tbuckley/cabot-search huggingface dataset:
Corticosteroid Effectiveness in IgA Nephropathy
Authors: Claudio Pozzi, Simeone Andrulli, Lucia Del Vecchio, Patrizia Melis, Giovanni B. Fogazzi, Paolo Altieri, Claudio Ponticelli, Francesco Locatelli
Journal: Journal of the American Society of Nephrology (2004)

Proteinuria plays a causal role in the progression of IgA nephropathy (IgAN). A previous controlled trial showed that steroids are effective in reducing proteinuria and preserving renal function in patients with IgAN. The objective of this study was to evaluate the long-term effectiveness of steroids in IgAN, examine the trend of proteinuria during follow-up (starting from the hypothesis that the degree of reduction in proteinuria may influence IgAN outcome), and evaluate how histologic scores can influence steroid response. A secondary analysis of a multicenter, randomized, controlled trial of 86 adult IgAN patients who were receiving supportive therapy or intravenous methylprednisolone plus oral prednisone for 6 mo was conducted. Ten-year renal survival was significantly better in the steroid than in the control group (97% versus 53%; log rank test P = 0.0003). In the 72 patients who did not reach the end point (doubling in baseline serum creatinine), median proteinuria significantly decreased (1.9 g/24 h at baseline, 1.1 g/24 h after 6 mo, and 0.6 g/24 h after a median of 7 yr). In the 14 progressive patients, proteinuria increased from a median of 1.7 g/24 h at baseline to 2.0 g/24 h after 6 mo and 3.3 g/24 h after a median of 5 yr. Steroids were effective in every histologic class. Cox multivariate regression analyses showed that, in addition to steroids, a low baseline histologic score, a reduction in proteinuria after 6 mo, and no increase in proteinuria during follow-up all were independent predictors of a beneficial outcome. Steroids significantly reduce proteinuria and protect against renal function deterioration in IgAN. The histologic picture and proteinuria during early and late follow-up improve the prediction of outcome, but considerable variability remains outside the model.
Effects of airway infection by Pseudomonas aeruginosa: a computed tomographic study
Authors: K. A. Miszkiel, A. U. Wells, M. B. Rubens, P. J. Cole, D. M. Hansell
Journal: Thorax (1997)

Pseudomonas aeruginosa commonly infects the airways of patients with bronchiectasis. A study was undertaken to examine the relationship between infection of the airways with this pathogen, the morphological pattern of bronchiectasis on thin section computed tomographic (CT) scanning, symptom duration, smoking habits of the patients, and the presence of airflow obstruction.Thin section CT scans of 22 adult patients with bronchiectasis and concurrent sputum infected by P aeruginosa (Pa +ve) and those of 45 randomly selected patients not infected by P aeruginosa (Pa -ve) were analysed independently by two thoracic radiologists. Patients with cystic fibrosis were excluded. Each scan was scored at a lobar level for extent of bronchiectasis, severity of bronchial wall thickening and dilatation, predominant pattern of bronchiectasis, presence of mucus plugging, and degree of decreased attenuation of the lung parenchyma.The Pa +ve group had more extensive bronchiectasis and a greater degree of bronchial wall thickening and dilatation on the CT scan than the Pa -ve group; more extensive decreased attenuation was seen in the Pa +ve group. These findings were robust on multivariate analysis; decreased attenuation was also independently related to the duration of sputum production.Patients with bronchiectasis infected by P aeruginosa have more extensive and severe bronchiectasis on thin section CT scanning than those without P aeruginosa infection. The bronchi and small airways are both involved, reflecting the end result of complex interactions between host airways and the numerous virulence factors produced by P aeruginosa.
A Novel Peptide Specifically Binding to Nasopharyngeal Carcinoma For Targeted Drug Delivery
Authors: Tong-Young Lee, Han-Chung Wu, Yun-Long Tseng, Chin-Tarng Lin
Journal: Cancer Research (2004)

