tbuckley/cabot-search huggingface dataset:
Effect of aging and hypertension on myosin biochemistry and gene expression in the rat heart.
Authors: P Buttrick, A Malhotra, S Factor, D Greenen, L Leinwand, J Scheuer
Journal: Circulation Research (1991)

The mechanisms by which the aged heart adapts to a superimposed pressure load such as hypertension have not been described. We therefore investigated biochemical and molecular genetic adaptations in the 24-month-old rat heart subjected to renovascular hypertension. Compared with 4-month-old rats, aging was associated with a 68% increase in left ventricular mass without any change in heart weight-to-body weight ratio, a 33% reduction in calcium-activated myosin ATPase activity, and a shift from a V1 to a V3 predominant myosin heavy chain (MHC) isoform distribution. A 46% reduction in alpha-MHC mRNA and a reciprocal increase in beta-MHC mRNA was seen. When hypertension was superimposed, there was a further 75% increase in ventricular mass, a 63% increase in heart weight-to-body weight ratio, and a 19% reduction in myosin ATPase. Myosin isozyme distribution was further shifted to V3, and the ratio of alpha-MHC to beta-MHC mRNA was reduced. In addition, with hypertension a significant (greater than 50%) reduction in the mRNA level of the cardiac sarcoplasmic reticular calcium-activated ATPase was seen. These data demonstrate that the aged myocardium is able to respond to a superimposed pressure load with a molecular genetic and protein synthetic pattern of hypertrophy analogous to that seen in younger animals.
Oral Immunotherapy for Treatment of Egg Allergy in Children
Authors: A. Wesley Burks, Stacie M. Jones, Robert A. Wood, David M. Fleischer, Scott H. Sicherer, Robert W. Lindblad, Donald Stablein, Alice K. Henning, Brian P. Vickery, Andrew H. Liu, Amy M. Scurlock, Wayne G. Shreffler, Marshall Plaut, Hugh A. Sampson
Journal: New England Journal of Medicine (2012)

For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy.In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months.After 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months.These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.).
The role of glial cells and apoptosis of enteric neurones in the neuropathology of intractable slow transit constipation
Authors: G Bassotti
Journal: Gut (2005)

Idiopathic slow transit constipation is one of the most severe and often intractable forms of constipation. As motor abnormalities are thought to play an important pathogenetic role, studies have been performed on the colonic neuroenteric system, which rules the motor aspects of the viscus.We hypothesised that important neuropathological abnormalities of the large bowel are present, that these are not confined to the interstitial cells of Cajal and ganglion cells, and that the previously described reduction of enteric neurones, if confirmed, might be related to an increase in programmed cell death (apoptosis).Surgical specimens from 26 severely constipated patients were assessed by conventional and immunohistochemical methods. Specific staining for enteric neurones, glial cells, interstitial cells of Cajal, and fibroblast-like cells associated with the latter were used. In addition, gangliar cell apoptosis was evaluated by means of indirect and direct techniques. Data from patients were compared with those obtained in 10 controls.Severely constipated patients displayed a significant decrease in enteric gangliar cells, glial cells, and interstitial cells of Cajal. Fibroblast-like cells associated with the latter did not differ significantly between patients and controls. Patients had significantly more apoptotic enteric neurones than controls.Severely constipated patients have important neuroenteric abnormalities, not confined to gangliar cells and interstitial cells of Cajal. The reduction of enteric neurones may in part be due to increased apoptotic phenomena.
Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway
Authors: Jean Soulier, Thierry Leblanc, Jérôme Larghero, Hélène Dastot, Akiko Shimamura, Philippe Guardiola, Hélène Esperou, Christèle Ferry, Charlotte Jubert, Jean-Paul Feugeas, Annie Henri, Antoine Toubert, Gérard Socié, André Baruchel, François Sigaux, Alan D. D'Andrea, Eliane Gluckman
Journal: Blood (2004)
Randomized study of cyclophosphamide, doxorubicin, and etoposide (VP16-213) with or without cisplatinum in non-small cell lung cancer.
Authors: J Z Fuks, J Aisner, D A Van Echo, H Schipper, M Levitt, S Ostrow, P H Wiernik
Journal: Journal of Clinical Oncology (1983)

