tbuckley/cabot-search huggingface dataset:
Abstract 5212: Irradiation-induced uPAR promotes stemness via Wnt/β-catenin signaling in medulloblastoma cells
Authors: Swapna Asuthkar, Christopher S. Gondi, Arun Kumar Nalla, Kiran Kumar Velpula, Bharathi Gorantla, Jasti S. Rao
Journal: Cancer Research (2012)

Abstract Urokinase plasminogen activator receptor (uPAR) is known to promote invasion, migration and metastasis in cancer cells. In this study, we show that ionizing radiation (IR) induced uPAR has a role in Wnt/β-catenin signaling and mediates induction of cancer stem cells (CSC)-like properties in medulloblastoma cell lines UW228 and D283. We observed that IR induced the expression of uPAR, CSC markers such as CD44 and Msi-1, and activates Wnt/β-catenin signaling molecules. Overexpression of uPAR after IR treatment led to the activation of Wnt signaling, which was demonstrated by an increase in nuclear translocation of β-catenin and β-catenin-Lef/Tcf-mediated transactivation, thereby promoting cancer stemness. Quercetin, a potent Wnt/β-catenin inhibitor suppressed uPAR and uPAR-mediated Wnt/β-catenin activation. Treatment with shRNA specific for uPAR (pU) suppressed the β-catenin-Tcf/Lef-mediated transactivation both in vitro and in vivo. Further, we show that uPAR is physically associated with the Wnt effector molecule β-catenin using immunocytochemistry and immunohistochemistry; these results were confirmed by immunoprecipitation analysis. Most interestingly, we demonstrate for the first time that the localization of uPAR in the nucleus is associated with transcription factors (TF) and their specific response elements. The association of uPAR with β-catenin-Tcf/Lef complex and various other TF involved in neurogenesis during embryonic development and cancer demonstrates the receptor's possible role at generating CSC-like properties in primitive neuroectodermal tumor (PNET) cells of medulloblastoma. Considering all of the data, we conclude that uPAR is a potent activator of stemness, and the targeting of uPAR in combination with radiation has significant therapeutic implications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5212. doi:1538-7445.AM2012-5212
Sandy Holt-Wilson
Authors: R. Hardy
Journal: BMJ (2014)

Alexander Holt-Wilson (“Sandy”) was an ophthalmic surgeon who devoted his retirement years to tackling the problem of poor standards of eye care in the Gondar region of Ethiopia. He pioneered the restructuring and development of ophthalmic training in the region, and as a direct consequence of his work, 60 000 cataracts have been removed by nurse ophthalmic surgeons, an eye centre was built, and an ophthalmoscope costing less than £10 was developed.

Sandy’s interest in Ethiopia had deep roots. When Tewodros II, the emperor of Ethiopia, was defeated by General Napier’s army at the Battle of Magdala in 1868, his orphaned son, Prince Alemayehu, was brought to England, where Queen Victoria took a personal interest in his welfare. He was educated by Sandy’s great grandfather before progressing to Rugby School. This story attracted Sandy’s interest, and led to a longstanding fascination with Amharic culture and history, and Ethiopia …
Causes of Night Cramps-Reply
Authors: Paul Cutler
Journal: JAMA (1985)

In Reply.—  Dr Sugar believes that lumbar spondylosis could be a common cause of nocturnal cramps and suggests this hypothesis be tested in any low-back pain clinic. I would urge that he do so; anecdotal data have little value. Having searched the literature and textbooks, nowhere do I find nerve root irritation to be a cause of night cramps. Leg pain and low-back muscle spasm—yes! Leg pain and leg muscle spasm—no! The coincidence of night cramps and lumbar spondylosis may simply represent the concurrence of two common but unrelated problems in the elderly.  The theory presented by Dr Sugar seems plausible, but it is not substantiated by clinical research or published material. Furthermore, the pharmacologic reasons for the beneficial effects of quinine and diphenhydramine are far more complex than their actions on the myoneural junction.
Abstract 5154: Human umbilical cord matrix stem cells transfected with the interferon-β gene markedly attenuated the growth of bronchioloalveolar carcinoma xenografts in mice
Authors: Atsushi Kawabata, Chiyo Doi, Takaya Matsuzuka, Raja Shekar Rachakatla, Naomi Ohta, Marla Pyle, Frank Marini, Deryl Troyer, Masaaki Tamura
Journal: Cancer Research (2010)

