tbuckley/cabot-search huggingface dataset:
Potentiation of angiotensin II action by corticosteroids in vascular tissue
Authors: M Ullian
Journal: Cardiovascular Research (1996)

Studies were performed to determine if corticosteroids act directly on the vasculature to potentiate the vasoconstrictor action of angiotensin II and to determine whether corticosteroids upregulate angiotensin II receptors by receptor redistribution or by synthesis of new receptors.Aortic rings from normal Sprague-Dawley rats were incubated ex vivo with corticosteroids in aerated Krebs-Henseleit buffer to avoid secondary systemic effects prior to stimulated contraction. In cultured vascular smooth muscle cells, these experimental techniques were used: colchicine (blocker of microtubule assembly), chloroquine (inhibitor of endosomal pH gradients), measuring surface-bound 125I-Ang II internalization rate, immunoblotting of angiotensin AT1 receptor protein, and incorporation of [35S]methionine into AT1 receptor protein.Contractions to 100 nM angiotensin II in rings incubated with 1 microM aldosterone or dexamethasone for 10 min ex vivo were not different from contractions in control rings. However, angiotensin II-stimulated (but not KCl-stimulated) contractions were enhanced by almost 100% if ex vivo incubation with aldosterone (or corticosterone) lasted for 24 h. Endothelium-dependent relaxation was not significantly reduced by aldosterone pre-incubation. Incubation of cultured vascular smooth muscle cells with a number of corticosteroids for > 8 h resulted in concentration-dependent upregulation of angiotensin II receptor binding and was reversible upon removal of the corticosteroid. Aldosterone did not affect the rate of internalization of surface-bound angiotensin II. In addition, concomitant incubation of colchicine or chloroquine with aldosterone did not hamper angiotensin II receptor upregulation. Incubation of cells with various concentrations of aldosterone for 24 h resulted in concentration-dependent increases in total cell angiotensin II receptor protein content and increases in [35S]methionine incorporation into immunoprecipitated AT1 receptor protein.At least a portion of the enhancement of angiotensin II action by corticosteroids is via direct interaction of corticosteroids with the vasculature. Corticosteroids appear to upregulate angiotensin II receptors by synthesis of new receptor protein rather than by alterations in receptor trafficking.
Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.
Authors: C E Murry, R B Jennings, K A Reimer
Journal: Circulation (1986)

