tbuckley/cabot-search huggingface dataset:
A randomized, double-blind, placebo-controlled of vitamin D3 for Irish children with asthma: Baseline data
Authors: Conor Kerley, Peter Greally, David Coughlan, Basil Elnazir
Journal: European Respiratory Journal (2014)

Vitamin D deficiency (VDD) and asthma-incidence/severity share many common risk factors. Vitamin D has a number of biological effects that are likely important in regulating key mechanisms in asthma, including immunomodulatory effects as well as altering airway hyperresponsiveness, pulmonary function, airway smooth muscle-remodeling and response to anti-asthma therapy. Thus, VDD may result in increased prevalence and severity of childhood asthma.  In Winter 2013-2014 we recruited 43 children (23 male), aged 5-15 (mean 8.7y) with a mean body mass index of 19.9kg/m2 (13 - 32.6) all previously diagnosed with asthma (Dublin, Ireland, 53°N). We assessed vitamin D status (25[OH]D]) PTH, PO4, calcium, IgE, CRP, WBC + differential and asthma control. These children were randomized to either 2,000iu vitamin D3/day or placebo for 15 weeks.  Mean 25(OH)D was 51nmol/L (24-80). According to the IOM guidelines, 21 children had deficient 25(OH)D levels ( 50nmol/L). There was no significant difference in demographics (age, BMI), serum markers (PTH, PO4, IgE, CRP, WBC) or self reported measures of asthma control (Asthma Control Test or Paediatric Asthma Quality of Life Questionnaire) between the VDD group and the vitamin D sufficient group. However, pulmonary function was significantly higher in the vitamin D sufficient group, including FVC% (66.3 vs. 96.1%; p = 0.03) and FEV1% (92.85 vs. 101.9%; p = 0.46)  Our preliminary, baseline data indicate that vitamin D sufficiency may be important for pulmonary function in asthmatic children. We anticipate full follow up results of this randomized, controlled trial will be available in June 2014.
Chronotropic responses of chick atria to field stimulation after various neural crest ablations.
Authors: M L Kirby, T L Creazzo, J L Christiansen
Journal: Circulation Research (1989)

Three models of altered autonomic innervation of the chick heart have been developed in the last few years. These include sympathetically aneural heart, parasympathetically aneural heart, and heart with cholinergic innervation reconstituted from the nodose placodes. The neural status of these hearts has been assessed by a variety of morphological and biochemical methods, but the functional status of innervation is not known. In the present study, we have used electrocardiography and field stimulation to determine the functional neural status of the three different innervation models. The RR and QTc intervals were measured to assess the dominant autonomic tone and autonomic dysfunction in the heart. Even though the RR and QTc intervals were found to be identical in sham and experimental embryos, field stimulation of superfused atria showed that the sympathetically aneural heart has functional cholinergic innervation but lacks any sympathetic response. Hearts from embryos which were parasympathetically aneural lacked a cholinergic response to field stimulation and were judged to be functionally parasympathetically aneural. Hearts with cholinergic ganglia reconstituted from the nodose placodes have normal RR and QTc intervals as well as a normal cholinergic response to field stimulation. The results indicate that these neurons are functionally indistinguishable from neural crest-derived neurons.
Inhibition of Vaccinial Hemagglutinins by Sera of Patients with Coronary Heart Disease and Other Chronic Illnesses
Authors: Beverly Jean Neff, W. Wilbur Ackermann, Frederick H. Epstein, Thomas Francis
Journal: Circulation Research (1962)

Serum inhibitory titers to the agglutination of chicken red cells by vaccinial hemagglutinin have been measured in persons with a variety of chronic diseases and in a control sample of the general population. Between the ages of 30 and 74, elevated titers occurred in 63 per cent of the men and 56 per cent of the women with chronic diseases, but in only 40 per cent of the men and 36 per cent of the women in the "control" population. Patients with coronary heart disease tended to show the highest titers. The suggestion is made that the serum inhibitor under study may reflect, in part, relatively "nonspecific" pathological changes and tissue responses provoked by various biological stresses and is a promising approach to the recognition of cardiovascular disease and related disorders.
Phase I Clinical and Pharmacokinetic Study of Kahalalide F Administered Weekly as a 1-Hour Infusion to Patients with Advanced Solid Tumors
Authors: Beatriz Pardo, Luis Paz-Ares, Josep Tabernero, Eva Ciruelos, Margarita García, Ramón Salazar, Ana López, María Blanco, Antonio Nieto, José Jimeno, Miguel Ángel Izquierdo, José Manuel Trigo
Journal: Clinical Cancer Research (2008)

