tbuckley/cabot-search huggingface dataset:
Suppression of renal cell carcinoma growth by inhibition of Notch signaling in vitro and in vivo
Authors: Jonas Sjölund, Martin Johansson, Sugata Manna, Carl Norin, Alexander Pietras, Siv Beckman, Elise Nilsson, Börje Ljungberg, Håkan Axelson
Journal: Journal of Clinical Investigation (2008)

Loss of the tumor suppressor gene von Hippel–Lindau (VHL) plays a key role in the oncogenesis of clear cell renal cell carcinoma (CCRCC). The loss leads to stabilization of the HIF transcription complex, which induces angiogenic and mitogenic pathways essential for tumor formation. Nonetheless, additional oncogenic events have been postulated to be required for the formation of CCRCC tumors. Here, we show that the Notch signaling cascade is constitutively active in human CCRCC cell lines independently of the VHL/HIF pathway. Blocking Notch signaling resulted in attenuation of proliferation and restrained anchorage-independent growth of CCRCC cell lines. Using siRNA targeting the different Notch receptors established that the growth-promoting effects of the Notch signaling pathway were attributable to Notch-1 and that Notch-1 knockdown was accompanied by elevated levels of the negative cell-cycle regulators p21Cip1 and/or p27Kip1. Treatment of nude mice with an inhibitor of Notch signaling potently inhibited growth of xenotransplanted CCRCC cells. Moreover, Notch-1 and the Notch ligand Jagged-1 were expressed at significantly higher levels in CCRCC tumors than in normal human renal tissue, and the growth of primary CCRCC cells was attenuated upon inhibition of Notch signaling. These findings indicate that the Notch cascade may represent a novel and therapeutically accessible pathway in CCRCC.
Assessing the outcome of compulsory psychiatric treatment in the community: epidemiological study in Western Australia
Authors: N. J Preston
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To examine whether community treatment orders for psychiatric patients reduce subsequent use of health services in comparison with control patients not placed on an order. <b>Design:</b> Epidemiological study with a before and after, two stage design of matching and multivariate analysis, controlling for sociodemographic variables, clinical features, and psychiatric history. <b>Setting:</b> All community based and inpatient psychiatric services in Western Australia, covering a population of 1.7 million people. <b>Participants:</b> 228 subjects placed on a community treatment order, matched with an equal number of controls to give a total of 456 patients. <b>Main outcome measures:</b> Inpatient admissions, bed days, and outpatient contacts one year after subjects were placed on a community treatment order or the index date of matched controls. <b>Results:</b> Both subjects and their matched controls had reduced inpatient admissions and bed days in hospital. Subjects had significantly more outpatient contacts. Multivariate analysis indicated that being placed on a community treatment order was associated with increased outpatient contacts in the subsequent year compared with the control group. Otherwise, orders did not affect subsequent use of health services. Other factors associated with increased use of health services were age and inpatient admissions, bed days, and outpatient contacts before the order or index date. No covariates were shown to be associated with changes in within pair differences in inpatient admissions or bed days. <b>Conclusions:</b> The introduction of compulsory treatment in the community does not lead to reduced use of health services. <h3>What is already known on this topic</h3> Various forms of compulsory treatment in the community have been suggested as being effective in reducing use of services by patients with mental health disorders Studies have often lacked epidemiological sampling frames and control for possible confounding factors <h3>What this study adds</h3> Patients placed on community treatment orders and those not on such orders had reduced hospital admissions and bed days one year later Placement of an order did not predict subsequent use of services Community treatment orders may not be an effective alternative to assertive community treatment programmes
Learning How Phytochemicals Help Fight Disease
Authors: Charles Marwick
Journal: JAMA (1995)

WHILE MANY organizations such as the National Cancer Institute (NCI) and American Heart Association continue to recommend diets low in fat and high in fiber to reduce the chance of developing cancer and heart disease, it is becoming clear that research into the connection between foods and disease has moved onto a more sophisticated plane. Detailed studies at the biochemical and even molecular level are providing new information about the role phytochemicals, the active compounds in dietary fruits and vegetables, play in preventing, and sometimes treating, malignant disease. Most of this research has been done during the past 7 years, said Ritva R. Butrum, PhD, vice president of the American Institute for Cancer Research, who was interviewed during the group's annual meeting in Washington, DC. The meeting attracted some 400 scientists, the largest attendance in the history of the 12-year-old organization. "We are far from definitive findings, but I think
Fat Utilization in Adults on a Diet of Cows' Milk
Authors: R. Hecker, W. H. H. Andrews
Journal: BMJ (1954)

