tbuckley/cabot-search huggingface dataset:
Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.
Authors: M Pontoglio, S Sreenan, M Roe, W Pugh, D Ostrega, A Doyen, A J Pick, A Baldwin, G Velho, P Froguel, M Levisetti, S Bonner-Weir, G I Bell, M Yaniv, K S Polonsky
Journal: Journal of Clinical Investigation (1998)

Mutations in the gene for the transcription factor hepatocyte nuclear factor (HNF) 1alpha cause maturity-onset diabetes of the young (MODY) 3, a form of diabetes that results from defects in insulin secretion. Since the nature of these defects has not been defined, we compared insulin secretory function in heterozygous [HNF-1alpha (+/-)] or homozygous [HNF-1alpha (-/-)] mice with null mutations in the HNF-1alpha gene with their wild-type littermates [HNF-1alpha (+/+)]. Blood glucose concentrations were similar in HNF-1alpha (+/+) and (+/-) mice (7.8+/-0.2 and 7.9+/-0.3 mM), but were significantly higher in the HNF-1alpha (-/-) mice (13.1+/-0.7 mM, P < 0.001). Insulin secretory responses to glucose and arginine in the perfused pancreas and perifused islets from HNF-1alpha (-/-) mice were < 15% of the values in the other two groups and were associated with similar reductions in intracellular Ca2+ responses. These defects were not due to a decrease in glucokinase or insulin gene transcription. beta cell mass adjusted for body weight was not reduced in the (-/-) animals, although pancreatic insulin content adjusted for pancreas weight was slightly lower (0.06+/-0.01 vs. 0.10+/-0.01 microg/mg, P < 0.01) than in the (+/+) animals. In summary, a null mutation in the HNF-1alpha gene in homozygous mice leads to diabetes due to alterations in the pathways that regulate beta cell responses to secretagogues including glucose and arginine. These results provide further evidence in support of a key role for HNF-1alpha in the maintenance of normal beta cell function.
Use of inductively coupled plasma-mass spectrometry in boron-10 stable isotope experiments with plants, rats, and humans.
Authors: R A Vanderpool, D Hoff, P E Johnson
Journal: Environmental Health Perspectives (1994)

The commercial availability of inductively coupled plasma-mass spectrometry technology (ICP-MS) has presented the opportunity to measure the boron concentrations and isotope ratios in a large number of samples with minimal sample preparation. A typical analytical sequence for fecal samples consists of 25 acid blanks, 1 digestion blank, 5 calibration solutions, 4 standard reference material solutions, 10 samples, and 4 natural abundance bias standards. Boron detection limits (3 x 1 sigma) for acid blanks are 0.11 ppb for 10B, and 0.40 ppb for 11B. Isotope ratios were measured in fecal samples with 20 to 50 ppb boron with < 2% relative standard deviation. Rapid washout and minimal memory effects were observed for a 50 ppb beryllium internal standard, but a 200 ppb boron biological sample had a 1.0 ppb boron memory after a 6-min washout. Boron isotope ratios in geological materials are highly variable; apparently this variability is reflected in plants of a fixed natural abundance value for boron requires that a natural abundance ratio be determined for each sample or related data set. The natural abundance variability also prevents quantitation and calculation of isotope dilution by instrument-supplied software. To measure boron transport in animal systems, 20 micrograms of 10B were fed to a fasted rat. During the 3 days after a 10B oral dose, 95% of the 10B was recovered from the urine and 4% from the feces. Urinary isotope ratios, 11B/10B, changed from a natural abundance of 4.1140 to an enriched value of 0.95077, a 77% change.(ABSTRACT TRUNCATED AT 250 WORDS)
Perilesional brain oedema and seizure activity in patients with calcified neurocysticercosis: a prospective cohort and nested case–control study
Authors: Theodore E Nash, E Javier Pretell, Andres G Lescano, Javier A Bustos, Robert H Gilman, Armando E Gonzalez, Héctor H Garcia
Journal: The Lancet Neurology (2008)
GMC to gather data on prescribing errors after criticism
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

The UK General Medical Council will fund new research into the prevalence and causes of errors in prescribing in the NHS—after media reports blamed the poor teaching of therapeutics to medical students for an apparent rise in safety incidents caused by poor prescribing. 

