tbuckley/cabot-search huggingface dataset:
Inheritance of Low Immunoreactive Human Plasma Dopamine-β-Hydroxylase
Authors: Joel Dunnette, Richard Weinshilboum
Journal: Journal of Clinical Investigation (1977)

Inheritance plays an important role in the determination of human plasma dopamine-β-hydroxylase (DBH) enzymatic activity. It has been demonstrated that an allele (d) for very low enzymatic plasma DBH is inherited as an autosomal recessive trait. A radioimmunoassay for human DBH was developed to test the hypothesis that the presence of this allele results in a decrease in plasma DBH protein levels. The mean immunoreactive DBH (IDBH) in blood from a randomly selected population of adolescents was 824±38 ng/ml (mean±SEM, n = 134). The correlation coefficient of enzymatic DBH with IDBH for this group of 134 adolescents was 0.84 (P < 0.001). Of these subjects, 3.7% had values of < 100 ng/ml and appeared to compose a separate subgroup analogous to the 3-4% of the population that is homozygous for the allele for low enzymatic activity. There was a significant sibling-sibling correlation of IDBH values in the 14 sibling pairs included among the 134 subjects studied (r = 0.60, P < 0.025). IDBH was also measured in blood from 56 subjects homozygous (dd) for the allele for low enzymatic DBH (enzymatic activity < 50 U/ml) and in blood of 80 first-degree relatives of homozygous probands. All but two dd subjects had IDBH levels of <100 ng/ml. Results of family studies were compatible with the autosomal recessive inheritance of an allele for IDBH levels of less than 100 ng/ml which segregates with the allele for very low enzymatic activity. Average IDBH in blood of 37 obligate heterozygotes as determined by family studies (Dd) was 599±53 ng/ml (mean ± SEM), significantly lower than the IDBH values found in a randomly selected population (P < 0.005). These results are compatible with the conclusion that the presence of the allele for low plasma enzymatic DBH results in a decrease in the quantity of DBH protein in human plasma.
A double-blind, placebo-controlled trial of pegylated recombinant human megakaryocyte growth and development factor as an adjunct to induction and consolidation therapy for patients with acute myeloid leukemia
Authors: Charles A. Schiffer, Kenneth Miller, Richard A. Larson, Philip C. Amrein, Joseph H. Antin, Valter J. Zani, Richard M. Stone
Journal: Blood (2000)
451. A Novel Cell Cycle Dependent Conditionally Replicating Adenovirus Vector for Targeting a Broad-Spectrum of Cancer
Authors: Phillip H. Abbosh, Kenneth P. Nephew
Journal: Molecular Therapy (2004)

