tbuckley/cabot-search huggingface dataset:
Biomarkers of Bone Remodeling in Multiple Myeloma Patients to Tailor Bisphosphonate Therapy
Authors: Chirayu G. Patel, Andrew J. Yee, Tyler A. Scullen, Neeharika Nemani, Loredana Santo, Paul G. Richardson, Jacob P. Laubach, Irene M. Ghobrial, Robert L. Schlossman, Nikhil C. Munshi, Kenneth C. Anderson, Noopur S. Raje
Journal: Clinical Cancer Research (2014)

Patients with multiple myeloma may be susceptible to osteonecrosis of the jaw (ONJ) and stress fractures due to long-term aminobisphosphonate (aBP) therapy. However, it is unknown whether urinary N-telopeptide (NTX) or other bone biomarkers are predictive of skeletal-related events (SRE) or the impact of cessation of aBP therapy on bone remodeling.We studied markers of bone turnover over a 6-month period after a single dose of zoledronic acid in 29 patients with multiple myeloma in remission who previously received 8 to 12 doses of pamidronate or zoledronate (NCT00577642). Our primary objective was to determine the duration of time urinary NTX levels remain suppressed after a single dose of zoledronate. A secondary objective was to identify and correlate other markers of bone remodeling with NTX changes. Thirty cytokines, based on their possible role in bone remodeling, were tested using cytokine arrays. Candidates were confirmed by ELISA.All patients had continued suppression of NTX levels, except 1 patient who had an increase in NTX levels associated with an SRE. GDF-15 and decorin were found to decrease, whereas bone-specific alkaline phosphatase (BSALP) increased. Although not significant in aggregate, osteopontin and osteoprotegerin levels increased in at least half of the patients.Our data show that NTX levels continue to be suppressed after aBP therapy, and suggest that suppressed NTX levels may be predictive of freedom from SRE in this patient population. Furthermore, osteoblast suppression by aBP may be reversible in myeloma. These data provide the basis for less frequent dosing of aBPs.
SODIUM AURATE: A NON-IRRITATING LOCAL ANTISEPTIC OF REMARKABLE POWER.
Authors: F. H. VERHOEFF
Journal: JAMA (1906)

disregard or even combat new ideas and methods defeat our best efforts.Finally, the profession must adopt a general plan of action if it would hope to execute a winning fight against the great wrong, and I would respectfully submit a series of lines of attack to be included in such a plan :1. Agitation through co-operative effort on the part of high-class journals, medical writers and medical or- ganizations with a view to enlightening the profession and elevating the standard of the profession.2. The enlightenment of the public by the agencies noted under 1 with the aid of the influential lay press, which has already rendered excellent pioneer service.3. Medical schools and medical journals should aim to educate physicians regarding official preparations and proprietary articles whose composition is known and of proved usefulness.4. The proper training of medical students in the science and art of pharmacy, including prescription writing.5. Co-operative effort on the part of physicians and scientific pharmacists is to be encouraged, e. g., such as the admirable work that is being carried out by the Council on Pharmacy and Chemisjtry of the American Medical Association.6. Continued exposure of "patent medicine" and nos- trum methods and the disclosure of the composition of these preparations by the lay and medical press (to the public) is urgently needed.7. The creation of a professional sentiment to the effect that trade-marked nostrums are unworthy of being prescribed.8. Attempts to emancipate a shackled medical and lay press must be persistently maintained. 9.The enactment of appropriate legislation-a line of action in which it will be hard to demonstrate practical results in the immediate future, owing to powerful organized opposition.10.The furtherance of the aims of the upheaval in progress by completing the organization of the medical profession of America in accordance with the plan pro- posed by the American Medical Association in 1900.
Predictors of end stage lung disease in systemic sclerosis
Authors: V Steen
Journal: Annals of the Rheumatic Diseases (2003)

Recognition of the two types of lung disease is important because their predictors and treatment differ

Pulmonary disease is now the leading cause of death in patients with scleroderma. Of the 2000 patients in the Pittsburgh scleroderma databank, 211 patients have died of lung disease over the past 20 years. One hundred and thirteen died from isolated pulmonary hypertension and 98 died of pulmonary interstitial fibrosis. These account for 21.5% of the 981 deaths and 44% of the scleroderma related deaths. Recently, progress has been made in the treatment of specific lung problems in scleroderma so it is imperative that we have a better understanding of the predictors of these complications. Most important is the acknowledgement and recognition that there are two types of lung disease in scleroderma which are very different in their pathogenesis, clinical associations, predictive factors, and treatment. The investigators of “Predictors of end stage lung disease in a cohort of patients with scleroderma” in this issue of the Annals admit that a limitation of their study was that they were unable to separate their patients into the two types of lung disease.1 By combining these two types of lung disease they were unable to identify factors that would have likely been predictors of one of the forms of lung disease. It is extremely important to look carefully at the two types of lung disease individually and not lump them all together as end stage lung disease.

