tbuckley/cabot-search huggingface dataset:
Cryopreservation of testicular tissue in young cancer patients
Authors: Outi Hovatta
Journal: Human Reproduction Update (2001)

Cryopreservation of testicular tissue might benefit prepubertal boys who must undergo chemotherapy or radiotherapy. Cryopreservation of testicular tissue and testicular cells for intracytoplasmic sperm injection (ICSI) is feasible and widely applied. Testicular tissue from prepubertal boys can also be frozen, by applying techniques used with other tissues and with testicular tissue from adult men before ICSI. Good results have been obtained when propanediol is used as a cryoprotectant, but glycerol has also been used when freezing testicular tissue. Spermatogonia might also be isolated and cryopreserved as a cell suspension, though practical experience in humans is lacking. Transplantation of the frozen-thawed cells back to the testes after cancer treatment might result in restoration of spermatogenesis. Live offspring have been born to mice after transplantation of fresh, but not cryopreserved, testicular cells. Transplantation is technically feasible also in larger species, but to date no offspring have been born. Spermatogenesis in vitro would be an excellent option for boys with haematological malignancies who carry a risk of relapse after transplantation; however, at present the method is feasible only for the late stages of spermatogenesis.
A pathway-based approach investigating the genes encoding interleukin-1β, interleukin-6 and the interleukin-1 receptor antagonist provides new insight into the genetic susceptibility of Achilles tendinopathy
Authors: Alison V September, Erica-Mari Nell, Kevin O'Connell, Jill Cook, Christopher J Handley, Lize van der Merwe, Martin Schwellnus, Malcolm Collins
Journal: British Journal of Sports Medicine (2011)

Objectives Achilles tendinopathy (AT) is a multifactorial condition for which genetic risk factors have been identified. A pathway-based approach was used to investigate genes within the inflammatory pathway. Methods Functional polymorphisms within IL-1β (−31T→C and −511C→T), IL-1RN (variable number tandem repeat) and IL-6 (−172G→C) were investigated for associations with AT in a South African (SA) and Australian (AUS) case–control studies. A total of 369 (161 SA and 208 AUS) asymptomatic control participants (CON) and 175 (90 SA and 85 AUS) participants with AT (TEN) were genotyped. Allele combinations were constructed using the above polymorphisms in combination with the COL5A1 Bst UI RFLP. Results Independently, no associations were observed between any of the polymorphisms tested and risk of TEN. The allele combinations of five polymorphisms were, however, found to have a highly significant relationship with AT (p=0.005), after adjusting for gender and country (SA or AUS). Conclusions Variations within the interleukin genes and the COL5A1 Bst UI CC genotype are collectively significantly associated with risk of AT. This research emphasises that a pathway-based genetic association study may be a more effective approach to capture and understand the genetic risk factors underlying the multifactorial conditions, such as AT.
Diaphragm dysfunction in chronic obstructive pulmonary disease: a role for heparan sulphate?
Authors: C. A. C. Ottenheijm, G. J. Jenniskens, M. C. P. Geraedts, T. Hafmans, L. M. A. Heunks, T. H. van Kuppevelt, P. N. R. Dekhuijzen
Journal: European Respiratory Journal (2007)

In the present study, phage display-derived antibodies were used to investigate the topology of glycosaminoglycan epitopes in the diaphragm of chronic obstructive pulmonary disease (COPD) and non-COPD patients. Furthermore, the potential physiological significance of changes in the occurrence of glycosaminoglycan epitopes in the diaphragm of COPD patients was studied by determining the overlap in epitope recognition of glycosaminoglycan antibodies and growth factors. Diaphragm cryosections from non-COPD (n = 5) and COPD patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II; n = 9) were incubated with antibodies directed against heparan sulphate, chondroitin sulphate and dermatan sulphate epitopes. Antibodies were visualised immunofluorescently. In addition, interference of antibody and growth factor binding with heparan sulphate epitopes was tested. Specific glycosaminoglycan epitopes showed increased expression in the diaphragm of COPD patients, whereas other epitopes were decreased or unaffected. Interestingly, the anti-heparan sulphate antibody HS4C3, which is directed against a downregulated epitope, interfered with the binding of hepatocyte growth factor. Three patients with the most severe airway obstruction also demonstrated interference of heparan sulphate antibody A04B08 with hepatocyte growth factor binding. Results indicate changes in glycosaminoglycan composition in the diaphragm of patients with chronic obstructive pulmonary disease. This may affect cellular physiology via alterations in growth factor handling and might be related to reduced levels of contractile protein in the diaphragm of these patients.
School-Community Partnerships
Authors: Kristine Madsen, Hannah Thompson, Amy Adkins, Yashica Crawford
Journal: JAMA Pediatrics (2013)

