tbuckley/cabot-search huggingface dataset:
Highly Efficient Gene Delivery for Bladder Cancers by Intravesically Administered Replication-Competent Retroviral Vectors
Authors: Eiji Kikuchi, Silvia Menendez, Choichiro Ozu, Makoto Ohori, Carlos Cordon-Cardo, Christopher R. Logg, Noriyuki Kasahara, Bernard H. Bochner
Journal: Clinical Cancer Research (2007)

Abstract Purpose: In an attempt to improve viral delivery of potentially therapeutic genes via an intravesical route, we have recently developed murine leukemia virus-based replication-competent retrovirus (RCR) vectors. Experimental Design: We evaluated the transduction efficiency of intravesically administered RCR vectors to bladder tumor using orthotopic animal models to determine their potential as delivery vectors for bladder cancer. Results: The RCR vector containing green fluorescent protein (GFP) marker gene achieved efficient in vitro transmission of the GFP transgene. Murine bladder tumor-2 mouse bladder tumors exposed to intravesically administered RCR vectors exhibited 0%, 9.2 ± 2.9%, and 30.0 ± 6.2% of GFP expression at 9, 18, and 27 days after exposure in the orthotopic model, respectively. Orthotopic KU-19-19 human bladder tumors exposed to intravesically administered RCR vectors exhibited 3%, 85 ± 1.0%, and 100% of GFP expression at 7, 21, and 35 days after exposure, respectively. GFP staining was observed only in the tumor cells in the bladder. No detectable PCR products of GFP gene could be observed in distant organs. Treatment with RCR vectors containing yeast cytosine deaminase (CD) gene plus 5-fluorocytosine (5-FC) dramatically inhibited the growth of preestablished murine bladder tumor-2 tumors. A single course of 5-FC treatment resulted in a 50% animal survival in mice exposed to RCR-CD compared with a 0% survival in all controls over a 70-day follow-up period. Conclusions: Intravesically administered RCR vectors can efficiently deliver genes to orthotopic bladder tumor without viral spread in distant organs. RCR-CD/5-FC suicide gene therapy promises to be a novel and potentially therapeutic modality for bladder cancer.
Prevention strategies for Alzheimer’s disease
Authors: Serge Gauthier, Liyong Wu, Pedro Rosa-Neto, Jianping Jia
Journal: Translational Neurodegeneration (2012)

Symptomatic treatment during the dementia stage of Alzheimer's disease(AD) cannot delay or halt the progression of this disease. Therefore, prevention in the preclinical stage is likely the most effective way to decrease the incidence of this age-associated neurodegenerative condition, and its associated burden for individuals and society. Age, gender, family history, ApoE4, systolic blood pressure, body mass index, total cholesterol level and physical activity are all used as component of dementia risk score. There have been numerous challenges in conducting primary prevention trials in AD. Enrichment strategies for prevention studies include studying those subjects with more risk factors for AD, such as older age, those with a positive family history of late onset AD, and those who are ApoE4 positive. Each of these strategies is designed to increase the probability of developing AD thereby decreasing the sample size or the duration of follow up. Another strategy would be to target directly the pathophysiology of AD in its preclinical stages and use the biomarkers in prevention trial as surrogate markers. This will be done first in carriers of dominantly inherited early onset AD. As this research takes place networks of memory clinics must prepare to transfer new knowledge to persons interested in a preventive approach to AD.
Interaction between ABO and Rhesus blood groups, the site of origin of gastric cancers, and the age and sex of the patient
Authors: G. A. Glober, E. G. Cantrell, R. Doll, R. Peto
Journal: Gut (1971)

ABO and Rhesus blood group data have been examined for 1,680 patients treated for gastric cancer in four London hospitals. The risk of developing gastric cancer was estimated to be 16% higher for group A subjects than for group O subjects, in close agreement with many previous reports throughout the world. More detailed analysis failed to support the suggestion that there was any special correlation between either ABO or Rhesus blood groups and the site of origin of the tumour within the stomach or the sex or age of the patient. Male predominance among the patients was noted to be greater at ages 40-69 years than at other ages and greater for tumours of the upper two thirds of the stomach than for tumours that arose distally.
Adrenal suppression with inhaled budesonide and fluticasone propionate given by large volume spacer to asthmatic children.
Authors: D. J. Clark, R. A. Clark, B. J. Lipworth
Journal: Thorax (1996)

