tbuckley/cabot-search huggingface dataset:
A NEW MATHEMATICAL METHOD FOR THE EVALUATION OF ENDOGENOUS INSULIN SECRETION
Authors: M. M. Miller, O. P. Allen
Journal: Annals of Internal Medicine (1939)

Article1 October 1939A NEW MATHEMATICAL METHOD FOR THE EVALUATION OF ENDOGENOUS INSULIN SECRETIONM. M. MILLER, M.D., O. P. ALLEN, M.D.M. M. MILLER, M.D.Search for more papers by this author, O. P. ALLEN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-13-4-636 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt has been said that insulin administration cannot be calculated by mathematical equations; that no one knows the exact amount of carbohydrate that will be metabolized by a given amount of insulin.1Probably every physician of experience in the treatment of diabetes mellitus has been puzzled at times to know how much insulin a given patient requires. We have all been confronted with the widely varied responses of different patients, as well as of the same patient at different times, to comparable doses of insulin.This dissimilarity of response of different patients to comparable doses, or of the same patient...Bibliography1. SHARKEY TP: Diabetic coma, Ohio State Med. Jr., 1936, xxxii, 123-130. Google Scholar2. HARTMANN AF: Diabetes mellitus in infants and children, Med. Clin. North Am., 1925, ix, 69-99. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Akron, Ohio*Received for publication July 19, 1938. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byKasuistik 1 October 1939Volume 13, Issue 4Page: 636-649KeywordsCarbohydratesDiabetes mellitusInsulinInsulin secretion ePublished: 1 December 2008 Issue Published: 1 October 1939 PDF downloadLoading ...
Chemotherapy Dose Adjustment For Obese Patients Undergoing Hematopoietic Stem Cell Transplantation (HSCT): A Survey On Behalf Of The ALWP Of The EBMT
Authors: Noga Shem-Tov, Myriam Labopin, Leila Moukhtari, Fabio Ciceri, Jordi Esteve, Sebastian Giebel, Norbert-Claude Gorin, Hansjoerg Schmid, Avichai Shimoni, Arnon Nagler, Mohamad Mohty
Journal: Blood (2013)
Country-wide HIV incidence study complementing HIV surveillance in Germany
Authors: J Bätzing-Feigenbaum, S Loschen, S Gohlke-Micknis, R Zimmermann, A Herrmann, O Kamga Wambo, C Kücherer, O Hamouda
Journal: Eurosurveillance (2008)

Serological methods exist that allow differentiating between recent and long-standing infections in persons infected with HIV. During a pilot study in Berlin between 2005 and 2007 methodologies have been evaluated. In a cross-sectional study blood samples, demographic, laboratory, clinical and behavioural data based on a KABP survey were collected from patients with newly diagnosed HIV infections. The BED-CEIA was used to determine recency of infection. Recent HIV infections contributed 54% (CI [95%]: 45; 64) in MSM and 16% (CI [95%]: 0; 39) in patients with other transmission risks (p=0.041). Proportions of recent infections were significantly higher in MSM ≤30 years (p=0.019). The mean age was 33.9 (median 34 years) in recent compared with 38.6 years (median: 38 years) in long-standing infections (p=0.011). High-risk behaviour indicated through very low condom use in recently HIV infected MSM could be identified. The results of the pilot study support expectations that the modified application of the method may contribute to improving HIV prevention efforts in Germany. On this basis the Robert Koch Institute implemented a countrywide HIV incidence study to complement HIV surveillance in early 2008. The study is funded by the German Ministry of Health. Data on recent HIV infections and current HIV transmission risks are collected. Design, methods and impact are described in detail.
Abstract 798: Androgen receptor, PI3K/mTOR and PSMA: Exploring and exploiting the interplay between therapeutic targets in prostate cancer
Authors: Jose D. Murga, Wells W. Magargal, Sameer M. Moorji, Vincent A. DiPippo, William C. Olson
Journal: Cancer Research (2014)