Abstract Nasopharyngeal carcinoma (NPC) is a common cancer among Chinese living in southern China, Taiwan, and Singapore. The 5-year survival rate in the early stage of NPC has been reported as high as 90 to 95% with the use of radiotherapy, but in the advanced cases, even with the use of both chemotherapy and radiotherapy, the survival rate is still &amp;lt;50%. To improve the survival rate, we identify a 12-mer peptide (l-peptide) specifically binding to NPC cells with a phage displayed random peptide library. The l-phage and synthetic l-peptide bound to the tumor cell surfaces of most NPC cell lines and biopsy specimens, but not normal nasal mucosal cells, and the l-peptide–linked liposomes containing fluorescent substance (l-peptide-Lipo-HPTS) were capable of binding to and translocating across plasma membranes. l-Peptide–linked liposomes that carried doxorubicin (l-peptide-Lipo-Dox) caused marked cytotoxicity in NPC cells. In SCID mice bearing NPC xenografts, the l-phages specifically bound to the tumor mass, an effect that was inhibited by competition with synthetic l-peptide. In addition, the l-peptide-Lipo-Dox suppressed tumor growth better than Lipo-Dox. These results indicate that the novel l-peptide specifically binds NPC cells and is a good candidate for targeted drug delivery to NPC solid tumors.
Imaging modalities for the classification of gout: systematic literature review and meta-analysis
Authors: Alexis Ogdie, William J Taylor, Mark Weatherall, Jaap Fransen, Tim L Jansen, Tuhina Neogi, H Ralph Schumacher, Nicola Dalbeth
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Although there has been major progress in gout imaging, no gout classification criteria currently include advanced imaging techniques. <h3>Objective</h3> To examine the usefulness of imaging modalities in the classification of gout when compared to monosodium urate (MSU) crystal confirmation as the gold standard, in order to inform development of new gout classification criteria. <h3>Methods</h3> We systematically reviewed the published literature concerning the diagnostic performance of plain film radiography, MRI, ultrasound (US), conventional CT and dual energy CT (DECT). Only studies with MSU crystal confirmation as the gold standard were included. When more than one study examined the same imaging feature, the data were pooled and summary test characteristics were calculated. <h3>Results</h3> 11 studies (9 manuscripts and 2 meeting abstracts) satisfied the inclusion criteria. All were set in secondary care, with mean gout disease duration of at least 7 years. Three features were examined in more than one study: the double contour sign (DCS) on US, tophus on US, and MSU crystal deposition on DECT. The pooled (95% CI) sensitivity and specificity of US DCS were 0.83 (0.72 to 0.91) and 0.76 (0.68 to 0.83), respectively; of US tophus, were 0.65 (0.34 to 0.87) and 0.80 (0.38 to 0.96), respectively; and of DECT, were 0.87 (0.79 to 0.93) and 0.84 (0.75 to 0.90), respectively. <h3>Conclusions</h3> US and DECT show promise for gout classification but the few studies to date have mostly been in patients with longstanding, established disease. The contribution of imaging over clinical features for gout classification criteria requires further examination.
Developmental aspects of cardiac arrhythmogenesis
Authors: A. V. Postma, V. M. Christoffels, C. R. Bezzina
Journal: Cardiovascular Research (2011)

The transcriptional regulation orchestrating the development of the heart is increasingly recognized to play an essential role in the regulation of ion channel and gap junction gene expression and consequently the proper generation and conduction of the cardiac electrical impulse. This has led to the realization that in some instances, abnormal cardiac electrical function and arrhythmias in the postnatal heart may stem from a developmental abnormality causing maintained (epigenetic) changes in gene regulation. The role of developmental genes in the regulation of cardiac electrical function is further underscored by recent genome-wide association studies that provide strong evidence that common genetic variation, at loci harbouring these genes, modulates electrocardiographic indices of conduction and repolarization and susceptibility to arrhythmia. Here we discuss recent findings and provide background insight into these complex mechanisms.
Meconium ileus equivalent in older patients with cystic fibrosis.
Authors: J G Hanly, M X Fitzgerald
Journal: BMJ (1983)

Meconium ileus equivalent is one of the lesser known manifestations of cystic fibrosis, and occurs most often in older patients. With the improved overall survival of patients with cystic fibrosis, one would expect to see this condition more often in the future. Of 53 patients attending our cystic fibrosis clinic for adolescents and adults, eight had experienced a total of 25 episodes of meconium ileus equivalent. Recurrent attacks occurred in seven patients, of whom four had at least four separate, well documented episodes: these episodes were associated with obvious recognised precipitating factors in only three patients. All patients responded to appropriate medical treatment with acetylcysteine or sodium diatrizoate, including three who had previously undergone surgery for meconium ileus equivalent elsewhere. Controversies remain, however, concerning the role of prophylactic medical management with acetylcysteine, sodium diatrizoate, and pancreatic supplements.
Idiopathic Ventricular Tachycardia
Authors: Gregory T. Altemose, MD, Alfred E. Buxton, MD
Journal: Annual Review of Medicine (1999)