Identifying community-based programs that increase physical activity among diverse youth could yield sustainable tools to reduce obesity and obesity disparities.To evaluate the impact of a community-based after-school soccer and youth development program, America SCORES, on students' physical activity, weight status, and fitness.Cluster-randomized trial. Study measures were collected in the fall (baseline), winter (midpoint), and spring (end point) of the 2009-2010 school year.After-school programs in 6 schools within a large urban school district.All 4th and 5th grade students in after-school programs at the study schools were eligible.Three schools were randomized to receive the SCORES after-school program, delivered via the train-the-trainer model.Change in minutes of after-school moderate-to-vigorous physical activity (MVPA), fitness (maximal oxygen consumption), and body mass index over 1 school year.Participants (n = 156) were diverse (42% Latino, 32% Asian, and 12% African American) and 76 (49%) had a body mass index at or above the 85th percentile. There were no significant group differences in the change in physical activity, fitness, or weight status among all students. However, among students with a body mass index at or above the 85th percentile, SCORES significantly increased MVPA after school (3.4 min/d; 95% CI, 0.3-6.5) and on Saturdays (18.5 minutes; 95% CI, 3.4-33.6).Existing community-based programs such as SCORES can increase physical activity among low-income youth, particularly those most at risk for weight-related comorbidities. While evaluating existing programs presents special challenges, partnerships between communities, schools, and researchers are an important component of translational research to address obesity.clinicaltrials.gov Identifier: NCT01156103.
Prospective cohort study of routine use of risk assessment scales for prediction of pressure ulcers
Authors: L. Schoonhoven
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective</b>: To evaluate whether risk assessment scales can be used to identify patients who are likely to get pressure ulcers. <b>Design</b>: Prospective cohort study. <b>Setting</b>: Two large hospitals in the Netherlands. <b>Participants</b>: 1229 patients admitted to the surgical, internal, neurological, or geriatric wards between January 1999 and June 2000. <b>Main outcome measure</b>: Occurrence of a pressure ulcer of grade 2 or worse while in hospital. <b>Results</b>: 135 patients developed pressure ulcers during four weeks after admission. The weekly incidence of patients with pressure ulcers was 6.2% (95% confidence interval 5.2% to 7.2%). The area under the receiver operating characteristic curve was 0.56 (0.51 to 0.61) for the Norton scale, 0.55 (0.49 to 0.60) for the Braden scale, and 0.61 (0.56 to 0.66) for the Waterlow scale; the areas for the subpopulation, excluding patients who received preventive measures without developing pressure ulcers and excluding surgical patients, were 0.71 (0.65 to 0.77), 0.71(0.64 to 0.78), and 0.68 (0.61 to 0.74), respectively. In this subpopulation, using the recommended cut-off points, the positive predictive value was 7.0% for the Norton, 7.8% for the Braden, and 5.3% for the Waterlow scale. <b>Conclusion</b>: Although risk assessment scales predict the occurrence of pressure ulcers to some extent, routine use of these scales leads to inefficient use of preventive measures. An accurate risk assessment scale based on prospectively gathered data should be developed.
EVIDENCE FOR HETEROSEXUAL TRANSMISSION AND CLINICAL MANIFESTATIONS OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION AND RELATED CONDITIONS IN LUSAKA, ZAMBIA
Authors: Mads Melbye, Anne Bayley, J.K. Manuwele, SusanA. Clayden, WilliamA. Blattner, Richard Tedder, E.K. Njelesani, K. Mukelabai, F.J. Bowa, Arthur Levin, RobinA. Weiss, RobertJ. Biggar
Journal: The Lancet (1986)
Management of acute childhood asthma: a prospective multicentre study
Authors: T.N. Hilliard, H. Witten, I.A. Male, S. Langton Hewer, P.C. Seddon
Journal: European Respiratory Journal (2000)

