tbuckley/cabot-search huggingface dataset:
Rapid development of renal resistance to low doses of synthetic bovine parathyroid hormone fragment 1-34. Dissociation of urinary cyclic adenosine monophosphate, phosphaturic, and calciuric responses.
Authors: W M Law, H Heath
Journal: Journal of Clinical Investigation (1983)

The designing of parathyroid hormone (PTH)-renal dose-response studies in human beings is complicated by the possibility of rapid homologous receptor down-regulation, a phenomenon that is clearly shown to occur in vitro. Large amounts of PTH given to human subjects as serial injections or prolonged infusions cause decreased urinary 3',5'-cyclic adenosine monophosphate (cAMP) responses to subsequent PTH doses, but it is uncertain whether lower doses given over shorter periods similarly cause renal tachyphylaxis to PTH action. Thus, in seven water-loaded adults, we infused in ascending order 10, 30, 75, 150, and 300 U of synthetic bovine PTH fragment 1-34 (bPTH 1-34) per 70 kg body wt over 15 min on widely separated days ("separate day administration"). On another day, each subject received all five 15-min doses in ascending order at 75-min intervals ("single day administration"). Urine collection intervals were control, 0-30 min (including the PTH infusion), and 30-60 min. Peak nephrogenous cAMP (NcAMP, nmol/100 ml glomerular filtrate) response was linearly related to the dose of PTH (separate day study, r = 0.94, P less than 0.001; single day study, r = 0.88, P less than 0.001). However, the slope of NcAMP responses plotted against PTH dose for the single day study was only 36% of that derived from separate day administration of the same PTH doses (P less than 0.001). After only 40 U (10 + 30) of bPTH 1-34/70 kg, the NcAMP response to 75 U was reduced 44%, and the effect of 300 U/70 kg, when given as the last of the sequential single day infusions, was 64% less than the response to 300 U of bPTH 1-34 given alone (P less than 0.001). The phosphaturic response (fractional excretion of phosphorus, FEP [percent]) was also linearly related to bPTH 1-34 dose, but combined administration of the PTH infusions on one day increased FEP at each dose identically with the effects of separate day administration. A transient, dose-related, early hypercalciuric response to bPTH 1-34 also occurred, and was of equal magnitude in both protocols. These studies demonstrate that significant blunting of the NcAMP response to bPTH 1-34 occurs rapidly and follows brief exposure to relatively low doses of hormone. In contrast, there is no effect of recent PTH administration on the phosphaturic and early hypercalciuric actions of bPTH 1-34. This seeming dissociation of PTH effects makes unclear the physiologic importance of PTH-induced cAMP tachyphylaxis in the regulation of final PTH actions. In any case, studies of NcAMP responses in which the occurrence of tachyphylaxis would be undesirable should be designed to avoid prolonged or closely spaced administrations of the hormone.
1098. Duration of Expression of Sleeping Beauty Transposase by Hydrodynamic Injection of C57/BL6 Mice
Authors: Jason B. Bell, Elena L. Aronovich, Beth E. Larson-DeBruzzi, Brenda L. Koniar, Roland Gunther, Chester B. Whitley, R. Scott McIvor, Perry B. Hackett
Journal: Molecular Therapy (2005)

The Sleeping Beauty (SB) transposon system is extremely effective at integrating precise DNA sequences into vertebrate genomes, including those of humans. One potential use of this system is for gene therapy. The SB vector system has 2 components: 1) a transposon containing genetic cargo and 2) the catalytic transposase enzyme. In most cases the source of SB transposase has been a plasmid. This delivery strategy may allow extended periods of transposase activity that could cause deleterious effects were the transposons to be multiply remobilized. We have made several constructs to determine the duration of expression of SB transposase when delivered via a plasmid to cells in livers of mice. Three constructs contained the transposon and transposase on the same plasmid (cis constructs): pT2/mCAGGS-IDUA//Ub-SB11, pT2/mCAGGS-IDUA//MT-SB11, pT2/mCAGGS-GUSB//CMV-SB11. Another two constructs contained only a transposase gene with the transposon placed on separate plasmids (trans constructs): pT2/CAGGS-GUSB with PGK-SB11 and pT2/CAGGS-GUSB with SB11 RNA. MCAGGS is a shortened version, for driving the iduronidase (IDUA) gene, of the CAGGS promoter, which we use to drive glucuronidase B (GUSB) gene expression. We used high-pressure (hydrodynamic), tail-vein injection to deliver these constructs to the livers of C57/BL6 mice. The injections were evaluated 24hr post injection by expression assays of either the GUSB or IDUA genes. Mice will be euthanized at 6,5,4,3,2 months 6,4,2,1 weeks and 6,5,4,3,2,1 days and livers will be extracted. SB expression and functionality will be measured respectively by Western blot and excision PCR analyses. Linker-mediated PCR will be done to clone transposon insertions and integration as evidence of SB-mediated transposition events.
Development of radiolabeled bombesin analogs for the detection of gastrin-releasing peptide receptor expressing prostate cancer
Authors: Buck E. Rogers, Thomas S. Kelly, Rebecca Andrews, Jesse J. Parry
Journal: Clinical Cancer Research (2006)