Sixty-eight patients with non-small cell lung cancer were treated in a prospectively randomized study with cyclophosphamide, doxorubicin (Adriamycin), and etoposide (VP16-213) with cisplatinum (CAE +/- P). Response rate, time to progression, and survival of CAE-P treated patients were each superior compared to those of patients who received CAE therapy. Of 36 patients, 10 (4 complete remissions, 6 partial remissions) responded to CAE-P and of 29 patients 3 (1 complete remission, 2 partial remissions) responded to CAE (p = 0.073). The median time to treatment failure was 22.9 wk for the CAE-P regimen and 15.0 wk for CAE (p = 0.032). The median survival for patients treated on the regimen with and without cisplatinum was 34.5 and 22.5 wk, respectively (p = 0.04). There were two CAE-P and one CAE drug-related deaths. Toxic effects were more severe in the CAE-P regimen. The addition of cisplatinum to the CAE combination produced an increase in response rate with significant prolongation in both time to progression and survival, but did add morbidity. These results suggest that the combined use of cisplatinum with at least one of the chemotherapeutic agents in the CAE regimen is synergistic.
<i>PHOX2B</i> Mutation–confirmed Congenital Central Hypoventilation Syndrome
Authors: Nick A. Antic, Beth A. Malow, Neale Lange, R. Doug McEvoy, Amy L. Olson, Peter Turkington, Wolfram Windisch, Martin Samuels, Cathy A. Stevens, Elizabeth M. Berry-Kravis, Debra E. Weese-Mayer
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Congenital central hypoventilation syndrome (CCHS) typically presents in the newborn period. A case series of five adults is presented, each heterozygous for a documented polyalanine expansion mutation in the PHOX2B gene and evidence of nocturnal alveolar hypoventilation. All cases had symptoms in childhood, but survived to adulthood without ventilatory support. After identification of physiologic compromise, artificial ventilation was initiated. These adults have the mildest of the CCHS-related PHOX2B polyalanine expansion mutations, coding for only five extra alanines; three of the adults have affected offspring. Report of these cases should lead to a more rapid identification of CCHS presenting in adulthood.
Expression of p8 in Human Pancreatic Cancer
Authors: Shi-Bing Su, Yoshiharu Motoo, Juan Lucio Iovanna, Min-Jue Xie, Hisatsugu Mouri, Koushiro Ohtsubo, Yasushi Yamaguchi, Hiroyuki Watanabe, Takashi Okai, Fujitsugu Matsubara, Norio Sawabu
Journal: Clinical Cancer Research (2001)

The p8 gene is a recently identified gene with mitogenic activity. p8 expression is induced in acute pancreatitis, pancreatic development, and regeneration. However, the expression of p8 in pancreatic cancer is not reported. We investigated p8 expression in 72 human pancreatic tissues, including 38 pancreatic cancers (PCs), by immunohistochemistry. p8 was overexpressed (positive cells >25% in 1,000 cells) in 71% (27 of 38) of PCs, but in only 17% (3 of 18) of chronic pancreatitis cases. There was no overexpression in mucinous cystadenoma or in normal pancreas. The p8 overexpression rate in PC was significantly higher than that in other conditions (P  2) in 75% (3 of 4) of PCs. p8 was overexpressed also in human pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). These results suggest that p8 is involved in the development of pancreatic cancer, reflecting its mitogenic activity.
Routine Versus Catastrophic Influences on the Developing Child
Authors: Candice L. Odgers, Sara R. Jaffee
Journal: Annual Review of Public Health (2013)

Exposure to toxic stress accelerates the wear and tear on children's developing bodies and leaves a lasting mark on adult health. Prior research has focused mainly on children exposed to extreme forms of adversity, such as maltreatment and extreme neglect. However, repeated exposure to less severe, but often chronic stressors is likely to play as large, if not larger, of a role in forecasting children's future mental and physical health. New tools from neuroscience, biology, epigenetics, and the social sciences are helping to isolate when and how the foundations for adult health are shaped by childhood experiences. We are now in the position to understand how adversity, in both extreme and more mundane forms, contributes to the adult health burden and to identify features in children's families and environments that can be strengthened to buffer the effects of toxic stressors. We are also positioned to develop and implement innovative approaches to child policy and practice that are rooted in an understanding of how exposure to toxic stressors can become biologically embedded. The stage is set for the creation of new interventions--on both grand and micro scales--to reduce previously intractable health disparities.
Surveillance and Treatment Protocols to Detect and Treat Hepatitis B Virus Reactivation in Hepatitis B Surface Antigen–Negative/Antibody to Hepatitis B Core Antigen–Positive Patients Receiving Chemotherapy for Onco-Hematologic Malignancies
Authors: Massimo Marignani, Alfredo Marzano
Journal: Journal of Clinical Oncology (2011)

