk for cardiovascular events (1.07, 0.95–1.21). The risk for bias, especially selection bias, was high. In conclusion, persons using catheters for hemodialysis seem to have the highest risks for death, infections, and cardiovascular events compared with other vascular access types, and patients with usable fistulas have the lowest risk.
Bronchial hyperresponsiveness to methacholine/AMP and the bronchodilator response in asthmatic children
Authors: D.I. Suh, J.K. Lee, C.K. Kim, Y.Y. Koh
Journal: European Respiratory Journal (2010)

Bronchodilator response (BDR) is assessed to estimate the reversibility of airflow obstruction. Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma and is usually measured by means of bronchial challenges using direct or indirect stimuli. The aim of the present study was to compare BHR to methacholine (direct) and that to adenosine 5’-monophosphate (AMP) (indirect) with regard to their relationships to BDR in asthmatic children. Methacholine and AMP challenge tests were performed on 138 children with mild-to-moderate asthma, and the provocative concentration causing a 20% decline in forced expiratory volume in 1 s (FEV 1 ) (PC 20 ) was determined for each challenge. BDR was calculated as the change in FEV 1 , expressed as a percentage of the initial value, after inhalation of 400 μg salbutamol. Methacholine PC 20 correlated significantly but weakly with BDR (r = -0.254; p = 0.003). However, there was a significant and strong correlation between AMP PC 20 and BDR (r = -0.489; p = 0.000). For AMP PC 20 , the relationship was closer than for methacholine PC 20 (p = 0.024 for comparison between correlation coefficients). The same figures were observed when BDR was expressed as a percentage of the predicted value. A stronger correlation of BDR with AMP PC 20 than with methacholine PC 20 suggests that BDR may be better reflected by BHR as assessed by AMP challenge than by methacholine challenge.
Southern Dietary Pattern Is Associated With Hazard of Acute Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: James M. Shikany, Monika M. Safford, P. K. Newby, Raegan W. Durant, Todd M. Brown, Suzanne E. Judd
Journal: Circulation (2015)

The association of overall diet, as characterized by dietary patterns, with risk of incident acute coronary heart disease (CHD) has not been studied extensively in samples including sociodemographic and regional diversity.
<i>In vivo</i>Drug-Linker Stability of an Anti-CD30 Dipeptide-Linked Auristatin Immunoconjugate
Authors: Russell J. Sanderson, Michelle A. Hering, Stephanie F. James, Michael M.C. Sun, Svetlana O. Doronina, Anthony W. Siadak, Peter D. Senter, Alan F. Wahl
Journal: Clinical Cancer Research (2005)

Effective antibody-drug conjugates (ADC) combine high drug-linker stability in circulation and efficient intratumoral release of drug. Conjugation of monomethyl auristatin E (MMAE) to the anti-CD30 monoclonal antibody (mAb), cAC10, produced a selective and potent ADC against CD30(+) anaplastic large cell lymphoma and Hodgkin's disease models. This ADC, cAC10-valine-citrulline-MMAE, uses a protease-sensitive dipeptide linker designed to release MMAE by lysosomal cathepsin B in target cells but maintain a stable linkage and attenuate drug potency in circulation. To evaluate ADC stability in vivo, we developed methods for measuring drug/mAb ratios at progressive times in plasma from ADC-treated mice and nonhuman primates. Anti-idiotype mAb permitted the capture and quantitation of mAb cAC10, whereas antidrug mAb and MMAE-conjugated horseradish peroxidase reporter provided quantitative detection of conjugated drug following its in vitro release by cathepsin B. These data were validated by an alternative ELISA using anti-idiotype and anti-MMAE mAbs for capture and detection, respectively. Both methods differentiated ADC with variable levels of drug loading and were subsequently applied to stability studies in severe combined immunodeficient mice and cynomolgus monkeys. Evaluation of ADC from mouse circulation showed the linker half-life to be approximately 144 hours (6.0 days), significantly greater than that reported for disulfide- or hydrazone-linked ADCs in mice or human trials. In cynomolgus monkey, the apparent linker half-life was approximately 230 hours (9.6 days), suggesting that the drug-linker will be highly stable in humans. These data represent the longest reported drug-linker half-life to date and provide the basis for the pronounced specificity and antitumor activity of cAC10-valine-citrulline-MMAE.
Contemporary Role of Systematic Prostate Biopsies: Indications, Techniques, and Implications for Patient Care
Authors: Osamu Ukimura, Jonathan A. Coleman, Alex de la Taille, Mark Emberton, Jonathan I. Epstein, Stephen J. Freedland, Gianluca Giannarini, Adam S. Kibel, Rodolfo Montironi, Guillaume Ploussard, Monique J. Roobol, Vincenzo Scattoni, J. Stephen Jones
Journal: European Urology (2012)
Heparin Proteoglycans Released From Rat Serosal Mast Cells Inhibit Proliferation of Rat Aortic Smooth Muscle Cells in Culture
Authors: Yenfeng Wang, Petri T. Kovanen
Journal: Circulation Research (1999)

