tbuckley/cabot-search huggingface dataset:
Abstract 3926: Molecular imaging of VEGFR expression modulation by antiangiogenic therapy in mouse model of human breast cancer.
Authors: Wenlian Zhu, Yoshinori Kato, Ronnie C. Mease, Susanta Sarkar, Marina V. Backer, Joseph M. Backer, Dmitri Artemov
Journal: Cancer Research (2013)

Abstract Antiangiogenic therapy targeting VEGF/VEGFR signaling is an important strategy for cancer treatment, which is currently used in mono-therapy or combination therapy settings. However, the emerging resistance to antiangiogenic therapy as well as varied clinical response calls for the development of early, preferably noninvasive, markers of treatment response. In this study we used a recently developed molecular imaging tracer, site-specifically 99mTc-labeled engineered single-chain VEGF derivative, to monitor the VEGF receptor expression during the course of sunitinib antiangiogenic therapy in orthotopic human breast cancer model MDA-MB-231. The treatment protocol included two cycles of therapy delivered daily for 5 days (80mg/kg, orally) with a 5-day vacation between the cycles. Micro SPECT/CT imaging was performed longitudinally up to day 16. Animals in the control group received vehicle solution only. Tumors were excised and stained for the expression of CD31 endothelial cell marker. Experimental results suggest a highly heterogeneous vascular regression response to the first round of treatment, with significantly decreased tracer uptake and CD31 prevalence in some but not all tumors. As judged by the increase in tracer uptake and CD31 prevalence, a significant vascular rebound took place in all tumors after the vacation period. Judging by the same criteria, the second round of treatment was significantly less effective than the first round. Taken together, these results suggests that noninvasive molecular imaging of VEGF receptors reflects vascular regression and rebound in individual tumors and can provide clinically relevant information for monitoring and scheduling antiangiogenic therapy. Citation Format: Wenlian Zhu, Yoshinori Kato, Ronnie C. Mease, Susanta Sarkar, Marina V. Backer, Joseph M. Backer, Dmitri Artemov. Molecular imaging of VEGFR expression modulation by antiangiogenic therapy in mouse model of human breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3926. doi:10.1158/1538-7445.AM2013-3926
The Effect of the Insulin Analog Lispro on Nighttime Blood Glucose Control in Type 1 Diabetic Patients
Authors: Abu Baker E Ahmed, Philip D Home
Journal: Diabetes Care (1998)

OBJECTIVE Unmodified regular insulin has a long absorption tail, unlike the fast-acting insulin analog lispro, and may contribute to hypoglycemia in the early part of the night. A randomized crossover double-blind study was performed to compare blood glucose concentrations in the early part of the night in type 1 diabetic patients receiving lispro or unmodified regular human insulin, in random order, on 2 separate study days. RESEARCH DESIGN AND METHODS We studied 23 C-peptide-negative patients; 12 were using a premeal plus basal insulin regimen, and 11 were using twice-daily insulin injections. Patients were admitted to the investigation unit at 5:00 P.M. and received a single dose of lispro or unmodified regular human insulin before the evening meal. In both groups, the NPH insulin dose remained unchanged. Identical meals and snacks were eaten at the same time during both study days. RESULTS Average postprandial (6:00−10:00 P.M.) blood glucose concentrations were significantly lower after lispro therapy compared with human insulin (7.1 ± 0.4 [SE] vs. 8.5 ± 0.4 mmol/l, P = 0.0002). Nighttime (midnight to 4:00 A.M.) blood glucose concentrations were significantly higher after lispro compared with human insulin (10.3 ± 0.4 vs. 9.1 ± 0.4 mmol/l, P = 0.02). This difference was greatest in patients on the premeal plus basal insulin regimen (11.6 ± 0.5 vs. 8.7 ± 0.4 mmol/l, P &amp;lt; 0.001). The incidence of nocturnal hypoglycemia (midnight to 4:00 A.M., blood glucose &amp;lt; 3.5 mmol/l) was less with lispro compared with unmodified insulin (1 vs. 6 patients, P = 0.04). Nighttime (midnight to 4:00 A.M.) 3-hydroxybutyrate (102 ± 13 vs. 51 ± 7 mumol/l, P = 0.000) and glycerol (52 ± 3 vs. 42 ± 2 mumol/l, P &amp;lt; 0.01) were significantly higher after lispro therapy compared with human insulin in patients on the premeal plus bolus insulin regimen. CONCLUSIONS Lispro can improve postprandial blood glucose control and reduce the incidence of nocturnal hypoglycemia at the expense of nocturnal hyperglycemia and hyperketonemia in patients using a premeal plus basal insulin regimen.
Hand2 Loss-of-Function in <i>Hand1</i> -Expressing Cells Reveals Distinct Roles in Epicardial and Coronary Vessel Development
Authors: Ralston M. Barnes, Beth A. Firulli, Nathan J. VanDusen, Yuka Morikawa, Simon J. Conway, Peter Cserjesi, Joshua W. Vincentz, Anthony B. Firulli
Journal: Circulation Research (2011)

