tbuckley/cabot-search huggingface dataset:
Maternal Modification of Self-Recognition in Ova-Transfer Substrains of C3H Mice
Authors: Delta E. Uphoff
Journal: JNCI Journal of the National Cancer Institute (1972)

Bone marrow was transplanted to test 3 substrains derived from C3H (C3HfB, C3HeB, and C3HeD) for an altered ability to recognize C3H as “self” and to be recognized as “self” by the other substrains. Foster nursing removed the viral antigen of the mammary tumor agent in the ancestral strain C3H. It was assumed that the secondary disease syndrome, present in C3H recipients of marrow from derived substrains but absent in the C3HfB recipients of substrain marrow, was a response to this viral antigen. The greater response elicited in C3H recipients by marrow of the ova-transfer substrains, as compared with the foster-nursed substrain, suggests an increased responsiveness transferred from the strain of the foster mother. An altered antigenicity of the ova-transfer substrains, C3HeB and C3HeD, as compared with the foster-nursed substrain C3HfB, was detected by marrow of the ancestral C3H donors. C3HeD recipients, like C3H recipients, had a significantly more severe secondary disease syndrome after the inoculation of marrow from the “syngeneic” substrains. However, C3HeD recipients lacked the viral antigen present in C3H mice, indicating an increase in the tissue antigenicity of this derived substrain. The changes in ability to recognize “self” and to be recognized as “self” by derived substrains may be a function of the genetic disparity between the ancestral strain and that of the foster mother. These phenotypic alterations are permanent and vertically transmitted from mother to offspring for many generations.
Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib
Authors: Anne Lynn S. Chang, James A. Solomon, John D. Hainsworth, Leonard Goldberg, Edward McKenna, Bann-mo Day, Diana M. Chen, Glen J. Weiss
Journal: Journal of the American Academy of Dermatology (2013)

Vismodegib, a first-in-class Hedgehog pathway inhibitor, was US Food and Drug Administration (FDA) approved for advanced basal cell carcinomas (BCCs) based on a single, nonrandomized, phase-II trial. Consequently, additional clinical data are critical to confirm the efficacy and safety of vismodegib.We sought to assess efficacy and safety of vismodegib, while providing early drug access to patients with advanced BCC and limited treatment options.This was an open-label, multicenter study in patients with advanced BCC inappropriate for radiotherapy or surgery. Patients received 150 mg vismodegib daily until disease progression or intolerable toxicity. Tumor response was assessed via Response Evaluation Criteria in Solid Tumors version 1.0.A total of 119 patients with advanced BCC took vismodegib for a median of 5.5 months. Objective responses occurred in 46.4% of locally advanced BCC and 30.8% of patients with metastatic BCC. Response was negatively associated with prior systemic therapy in patients with locally advanced BCC (P = .002). Mean follow-up for safety was 6.5 months, with muscle spasms (70.6%), dysgeusia (70.6%), alopecia (58.0%), and diarrhea (25.2%) as the most common adverse events.Abbreviated follow-up time because of study termination upon FDA approval was a limitation.This study provides important clinical data supporting the efficacy and safety of vismodegib. Larger studies are underway to assess predictors of response and long-term outcomes.
Screening Primary Care Patients for Hereditary Hemochromatosis with Transferrin Saturation and Serum Ferritin Level: Systematic Review for the American College of Physicians
Authors: Brian Schmitt, Robert M. Golub, Richard Green
Journal: Annals of Internal Medicine (2005)