BACKGROUND: The aim of this study was to compare the systemic bioactivity of inhaled budesonide (B) and fluticasone propionate (F), each given by large volume spacer, on a microgram equivalent basis in asthmatic children. METHODS: Ten stable asthmatic children of mean age 11 years and forced expiratory volume in one second (FEV1) 81.6% predicted, who were receiving treatment with &lt; or = 400 micrograms/day of inhaled corticosteroid, were studied in a placebo controlled single blind (investigator blind) randomised crossover design comparing single doses of inhaled budesonide and fluticasone propionate 400 micrograms, 800 micrograms, and 1250 micrograms. Doses were given at 20.00 hours with mouth rinsing and an overnight 12 hour urine sample was collected for estimation of free cortisol and creatinine excretion. RESULTS: The results of overnight 12 hour urinary cortisol output (nmol/12 hours) showed suppression with all doses of fluticasone propionate (as geometric means): F400 micrograms (11.99), F800 micrograms (6.49), F1250 micrograms (7.00) compared with placebo (24.43), whereas budesonide caused no suppression at any dose. A comparison of the drugs showed that there were differences at 800 micrograms and 1250 micrograms levels for urinary cortisol: B800 micrograms versus F800 micrograms (2.65-fold, 95% CI 1.26 to 5.58), B1250 micrograms versus F1250 micrograms (2.94-fold, 95% CI 1.67 to 5.15). The results for the cortisol/creatinine ratio were similar to that of urinary cortisol, with fluticasone causing suppression at all doses and with differences between the drugs at 800 micrograms and 1250 micrograms. CONCLUSIONS: Single doses of inhaled fluticasone produce greater systemic bioactivity than budesonide when given by large volume spacer on a microgram equivalent basis in asthmatic children. The systemic bioactivity of fluticasone, like budesonide, is due mainly to lung bioavailability.
Melanomas in renal transplant recipients: the London experience, and invitation to participate in a European study: reply from authors
Authors: B. Imko-Walczuk, A. Lally, L. Le Mire, D. Casabonne, K. Hollowood, C. Bordea, F. Wojnarowska
Journal: British Journal of Dermatology (2006)

Conflicts of interest: none declared. Sir, We are pleased that our previous results showing an eightfold increased risk of melanoma in renal transplant recipients (RTRs)1 is supported and confirmed by the study from London. However, we have re‐examined the incidence in our cohort because these two reports included melanoma in situ, which has a different prognosis and management from invasive melanoma and could give a higher incidence ratio compared with other centres that excluded in situ melanoma. Moreover, since 2002 we have had further new cases of melanoma in RTRs in Oxford, including recently a case of invasive melanoma in an Asian patient, indicating that immunosuppression may be an independent pathogenetic mechanism for melanoma. All new cases of invasive melanoma that occurred after 2002 in organ transplant recipients at the Oxford Transplant Centre were added to our previous data and cases of in situ melanoma were excluded. Data were taken from the Oxford Transplant Centre Clinical Database, on which all information on organ transplant patients and graft outcome are entered prospectively. We estimated the incidence of melanoma among patients who underwent organ transplantation between May 1964 and March 2006. Standardized incidence ratios (SIRs) were calculated by dividing the observed number in the Oxford transplant cohort by the expected number in the Oxford region (Berkshire, Buckinghamshire, Northamptonshire and Oxfordshire). Expected numbers of invasive melanoma were calculated by multiplying the age, gender and 5‐year calendar period (1963–2003) specific incidence rates of the region by the corresponding person‐years at risk in the Oxford cohort. Person‐years were derived from the date of transplantation up to the date of melanoma, the date of failure of last transplantation, the date of death or the last follow‐up, whichever came first. Assuming a Poisson distribution of the observed numbers, the 95% confidence intervals (CIs) and two‐sided P‐values were derived.
The Voltage-Gated Potassium Channel Subfamily KQT Member 4 (KCNQ4) Displays Parallel Evolution in Echolocating Bats
Authors: Y. Liu, N. Han, L. F. Franchini, H. Xu, F. Pisciottano, A. B. Elgoyhen, K. E. Rajan, S. Zhang
Journal: Molecular Biology and Evolution (2011)

