tbuckley/cabot-search huggingface dataset:
Relevance of T2 signal changes in the assessment of progression of glioblastoma according to the Response Assessment in Neurooncology criteria
Authors: A. Radbruch, K. Lutz, B. Wiestler, P. Baumer, S. Heiland, W. Wick, M. Bendszus
Journal: Neuro-Oncology (2011)

According to the Response Assessment in Neurooncology (RANO) criteria, significant nonenhancing signal increase in T2-weighted images qualifies for progression in high-grade glioma (T2-progress), even if there is no change in the contrast-enhancing tumor portion. The purpose of this retrospective study was to assess the frequency of isolated T2-progress and its predictive value on subsequent T1-progress, as determined by a T2 signal increase of 15% or 25%, respectively. The frequency of T2-progress was correlated with antiangiogenic therapy.MRI follow-up examinations (n = 777) of 144 patients with histologically proven glioblastoma were assessed for contrast-enhanced T1 and T2-weighted images. Examinations were classified as T1-progress, T2-progress with 15% or 25% T2-signal increase, stable disease, or partial or complete response.Thirty-five examinations revealed exclusive T2-progress using the 15% criterion, and only 2 examinations qualified for the 25% criterion; 61.8% of the scans presenting T2-progress and 31.5% of the scans presenting stable disease revealed T1-progress in the next follow-up examination. The χ(2) test showed a highly significant correlation (P < .001) between T2-progress, with the 15% criterion and subsequent T1-progress. No correlation between antiangiogenic therapy and T2-progress was shown.Tumor progression, as determined by both contrast-enhanced T1 and T2 sequences is more frequently diagnosed than when considering only contrast-enhanced T1 sequences. Definition of T2-progress by a 15% T2-signal increase criterion is superior to a 25% criterion. The missing correlation of T2-progress and antiangiogenic therapy supports the hypothesis of T2-progress as part of the natural course of the tumor disease.
Cytoplasmic staining, ANA negative status, and ENA testing in rheumatic diseases.
Authors: W F Lems, D van Schaardenburg, R J van de Stadt
Journal: Annals of the Rheumatic Diseases (1995)

Effect of gold treatment on cytokine expression in synoviumA recent paper in this journal described the effect of intramuscular gold treatment on cytokine expression in synovial membranes from patients with rheumatoid arthritis.1In that paper, the authors described changes in synovial membrane expression of interleukins (IL) IL-1a, IL-1,, IL-6, and tumour necrosis factor a in patients who had received intra- muscular gold treatment.However, the authors failed to mention that some of the results had been published in another journal by a similar group of authors.2Neither paper is cross referenced in the other, and it is not clear from these two papers whether the authors are reporting the same set of results in two different papers.In one paper,2 the authors described a significant failure rate with blind needle biopsy of the synovial membrane, which is particularly a problem with studies involving sequential biopsying as was performed in these two studies.Our experience is similar with this technique and we have now changed to performing all synovial biopsying under direct vision through a needle arthroscope under local anaesthesia.However, despite the fact that the two patient groups appear to be similar, if not identical, in these two papers, one paper states that only seven of 18 patients recruited in the study gave three satisfactory sequential synovial biopsy specimens,2 while the other paper implies, though does not clearly state, that satisfactory synovial biopsy specimens were obtained in all 10 patients for all time points (0, 2, and 12 weeks).1This suggests either that the authors' biopsying technique or success rate has changed dramatically during the period between preparation of the two papers, or that additional patients were obtained to 'make up the numbers'.Could the authors please confirm whether:(1) The patient groups studied in these two papers are, in fact, identical.(2) The same results for IL-1,B have been published in two different papers in two different journals.(3) All the patients reported in one paper' provide adequate synovial biopsy specimens for all three time points and, if so, how was this possible in view of the results and discussion in the other paper from the same group.2
Diagnostic Accuracy of Noninvasive Coronary Angiography in Patients After Bypass Surgery Using 64-Slice Spiral Computed Tomography With 330-ms Gantry Rotation
Authors: Dieter Ropers, Falk-Karsten Pohle, Axel Kuettner, Tobias Pflederer, Katharina Anders, Werner G. Daniel, Werner Bautz, Ulrich Baum, Stephan Achenbach
Journal: Circulation (2006)