Most ventricular tachycardias encountered in clinical practice occur in patients who have structural heart disease. Idiopathic ventricular tachycardia refers to those arrhythmias that occur in patients without structural heart disease, metabolic/electrolyte abnormalities, or the long QT syndrome. Three commonly recognized forms of idiopathic ventricular tachycardia include: (a) ventricular tachycardia associated with mitral valve prolapse, (b) ventricular tachycardia originating from the right ventricular outflow tract, and (c) ventricular tachycardia originating from the left ventricle. Recently, a fourth type of idiopathic ventricular tachycardia, termed the Brugada syndrome, has been identified as responsible for some cases of cardiac arrest in persons without apparent structural heart disease. Each form of ventricular tachycardia may be considered a discrete syndrome based on its electrocardiographic characteristics, mechanisms, responses to pharmacologic intervention, and prognosis (good in most cases). Ventricular tachycardias range from the common to the exotic, but all represent syndromes with which the internist and general cardiologist should be familiar.
Characteristics of coronary endothelial dysfunction in experimental diabetes
Authors: M Zsófia Koltai
Journal: Cardiovascular Research (1997)

To study the influence of diabetes on the endothelium-dependent vasodilation in the coronary arterial bed.The effects of acetylcholine (ACh 2-36 pmol.kg-1; 18 nmol.1(-1)-9.8 mumol.1(-1); 0.1-10 mumol.1(-1), L-arginine (1 mmol.1(-1) and sodium nitroprusside (1 nmol.1(-1)-100 mumol.1(-1)) were measured on coronary conductivity, vascular tone and cGMP release (RIA) in healthy and diabetic dogs.ACh-mediated (in cumulative intra-arterial infusion) increase in coronary conductivity was reduced (P < 0.01) in the diabetic dogs in vivo, whereas no increase in cGMP release was observed in isolated diabetic coronaries (P < 0.05) which could not be enhanced by L-arginine (P < 0.05). Inhibition of cyclo-oxygenase after 20 min further impaired (P < 0.01) responsiveness to ACh in vivo and diminished the ACh response in isolated coronary strips of the diabetic dogs, but not in those of the controls. Relaxation in response to sodium nitroprusside was not altered by diabetes.Diminished vasodilation in diabetes is due to a defect in endothelial nitric oxide production and action. Vasodilating prostanoids do not sufficiently compensate this defect.
The Androgen Derivative 5α-Androstane-3β,17β-Diol Inhibits Prostate Cancer Cell Migration Through Activation of the Estrogen Receptor β Subtype
Authors: Vittoria Guerini, Daniela Sau, Eugenia Scaccianoce, Paola Rusmini, Paolo Ciana, Adriana Maggi, Paolo G.V. Martini, Benita S. Katzenellenbogen, Luciano Martini, Marcella Motta, Angelo Poletti
Journal: Cancer Research (2005)

Abstract Prostate cancer growth depends, in its earlier stages, on androgens and is usually pharmacologically modulated with androgen blockade. However, androgen-ablation therapy may generate androgen-independent prostate cancer, often characterized by an increased invasiveness. We have found that the 5α-reduced testosterone derivative, dihydrotestosterone (the most potent natural androgen) inhibits cell migration with an androgen receptor–independent mechanism. We have shown that the dihydrotestosterone metabolite 5α-androstane-3β,17β-diol (3β-Adiol), a steroid which does not bind androgen receptors, but efficiently binds the estrogen receptor β (ERβ), exerts a potent inhibition of prostate cancer cell migration through the activation of the ERβ signaling. Very surprisingly, estradiol is not active, suggesting the existence of different pathways for ERβ activation in prostate cancer cells. Moreover, 3β-Adiol, through ERβ, induces the expression of E-cadherin, a protein known to be capable of blocking metastasis formation in breast and prostate cancer cells. The inhibitory effects of 3β-Adiol on prostate cancer cell migration is counteracted by short interfering RNA against E-cadherin. Altogether, the data showed that (a) circulating testosterone may act with estrogenic effects downstream in the catabolic process present in the prostate, and (b) that the estrogenic effect of testosterone derivatives (ERβ-dependent) results in the inhibition of cell migration, although it is apparently different from that linked to estradiol on the same receptor and may be protective against prostate cancer invasion and metastasis. These results also shed some light on clinical observations suggesting that alterations in genes coding for 3β-hydroxysteroid dehydrogenases (the enzymes responsible for 3β-Adiol formation) are strongly correlated with hereditary prostate cancer.
Association of IFNG gene polymorphism with asthma in the Indian population
Authors: Rana Nagarkatti, Chandrika B. Rao, Jai Prakash Rishi, Rajesh Chetiwal, Vipul Shandilya, Vannankandi Vijayan, Raj Kumar, Harish K. Pemde, Surendra K. Sharma, Sweety Sharma, Anand B. Singh, Sharad V. Gangal, Balaram Ghosh
Journal: Journal of Allergy and Clinical Immunology (2002)
Phase III, Double-Blind Study of Depot Octreotide Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy: Results of North Central Cancer Treatment Group N00CA
Authors: James A. Martenson, Michele Y. Halyard, Jeff A. Sloan, Gary M. Proulx, Robert C. Miller, Richard L. Deming, Stephen J. Dick, Harold A. Johnson, T.H. Patricia Tai, Angela W. Zhu, Joan Keit, Kathy J. Stien, Pamela J. Atherton
Journal: Journal of Clinical Oncology (2008)