Anaplastic thyroid cancer is one of the most deadly and untreatable neoplasms, with universal lethality within one year and average life expectancy around 6 months after diagnosis. Recent studies on late stage human thyroid tumors showed that mutations on critical residues which mediate β-catenin degradation lead to nuclear localization and β-catenin signaling activity. The purpose of this study was to determine if thyroid cancer cell lines have active Wnt/β-catenin signaling and if this pathway could be harnessed to drive a replication-restricted adenovirus. Additionally, we tested whether RGD-inserted knob protein can enhance adenoviral tropism. To show that β-catenin signaling is activated in thyroid cancer cell lines, Western blot analysis of thyroid cancer cell nuclear extracts was performed. Accumulation of β-catenin in the nuclear fraction was observed, and this accumulation correlates with transcriptional activity from a TCF/LEF reporter plasmid. Because anaplastic thyroid cancer prognosis is hopeless and current treatment options are extremely limited, we created a conditionally replicative adenovirus (CRAd) that targets the Wnt/β-catenin pathway by placing two TCF/LEF response elements upstream of both the E1a and E1b TATA boxes (the remaining adenoviral genome remained intact). The CRAd construct used in this study replicates only in thyroid cancer cell lines aberrantly activated in the Wnt/β-catenin pathway or non-thyroid cancer cell lines with an active Wnt/β-catenin pathway, such as those originating from colorectal cancers. To determine if insertion of the RGD motif into the adenoviral knob increased infection efficiency for thyroid cancer cell lines, AdCMV-luc constructs with either wild type or RGD-inserted knob were used in reporter assays across a panel of cell lines. Reporter activity from Ad-RGD-luc infected thyroid cancer cells is 2 to 25 fold higher than Ad-WTknob-luc infected cells (at all MOI tested between 1 and 100). The highest increase in reporter activity occurred at the lowest MOI, indicating a clear advantage to the RGD insertion at these doses. To summarize, we show that the β-catenin pathway is active in thyroid cancer and that we can use this co-activator to drive replication of a CRAd vector to kill thyroid cancer cells selectively. We also demonstrate that insertion of the RGD motif into the adenoviral knob results in greatly increased transduction, of thyroid cancer cells. We expect that by using a CRAd vector targeted specifically to cancer cells and by increasing the transductional efficiency of cancer cells with the RGD-knob, we can overcome some of the limitations encountered in gene therapy applications. In the future we will be testing the vector in xenograft models of thyroid cancer.
Targeted inhibition of Gatekeeper variant “T315I” of BCR-ABL by a purine based ATP-competitive inhibitor
Authors: Mohammad Azam, William C. Shakespeare, Tomi K. Sawyer, George Q. Daley
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4852 

In patients with chronic myeloid leukemia (CML), kinase domain mutations account for imatinib resistance in about 50-90% of cases. Mutations cause either a direct steric hindrance to drug binding or a conformational change that favors kinase activation, which therefore precludes imatinib binding. We have analyzed two dual Src-Abl kinase inhibitors, AP23464 and PD166326, for structure activity relationship (SAR). Both of these compounds have effectively suppressed the cell growth of native and imatinib resistant variants of BCR-ABL though with varying degree of sensitivity, except the gatekeeper residue (T315I). Imatinib resistance due to T315I substitutions represents 25-30 % of total resistance and is not inhibited by any BCR-ABL inhibitors. Earlier, we have demonstrated that the combination of different conformation specific inhibitors such as AP23464 (active conformation), PD166326 (intermediate conformation) and Imatinib (inactive conformation) essentially captures all resistance conferring mutations with notable exception of T315I. Based on our in vitro and in silico analysis we modified the AP23464 to develop AP23846 and AP23994 in order to inhibit T315I variants. Both of these compounds are effective in inhibiting the tyrosine kinase activity of native and T315I variants of BCR-ABL within 400-600 nM range. However, it also inhibited the parental cells, most likely by inhibiting some unknown target. Later, we redesigned these molecules to create AP24163 in order to have selectivity for T315I variant and lack of toxicity on parental cells. Indeed AP24163 inhibits the native and T315I variant of BCR-ABL kinase activity with IC50 values of 5nM and 350 nM, respectively. While the proliferation of parental BAF3 cells was not affected up to 5000 nM. This in-vitro study is a paradigm applicable to a list of target-directed agents and means to understand structure activity relationship in order to develop more potent inhibitors to combat resistance.
Scientists Set to Decode Influenza Genome
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
Abstract 20385: Pregnancy-Induced Cardiac Hypertrophy is Accompanied by Unique Contractile Properties Not Seen in Other Forms of Physiological Hypertrophy
Authors: Jessica Tyrrell, Kaitlyn Kennard, Catherine Makarewich, Beth A Bailey
Journal: Circulation (2014)