Multidetector computed tomographic angiography (MDCT) has been shown to allow detection of coronary artery bypass graft (CABG) occlusions and stenoses. However, the assessment of native coronary arteries in addition to CABG has thus far not been sufficiently validated.Fifty patients with a total of 138 CABG (34 mammary grafts, 3 radial grafts, 101 venous grafts) were investigated by MDCT (0.6-mm collimation, 32 detector rows, 2 focal points, 330-ms rotation) 9 to 252 months (mean, 106 months) after surgery. CABG and all native coronary arteries with a diameter of > 1.5 mm were evaluated for the presence of significant stenoses (> or = 50% diameter reduction). Results were compared with quantitative coronary angiography. By MDCT, all CABG were evaluable and were correctly classified as occluded (n=38) or patent (n=100). Sensitivity for stenosis detection in patent grafts was 100% (16/16) with a specificity of 94% (79/84). For the per-segment evaluation of native coronary arteries and distal runoff vessels, sensitivity in evaluable segments (91%) was 86% (87/101) with a specificity of 76% (354/465). If evaluation was restricted to nongrafted arteries and distal runoff vessels, sensitivity was 86% (38/44) with a specificity of 90% (302/334). On a per-patient basis, classifying patients with at least 1 detected stenosis in a CABG, a distal runoff vessel, or a nongrafted artery or with at least 1 unevaluable segment as "positive," MDCT yielded a sensitivity of 97% (35/36) and specificity of 86% (12/14).We found that 64-slice MDCT permits the evaluation of bypass grafts and the assessment of the native coronary arteries for the presence of stenosis.
Endocrine Treatment of Breast Cancer in Women
Authors: RICHARD J. SANTEN, ANDREA MANNI, HAROLD HARVEY, CAROL REDMOND
Journal: Endocrine Reviews (1990)

Hormonal therapy for breast carcinoma began with the observation by George Beatson (1) in 1898 that bilateral oophorectomy caused tumor regression in selected premenopausal patients. Huggins and Bergenstal (2) later introduced surgical adrenalectomy as a form of hormone ablative treatment for postmenopausal women. To these methods were added surgical hypophysectomy and hormonal additive therapies such as the use of androgens, estrogens, progestins, and glucocorticoids (3). Since only one-third of patients experienced objective tumor regression with any of these hormonal therapies, clinicians began to favor use of cytotoxic chemotherapies in the 1960s and 1970s. During this time multiple chemotherapeutic regimens were developed which gained wide acceptance and enthusiastic support (3). However, when hormone receptor measurements were introduced in the mid-1970s, better selection of patients with hormonally responsive tumors became possible, and new impetus was provided for optimizing hormonal therapies. These developments led to the accumulation of a large body of clinical data regarding hormonal agents and provided clinicians with a broad armamentarium for the treatment of patients at the present time. We will summarize this information with the goals of highlighting specific endocrinological aspects of breast cancer treatment and providing practical perspective for choosing among various agents. Where recent comprehensive reviews are readily available, only pertinent concepts are highlighted.
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Cooperates with Anticancer Drugs to Overcome Chemoresistance in Antiapoptotic Bcl-2 Family Members Expressing Jurkat Cells
Authors: Alberto Ballestrero, Alessio Nencioni, Davide Boy, Ilaria Rocco, Anna Garuti, Giuseppe Sandro Mela, Luk Van Parijs, Peter Brossart, Sebastian Wesselborg, Franco Patrone
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Overexpression of antiapoptotic Bcl-2 family members has recently been related to resistance to chemo/radiotherapy in several human malignancies, particularly lymphomas. Hence, innovative approaches bypassing this resistance mechanism are required in the therapeutic approach. This study evaluated whether chemoresistance associated with Bcl-2 and Bcl-xL overexpression would be overcome by activating the death receptor pathway by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in the Jurkat cell model Experimental Design: We made use of genetically modified Jurkat cells to evaluate the effect of Bcl-2 or Bcl-xL overexpression on the cytotoxic effect produced by the anticancer drugs doxorubicin, etoposide, and oxaliplatin and TRAIL. Caspase activation was detected by cleavage of caspase-8 and -3. The mitochondrial transmambrane potential was assessed by staining with DiOC6 and flow cytometry. Caspase activity was blocked by the broad-spectrum caspase inhibitor zVAD-fmk. Results: Bcl-2 and Bcl-xL overexpression but not lack of caspase-8 protects the Jurkat cells from the anticancer drug-induced cytolysis. However, Bcl-2/Bcl-xL Jurkat cells retained some susceptibility to TRAIL-induced cytolysis. A highly synergistic cytotoxic effect of the combination of TRAIL with any of the antiblastic used in this study was detected in the chemoresistant cells. This effect was associated with mitochondrial disassemblage and dependent on caspase activation Conclusions: The combination of TRAIL with conventional anticancer drugs may prove to be useful in the treatment of antiapoptotic Bcl-2 family proteins-expressing malignancies.
Differential effects of endocrine dysfunction on the axial and the appendicular skeleton.
Authors: E Seeman, H W Wahner, K P Offord, R Kumar, W J Johnson, B L Riggs
Journal: Journal of Clinical Investigation (1982)