To assess the effectiveness of depot octreotide for the prevention of diarrhea during pelvic radiation therapy.Patients receiving pelvic radiation therapy (planned minimum dose, 45 Gy; 1.7 to 2.1 Gy daily) were eligible for the study. From May 10, 2002, through October 14, 2005, 125 patients were randomly allocated in a double-blind fashion to receive octreotide (100 microg, administered subcutaneously on day 1, followed by depot octreotide, 20 mg, administered intramuscularly on days 2 and 29; n = 62) or to receive a placebo (n = 63).Grade 0, 1, 2, and 3 diarrhea were observed in 18%, 31%, 31%, and 21% of patients in the octreotide arm, respectively, and in 25%, 32%, 22%, and 21% of patients in the placebo arm, respectively (P = .64). Grade 0, 1, 2, and 3 abdominal cramps were observed in 32%, 45%, 21%, and 2% of patients receiving octreotide, respectively, and in 51%, 24%, 21%, and 5% of patients receiving the placebo, respectively (P = .053). Some patient-reported symptoms were worse in the octreotide group, including nocturnal bowel movements (70% v 45%; P = .004), clustering of bowel movements (90% v 69%; P = .004), and bleeding with bowel movements (57% v 35%; P = .01).As administered in this study, octreotide did not decrease diarrhea during pelvic radiation therapy. Some gastrointestinal symptoms were worse in patients treated with octreotide. Octreotide is not indicated for prevention of diarrhea during pelvic radiation therapy.
On qualia, relations, and structure in color experience
Authors: Stephen E. Palmer
Journal: Behavioral and Brain Sciences (1999)

In this Response, I defend the notion of intrinsic qualities of experience, discuss the distinction between relational experience and relational structure, clarify the difference between narrow and broad interpretations of color experience, argue against externalist approaches to color experience, defend the concept of isomorphism as a limitation in understanding color experiences, examine critiques of the color machine and color room arguments, and counter objections to within-subject experiments based on memory limitations.
Chromosome 1q21.1 Contiguous Gene Deletion Is Associated With Congenital Heart Disease
Authors: Jesse Christiansen, John D. Dyck, Basil G. Elyas, Margaret Lilley, J. Stephen Bamforth, Mark Hicks, Kathleen A. Sprysak, Robert Tomaszewski, Shelagh M. Haase, Leanne M. Vicen-Wyhony, Martin J. Somerville
Journal: Circulation Research (2004)

Congenital heart disease (CHD), comprising structural or functional abnormalities present at birth, is the most common birth defect in humans. Reduced expression of connexin40 (Cx40) has been found in association with atrial fibrillation, and deletion of Cx40 in a mouse model causes various structural heart abnormalities in 18% of heterozygotes. We screened 505 unrelated CHD cases for deletions or duplications of the Cx40 gene (GJA5) by real-time quantitative PCR, in order to determine whether altered copy number of this gene may be associated with a cardiac phenotype in humans. Dosage of Cx40 flanking genes (ACPL1 and Cx50 gene, GJA8) was determined by real-time PCR for all apparent positive cases. In total, 3 cases were found to carry deletions on chromosome 1q21.1 spanning ACPL1, Cx40, and Cx50 genes. Absence of heterozygosity was observed in all 3 index cases over a 1.5- to 3-Mb region. Samples from the parents of two cases were obtained, and microsatellites across 1q21.1 were genotyped. One of the apparently unaffected parents was found to carry this deletion. All 3 index cases presented with obstruction of the aortic arch as the common structural cardiac malformation, and had no consistent dysmorphic features. Genotyping of 520 unrelated normal controls for this deletion was negative. We hypothesize that this 1q21.1 multigene deletion is associated with a range of cardiac defects, with anomalies of the aortic arch being a particular feature.
Thermic effect of glucose in man. Obligatory and facultative thermogenesis.
Authors: K J Acheson, E Ravussin, J Wahren, E Jéquier
Journal: Journal of Clinical Investigation (1984)