We have previously shown that a brief episode of ischemia slows the rate of ATP depletion during subsequent ischemic episodes. Additionally, intermittent reperfusion may be beneficial to the myocardium by washing out catabolites that have accumulated during ischemia. Thus, we proposed that multiple brief ischemic episodes might actually protect the heart from a subsequent sustained ischemic insult. To test this hypothesis, two sets of experiments were performed. In the first set, one group of dogs (n = 7) was preconditioned with four 5 min circumflex occlusions, each separated by 5 min of reperfusion, followed by a sustained 40 min occlusion. The control group (n = 5) received a single 40 min occlusion. In the second study, an identical preconditioning protocol was followed, and animals (n = 9) then received a sustained 3 hr occlusion. Control animals (n = 7) received a single 3 hr occlusion. Animals were allowed 4 days of reperfusion thereafter. Histologic infarct size then was measured and was related to the major baseline predictors of infarct size, including the anatomic area at risk and collateral blood flow. In the 40 min study, preconditioning with ischemia paradoxically limited infarct size to 25% of that seen in the control group (p less than .001). Collateral blood flows were not significantly different in the two groups. In the 3 hr study, there was no difference between infarct size in the preconditioned and control groups. The protective effect of preconditioning in the 40 min study may have been due to reduced ATP depletion and/or to reduced catabolite accumulation during the sustained occlusion. These results suggest that the multiple anginal episodes that often precede myocardial infarction in man may delay cell death after coronary occlusion, and thereby allow for greater salvage of myocardium through reperfusion therapy.
A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer.
Authors: Jean-Jacques Body, Thierry Facon, Robert E Coleman, Allan Lipton, Filip Geurs, Michelle Fan, Donna Holloway, Mark C Peterson, Pirow J Bekker
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for the differentiation, function, and survival of osteoclasts, which play a key role in establishment and propagation of skeletal disease in patients with multiple myeloma or bone metastases as well as many other skeletal diseases. Denosumab (AMG 162), a fully human monoclonal antibody to RANKL, was developed to treat patients with skeletal diseases. EXPERIMENTAL DESIGN: This was a randomized, double-blind, double-dummy, active-controlled, multicenter study to determine the safety and efficacy of denosumab in patients with breast cancer (n = 29) or multiple myeloma (n = 25) with radiologically confirmed bone lesions. Patients received a single dose of either denosumab (0.1, 0.3, 1.0, or 3.0 mg/kg s.c.) or pamidronate (90 mg i.v.). Bone antiresorptive effect was assessed by changes in urinary and serum N-telopeptide levels. Pharmacokinetics of denosumab also were assessed. RESULTS: Following a single s.c. dose of denosumab, levels of urinary and serum N-telopeptide decreased within 1 day, and this decrease lasted through 84 days at the higher denosumab doses. Pamidronate also decreased bone turnover, but the effect diminished progressively through follow-up. Denosumab injections were well tolerated. Mean half-lives of denosumab were 33.3 and 46.3 days for the two highest dosages. CONCLUSIONS: A single s.c. dose of denosumab given to patients with multiple myeloma or bone metastases from breast cancer was well tolerated and reduced bone resorption for at least 84 days. The decrease in bone turnover markers was similar in magnitude but more sustained than with i.v. pamidronate.
Phosphorylation of the src Epithelial Substrate Trask Is Tightly Regulated in Normal Epithelia but Widespread in Many Human Epithelial Cancers
Authors: Ching Hang Wong, Frederick L. Baehner, Danislav S. Spassov, Deepika Ahuja, Donghui Wang, Byron Hann, Jimmy Blair, Kevan Shokat, Alana L. Welm, Mark M. Moasser
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The frequently elevated activities of the c-src and c-yes products in human epithelial tumors suggest that these activated tyrosine kinases have tumorigenic functions analogous to the v-src and v-yes oncogene products. Studies of v-src–transformed fibroblasts have identified many of the effectors of this potent oncogene; however, because c-src and c-yes lack the mutational and promiscuous activities of their retroviral oncogene homologues, their presumptive tumorigenic functions in human epithelial tumors are more subtle, less well-defined, and await identification of possible effectors more directly relevant to epithelial cells. Experimental Design: We recently identified a transmembrane glycoprotein named Trask that is expressed in epithelial tissues but not fibroblasts and is phosphorylated by SRC kinases in mitotic epithelial cells. In this study, we have surveyed the expression and phosphorylation of Trask in many human epithelial cancer cell lines and surgical tissues and tumors. Results: Trask is widely expressed in human epithelial tissues, but its phosphorylation is tightly regulated and restricted to detached mitotic cells or cells undergoing physiologic shedding. However, abberant Trask phosphorylation is seen in many epithelial tumors from all stages including preinvasive, invasive, and metastatic tumors. Trask phosphorylation requires SRC kinases, and is also aberrantly hyperphosphorylated in the SRC-activated PyMT mouse epithelial tumors and dephosphorylated by the SRC inhibitor treatment of these tumors. Conclusions: The widespread phosphorylation of Trask in many human epithlelial cancers identifies a new potential effector of SRC kinases in human epithelial tumorigenesis.
Reduced Relationship to Cortical White Matter Volume Revealed by Tractography-Based Segmentation of the Corpus Callosum in Young Children With Developmental Delay
Authors: Carissa Cascio, Martin Styner, Rachel G. Smith, Michele D. Poe, Guido Gerig, Heather C. Hazlett, Matthieu Jomier, Roland Bammer, Joseph Piven
Journal: American Journal of Psychiatry (2006)