A70  Introduction: Bombesin (BN) is a tetradecapeptide that binds with high affinity to the gastrin-releasing peptide receptor (GRPR), which is expressed on prostate tumors. It has been demonstrated that BN analogs can be radiolabeled with a variety of radiometals for potential diagnosis and treatment of GRPR-positive tumors. We have previously evaluated a BN analog that consists of the eight C-terminal amino acids of BN (BN(7-14)) conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) via an 8 carbon linker (Aoc) to yield DOTA-Aoc-BN(7-14). This was radiolabeled with the positron-emitter, 64Cu, and evaluated in mice bearing human prostate cancer xenografts. GRPR-mediated tumor uptake was observed by microPET imaging; however, there was also significant liver and kidney uptake. In the present study, we sought to reduce this liver and kidney uptake by replacing the Aoc linker with amino acid linkers. Experimental Procedures: The peptides were synthesized by solid phase peptide synthesis to contain linkers with either glycine (G), serine (S), or glutamic acid (E). DOTA was conjugated to BN(7-14) using the three amino acid linkers to form DOTA-linker-BN(7-14). The resulting peptides were DOTA-GGG-BN(7-14), DOTA-GSG-BN(7-14), DOTA-GEG-BN(7-14), DOTA-GSS-BN(7-14), and DOTA-GEE-BN(7-14). The unlabeled peptides were evaluated in a competitive binding assay using human PC-3 androgen independent prostate cancer cells to determine IC50 values. These peptides were radiolabeled with 64Cu and evaluated for internalization into PC-3 cells and for their biodistribution in mice bearing PC-3 tumor xenografts. Results: The competitive binding assay gave IC50 values of 50, 82, 2156, 32, and 19255 nM for the analogs with the GGG, GSG, GEG, GSS, and GEE linkers respectively. The GGG, GSG, and GSS analogs showed good internalization with 555, 680, and 666 fmol/mg being internalized at 24 h, while GEG and GEE did not internalize. The biodistribution studies showed that the tumor uptake for the GGG, GSG, and GSS analogs at 1 h after injection was 4.6, 2.8, and 3.8 percent of the injected dose per gram of tumor (% ID/g), respectively. This tumor uptake was greater than the uptake in all other tissues except for the liver, kidney and the GRPR-positive pancreas. Only the GGG linker demonstrated better tumor to liver and kidney ratios at 4 h compared to the original Aoc linker. In addition, administration of an excess of unlabeled BN demonstrated that the tumor uptake was GRPR-mediated. Conclusions: The tumor uptake of the GGG, GSG, and GSS analogs indicate that they might be useful for PET imaging of GRPR-expressing prostate cancer. MicroPET imaging studies using these analogs in tumor bearing mice are currently underway.
Book: Gender Inequalities in Health
Authors: A. M. Rossignol
Journal: BMJ (2000)

Eds Ellen Annandale, Kate Hunt Open University Press, £15.99, pp 192 ISBN 0 335 20364 7 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Gender differences in the opportunity to enjoy good health are related to the biological differences between men and women. Gender inequalities, on the other hand, are related to power and have an ethical component that biology does not. In understanding gender inequalities in health, it is helpful to ask the following questions: Who has power to access the healthcare system and the social, political, and economic arrangements that determine health status? Who has little power? Who is not willing to share … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Abstract 2086: PLK1 promotes epithelial-to-mesenchymal transition, confers oncogenic potential, and targets metastasis in prostate cancer
Authors: Jianguo Wu, Andrei Ivanov, Jinglei Zhang, Zheng Fu
Journal: Cancer Research (2014)