Background: Therapeutic phlebotomy for hereditary hemochromatosis is relatively safe and presumably efficacious when offered before cirrhosis develops, so screening primary care patients is of substantial interest. Purpose: To conduct a systematic review of the evidence on 1) the prevalence of the disease in primary care, 2) the risk for morbid or fatal complications for untreated patients, 3) the diagnostic usefulness of transferrin saturation and serum ferritin level in identifying early disease, 4) the efficacy of early treatment, and 5) whether the benefits of screening outweigh the risks. Data Sources: MEDLINE search from 1966 through April 2004, complemented by reference review of identified original studies and review articles published in English. Study Selection: PubMed Clinical Queries filters search of prognosis, diagnosis, etiology, or treatment were used depending on the question. Two authors reviewed all titles and abstracts. Data Extraction: Two investigators independently reviewed extracted data. Data Synthesis: The prevalence of hereditary hemochromatosis was 1 in 169 patients to 1 in 556 patients (n = 3 studies). Uncontrolled, prospective studies of genetic homozygous patients did not consistently identify a link to overt hereditary hemochromatosis. A serum ferritin level less than 1000 µg/L was predictive of absence of cirrhosis. Six studies demonstrated reduced survival in patients with cirrhosis. Diagnostic studies varied with respect to case definition. No blinded, independent comparisons of screening tests with the gold standard (biopsy or results of quantitative phlebotomy) or randomized, controlled trials of phlebotomy were identified. Cost-effectiveness analysis was limited by lack of prospective data on the natural history of the disease. Limitations: Varied case definition and lack of prospective cohort studies or randomized trials. Conclusions: The available evidence does not demonstrate that benefits outweigh the risks and costs of screening for hemochromatosis.
Inhibition of CaMKII Phosphorylation of RyR2 Prevents Induction of Atrial Fibrillation in FKBP12.6 Knockout Mice
Authors: Na Li, Tiannan Wang, Wei Wang, Michael J. Cutler, Qiongling Wang, Niels Voigt, David S. Rosenbaum, Dobromir Dobrev, Xander H.T. Wehrens
Journal: Circulation Research (2011)

Abnormal calcium release from sarcoplasmic reticulum (SR) is considered an important trigger of atrial fibrillation (AF). Whereas increased Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity has been proposed to contribute to SR leak and AF induction, downstream targets of CaMKII remain controversial. To test the hypothesis that inhibition of CaMKII-phosphorylated type-2 ryanodine receptors (RyR2) prevents AF initiation in FKBP12.6-deficient (-/-) mice. Mice lacking RyR2-stabilizing subunit FKBP12.6 had a higher incidence of spontaneous and pacing-induced AF compared with wild-type mice. Atrial myocytes from FKBP12.6-/- mice exhibited spontaneous Ca(2+) waves (SCaWs) leading to Na(+)/Ca(2+)-exchanger activation and delayed afterdepolarizations (DADs). Mutation S2814A in RyR2, which inhibits CaMKII phosphorylation, reduced Ca(2+) spark frequency, SR Ca(2+) leak, and DADs in atrial myocytes from FKBP12.6-/-:S2814A mice compared with FKBP12.6-/- mice. Moreover, FKBP12.6-/-:S2814A mice exhibited a reduced susceptibility to inducible AF, whereas FKBP12.6-/-:S2808A mice were not protected from AF. FKBP12.6 mice exhibit AF caused by SR Ca(2+) leak, Na(+)/Ca(2+)-exchanger activation, and DADs, which promote triggered activity. Genetic inhibition of RyR2-S2814 phosphorylation prevents AF induction in FKBP12.6-/- mice by suppressing SR Ca(2+) leak and DADs. These results suggest suppression of RyR2-S2814 phosphorylation as a potential anti-AF therapeutic target.
Soluble TNF‐α and interleukin‐6 receptors in the urine of heart failure patients. Their clinical value and relationship with plasma levels
Authors: Miguel Rivera, Raquel Taléns‐Visconti, Rafael Sirera, Vicente Bertomeu, Antonio Salvador, Raquel Cortés, Fernando García de Burgos, Vicente Climent, Rafael Payá, Luis Martinez‐Dolz, Maria Jose Sancho‐Tello, Andrés González‐Molina
Journal: European Journal of Heart Failure (2004)
Sequential chemotherapy, high-dose thiotepa, circulating progenitor cell rescue, and radiotherapy for childhood high-grade glioma
Authors: Maura Massimino, Lorenza Gandola, Roberto Luksch, Filippo Spreafico, Daria Riva, Carlo Solero, Felice Giangaspero, Franco Locatelli, Marta Podda, Fabio Bozzi, Emanuele Pignoli, Paola Collini, Graziella Cefalo, Marco Zecca, Michela Casanova, Andrea Ferrari, Monica Terenziani, Cristina Meazza, Daniela Polastri, Davide Scaramuzza, Fernando Ravagnani, Franca Fossati-Bellani
Journal: Neuro-Oncology (2005)