Abstract Introduction: Androgen receptor (AR), the PI3K/mTOR signaling pathway and prostate-specific membrane antigen (PSMA) represent significant potential targets for prostate cancer therapy. The present study examined the cross-regulation and co-targeting of these molecular pathways. Methods: Cytotoxicity and the kinetics of antigen expression were evaluated in prostate cancer cell lines (LNCaP and C4-2) that vary according to androgen dependence. Expression of PSMA, prostate-specific antigen (PSA), and AR was evaluated in cells cultured in rapamycin and AR inhibitors. Cells were tested for susceptibility to PI3K/mTOR inhibitors used alone and in combination with PSMA ADC, a fully human PSMA monoclonal antibody conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE). Potential drug synergy or antagonism was evaluated using the Bliss independence method. Results: In androgen-dependent LNCaP cells, rapamycin exerted antiproliferative effects that were accompanied by an increase in AR expression and signaling in the absence of any significant effect on PSMA expression. In androgen-independent C4-2 cells, rapamycin increased AR expression/signaling and PSMA expression in the absence of any significant anti-proliferative effect. AR inhibitors synergized with PSMA ADC in LNCaP and C4-2 cells, but PI3K/mTOR pathway inhibitors synergized with PSMA ADC in C4-2 cells only. More modest synergy was observed by combining non-targeted microtubule inhibitors with inhibitors of AR or mTOR. Compared with rapamycin, GDC0941 (PI3K inhibitor) and MK-2206 (Akt inhibitor), both upstream of mTOR, synergized less strongly with PSMA ADC in C4-2 cells. Conclusions: In this study, AR and PI3K/mTOR pathways exhibited cross-regulation impacting PSMA expression. PSMA ADC synergized with AR and mTOR inhibitors via a multimodal mechanism involving increased PSMA expression and disruption of microtubule function. The findings support clinical exploration of regimens combining PSMA-targeted therapies with inhibitors of the AR and/or PI3K/mTOR signaling pathways. Citation Format: Jose D. Murga, Wells W. Magargal, Sameer M. Moorji, Vincent A. DiPippo, William C. Olson. Androgen receptor, PI3K/mTOR and PSMA: Exploring and exploiting the interplay between therapeutic targets 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 798. doi:10.1158/1538-7445.AM2014-798
Abstract 13926: Testosterone Drop Predicts Glucose Rise in Men on Statins
Authors: Beatrice A Golomb, Alexis K Bui
Journal: Circulation (2014)

Background:  Data from the UCSD Statin Study previously showed that statins significantly reduce testosterone in men, with magnitude of drop related to LDL-drop on simvastatin and to HDL-rise on pravastatin. Since lower testosterone is linked to greater diabetes risk in men: we conjectured that testosterone drop on statins might contribute to instances of glucose rise on statins.   Methods:  1016 participants in the UCSD Statin Study underwent sex-stratified randomization equally to simvastatin 20mg, pravastatin 40mg or placebo for 6 months; 692 were men (age 20-85). Fasting glucose (mg/dL) and testosterone (ng/mL) were assessed at baseline and 6 months. Regression analysis with robust standard errors evaluated the relation of change in testosterone to change in glucose in men, adjusted for baseline testosterone and baseline glucose. Analyses were stratified by randomization assignment and age (≥55, N=353 vs age   Results:  Change in testosterone predicted change in glucose on statins [[Unable to Display Character: –]] and also on placebo (consistent with previously known relationships of testosterone to glucose in men). The magnitude of association was apparently larger on statins, particularly simvastatin, than on placebo in older age (≥ 55).   Discussion:  Statin induced reductions in testosterone, coupled with association of testosterone drop to glucose rise, may contribute to instances of glucose elevation in men on statins.
In Vitro Inhibition of Chick Embryo Lysyl Hydroxylase by Homogentisic Acid
Authors: John C. Murray, Kenneth A. Lindberg, Sheldon R. Pinnell
Journal: Journal of Clinical Investigation (1977)

Homogentisic acid inhibits the in vitro activity of chick embryo lysyl hydroxylase, a microsomal enzyme which catalyzes the transformation of certain lysyl residues in collagen to hydroxylysine. Chick embryo lysyl hydroxylase activity was measured as specific tritium release as tritium water from a [4,5-3H]lysine-labeled unhydroxylated collagen substrate prepared from chick calvaria. Kinetic studies revealed a linear, noncompetitive type of inhibition with respect to collagen substrate with a Ki of 120-180 μM. The inhibition by homogentisic acid was reversible in that enzyme activity could be restored after dialysis of preincubated mixtures of homogentisic acid with enzyme or substrate. The inhibition by homogentisic acid was competitive with respect to ascorbic acid, and the addition of reducing agents, such as ascorbic acid or 1,4-dithiothreitol, protected lysyl hydroxylase activity from homogentisic acid inhibition.
A randomized placebo‐controlled trial of rush preseasonal depigmented polymerized grass pollen immunotherapy*
Authors: O. Pfaar, Z. Urry, D. S. Robinson, A. Sager, D. Richards, C. M. Hawrylowicz, M. Bräutigam, L. Klimek
Journal: Allergy (2011)