In 100 patients with various types of endocrine dysfunction, we measured bone mineral density (BMD) at the midradius (greater than 95% cortical bone) and distal radius (75% cortical and 25% trabecular bone) by single photon absorptiometry and at the lumbar spine (greater than 66% trabecular bone) using the new technique of dual photon absorptiometry. BMD in each endocrine disorder deviated in at least one site from the sex-specific age regression of 187 normal subjects. For patients with primary hyperparathyroidism, hypercortisolism, and hyperthyroidism this deviation was negative (suggesting bone loss), whereas for patients with secondary hyperparathyroidism due to chronic renal failure, acromegaly, and postsurgical hypoparathyroidism it was positive (suggesting bone gain). When all six states of endocrine dysfunction were compared concomitantly by multivariate analysis of variance, the profile of the changes in BMD differed significantly (P less than 0.001), indicating a nonuniform response of bone to the various hormonal alterations. When values for BMD at each of the three scanning sites were compared the midradius and distal radius did not differ significantly; either of the radius measurements, however, differed significantly (P less than 0.001) from the lumbar spine. Thus, the BMD of the axial skeleton cannot be reliably predicted from measurements made in the appendicular skeleton. We conclude that the effects of endocrine dysfunction on bone density are complex and are both disease and site specific.
The effect of sulfonylurea drugs on rabbit myocardial contractility, canine purkinje fiber automaticity, and adenyl cyclase activity from rabbit and human hearts
Authors: Kenneth C. Lasseter, Gerald S. Levey, Roger F. Palmer, Jeane S. McCarthy
Journal: Journal of Clinical Investigation (1972)

Long-term clinical studies have associated tolbutamide therapy with an increased incidence of cardiovascular deaths. The effects of this and other sulfonylurea drugs on contractility and rate of isolated rabbit atria, automaticity of isolated dog Purkinje fibers, and adenyl cyclase activity in particulate preparations of rabbit and human hearts were studied. At concentrations that are attained clinically, tolbutamide (10 mg/100 ml) increased contractility of driven rabbit atria to 124±5% of control, acetohexamide (3.9 mg/100 ml) to 140±5%, chlorpropamide (8.3 mg/100 ml) to 139±6%, and tolazamide (3.1 mg/100 ml) to 119±6%. These effects were accentuated in the presence of 2.5 × 10-4 M theophylline and were not blocked by 1 × 10-5 M propranolol. Adenyl cyclase was activated by each of these drugs at concentrations below those which increase contractility. The drugs also increased the rate and slope of phase 4 depolarization in spontaneously beating Purkinje fibers, but did not alter the spontaneous rate of isolated rabbit atria. Since inotropic and chronotropic stimulation can be deleterious in some clinical settings, these findings may be of significance in interpretation of cardiovascular mortality data.
Selective effects of nutrients on gut sensitivity and reflexes
Authors: M P Caldarella, F Azpiroz, J-R Malagelada
Journal: Gut (2006)