We read with interest the article by Niitsu et al, 1 and we compliment the authors for having focused their attention on the group of hepatitis B surface antigen-negative/antibody to hepatitis B core antigen-positive patients who are undergoing chemotherapy for onco-hematologic malignancies and who are at high risk for hepatitis B reactivation, especially if receiving rituximab-based protocols. 2][4] However, some specific questions regarding the article do arise.What is the cost of monthly dosing of HBV-DNA and the antibody to the hepatitis B surface antigen titer?Has the cost-effectiveness profile of this approach been addressed or compared with alternative strategies?What HBV-DNA levels were detected at reactivation?It would be interesting to provide this information, given that the decision to use a high-potency/high-genetic barrier antiviral such as entecavir to treat low-level HBV-DNA reactivation might be excessive.Actually, in patients with reactivation that is characterized by low levels of HBV-DNA, lamivudine still presents an attractive treatment solution, given its relative availability, effectiveness, and low cost. 2 The use of other, more potent antivirals such as entecavir could be considered for the management of patients with higher levels of HBV-DNA or acute hepatitis that develops as a result of HBV reactivation. 5In addition, the strategy of lamivudine prophylaxis in selected high-risk groups may present an additional option to be considered in the setting of immunosuppression during the treatment of onco-hematologic malignancies. 3,4Answers to these questions are crucial to define the applicability of the authors' findings to everyday practice, especially in countries in which the availability of high-cost medications and surveillance protocols might hamper the feasibility of this approach.Definition of surveillance strategies for isolated patients with an antibody to the hepatitis B core antigen who are undergoing chemotherapy and are at risk for HBV reactivation, and how to manage the manifestations of reactivation, which range from isolated increases of HBV-DNA to severe acute hepatitis and liver failure, still remain debated issues.
THE COLLOIDAL GOLD AND OTHER TESTS APPLIED TO THE SPINAL FLUID IN PSYCHIATRY
Authors: PAUL G. WESTON, IRA A. DARLING, PHILIP B. NEWCOMB
Journal: American Journal of Psychiatry (1915)

I. In the cases diagnosed clinically as cerebrospinal syphilis the Wassermann reaction upon the spinal fluid was always positive and the colloidal gold test showed a reaction in the paretic zone. II. In paresis the colloidal gold test was always found positive in cases where the spinal fluid showed a similar reaction to the Wassermann test, in addition to which there is one instance noted in which the fluid Wassermann was negative, but a reaction in the luetic zone obtained by the gold solution. III. In dementia præcox, manic-depressive insanity, arteriosclerotic dementia and epilepsy there were no positive Wassermann reactions upon the fluid, and likewise no response to the gold solution in the typical "paretic zone". However, the latter reagent did furnish in eight cases of the 152 examined a reaction within the minor limits of the "luetic zone." IV. In the unclassffied psychoses the calloidal gold and the Wassermann reactions upon the fluid ran a parallel course, except in one case, which showed a negative response to the Wassermann test upon the fluid, but gave a gold reaction in the "paretic zone." This instance is clinically a possible case of paresis. V. From our work the opinion is drawn that the colloidal gold reaction forms a useful adjuvant to the Wassermann, is apparently as reliable and, in some instances, by reason of positive response in the absence of the Wassermann in clinically luetic cases, has seemed to point towards the possible appearance of a later positive Wassermann in the suspected individuals.
1352 INTEROBSERVER CONCORDANCE IN CONTROLLED ATTENUATION PARAMETER (CAP) MEASUREMENT, A NOVEL TOOL FOR THE ASSESSMENT OF HEPATIC STEATOSIS BASED ON TRANSIENT ELASTOGRAPHY
Authors: E. Recio, K. Neukam, C. Cifuentes, M. Mancebo, J. Macías, C. Almeida, N. Merchante, J.A. Mira, A. Rivero-Juárez, J.A. Pineda
Journal: Journal of Hepatology (2013)
Interaction of Cisplatin with the Human Organic Cation Transporter 2
Authors: Kelly K. Filipski, Walter J. Loos, Jaap Verweij, Alex Sparreboom
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Cisplatin is predominantly eliminated in the urine through active secretion. As the solute carrier organic cation transporter 2 (OCT2) is highly expressed in the basolateral membrane of proximal tubules, we determined its contribution to cisplatin transport and assessed the relation of variation in the gene encoding OCT2 (SLC22A2) with the disposition of cisplatin. Experimental Design: Cell lines were transfected using the Flp-In 293 system with the full-length OCT2 cDNA, and platinum concentrations were measured using flameless atomic absorption spectrometry. Pharmacokinetic data were available from 106 cancer patients, and DNA was screened for eight nonsynonymous SLC22A2 variants using direct sequencing. Results: mRNA expression was 36-fold higher and uptake of the model substrate tetraethylammonium was significantly increased (P &amp;lt; 0.0001) in OCT2-transfected cells compared with empty vector-transfected controls. OCT2-mediated transport of cisplatin was saturable, and uptake was increased by ∼4-fold (P &amp;lt; 0.0001) relative to control cells. Cisplatin inhibited OCT2-mediated transport of tetraethylammonium by up to 97%. The mean ± SD systemic clearance of unbound cisplatin-derived platinum in the patient population was 29.2 ± 8.39 L/h, and renal clearance was particularly variable. Only one single nucleotide polymorphism (Ala270Se; rs316019) was identified (minor allele frequency, 7.6%), and it was not found to be associated with any of the studied pharmacokinetic variables (P &amp;gt; 0.05). Conclusion: These findings support the hypothesis that OCT2 is a key renal transporter involved in cisplatin elimination. However, known variants in SLC22A2 do not substantially contribute to explaining interindividual pharmacokinetic variability, suggesting that other mechanisms, controlling OCT2 expression, might be involved.
Disease Management Program for Chronic Obstructive Pulmonary Disease
Authors: Kathryn L. Rice, Naresh Dewan, Hanna E. Bloomfield, Joseph Grill, Tamara M. Schult, David B. Nelson, Sarita Kumari, Mel Thomas, Lois J. Geist, Caroline Beaner, Michael Caldwell, Dennis E. Niewoehner
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