Urea.-The method of Karr (1924) was applied to both urine and tungstate filtrates of plasma in appropriate dilution.The final colorimetric estimation was carried out in a Coleman junior spectrophotometer set at a wave- length of 5,000 A.Creatinine.-Diluted urine samples and tungstate filtrates of plasma were treated by an alkaline picrate method (W. S. S. Ladell, 1951, personal communication), the final estimation being carried out in the Coleman junior spectro- photometer set at a wavelength of 5,200 A. ResultsFrom the values for plasma concentration, urine con- centration, and urine flow were calculated the clearance values for the two substances by the usual formula.The results obtained are set out in the Table, together with the mean values and the standard deviations of the observations.The table also records the mean values obtained on a group of European subjects examined under the same conditions.The values for urea clearance have been divided into two groups-those obtained at urine flows less than 2 ml. a minute and those obtained at higher rates of flow.In both cases the true clearance value is recorded; the empirical standardization of the values obtained at low flows has not been employed.
Stimulus interval-dependent differences in Ca2+ transients and contractile responses of diabetic rat cardiomyocytes
Authors: G Kotsanas
Journal: Cardiovascular Research (2000)

Objective: The aim of this study was to gain further insights into the consequences of insulin-dependent diabetes mellitus on cardiomyocyte calcium handling. Methods: The effects of steady state and transient changes in stimulus frequency on the intracellular Ca2+ transient and cell shortening were examined in left ventricular cardiomyocytes isolated from the hearts of control and streptozotocin-induced diabetic rats. Results: During steady state stimulation diabetic rat cardiomyocytes displayed a slower decay of the Ca2+ transient and longer times for maximum cell shortening and re-lengthening. At 1.5 mM extracellular [Ca2+], increasing stimulus frequency over the range 0.2–1.0 Hz led to an increase in resting and peak [Ca2+]i as well as the amplitude of the transient in both the control and diabetic groups. At frequencies greater than 0.4 Hz the amplitude of the transient was significantly depressed in diabetic rat cells and this was not normalized by increasing extracellular [Ca2+] to 2.5 mM. Recovery of sarcoplasmic reticulum (SR) Ca2+ release was measured from the time course of restitution of the intracellular Ca2+ transient. In both control and diabetic rat cardiomyocytes recovery of the transient occurred in two phases. In diabetic rat myocytes, the initial rapid phase of restitution at intervals <1 s was markedly slowed. The fraction of Ca2+ recirculating between the SR and the cytosol was estimated from the decline in amplitude of transients following post-rest potentiation. There was no difference in this fraction between control and diabetic rat cells either at 1.5 or 2.5 mM extracellular [Ca2+]. Conclusion: The blunted frequency response of diabetic rat cardiomyocytes at frequencies greater than 0.4 Hz is consistent with reduced SR Ca2+ uptake leading to reduced SR Ca2+ content and subsequent release. At stimulus intervals greater than 1 Hz this is likely to be exacerbated by slower recovery of SR Ca2+ release. Despite the evidence for depressed SR Ca2+ uptake, the relative amount of Ca2+ recirculating within diabetic rat cardiomyocytes remains unaltered. This is most likely due to an accompanying reduction in Ca2+ efflux from the cell due either to depressed Na+/Ca2+ exchanger activity, or an elevation in intracellular Na+ levels.
Role of HSP90, CDC37, and CRM1 as modulators of P16<sup>INK4A</sup>activity in rat liver carcinogenesis and human liver cancer
Authors: Rosa M. Pascale, Maria M. Simile, Diego F. Calvisi, Maddalena Frau, Maria R. Muroni, Maria A. Seddaiu, Lucia Daino, Maria D. Muntoni, Maria R. De Miglio, Snorri S. Thorgeirsson, Francesco Feo
Journal: Hepatology (2005)