Children with acute asthma account for a significant proportion of paediatric hospital admissions, and clear guidelines exist for their care. The aim of this study was to determine their management in the UK. Over 1 year (February 1995 to January 1996), children aged 1-14 yrs admitted with acute asthma were studied in both teaching and district general hospitals. An admission pro forma was used to collect data prospectively, with a computer-based information management system for the input of admissions in each centre. Ten centres collected data prospectively, with 1,578 admissions involving 1,352 children (median age 3.6 yrs). Sixty two per cent of children were &lt;5 yrs of age. Sixty three per cent of admissions had initial arterial oxygen saturation (Sa,O2) recorded, and, in those older than 5 yrs, 36% had their initial peak expiratory flow rate recorded. Systemic steroids were given to 78%. An initial Sa,O2 of &lt;92% was associated with a longer stay in hospital, and also with intravenous treatment. Preventative treatment increased from 42% on admission to 53% on discharge. The rates of documented education were low. This is the largest UK study following publication of national guidelines and shows that there is still room for improvement in the management of children admitted with acute asthma.
An Overview of T-Suppressor Cell Circuits
Authors: G L Asherson, V Colizzi, M Zembala
Journal: Annual Review of Immunology (1986)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Gratitude in the Setting of Stage IV Lung Cancer: How Innovative Caregivers Help the Success of Treatment
Authors: Nila J Webster
Journal: Annals of Internal Medicine (2013)

On Being a Patient1 January 2013Gratitude in the Setting of Stage IV Lung Cancer: How Innovative Caregivers Help the Success of TreatmentNila J. Webster, MANila J. Webster, MAFrom Revere, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-1-201301010-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail As I waited in the office of the infectious disease specialist, I knew that management of empyema in the setting of advanced lung cancer was not ideal. But foremost on my mind was whether this doctor would go forward with standard protocol—intravenous antibiotics through a peripherally inserted central catheter (PICC) line for 8 weeks—or let me try oral antibiotics instead.I dreaded the thought of a PICC line. Two days earlier, when I went for the insertion, it had not gone well. The interventional radiologist could not understand that I had questions. He literally threw his clipboard on the table ... Author, Article, and Disclosure InformationAffiliations: From Revere, Massachusetts.Corresponding Author: Nila J. Webster, MA, 1 Carey Circle 404, Revere, MA 02151; e-mail, [email protected]. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFrom the First Visit On: Information Technology and Communication 1 January 2013Volume 158, Issue 1Page: 71-72KeywordsAntibioticsCaregiversGratitudeImmune systemInfectious diseasesLung and intrathoracic tumorsLungsNursesPeripherally inserted central cathetersRadiologists ePublished: 1 January 2013 Issue Published: 1 January 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Superior Efficacy of Tumor Cell Vaccines Grown in Physiologic Oxygen
Authors: Michael R. Olin, Brian M. Andersen, David M. Zellmer, Patrick T. Grogan, Flavia E. Popescu, Zhengming Xiong, Colleen L. Forster, Charlie Seiler, Karen S. SantaCruz, Wei Chen, Bruce R. Blazar, John R. Ohlfest
Journal: Clinical Cancer Research (2010)

