tbuckley/cabot-search huggingface dataset:
History of the Pancreas: Mysteries of a Hidden Organ
Authors: N. Joseph Espat
Journal: JAMA (2003)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Subfunctionalization via Adaptive Evolution Influenced by Genomic Context: The Case of Histone Chaperones ASF1a and ASF1b
Authors: Federico Abascal, Armelle Corpet, Zachary A. Gurard-Levin, David Juan, Françoise Ochsenbein, Daniel Rico, Alfonso Valencia, Geneviève Almouzni
Journal: Molecular Biology and Evolution (2013)

Gene duplication is regarded as the main source of adaptive functional novelty in eukaryotes. Processes such as neo- and subfunctionalization impact the evolution of paralogous proteins where functional divergence is frequently key to retain the gene copies. Here, we examined antisilencing function 1 (ASF1), a conserved eukaryotic H3–H4 histone chaperone, involved in histone dynamics during replication, transcription, and DNA repair. Although yeast feature a single ASF1 protein, two paralogs exist in most vertebrates, termed ASF1a and ASF1b, with distinct cellular roles in mammals. To explain this division of tasks, we integrated evolutionary and comparative genomic analyses with biochemical and structural approaches. First, we show that a duplication event at the ancestor of jawed vertebrates, followed by ASF1a relocation into an intron of the minichromosome maintenance complex component 9 (MCM9) gene at the ancestor of tetrapods, provided a different genomic environment for each paralog with marked differences of GC content and DNA replication timing. Second, we found signatures of positive selection in the N- and C-terminal regions of ASF1a and ASF1b. Third, we demonstrate that regions outside the primary interaction surface are key for the preferential interactions of the human paralogs with distinct H3–H4 chaperones. On the basis of these data, we propose that ASF1 experienced subfunctionalization shaped by the adaptation of the genes to their respective genomic context, reflecting a case of genomic context-driven escape from adaptive conflict.
Alpha 1-antitrypsin and Protease Complexation Is Induced by Lipopolysaccharide, Interleukin-1 β , and Tumor Necrosis Factor- α in Monocytes
Authors: DAREN L. KNOELL, DAVID R. RALSTON, KRISTIN R. COULTER, MARK D. WEWERS
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Local regulation of alpha1-antitrypsin (alpha1-AT) may have importance in maintenance of the protease-antiprotease balance in the microenvironment of inflammatory cells. We therefore studied whether lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNFalpha) affect the pericellular concentration of alpha1-AT in human peripheral blood mononuclear cells (PBMC). PBMC taken from normal healthy volunteers were treated with LPS, IL-1beta, and TNFalpha, and the concentration of human alpha1-AT in conditioned supernatants was measured. When compared with unstimulated control supernatants (147 +/- 19 ng/ml), LPS (439 +/- 66 ng/ml; p < or = 0.001), IL-1beta (263 +/- 37 ng/ml; p < or = 0.01), and TNFalpha (316 +/- 59 ng/ml; p < or = 0.05) induced a 2- to 3-fold increase of alpha1-AT. Up-regulation of alpha1-AT protein correlated with an increase in alpha1-AT mRNA, suggesting a simultaneous increase in alpha1-AT synthesis. Despite the increase in alpha1-AT concentration, functional antiprotease activity could not be detected. Furthermore, protease activity was present in all samples, with the amount of activity being inversely related to the amount of alpha1-AT measured in supernatants. These findings suggest that local inflammatory conditions up-regulate alpha1-AT production by monocytes which complex with a protease derived from the PBMC population.
Health and Economic Benefits of Well-Designed Evaluations: Some Lessons From Evaluating Neuroblastoma Screening
Authors: Lee Soderstrom, William G. Woods, Mark Bernstein, Leslie L. Robison, Mendel Tuchman, Bernard Lemieux
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Well-designed evaluations of health services are frequently made today. However, the extent of the evaluations' benefits and costs is not well documented, creating uncertainty whether their use is optimal from society's perspective. We examined these costs and benefits using data from one well-designed evaluation, the Quebec Neuroblastoma Screening Project (QNSP). It screened most Quebec newborns between 1989 and 1994 for neuroblastoma. As previously reported, the screening did not reduce neuroblastoma mortality and caused adverse health effects. Methods: We compared the cost of doing the QNSP with its benefits. Had the QNSP not been undertaken, neuroblastoma screening would have been implemented throughout North America. We assume that screening would have started in 1989 and ended in 2002. The QNSP's benefits include the health costs and adverse health effects averted by not using ineffective screening during those 14 years. In our calculations we used neuroblastoma incidence data for the QNSP and for Ontario where there was no screening, detailed data describing the health services used by the patients, and Quebec cost data for those services. Results: The QNSP cost $8.77 million (2002 US dollars). By not implementing similar screening programs between 1989 and 2002, the United States and Canada avoided $574.1 million in health costs, the unnecessary treatment of 9223 children, and false-positive findings for 5003 children screened. Conclusions: The health care costs and adverse health effects averted by the QNSP justify its costs. These results show that well-designed evaluations can yield—at least sometimes—benefits substantially greater than their high costs. This raises an important policy issue: are these evaluations now being under- or over used?
Tumour tissue sampling for lung cancer management in the era of personalised therapy: what is good enough for molecular testing?
Authors: Lucia Kim, Ming Sound Tsao
Journal: European Respiratory Journal (2014)