Pulmonary interstitial fibrosis is felt to result from an alveolitis, which leads to interstitial fibrosis.2 In some patients there may be a significant vascular component, as there is in other manifestations of the disease. However, the interactions of these two components is incompletely understood and thus, we will focus primarily on the inflammation and fibrosis component. In interstitial …
Induction of Androgen Receptor-Dependent Apoptosis in Prostate Cancer Cells by the Retinoblastoma Protein
Authors: Xintao Wang, Haiyun Deng, Indranil Basu, Liang Zhu
Journal: Cancer Research (2004)

Abstract Re-expression of a tumor suppressor in tumor cells that lack it is an effective way to study its functional activities. However, because tumor cells contain multiple mutations, tumor suppressor functions that are dependent on (an)other regulators are unlikely to be identified by its re-expression alone if the other regulators are also mutated. In this study, we show that re-expression of retinoblastoma (RB) together with the androgen receptor (AR) in RB- and AR-deficient prostate cancer DU-145 cells resulted in an apoptotic activity, acting through the mitochondria damage-initiated caspase activation pathway, which was not present when RB, or the AR, was re-expressed alone. The ability of RB + AR to induce mitochondria damage was dependent on the proapoptotic proteins Bax and Bak and could be blocked by the antiapoptotic protein Bcl-xL. Coexpressed AR did not detectably change RB’s regulation of E2F and cell cycle progression in culture. On the other hand, coexpressed RB could activate the transactivation activity of the AR in an androgen-depleted media. Although androgen induced greater AR transactivation activity in this condition, it did not induce apoptosis in the absence of coexpressed RB. Analysis of mutants of RB and the AR indicated that intact pocket function of RB and the transactivation activity of the AR were required for RB + AR-induced apoptosis. These results provide direct functional data for an AR-dependent apoptosis-inducing activity of RB and highlight the importance of cell type-specific regulators in obtaining a more complete understanding of RB.
Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease
Authors: Vasileios Karantalis, Joshua M. Hare
Journal: Circulation Research (2015)

Despite substantial clinical advances over the past 65 years, cardiovascular disease remains the leading cause of death in America. The past 15 years has witnessed major basic and translational interest in the use of stem and precursor cells as a therapeutic agent for chronically injured organs. Among the cell types under investigation, adult mesenchymal stem cells are widely studied, and in early stage, clinical studies show promise for repair and regeneration of cardiac tissues. The ability of mesenchymal stem cells to differentiate into mesoderm- and nonmesoderm-derived tissues, their immunomodulatory effects, their availability, and their key role in maintaining and replenishing endogenous stem cell niches have rendered them one of the most heavily investigated and clinically tested type of stem cell. Accumulating data from preclinical and early phase clinical trials document their safety when delivered as either autologous or allogeneic forms in a range of cardiovascular diseases, but also importantly define parameters of clinical efficacy that justify further investigation in larger clinical trials. Here, we review the biology of mesenchymal stem cells, their interaction with endogenous molecular and cellular pathways, and their modulation of immune responses. Additionally, we discuss factors that enhance their proliferative and regenerative ability and factors that may hinder their effectiveness in the clinical setting.
Mechanics of postextrasystolic potentiation in normal subjects and patients with valvular heart disease.
Authors: T Wisenbaugh, S Nissen, A DeMaria
Journal: Circulation (1986)

To determine the relative influence of preload, afterload, and inotropic state on postextrasystolic potentiation (PESP) of ventricular performance in man, we computed angiographic left ventricular volume and wall stress frame by frame for a control and potentiated beat in each of 31 patients. In 10 normal subjects, PESP increased ejection fraction by 14%, while left ventricular end-diastolic volume increased by 8% (p less than .001) and end-systolic stress fell by 21% (p less than .005). Enhanced diastolic filling (+6%, p less than .005) with a small decline in end-systolic stress (-8%, p = NS) likewise contributed to potentiation of ejection fraction (+14%, p less than .001) in seven patients with aortic stenosis. Diastolic filling was not significantly augmented during the compensatory pause in six patients with isolated mitral regurgitation, nor in eight patients with aortic regurgitation (+2%, p = NS for both). Although afterload tended to fall for potentiated beats in patients with aortic (-11%, p = NS) and mitral regurgitation (-23%, p = NS), analysis of ejection fraction-end-systolic stress relationships demonstrated an independent effect of inotropic state on potentiated ejection performance. Thus, utilization of preload reserve contributed to PESP in normal subjects and patients with aortic stenosis, but not in those with volume overload imposed by chronic valvular regurgitation. Enhanced inotropic state independent of small changes in afterload was demonstrated in all subgroups.
A rapid increase in skin extensibility due to prednisolone
Authors: J.L. BURTON, SAM SHUSTER
Journal: British Journal of Dermatology (1973)