A dose-escalation, phase I study evaluated the safety, pharmacokinetics, and efficacy of a weekly 1-h regimen of kahalalide F, a cyclic depsipeptide isolated from the marine mollusk Elysia rufescens, in adult patients with advanced solid tumors and no standard treatment available.Patients received an i.v. 1-h infusion of kahalalide F once weekly until disease progression or unacceptable toxicity. The starting kahalalide F dose was 266 microg/m(2), and dose escalation proceeded based on the worst toxicity found in the previous cohort.Thirty-eight patients were enrolled at three Spanish institutions and received once-weekly kahalalide F 1-h infusions at doses between 266 and 1,200 microg/m(2). Dose-limiting toxicities consisted of transient grade 3/4 increases in transaminase blood levels. The maximum tolerated dose for this kahalalide F schedule was 800 microg/m(2), and the recommended dose for phase II studies was 650 microg/m(2). No accumulated toxicity was found. One patient with malignant melanoma had unconfirmed partial response, one patient with metastatic lung adenocarcinoma had minor response, and six patients with different types of metastatic solid tumors had stable disease for 2.8 to 12.7 months. The noncompartmental pharmacokinetics of this kahalalide F schedule was linear and showed a narrow distribution and short body residence. The transaminitis associated with kahalalide F was dose dependent.The maximum tolerated dose was 800 microg/m(2). Dose-limiting toxicities with weekly kahalalide F 1-h i.v. infusions were transient grade 3/4 increases in blood transaminase levels, and 650 microg/m(2) was declared the recommended dose for phase II studies. This schedule showed a favorable safety profile and hints of antitumor activity.
Evidence for an Association Between Chlamydia psittaci and Ocular Adnexal Lymphomas
Authors: A. J. M. Ferreri, M. Guidoboni, M. Ponzoni, C. De Conciliis, S. Dell'Oro, K. Fleischhauer, L. Caggiari, A. A. Lettini, E. Dal Cin, R. Ieri, M. Freschi, E. Villa, M. Boiocchi, R. Dolcetti
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Ocular adnexal lymphomas may be antigen-driven disorders; however, the source of the putative antigen or antigens is still unknown. Hence, we assessed whether Chlamydiae infection is associated with the development of ocular adnexal lymphomas. Methods: The presence of Chlamydia psittaci, trachomatis, and pneumoniae DNA was investigated by polymerase chain reaction in 40 ocular adnexal lymphoma samples, 20 nonneoplastic orbital biopsies, 26 reactive lymphadenopathy samples, and peripheral blood mononuclear cells (PBMCs) from 21 lymphoma patients and 38 healthy individuals. Seven patients with chlamydia-positive PBMCs were treated with the antibiotic doxycycline, and objective response was assessed in four patients with measurable lymphoma lesions. Differences in Chlamydiae DNA detection between the case patients and the control subjects were analyzed using the Fisher exact test. All statistical tests were two-sided. Results: Thirty-two of the 40 (80%) ocular adnexal lymphoma samples carried C. psittaci DNA, whereas all lymphoma samples were negative for C. trachomatis and C. pneumoniae. In contrast, none of the 20 nonneoplastic orbital biopsies (0% versus 80%; P<.001) and only three of 26 (12%) reactive lymphadenopathy samples (12% versus 80%; P<.001) carried the C. psittaci DNA. Nine of 21 (43%) patients with chlamydia-positive lymphomas carried C. psittaci DNA in their PBMCs, whereas none (0%) of the healthy PBMC donors carried C. psittaci DNA in their PBMCs (43% versus 0%; P<.001). One month after doxycycline treatment, chlamydial DNA was no longer detectable in the PBMCs of all seven treated patients, and objective response was observed in two of the four evaluable patients. Conclusion: Patients with ocular adnexal lymphoma had a high prevalence of C. psittaci infection in both tumor tissue and PBMCs. Persistent C. psittaci infection may contribute to the development of these lymphomas, as was also supported by the clinical responses observed in this study with C. psittaci–eradicating antibiotic therapy.
Gestational Diabetes Mellitus in Women of Single Gravidity in Tianjin City, China
Authors: Xilin Yang, Bridget Hsu-Hage, Hong Zhang, Lichun Yu, Ling Dong, Jingchun Li, Ping Shao, Changjun Zhang
Journal: Diabetes Care (2002)