In the era of personalised cancer therapy, the demand for molecular profiling of the patient's tumour is steadily increasing. In advanced nonsmall cell lung cancer (NSCLC) patients, testing for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements has become an essential component of clinical practice to select patients who are most likely to benefit from EGFR and ALK tyrosine kinase inhibitors, respectively. Furthermore, obtaining tissue specimens from recurrent or metastatic tumours or from patients who develop resistance to initial effective therapies are essential for our understanding of the molecular basis of tumour progression and development of drug resistance. Therefore, the sampling of tumour tissue that is representative and is adequate in quantity and quality for pathological diagnosis and genomic profiling is crucial. In this review, we will discuss factors that should be considered in obtaining and processing biopsy specimens to enable routine molecular analysis in NSCLC patients.
Metabolism in immunoreactive parathyroid hormone in the dog. The role of the kidney and the effects of chronic renal disease.
Authors: K A Hruska, R Kopelman, W E Rutherford, S Klahr, E Slatopolsky, A Greenwalt, T Bascom, J Markham
Journal: Journal of Clinical Investigation (1975)

The role of the kidney in the metabolism of parathyroid hormone (PTH) was examined in the dog. Studies were performed in awake normal and uremic dogs after administration of bovine parathyroid hormone (b-PTH) or synthetic amino terminal tetratricontapeptide of b-PTH (syn b-PTH 1-34). The renal clearance of immunoreactive PTH was determined from the product of renal plasma flow and the percent extraction of PTH immunoreactivity by the kidney. Blood levels of circulating immunoreactive PTH were determined by radioimmunoassay. The normal dog kidney extracted 20 plus or minus 1% of the immunoreactive b-PTH delivered to it, and renal clearance (RC) of immunoreactivity was 60 ml/min. When RC was compared to an estimate of total metabolic clearance (MCR) of immunoreactivity, it accounted for 61% of the total. Both MCR and RC were markedly decreased in dogs with chronic renal disease. However, the percent extraction of immunoreactive PTH was unchanged in chronic renal disease, and the observed decrease in RC was due to changes in renal plasma flow. The largest portion of the reduction in total MCR was accounted for by the decrease in RC, and there was no compensation for the decrease in RC by extrarenal sites of PTH metabolism.
Oxidant stress with hydrogen peroxide attenuates calcium paradox injury: role of protein kinase C and ATP-sensitive potassium channel
Authors: Hiroshi Miyawaki, Yigang Wang, Muhammad Ashraf
Journal: Cardiovascular Research (1998)

