tbuckley/cabot-search huggingface dataset:
Abstract 4943: Genetically engineered osteoprotegerin for multiple myeloma osteolytic bone damage
Authors: Jerome T. Higgs, John Jarboe, Selverangan Ponnazhagan
Journal: Cancer Research (2012)

Abstract Current treatments for osteolytic cancers include a combination of radiation, chemotherapy and cytotoxic products, but toxic side effects are still of major concern. Studies have shown that osteoclast activity is increased in patients with osteolytic cancers such as Multiple Myeloma (MM), through increased expression of Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) leading to RANKL/RANK signaling, resulting in osteoclast activation and ultimately bone resorption. Moreover, Osteoprotegerin (OPG) is drastically decreased in these patients who presents with bone lesion. Thus, the use of OPG as a therapeutic molecule would greatly decrease osteolytic damage and reduce morbidity. However, despite the of OPG potential in inhibiting the activation of bone resorbing osteoclast, OPG also binds to tumor related apoptosis-inducing ligand (TRAIL) making tumor cells resistant to apoptosis. TRAIL binds to the Death Receptor 4 and 5 (DR4, DR5) and initiate cell death of Transformed cells such as MM. The present study was designed to develop a novel therapeutic approach to the treatment of osteolytic bone damage by use of genetically altered OPG retaining RANKL binding but abolished of TRAIL binding. In order to eliminate TRAIL binding while maintaining RANKL binding, we created mutant OPG-Fc constructs by site directed mutagenesis based on interactive domain identification and by superimposing structural models of TRAIL, OPG and DR5. The mutant OPGs were produced in HEK 293 cells for characterization of potential mutants and their TRAIL binding ability. We conclude that using site-directed mutagenesis at the N-terminal of OPG effectively retains RANKL binding property but abolishes TRAIL binding property as determined by osteoclast and TRAIL assays respectively. 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 4943. doi:1538-7445.AM2012-4943
Neurokinins Modulate Hyperventilation-induced Bronchoconstriction in Canine Peripheral Airways
Authors: Arthur N. Freed, Sharron McCulloch, Teresa Meyers, Ryoichi Suzuki
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

This study was designed to test the hypotheses that (1) neurokinin (NK) receptor activity modulates hyperventilation-induced bronchoconstriction (HIB) in canine peripheral airways and (2) NK receptor activity is stimulated via hyperventilation-induced eicosanoid production and release. A bronchoscope was used in anesthetized dogs to record peripheral airway resistance (Rp); to test airway reactivity to NK A (NKA), substance P, and hypertonic saline; and to examine HIB before and after combined treatment with NK-1 (CP 99,994) and NK-2 (SR 48,968) receptor antagonists. Bronchoalveolar lavage fluid cells, prostaglandin D2, and cysteinyl leukotrienes from hyperventilated airways pretreated with either vehicle or NK antagonists were also measured. Pretreatment with NK-1 and NK-2 antagonists significantly attenuated HIB and the response to substance P, virtually abolished the response to NKA, and had little effect on the response to HS. Blockade of NK-1 and NK-2 receptors did not affect either the cell profiles or the mediator concentrations recovered in bronchoalveolar lavage fluid after hyperventilation. We conclude that NKs modulate the development of HIB and appear to do so via hyperventilation-induced eicosanoid production and release.
Inhibition of c-fes expression by an antisense oligomer causes apoptosis of HL60 cells induced to granulocytic differentiation.
Authors: R Manfredini, A Grande, E Tagliafico, D Barbieri, P Zucchini, G Citro, G Zupi, C Franceschi, U Torelli, S Ferrari
Journal: The Journal of Experimental Medicine (1993)

The c-fes protooncogene is expressed at high levels in the terminal stages of granulocytic differentiation, but so far no definite function has been attributed to the product of this oncogene. To tackle this problem, the c-fes protooncogene expression has been inhibited in HL60 cells, and fresh leukemic promyelocytes of acute promyelocytic leukemia have been induced to differentiate with retinoic acid (RA) and dimethylsulfoxide (DMSO). Inhibition was obtained by incubating the cells with a specific c-fes antisense oligodeoxynucleotide. It was observed that the cells, rather than differentiating, underwent premature cell death showing the morphological and molecular characteristics of apoptosis. This process was inhibited by granulocyte and granulocyte/macrophage colony-stimulating factor, but not by interleukin 3 (IL-3), IL-6, or stem cell factor. Our present results demonstrate that the loss of cell viability that occurs during the in vitro differentiation of myeloid cells, after the complete inhibition of the c-fes gene product and treatment with RA-DMSO, is due to activation of programmed cell death. It is concluded that a possible role of the c-fes gene product is to exert an antiapoptotic effect during granulocytic differentiation.
Alternate Site Testing for HbA1c Using the Primus CLC330 GHb Analyzer
Authors: George Phillipov, Peter Charles, Clive Beng, Patrick J Phillips
Journal: Diabetes Care (1997)