Abstract Mesenchymal stem cells derived from the human umbilical cord matrix (UCMSC) have great potential for therapeutic use in multiple diseases including cancer. UCMSC can be used as carriers for targeted delivery of genes or therapeutics and for local production of biologic agents. The therapeutic strategy using UCMSC as cellular vehicles for targeted gene delivery can avoid the problem of short life or excessive toxicity of a particular gene product in vivo. Interferon-β (IFN-β) has demonstrated a potent anti-tumor effect on many tumor cell lines in vitro. However, in vivo inhibition of tumor cell growth by IFN-β required blood concentrations much higher than the maximally tolerated dose. Therefore, clinical therapy by systemic administration of IFN-β was not possible. The aim of this study was to determine the anti-cancer effect of IFN-β gene transfected-UCMSC (IFN-UCMSC) on bronchioloalveolar carcinoma (BAC) cell lines in vitro and in vivo. The conditioned medium derived from IFN-UCMSC significantly attenuated cell growth of H358 and SW1573 BAC cell lines in vitro compared to the medium derived from non-transfected UCMSC. The percentage of dead cells, as measured by the trypan blue exclusion test, was significantly higher in the cells treated with the medium derived from IFN-UCMSC than UCMSC alone. The co-culture of IFN-UCMSC with cancer cells inhibited cell growth significantly through stimulation of apoptosis. Finally, systemic administration of IFN-UCMSC (0.3 million cells/injection, 5 day interval for four times) markedly attenuated tumor multiplicity and size of orthotopic H358 BAC xenografts in SCID mouse lungs. Histochemical analysis of the tumors indicated tumor-targeted localization of UCMSC and significant reduction of tumor cell proliferation index as measured by Ki-67 staining. These results clearly indicated that IFN-β production by IFN-UCMSC attenuated growth of BAC cells by inducing programmed cell death both in vitro and in vivo. This research clearly demonstrated that IFN-UCMSC are a powerful anti-cancer therapeutic tool as delivery vehicles for IFN-β. This work was supported by the KSU Terry C. Johnson Center for Basic Cancer Research, KSU Provost's Fund, KSU CVM Dean's Fund, NIH P20 RR017686 and a Joan's Legacy Research Grant. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5154.
ACIDIFYING AND NON-ACIDIFYING CARBOXYLIC RESIN MIXTURES USED ALONE AND WITH ACTH OR CORTISONE
Authors: J. H. Peters, T. S. Danowski, L. Greenman, F. A. Weigand, C. E. Clarke, K. Garver, F. M. Mateer, R. Tarail
Journal: Journal of Clinical Investigation (1951)
Coronary microvascular dysfunction is an early feature of cardiac involvement in patients with Anderson–Fabry disease
Authors: Benedetta Tomberli, Franco Cecchi, Roberto Sciagrà, Valentina Berti, Francesca Lisi, Francesca Torricelli, Amelia Morrone, Gabriele Castelli, Magdi H. Yacoub, Iacopo Olivotto
Journal: European Journal of Heart Failure (2013)
Re: Sanjay Kulkarni, Guido Barbagli, Deepak Kirpekar, et al. Lichen Sclerosus of the Male Genitalia and Urethra: Surgical Options and Results in a Multicenter International Experience with 215 Patients. Eur Urol 2009;55:945–56
Authors: Christopher B. Bunker
Journal: European Urology (2010)
Cellular origins of the transient inward current in cardiac myocytes. Role of fluctuations and waves of elevated intracellular calcium.
Authors: J R Berlin, M B Cannell, W J Lederer
Journal: Circulation Research (1989)

Activation of the transient inward current (ITI) by a rise in intracellular calcium concentration ([Ca2+]i) is believed to be responsible for generating triggered cardiac arrhythmias. In this study, the cellular basis of the rise in [Ca2+]i that activates ITI and aftercontractions in single rat ventricular myocytes was examined. [Ca2+]i was measured both indirectly by cell contraction and directly with fura-2. Under conditions that caused steady-state [Ca2+]i to increase (i.e., calcium overload) membrane repolarization after a voltage-clamp depolarization resulted in the appearance of ITI that was similar in many respects to that observed in multicellular preparations. This ITI occurred at the same time that [Ca2+]i spontaneously increased and preceded the aftercontraction by 60-90 msec. However, ITI recorded from a single cell was variable in time course and amplitude (unlike that observed in multicellular preparations). Examination of cell contraction and digital imaging of fura-2 fluorescence showed that ITI was often associated with propagating regions of increased [Ca2+]i, which arose from discrete sites of origin within the cell. Apparently synchronous aftercontractions could also be associated with multiple propagating waves of [Ca2+]i. The variation in the time course and amplitude of ITI in single cells appeared to be due to changes in the location and number of sites of origin for the waves of [Ca2+]i. After the first aftercontraction and ITI, desynchronization of the sites of origin of increased [Ca2+]i occurred, and this resulted in a decrease in the amplitude of ITI and an increase in its duration. We conclude that the variability seen in single cells arises from changes in the pattern of spontaneous Ca2+ release. Such phenomena will seriously complicate interpretation of multicellular data, even when [Ca2+]i is measured directly.
STIMULUS-RESPONSE IN THE MIXED LYMPHOCYTE REACTION
Authors: Michael R. Harrison, William E. Paul
Journal: The Journal of Experimental Medicine (1973)