Abstract Polo-like kinase 1 (PLK1) has been well characterized as a master cell cycle regulator and implicated in the initiation and progression of different types of cancer and subsequently highlighted as a promising target for cancer therapy. It is canonically regarded that PLK1 deregulation promotes cancer development via catastrophic cell cycle events such as centrosome replication disturbance and chromosome instability. Recently, PLK1 has been shown to act as a regulator of cancer cell invasion, however, mechanisms underlying the effects of PLK1 on cell motility remain elusive. PLK1 is frequently upregulated in prostate cancer (PCa) and its expression level positively correlates with tumor grade and prognosis. Whether and how PLK1 contributes to the development and dissemination of PCa are still need to be investigated. Here, we showed PLK1 induces EMT in prostate epithelial cells and is required for prostate cancer cell lines to keep mesenchymal properties. We demonstrated that enhanced PLK1 expression transforms prostate epithelial cells to malignancy. Moreover, we found that PLK1 promotes invasion and is required for the metastasis of prostate cancer cells. Our data indicate that PLK1 is an EMT player and acts as an oncogene. These findings provide new sights into the non-mitotic function of PLK1 and suggest PLK1 as a potential target for intervention of the metastasis of prostate cancer. Note: This abstract was not presented at the meeting. Citation Format: Jianguo Wu, Andrei Ivanov, Jinglei Zhang, Zheng Fu. PLK1 promotes epithelial-to-mesenchymal transition, confers oncogenic potential, and targets metastasis in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2086. doi:10.1158/1538-7445.AM2014-2086
Intermittent short courses of cyclosporin (Neoral®) for psoriasis unresponsive to topical therapy: a 1-year multicentre, randomized study
Authors: None Ho, None Griffiths, None Albrecht, None Vanaclocha, None León-Dorantes, None Atakan, None Reitamo, None Ohannesson, None Mørk, None Clarke, None Pfister, None Paul
Journal: British Journal of Dermatology (1999)

We performed a 1-year study to determine whether intermittent short courses of the microemulsion formulation of cyclosporin (Neoral®) could effectively control plaque psoriasis and whether tapering or abrupt cessation of cyclosporin therapy would influence time to relapse. Four hundred patients with plaque psoriasis were included in this open, multicentre, randomized study. All patients commenced cyclosporin at a dose of 2.5 mg/kg daily. Cyclosporin dosage could be increased to a maximum of 5 mg/kg daily. Treatment was continued until clearance of psoriasis or for a maximum of 12 weeks. Patients were then randomly assigned either to stop cyclosporin abruptly or to have the dose reduced by 1 mg/kg daily each week until cessation. On relapse, patients were given another course of cyclosporin. Patients were followed for at least 1 year, during which they could receive as many treatment courses as necessary. The number of patients who required one, two, three and four treatment courses was 400, 259, 117 and 26, respectively. The median time to relapse after the end of the first treatment period was 109 days in the group of patients randomized to stop cyclosporin abruptly and 113 days in patients randomized to taper off cyclosporin (P = 0.038). More than 30% of patients had not relapsed 6 months after having stopped treatment. After each treatment course, the Kaplan–Meier probability of achieving 75% or more reduction in disease area by day 84 of treatment was 83%, 76%, 73% and 66%, respectively. Mean serum creatinine concentration and blood pressure did not show any clinically significant changes over time. Our results show that intermittent short-course therapy with Neoral®, when used in conjunction with topical therapy, is well tolerated and provides effective control of plaque psoriasis for 1 year. Tapering off cyclosporin on treatment cessation induces a slight delay in psoriasis relapse.
Infliximab plus Prednisone or Placebo plus Prednisone for the Initial Treatment of Polymyalgia Rheumatica
Authors: Carlo Salvarani, PierLuigi Macchioni, Carlo Manzini, Giuseppe Paolazzi, Aldo Trotta, Paolo Manganelli, Marco Cimmino, Roberto Gerli, Maria Grazia Catanoso, Luigi Boiardi, Fabrizio Cantini, Catherine Klersy, Gene G. Hunder
Journal: Annals of Internal Medicine (2007)