Objective: The corpus callosum is the primary anatomical substrate for interhemispheric communication, which is important for a range of adaptive and cognitive behaviors in early development. Previous studies that have measured the corpus callosum in developmental populations have been limited by the use of rather arbitrary methods of subdividing the corpus callosum. The purpose of this study was to measure the corpus callosum in a clinical group of developmentally delayed children using a subdivision that more accurately reflected the anatomical properties of the corpus callosum. Method: The authors applied tractography to subdivide the corpus callosum into regions corresponding to the cortical regions to and from which its fibers travel in a clinical group of very young children with developmental delay, a precursor to general mental retardation, in comparison with typically developing children. Results: The data demonstrate that the midsagittal area of the entire corpus callosum is reduced in children presenting with developmental delay, reflected in the smaller area of each of the fiber-based callosal subdivisions. In addition, while the area of each subdivision was strongly and significantly correlated with the corresponding cortical white matter volume in comparison subjects, this correlation was prominently absent in the developmentally delayed group. Conclusions: A fiber-based subdivision successfully separates lobar regions of the corpus callosum, and the areas of these regions distinguish a developmentally delayed clinical group from the comparison group. This distinction was evident both in the area measurements themselves and in their correlation to the white matter volumes of the corresponding cortical lobes.
PATHOGENESIS AND CAUSATIVE AGENT OF "TULIP FINGER"
Authors: G. A. W. VERSPYCK MIJNSSEN
Journal: British Journal of Dermatology (1969)

Journal Article PATHOGENESIS AND CAUSATIVE AGENT OF “TULIP FINGER” Get access G. A. W. VERSPYCK MIJNSSEN G. A. W. VERSPYCK MIJNSSEN Institute for Preventive Medicine TNO Leiden, Department of Occupational Medicine (head: Dr F. H. Bonjer) and Department of Dermatology (head: Prof. Dr M. K. Polano), University Hospital, Leiden, Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 10, 1 October 1969, Pages 737–745, https://doi.org/10.1111/j.1365-2133.1969.tb15933.x Published: 01 October 1969 Article history Accepted: 04 March 1969 Published: 01 October 1969
THE OCCURRENCE AND TREND OF SPONTANEOUS VARIATIONS IN ORGAN WEIGHTS OF NORMAL RABBITS
Authors: Wade H. Brown, Louise Pearce, C.M. Van Allen
Journal: The Journal of Experimental Medicine (1926)

Records of organ weights of normal rabbits covering a period of 3(1/2) years were analyzed with a view to determining first, whether any significant variations of an orderly character could be demonstrated and, second, the general trend of the variations that occurred. It was found that many organs showed decided variations in weight which assumed the form of definite annual cycles. In addition, there was some evidence of a second cycle covering a period of years. These changes were most marked in the case of the endocrine glands (including the testicles), the lymphoid organs, and the liver.
Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study
Authors: Anja Wagner, Heiko Mahrholdt, Thomas A Holly, Michael D Elliott, Matthias Regenfus, Michele Parker, Francis J Klocke, Robert O Bonow, Raymond J Kim, Robert M Judd
Journal: The Lancet (2003)
Markers for the Early Detection of Prostate Cancer: Some Principles for Statistical Reporting and Interpretation
Authors: Andrew J. Vickers
Journal: Journal of Clinical Oncology (2014)

In the article that accompanies this editorial, Wei et al report the results of a National Cancer Institute Early Detection Research Network (EDRN) validation study of PCA3, a commercially available marker used as a reflex test in the early detection of prostate cancer. The study design followed the EDRN=s rigorous methodology, including fully blinded analysis of samples at an independent laboratory and statistical correction for overfit. The study was also well powered, with more than 800 men recruited at 11 centers. Given that typical marker studies involve novel markers, small samples (median less than 100), and little attempt to control for overfit, there is much to like about this article. The authors are to be congratulated for completing such a large and rigorous study. All of which, of course, begs the question of what the results actually mean. At least part of the problem is that Wei et al, like many investigators, focus on statistical abstractions, such as area-under-thecurve and specificity, that have questionable clinical interpretability. Also in common with other investigators, Wei et al dichotomize their marker and include any grade prostate cancer as an end point, both problematic approaches. I will deal with each of these points in turn.
Patient Age, Ethnicity, Medical History, and Risk Factor Profile, but Not Drug Insurance Coverage, Predict Successful Attainment of Glycemic Targets
Authors: Hwee Teoh, Manoela F.B. Braga, Amparo Casanova, Denis Drouin, Shaun G. Goodman, Stewart B. Harris, Anatoly Langer, Mary K. Tan, Ehud Ur, Andrew T. Yan, Bernard Zinman, Lawrence A. Leiter
Journal: Diabetes Care (2010)