Journal Article A rapid increase in skin extensibility due to prednisolone Get access J.L. BURTON, J.L. BURTON Wellcome Laboratories for Research into Skin Disease, University Department of Dermatology, Newcastle‐upon‐Tyne Reprint requests to Dr J.L.Burton, Department of Dermatology, Bristol Royal Infirmary, Bristol. Search for other works by this author on: Oxford Academic Google Scholar SAM SHUSTER SAM SHUSTER Wellcome Laboratories for Research into Skin Disease, University Department of Dermatology, Newcastle‐upon‐Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue 5, 1 November 1973, Pages 491–495, https://doi.org/10.1111/j.1365-2133.1973.tb03010.x Published: 01 November 1973 Article history Accepted: 02 April 1973 Published: 01 November 1973
Linkage of Circulating Eosinophils to Markers on Chromosome 5q
Authors: FERNANDO D. MARTINEZ, SUSAN SOLOMON, CATHARINE J. HOLBERG, PENELOPE E. GRAVES, MAURO BALDINI, ROBERT P. ERICKSON
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Although peripheral blood eosinophilia is strongly associated with the risk of developing asthma, genetic determinants of eosinophilia have not been extensively studied. We used sib-pair analysis to assess linkage of circulating eosinophils (as a percent of total white blood cells [WBC]) to nine markers located in chromosome 5q31–33. The study was divided into two phases. Of 246 sib pairs available for the first phase, 35 were classified as low concordant (LC) (both sibs had ⩽ 2% circulating eosinophils), 18 were defined as high concordant (HC) (both sibs had 5% or more circulating eosinophils), and 26 were defined as discordant (one sib had ⩽ 2% and the other sib had 5% or more circulating eosinophils). Significant evidence for linkage among low concordant sib pairs was found for several markers in the region under study, with a peak for marker D5S500 (proportion of alleles shared identical by descent [ibd] = 0.68 ± 0.05 [mean ± SE], p = 0.0004). A cross-validating study was done in which an additional 19 sib pairs that were low concordant for circulating eosinophils were studied. Evidence for linkage was also observed in this subset. Results were independent of current wheezing, total serum IgE levels, and other potential confounders. A multipoint analysis done for all low-concordant sib pairs available showed that the maximal logarithm of the odds favoring genetic linkage (LOD) score (2.4, p = 0.0004) was observed in correspondence with marker D5S658. We conclude that a locus or loci may be present in chromosome 5q31–33 that controls for circulating eosinophils as a proportion of total WBC.
CAN SLEEP-DISORDERED BREATHING BE AN INDEPENDENT PREDICTOR OF MALIGNANT VENTRICULAR ARRHYTHMIAS IN PATIENTS WITH HEART FAILURE?
Authors: Naoki Serizawa, Dai Yumino, Daigo Yagishita, Yoshimi Yagishita, Koichiro Ejima, Tetsuyuki Manaka, Atsushi Takagi, Morio Shoda, Nobuhisa Hagiwara
Journal: Journal of the American College of Cardiology (2010)
Effectiveness of recombinant desulphatohirudin in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.
Authors: I J Sarembock, S D Gertz, L W Gimple, R M Owen, E R Powers, W C Roberts
Journal: Circulation (1991)