Some patients with polymyalgia rheumatica have a chronic relapsing course and require long-term glucocorticoid therapy. A small case series suggested that infliximab could reduce the glucocorticoid...
Better Bandage for Bleeding
Authors: Phil Gunby
Journal: JAMA (1999)

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 19766: Prediction of Clinical Atrial Fibrillation induced during Typical Atrial Flutter Ablation
Authors: Jorge Romero, Rodolfo Estrada, Anthony Holmes, David Goodman, Norman Roth, Anjani Golive, Jay Doshi, Eric Manheimer, John D Fisher, Jay Gross, Andrew Krumerman, Kevin Ferrick, Soo Kim, Luigi Di Biase
Journal: Circulation (2014)

Background: Atrial fibrillation (AF) and isthmus dependent atrial flutter (AFL) are two separate entities that in many patients coexist. We sought to investigate whether AF inducibility (spontaneous or drug induced) during isthmus AFL ablation predicted the occurrence of AF at follow up after successful AFL ablation. Methods: Two hundred seventy three consecutive patients with isthmus dependent AFL undergoing ablation of AFL at our institution were enrolled in this study. 119 (43%) patients were excluded since they had evidence of AF prior to AFL ablation. Univariate and multivariate analyses were performed. Results: A total of 154 patients (male: 72%, age: 61 ±13) with AFL and without history of AF composed our patient population. All patients underwent successful AFL ablation. During ablation, AF was induced in 28 (18%) patients. After a mean follow up of 34 ± 23.5 months a total of 50 (32%) experienced AF. Univariate and multivariate analyses showed that only age and AF inducibility during AFL ablation were predictors of AF. Univariate analysis (age: p=0.038 and inducible AF p=0.032 and multivariate analysis (age: p=0.011 inducible AF: p=0.016) ) with and adjusted odds ratio of 3.3 [95% CI (1.250-8.676)] (Table 1). A total of 169 (62%) patients experienced AF before or after AFL ablation. Conclusion: AF inducibility in patients undergoing isthmus dependent AFL without history of AF is a strong predictor of AF recurrence. This has an important clinical relevance on anticoagulation management of these patients.
Genomes in the Pipeline
Authors: Tracy Hampton
Journal: JAMA (2005)

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
T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: advantage of T-cell antibodies with narrow specificities.
Authors: Richard E. Champlin, Jakob R. Passweg, Mei Jie Zhang, Philip A. Rowlings, Corey J. Pelz, Kerry A. Atkinson, A. John Barrett, Jean Yves Cahn, William R. Drobyski, Robert Peter Gale, John M. Goldman, Alois Gratwohl, Edward C. Gordon-Smith, P. Jean Henslee-Downey, Roger H. Herzig, John P. Klein, Alberto M. Marmont, Richard J. O'Reilly, Olle Ringdén, Shimon Slavin, Kathleen A. Sobocinski, Bruno Speck, Roy S. Weiner, Mary M. Horowitz
Journal: Blood (2000)
646. Covalently-Closed, Dumbbell-Shaped Double-Stem-Loop DNA Constructs (dSLIM) with Specific Immunomodulatory Function
Authors: Nicole Hagner, Astrid Sander, Juliana Köck, Sven A. König-Merediz, Burghardt Wittig, Manuel Schmidt
Journal: Molecular Therapy (2004)