OBJECTIVE To identify factors in patients with type 2 diabetes and A1C &amp;gt;7.0% associated with attainment of A1C ≤7.0%. RESEARCH DESIGN AND METHODS We used a prospective registry of 5,280 Canadian patients in primary care settings enrolled in a 12-month glycemic pharmacotherapy optimization strategy based on national guidelines. RESULTS At close out, median A1C was 7.1% (vs. 7.8% at baseline) with 48% of subjects achieving A1C ≤7.0% (P &amp;lt; 0.0001). Older patients of Asian or black origin, those with longer diabetes duration, those with lower baseline A1C, BMI, LDL cholesterol, and blood pressure, and those on angiotensin receptor blockers and a lower number of antihyperglycemic agents, were more likely to achieve A1C ≤7.0% at some point during the study (all P &amp;lt; 0.0235). Access to private versus public drug coverage did not impact glycemic target realization. CONCLUSIONS Patient demography, cardiometabolic health, and ongoing pharmacotherapy, but not access to private drug insurance coverage, contribute to the care gap in type 2 diabetes.
Inhalation of stable dust extract prevents allergen induced airway inflammation and hyperresponsiveness
Authors: M Peters
Journal: Thorax (2005)

<b>Background:</b> Recent epidemiological studies have shown that growing up on a traditional farm provides protection from the development of allergic disorders such as hay fever and allergic asthma. We present experimental evidence that substances providing protection from the development of allergic diseases can be extracted from dust collected in stables of animal farms. <b>Methods:</b> Stable dust was collected from 30 randomly selected farms located in rural regions of the Alps (Austria, Germany and Switzerland). The dust was homogenised with glass beads and extracted with physiological sodium chloride solution. This extract was used to modulate immune response in a well established mouse model of allergic asthma. <b>Results:</b> Treatment of mice by inhalation of stable dust extract during sensitisation to ovalbumin inhibited the development of airway hyperresponsiveness and airway eosinophilia upon challenge, as well as the production of interleukin 5 by splenocytes and of antigen specific IgG<sub>1</sub> and IgE. Dust extract also suppressed the generation of human dendritic cells in vitro. The biological activity of the dust extract was not exclusively mediated by lipopolysaccharide. <b>Conclusions:</b> Stable dust from animal farms contains strong immune modulating substances. These substances can interfere with the development of both cellular and humoral immunity against allergens, thus suppressing allergen sensitisation, airway inflammation, and airway hyperresponsiveness in a murine model of allergic asthma.
Circadian rhythm of peak expiratory flow in asthmatic and normal children.
Authors: A J Henderson, F Carswell
Journal: Thorax (1989)