OBJECTIVE To determine whether the Primus high-pressure liquid chromatography (HPLC) is suited to alternate site testing (AST) for HbA1c in a hospital diabetes outpatient clinic. RESEARCH DESIGN AND METHODS Patients were attending the clinic for routine management of their diabetes. A number of diabetic patients with uremia (n = 11) were also investigated. HbA1c levels were measured in the outpatient setting by the Primus HPLC and in a more limited study the DCA-2000 instrument using the new 6-min assay cartridge. HbA1c measurements were also performed with Pierce affinity minicolumns and a Bio-Rad Variant HPLC. RESULTS The Primus HPLC assay had low imprecision of 2.3, 1.6, and 1.0% for HbA1c levels of 4.7, 7.3, and 11.1%, respectively, and was not prone to interference by carbamylated hemoglobin as found for the ion-exchange Variant HPLC method. Method comparison studies showed that the bias and proportional error between the Pierce affinity minicolumn procedure (standardized with respect to an external quality control program) and the Primus HPLC (Y) was −0.4 and 1.2% respectively (n = 32). Similarly the bias and proportional error between the Primus and DCA-2000 methods was 0.7 and −2.5%. The Primus was shown to give falsely elevated HbA1c concentrations if the time between sequential injections was &amp;gt; 28 min. CONCLUSIONS The Primus HPLC has a decided advantage over specialty AST instruments, like the DCA-2000, in not only meeting AST requirements but also allowing rapid automated batch processing of all laboratory HbA1c samples.
DCIS Patients Overestimate Breast Cancer Risks
Authors: L. Savage, A. Widener
Journal: JNCI Journal of the National Cancer Institute (2008)

DCIS Patients Overestimate Breast Cancer RisksMany women diagnosed with ductal carcinoma in situ (DCIS) have inaccurate perceptions of their breast cancer risks, according to a study published online February 12 in the Journal of the National Cancer Institute.DCIS is a noninvasive precancer in which abnormal cells are found in the lining of a breast duct.Women with DCIS generally have a favorable prognosis -recurrence rates are low and only about one percent of DCIS patients die from breast cancer.Nonetheless, studies suggest that DCIS patients overestimate their risks of DCIS recurrence and developing invasive breast cancer.Ann Partridge, M.D., and colleagues at Dana-Farber Cancer Institute in Boston investigated perceived breast cancer risks among women with newly diagnosed DCIS and how these risk perceptions were associated with anxiety and depression.They surveyed nearly 500 newly diagnosed DCIS patients about their quality of life (including depression and anxiety) and their perceived risk of recurrence or invasive breast cancer.The surveys were completed at enrollment in the trial and then again at 9 and 18 months.
Vascular Biomarkers and Surrogates in Cardiovascular Disease
Authors: Jean-Claude Tardif, Therese Heinonen, David Orloff, Peter Libby
Journal: Circulation (2006)

Cardiovascular biomarker research efforts have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. The United States Food and Drug Administration has relied on biomarkers to support clinical applications in many therapeutic fields, including cardiovascular disease. The appropriate application of cardiovascular biomarkers requires an understanding of disease natural history, the mechanism of the intervention, and the characteristics and limitations of the biomarker. Channels of communication among researcher, developer, and regulator must remain open to maximize the success of future biomarker efforts. In 2003, 2004, and 2005, an international panel of cardiovascular biomarker experts convened at the “Cardiovascular Biomarker and Surrogate Endpoints Symposia” held in Bethesda, Md, to discuss the use of biomarkers in the development of improved cardiovascular diagnostics and therapeutics. The information presented in the present report summarizes the authors’ perspective distilled from these proceedings.
Abstract 5646: Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion and angiogenesis of SW480 human colon cancer cells by modulating Wnt/b-catenin signaling
Authors: Kyoung-Sub Song, Ge Li, Tae-Dong Kim, Jong-Seok Kim, So-Yeon Shin, Kaipeng Jing, Jong-Il Park, Gi-Ryang Kweon, Byung-Doo Hwang, Wan-Hee Yoon, Kyu Lim
Journal: Cancer Research (2010)