Atmospheric oxygen (∼20% O(2)) has been the universal condition employed to culture tumor cells used as vaccine antigen. We tested the hypothesis that reducing oxygen tension would increase the efficacy of tumor cell lysate vaccines.GL261 glioma cells and EMT6 breast carcinoma cells were grown in 5% or 20% O(2). Syngeneic tumor-bearing mice were vaccinated with these tumor cell lysates mixed with CpG oligodeoxynucleotides as an adjuvant. Tumor infiltrating T cells and apoptotic GL261 cells were quantified by immunohistochemistry. Tumor-reactive immunoglobulin was detected by Western blot. Ovalbumin and gp100-derived peptides were mixed with GL261 lysates as marker antigens to detect changes in presentation of exogenous antigen on MHC class I in vitro, and in vivo following adoptive transfer of gp100-specific CD8(+) T cells.Mice bearing orthotopic glioma and breast carcinoma survived significantly longer when vaccinated with 5% O(2) lysates. Antigen-specific CTL activation was significantly enhanced following stimulation with lysates derived from GL261 cells grown in 5% O(2) versus 20% O(2) through a mechanism that involved enhanced cross-presentation of exogenous antigen on MHC I. Vaccination with 5% O(2) GL261 cell lysates caused a significant increase in CTL proliferation, tumoricidal function, and trafficking into brain tumor sites, whereas 20% O(2) lysate vaccines predominantly evoked an antibody response.Tissue culture oxygen functions as an "immunologic switch" by dictating the cellular and humoral immune responses elicited by tumor cell lysates. These results have profound implications for cancer vaccines that utilize tumor cells as the source of antigen.
The CD40/CD40 ligand system is expressed in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum
Authors: M. Caproni, D. Torchia, E. Schincaglia, W. Volpi, A. Frezzolini, D. Schena, A. Marzano, P. Quaglino, C. De Simone, A. Parodi, E. Barletta, P. Fabbri
Journal: British Journal of Dermatology (2005)

Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity.To evaluate the effector role of cellular immunity and the involvement of the CD40/CD40 ligand (CD40L) system in the pathogenesis of EM and SJS/TEN.Biopsy specimens from eight patients with EM and six with SJS/TEN were stained for immunohistochemical examination using the alkaline phosphatase/antialkaline phosphatase method. The monoclonal antibodies used included those to CD1a, CD4, CD8, CD40, CD40L, CD68, Fas, Fas ligand (FasL) and myeloperoxidase.The cellular infiltrate in both EM and SJS/TEN lesions was composed mainly of T lymphocytes and CD68+ macrophages. We also detected large amounts of neutrophils. Fas and FasL were very highly expressed in SJS and TEN, but weakly in EM. CD40 staining was strong in all tissue sections; there were numerous CD40L+ cells in SJS/TEN but much fewer in EM.Activated T lymphocytes and macrophages, but also neutrophils, are presumably the main triggers of mucocutaneous damage in the SJS/TEN disease spectrum. The Fas/FasL system is significantly expressed in SJS/TEN lesions, but not in EM, where this apoptotic pathway presumably does not play a pivotal role in the epidermal damage. We suggest that the CD40/CD40L system may represent an important pathway of induction of SJS/TEN lesions, while in EM it would contribute to the immunoinflammation only as a second-line mechanism.
Heme synthetase deficiency in human protoporphyria. Demonstration of the defect in liver and cultured skin fibroblasts.
Authors: H L Bonkowsky, J R Bloomer, P S Ebert, M J Mahoney
Journal: Journal of Clinical Investigation (1975)

The final step in heme biosynthesis is chelation of porphyrin with Fe++ catalyzed by the mitochondrial enzyme heme synthetase. We have employed a sensitive radiochemical assay for this enzyme, using 59Fe and deuteroporphyrin or protoporphyrin as substrates. In this method iron is maintained in the ferrous state, oxygen is excluded from the incubation system, and labeled heme product is extracted into ethyl acetate. This assay has been used to measure the activity of heme synthetase in homogenates of liver, obtained by needle biopsy, and in sonicates of human skin fibroblasts, cultured in vitro. In addition, activity of the first enzyme of the heme synthetic pathway, delta-aminolevulinic acid synthetase, has been measured in fibroblast lysates. Lysates of fibroblasts from eight patients with protoporphyria had activities of delta-aminolevulinic acid synthetase which did not differ significantly from those of eight normal fibroblast lines, whereas activity of heme synthetase, with either deuteroporphyrin or protoporphyrin as substrate, was markedly decreased in sonicates of skin fibroblasts from these patients, the mean being 8% of control with deuteroporphyrin and 14% with protoporphyrin as substrate. In homogenates of liver from five patients with protoporphyria, activity of heme synthetase was also significantly less than that found in six patients without prophyria, the mean being 13% of control with protoporphyrin as substrate. These results provide evidence that decreased activity of heme synthetase is the basic defect in the heme synthetic pathway in protoporphyria. This deficiency is probably responsible for protoporphyrin accumulation and hence the biochemical and clinical features observed in protoporphyria.
Clinical, radiological and pathological features of ABCA3 mutations in children
Authors: M L Doan, R P Guillerman, M K Dishop, L M Nogee, C Langston, G B Mallory, M M Sockrider, L L Fan
Journal: Thorax (2007)