The GMC, which regulates doctors in the United Kingdom and sets the undergraduate curriculum in medical schools, says that no evidence supports recent claims that trainee doctors are insufficiently prepared for prescribing when they reach the wards or that they are …
Fetal Cell Microchimerism in Papillary Thyroid Cancer: A Possible Role in Tumor Damage and Tissue Repair
Authors: Valentina Cirello, Maria Paola Recalcati, Marina Muzza, Stefania Rossi, Michela Perrino, Leonardo Vicentini, Paolo Beck-Peccoz, Palma Finelli, Laura Fugazzola
Journal: Cancer Research (2008)

Abstract Fetal cells enter the maternal circulation during pregnancy and can persist in the maternal blood or tissues for decades, creating a physiologic microchimerism. Because papillary thyroid cancer (PTC) is more frequent in women, the role of persisting fetal male cells in this tumor has been investigated. Tumor tissue specimens were obtained from 63 women with PTC who had a male pregnancy before the diagnosis. Male cells, identified by PCR amplification of a male-specific gene, the sex-determining region Y, was detected in 47.5% of women. By fluorescence in situ hybridization (FISH) analyses, the total number of microchimeric cells was significantly higher in neoplastic tissue than in controlateral normal sections. By combined FISH and immunohistochemistry (immuno-FISH), male cells expressing thyroglobulin were found in tumor and normal tissues, whereas male microchimeric cells stained with the CD45 antigen were detected only in tumor sections. Microchimeric cells negative for either marker were detected both in tumor and normal tissues. Moreover, both CD45+ and Tg+ fetal cells did not express MHC II antigens. In conclusion, fetal microchimerism has been documented in a high proportion of women with PTC. The immuno-FISH studies indicate that CD45+/MHC II− male cells found in neoplastic tissues might be committed to destroy tumor cells, whereas Tg+/MHC II− cells could have a repair function. Finally, microchimeric cells negative for either CD45 or Tg could have “progenitor-like” properties able to transdifferentiate in different cellular types. Although a pathogenetic mechanism cannot be excluded, the whole of the present results indicates a protective role of microchimerism in thyroid cancer. [Cancer Res 2008;68(20):8482–8]
Ghost Authorship in Industry-Initiated Randomised Trials
Authors: Peter C Gøtzsche, Asbjørn Hróbjartsson, Helle Krogh Johansen, Mette T Haahr, Douglas G Altman, An-Wen Chan
Journal: PLoS Medicine (2007)

Background Ghost authorship, the failure to name, as an author, an individual who has made substantial contributions to an article, may result in lack of accountability. The prevalence and nature of ghost authorship in industry-initiated randomised trials is not known. Methods and Findings We conducted a cohort study comparing protocols and corresponding publications for industry-initiated trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg in 1994–1995. We defined ghost authorship as present if individuals who wrote the trial protocol, performed the statistical analyses, or wrote the manuscript, were not listed as authors of the publication, or as members of a study group or writing committee, or in an acknowledgment. We identified 44 industry-initiated trials. We did not find any trial protocol or publication that stated explicitly that the clinical study report or the manuscript was to be written or was written by the clinical investigators, and none of the protocols stated that clinical investigators were to be involved with data analysis. We found evidence of ghost authorship for 33 trials (75%; 95% confidence interval 60%–87%). The prevalence of ghost authorship was increased to 91% (40 of 44 articles; 95% confidence interval 78%–98%) when we included cases where a person qualifying for authorship was acknowledged rather than appearing as an author. In 31 trials, the ghost authors we identified were statisticians. It is likely that we have overlooked some ghost authors, as we had very limited information to identify the possible omission of other individuals who would have qualified as authors. Conclusions Ghost authorship in industry-initiated trials is very common. Its prevalence could be considerably reduced, and transparency improved, if existing guidelines were followed, and if protocols were publicly available.
667. Gene Therapy for Beta Thalassemia: Preclinical Studies on Human Cells
Authors: Emanuela A. Roselli, Rossano Cesari, Annarita Miccio, Francesca Tiboni, Paola Corbella, Claudia Rossi, Erika Biral, Sarah Marktel, Michael Antoniou, Marco Andreani, Guido Lucarelli, Giuliana Ferrari
Journal: Molecular Therapy (2006)