Abstract It is known that polysaccharide extracted from Phellinus linteus (PL) mushroom possess antitumor activity. We previously have demonstrated that PL has direct antitumor effect through apoptosis and G2/M cell cycle blockade in SW480 human colon cancer cells. However, the molecular mechanisms responsible for antitumor and antiinvasive behavior of PL remain to be explored. Employing SW480 colon cancer cells which are overexpressed B-catenin, we demonstratd that PL significantly inhibited cellular proliferation and remarkable decrease of B-catenin expression on Western blot and indirect immunofluorescence detection in PL treated cells. Cyclin D1, one of the B-catenin controlled downstream genes and TCF/LEF transcription activity were also significantly reduced when PL was treated. PL inhibited in vitro invasion and motility of SW480 cells and the activity of matrix metalloproteinase (MMP)-9 on zymography. In addition, PL inhibited human umbilical vein endothelial cell (HUVEC) proliferation and capillary tube formation. Tumor growth of SW480 cells implanted into nude mice were significantly inhibited with PL treatment in a dose-dependent manner. Immunohistochemical analysis of xenografted tumor tissue showed that apoptotic index was markedly increased and nuclear staining of b-catenin was decreased. However, the proliferation index and microvessel density were significantly decreased. These data demonstrate that PL downregulates Wnt/b-catenin signaling pathway and inhibits multiple steps in tumor invasion in certain colon cancer cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5646.
TG4010 Immunotherapy Combined with First-Line Chemotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC). Phase 2B Results of the Time Study
Authors: E. Quoix, J. Nemunaitis, Z. Papai, H. Lena, D. Genet, C. Louis, M. Cobo, Y. Al Farhat, B. Marie-Bastien, J.M. Limacher
Journal: Annals of Oncology (2015)

Aim: TG4010 immunotherapy product is a poxvirus (MVA) coding for MUC1tumor-associated antigen and interleukin-2. Previous Phase 2 trials have demonstrated the safety and efficacy of TG4010 in combination with chemotherapy for the treatment of advanced NSCLC. In addition, a previous study showed that a normal level of Triple Positive Activated Lymphocytes (TrPAL, CD16 + CD56 + CD69+) at baseline might be a predictive biomarker for TG4010 efficacy. Methods: TIME is a double-blind randomized phase 2b/3 study comparing the combination of first-line chemotherapy with TG4010 or placebo NCT01383148). Phase IIB part objective is to validate the TrPAL biomarker with a Bayesian approach. Primary endpoint is PFS according to RECIST 1.1; secondary objectives are response rate (RR), safety, overall survival (OS) and subgroup analyses. Results: At the time of this analysis, 221 patients were enrolled out of which 170 had a normal TrPAL level at baseline. The analysis of PFS was conducted after 144 events of progression in this cohort: the hazard ratio (HR) was 0.74 (95% CI:0.53-1.02) which corresponds to a 98.6% Bayesian probability that the true HRis <1, passing the threshold of 95% necessary to meet the efficacy endpoint in patients with normal TrPAL. When looking at the 75% of patients with the lowest baseline level of TrPAL at screening (n = 152) PFS analysis shows a HR of 0.66 (95% CI: 0.46-0.96, p = 0.014). Sub-group analysis in patients with non-squamous tumors show also a statistically significant improvement in PFS when treated with TG4010 (n = 195, HR = 0.71; CI: 0.51-0.97; p = 0.016). In the whole study population RR was 39.1% with TG4010 versus 28.8% with placebo (p = 0.03). OS data will be presented at the time of the meeting. TG4010 was generally well tolerated with TG4010 related adverse events limited to mild or moderate injection site reactions, as reported in 31% of the patients. Conclusions: These data confirm the efficacy and safety profile of TG4010 in stage IV NSCLC especially in patients with non-squamous tumors and/or a low level of TrPAL at baseline. They support the continuation of the TIME study to the Phase 3 part. Clinical trial identification: NCT01383148 Disclosure: E. Quoix: Investigator and Advisor, Transgene SA. J. Nemunaitis: Investigator and advisor honorarium. Z. Papai: Investigator honorarium, Transgene SA. B. Marie-Bastien: Employee and stock ownership. J.M. Limacher: Employee and stock ownership, Transgene SA. All other authors have declared no conflicts of interest.
ABC of colorectal diseases. Colorectal disorders in elderly people.
Authors: J. A. Barrett
Journal: BMJ (1992)