Background: Cardiac hypertrophy accompanying pregnancy has generally been categorized as physiologic hypertrophy similar to that seen with exercise, however a reduction in cardiac function in late pregnancy has been suggested. Furthermore, the hemodynamic stress of pregnancy can induce a maladaptive, pathologic hypertrophy in a small number of women. This study seeks to characterize the contractile properties of late-pregnant myocardium. Methods and Results: Late Pregnancy (LP) Female Swiss-Webster mice were bred then studied at near term (Embryonic day 17-19) and compared to age-matched, non-pregnant (NP) controls. Individual cardiac myocytes were isolated using collagenase-based perfusion technique. Two-dimensional Surface Area measured in quiescent cells was elevated (p&lt;.01) in LP myocytes (LPM) (3609± 132u 2 ) vs NP myocytes (NPM) (2736± 88u 2 ), and this increase was due to increases in both length (8.5%) and width (15.6%). Western Blot analysis showed a reduction in Ryanodine Receptor protein in LP, but no differences in L-type Ca Channel, SERCA or Phospholamban levels. Sarcomere length (light diffraction) and Ca 2+ transients (fluo-3) were measured at pacing rates of 1 Hz and at bath [Ca] of 2mM. Duration of twitch contraction was prolonged (p&lt;.05) in LPM as measured by Time to 75% Recovery (.42 ± .02 vs .37 ±.01 sec in NPM) and Time to 90% recovery (.51 ± .02 vs .45 ± .02 sec in NPM). There were no differences in other contractile parameters measured or in the fluo-3 calcium transient properties. 10 -7 M Isoproterenol (ISO) was used to determine the responsiveness to adrenergic stimulation. ISO induced significantly enhanced contractility in both LPM and NPM, and the response was heightened in LPM such that the presence of ISO normalized the differences in the duration of twitch contraction between LPM and NPM. Conclusions: These results suggest that hypertrophied LPM have characteristics of both physiologic and pathologic hypertrophy including enhanced responsiveness to ISO and a prolonged relaxation phase. The prolongation of relaxation is not seen in physiologic hypertrophy induced by exercise and may contribute to the diastolic dysfunction reported in some pregnancies. Enhanced response to ISO suggests an increased cardiac reserve in LPM.
Abstract 4113: Restricted ketogenic diet reduces growth and distant organ metastasis in the murine VM-M3 metastatic tumor model
Authors: Zeynep Akgoc, Laura M. Shelton, David Ryan, Xijun Zhu, Thomas N. Seyfried
Journal: Cancer Research (2014)

Abstract Metastasis involves the spread of tumor cells throughout the body and is one of the leading causes of cancer death. Most current drug therapies for metastatic cancer are toxic and only marginally effective in providing long-term management. Respiratory insufficiency with compensatory aerobic fermentation (Warburg effect) is the hallmark biochemical phenotype of nearly all neoplastic cells within tumors. Most tumor cells are incapable of utilizing ketone bodies for energy due to their respiratory insufficiency. Calorie restriction, which lowers blood glucose and elevates ketone bodies, is known to reduce tumor growth. We previously showed that ketogenic diets with high fat/protein + carbohydrate ratios of 3-4:1 are better able to lower blood glucose and elevate ketone levels than is calorie restriction alone. We evaluated the influence of a new ketogenic diet formula from Solace Nutrition (KetoGen) on the growth and metastatic spread of the VM-M3 tumor. VM-M3 is a highly metastatic macrophage-like tumor that arose spontaneously in the brain of the syngeneic inbred VM/Dk mouse strain. The VM-M3 cells spread rapidly (within days) to lungs, liver, spleen, kidney, and brain with 100% fidelity following subcutaneous implantation. Tumor bearing VM mice were fed either a standard lab chow diet in unrestricted amounts (SD-UR), a standard lab chow restricted to obtain an 18% reduction in body weight (SD-R), or the KetoGen diet restricted (KG-R) to match the body weights of the SD-R control group. Tumor size was significantly smaller and organ metastasis was significantly less in the KG-R group than in the SD-UR or SD-R groups. Although blood glucose was reduced similarly in both the SD-R and KG-R groups, blood ketones were 3-fold higher in the KG-R group than in the SD-R group. These results show that VM-M3 tumor growth and systemic metastasis was managed better with the restricted KetoGen KD than with calorie restriction of a high carbohydrate standard diet. As all human and mouse tumors cells suffer from respiratory insufficiency, our findings suggest that the KetoGen diet should be an effective non-toxic therapy against systemic metastatic cancer. Citation Format: Zeynep Akgoc, Laura M. Shelton, David Ryan, Xijun Zhu, Thomas N. Seyfried. Restricted ketogenic diet reduces growth and distant organ metastasis in the murine VM-M3 metastatic tumor model. [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 4113. doi:10.1158/1538-7445.AM2014-4113
Abstract 17218: Reduced Left Atrial Compliance in Heart Failure With Preserved Ejection Fraction: New Insights Into Pathophysiology
Authors: Rosita Zakeri, Qiang Chai, Gilles Moulay, Ozgur Ogut, Saad Hussain, Hiroyuki Takahama, Tong Lu, Xiao-Li Wang, Wolfgang A Linke, Hon-Chi Lee, Margaret M Redfield
Journal: Circulation (2014)