To cite this article: Pfaar O, Urry Z, Robinson DS, Sager A, Richards D, Hawrylowicz CM, Bräutigam M, Klimek L. A randomized placebo‐controlled trial of rush preseasonal depigmented polymerized grass pollen immunotherapy. Allergy 2012; 67 : 272–279. Abstract: Background: Specific subcutaneous immunotherapy (SCIT) for seasonal rhinoconjunctivitis with unmodified allergen extracts is effective, but limited by risk of side‐effects and involves treatment over 3 years. We examined a depigmented polymerized grass pollen extract for immunogenicity and for clinical efficacy in a rush preseasonal regimen. Methods: Depigmented polymerized grass pollen extract was tested for proliferation and cytokine production by peripheral blood mononuclear cells. A prospective, double‐blind, placebo‐controlled trial of 195 grass pollen allergic patients treated with preseasonal rush immunotherapy using depigmented polymerized allergenic extract of mixed grass pollen was performed over 2 years. Primary outcome was combined symptom and medication score (SMS) during the peak of the second grass pollen season. Secondary outcomes included combined score over the whole season, during the first grass pollen season, individual symptom and medication scores, quality of life, well days/hell days and responder analysis. Adverse events were classified using the EAACI scale. Grass pollen‐specific IgE and IgG4 were measured before and during treatment. Results: Depigmented polymerized extract stimulated dose‐dependent T‐cell proliferation and cytokine production. Patients treated with preseasonal SCIT showed improved combined scores during peak season at year 2 (median 3.93, interquartile range 0.77–6.27 vs median 5.86 for placebo, 3.11–8.36, P &lt; 0.01). Most secondary outcomes were significantly better for active treatment. Side‐effects were minimal, with no grade 3 or 4 reactions. Conclusions: Depigmented polymerized grass pollen extract is immunogenic and clinically effective in rush preseasonal SCIT. This form of immunotherapy may be an attractive option for some patients.
Abstract 13479: Identification of microRNAs that Target mRNA Encoding Atrial Natriuretic Peptide
Authors: Connie Wu, Pankaj Arora, Marie Jose Goumans, Dongjian Hu, Ibrahim Domian, Pawina Jiramongkolchai, Kasey C Vickers, Akiko Hata, Emmanuel Buys, Christopher Newton-Cheh, Thomas J Wang, Donald B Bloch, Kenneth D Bloch
Journal: Circulation (2014)

Introduction: The minor allele of a common variant (rs5068) in the 3’UTR of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with increased plasma ANP levels, lower blood pressure, and reduced risk of hypertension. A microRNA (miR-425) expressed in the human heart binds to a sequence spanning rs5068 for the major but not the minor allele leading to reduced ANP biosynthesis. mRNAs typically contain multiple miR-binding sites, and binding of different miRs often coordinately regulates the function of any given mRNA. Hypothesis: We hypothesize that miRs, in addition to miR-425, target NPPA mRNA and that interference with miR-based silencing of NPPA mRNA using miR antagonists (antimiRs) could be used to increase ANP biosynthesis. Methods: Luciferase reporter assays were used to screen 10 miRs that are predicted in silico to interact with the NPPA 3’UTR. The expression levels of validated miRs in human atria were determined. Human cardiomyocyte progenitor cells (hCMPCs) or human embryonic stem cell (HUES 9)-derived cardiomyocytes (hESC-CMs) were transfected with antimiRs targeting the validated miRs, and the levels of NPPA mRNA were measured. Results: Of the 10 miRs predicted in silico to interact with the NPPA 3’UTR, we identified 3 miRs (miRs-103, -105, and -107) that reduced luciferase activity in cells containing a luciferase-NPPA 3’UTR construct (miR-103, p=0.034; miR-105, p=0.0009; and miR-107, p=0.021), but the miRs had no effect on luciferase activity in cells containing a luciferase construct in which the predicted miR-binding site in the NPPA 3’UTR was mutated. Using qRT-PCR, the three miRs were detected in human atria. Transfection of an antimiR directed against miR-103, miR-105, or miR-107 increased NPPA mRNA levels in hCMPCs (antimiR-103, p=0.024; antimiR-105, p=0.039; and antimiR-107, p=0.036). Similar results were observed in hESC-CMs. Conclusions: Our studies suggest that miRs-103, -105, and -107 regulate NPPA expression in human cardiomyocytes. AntimiRs directed against these miRs increased NPPA mRNA in human cardiomyocytes. AntimiR-based methods to increase ANP levels may represent a novel approach to the treatment of hypertension.
Abstract #5487: XmAb®5592: Fc-engineered anti-HM1.24 monoclonal antibody with potent in vitro and in vivo efficacy against multiple myeloma
Authors: Umesh Muchhal, Holly Horton, Hanh Nguyen, Matthew Bernett, Sher Karki, John Richards, John Desjarlais
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