Linear, single-stranded oligonucleotide sequences (ODN) with unmethylated cytosine-guanine (CpG) motifs are immunomodulatory since they resemble bacterial DNA and serve as “danger signals”. These CpG-ODNs promote predominately a TH1-response, with secretion of IL-12 and IFN-γ, and B-cell, natural killer (NK)-cell and dendritic cell (DC) activation. They have a wide potential utility as therapeutic agents, i.e. for cancer gene therapy and as immunomodulators for the treatment of allergic diseases. Distinct groups of CpG-ODNs were characterized differing in structure and function: one group promotes B-cell proliferation, monocyte stimulation and secretion of IgM, IL-12 and IL-6; another activates γδT- and NK-cells to express CD69 and secrete IFN-γ, a third stimulating DC to produce IFN-α/IFN-β. Phosphorothioate (PS) modifications, usually introduced to enhance stability, result in several side-effects, like prolongation of the blood clotting time, non-specific binding to various proteins and acute toxicities in primates. A possibility to avoid PS-modifaction is to protect the open ends of linear phosphorodiester (PO)-ODN via generation of a short covalently-closed dumbbell-like structure. Here, we analyzed the stimulatory potential of a new class of molecules, double-stem-loop immunomodulators (dSLIM) with phosphorodiester (PO) backbones and a dumbbell-like structure: dSLIM-30L1 with CG motifs in both loops. We found a general stimulatory pattern of dSLIM-30L1 with enhanced surface expression of CD80/B7.1, CD40, HLA-DR and CD54/ICAM-1, which was concentration-dependent and restricted to a cell line of the B-lineage, while no such effect was detected in T-, NK-cells or monocytes. Interestinly, the level of expression was strictly dependent on molecule structure, size and backbone chemistry (PS vs. PO): Lin-30L1, a linear PS-ODN, had a similar effect compared to dSLIM-30L1, whereas changes in structure or CG content diminished their potential, testing molecules with only one loop, with CG motifs only in one loop, with a smaller size and a linear PO-ODN. Interestingly, dSLIM-30L1 significantly increased IL-12p40 production by B-cells, and IFN-γ production by NK-cells. Using total PBMCs, we found induction of a specific cytokine pattern by dSLIM-30L1 with levels of IFN-γ, IFN-α and IL-12p40 which is distinct from the pattern induced by the linear, PS-based lin-30L1. Furthermore, the PO-based dSLIM had significantly less prolonged blood clotting time compared to PS-based lin-30L1.
Abstract 16983: Inhibition of Dynamin-Related Protein 1 Accelerates Vascular Calcification in apoE-Deficient Mice through AKT Activation
Authors: Maximillian Rogers, Natalia Maldonado, Tyler Fiats, Claudia Goettsch, Joshua D Hutcheson, Iwao Yamada, Masanori Aikawa, Elena Aikawa
Journal: Circulation (2014)

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of cardiovascular disease. Dynamin-related protein 1 (DRP1) regulates mitochondrial function by driving membrane fission and allowing mitochondria to divide. How DRP1 acts in atherosclerosis, including the development of vascular calcification however remains unknown. Methods and Results: Aortic smooth muscle mitochondria from apoE-deficient mice (apoE-/-) exhibited a 47% increase in size compared to mitochondria from wild-type mice fed the same atherogenic diet for 18 weeks (N=103-129 mitochondria from 3 mice/group; p&lt;0.05). In agreement with the observed changes in mitochondrial morphology, inhibitory phosphorylation of DRP1 on Ser637 was enriched in apoE-/- mouse aortas. DRP1 immunoreactivity increased around calcified areas of apoE-/- mouse aortic sections. Additionally, DRP1 mRNA was increased 1.8-fold in calcified over non-calcified areas (N=8; p&lt;0.05). To determine the role of DRP1 inhibition on aortic lesion calcification, apoE-/- mice maintained on an atherogenic diet for 13 weeks (a point prior to calcified lesion development) were subsequently given the DRP1 inhibitor, MDIVI-1 (50mg/kg, i.p., once a week) for 5 more weeks. MDIVI-1 administration led to a 65% increase in calcified lesion area without altering lesion size (N=26 mice/group; p&lt;0.05). A single injection of MDIVI-1 resulted in a 3-fold increase in the ratio of phospho-AKT to total pan-AKT along with a strong increase in Runx2 protein in the apoE-/- mouse aorta 6 hours post-injection. MDIVI-1 administration did not alter bone remolding as detected by micro-CT in wild type or apoE-/- mice (N=5 mice/group). Conclusion: We provide novel roles of the mitochondrial fission protein DRP1 in the vascular calcification process, and demonstrate that inhibition of DRP1 through administration of the DRP1 inhibitor MDIVI-1 in apoE-/- mice accelerates vascular calcification through the AKT/Runx2 pathway.