Bats are the only mammals that use highly developed laryngeal echolocation, a sensory mechanism based on the ability to emit laryngeal sounds and interpret the returning echoes to identify objects. Although this capability allows bats to orientate and hunt in complete darkness, endowing them with great survival advantages, the genetic bases underlying the evolution of bat echolocation are still largely unknown. Echolocation requires high-frequency hearing that in mammals is largely dependent on somatic electromotility of outer hair cells. Then, understanding the molecular evolution of outer hair cell genes might help to unravel the evolutionary history of echolocation. In this work, we analyzed the molecular evolution of two key outer hair cell genes: the voltage-gated potassium channel gene KCNQ4 and CHRNA10, the gene encoding the α10 nicotinic acetylcholine receptor subunit. We reconstructed the phylogeny of bats based on KCNQ4 and CHRNA10 protein and nucleotide sequences. A phylogenetic tree built using KCNQ4 amino acid sequences showed that two paraphyletic clades of laryngeal echolocating bats grouped together, with eight shared substitutions among particular lineages. In addition, our analyses indicated that two of these parallel substitutions, M388I and P406S, were probably fixed under positive selection and could have had a strong functional impact on KCNQ4. Moreover, our results indicated that KCNQ4 evolved under positive selection in the ancestral lineage leading to mammals, suggesting that this gene might have been important for the evolution of mammalian hearing. On the other hand, we found that CHRNA10, a gene that evolved adaptively in the mammalian lineage, was under strong purifying selection in bats. Thus, the CHRNA10 amino acid tree did not show echolocating bat monophyly and reproduced the bat species tree. These results suggest that only a subset of hearing genes could underlie the evolution of echolocation. The present work continues to delineate the genetic bases of echolocation and ultrasonic hearing in bats.
Absence of MyD88 Signaling Induces Donor-Specific Kidney Allograft Tolerance
Authors: Huiling Wu, Gerda A. Noordmans, Maya R. O’Brien, Jin Ma, Cathy Y. Zhao, Geoff Y. Zhang, Tony K.T. Kwan, Stephen I. Alexander, Steven J. Chadban
Journal: Journal of the American Society of Nephrology (2012)

Toll-like receptors (TLRs) play a fundamental role in innate immunity and provide a link between innate and adaptive responses to an allograft; however, whether the development of acute and chronic allograft rejection requires TLR signaling is unknown. Here, we studied TLR signaling in a fully MHC-mismatched, life-sustaining murine model of kidney allograft rejection. Mice deficient in the TLR adaptor protein MyD88 developed donor antigen-specific tolerance, which protected them from both acute and chronic allograft rejection and increased their survival after transplantation compared with wild-type controls. Administration of an anti-CD25 antibody to MyD88-deficient recipients depleted CD4+CD25+FoxP3+ cells and broke tolerance. In addition, defective development of Th17 immune responses to alloantigen both in vitro and in vivo occurred, resulting in an increased ratio of Tregs to Th17 effectors. Thus, MyD88 deficiency was associated with an altered balance of Tregs over Th17 cells, promoting tolerance instead of rejection. This study provides evidence that targeting innate immunity may be a clinically relevant strategy to facilitate transplantation tolerance.
Absence of functioning alpha-adrenergic receptors in mature canine coronary collaterals.
Authors: D G Harrison, W M Chilian, M L Marcus
Journal: Circulation Research (1986)