We tested the hypotheses that low concentration of H2O2 attenuates the Ca2+ paradox (Ca2+ PD) injury, and that activation of protein kinase C (PKC) and/or ATP-sensitive potassium channel (KATP) are involved in the protective effects of H2O2.Langendorff-perfused rat hearts were subjected to the Ca2+ PD (10 min of Ca2+ depletion followed by 10 min of Ca2+ repletion). Functional and biochemical effects of H2O2 and other interventions on the cell injury induced by the Ca2+ PD were assessed.In the Ca2+ PD hearts pretreated with 20 mumol/l H2O2, left ventricular end-diastolic pressure and coronary flow were significantly preserved. Furthermore, peak lactate dehydrogenase release was significantly decreased and ATP contents were more preserved, compared with non-treated Ca2+ PD hearts. H2O2-treated hearts also showed remarkable preservation of cell structure. Addition of a specific PKC inhibitor, chelerythrine during H2O2 treatment completely abolished the beneficial effects of H2O2 on the Ca2+ PD. Similarly, an activator of PKC. Phorbol 12-myristate 13 acetate mimicked the protection by H2O2. Furthermore, pretreatment with a KATP opener, cromakalim also provided protection similar to H2O2 against the Ca2+ PD injury. However, a specific KATP inhibitor, glibenclamide was not able to completely block the effects of H2O2.These findings suggest that pretreatment with low concentration of H2O2 provides significant protection against the lethal injury of Ca2+ PD in rat hearts. PKC-mediated signaling pathways appear to play a crucial role in the protection against the Ca2+ PD injury.
663 PREDICTIVENESS OF WASH-OUT TIME INTENSITY CURVE ON HEPATOCELLULAR CARCINOMA RECURRENCE
Authors: C.D.M. Witjes, F.E.J.A. Willemssen, J. Verheij, S.J. van der Veer, B.E. Hansen, C. Verhoef, R.A. de Man, J.N.M. Ijzermans
Journal: Journal of Hepatology (2011)
VACCINES IN SKIN DISEASES
Authors: A. G. Shera
Journal: BMJ (1918)

<h3>Aims</h3> To evaluate the contribution of light microscopy to detecting <i>Candida</i> spp infection in patients with complicated intra-abdominal infections (IAIs) admitted for acute abdomen to a quality assurance (QA)-certified surgical emergency ward. <h3>Methods</h3> We conducted a retrospective study (2008–2012) of 809 abdominal intraoperative or biopsy tissue specimens obtained from patients admitted with acute abdomen and microbiological samples positive for <i>Candida</i> spp. Demographic data, mortality, comorbidities, specimen type, microscopy results, special histological staining performed, antimicrobial therapy were collected and analysed. Any comments at the multidisciplinary team meeting was recorded in minutes of and approved. <h3>Results</h3> Sixty-six patients with complicated IAIs due to <i>Candida</i> spp were identified (39 male, 27 female, mean±SD age 75±20 years). <i>Candida albicans</i> was isolated in 35 cases and <i>Candida non-albicans</i> spp in 31 cases. <i>Candida</i> spp were isolated from blood in 50% of all selected microbiological specimens. Patients were stratified according to <i>Candida</i> spp <i>(albicans</i> vs <i>non-albicans)</i>, underlying cancer disease and no previous antimicrobial administration, and a positive correlation with <i>C. albicans</i> isolation was found (p=0.009 and p=0.048, respectively). Out of 41 cases with microscopic evaluation, we identified yeast forms, pseudohyphae or both, indicative of <i>Candida</i> spp, in 23. Identification of <i>Candida</i> spp in histological specimens was higher in <i>C. albicans</i> cases than in <i>C. non-albicans</i> cases (73% vs 37.5%). Microscopy allowed prompt treatment of all patients. <h3>Conclusions</h3> Light microscopy still has great diagnostic significance, being a solid QA step. It provides rapid information and clues in patients who may harbour impaired defence mechanisms, concurrent chronic conditions and/or cancer.
The chemopreventive retinoid 4HPR impairs prostate cancer cell migration and invasion by interfering with FAK/AKT/GSK3β pathway and β-catenin stability
Authors: Roberto Benelli, Stefano Monteghirfo, Roberta Venè, Francesca Tosetti, Nicoletta Ferrari
Journal: Molecular Cancer (2010)