Mixed lymphocyte reactions occur when mouse spleen cell populations depleted of thymus-derived (T) lymphocytes are cultured with allogeneic target cells inactivated by mitomycin C or X irradiation, and when F(1) hybrid responder cells are cultured with inactivated parental target cells. These responses might be interpreted as indicating that T lymphocytes are not required for responsiveness and that F(1) lymphocytes recognize parental alloantigens. Data reported here indicate that the more likely explanation for these surprising results is that inactivated target cells recognize the "responding" cells and this recognition leads to the response observed.
As for Heart Transplants...
Authors: Phil Gunby
Journal: JAMA (1988)

AS ARTIFICIAL HEART studies continue, the number of human hearts transplanted each year is increasing. There are predictions that, when the worldwide total for the past year is tallied, it will exceed 4000 (<i>JAMA</i>1987;258:3084-3085). The American Heart Association says 1024 human heart transplants were performed in the United States alone in 1986, the latest year for which complete data are available. That total, the association says, is about three times greater than the US total for 1984. At a seminar in New Orleans, association officials estimated that cardiovascular diseases' societal bill will be $83.7 billion this year in medical services and lost productivity. They note also that, despite recent declines in the mortality rate attributable to heart and blood vessel diseases, cardiovascular disorders still cause a death in this country on an average of every 32 seconds. And, the association staff says, cardiovascular diseases are blamed for 991 282
Inhibition of prostaglandin synthesis by indomethacin augments the renal vasodilator response to bradykinin in the anesthetized dog.
Authors: A J Lonigro, M H Hagemann, A H Stephenson, C L Fry
Journal: Circulation Research (1978)

It has been proposed that the increase in renal blood flow (RBF) produced by bradykinin (BK) is mediated or amplified by the intrarenal generation of prostaglandins. The present investigation was designed to explore these relationships further. In anesthetized dogs, the renal arterial infusion of BK (100 ng/kg per min), prior to the intravenous administration of indomethacin, produced a 93 +/- 14% increase in RBF and an increase in the renal venous concentration of a prostaglandin E-like substance ("PGE") from 51 +/- 23 to 235 +/- 73 pg/ml as determined by bioassay. Following indomethacin (5 mg/kg), the same dose of BK produced a 151 +/- 18% increase in RBF (P less than 0.001 compared to the preindomethacin increase) and the concentration of "PGE" remained largely below the threshold of sensitivity of the bioassay system. In three experiments, a highly sensitive and specific radioimmunoassay technique was used to obtain better quantitative estimates of concentrations of E2-like ("PGE2") and F2alpha-like ("PGF2alpha") substances so that determinations of renal efflux could be made. Thus, prior to indomethacin, BK administration increased RBF by 142 +/- 39 ml/min and was associated with a 26-fold increase in renal efflux of "PGE2" and a 12-fold increase in "PGF2alpha." After indomethacin, the effluxes of both "PGE2" and "PGF2alpha" decreased to negligible levels and were not influenced by BK infusion, although RBF increased by 225 +/- 75 ml/min. These results are not compatible with the hypothesis that intrarenal prostaglandins mediate or amplify the renal vasodilator response to BK.
Exponential Enhancement of Oncolytic Vesicular Stomatitis Virus Potency by Vector-mediated Suppression of Inflammatory Responses In Vivo
Authors: Jennifer Altomonte, Lan Wu, Li Chen, Marcia Meseck, Oliver Ebert, Adolfo García-Sastre, John Fallon, Savio LC Woo
Journal: Molecular Therapy (2007)