Background: Reduced left atrial (LA) compliance (LAC) contributes to pulmonary venous hypertension in heart failure with preserved ejection fraction (HFpEF); however the underlying mechanisms are poorly defined. We hypothesized that microvascular inflammation with rarefaction and impaired nitric oxide (NO) signaling, LA titin hypophosphorylation and fibrosis may each contribute to reduced LAC in HFpEF. Methods: Invasive LA pressure-volume (PV) analyses (open-chest; pericardiotomy; admittance catheter) were performed in 9 aged dogs with experimental hypertension (bilateral renal wrap + DOCA; HFpEF) compared to 13 sham-operated young adult dogs (control). LAC was measured at end-LA reservoir during acute preload reduction (cava occlusion). LA tissue and LA microvascular function were analyzed. Results: Compared to controls, the curvilinear end-LA reservoir PV relationship ( Fig A ) was shifted upward/leftward in HFpEF (LA diastolic stiffness constant 0.08 vs 0.16 mmHg/mL in controls, p=0.005). LA microvascular density (MVD; CD31 stain) tended to be lower in HFpEF than controls (2154±578 vs 2650±523 vessels/mm 2 , p=0.07) and LA MVD negatively correlated with the LA diastolic stiffness constant (r=-0.66, p=0.006). LA microvessels from HFpEF dogs showed impaired endothelium-dependent shear stress-mediated dilation compared to controls, consistent with impaired NO signaling ( Fig B ). Titin isoform expression was similar between groups, but isoform N2B (stiffer) was (p=0.03) and N2BA (compliant) tended to be (p=0.09) hypophosphorylated in HFpEF LA appendage (LAA) tissue. Fibrosis (Picrosirius Red) was similar between groups in the LA free wall and LAA, but increased in areas adjacent to the pulmonary veins in HFpEF (27±12% vs controls 15±8%, p=0.01). Conclusion: In experimental HFpEF, LAC was reduced in association with evidence of LA microvascular rarefaction and impaired NO signaling, titin hypophosphorylation and regional increases in LA fibrosis.
Breaking Barriers in Transdermal Drug Delivery
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
Ryk-deficient mice exhibit craniofacial defects associated with perturbed Eph receptor crosstalk
Authors: Michael M. Halford, Jane Armes, Michael Buchert, Virginia Meskenaite, Dianne Grail, Margaret L. Hibbs, Andrew F. Wilks, Peter G. Farlie, Don F. Newgreen, Christopher M. Hovens, Steven A. Stacker
Journal: Nature Genetics (2000)
The jewel in welfare's crown
Authors: N. Timmins
Journal: BMJ (1998)

“On Monday morning you will wake up in a new Britain, in a state which ‘takes over’ its citizens six months before they are born, providing care and free services for their birth, for their early years, their schooling, sickness, workless days, widowhood and retirement. All this with free doctoring, dentistry and medicine—free bath-chairs, too, if needed—for 4/11d out of your weekly pay packet. You begin paying next Friday.”