OBJECTIVE—The aim of this study was to investigate the prevalence of gestational diabetes mellitus (GDM) and risk factors for the development of GDM in pregnant women in Tianjin, China, where the prevalence of GDM is still unknown. STUDY DESIGN AND METHODS—A total of 9,471 pregnant women living in the six urban districts of Tianjin, China, took part in the initial screening between December 1998 and December 1999. The screening test consisted of a 50-g 1-h glucose test. Women with a reading ≥7.8 mmol/l at the initial screening were invited to undergo a 75-g 2-h oral glucose tolerance test (OGTT). GDM was confirmed using the World Health Organization’s diagnostic criteria. RESULTS—At the initial screening test, 888 women had a glucose reading of ≥7.8 mmol/l. A total of 701 (79%) women took a subsequent OGTT. Of these, 174 women were confirmed to have GDM (154 with impaired glucose tolerance [IGT] and 20 with diabetes). The prevalence of GDM was 2.31% (2.03% for IGT and 0.28% for diabetes), adjusting for serum glucose levels at the initial screening test. Independent predictors for GDM were maternal age, stature, prepregnancy BMI, weight gain in pregnancy before screening, diabetes in first-degree relatives, and habitual cigarette smoking during pregnancy. Women who smoked or had a short stature are more likely to develop GDM than their counterparts. CONCLUSIONS—The prevalence of GDM in pregnant women in the city of Tianjin, China, was 2.31%. Short stature and smoking in pregnancy were additional risk factors for GDM.
Volumetric Analysis of Glomerular Size in Kidneys of Mammals Living in Desert, Semidesert or Water-Rich Environment in the Sudan
Authors: I. MUNKáCSI, M. PALKOVITS
Journal: Circulation Research (1965)

The glomerular volumes in the kidneys were studied in four species of mammals, including a desert rodent, the jerboa ( Jaculus jaculus ); the laboratory white rat ( Rattus norvegicus ); a semidesert-living subprimate, the "bush baby" ( Galago senegalensis senegalensis ); and a primate, the grivet monkey ( Cercopitheus aethiops aethiops ). The measurements of volume were made according to the method of Palkovits and Zolnai which gives quantitative statistical values for the relative volumes of the glomeruli. An exact relationship between the average of the glomerular volumes, kidney weight, and body weight was not found in these different mammals when compared to each other. If the average volumes of the cortical and of the juxtamedullary glomeruli are compared separately then it is seen that the desert-living animals have a much bigger difference in volume between the cortical and the juxtamedullary glomeruli than those animals which require free access to water. In the kidney of the desert rodent (jerboa) the difference in volume between the cortical and the juxtamedullary glomeruli is 101% and, in the semidesert-living "bush baby," 169%. On the other hand the corresponding difference of volume in the laboratory white rat is only 21% and in the grivet monkey 28%. Considering the great functional importance of the juxtamedullary glomeruli and deep nephrons of the kidney in relation to dehydration, the large size of these structures can be regarded as an adaptation to life in an arid environment.
Knockdown of XAB2 Enhances All-<i>Trans</i> Retinoic Acid–Induced Cellular Differentiation in All-<i>Trans</i> Retinoic Acid–Sensitive and –Resistant Cancer Cells
Authors: Kumiko Ohnuma-Ishikawa, Tomohiro Morio, Takayuki Yamada, Yuji Sugawara, Makoto Ono, Masayuki Nagasawa, Akio Yasuda, Chikao Morimoto, Kei Ohnuma, Nam H. Dang, Hajime Hosoi, Eric Verdin, Shuki Mizutani
Journal: Cancer Research (2007)

Abstract Xeroderma pigmentosum group A (XPA)–binding protein 2 (XAB2) is composed of 855 amino acids, contains 15 tetratricopeptide repeat motifs, and associates with Cockayne syndrome group A and B proteins and RNA polymerase II, as well as XPA. In vitro and in vivo studies showed that XAB2 is involved in pre-mRNA splicing, transcription, and transcription-coupled DNA repair, leading to preimplantation lethality, and is essential for mouse embryogenesis. Retinoids are effective for the treatment of preneoplastic diseases including xeroderma pigmentosum and other dermatologic diseases such as photoaging. We therefore focused on defining the effect of XAB2 on cellular differentiation in the presence of ATRA treatment. In the present study, we showed that overexpression of XAB2 inhibited ATRA-induced cellular differentiation in human rhabdomyosarcoma cell line, and that knockdown of XAB2 by small interfering RNA (siRNA) increased ATRA-sensitive cellular differentiation in the human promyelocytic leukemia cell line HL60 at both physiologic (10−9–10−8 mol/L) and therapeutic (10−7 mol/L) concentrations of ATRA. Moreover, we found that XAB2 was associated with retinoic acid receptor α (RARα) and histone deacetylase 3 in the nuclei. Finally, using siRNA against XAB2, we showed that the ATRA-resistant neuroblastoma cell line IMR-32 underwent cellular differentiation induced by ATRA at a therapeutic concentration (10−6 mol/L). These results strongly suggest that XAB2 is a component of the RAR corepressor complex with an inhibitory effect on ATRA-induced cellular differentiation and that XAB2 plays a role in ATRA-mediated cellular differentiation as an important aspect of cancer therapy. [Cancer Res 2007;67(3):1019–29]
Phase II Study of Lenalidomide and Rituximab As Salvage Therapy for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Authors: Xavier C. Badoux, Michael J. Keating, Sijin Wen, William G. Wierda, Susan M. O'Brien, Stefan Faderl, Rachel Sargent, Jan A. Burger, Alessandra Ferrajoli
Journal: Journal of Clinical Oncology (2012)