A study was undertaken to examine the circadian rhythm of peak flow rate in asthmatic and normal children in the community by means of cosinor analysis. An initial study of 12 matched pairs of asthmatic and normal children was used to determine the mean amplitude of peak expiratory flow (PEF) variability in the two groups (7.8% and 4.4%) and the number of subjects required to show a significant difference. On the basis of this study 37 community based children with asthma diagnosed by questionnaire and 40 control subjects measured PEF four times daily for 14 days. Cosinor analysis of the data produced a significant fit in 20 asthmatic and 18 control children. A small but significant difference in amplitude was observed between the asthmatic (6.2%) and the control (4.2%) children. There was no significant phase difference between the rhythms in the two groups. Cosinor analysis explained 14% of PEF variance. It did not provide a reproducible estimate of phase between week 1 and week 2; the acrophase changed by more than one hour in 26 of 37 asthmatic children. The cosinor model may be inappropriate for the investigation of low amplitude circadian rhythms, especially when measurements are made infrequently.
The Effects of Exercise on Right Ventricular Contractility and Right Ventricular–Arterial Coupling in Pulmonary Hypertension
Authors: Onno A. Spruijt, Frances S. de Man, Herman Groepenhoff, Frank Oosterveer, Nico Westerhof, Anton Vonk-Noordegraaf, Harm-Jan Bogaard
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Exercise tolerance is decreased in patients with pulmonary hypertension (PH). It is unknown whether exercise intolerance in PH coincides with an impaired rest-to-exercise response in right ventricular (RV) contractility.Objectives: To investigate in patients with PH the RV exertional contractile reserve, defined as the rest-to-exercise response in end-systolic elastance (ΔEes), and the effects of exercise on the matching of Ees and RV afterload (Ea) (i.e., RV–arterial coupling; Ees/Ea). In addition, we compared ΔEes with a recently proposed surrogate, the rest-to-exercise change in pulmonary artery pressure (ΔPAP).Methods: We prospectively included 17 patients with precapillary PH and 7 control subjects without PH who performed a submaximal invasive cardiopulmonary exercise test between January 2013 and July 2014. Ees and Ees/Ea were assessed using single-beat pressure–volume loop analysis.Measurements and Main Results: Exercise data in 16 patients with PH and 5 control subjects were of sufficient quality for analysis. Ees significantly increased from rest to exercise in control subjects but not in patients with PH. Ea significantly increased in both groups. As a result, exercise led to a decrease in Ees/Ea in patients with PH, whereas Ees/Ea was unaffected in control subjects (Pinteraction = 0.009). In patients with PH, ΔPAP was not related to ΔEes but significantly correlated to the rest-to-exercise change in heart rate.Conclusions: In contrast to control subjects, patients with PH were unable to increase Ees during submaximal exercise. Failure to compensate for the further increase in Ea during exercise led to deterioration in Ees/Ea. Furthermore, ΔPAP did not reflect ΔEes but rather the change in heart rate.
Circulating vascular endothelial growth factor in cutaneous malignant melanoma
Authors: F. Pelletier, L. Bermont, E. Puzenat, D. Blanc, S. Cairey-Remonnay, C. Mougin, R. Laurent, P. Humbert, F. Aubin
Journal: British Journal of Dermatology (2005)

Angiogenesis has been reported as a parameter of potential prognostic value in solid tumours, as it may facilitate tumour growth and metastasis. One of the most important growth factors involved in angiogenesis is vascular endothelial growth factor (VEGF).To determine the predictive value of circulating VEGF levels in a cohort of patients with melanoma.In a prospective cohort study, 324 patients with cutaneous melanoma at different clinical stages were investigated over 2 years (2002-04). VEGF was measured in plasma using enzyme-linked immunosorbent assay. Two hundred and eight patients were able to be followed up for progression of their disease and for blood sample collection (mean +/- SD follow-up 13.4 +/- 0.8 months). Data were compared with the extent of the disease and the clinical course.A significant increase in plasma VEGF levels was found in patients with melanoma compared with healthy controls, with statistically significant differences between patients in stages I, II and III vs. those in stage IV, but not between patients in stages I, II and III. When considering the 237 patients in stages I and II, no statistical correlation was found between plasma VEGF levels and tumour thickness. Baseline plasma VEGF levels were not significantly higher in patients who relapsed compared with nonprogressing patients. Among the 35 patients (two stage I, eight stage II and 25 stage III) who experienced a progression during follow-up, an increase in plasma VEGF level to > 100 pg mL(-1) was found in 20 (sensitivity 57.1%), while 38 of the 173 remaining nonprogressing patients demonstrated an increase in VEGF level, indicating a specificity of 78%. In addition, an increase in plasma VEGF level was found in 58 patients during follow-up, of whom 20 showed evidence of progression, indicating a positive predictive value of 34.5%. However, among the 150 remaining patients who did not demonstrate any increase in plasma VEGF level during follow-up, only 15 experienced a progression, indicating a negative predictive value of 90%.Our data confirm that blood VEGF levels are significantly increased in patients with melanoma and, more interestingly, that the absence of plasma VEGF level increase during follow-up appears to be associated with remission.