Current evidence indicates that neoplastic nodules induced in liver of Brown Norway (BN) rats genetically resistant to hepatocarcinogenesis are not prone to evolve into hepatocellular carcinoma. We show that BN rats subjected to diethylnitrosamine/2-acetylaminofluorene/partial hepatectomy treatment with a "resistant hepatocyte" protocol displayed higher number of glutathione-S-transferase 7-7(+) hepatocytes when compared with susceptible Fisher 344 (F344) rats, both during and at the end of 2-acetylaminofluorene treatment. However, DNA synthesis declined in BN but not F344 rats after completion of reparative growth. Upregulation of p16INK4A, Hsp90, and Cdc37 genes; an increase in Cdc37-Cdk4 complexes; and a decrease in p16INK4A-Cdk4 complexes occurred in preneoplastic liver, nodules, and hepatocellular carcinoma of F344 rats. These parameters did not change significantly in BN rats. E2f4 was equally expressed in the lesions of both strains, but Crm1 expression and levels of E2f4-Crm1 complex were higher in F344 rats. Marked upregulation of P16INK4A was associated with moderate overexpression of HSP90, CDC37, E2F4, and CRM1 in human hepatocellular carcinomas with a better prognosis. In contrast, strong induction of HSP90, CDC37, and E2F4 was paralleled by P16INK4A downregulation and high levels of HSP90-CDK4 and CDC37-CDK4 complexes in hepatocellular carcinomas with poorer prognosis. CDC37 downregulation by small interfering RNA inhibited in vitro growth of HepG2 cells. In conclusion, our findings underline the role of Hsp90/Cdc37 and E2f4/Crm1 systems in the acquisition of a susceptible or resistant carcinogenic phenotype. The results also suggest that protection by CDC37 and CRM1 against growth restraint by P16INK4A influences the prognosis of human hepatocellular carcinoma.(HEPATOLOGY 2005;42:1310–1319.)
Restoration of Diastolic Function in Senescent Rat Hearts Through Adenoviral Gene Transfer of Sarcoplasmic Reticulum Ca <sup>2+</sup> -ATPase
Authors: Ulrich Schmidt, Federica del Monte, Michael I. Miyamoto, Takashi Matsui, Judith K. Gwathmey, Anthony Rosenzweig, Roger J. Hajjar
Journal: Circulation (2000)

Background —Senescent hearts are characterized by diastolic dysfunction and a decrease in sarcoplasmic reticulum (SR) Ca 2+ -ATPase protein (SERCA2a). Methods and Results —To test the hypothesis that an increase in SERCA2a could improve cardiac function in senescent rats (age 26 months), we used a catheter-based technique of adenoviral gene transfer to achieve global myocardial transduction of SERCA2a in vivo. Adult rat hearts aged 6 months and senescent rat hearts infected with an adenovirus containing the reporter gene β-galactosidase were used as controls. Two days after infection, parameters of systolic and diastolic function were measured in open-chest rats. Cardiac SERCA2a protein and ATPase activity were significantly decreased in senescent hearts compared with adult rats (Δ −30±4% and −49±5%) and were restored to adult levels after infection with Ad.SERCA2a. At baseline, left ventricular systolic pressure and +dP/dt were unaltered in senescent hearts; however, diastolic parameters were adversely affected with an increase in the left ventricular time constant of isovolumic relaxation and diastolic pressure (Δ +29±9% and +38±12%) and a decrease in −dP/dt (Δ −26±11%). Overexpression of SERCA2a did not significantly affect left ventricular systolic pressure but did increase +dP/dt (Δ +28±10%) in the senescent heart. Overexpression of SERCA2a restored the left ventricular time constant of isovolumic relaxation and −dP/dt to adult levels. Infection of senescent hearts with Ad.SERCA2a markedly improved rate-dependent contractility and diastolic function in senescent hearts. Conclusions —These results support the hypothesis that decreased Ca 2+ -ATPase activity contributes to the functional abnormalities observed in senescent hearts and demonstrates that Ca 2+ cycling proteins can be targeted in the senescent heart to improve cardiac function.
TCT-104 Feasibility Study of the Repositionable Lotus Aortic Valve Replacement System: 3-Month Outcomes in 11 Patients at High Surgical Risk (REPRISE I)
Authors: Ian Meredith, Stephen Worthley, Robert Whitbourn, Paul Antonis, Joseph Montarello, Andrew Newcomb, Dominic Allocco, Keith Dawkins
Journal: Journal of the American College of Cardiology (2012)
Role of Insulin in Management of Surgical Patients With Diabetes Mellitus
Authors: Irl B Hirsch, Janet B McGill
Journal: Diabetes Care (1990)