More than a half of elderly people with mobilisation problems have constipation.Most elderly people have a normal bowel habit, but their use of laxatives is increased.Constipation is the main colorectal abnormality, especially in those with mobility problems.Other important contributory physiological changes in constipation or faecal impaction include deficient colonic propulsion, difficulty defecating, and impaired rectal sensation.A history of chronic constipation, although common in these patients, is not always present.The possibility of other colonic disease should also be considered.Whole gut transit time does not seem to change with age but has been found to be considerably prolonged (longer than 14 days) in immobile constipated patients.This delay seems to occur mainly in the sigmoid colon and rectum.Constipation is often associated with "faecal impaction" in elderly people.The term "faecal impaction" has traditionally indicated loading of the rectum with hard faeces.Many elderly patients, however, have massive faecal loading with soft or even liquid faeces and they are more likely to experience faecal soiling. Causes of faecal incontinence-. et6 -;4 14 14) 12 *m 10 ..8 c 6 Z 4 2 Comparison of external anal sphincter pressures.Bars are 95% confidence intervals.Comparison of internal anal sphincter pressures.Bars are 95% confidence intervals.eaFaecal incontinence is a distressing problem that is usually due to a combination offactors in elderly people and is nearly always associated with urinary incontinence.Its onset often leads to the breakdown of community care, which may explain its low prevalence in the community (<1%) and higher prevalence in institutions (25-35%).Diarrhoea Faecal incontinence may be the presenting feature of colorectal diseases causing diarrhoea, especially infective diarrhoea, colorectal carcinoma, inflammatory bowel disease, ischaemic colitis, diverticular disease, or the result of drugs (especially laxatives).Causes of faecal incontinence * Colorectal disease that causes diarrho * Anorectal incontinence (idiopathic fae incontinence) * Faecal impaction *
Noninvasive assessment of speed and stability of infarct-related artery reperfusion: Results of the GUSTO ST segment monitoring study
Authors: Anatoly Langer, Mitchell W. Krucoff, Peter Klootwin, Rolf Veldkamp, Maarten L. Simoons, Christopher Granger, Robert M. Califf, Paul W. Armstrong, None GUSTO Investigators
Journal: Journal of the American College of Cardiology (1995)
EVALUATION OF PLEXONAL AS A TRANQUILIZER IN THE GERIATRIC CARDIAC PATIENT
Authors: H. DAVANLOO
Journal: American Journal of Psychiatry (1961)

This study indicates that the integrated activity of the ingredients in Plexonal makes it an effective and well-tolerated preparation for the relief of anxiety and restlessness in the geriatric patient. A significant finding was the relief of insomnia which carried over from the daytime use of Plexonal.
Therapy of Hydatid Disease
Authors: W. C. Campbell
Journal: JAMA (1974)

To the Editor.—  Two recent reports 1,2 indicate that the anthelmintic drug mebendazole is highly effective in killing certain tapeworm larvae in mice, including the secondary hydatid cysts of Echinococcus granulosus . Although the dosage used was much higher than that used for other purposes in man, the reports are of the utmost importance in relation to the possibility of treating hydatid disease in man. We too have found mebendazole effective against the secondary hydatids of E multilocularis —the species responsible for the alveolar form of hydatid disease in man.  In our experiments, mebendazole was used as the commercial veterinary formulation Telmin. Albino mice (maintained on a hydrocortisone-supplemented diet to promote parasite growth) were treated for three days, beginning 22 days after intraperitoneal inoculation with protoscolices of E multilocularis . Twelve days after treatment, eight saline-treated control mice yielded cystic masses ranging from 105 to 2,274 mg, with a mean of 819.9
John Patrick Sexton
Authors: M. Sexton
Journal: BMJ (2010)

John Patrick Sexton (“Jack”), who died recently at the age of 93, had two careers, first in the Colonial Medical Service in Nigeria, and second in health service management in Scotland.