Childhood malignant gliomas are rare, but their clinical behavior is almost as aggressive as in adults, with resistance to therapy, rapid progression, and not uncommonly, dissemination. Our study protocol incorporated sequential chemotherapy and high-dose thiotepa in the preradiant phase, followed by focal radiotherapy and maintenance with vincristine and lomustine for a total duration of one year. The induction treatment consisted of two courses of cisplatin (30 mg/m2) plus etoposide (150 mg/m2) x 3 days and of vincristine (1.4 mg/m2) plus cyclophosphamide (1.5 g/m2) plus high-dose methotrexate (8 g/m2), followed by high-dose thiotepa (300 mg/m2 x 3 doses), with harvesting of peripheral blood progenitor cells after the first cisplatin/etoposide course. From August 1996 to March 2003, 21 children, 14 females and 7 males, with a median age of 10 years were enrolled, 18 presenting with residual disease after surgery. Histologies were glioblastoma multiforme in 10, anaplastic astrocytoma in nine, and anaplastic oligodendroglioma in two; sites of origin were supratentorial areas in 17, spine in two, and posterior fossa in two. Of the 21 patients, 12 have died (10 after relapse, with a median time to progression for the whole series of 14 months; one with intratumoral bleeding at 40 months after diagnosis; and one affected by Turcot syndrome for duodenal cancer relapse). Four of 12 relapsed children had tumor dissemination. At a median follow-up of 57 months, overall survival and progression-free survival at four years were 43% and 46%, respectively. Sequential and high-dose chemotherapy can be afforded in front-line therapy of childhood malignant glioma without excessive morbidity and rather encouraging results.
Cannulation technique influences arteriovenous fistula and graft survival
Authors: Maria Teresa Parisotto, Volker U. Schoder, Cristina Miriunis, Aileen H. Grassmann, Laura P. Scatizzi, Peter Kaufmann, Andrea Stopper, Daniele Marcelli
Journal: Kidney International (2014)

Hemodialysis patient survival is dependent on the availability of a reliable vascular access. In clinical practice, procedures for vascular access cannulation vary from clinic to clinic. We investigated the impact of cannulation technique on arteriovenous fistula and graft survival. Based on an April 2009 cross-sectional survey of vascular access cannulation practices in 171 dialysis units, a cohort of patients with corresponding vascular access survival information was selected for follow-up ending March 2012. Of the 10,807 patients enrolled in the original survey, access survival data were available for 7058 patients from nine countries. Of these, 90.6% had an arteriovenous fistula and 9.4% arteriovenous graft. Access needling was by area technique for 65.8%, rope-ladder for 28.2%, and buttonhole for 6%. The most common direction of puncture was antegrade with bevel up (43.1%). A Cox regression model was applied, adjusted for within-country effects, and defining as events the need for creation of a new vascular access. Area cannulation was associated with a significantly higher risk of access failure than rope-ladder or buttonhole. Retrograde direction of the arterial needle with bevel down was also associated with an increased failure risk. Patient application of pressure during cannulation appeared more favorable for vascular access longevity than not applying pressure or using a tourniquet. The higher risk of failure associated with venous pressures under 100 or over 150 mm Hg should open a discussion on limits currently considered acceptable.
Dissociation of airway inflammation and hyperresponsiveness by cyclooxygenase inhibition in allergen challenged mice
Authors: L. Swedin, T. Neimert-Andersson, J. Hjoberg, S. Jonasson, M. van Hage, M. Adner, Å. Ryrfeldt, S-E. Dahlén
Journal: European Respiratory Journal (2009)