Because surgery is a likely event during the lifetime of patients with diabetes, health-care team members need to be aware of the metabolic problems that may occur during the perioperative period. Surgery, especially in the presence of general anesthesia, will produce a diabetogenic response. This is generally due to an elevation of counterregulatory hormones, although endogenous insulin is also suppressed. The excessive lipolysis and ketogenesis that can occur during surgery can have particularly deleterious effects for patients with diabetes. Thus, sufficient insulin must be provided during this period to suppress these catabolic processes. The major controversy regarding surgery and diabetes concerns the route of insulin administration. This article reviews the various treatment options for patients with insulin-dependent and non-insulin-dependent diabetes mellitus, with particular emphasis on the role of insulin. Special situations, e.g., outpatient surgery, coronary artery bypass, and emergency surgery, are also discussed.
Splenectomy for Relapsing Thrombotic Thrombocytopenic Purpura
Authors: John G. Kelton
Journal: Annals of Internal Medicine (1997)

Letters1 June 1997Splenectomy for Relapsing Thrombotic Thrombocytopenic PurpuraJohn G. Kelton, MDJohn G. Kelton, MDMcMaster University Medical Centre, Hamilton, Ontario L8N 375, CanadaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-11-199706010-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Rice raises two questions about our study, in which we demonstrated that splenectomy prevents further relapses in patients with relapsing thrombotic thrombocytopenic purpura. The first question is whether our observation of a significant reduction in the rate of relapses after splenectomy compared with before splenectomy represents a clinically relevant observation (as Dr. Rice suggests) or whether it reflects the natural history of the condition. Increasing evidence now indicates that about one third of patients who survive the initial episode will have at least one relapse. These relapses could be temporally clustered around the first episode (as Dr. ...REFERENCE1. Shumak KH, Rock GA, Nair RC. Late relapses in patients successfully treated for thrombotic thrombocytopenic purpura. Canadian Apheresis Group. Ann Intern Med. 1995; 122:569-72. Google Scholar Author, Article, and Disclosure InformationAuthors: John G. Kelton, MDAffiliations: McMaster University Medical Centre, Hamilton, Ontario L8N 375, Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1997Volume 126, Issue 11Page: 915KeywordsApheresisBlood plasmaMorbidityProspective studiesSplenectomyStrokeThrombotic thrombocytopenic purpura ePublished: 15 August 2000 Issue Published: 1 June 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Pathologic mechanisms of type 1 VWD mutations R1205H and Y1584C through in vitro and in vivo mouse models
Authors: Cynthia M. Pruss, Mia Golder, Andrea Bryant, Carol A. Hegadorn, Erin Burnett, Kimberly Laverty, Kate Sponagle, Aly Dhala, Colleen Notley, Sandra Haberichter, David Lillicrap
Journal: Blood (2011)
Baroreceptor dynamics and their relationship to afferent fiber type and hypertension.
Authors: A M Brown, W R Saum, S Yasui
Journal: Circulation Research (1978)