The effect of disease management for chronic obstructive pulmonary disease (COPD) is not well established.To determine whether a simplified disease management program reduces hospital admissions and emergency department (ED) visits due to COPD.We performed a randomized, adjudicator-blinded, controlled, 1-year trial at five Veterans Affairs medical centers of 743 patients with severe COPD and one or more of the following during the previous year: hospital admission or ED visit for COPD, chronic home oxygen use, or course of systemic corticosteroids for COPD. Control group patients received usual care. Intervention group patients received a single 1- to 1.5-hour education session, an action plan for self-treatment of exacerbations, and monthly follow-up calls from a case manager.We determined the combined number of COPD-related hospitalizations and ED visits per patient. Secondary outcomes included hospitalizations and ED visits for all causes, respiratory medication use, mortality, and change in Saint George's Respiratory Questionnaire. After 1 year, the mean cumulative frequency of COPD-related hospitalizations and ED visits was 0.82 per patient in usual care and 0.48 per patient in disease management (difference, 0.34; 95% confidence interval, 0.15-0.52; P < 0.001). Disease management reduced hospitalizations for cardiac or pulmonary conditions other than COPD by 49%, hospitalizations for all causes by 28%, and ED visits for all causes by 27% (P < 0.05 for all).A relatively simple disease management program reduced hospitalizations and ED visits for COPD. Clinical trial registered with www.clinicaltrials.gov (NCT00126776).
Radiographic progression and remission rates in early rheumatoid arthritis - MRI bone oedema and anti-CCP predicted radiographic progression in the 5-year extension of the double-blind randomised CIMESTRA trial
Authors: M. L. Hetland, K. Stengaard-Pedersen, P. Junker, M. Ostergaard, B. J. Ejbjerg, S. Jacobsen, T. Lottenburger, I. Hansen, U. Tarp, L. S. Andersen, A. Svendsen, J. K. Pedersen, U. B. Lauridsen, T. Ellingsen, H. Lindegaard, J. Podenphant, A. Vestergaard, A. G. Jurik, K. Horslev-Petersen
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> At 5 years9 follow-up of early (&lt;6 months) rheumatoid arthritis patients to (1) investigate whether initial combination therapy with methotrexate (MTX) and ciclosporin (CSA) (n=80) is superior to initial monotherapy with MTX (n=80) with respect to prevention of radiographic progression, (2) investigate whether the favourable clinical and radiographic response reported at 2 years in the CIMESTRA trial can be maintained and (3) identify predictors of radiographic outcome. <h3>Methods</h3> 139 patients completed 5 years9 follow-up with maintained double-blinding and a strict synovitis suppressive treatment strategy with intra-articular betamethasone injections (intra-articular glucocorticosteroid (GC)) and escalation of disease-modifying anti-rheumatic drug treatment. Disease activity, total Sharp-van der Heijde Score (TSS) of hands, wrists and forefeet were assessed at baseline and after 3, 4 and 5 years. MRI of the wrist and anti-cyclic citrullinated peptide (anti-CCP) were assessed at baseline. <h3>Results</h3> At 5 years, TSS progression rate was &lt;1 unit/year and 47% had not progressed radiographically since baseline. 78% were in Disease Activity Score remission, 56% in American College of Rheumatology remission and 17% withdrawn from treatment due to remission. There were no differences between initial treatment groups. MRI-bone marrow oedema, TSS and anti-CCP predicted radiographic progression at 5 years. <h3>Conclusion</h3> Early and strict synovitis suppressive treatment with MTX and intra-articular GC lead to high remission rates and halting of erosive progression at 5 years. No additional effect of initial combination therapy with CSA was found. The results parallel those reported for tumour necrosis factor α antagonists. Baseline MRI-bone oedema, TSS and anti-CCP predicted radiographic progression.