Rationale: The basic helix–loop–helix (bHLH) transcription factors Hand1 and Hand2 are essential for embryonic development. Given their requirement for cardiogenesis, it is imperative to determine their impact on cardiovascular function. Objective: To deduce the role of Hand2 within the epicardium. Method and Results: We engineered a Hand1 allele expressing Cre recombinase. Cardiac Hand1 expression is largely limited to cells of the primary heart field, overlapping little with Hand2 expression. Hand1 is expressed within the septum transversum, and the Hand1 lineage marks the proepicardial organ and epicardium. To examine Hand factor functional overlap, we conditionally deleted Hand2 from Hand1 -expressing cells. Hand2 mutants display defective epicardialization and fail to form coronary arteries, coincident with altered extracellular matrix deposition and Pdgfr expression. Conclusions: These data demonstrate a hierarchal relationship whereby transient Hand1 septum transversum expression defines epicardial precursors that are subsequently dependent on Hand2 function.
Interaction between the HCV NS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses
Authors: Motoyuki Otsuka, Naoya Kato, Masaru Moriyama, Hiroyoshi Taniguchi, Yue Wang, Narayan Dharel, Takao Kawabe, Masao Omata
Journal: Hepatology (2005)

The persistent nature of hepatitis C virus (HCV) infection suggests that HCV encodes proteins that enable it to overcome host antiviral responses. Toll-like receptor 3 (TLR3)-mediated signaling, which recognizes the double-stranded RNA that is produced during viral replication and induces type I interferons, including interferon β (IFN-β), is crucial to the host defense against viruses. Recent studies suggest that a TIR domain–containing adaptor protein, TRIF, and two protein kinases, TANK-binding kinase-1 (TBK1) and IκB kinase-ϵ (IKKϵ), play essential roles in TLR3-mediated IFN-β production through the activation of the transcriptional factor interferon regulatory factor 3 (IRF-3). We report that the HCV NS3 protein interacts directly with TBK1, and that this binding results in the inhibition of the association between TBK1 and IRF-3, which leads to the inhibition of IRF-3 activation. In conclusion, these results suggest the mechanisms of the inhibition of the innate immune responses of HCV infection by NS3 protein. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005;41:1004–1012.)
BONE-MARROW TRANSPLANTATION HAS A LIMITED ROLE IN PROLONGING SECOND MARROW REMISSION IN CHILDHOOD LYMPHOBLASTIC LEUKAEMIA
Authors: J.M. Chessells, A.D. Leiper, P.N. Plowman, R. Levinsky, D.W. Rogers, H. Blacklock, S. Richards, H. Festenstein
Journal: The Lancet (1986)
Inhibition of hepatitis B virus-associated liver cancer by antiplatelet therapy: A revolution in hepatocellular carcinoma prevention?
Authors: Diego F. Calvisi
Journal: Hepatology (2013)

Abstract Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV-associated HCC involves both viral and host factors. The latter include a functionally inefficient CD8+ T-cell response that fails to clear the infection from the liver but sustains a chronic necroinflammatory process that contributes to the development of HCC. According to this scenario, amelioration of immune-mediated chronic liver injury may prevent HCC. Because platelets facilitate immune-mediated liver injury by promoting the hepatic accumulation of virus-specific CD8+ T cells, we evaluated the long-term consequences of antiplatelet therapy in an HBV transgenic mouse model of chronic immune-mediated necroinflammatory liver disease that progresses to HCC. Treatment with aspirin and clopidogrel during the chronic phase of the disease diminished the number of intrahepatic HBV-specific CD8+ T cells and HBV-nonspecific inflammatory cells, the severity of liver fibrosis, and the development of HCC. Antiplatelet therapy improved overall survival without causing significant side effects. In contrast, the same antiplatelet regimen had no antitumor effect when HCC was induced nonimmunologically by chronic exposure to a hepatotoxic chemical. The unprecedented observation that antiplatelet therapy inhibits or delays immune-mediated hepatocarcinogenesis suggests that platelets may be key players in the pathogenesis of HBV-associated liver cancer and supports the notion that immune-mediated necroinflammatory reactions are an important cause of hepatocellular transformation during chronic hepatitis .
Calcipotriol improves the response of psoriasis to PUVA
Authors: E.L. SPEIGHT, P.M. FARR
Journal: British Journal of Dermatology (1994)