Abstract Background Prostate cancer shows an extremely slow progression, appearing in its metastatic, hormone refractory phenotype mostly in elderly men. The chemopreventive targeting of this tumor could accordingly delay its malignancy over life expectancy. The cancer chemopreventive retinoid N -(4 hydroxyphenyl)retinamide (4HPR) has already been shown to restrain prostate cancer growth in vitro and in vivo, though its mechanisms of action are only partially explained. Results We found that 4HPR impairs DU145 and PC3 prostate cancer cells migration and invasion by down-regulating FAK and AKT activation and by enhancing β-catenin degradation, causing the downregulation of target genes like cyclin D1, survivin and VEGF. This non-migratory phenotype was similarly produced in both cell lines by stable silencing of β-catenin. 4HPR was able to decrease AKT phosphorylation also when powerfully upregulated by IGF-1 and, consequently, to impair IGF-1-stimulated cell motility. Conversely, the expression of constitutively active AKT (myr-AKT) overcame the effects of 4HPR and β-catenin-silencing on cell migration. In addition, we found that BMP-2, a 4HPR target with antiangiogenic activity, decreased prostate cancer cell proliferation, migration and invasion by down-regulating the pathway described involving AKT phosphorylation, β-catenin stability and cyclin D1 expression. Conclusion These data point to 4HPR as a negative regulator of AKT phosphorylation, effectively targeting the β-catenin pathway and inducing a relatively benign phenotype in prostate cancer cells, limiting neoangiogenesis and cell invasion.
Targeted Delivery of <i>microRNA-29b</i> by Transferrin-Conjugated Anionic Lipopolyplex Nanoparticles: A Novel Therapeutic Strategy in Acute Myeloid Leukemia
Authors: Xiaomeng Huang, Sebastian Schwind, Bo Yu, Ramasamy Santhanam, Hongyan Wang, Pia Hoellerbauer, Alice Mims, Rebecca Klisovic, Alison R. Walker, Kenneth K. Chan, William Blum, Danilo Perrotti, John C. Byrd, Clara D. Bloomfield, Michael A. Caligiuri, Robert J. Lee, Ramiro Garzon, Natarajan Muthusamy, Ly James Lee, Guido Marcucci
Journal: Clinical Cancer Research (2013)

miR-29b directly or indirectly targets genes involved in acute myeloid leukemia (AML), namely, DNMTs, CDK6, SP1, KIT, and FLT3. Higher miR-29b pretreatment expression is associated with improved response to decitabine and better outcome in AML. Thus, designing a strategy to increase miR-29b levels in AML blasts may be of therapeutic value. However, free synthetic miRs are easily degraded in bio-fluids and have limited cellular uptake. To overcome these limitations, we developed a novel transferrin-conjugated nanoparticle delivery system for synthetic miR-29b (Tf-NP-miR-29b).Delivery efficiency was investigated by flow cytometry, confocal microscopy, and quantitative PCR. The expression of miR-29b targets was measured by immunoblotting. The antileukemic activity of Tf-NP-miR-29b was evaluated by measuring cell proliferation and colony formation ability and in a leukemia mouse model.Tf-NP-miR-29b treatment resulted in more than 200-fold increase of mature miR-29b compared with free miR-29b and was approximately twice as efficient as treatment with non-transferrin-conjugated NP-miR-29b. Tf-NP-miR-29b treatment significantly downregulated DNMTs, CDK6, SP1, KIT, and FLT3 and decreased AML cell growth by 30% to 50% and impaired colony formation by approximately 50%. Mice engrafted with AML cells and then treated with Tf-NP-miR-29b had significantly longer survival compared with Tf-NP-scramble (P = 0.015) or free miR-29b (P = 0.003). Furthermore, priming AML cell with Tf-NP-miR-29b before treatment with decitabine resulted in marked decrease in cell viability in vitro and showed improved antileukemic activity compared with decitabine alone (P = 0.001) in vivo.Tf-NP effectively delivered functional miR-29b, resulting in target downregulation and antileukemic activity and warrants further investigation as a novel therapeutic approach in AML.
Assessment of the relative systemic potency of inhaled fluticasone and budesonide
Authors: M. Boorsma, N. Andersson, P. Larsson, A. Ullman
Journal: European Respiratory Journal (1996)