Thus the Daily Mail in its leader column greeted the imminent arrival of the National Health Service on 5 July 1948. It is often forgotten that the birth of the NHS was not just an isolated event. It was part of the biggest single tranche of welfare state reconstruction that the United Kingdom has seen. Its arrival coincided with dramatic improvements to social security—the creation of family allowances, retirement pensions for all, new industrial injuries schemes, the raising of the school leaving age to 15, and the start of a great explosion in council house building.

It was just one part of the huge effort in postwar reconstruction presaged in the Beveridge report of 1942 and made possible by the immense sense of social solidarity generated by …
Corrigendum to “Intratunical Injection of Human Adipose Tissue–derived Stem Cells Prevents Fibrosis and Is Associated with Improved Erectile Function in a Rat Model of Peyronie's Disease” [Eur Urol 2013;63:551–60]
Authors: Fabio Castiglione, Petter Hedlund, Frank Van der Aa, Trinity J. Bivalacqua, Patrizio Rigatti, Hein Van Poppel, Francesco Montorsi, Dirk De Ridder, Maarten Albersen
Journal: European Urology (2013)
The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor
Authors: Sujit Basu, Janice A. Nagy, Soumitro Pal, Eliza Vasile, Isabelle A. Eckelhoefer, V. Susan Bliss, Eleanor J. Manseau, Partha S. Dasgupta, Harold F. Dvorak, Debabrata Mukhopadhyay
Journal: Nature Medicine (2001)
Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study
Authors: X. Pivot, J. Gligorov, V. Müller, G. Curigliano, A. Knoop, S. Verma, V. Jenkins, N. Scotto, S. Osborne, L. Fallowfield, Lesley Fallowfield, Valerie Jenkins, Justine Kilkerr, Carolyn Langridge, Kathryn Monson, Erik Hugger Jakobsen, Mette Holck Nielsen, Soeren Linnet, Ann Knoop, Xavier Pivot, Herve Bonnefoi, Mireille Mousseau, Laurent Zelek, Hugues Bourgeois, Claudia Plesse Lefeuvre, Thomas Bachelot, Thierry Petit, Etienne Brain, Christelle Levy, Joseph Gligorov, Doris Augustin, Heiko Graf, Georg Heinrich, Hendrik Kroening, Sherko Kuemmel, Volkmar Müller, Friedrich Overkamp, Tjoung-Won Park-Simon, Marcus Schmidt, Lidia Perlova-Griff, Christopher Wolf, Marco Colleoni, Alberto Ballestrero, Antonio Bernardo, Angela Stefania Ribecco, Luca Gianni, Giuseppe Curigliano, Elżbieta Brewczynska, Jacek Jassem, Vadim Shirinkin, Alexey Manikhas, Victoria Dvornichenko, Mikhail Lichinitser, Vladimir Semiglazov, Guzel Mukhametshina, Irina Bulavina, Enrique Espinosa Arranz, Francisco Carabantes Ocon, Guillermo López Vivanco, Javier Salvador Bofill, Ignacio Porras Quintela, Alfonso Sanchez Muñoz, Yolanda Fernández Pérez, Javier Cassinello Espinosa, José Valero Alvarez, Rodrigo Lastra del Prado, LuisLa Cruz De Merino, José Manuel Pérez García, Santos Enrech Frances, Per Edlund, Bengt Norberg, Anna-Karin Wennstig, Pehr Lind, Nik Hauser, Christoph Tausch, Celalettin Camci, Fikret Arpaci, Huseyin Abali, Ruchan Uslu, Saad Tahir, Duncan Wheatley, Stephen Chan, Peter Barrett-Lee, Karen McAdam, Richard Simcock, Russell Burcombe, Robert El-Maraghi, Nadia Califaretti, Silvana Spadafora, Sandeep Sehdev, Amer Sami, Sunil Verma
Journal: Annals of Oncology (2014)