Gene therapy for beta-thalassemia is based on the transplantation of genetically-modified autologous hematopoietic stem cells (HSC) into patients affected by the severe form of disease. The genetic treatment of the hemoglobinopathies poses the general challenge of efficient level of gene transfer into HSC and high and persistent transgene expression in vivo, in the differentiated progeny of a genetically modified stem cell. Recently, it was demonstrated that the efficient LV-mediated beta-globin gene transfer in CD34+ cells from thalassemic patients leads to the correction of some biological features, measured after erythroid differentiation in vitro and in the murine hematological chimera. The validation of a gene therapy approach to thalassemia requires to obtain results of gene correction in a broad number of patients' cells, since different molecular defects in the beta-globin gene lead to the clinical phenotype. The heterogeneity in the molecular defects and in the proportion of alpha and non-alpha (beta, gamma and delta) chains will represent a key element to set a threshold in the amount of vector-derived beta- chain required to correct a thalassemic phenotype. Additionally, the impact of some biological parameters, such as the degree of BM erythroid hyperplasia, the BM subpopulations proportion and the apoptotic index, on the successful correction of thalassemic phenotype needs to be studied in the perspective of clinical translation. In order to address these issues, we collected samples from BM aspirates and isolated CD34+ cells from 20 beta+ and beta0 thalassemic patients, characterized by different genotypes and biochemical profiles of globin chains synthesis. A novel, erythroid specific LV expressing human beta-globin from a minimal promoter enhanced by only 2 LCR elements (HS2 and HS3) was used to transduce BM derived CD34+ cells at high efficiency (>80%). The efficacy of the beta-globin LVs in correcting the human thalassemic phenotype was tested in an in vitro model of erythropoiesis and in the human-mouse hematological chimera. Upon transduction, normal level of HbA expression was achieved in erythroblastic cultures and BFU-E, associated with a progression towards erythroid maturation, which was impaired in mock-transduced thalassemic cells. Molecular analysis showed proviral integrity, with no detectable rearrangements and an average proviral copy number of 2.4. Analysis of specific globin chains proportion and contribution to phenotype correction in the context of different genotypes is under evaluation.
Persistent Expression of PEDF in the Eye Using High-capacity Adenovectors
Authors: Ping Chen, Melissa Hamilton, Charles A Thomas, Kurt Kroeger, Miguel Carrion, Randall S MacGill, Peter Gehlbach, Douglas E Brough, Lisa L Wei, C Richter King, Joseph T Bruder
Journal: Molecular Therapy (2008)