BACKGROUND The effectiveness of balloon angioplasty is limited by a restenosis rate of approximately 30%. Recombinant desulphatohirudin (r-hirudin [CGP 39393]) has been found to be highly effective in preventing acute platelet-rich thrombosis after deep arterial injury as compared with heparin. METHODS AND RESULTS This study evaluated the effect of intravenous r-hirudin, a selective inhibitor of thrombin, on restenosis after balloon angioplasty in 29 rabbits. Focal femoral atherosclerosis was induced by air desiccation endothelial injury followed by a 2% cholesterol diet for 1 month. At angioplasty (2.5-mm balloon with three 60-second, 10-atm inflations 60 seconds apart), the rabbits received heparin (150 units/kg bolus, n = 16) or r-hirudin (1 mg/kg bolus followed by infusions of 1 mg/kg for the first hour and 0.5 mg/kg for the second hour, n = 13). Angiograms performed before and after angioplasty and before death were analyzed quantitatively by a blinded observer. Rabbits were killed 2 hours (n = 14) or 28 days (n = 15) after angioplasty. Femoral arteries were fixed in situ by perfusion of 10% formaldehyde at 100 mm Hg. The mean luminal diameter of the arteries with successful angioplasty (greater than or equal to 20% increase in luminal diameter) in rabbits treated with heparin (n = 8 arteries) increased from 1.18 +/- 0.29 mm before angioplasty to 1.86 +/- 0.24 mm immediately after angioplasty (p less than 0.001) and decreased to 0.94 +/- 0.69 mm (p = 0.0004) at 28 days after angioplasty. In rabbits treated with r-hirudin (n = 11 arteries), the mean luminal diameter increased from 1.14 +/- 0.17 mm before angioplasty to 1.68 +/- 0.20 mm immediately after angioplasty (p less than 0.001) and decreased to 1.37 +/- 0.47 mm (p = 0.01) at 28 days after angioplasty. The mean reduction in luminal diameter by angiography was less in the r-hirudin-treated group than in the heparin-treated group (0.30 +/- 0.33 versus 0.92 +/- 0.61 mm, p = 0.01). Blinded planimetric analysis of stained histological sections of the femoral arteries also showed less cross-sectional area narrowing by plaque in rabbits treated with r-hirudin compared with those treated with heparin (22 +/- 16% verus 48 +/- 29%, p = 0.01). Both groups had similar numbers of arteries with histological evidence of balloon-induced plaque tear (12 of 13 versus 13 of 15). CONCLUSIONS Rabbits receiving r-hirudin at the time of experimental balloon angioplasty had significantly less restenosis by angiography and by quantitative histopathology than rabbits receiving heparin.
S-Nitrosylation of N-Ethylmaleimide Sensitive Factor Mediates Surface Expression of AMPA Receptors
Authors: Yunfei Huang, Heng-Ye Man, Yoko Sekine-Aizawa, Yefei Han, Krishna Juluri, Hongbo Luo, Jaime Cheah, Charles Lowenstein, Richard L. Huganir, Solomon H. Snyder
Journal: Neuron (2005)
Clinical Trial of P.A.S. Salt of Isoniazid in Treatment of Pulmonary Tuberculosis
Authors: J. W. Clegg
Journal: BMJ (1955)

In 1953 Smith and Wiederkehr reported on the bacterio- static properties against M. tuberculosis of a new drug then called GEWO 339.This is an additive compound between P.A.S. and isoniazid to which the following formula is attributed: CO.NH.NH3.0.C= 0 N NH2This substance was said to inhibit the growth of ordinary strains of tubercle bacilli at a concentration of 0.1 ug. per ml. of medium.It was also claimed that strains which were resistant to isoniazid and P.A.S., either alone or in combination, though not as sensitive as normal strains to GEWO 339, were nevertheless still sensitive at therapeutic levels.Strains which grew normally on media containing 100 jug. of isoniazid and also media containing 100 lug. of P.A.S. were inhibited by 5 jug.per ml. of GEWO 339.Brodhage, of the
Diabetes Mellitus, Glycoprotein IIb/IIIa Blockade, and Heparin
Authors: Neal S. Kleiman, A. Michael Lincoff, Dean J. Kereiakes, Dave P. Miller, Frank V. Aguirre, Keaven M. Anderson, Harlan F. Weisman, Robert M. Califf, Eric J. Topol
Journal: Circulation (1998)