HM1.24 (also known as CD317 or BST2) is a type II glycoprotein that is preferentially and highly expressed on malignant plasma cells, representing an attractive immunotherapy target for multiple myeloma. Here we present the characterization of a novel Fc-engineered and humanized anti-HM1.24 antibody (XmAb5592) that was generated using our XmAb® antibody engineering technologies. The main features of this antibody are i) increased affinity for Fc gamma receptors (Fc\#947;R), ii) improved effector function, and iii) significantly increased antitumor potency. The Fv region was humanized and engineered to maintain high affinity and specificity, increase stability and expression, and decrease immunogenicity. The antibody-dependent cell-mediated cytotoxicity (ADCC) of XmAb5592 was substantially higher relative to a native/non Fc-engineered version (anti-HM1.24 IgG1) of the antibody when tested in vitro against a panel of multiple myeloma cell lines including RPMI 8226, OPM-2, U266, LP-1 and EJM. ADCC efficacy (% lysis) of Fc-engineered antibody ranged from 50-90%, whereas the IgG1 version mediated little ADCC (10-30% lysis) on different cell lines. HM1.24 antigen is expressed on the surface of these myeloma cell lines to a varying degree, with maximal expression seen on RPMI 8226. XmAb5592 also induced robust anti-proliferative activity against RPMI 8226. The in vivo efficacy of XmAb5592 was evaluated in murine subcutaneous (sc) xenograft models using the RPMI 8226 myeloma cell line. Administration of XmAb5592 (9mg/kg, ip, 2x/week for 4 weeks) led to a significant reduction in growth of established tumors compared to a non-engineered IgG1 anti-HM1.24 analog. At the end of the study 7/15 mice were tumor free in XmAb treatment group versus only 1/15 tumor free mice in the IgG1 group. An anti-HM1.24 antibody with Fc region engineered to completely ablate binding to Fc\#947;Rs (knock-out) behaved equivalent to the PBS vehicle control in these studies, again underlining the significance of interaction with Fc\#947;R for anti-tumor efficacy. These results suggest that XmAb5592, an anti-HM1.24 antibody engineered for increased effector function is a promising next-generation immunotherapeutic for the treatment of multiple myeloma.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5487.
Abstract 4384: Targeting <i>miR-124</i> inhibits growth of prostate cancer xenografts and sensitized prostate cancer cells to anti-androgen
Authors: Xu-Bao Shi, Aihong Ma, Lingru Xue, Ralph W. deVere White
Journal: Cancer Research (2014)