The contribution of the sympathetic nervous system to the thermic effect of intravenously infused glucose and insulin was studied in 10 healthy young men before and after beta-adrenergic receptor blockade with propranolol during conditions of normoglycemia (90 mg/dl) at two levels of hyperinsulinemia (approximately 90 microU/ml and approximately 620 microU/ml). During steady state conditions of glucose uptake (0.515 +/- 0.046 and 0.754 +/- 0.056 g/min), significant increases were observed in energy expenditure (0.10 +/- 0.02 kcal/min, P less than 0.001, and 0.21 +/- 0.02 kcal/min, P less than 0.01, respectively). Similarly, glucose oxidation increased from 0.100 +/- 0.015 to 0.266 +/- 0.022 g/min (P less than 0.001) at approximately microU/ml insulin and from 0.082 +/- 0.013 to 0.295 +/- 0.018 g/min (P less than 0.001) at approximately 620 microU/ml insulin. Concomitantly, the rate of nonoxidative glucose disposal or "glucose storage" was 0.249 +/- 0.033 and 0.459 +/- 0.048 g/min, respectively. At this time the thermic effect of infused glucose/insulin was 5.3 +/- 0.9 and 7.5 +/- 0.7%, and the energy cost of "glucose storage" was 0.50 +/- 0.16 kcal/g and 0.47 +/- 0.04 kcal/g at the two different levels of glucose uptake. After beta-adrenergic receptor blockade with propranolol, glucose uptake, oxidation, and "storage" were unchanged in both studies, but significant decreases in energy expenditure were observed (1.41 +/- 0.06-1.36 +/- 0.05 kcal/min, P less than 0.01 at approximately 90 microU/ml insulin, and 1.52 +/- 0.07-1.43 +/- 0.05 kcal/min, P less than 0.005 at approximately 620 microU/ml insulin) causing significant falls in both the estimated thermic effect of infused glucose/insulin and the energy cost of "glucose storage". Regression analysis of the results from both studies indicated a mean energy cost for "glucose storage" of 0.36 kcal/g (r = 0.74, P less than 0.001), which fell significantly (P less than 0.005) to 0.21 kcal/g (r = 0.49, P less than 0.05) during beta-adrenergic receptor blockade with propranolol. The latter is in close agreement with that calculated on theoretical grounds for the metabolic cost of glucose storage as glycogen, i.e., obligatory thermogenesis. It is concluded that beta-adrenergically mediated sympathetic nervous activity is responsible for almost the entire rise in energy expenditure in excess of the obligatory requirements for processing and storing glucose during conditions of normoglycemia and hyperinsulinemia in healthy man, and that the energy cost of "glucose storage" is not different at normal (approximately 90 microU/ml) and supraphysiological (approximately 620 microU/ml) plasma insulin concentrations.
Diminished Hepatocellular Proliferation in Mice Humanized for the Nuclear Receptor Peroxisome Proliferator-Activated Receptor α
Authors: Connie Cheung, Taro E. Akiyama, Jerrold M. Ward, Christopher J. Nicol, Lionel Feigenbaum, Charles Vinson, Frank J. Gonzalez
Journal: Cancer Research (2004)

Abstract Lipid-lowering fibrate drugs function as agonists for the nuclear receptor peroxisome proliferator-activated receptor α (PPARα). Sustained activation of PPARα leads to the development of liver tumors in rats and mice. However, humans appear to be resistant to the induction of peroxisome proliferation and the development of liver cancer by fibrate drugs. The molecular basis of this species difference is not known. To examine the mechanism determining species differences in peroxisome proliferator response between mice and humans, a PPARα-humanized mouse line was generated in which the human PPARα was expressed in liver under control of the tetracycline responsive regulatory system. The PPARα-humanized and wild-type mice responded to treatment with the potent PPARα ligand Wy-14643 as revealed by induction of genes encoding peroxisomal and mitochondrial fatty acid metabolizing enzymes and resultant decrease of serum triglycerides. However, surprisingly, only the wild-type mice and not the PPARα-humanized mice exhibited hepatocellular proliferation as revealed by elevation of cell cycle control genes, increased incorporation of 5-bromo-2′-deoxyuridine into hepatocyte nuclei, and hepatomegaly. These studies establish that following ligand activation, the PPARα-mediated pathways controlling lipid metabolism are independent from those controlling the cell proliferation pathways. These findings also suggest that structural differences between human and mouse PPARα are responsible for the differential susceptibility to the development of hepatocarcinomas observed after treatment with fibrates. The PPARα-humanized mice should serve as models for use in drug development and human risk assessment and to determine the mechanism of hepatocarcinogenesis of peroxisome proliferators.