Combining PUVA with other therapeutic agents which reduce the UVA dose required for clearance of psoriasis may be of benefit by reducing the long‐term risk of cutaneous malignancy and by increasing the efficacy of treatment. We have therefore studied the effect of calcipotriol in 13 patients with plaque‐type psoriasis who were about to start twice weekly PUVA. In each patient, from the start of PUVA treatment, two plaques on symmetrical body sites were selected for assessment. Calcipotriol ointment was applied to one twice daily, and placebo to the other. Response was assessed weekly for 6 weeks: an investigator, unaware of treatment allocation. compared psoriasis severity within each of the plaques, and blood flux was measured using a scanning laser‐Doppler velocimeter. Of the 11 patients who completed the study, in nine the calcipotriol‐treated plaque either cleared before the placebo‐treated plaque (n=7) or was consistently judged to be better (n = 2). From the third week of the trial, mean blood flux was significantly lower in the calcipotriol‐treated plaques than in those treated with placebo. In the seven patients whose psoriasis was clear in at least one plaque at the end of the study period, there was a median reduction in UVA dose of 26·5% for calcipotriol compared with placebo. With the exception of one patient, the improved response was not associated with earlier relapse.
Mechanism of Iodide Action on Cholesterol Metabolism
Authors: HELEN B. BROWN, IRVINE H. PAGE
Journal: Circulation (1952)

Iodide retards or prevents hypercholesterolemia and the development of experimental atherosclerosis in rabbits. "Protection" is estimated from reduction of plasma and/or hepatic cholesterol. Small doses of iodide do not "protect." Iodide in large doses prevents the hypercholesterolemia resulting from exogenous cholesterol and reduces hepatic cholesterol. This effect is independent of the thyroid gland and is not related to "thyroxin-like" plasma iodine. The influence of iodide on cholesterol metabolism seems to be related to the presence of a butanol-insoluble protein-bound iodine compound in the plasma.
Mapping of the gene for autosomal recessive polycystic kidney disease (ARPKD) to chromosome 6p21–cen
Authors: K. Zerres, G. Mücher, L. Bachner, G. Deschennes, T. Eggermann, H. Kääriäinen, M. Knapp, T. Lennert, J. Misselwitz, K. E. von Mühlendahl, H. P. H. Neumann, Y. Pirson, S. Rudnik-Schöneborn, V. Steinbicker, B. Wirth, K. Schärer
Journal: Nature Genetics (1994)
Cytosolic Phospholipase A2α Regulates Cell Growth in <i>RET/PTC</i>-Transformed Thyroid Cells
Authors: Stefania Mariggiò, Beatrice Maria Filippi, Cristiano Iurisci, Luana Katia Dragani, Valentina De Falco, Massimo Santoro, Daniela Corda
Journal: Cancer Research (2007)

Abstract Modulation of cytosolic phospholipase A2 (PLA2) expression levels and production of its metabolites have been reported in several tumor types, indicating involvement of arachidonic acid and its derivatives in tumorigenesis. Following our demonstration that the PLA2 group IV isoform α (PLA2IVα) controls TSH-independent growth of normal thyroid (PCCl3) cells, we have investigated the mitogenic role of PLA2IVα in rat thyroid cells transformed by the RET/PTC oncogenes (PC-PTC cells). We now report that PLA2IVα acts downstream of the RET/PTC oncogenes in a novel pathway controlling RET-dependent cell proliferation. In addition, we show that PLA2IVα is in its phosphorylated/active form not only in RET/PTC-transformed cells and in cells derived from human papillary carcinomas but also in lysates from tumor tissues, thus relating constitutive activation of PLA2IVα to RET/PTC-dependent tumorigenesis. Moreover, p38 stress-activated protein kinase is the downstream effector of RET/PTC that is responsible for PLA2IVα phosphorylation and activity. In summary, our data elucidate a novel mechanism in the control of thyroid tumor cell growth that is induced by the RET/PTC oncogenes and which is distinguishable from that of other oncogenes, such as BRAF. This mechanism is mediated by PLA2IVα and should be amenable to targeted pharmacologic intervention. [Cancer Res 2007;67(24):11769–78]
Targeting Tumor Vasculature With an Oncolytic Virus
Authors: Caroline J Breitbach, Naomi S De Silva, Theresa J Falls, Usaf Aladl, Laura Evgin, Jennifer Paterson, Yang Yang Sun, Dominic G Roy, Julia L Rintoul, Manijeh Daneshmand, Kelley Parato, Marianne M Stanford, Brian D Lichty, Aaron Fenster, David Kirn, Harold Atkins, John C Bell
Journal: Molecular Therapy (2011)