Oncolytic virotherapy is a promising strategy for treatment of malignancy, although its effectiveness is hampered by host antiviral inflammatory responses. The efficacy of treatment of oncolytic vesicular stomatitis virus (VSV) in rats bearing multifocal hepatocellular carcinoma (HCC) can be substantially elevated by antibody-mediated depletion of natural killer (NK) cells. In order to test the hypothesis that the oncotyic potency of VSV can be exponentially elevated by evasion of inflammatory responses in vivo, we constructed a recombinant VSV vector expressing equine herpes virus-1 glycoprotein G, which is a broad-spectrum viral chemokine binding protein (rVSV-gG). Infusion of rVSV-gG via the hepatic artery into immune-competent rats bearing syngeneic and multifocal HCC in their livers, resulted in a reduction of NK and NKT cells in the tumors and a 1-log enhancement in intratumoral virus titer in comparison with a reference rVSV vector. The treatment led to increased tumor necrosis and substantially prolonged animal survival without toxicities. These results indicate that rVSV-gG has the potential to be developed as an effective and safe oncolytic agent to treat patients with advanced HCC. Furthermore, the novel concept that oncolytic potency can be substantially enhanced by vector-mediated suppression of host antiviral inflammatory responses could have general applicability in the field of oncolytic virotherapy for cancer.
USE OF CARDIOPULMONARY BYPASS FOR CORONARY GRAFT SURGERY IN PATIENTS WITH POOR VENTRICULAR FUNCTION
Authors: Basel Ramlawi, Luis J. Garcia-Morales, Elizabeth A. David, Tadashi Motomura, Faisal Masud, Michael J. Reardon, Mahesh Ramchandani
Journal: Journal of the American College of Cardiology (2011)
Evidence against Transmission of Hodgkin's Disease in High Schools
Authors: Seymour Grufferman, Philip Cole, Thelma R. Levitan
Journal: New England Journal of Medicine (1979)

A survey in Greater Boston identified 1577 new cases of histologically diagnosed Hodgkin's disease between 1959 and 1973. Of these cases, 448 were of ages such that the patients might have attended high school during 1960–73. For 96 per cent of these persons high-school attendance was ascertained. First of all, we studied Hodgkin's disease at high schools in two time periods. The 13 high schools with cases present in 1960–64 were matched with 26 schools that had no cases in this period, and we compared these two groups for the occurrence of Hodgkin's disease during 1965–69. The proportion of "exposed" high schools that had cases diagnosed in the second period was 0.62, and that for the matched high schools was 0.65. We performed this two-time-period analysis for 25 additional combinations of time periods; in none of them did we find a statistically significant positive result. Secondly, we studied the risk of Hodgkin's disease among persons who had attended high school at the same time as a diagnosed case. We followed these "exposed" persons through 1973 and observed 12 cases among them, whereas the expected number of cases was 13.9. Thirdly, we evaluated the extent to which members of all possible pairs of cases had attended the same or nearby high schools at the same time. We found no excess of classmate pairs than might have occurred by chance alone. These data suggest that there is no transmission of an etiologic agent for Hodgkin's disease at high schools. (N Engl J Med 300:1006–1011, 1979)
Fifty six continence advisers, one peripatetic teacher.
Authors: C. Hall, C. M. Castleden, G. J. Grove
Journal: BMJ (1988)

The increasing demand for the services of a continence nurse led to a novel plan to combat such demand in Leicestershire. The district nursing service seconded a nurse to be trained as an adviser and then to return to the community to set up continence clinics in each health centre. The adviser selected nurses to run these clinics and taught them the skills required to do so. She also carried her own caseload. One hundred and one patients were seen in the clinics in the first year, of whom 30 were cured. In a further one third continence was greatly improved, and the remainder benefited from advice and consultation. The adviser has worked in only six health centres but has had a greater impact on dealing with incontinence than a series of lectures and seminars for district nurses over many years had had.
Insulin regulation of renal glucose metabolism in conscious dogs.
Authors: E Cersosimo, R L Judd, J M Miles
Journal: Journal of Clinical Investigation (1994)