Mutations in the ABCA3 gene can result in fatal surfactant deficiency in term newborn infants and chronic interstitial lung disease in older children. Previous studies on ABCA3 mutations have focused primarily on the genetic abnormalities and reported limited clinical information about the resultant disease. A study was undertaken to analyse systematically the clinical presentation, pulmonary function, diagnostic imaging, pathological features and outcomes of children with ABCA3 mutations.The records of nine children with ABCA3 mutations evaluated at Texas Children's Hospital between 1992 and 2005 were reviewed and their current clinical status updated. Previous diagnostic imaging studies and lung biopsy specimens were re-examined. The results of DNA analyses were confirmed.Age at symptom onset ranged from birth to 4 years. Cough, crackles, failure to thrive and clubbing were frequent findings. Mean lung function was low but tended to remain static. CT scans commonly revealed ground-glass opacification, septal thickening, parenchymal cysts and pectus excavatum. Histopathological patterns included pulmonary alveolar proteinosis, desquamative interstitial pneumonitis and non-specific interstitial pneumonitis, and varied with age. Dense abnormalities of lamellar bodies, characteristic of ABCA3 mutations, were seen by electron microscopy in all adequate specimens. Outcomes varied with the age at which the severity of lung disease warranted open lung biopsy, and some patients have had prolonged survival without lung transplantation.The presentation and course of interstitial lung disease due to ABCA3 mutations are variable, and open lung biopsy and genetic testing are warranted early in the evaluation of children with a consistent clinical picture.
Chronic Proteasome Inhibition Contributes to Coronary Atherosclerosis
Authors: Joerg Herrmann, Ardan M. Saguner, Daniele Versari, Timothy E. Peterson, Alejandro Chade, Monica Olson, Lilach O. Lerman, Amir Lerman
Journal: Circulation Research (2007)

The proteasome is responsible for the degradation of oxidized proteins, and proteasome inhibition has been shown to generate oxidative stress in vitro. Atherosclerosis is thought to be initiated as a consequence of increased endogenous oxidative stress. The current study was designed to assess whether chronic proteasome inhibition is associated with early coronary atherosclerosis. Female pigs, 3 months of age, were randomized to a normal (N) or high-cholesterol (HC) diet (2% cholesterol, 15% lard) without or with twice weekly subcutaneous injections of the proteasome inhibitor (PSI) MLN-273 (0.08 mg/kg, N+PSI and HC+PSI) for a period of 12 weeks (n=5 per group). Coronary vasorelaxation to bradykinin (10 −10.5 to 10− 6.5 mol/L) and sodium nitroprusside (10 −9 to 10 −5 mol/L) was assessed by in vitro organ chamber experiments, intima–media ratio by morphometric analysis of Elastica–van Gieson–stained slides, and intima superoxide production by dihydroethidium fluorescence. Vasorelaxation to 10 −6.5 mol/L bradykinin was reduced in HC compared with N (69±7 versus 90±2%, P &lt;0.05) and further reduced in N+PSI and HC+PSI (57±6 and 48±13%, P &lt;0.05 versus N and HC for each). Compared with N (0.03±0.01), intima–media ratio was higher in N+PSI (0.09±0.04, P &lt;0.01) and HC+PSI (0.15±0.06, P &lt;0.05). Compared with N (0.6±0.9% of intima area), dihydroethidium fluorescence was higher in HC, N+PSI, and HC+PSI (8.9±1.6, 6.0±3.5, and 7.2±3.9% of intima area, P &lt;0.05 for all). Thus, chronic proteasome inhibition is associated with increased coronary artery oxidative stress and early atherosclerosis. These findings support the significance of the proteasome and related protein quality control for vascular biology and pathology.