Oncolytic viruses (OVs) have been engineered or selected for cancer cell-specific infection however, we have found that following intravenous administration of vesicular stomatitis virus (VSV), tumor cell killing rapidly extends far beyond the initial sites of infection. We show here for the first time that VSV directly infects and destroys tumor vasculature in vivo but leaves normal vasculature intact. Three-dimensional (3D) reconstruction of infected tumors revealed that the majority of the tumor mass lacks significant blood flow in contrast to uninfected tumors, which exhibit relatively uniform perfusion. VSV replication in tumor neovasculature and spread within the tumor mass, initiates an inflammatory reaction including a neutrophil-dependent initiation of microclots within tumor blood vessels. Within 6 hours of intravenous administration of VSV and continuing for at least 24 hours, we observed the initiation of blood clots within the tumor vasculature whereas normal vasculature remained clot free. Blocking blood clot formation with thrombin inhibitors prevented tumor vascular collapse. Our results demonstrate that the therapeutic activity of an OV can go far beyond simple infection and lysis of malignant cells. Oncolytic viruses (OVs) have been engineered or selected for cancer cell-specific infection however, we have found that following intravenous administration of vesicular stomatitis virus (VSV), tumor cell killing rapidly extends far beyond the initial sites of infection. We show here for the first time that VSV directly infects and destroys tumor vasculature in vivo but leaves normal vasculature intact. Three-dimensional (3D) reconstruction of infected tumors revealed that the majority of the tumor mass lacks significant blood flow in contrast to uninfected tumors, which exhibit relatively uniform perfusion. VSV replication in tumor neovasculature and spread within the tumor mass, initiates an inflammatory reaction including a neutrophil-dependent initiation of microclots within tumor blood vessels. Within 6 hours of intravenous administration of VSV and continuing for at least 24 hours, we observed the initiation of blood clots within the tumor vasculature whereas normal vasculature remained clot free. Blocking blood clot formation with thrombin inhibitors prevented tumor vascular collapse. Our results demonstrate that the therapeutic activity of an OV can go far beyond simple infection and lysis of malignant cells.
New redistribution index of nutritive blood flow to skeletal muscle during dynamic exercise.
Authors: H Asanoi, O Wada, K Miyagi, S Ishizaka, T Kameyama, H Seto, S Sasayama
Journal: Circulation (1992)

Cardiac output is effectively redistributed to working muscle by regional changes in vascular resistance. However, there has been no suitable method to quantify blood flow distribution to large working and nonworking muscles involved in ergometer or treadmill exercise.To quantify the redistribution of blood flow, we compared thallium activity in a bicycle pedaling leg with that in the contralateral resting leg in 10 normal subjects. The regional thallium activity was expressed as a percentage of the whole-body radioisotope activity. Comparison of thallium activity between legs was performed at rest and at the work rates of anaerobic threshold and peak exercise during one-leg exercise. Thallium distribution of both legs was essentially the same at rest. At the anaerobic threshold, thallium activity increased about threefold to fourfold in the exercising thigh and about twofold in the exercising calf. The thallium distribution in these muscles at peak exercise was the same as at the anaerobic threshold. In the nonexercising calf, thallium distribution during exercise decreased significantly, and it was unchanged in the nonexercising thigh. Consequently, the ratio of thallium activity between the exercising and nonexercising thighs increased from 1.1 +/- 0.1 to 4.0 +/- 0.9 at the anaerobic threshold and to 3.3 +/- 0.6 at peak exercise. Similarly, the ratio between the exercising and nonexercising calves increased from 1.0 +/- 0.0 to 3.8 +/- 1.3 at the anaerobic threshold and to 3.5 +/- 1.0 at peak exercise. The ratios at peak exercise, however, did not differ significantly from those at the anaerobic threshold.These findings suggest that the redistribution of blood flow occurs predominantly during mild to moderate exercise; therefore, blood flow in the leg during strenuous exercise would depend primarily upon an increased cardiac output. Thus, the thallium activity ratio of exercising and nonexercising legs reflects the difference in vascular tone of each leg and could provide a noninvasive and quantitative index of blood flow redistribution.
Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin.
Authors: J E Gerich, M Lorenzi, D M Bier, E Tsalikian, V Schneider, J H Karam, P H Forsham
Journal: Journal of Clinical Investigation (1976)