To determine if mature coronary collateral vascular smooth muscle contains functioning alpha-adrenergic receptors, we studied 13 dogs, 6-10 months after circumflex ameroid occlusion. Regional myocardial blood flow was measured with radioactive microspheres in a blood-perfused heart preparation at constant aortic pressure (80 mm Hg). Normal zone resistance was calculated as aortic pressure divided by normal zone flow, and transcollateral resistance was calculated as aortic pressure minus circumflex pressure distal to the ameroid constrictor divided by coronary collateral flow. Flow and resistance were measured during adenosine vasodilation before and during graded doses of a constant infusion of the alpha-adrenergic agonist methoxamine (n = 6) or the alpha 2-adrenergic agonist clonidine (n = 7). In the hearts that received methoxamine, normal zone resistance increased from a control of 0.29 +/- 0.06 to 0.39 +/- 0.06 mm Hg X min/ml per 100 g (resistance units) during infusion of 10(-5)M methoxamine (p less than 0.05). In contrast transcollateral resistance averaged 0.24 +/- 0.02 resistance units under control conditions and did not change during methoxamine infusion. In the hearts that received clonidine, normal zone resistance averaged 0.24 +/- 0.03 resistance units and increased to 0.39 +/- 0.07 resistance units (p less than 0.05) with the highest dose of clonidine administered (10(-5) M). Transcollateral resistance averaged 0.17 +/- 0.03 resistance units during control conditions and did not change with clonidine infusion. In separate studies isometric tension development by the left anterior descending and coronary collateral vessels was examined in organ baths. The left anterior descending coronary artery demonstrated dose-dependent constriction to phenylephrine (peak response 22 +/- 5% of the response to 100 mM KCl). Clonidine produced weak constrictor responses in the left anterior descending coronary artery (5 +/- 2.5% maximal KCl response). In contrast, neither phenylephrine nor clonidine produced responses in mature collaterals. We also examined responses of mature collateral vessels to nonadrenergic agonists. In the vascular ring preparation the mature collaterals developed tension in the presence of KCl (2.3 +/- 0.9 g), prostaglandin F2 alpha (16 +/- 18% of the KCl responses), and vasopressin (90 +/- 30% of the KCl response). In adenosine-vasodilated hearts, pharmacologic doses of vasopressin caused a two-fold increase in transcollateral resistance. Thus, these studies performed on intact hearts and isolated vascular rings demonstrate that mature coronary collaterals do not contain functioning alpha-adrenergic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Underlying Mechanisms of Postoperative Pain After Laparoscopic Surgery
Authors: Samad E. J. Golzari, Nader D. Nader, Ata Mahmoodpoor
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Interactions of Lymphocytes With Reed-Sternberg Cells Within Hodgkins Disease Lymph Nodes.
Authors: John H. Frenster
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Interactions of Lymphocytes With Reed-Sternberg Cells Within Hodgkins Disease Lymph Nodes.John H. Frenster, M.D., R. Brent Archibald, B.S.John H. Frenster, M.D.Search for more papers by this author, R. Brent Archibald, B.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-794_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlthough the blood lymphocytes of patients with Hodgkin's disease may display a reduced in vitro response to antigens and phytohemagglutinin, lymphocytic infiltration of Hodgkin's disease lymph nodes does correlate positively with a favorable prognosis (Cancer 22:487, 1968). Such infiltration is thought to represent a host immune response to the neoplastic Reed-Sternberg cells and their precursors (J Nat Cancer Inst 39:557, 1967).Lymph node biopsies positive for Reed-Sternberg cells from previously-untreated patients were examined by electron microscopy. Reed-Sternberg cells (class 5) and their precursor cells (classes 2 to 4) were identified and were graded for ultrastructural toxic changes (A = none;... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Stanford, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byImmune Deficiency States Associated with Malignant Disease in Man 1 May 1970Volume 72, Issue 5Page: 794-794KeywordsBiopsyBloodCellsElectron microscopyHodgkin lymphomaImmune responseLymph nodesLymphocytesPhytohemagglutininsPrecursor cells Issue Published: 1 May 1970 PDF downloadLoading ...
Mannose-binding lectin deficiency and disease severity in non-cystic fibrosis bronchiectasis: a prospective study
Authors: James D Chalmers, Brian J McHugh, Catherine Doherty, Maeve P Smith, John R Govan, David C Kilpatrick, Adam T Hill
Journal: The Lancet Respiratory Medicine (2013)