Studies using dry powder devices have suggested that fluticasone propionate (FP) has a greater systemic effect than budesonide (BUD). The aim of the present study was to investigate and compare the relative systemic potency of FP and BUD from their respective pressurized metered-dose inhalers (pMDIs). A placebo-controlled, open, randomized, cross-over study was conducted in 21 healthy male volunteers. Placebo, BUD (200, 400 and 1,000 micrograms b.i.d.) and FP (200, 375 and 1,000 micrograms b.i.d.) were inhaled for 4 days, with a wash-out period of at least 3 days between treatments. Blood samples for cortisol analysis were drawn during the last 24 h of each treatment period. Cortisol levels, measured as 24 h pooled plasma cortisol, were statistically significantly lower (p = 0.0001) for all dose levels during FP pMDI treatment (21, 39 and 84% suppression from placebo) than during BUD pMDI treatment (1, 3 and 27% suppression from placebo). The relative systemic potency FP:BUD was 3.7:1 (95% confidence interval (95% CI) 2.9-4.8)). The relative systemic potency based on the single 08:00 h samples was 5.2:1 (95% CI 3.0-9.3). In conclusion, in healthy male volunteers using pressurized metered-dose inhalers, fluticasone propionate was shown to have a stronger systemic effect than budesonide.
Cis and trans regulatory elements in NPHS2 promoter: Implications in proteinuria and progression of renal diseases
Authors: M. Di Duca, R. Oleggini, S. Sanna-Cherchi, L. Pasquali, A. Di Donato, S. Parodi, R. Bertelli, G. Caridi, G. Frasca, G. Cerullo, A. Amoroso, F.P. Schena, F. Scolari, G.M. Ghiggeri, None The European IgA Nephropathy Consortium
Journal: Kidney International (2006)
Electronic Health Records and Quality of Diabetes Care
Authors: Randall D. Cebul, Thomas E. Love, Anil K. Jain, Christopher J. Hebert
Journal: New England Journal of Medicine (2011)

Available studies have shown few quality-related advantages of electronic health records (EHRs) over traditional paper records. We compared achievement of and improvement in quality standards for diabetes at practices using EHRs with those at practices using paper records. All practices, including many safety-net primary care practices, belonged to a regional quality collaborative and publicly reported performance.
Study Discovers Key Switch in Breast Cancer Metastases
Authors: M. Fillon
Journal: JNCI Journal of the National Cancer Institute (2012)

according to a computational mechanical model. The cytoskeleton, present in all cells, is cellular scaffolding contained within the cytoplasm and made from protein. Previous studies have shown that elevated expression of p38 is associated with lower overall survival of patients with breast cancer. “Taken together, our results offer a detailed characterization of how p38 contributes to breast cancer progression.”
Targeted Toxin Therapy for the Treatment of Cancer
Authors: D. FitzGerald, I. Pastan
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Targeted Toxin Therapy for the Treatment of Cancer Get access David FitzGerald, David FitzGerald * Laboratory of Molecular Biology, National Cancer Institute, National Institutes of HealthBethesda, MD *Correspondence to: Dr. David FitzGerald, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bldg. 37, Rm. 4B27, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ira Pastan Ira Pastan Laboratory of Molecular Biology, National Cancer Institute, National Institutes of HealthBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 19, 4 October 1989, Pages 1455–1463, https://doi.org/10.1093/jnci/81.19.1455 Published: 04 October 1989 Article history Received: 02 May 1989 Accepted: 09 May 1989 Published: 04 October 1989
Increasing Prevalence of the Metabolic Syndrome Among U.S. Adults
Authors: Earl S. Ford, Wayne H. Giles, Ali H. Mokdad
Journal: Diabetes Care (2004)

OBJECTIVE—The prevalence of the metabolic syndrome is high among U.S. adults. Our purpose was to determine whether the prevalence of this syndrome has changed since 1988–1994. RESEARCH DESIGN AND METHODS—A total of 6,436 men and women aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and 1,677 participants from NHANES 1999–2000 were included in the analyses. We used the definition of the metabolic syndrome developed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. RESULTS—The unadjusted prevalence of the metabolic syndrome was 23.1% in NHANES III and 26.7% in NHANES 1999–2000 (P = 0.043), and the age-adjusted prevalences were 24.1 and 27.0% (P = 0.088), respectively. The age-adjusted prevalence increased by 23.5% among women (P = 0.021) and 2.2% among men (P = 0.831). Increases in high blood pressure, waist circumference, and hypertriglyceridemia accounted for much of the increase in the prevalence of the metabolic syndrome, particularly among women. CONCLUSIONS—The increased prevalence of the metabolic syndrome is likely to lead to future increases in diabetes and cardiovascular disease.