To study the individual effects of glucagon and growth hormone on human carbohydrate and lipid metabolism, endogenous secretion of both hormones was simultaneously suppressed with somatostatin and physiologic circulating levels of one or the other hormone were reproduced by exogenous infusion. The interaction of these hormones with insulin was evaluated by performing these studies in juvenile-onset, insulin-deficient diabetic subjects both during infusion of insulin and after its withdrawal. Infusion of glucagon (1 ng/kg-min) during suppression of its endogenous secretion with somatostatin produced circulating hormone levels of approximately 200 pg/ml. When glucagon was infused along with insulin, plasma glucose levels rose from 94 +/- 8 to 126 +/- 12 mg/100 ml over 1 h (P less than 0.01); growth hormone, beta-hydroxy-butyrate, alanine, FFA, and glycerol levels did not change. When insulin was withdrawn, plasma glucose, beta-hydroxybutyrate, FFA, and glycerol all rose to higher levels (P less than 0.01) than those observed under similar conditions when somatostatin alone had been infused to suppress glucagon secretion. Thus, under appropriate conditions, physiologic levels of glucagon can stimulate lipolysis and cause hyperketonemia and hyperglycemia in man; insulin antagonizes the lipolytic and ketogenic effects of glucagon more effectively than the hyperglycemic effect. Infusion of growth hormone (1 mug/kg-h) during suppression of its endogenous secretion with somastostatin produced circulating hormone levels of approximately 6 ng/ml. When growth hormone was administered along with insulin, no effects were observed. After insulin was withdrawn, plasma beta-hydroxybutyrate, glycerol, and FFA all rose to higher levels (P less than 0.01) than those observed during infusion of somatostatin alone when growth hormone secretion was suppressed; no difference in plasma glucose, alanine, and glucagon levels was evident. Thus, under appropriate conditions, physiologic levels of growth hormone can augment lipolysis and ketonemia in man, but these actions are ordinarily not apparent in the presence of physiologic levels of insulin.
Lead poisoning from aphrodisiacs: potential hazard in immigrants.
Authors: R L Brearley, A M Forsythe
Journal: BMJ (1978)

Healthy adults (n=922) * Dog breeders and i 40 1 | exhibitors (n= 102) 0 "6c 30 t 91 Elisa values C associated with ' 20 toxocariasis _ 0. 10 0 M <0 20 0 30 0-40 0 50 0*75 1 0 >1*0 Toxocara-Elisavalue (E405Jpper class limits) Distribution of toxocara ELISA values among 922 healthy adults and 102 dog breeders and exhibitors.ELISA values above 0 5 indicate current or past toxocaral infection.there is in general no relationship between ELISA values and age4 among healthy controls, there were 23-1 % of positive reactors among the 52 volunteer exhibitors in this study who were over 40 years of age compared with only 8 % of positive reactors among the 50 volunteers under that age.This difference is statistically significant (P< 0-02) and is consistent with increasing exposure to infection with long contact with breeding animals.Country-dwellers, who had on average been breeding from 7-4 bitches for 19-4 years, gave more positive ELISA readings (28-1 %) than inhabitants of villages, towns, or cities (10%, P< 05) who had owned on average 4-7 animals for 12-5 years.*Atomic absorption spectroscopy.
Islet-Cell Antibodies and Beta-Cell Function in Monozygotic Triplets and Twins Initially Discordant for Type I Diabetes Mellitus
Authors: S. Srikanta, Om P. Ganda, George S. Eisenbarth, J. Stuart Soeldner
Journal: New England Journal of Medicine (1983)

Type I diabetes mellitus has until recently been considered a disease that has an acute onset and is characterized by the sudden appearance of metabolic abnormalities in previously "healthy" people. Recent studies have suggested that there is a latent period before the development of overt diabetes, during which islet-cell antibodies arc present.1 2 3 4 In an ongoing prospective study of "genetic prediabetes," conducted by one of us (J.S.S.) and co-workers at the Joslin Diabetes Center, a set of monozygotic triplets5 and a set of monozygotic twins initially discordant for Type I diabetes were identified. These patients were unique in that their beta-cell . . .