The aim of the current study was to define how cyclooxygenase (COX)-activity affects airway hyperresponsiveness (AHR) and inflammation using interventions with COX inhibitors at different time points during allergen challenge and/or prior to measurement of AHR in an eosinophil-driven allergic mouse model. Inflammatory cells were assessed in bronchioalveolar lavage (BAL) and AHR was evaluated as the total lung resistance to methacholine (MCh) challenge. Administration of FR122047 (COX-1 inhibitor) during ovalbumin (OVA) challenge and prior to MCh challenge enhanced AHR without affecting the inflammatory cell response. In contrast, administration of lumiracoxib (COX-2 inhibitor) during the same time period had no effect on AHR but reduced the inflammatory cells in BAL. Nonselective COX inhibition with diclofenac both enhanced the AHR and reduced the inflammatory cells. Administration of diclofenac only during OVA challenge reduced the cells in BAL without any changes in AHR, whereas administration of diclofenac only prior to MCh challenge enhanced AHR but did not affect the cells in BAL. The present study implicates distinct roles of prostanoids generated along the COX-1 and COX-2 pathways and, furthermore, that inflammatory cells in BAL do not change in parallel with AHR. These findings support the fact that AHR and the inflammatory response are distinct and, at least in part, uncoupled events.
Role of Coronin 1B in PDGF-Induced Migration of Vascular Smooth Muscle Cells
Authors: Holly C. Williams, Alejandra San Martín, Candace M. Adamo, Bonnie Seidel-Rogol, Lily Pounkova, Srinivasan Raju Datla, Bernard Lassègue, James E. Bear, Kathy Griendling
Journal: Circulation Research (2012)

Rationale: The type I subclass of coronins, a family of actin-binding proteins, regulates various actin-dependent cellular processes, including migration. However, the existence and role of coronins in vascular smooth muscle cell (VSMC) migration has yet to be determined. Objective: The goal of the present study was to define the mechanism by which coronins regulate platelet-derived growth factor (PDGF)–induced VSMC migration. Methods and Results: Coronin 1B (Coro1B) and 1C (Coro1C) were both found to be expressed in VSMCs at the mRNA and protein levels. Downregulation of Coro1B by siRNA increases PDGF-induced migration, while downregulation of Coro1C has no effect. We confirmed through kymograph analysis that the Coro1B-downregulation-mediated increase in migration is directly linked to increased lamellipodial protraction rate and protrusion distance in VSMC. In other cell types, coronins exert their effects on lamellipodia dynamics by an inhibitory interaction with the ARP2/3 complex, which is disrupted by the phosphorylation of Coro1B. We found that PDGF induces phosphorylation of Coro1B on serine-2 via PKCɛ, leading to a decrease in the interaction of Coro1B with the ARP2/3 complex. VSMCs transfected with a phosphodeficient S2A Coro1B mutant showed decreased migration in response to PDGF, suggesting that the phosphorylation of Coro1B is required for the promotion of migration by PDGF. In both the rat and mouse, Coro1B phosphorylation was increased in response to vessel injury in vivo. Conclusions: Our data suggest that phosphorylation of Coro1B and the subsequent reduced interaction with ARP2/3·complex participate in PDGF-induced VSMC migration, an important step in vascular lesion formation.
Obesity and Breast Cancer Outcome: Adding to the Evidence
Authors: Rowan T. Chlebowski
Journal: Journal of Clinical Oncology (2011)