-Mast cells are present in the human arterial intima. To study whether mast-cell degranulation influences the rate of proliferation of smooth muscle cells, we cocultured sensitized (IgE-bearing) rat serosal mast cells and rat aortic smooth muscle cells (SMCs). When sensitized mast cells were stimulated to degranulate with antigen, the rate of proliferation of the cocultured SMCs decreased sharply. This inhibitory effect was found to be due mainly to the very high molecular weight (Mr) heparin proteoglycans (average Mr 750 000) released from the stimulated mast cells. When the heparin proteoglycans were purified from mast-cell granule remnants and added to the SMC culture, they were found to block the cell cycle at the G0-->S transition and the exit from the G2/M phase, their inhibitory effect resembling that of commercial heparin. However, in contrast to the reported dependence of the inhibitory effect of commercial heparin on the release of transforming growth factor-beta from serum, the inhibitory effect of the mast cell-derived heparin proteoglycans in the presence of serum was not transforming growth factor-beta dependent. Moreover, the effect of the mast cell-derived heparin proteoglycans was more efficient than that of commercial heparins of high (average Mr 15 000) and low (average Mr 5000) molecular weight. We also purified heparin glycosaminoglycans (average Mr 75 000) from the mast cell-derived heparin proteoglycans and found that they also inhibited SMC growth efficiently, although less strongly than their parent heparin proteoglycans. These results reveal, for the first time, that mast cells are able to regulate SMC growth. Thus, activated mast cells, by releasing heparin proteoglycans, possibly participate in the regulation of SMC growth in the human arterial intima, the site of atherogenesis.
Isolation of Legionella pneumophila from Hospital Shower Heads
Authors: Lester G. Cordes, Andrew M. Wiesenthal, George W. Gorman, John P. Phair, Herbert M. Sommers, Arnold Brown, Victor L. Yu, Margaret H. Magnussen, Richard D. Meyer, James S. Wolf, Kathryn N. Shands, David W. Fraser
Journal: Annals of Internal Medicine (1981)

Legionella pneumophila serogroup 6 was isolated from nine of 16 shower heads in a Chicago hospital ward where three patients had contracted Legionnaires' disease caused by serogroup 6 L. pneumophila. Each patient had showered there 2 to 10 days before the onset of disease symptoms. We also isolated the bacteria in two other hospitals, and found the same serogroups as had been causing Legionnaires' disease in those hospitals: serogroup 1 in Pittsburgh and serogroups 1 and 4 in Los Angeles. However, showers from hospital wards where no patients had contracted Legionnaires' disease also yielded L. pneumophila. Shower heads at the Chicago hospital were sterilized with ethylene oxide but rapidly became recontaminated, suggesting that the potable water at these hospitals may have contained the organism. The question of whether aerosols of shower water or other exposures to potable water containing L. pneumophila may cause nosocomial Legionnaires' disease has not been resolved but deserves further study.