Previous studies indicating that postabsorptive renal glucose production is negligible used the net balance technique, which cannot partition simultaneous renal glucose production and glu- cose uptake. 10d after surgical placement of sampling cath- eters in the left renal vein and femoral artery and a nonobstruc- tive infusion catheter in the left renal artery of dogs, systemic and renal glucose and glycerol kinetics were measured with peripheral infusions of 13-3Hjglucose and [2-14Cjglycerol.After baseline measurements, animals received a 2-h intrarenal infusion of either insulin (a = 6) or saline (a = 6).Left renal vein insulin concentration increased from 41±8 to 92±23 pmol/l (P < 0.05) in the insulin group, but there was no change in either arterial insulin, (-50 pmol/1), glucose concentra- tions (-5.4 mmol/1), or glucose appearance (-18 ,Pmol * kg-' * min-).Left renal glucose uptake increased from 3.1±0.4 to 5.4±1.4Mmol.kg-l min' (P < 0.01) while left renal glucose production decreased from 2.6±0.9 to 0.7±0.5Ormolu kg-' * min-(P < 0.01 ) during insulin infusion.Renal gluconeogenesis from glycerol decreased from 0.23±0.06 to 0.17±0.04gmol * kg-' * min' (P < 0.05) during insulin infu- sion.These results indicate that renal glucose production and utilization account for -30% of glucose turnover in postab- sorptive dogs.Physiological hyperinsulinemia suppresses renal glucose production and stimulates renal glucose uptake by -75%.We conclude that the kidney makes a major contribu- tion to systemic glucose metabolism in the postabsorptive state.
Observations on the Regulation of Cerebral Blood Flow in Complete Heart Block
Authors: WILLIAM SHAPIRO, N. P. S. CHAWLA
Journal: Circulation (1969)

The simultaneous effects of right ventricular pacing on cerebral blood flow (CBF) and cardiac function in complete heart block have not been reported. Catheters in the jugular bulb, right ventricle, and pulmonary and brachial arteries of five patients, aged 49 to 78 years, allowed studies at initial rates of 30 to 40 and during the tenth minute of pacing at 60, 70, 90, and 100 per minute. Mean initial cardiac output (CO) was 2.8 L per minute and increased 29% to 3.6 at a rate of 60 per minute ( P &lt;0.01). Simultaneous mean control CBF was also low, but rose to 118% of control with pacing ( P &lt;0.05). Systemic, cerebral, and pulmonary vascular resistances declined with these increases in flow as the elevated mean venous and arterial pressures remained stable. Mean arterial oxygen and carbon dioxide tensions and pH were normal at all rates. The parameters measured were not materially altered by pacing at rates above 60 per minute. The changes in CBF were well correlated with those of CO (r=0.81, P &lt;0.01) and unrelated to simultaneous mean arterial or cerebral perfusion pressures. The alterations in CO were also unrelated to these pressures. The data clearly demonstrate a disturbance in CBF autoregulation, which may be a function of the low CO state.
332 Peginterferon alfa-2A (40KD) (PEGASYS®) in combination with ribavirin in African American and Caucasian patients with chronic hepatitis C HCV genotype 1: safety and tolerability
Authors: C HOWELL, L JEFFERS, W CASSIDY, K RAJENDERREDDY, S SHERIDAN, I HO, S KHOURI, G HARB
Journal: Hepatology (2003)
Volume Progression in Polycystic Kidney Disease
Authors: Jared J. Grantham, Vicente E. Torres, Arlene B. Chapman, Lisa M. Guay-Woodford, Kyongtae T. Bae, Bernard F. King, Louis H. Wetzel, Deborah A. Baumgarten, Phillip J. Kenney, Peter C. Harris, Saulo Klahr, William M. Bennett, Gladys N. Hirschman, Catherine M. Meyers, Xiaoling Zhang, Fang Zhu, John P. Miller
Journal: New England Journal of Medicine (2006)

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of cyst-filled kidneys.In a three-year study, we measured the rates of change in total kidney volume, total cyst volume, and iothalamate clearance in patients with ADPKD. Of a total of 241 patients, in 232 patients without azotemia who were 15 to 46 years old at baseline we used magnetic-resonance imaging to correlate the total kidney volume and total cyst volume with iothalamate clearance. Statistical methods included analysis of variance, Pearson correlation, and multivariate regression analysis.Total kidney volume and total cyst volume increased exponentially, a result consistent with an expansion process dependent on growth. The mean (+/-SD) total kidney volume was 1060+/-642 ml at baseline and increased by a mean of 204+/-246 ml (5.27+/-3.92 percent per year, P<0.001) over a three-year period among 214 patients. Total cyst volume increased by 218+/-263 ml (P<0.001) during the same period among 210 patients. The baseline total kidney volume predicted the subsequent rate of increase in volume, independently of age. A baseline total kidney volume above 1500 ml in 51 patients was associated with a declining glomerular filtration rate (by 4.33+/-8.07 ml per minute per year, P<0.001). Total kidney volume increased more in 135 patients with PKD1 mutations (by 245+/-268 ml) than in 28 patients with PKD2 mutations (by 136+/-100 ml, P=0.03).Kidney enlargement resulting from the expansion of cysts in patients with ADPKD is continuous and quantifiable and is associated with the decline of renal function. Higher rates of kidney enlargement are associated with a more rapid decrease in renal function.