Ocular neovascularization, the growth of abnormal blood vessels in the eye, is a factor shared by the most common blinding diseases in developed countries. Pigment epithelium-derived factor (PEDF) is a potent antiangiogenic and neuroprotective protein that is normally produced in the eye. When delivered via an adenovector, PEDF can block the growth of new blood vessels and trigger the selective regression of abnormal vessels in animal models of ocular disease. Because of the absence of adenoviral genes, high-capacity (HC) adenovectors offer the potential for persistent transgene expression and enhanced tolerability. We have assessed the durability of PEDF expression and the induction of ocular inflammation following delivery of a PEDF-expressing HC adenovector compared to earlier generation vectors. The HC vector mediated prolonged PEDF expression in tissue-cultured pigmented epithelial cells and when delivered by intravitreal injection into the mouse eye. Delivery of first-generation adenovectors resulted in a dose-dependent increase in cytokine/chemokine gene expression, which correlated with the infiltration of inflammatory cells in the eye. In comparison, the levels of inflammatory gene expression and the intraocular infiltrate were substantially reduced following delivery of the HC vector. These results support the development of the HC adenovector gene delivery system for ocular disease. Ocular neovascularization, the growth of abnormal blood vessels in the eye, is a factor shared by the most common blinding diseases in developed countries. Pigment epithelium-derived factor (PEDF) is a potent antiangiogenic and neuroprotective protein that is normally produced in the eye. When delivered via an adenovector, PEDF can block the growth of new blood vessels and trigger the selective regression of abnormal vessels in animal models of ocular disease. Because of the absence of adenoviral genes, high-capacity (HC) adenovectors offer the potential for persistent transgene expression and enhanced tolerability. We have assessed the durability of PEDF expression and the induction of ocular inflammation following delivery of a PEDF-expressing HC adenovector compared to earlier generation vectors. The HC vector mediated prolonged PEDF expression in tissue-cultured pigmented epithelial cells and when delivered by intravitreal injection into the mouse eye. Delivery of first-generation adenovectors resulted in a dose-dependent increase in cytokine/chemokine gene expression, which correlated with the infiltration of inflammatory cells in the eye. In comparison, the levels of inflammatory gene expression and the intraocular infiltrate were substantially reduced following delivery of the HC vector. These results support the development of the HC adenovector gene delivery system for ocular disease.
New Focus on Long-term Mental Health of Patients Who Survive Serious Illness
Authors: Mike Mitka
Journal: JAMA (2009)

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
Abstract 3533: DNA binding molecules as a new tool to regulate cancer cell fate
Authors: Hiroki Nagase, Makoto T. Kimura, Xiaofei Wang, Takayoshi Watanabe, Kyoko Fujiwara, Rajeev Mishra, Hiroshi Sugiyama, Noboru Fukuda, Tadashi Terui
Journal: Cancer Research (2011)

Abstract Pyrrole-Imidazole (PI) polyamide molecule was originally designed from structures of natural DNA binding molecule, such as Distamicine and Diocarbamicine and has been discovered as a synthetic molecule which recognizes the minor groove of Watson-Click base pair of double-stranded DNA in a sequence-dependent manner. We have recently developed a semi-automatic synthesis system for PI polyamide, which are able to regulate specific target gene-expression under specific transcription factor binding inhibition for biological functional studies and perhaps patients’ therapy. PI polyamide immediately penetrated the nucleus in vitro and in vivo without any vehicle. After intra venous injection It rapidly reduce the serum concentration, delivered to most of tissue cells, excreted to urine or bile juice and did not metabolize in animals. The PI polyamides, designed for anti-Tgfb1 and anti-MMP9 activity, were well tolerated, reduced target gene expression and showed therapeutic effects in animal models of human diseases. For instance, when performed two studies using I.V. treatment by either of two independent anti-MMP9 polyamides, tumor metastasis was significantly suppressed in both studies using the same mouse model of human liver metastasis of colon cancer. This new auto-synthetic chemicals can be designed for many transcriptional regulation of transcripts and applied to prove many biological hypothesis of transcriptional regulation for cancer research, and may be used for cancer therapy in the future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3533. doi:10.1158/1538-7445.AM2011-3533
The ePedsQL™ in Type 1 and Type 2 Diabetes
Authors: James W. Varni, Christine A. Limbers, Tasha M. Burwinkle, William P. Bryant, Don P. Wilson
Journal: Diabetes Care (2008)