Born in 1915 in Saugar, central India, son and grandson to career officers in the army in India, Jack spent most of his early life in that country and was educated at St Joseph’s College in Nainital.

When he decided on medicine as a profession his father sought the advice of the civil surgeon at Fyzabad. An Indian, he himself had trained in Edinburgh and recommended that Jack could not do better than be sent there.

However, on presenting himself to the medical school in Edinburgh, Jack was informed not only that the 1934 intake had already been picked but also that his Indian educational qualifications were not recognised. Undaunted, he decided to find private tutors to enable him to complete the necessary exams and was duly accepted …
Pityriasis rotunda as a cutaneous marker of hepatocellular carcinoma: a comparison with its prevalence in other diseases
Authors: I. BERKOWITZ, H.J. HODKINSON, M.C. KEW, A.M. DiBISCEGLIE
Journal: British Journal of Dermatology (1989)

In an attempt to substantiate the claim that pityriasis rotunda may be a useful cutaneous marker of hepatocellular carcinoma in South African Blacks, the prevalence of the rash in 63 unselected South African Blacks with this tumour was compared to that in 63 matched patients with active tuberculosis, 63 with other malignant tumours, and 63 with various forms of chronic benign hepatic disease. The prevalence of pityriasis rotunda in hepatocellular carcinoma was 15.9%, which was appreciably greater (P=0.0005) than the overall prevalence of the rash (2.6%) in the controls. The prevalence was 4.8% for tuberculosis (P=0.038), 0% for other malignant diseases (P= 0.0007), and 3.2% for chronic benign hepatic disease (P= 0.015). We conclude that the presence of pityriasis rotunda is a useful pointer to the diagnosis of hepatocellular carcinoma in South African Blacks.
Physical Activity and Heart Rate Variability in Older Adults
Authors: Luisa Soares-Miranda, Jacob Sattelmair, Paulo Chaves, Glen E. Duncan, David S. Siscovick, Phyllis K. Stein, Dariush Mozaffarian
Journal: Circulation (2014)

Cardiac mortality and electrophysiological dysfunction both increase with age. Heart rate variability (HRV) provides indices of autonomic function and electrophysiology that are associated with cardiac risk. How habitual physical activity among older adults prospectively relates to HRV, including nonlinear indices of erratic sinus patterns, is not established. We hypothesized that increasing the levels of both total leisure-time activity and walking would be prospectively associated with more favorable time-domain, frequency-domain, and nonlinear HRV measures in older adults.We evaluated serial longitudinal measures of both physical activity and 24-hour Holter HRV over 5 years among 985 older US adults in the community-based Cardiovascular Health Study. After multivariable adjustment, greater total leisure-time activity, walking distance, and walking pace were each prospectively associated with specific, more favorable HRV indices, including higher 24-hour standard deviation of all normal-to-normal intervals (Ptrend=0.009, 0.02, 0.06, respectively) and ultralow-frequency power (Ptrend=0.02, 0.008, 0.16, respectively). Greater walking pace was also associated with a higher short-term fractal scaling exponent (Ptrend=0.003) and lower Poincaré ratio (Ptrend=0.02), markers of less erratic sinus patterns.Greater total leisure-time activity, and walking alone, as well, were prospectively associated with more favorable and specific indices of autonomic function in older adults, including several suggestive of more normal circadian fluctuations and less erratic sinoatrial firing. Our results suggest potential mechanisms that might contribute to lower cardiovascular mortality with habitual physical activity later in life.
STEROID THERAPY IN ADDISON'S DISEASE
Authors: J. M. Rogoff
Journal: JAMA (1952)

<h3>To the Editor:</h3> —The prominence that has been given to steroid compounds has led to their empirical use in a large variety of conditions, including Addison's disease. Whatever may be said of their value in arthritis and some other conditions, they cannot be claimed as a panacea. Furthermore, I do not believe their use as substitutional hormone therapeutic agents, particularly in the treatment of Addison's disease, is based on sound physiological, pathological, or clinical premises. A water-soluble agent of proved potency "interrenalin," is, however, available for satisfactory clinical use. It preserves life and good health in animals whose adrenals have been completely removed and has been demonstrated to be effective as a substitutional hormone in treatment of cases of proved Addison's disease. Not long ago, I was confronted with a young woman in her early twenties who had grown considerable hair on parts of the body where there had been