Intestinal nutrients induce gut reflexes and modulate perception.To elucidate the relative potency and putative relationship of motor and sensory effects induced by different nutrients.By paired tests carried out in sequence on healthy patients, the effect of isocaloric duodenal infusions of carbohydrates and lipids was determined on gastric compliance and on perception of gastric distension. Gastric distension at stepwise tension increments was applied using a tensostat, and perception at each tension level was measured on a 0-6 scale. In separate groups (n = 8 each), three nutrient loads were tested: (A) low (0.2 kcal/min), (B) medium (0.5 kcal/min) and (C) high (1 kcal/min).Values are mean (standard error). (A) Low caloric loads: both gastric perception and compliance were similar with lipids (45 (2) g, 451 (28) ml tolerated) and carbohydrates (46 (1) g, 449 (22) ml tolerated). (B) Medium caloric loads: although perception remained unchanged (46 (1) g and 46 (2) g tolerated, respectively), lipids, but not carbohydrates, partially relaxed the stomach (559 (18) v 442 (31) ml intragastric volume, respectively; p<0.05). (C) High caloric loads: lipids markedly reduced gastric tolerance and increased compliance (22 (3) g, 635 (34) ml tolerated), whereas carbohydrates did not affect perception and induced only a partial gastric relaxation (46 (1) g, 565 (46) ml tolerated; p<0.05 v lipids for both).The effects of intestinal nutrients on gastric tone are more potent than those on gastric sensation, and both depend on the caloric load and the type of nutrient.
Effect of Natriuretic Peptide Family on the Oxidized LDL–Induced Migration of Human Coronary Artery Smooth Muscle Cells
Authors: Masakazu Kohno, Koji Yokokawa, Kenichi Yasunari, Hiroaki Kano, Mieko Minami, Makiko Ueda, Junichi Yoshikawa
Journal: Circulation Research (1997)

The migration of medial smooth muscle cells (SMCs) into the intima is proposed to be an important process of intimal thickening in atherosclerotic lesions. The present study examined the possible effect of a novel endothelium-derived relaxing peptide, C-type natriuretic peptide (CNP), on oxidized low-density lipoprotein (LDL)-induced migration of cultured human coronary artery SMCs by the Boyden's chamber method. The effect of CNP was compared with that of atrial and brain natriuretic peptides (ANP and BNP, respectively). Oxidized LDL stimulates SMC migration in a concentration-dependent manner between 20 and 200 micrograms/mL. This stimulation was chemotactic in nature but was not chemokinetic. By contrast, native LDL was without significant activity. CNP-22 clearly inhibited SMC migration stimulated with 200 micrograms/mL oxidized LDL in a concentration-dependent manner between 10(-9) and 10(-6) mol/L. ANP-(1-28) and BNP-32 also inhibited oxidized LDL-induced SMC migration at concentrations of 10(-7) and 10(-6) mol/L, but these effects were weaker than the effect of CNP-22. Such inhibition by these natriuretic peptides was paralleled by an increase in the cellular level of cGMP. Oxidized LDL-induced migration was significantly inhibited by a stable analogue of cGMP, 8-bromo-cGMP, or an activator of the cytosolic guanylate cyclase, sodium nitroprusside. These natriuretic peptides did not suppress the cell adhesion either in the absence or presence of oxidized LDL. These data indicate that oxidized LDL stimulates migration of human coronary artery SMCs and that natriuretic peptides, especially CNP, inhibit this stimulated SMC migration, at least in part, through a cGMP-dependent process. Taken together with the finding that oxidized LDL is present in the intima, CNP may play a role as a local antimigration factor during the process of intimal thickening in hypercholesterolemia-induced coronary atherosclerosis.
MHC control of CD4+ T cell subset activation.
Authors: J S Murray, J Madri, J Tite, S R Carding, K Bottomly
Journal: The Journal of Experimental Medicine (1989)

The present results demonstrate that CD4+ T cells activated in the primary in vivo response to antigen produce distinct patterns of cytokines depending upon the MHC class II haplotype of the responding mice. I-As mice were found to selectively activate IL-2/IFN-gamma-producing CD4+ T cells, whereas I-Ab mice exhibited selective activation of IL-4-producing CD4+ T cells in response to collagen IV. The effector response phenotype was found to correlate with the cytokine phenotype of CD4+ T cells activated in vivo; IL-2/IFN-gamma-producing cells giving rise to proliferative (cell-mediated) responses, IL-4-producing cells leading to secondary IgG (humoral) responses. Together the data support the notion that the outcome of a given immune response (e.g., protection vs. onset, tolerance vs. autoimmunity) may be determined in part by the type of CD4+ T cells initially activated by antigen. Moreover, the present experiments demonstrate for the first time that polymorphism in class II MHC can determine such selective activation of different cytokine-producing CD4+ T cell phenotypes.
Drug therapy in patients with Parkinson’s disease
Authors: Thomas Müller
Journal: Translational Neurodegeneration (2012)