Static characteristics of baroreceptors differ depending on whether receptors are connected to myelinated or unmyelinated axons (MBs and UBs) and whether they come from normotensive or spontaneously hypertensive rats (NTRs and SHRs).Dynamic characteristics are incompletely known and were examined using an in vitro rat aortic arch-aortic nerve preparation in which static characteristics are similar to those present in vivo.Small amplitude sinusoidal pressures were applied at frequencies varying from 0.1 to 20 Hz over the range of linear responses to pressure.MBs from SHRs and NTRs show peaking in curves relating gain to frequency, gain being the ratio of sinusoidal discharge-rate amplitude and sine wave pressure amplitude.Similar curves from UBs of NTRs and SHRs are overdamped and show no such peaking.In MBs, the response phase leads initially, starts to lag around resonant frequencies, and falls behind progressively thereafter.In UBs, the phase also leads initially, then lags monotonically to about -60°.The discharge rectifies at high frequencies probably as the result of nonlinear threshold properties of the spike-initiating zone.The dynamic response curves of SHR and NTR aortas also were determined and found to be flat to much higher frequencies than those of the baroreceptors.Thus aortic wall dynamics do not limit the frequency range of the baroreceptors.There are no differences between NTRs and SHRs in the dynamics of either their aortas or their baroreceptors.The differences in dynamics between MBs and UBs may be due to differences in mechanical coupling related to structural differences between their endings.
1056-161 Mental stress provokes ischemia in some coronary artery disease patients without exercise/adenosine-induced ischemia
Authors: Srikanth Ramachandruni, Michelle L Ruby, Courtney Butler, Roger B Fillingim, Carsten M Schmalfuss, Susan P McGorray, Gary R Cooper, David S Sheps
Journal: Journal of the American College of Cardiology (2004)
New Mutations May Develop in Recurrent Tumors
Authors: Tracy Hampton
Journal: JAMA (2014)

Recurrent tumors often develop a set of genetic mutations that are markedly different from the original tumor, reports an international group of scientists who analyzed the genomes of 23 low-grade gliomas and recurrences of those malignancies (Johnson BE et al. Science. 2014;343[6167]:189-193).
Constipation and a Low-Fiber Diet Are Not Associated With Diverticulosis
Authors: Anne F. Peery, Robert S. Sandler, Dennis J. Ahnen, Joseph A. Galanko, Adrian N. Holm, Aasma Shaukat, Leila A. Mott, Elizabeth L. Barry, David A. Fried, John A. Baron
Journal: Clinical Gastroenterology and Hepatology (2013)
Abstract 5167: A new panel of tissue markers for the prediction of bone metastatization from primary breast cancer
Authors: Laura Mercatali, Toni Ibrahim, Emanuele Sacanna, Emanuela Scarpi, Francesco Fabbri, Rossana Ricci, Daniele Calistri, Dino Amadori
Journal: Cancer Research (2011)

Abstract Background: It is known that numerous molecular markers associated with proliferation, invasion and adhesion processes, growth factors, chemokines and their receptors, and molecules with bone-like phenotype are involved in metastasization to bone. Only cancer cells with specific molecular profiles are capable of reaching and colonizing bone tissue. The early prediction of relapse in this site could be used to select candidates for tailored therapy with bone-specific drugs such as bisphosphonates or RANK-L inhibitors. In the present study we aimed to identify primary tumor markers capable of predicting relapse to bone. Material and methods: The expression of different markers was retrospectively analyzed in frozen breast cancer tissue samples from 40 patients comprising 15 cases with no evidence of disease (NEDP), 15 with bone metastases (BMP), and 10 with visceral metastases (VMP). Twelve transcripts were analyzed by Quantitative Real time PCR: trefoil factor 1(TFF1), DKK1, bone sialoprotein (IBSP), heparanase (HPSE), osteopontin (SPP1), Agr2, SPARC, CTGF, COMP, follistatin (FST), osteoprotegerin and RANK. The predictive accuracy of each marker was calculated using receiver operating characteristic (ROC) curves. Results: The analysis of marker expression in the 3 different subgroups showed twofold higher median values of COMP and HPSE in BMP with respect to either NEDP or VMP (no significant difference). Furthermore, TFF1 median value was about sevenfold higher in BMP than in the other 2 subgroups (p=0.05). The area under the curve (AUC) was 0.73 for TFF1 and 0.62 for COMP and HPSE. In the dichotomous variable analysis, the most important result was observed for TFF1; in particular, TFF1 positivity was observed in 67% of cases in the BMP subgroup compared to only 21% and 20 % in NEDP and VMP, respectively. The combination analysis of TFF1 and other markers showed that positivity to at least one of the three markers, TFF1, DKK1, or IBSP, was observed in 80% of cases for the BMP group, and in only in 21% and 20% of cases in NEDP and VMP subgroups, respectively (p=0.041). Conclusions: The results from this preliminary study suggest that Real-Time PCR analysis of gene expression and, in particular, the coexpression of some markers in primary breast cancer could identify patients destined to bone relapse who could benefit from adjuvant treatment with bone-specific drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5167. doi:10.1158/1538-7445.AM2011-5167