The Pediatric Quality of Life Inventory (PedsQL) is a modular instrument designed to measure health-related quality of life (HRQOL) in children and adolescents aged 2-18 years. The PedsQL 4.0 Generic Core Scales are child self-report and parent proxy-report scales developed as the generic core measure to be integrated with the PedsQL disease-specific modules. The electronic version of the PedsQL 4.0 (ePedsQL) was designed for Internet administration.Utilizing a randomized crossover design, the PedsQL scales were administered to 92 pediatric patients with type 1 or type 2 diabetes and 93 parents in electronic and paper formats.Missing values (0.76% child report, 0.37% parent report), internal consistency reliability (total scale score alpha = 0.90 child report, 0.92 parent report), and mean scores (total scale score M = 78.41 child report, 76.19 parent report) were equivalent between the electronic and paper-and-pencil modes of administration. The ePedsQL distinguished between healthy children and children with diabetes.The ePedsQL Internet mode of administration demonstrated equivalent measurement properties to the well-established PedsQL paper-and-pencil mode of administration.
Localized Sclerosing Cholangitis?
Authors: J. Panés, J.M. Bordas, M. Bruguera, M. Cortés, J. Rodés
Journal: Endoscopy (1985)

Primary sclerosing cholangitis presenting as a localized stricture affecting a segment of the extrahepatic biliary tree is seldom found. This article describes the case of a 56-year-old male admitted with obstructive jaundice, in whom endoscopic retrograde cholangiography showed a localized and smooth stricture at the common hepatic duct, initially diagnosed as cholangiocarcinoma. However, the histological examination of the resected stricture, common bile duct and gallbladder, and a liver biopsy performed 3.5 years later were consistent with primary sclerosing cholangitis, affecting both the extrahepatic and intrahepatic biliary tree.
Occult Splenic Rupture-Reply
Authors: Daniel C. Budd
Journal: JAMA (1977)

We appreciate the recent rethinking of the incidence of delayed rupture of the spleen through the routine use of paracentesis. Despite the reduced incidence mentioned in Dr Fischer's letter, the mechanism by which a true delayed rupture occurs is a valid one. The dilemma of an occult rupture stems from the fact that hemorrhage is tamponaded and contained by adjacent stomach, bowel, and omentum—preventing free intraperitoneal bleeding; thus, it is not amenable to diagnosis by paracentesis.
Lithium clearance (C1Li) and its predictive value on ascites-related complications in hepatic cirrhosis
Authors: Silvano Fasolato, Paolo Angeli, Raffaella Craighero, Andrea Quarello, Alessandra Galioto, Giovanna Serianni, Virna Dalla Libera, Antonietta Sticca, Franco Del Piccolo, Angelo Gatta
Journal: Journal of Hepatology (2002)
Insulin resistance in pulmonary arterial hypertension
Authors: R. T. Zamanian, G. Hansmann, S. Snook, D. Lilienfeld, K. M. Rappaport, G. M. Reaven, M. Rabinovitch, R. L. Doyle
Journal: European Respiratory Journal (2008)

Although obesity, dyslipidemia and insulin resistance (IR) are well known risk factors for systemic cardiovascular disease, their impact on pulmonary arterial hypertension (PAH) is unknown. The present authors’ previous studies indicate that IR may be a risk factor for PAH. The current study has investigated the prevalence of IR in PAH and explored its relationship with disease severity. Clinical data and fasting blood samples were evaluated in 81 nondiabetic PAH females. In total, 967 National Health and Nutrition Examination Surveys (NHANES) females served as controls. The fasting triglyceride to high-density lipoprotein cholesterol ratio was used as a surrogate of insulin sensitivity. While body mass index was similar in NHANES versus PAH females (28.6 versus 28.7 kg·m −2 ), PAH females were more likely to have IR (45.7 versus 21.5%) and less likely to be insulin sensitive (IS; 43.2 versus 57.8%). PAH females mostly (82.7%) had New York Heart Association (NYHA) class II and III symptoms. Aetiology, NYHA class, 6-min walk-distance and haemodynamics did not differ between IR and IS PAH groups. However, the presence of IR and a higher NYHA class was associated with poorer 6-months event-free survival (58 versus 79%). Insulin resistance appears to be more common in pulmonary arterial hypertension females than in the general population, and may be a novel risk factor or disease modifier that might impact on survival.