tre, and active comparator controlled investigation of the effect of pioglitazone, metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: The PIOCOMB study. Cardiovasc Diabetol 10:65, 2011 26. Wanders D, Plaisance EP, Judd RL: Pharmacological effects of lipidlowering drugs on circulating adipokines. World J Diabetes 1:116-128, 2010 27. Banga A, Unal R, Tripathi P, et al: Adiponectin translation is increased by the PPARgamma agonists pioglitazone and omega-3 fatty acids. Am J Physiol Endocrinol Metab 296:E480-E489, 2009 28. Oki K, Koide J, Nakanishi S, et al: Fenofibrate increases high molecular weight adiponectin in subjects with hypertriglyceridemia. Endocr J 54:431-435, 2007 29. Storka A, Vojtassakova E, Mueller M, et al: Angiotensin inhibition stimulates PPARgamma and the release of visfatin. Eur J Clin Invest 38:820-826, 2008 30. Nakamura T, Kawachi K, Saito Y, et al: Effects of ARB or ACE-inhibitor administration on plasma levels of aldosterone and adiponectin in hypertension. Int Heart J 50:501-512, 2009 31. Aggarwal BB: Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals. Annu Rev Nutr 30:173-199, 2010 32. Christodoulakos GE, Lambrinoudaki IV, Creatsa MG, et al: Circulating levels of atherogenesis-associated adipocytokines and apoptotic markers are differentially influenced by hormone therapy, tibolone and raloxifene in healthy postmenopausal women. Climacteric 11:155-165, 2008 33. Aguilar-Salinas CA, Garcia EG, Robles L, et al: High adiponectin concentrations are associated with the metabolically healthy obese phenotype. J Clin Endocrinol Metab 93:4075-4079, 2008 34. Inoue T, Kotooka N, Morooka T, et al: High molecular weight adiponectin as a predictor of long-term clinical outcome in patients with coronary artery disease. Am J Cardiol 100:569-574, 2007 35. Grossmann ME, Ray A, Dogan S, et al: Balance of adiponectin and leptin modulates breast cancer cell growth. Cell Res 18:1154-1156, 2008
Hyperglycemia-induced cholestasis in the isolated perfused rat liver
Authors: Jose J. G. Marin, Pilar Bravo, Fernando Perez Barriocanal, Mohamad Y. El-Mir, Gloria R. Villanueva
Journal: Hepatology (1991)

In a previous report we showed that cholestasis in diabetic rats is due in part to hyperglycemia. To gain information about the mechanism responsible for this phenomenon, bile flow was studied in isolated perfused rat livers. The perfusion media were modified erythrocyte-free Krebs-Henseleit solutions. Under these experimental conditions, no cholestasis was observed in isolated rat livers obtained from rats treated with streptozotocin (6 mg/100 gm body wt) 6 days before the experiments. We then proceeded to use normal animals. The composition of the perfusion media was modified to maintain the osmolality even after increasing D-glucose concentrations from 0 to 35 mmol/L. Bile flow was not affected with doses up to 15 mmol/L D-glucose. Beyond a threshold value for plasma D-glucose concentrations between 15 and 20 mmol/L, cholestasis was observed. Using D-glucose analogs such as L-glucose and 3-O-methyl-D-glucose, bile flow was also reduced (by 0.54 and 0.53 μl/min/gm liver, respectively). Isosmotic sucrose-containing perfusion media were also observed to impair bile flow (by 0.66 μl/min/gm liver). However, i-erythritol and D-mannitol failed to inhibit bile formation. The study of bile/plasma concentration ratios determined using tracer amounts of radioactive sugars indicated that this value was much lower for cholestatic sucrose (0.11) and L-glucose (0.31) than for noncholestatic i-erythritol (0.99) and D-mannitol (0.98). Cholestasis was partly reversed after induction by 35 mmol/L D-glucose if perfusion media were replaced by sugar-free ones, but also by media containing 25 mmol/L D-glucose. Insulin given during the perfusion with sugar-free media was observed to have no effect on bile flow. However, this hormone induced a significant increase in bile flow when cholestasis had previously been induced by hyperglycemia. This was not due to changes in plasma D-glucose concentrations. Insulin was also observed to reduce the cholestasis induced by 3-O-methyl-D-glucose but not by L-glucose. This suggests a process in which D-glucose transport rather than metabolism is involved. Biliary D-glucose output was very low up to a threshold value for plasma D-glucose concentration similar to those observed in hyperglycemia-induced cholestasis. Beyond this, it increased proportionally to plasma D-glucose concentrations. Insulin had no effect on biliary D-glucose output in livers perfused with sugar-free media, but a stimulation of this process was observed when the hormone was administered to livers perfused with cholestatic concentrations of D-glucose. The addition of phloridzin greatly increased (threefold) insulin-induced D-glucose output into bile, but it abolished insulin-induced reduction of cholestasis. In summary, these results confirm that hyperosmolality is not mandatory for hyperglycemia-induced cholestasis and that insulin deficiency may play a direct role in the cholestasis observed in diabetes. (HEPATOLOGY 1991;14:184–191.)
The FTA-ABS Test in Late Syphilis
Authors: Russell E. Harner
Journal: JAMA (1968)