Background —After angioplasty, major complications and ischemic events occur more frequently in diabetic than nondiabetic patients. To determine whether treatment with abciximab is effective in reducing these events in diabetics, we analyzed characteristics and outcomes of diabetic patients enrolled in a large multicenter study (EPILOG). Methods and Results —Of 2792 patients enrolled, 638 (23%) were diabetic. Diabetic patients were older, shorter, and heavier; more likely to be female and have three-vessel disease, prior coronary artery bypass graft surgery, a history of hypertension, or a recent myocardial infarction; and less likely to be current smokers than their nondiabetic counterparts. During hospitalization, death, myocardial infarction, or urgent revascularization occurred in 7.1% of diabetics and 7.5% of nondiabetics. By 6 months, the composite of death and myocardial infarction had occurred in 8.8% of diabetic patients and 7.4% of nondiabetics, whereas death, myocardial infarction, or revascularization had occurred in 27.2% and 22.6%, respectively. Abciximab treatment reduced death or myocardial infarction among diabetic and nondiabetic patients (hazard ratios, 0.28 [95% confidence interval (CI), 0.13 to 0.57] and 0.47 [95% CI, 0.33 to 0.70] at 30 days for diabetics and nondiabetics, respectively, and 0.36 [95% CI, 0.21 to 0.61] and 0.60 [95% CI, 0.44 to 0.82] at 6 months for diabetics and nondiabetics, respectively). Abciximab reduced target vessel revascularization among nondiabetic patients (hazard ratio, 0.78 [95% CI, 0.63 to 0.96]) but not among diabetics (hazard ratio, 1.4 [95% CI, 0.94 to 2.08]). When standard- and low-dose heparin adjuncts were compared, diabetics receiving abciximab with standard-dose heparin had marginally greater reductions in the composite of death and myocardial infarction and in target vessel revascularization than diabetics assigned to abciximab with low-dose heparin. Conclusions —Abciximab treatment in diabetic patients led to a reduction in the composite of death and myocardial infarction, which was at least as great as that seen in nondiabetic patients. However, target vessel revascularization was reduced in nondiabetic but not diabetic patients. This effect may be associated in part with lower doses of heparin. These differences may be related to differences in the platelet and coagulation systems between diabetics and nondiabetics, the greater extent of coronary artery disease in diabetics, or patient selection and management factors.
Saphenous Vein Graft Stenting and Major Adverse Cardiac Events
Authors: Alanna Coolong, Donald S. Baim, Richard E. Kuntz, A. James O’Malley, Sachin Marulkar, Donald E. Cutlip, Jeffrey J. Popma, Laura Mauri
Journal: Circulation (2008)

Treatment of saphenous vein graft (SVG) stenosis with percutaneous coronary intervention has a 15% to 20% incidence of major adverse cardiac events (MACE) within 30 days. Although MACE rates are reduced significantly by the use of embolic protection devices (EPDs), neither the level of baseline risk nor the benefit provided by EPDs has been well characterized.
Thrombin Up-regulates Cathepsin D which Enhances Angiogenesis, Growth, and Metastasis
Authors: Liang Hu, Jennifer M. Roth, Peter Brooks, Joanna Luty, Simon Karpatkin
Journal: Cancer Research (2008)

Abstract Cathepsin D (CD) up-regulation has been associated with human malignancy and poor prognosis. Thrombin up-regulated CD mRNA and protein in eight tumor cell lines as well as in human umbilical vascular endothelial cells (HUVEC). Thrombin increased the secretion of CD by 3- to 8-fold and enhanced chemotaxis (∼2-fold) in 4T1 murine mammary CA cells, which was completely inhibited with the knockdown of CD. Secreted 4T1 CD induced neoangiogenesis by 2.4-fold on a chick chorioallantoic membrane, which was blocked in CD-KD cells. The addition of pure CD (2 ng) to the chick chorioallantoic membrane increased angiogenesis by 2.1-fold, which was completely inhibited by Pepstatin A (Pep A). CD enhanced human HUVEC chemotaxis and Matrigel tube formation by 2-fold, which was then blocked by Pep A. CD enhanced HUVEC matrix metalloproteinase 9 (MMP-9) activity by ∼2-fold, which was completely inhibited by Pep A as well as a generic MMP inhibitor, GM6001. The injection of CD-KD 4T1 cells into syngeneic mice inhibited tumor growth by 3- to 4-fold compared with empty vector (EV) cells. Hirudin, a specific thrombin inhibitor, inhibited the growth of wild-type and EV cells by 2- to 3-fold, compatible with thrombin up-regulation of CD. CD and thrombin also contributed to spontaneous pulmonary metastasis; 4-fold nodule inhibition with CD versus EV and 4.6-fold inhibition with hirudin versus EV (P &amp;lt; 0.02). Thus, thrombin-induced CD contributes to the malignant phenotype by inducing tumor cell migration, nodule growth, metastasis, and angiogenesis. CD-induced angiogenesis requires the proteolytic activation of MMP-9. [Cancer Res 2008;68(12):4666–73]
Plasma serotonin is a predictor for deterioration of urinary albumin excretion in men with type 2 diabetes mellitus
Authors: Michiaki Fukui, Emi Shiraishi, Muhei Tanaka, Takafumi Senmaru, Kazumi Sakabe, Ichiko Harusato, Goji Hasegawa, Naoto Nakamura
Journal: Metabolism (2009)