Mannose-binding lectin (MBL) is a key component of innate immunity. MBL deficiency is common (10-30% of the general population depending on the definition used) and has been associated with disease progression in cystic fibrosis. We aimed to assess the effect of MBL deficiency on disease severity in non-cystic fibrosis bronchiectasis.We recruited patients with non-cystic fibrosis bronchiectasis and age-matched and sex-matched controls at a specialist bronchiectasis clinic in Edinburgh, UK. We assessed MBL function with genotyping (low-expressing genotype [deficiency] defined as homozygosity for exon 1 mutations [YO/YO] or compound heterozygosity [XA/YO]; YA/YO and XA/XA genotypes were defined as intermediate-expressing with all other genotypes defined as high-expressing) and serum measurements (deficiency defined with two parameters: <500 ng/mL or <200 ng/mL). We assessed rates of exacerbation, chronic bacterial colonisation, and lung function during 4 years of follow-up.We included 470 patients with bronchiectasis and 414 controls. MBL genotype frequencies and MBL serum concentrations did not differ between patients and controls. 55 (12%) patients with bronchiectasis had low-expressing genotypes. These patients had a mean of 2·7 exacerbations per year (SD 1·8), compared with 1·9 per year (1·2) for 135 patients with intermediate-expressing genotypes and 1·9 per year (1·3) for 280 patients with high-expressing genotypes (p<0·0001). Chronic colonisation with bacteria was most frequent in patients with low-expressing genotypes (47 [85%] patients vs 82 [61%] patients with intermediate-expressing genotypes and 183 [65%] patients with high-expressing genotypes; p=0·0041); especially P aeruginosa colonisation (19 [35%] patients vs 13 [10%] patients and 36 [13%] patients; p<0·0001). Patients with low-expressing genotypes were more likely to be admitted to hospital for severe exacerbations during follow-up (27 [49%] patients vs 42 [31%] patients and 87 [31%] patients; p=0·032). Patients with low-expressing genotypes also had increased scores for radiological severity and worse quality of life compared with the other two groups. MBL serum deficiency (<200 ng/mL) was associated with increased exacerbations, hospital admissions, and radiological severity. When <500 ng/mL was used as the definition of deficiency, the associations with exacerbation frequency and radiological severity were no longer significant.MBL might be an important modifier of disease severity in non-CF bronchiectasis.UK Medical Research Council, UK Chief Scientists Office.
Prospective Multicentre Evaluation of PCA3 and TMPRSS2-ERG Gene Fusions as Diagnostic and Prognostic Urinary Biomarkers for Prostate Cancer
Authors: Gisele H.J.M. Leyten, Daphne Hessels, Sander A. Jannink, Frank P. Smit, Hans de Jong, Erik B. Cornel, Theo M. de Reijke, Henk Vergunst, Paul Kil, Ben C. Knipscheer, Inge M. van Oort, Peter F.A. Mulders, Christina A. Hulsbergen-van de Kaa, Jack A. Schalken
Journal: European Urology (2012)
The Dysregulated Podocyte Phenotype
Authors: LAURA BARISONI, WILHELM KRIZ, PETER MUNDEL, VIVETTE D'AGATI
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Podocytes are highly differentiated, postmitotic cells, whose function is largely based on their complex cytoarchitecture. The differentiation of podocytes coincides with progressive expression of maturity markers, including WT-1, CALLA, C3b receptor, GLEPP-1, podocalyxin, and synaptopodin. In collapsing forms of focal segmental glomerulosclerosis (FSGS), including idiopathic FSGS and HIV-associated nephropathy, podocytes undergo characteristic, irreversible ultrastructural changes. This study analyzes the expression pattern of the above differentiation markers and of the proliferation marker Ki-67 in collapsing idiopathic FSGS and HIV-associated nephropathy compared with minimal change disease, membranous glomerulopathy, as well as normal adult and fetal human kidney. In minimal change disease and membranous glomerulopathy, all mature podocyte markers were retained at normal levels despite severe proteinuria and foot process fusion; no cell proliferation was observed. In contrast, in collapsing idiopathic FSGS and HIV-associated nephropathy, there was disappearance of all markers from all collapsed glomeruli and of synaptopodin from 16% of noncollapsed glomeruli. This phenotypic dysregulation of podocytes was associated with cell proliferation in both diseases. It is concluded that the loss of specific podocyte markers defines a novel dysregulated podocyte phenotype and suggests a common pathomechanism in collapsing FSGS, whether idiopathic or HIV-associated.