Serology tests were made on 1,985 blood specimens drawn between September 1963 and February 1967. Seven hundred and eighteen cases of late syphilis were identified with the fluorescent treponemal antibody absorption (FTAABS) test. Only 441 (61%) patients had a reactive venereal disease research laboratory test for syphilis (VDRL). A sizeable percentage of late syphilitic cases (39%) seen in this study may have been overlooked if only a reagin test had been used to exclude or confirm the diagnosis.
Influence of Levarterenol on Portal Venous Flow in Acute Hemorrhage
Authors: MATTHEW N. LEVY, F. Flatly Arthur, Harrison Zieske
Journal: Circulation Research (1958)

In anesthetized dogs, the effects of hemorrhage alone upon the mesenteric circulation have been compared with those of hemorrhage plus l-norepinephrine. With norepinephrine, the portal venous flow is slightly less than in the case of untreated hemorrhage. In view of the significantly higher blood pressure during the norepinephrine infusions, however, the mesenteric resistance is considerably greater during infusions of this agent than in untreated hemorrhage.
Prevalence and risk factors of asthma and wheezing among US adults: an analysis of the NHANES III data
Authors: A.A. Arif, G.L. Delclos, E.S. Lee, S.R. Tortolero, L.W. Whitehead
Journal: European Respiratory Journal (2003)

The prevalence of asthma has been on the increase in the USA and worldwide. To understand the worsening epidemiological trends of asthma, this study analysed the data from the third National Health and Nutrition Examination Survey (NHANES III) to determine the prevalence and risk factors for asthma and wheezing among US adults. This analysis used data from 18,825 US adults aged > or = 20 yrs who had participated in the NHANES III project. After excluding subjects with physician-diagnosed emphysema, a total of 18,393 subjects were included in the final analysis. The prevalence of current asthma (asthma) was 4.5% and the prevalence of wheezing in the previous 12 months (wheezing) was 16.4%. Mexican-Americans exhibited the lowest prevalence of asthma when compared with other race/ethnic groups. Multiple logistic regression analysis showed that Mexican-Americans were less likely to report asthma when compared to non-Hispanic whites. Low education level, female sex, current and past smoking status, pet ownership, lifetime diagnosis of physician-diagnosed hay fever and obesity were all significantly associated with asthma and/or wheezing. No significant effect of indoor air pollutants, as derived from the use of household heating/cooking appliances, on asthma and wheezing was observed in this study. In conclusion, this study observed racial/ethnic differences in the prevalence of asthma and wheezing and identified several important risk factors that may contribute to development and/or exacerbation of asthma and wheezing. Contrary to earlier reports, the proxy measures of indoor air pollution used in this study were not found to be associated with increased risk of asthma and wheezing.