Parkinson`s disease (PD) is a progressive, disabling neurodegenerative disorder with onset of motor and non-motor features. Both reduce quality of life of PD patients and cause caregiver burden. This review aims to provide a survey of possible therapeutic options for treatment of motor and non motor symptoms of PD and to discuss their relation to each other. MAO-B-Inhibitors, NMDA antagonists, dopamine agonists and levodopa with its various application modes mainly improve the dopamine associated motor symptoms in PD. This armentarium of PD drugs only partially influences the onset and occurrence of non motor symptoms. These PD features predominantly result from non dopaminergic neurodegeneration. Autonomic features, such as seborrhea, hyperhidrosis, orthostatic syndrome, salivation, bladder dysfunction, gastrointestinal disturbances, and neuropsychiatric symptoms, such as depression, sleep disorders, psychosis, cognitive dysfunction with impaired execution and impulse control may appear. Drug therapy of these non motor symptoms complicates long-term PD drug therapy due to possible occurrence of drug interactions, - side effects, and altered pharmacokinetic behaviour of applied compounds. Dopamine substituting compounds themselves may contribute to onset of these non motor symptoms. This complicates the differentiation from the disease process itself and influences therapeutic options, which are often limited because of additional morbidity with necessary concomitant drug therapy.
Vitamin A deficiency and colonic electrogenic absorption and secretion in the rat.
Authors: H C Nzegwu, R J Levin
Journal: Gut (1992)

The effects of vitamin A deficiency on electrogenic transport in the colon were examined in rats made vitamin A deficient at weaning by feeding a vitamin A deficient diet for 40 days. A pair fed control group was given the same diet but supplemented with soluble vitamin A in their drinking water. The basal and stimulated electrogenic secretory and absorptive functions of the muscle stripped proximal, mid, and distal colon were examined in vitro using the short circuit current (Isc) as the index of net ion transport. A significant increase in the basal and secretory Isc (mainly Cl-ions) induced by the cholinergic agonist bethanechol was observed in the mid-colon of the vitamin A deficient rats. In the distal colon, however, vitamin A deficiency caused a significant reduction in both the basal and secretory Isc response to bethanechol compared with the vitamin A supplemented pair fed control. Secretory Isc induced by dibutyryl cyclic adenosine monophosphate was not significantly altered by vitamin A deficiency. The condition abolished the response of the distal colon to luminal amiloride (0.1 mmol/l). Thyroid hormone induced reduction in the distal colonic response to aldosterone is implicated in this lack of response. This is the first experimental linkage between vitamin A action, the thyroid hormone and aldosterone on colonic function. The colonic changes induced by vitamin A deficiency, namely hypersecretion and a reduced electrogenic distal absorptive function, together with the previously described small intestine hypersecretion may be the underlying basis for the diarrhoea observed in human and animal vitamin A deficiency.
Comparative Genomic Analysis of Esophageal Adenocarcinoma and Squamous Cell Carcinoma
Authors: Nishant Agrawal, Yuchen Jiao, Chetan Bettegowda, Susan M. Hutfless, Yuxuan Wang, Stefan David, Yulan Cheng, William S. Twaddell, Nyan L. Latt, Eun J. Shin, Li-Dong Wang, Liang Wang, Wancai Yang, Victor E. Velculescu, Bert Vogelstein, Nickolas Papadopoulos, Kenneth W. Kinzler, Stephen J. Meltzer
Journal: Cancer Discovery (2012)

Esophageal cancer ranks sixth in cancer death. To explore its genetic origins, we conducted exomic sequencing on 11 esophageal adenocarcinomas (EAC) and 12 esophageal squamous cell carcinomas (ESCC) from the United States. Interestingly, inactivating mutations of NOTCH1 were identified in 21% of ESCCs but not in EACs. There was a substantial disparity in the spectrum of mutations, with more indels in ESCCs, A:T>C:G transversions in EACs, and C:G>G:C transversions in ESCCs (P < 0.0001). Notably, NOTCH1 mutations were more frequent in North American ESCCs (11 of 53 cases) than in ESCCs from China (1 of 48 cases). A parallel analysis found that most mutations in EACs were already present in matched Barrett esophagus. These discoveries highlight key genetic differences between EACs and ESCCs and between American and Chinese ESCCs, and suggest that NOTCH1 is a tumor suppressor gene in the esophagus. Finally, we provide a genetic basis for the evolution of EACs from Barrett esophagus.