Abstract Increasing evidence has shown that miR-124 is a tumor suppressor and plays an important role in pathogenesis of many types of human cancer. We previously found that miR-124 directly targets the androgen receptor (AR) and is significantly downregulated in clinical prostate cancer (CaP) samples. Moreover, overexpression of miR-124 induced apoptosis and inhibited cell proliferation and xenograft growth of CaP. In this study, we determined whether restoration of miR-124 may represent an adjunctively therapeutic option for CaP treatment. For this purpose, WST-1 and clonogenic assays were performed to evaluate the effects of miR-124 or miR-124 plus enzalutamide (one new androgen antagonist) on CaP cell proliferation. In animal experiment, male nude mice were inoculated s.c with CWR22 CaP cell suspensions. When tumor sizes reached ∼50 mm3, mice were treated with polyethylenimines (PEI)-complexed miR-124 (i.v., 10µg/day, thrice a week for 4 weeks) or PEI-miR-124 (i.v.) plus enzalutamide (p.o., 10mg/kg/day for 5 weeks). PEI can increase internalization and facilitate miRNA release into cytoplasm. After treatment, tumors were harvested for analyzing apoptosis and measuring miR-124 target levels. In in vitro experiment, 22Rv1 cells were separately treated with miR-124, enzalutamide or both. It was found that the combined treatment significantly increased growth inhibition of 22Rv1 cells. In addition, we established enzalutamide-resistant 22Rv1 subline (22Rv1-MDVR) by clone-selection in gradually increased doses (from 5μM to 40μM within four months). Treatment with miR-124 obviously inhibited clone formation of 22Rv1-MDVR cells. In mice receiving miR-124 or enzalutamide treatment, we observed tumor-inhibitory effects. However, the combination of miR-124 and enzalutamide exhibited more significant inhibition of tumor growth when compared to the single treatment. We examined the expression of AR and its variant 7 (AR-V7) that are targets of miR-124. Reduced levels of AR and AR-V7 were found in miR-124-treated tumors, indicating that PEI facilitates entry of miR-124 into the tumor cells. We also observed increased apoptosis in miR-124-treated tumors. Data from in vitro and in vivo studies show that miR-124 inhibited growth of CaP cells and sensitized CaP cells to anti-androgens, suggesting that miR-124 can be used as an adjunctively therapeutic agent for improved CaP treatment. Citation Format: Xu-Bao Shi, Aihong Ma, Lingru Xue, Ralph W. deVere White. Targeting miR-124 inhibits growth of prostate cancer xenografts and sensitized prostate cancer cells to anti-androgen. [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 4384. doi:10.1158/1538-7445.AM2014-4384
Abstract 4351: Targeting miRNA-driven aggressive behavior of pancreatic cancer stem cells by a novel drug
Authors: Evan Bao, Asfar Azmi, Ellen Zhang, Shadan Ali, Aamir Ahmad, Feras Zaiem, Bin Bao, Fazlul H. Sarkar
Journal: Cancer Research (2014)

Abstract Pancreatic cancer (PC) is a lethal malignant disease, which is in part due to lack of early detection biomarkers. Once diagnosed, the majority of PC patients are already in advanced stages. Currently there are no effective treatments in improving the overall survival. Therefore, the majority of PC patients die within 5-6 months due to therapeutic resistance and early metastatic disease. Recently, a sub-population of cancer stem cells (CSCs) (&amp;lt;0.1%) have been identified from many different tumors including PC, and these cells are believed to be responsible for treatment resistance, tumor recurrence and metastasis. Many studies have shown that the existence of CSCs has important clinical implications because CSCs are involved in cell migration/invasion, drug resistance, and metastasis, which leads to poor clinical outcome. Therefore, selective killing or complete elimination of CSCs by novel approaches would likely become newer treatment strategy for PC in the improvement of overall survival. However, the regulation of CSC characteristics during tumor development and progression has not been well understood. In this study, cell and molecular biology techniques were used to investigate the CSC characteristics and its regulation to find a new effective approach for the treatment of PC. We found that cancer stem-like cells (CSLCs) which is reminiscent of CSCs isolated from human PC cell line, MiaPaCa-2 cells as triple-marker positive cells (CD44+/CD133+/EpCAM+ cells) cells displayed aggressive phenotypes, such as increased clonogenicity, cell migration, and self-renewal capacity, along with over-expression of CSC marker microRNAs (miRNAs) such as miR-21 and miR-210. Under-expression of miR-21 and miR-210 by transfection of anti-miRNAs led to decreased clonogenicity, cell migration and self-renewal capacity, along with reduced expression of CSC-associated markers/mediators such as CD44, EpCAM, EZH2, Notch-1, and Snail in CSLCs. Similarly, under-expression of CSC-associated mediator Notch-1 led to decreased cell migration, self-renewal capacity, and expression of EpCAM and Snail in CSLCs. Finally, CDF, a novel synthetic small molecule showed reduced aggressive behavior of CSLCs such as cell survival/growth, migration, clonogenicity, self-renewal capacity, and decreased expression of miR-21 and miR-210. From these results, we conclude that CDF may serve as an effective anti-tumor agent via targeting miRNA-driven aggressive behavior of CSLCs. Citation Format: Evan Bao, Asfar Azmi, Ellen Zhang, Shadan Ali, Aamir Ahmad, Feras Zaiem, Bin Bao, Fazlul H. Sarkar. Targeting miRNA-driven aggressive behavior of pancreatic cancer stem cells by a novel drug. [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 4351. doi:10.1158/1538-7445.AM2014-4351