Purpose Lenalidomide is an immunomodulatory drug active as salvage therapy for chronic lymphocytic leukemia (CLL). We combined lenalidomide with rituximab to improve response rates in patients with relapsed or refractory CLL. Patients and Methods Fifty-nine adult patients (age 42 to 82 years) with relapsed or refractory CLL were enrolled onto a phase II study of lenalidomide and rituximab. Patients had received prior fludarabine-based therapy or chemoimmunotherapy. Rituximab (375 mg/m 2 intravenously) was administered weekly during cycle one and on day 1 of cycles three to 12. Lenalidomide was started on day 9 of cycle one at 10 mg orally and administered daily continuously. Each cycle was 28 days. Rituximab was administered for 12 cycles; lenalidomide could continue indefinitely if patients benefitted clinically. Results The overall response rate was 66%, including 12% complete responses and 12% nodular partial remissions. Time to treatment failure was 17.4 months. Median overall survival has not been reached; estimated survival at 36 months is 71%. The most common grade 3 or 4 toxicity was neutropenia (73% of patients). Fourteen patients (24%) experienced a grade 3 to 4 infection or febrile episode. There was one episode of grade 3 tumor lysis; one patient experienced renal failure during the first cycle of therapy, and one venous thromboembolic event occurred during the study. Conclusion The combination of lenalidomide and rituximab is active in patients with recurrent CLL and warrants further investigation.
Changes in intracellular concentration of amino acids in human saphenous vein during preparation for coronary artery bypass grafting
Authors: M.-S. Suleiman, D. Wallace, S. Birkett, G.D. Angelini
Journal: Cardiovascular Research (1995)

Objectives: Earlier research on human skeletal and cardiac muscle has shown a fall in the intracellular free amino acid pool, particularly the non-essential amino acids, during surgery. Surgical preparation of the human saphenous vein for coronary artery bypass grafting has been shown to provoke metabolic damage and may therefore induce changes in cellular amino acids which may have long-term implications for the performance of the grafted vein. This work investigates the hypothesis that surgical preparation of saphenous vein induces changes in amino acids. Methods: Changes in the intracellular free amino acid pool were monitored, using high-performance liquid chromatography (HPLC), in both freshly isolated and surgically prepared human saphenous veins during coronary artery bypass grafting. In order to asses the extent of metabolic damage incurred by surgical preparation, adenosine triphosphate (ATP) levels were also measured. Results: A substantial fall in intracellular free amino acid pool was associated with surgical preparation of human saphenous vein for coronary artery bypass grafting (190.8 ± 25 to 106 ± 18 μmol · g−1 protein, n = 10, P < 0.05). Although the fall was seen in most amino acids detected, it was marked and statistically significant (P < 0.05) for taurine (30.6 ± 3.1 to 9.0 ± 2.2 μmol · g−1 protein), glutamate (43.6 ± 5.6 to 18.2 ± 4.5 μmol · g−1 protein), glutamine (12.8 ± 1.6 to 3.3 ± 1.2 μmol · g−1 protein) and asparagine (9.6 ± 1.6 to 4.1 ± 1.0 μmol · g−1 protein). The fall in tissue taurine which would be largely due to transport showed a strong positive correlation with the fall seen in glutamate, glutamine and asparagine. ATP levels significantly decreased as a result of surgical preparation (279 ± 44 to 96 ±21 nmol · g−1 wet weight, P < 0.05). The fall in ATP was accompanied by an increase in alanine/glutamate ratio which may reflect increased glutamate-alanine transaminase activity and therefore metabolic changes. Conclusions: The metabolic damage associated with surgical preparation of human saphenous vein for coronary artery bypass grafting is accompanied by a fall in the intracellular free amino acid pool which is marked and statistically significant for glutamate, taurine, glutamine and asparagine. The fall is likely to be due to transport although metabolism may also contribute. This may have important implications for the functional recovery of the grafted vein.
CARVEDILOL ATTENUATES ATRIAL FIBRILLATION PROMOTION VIA ANTIOXIDANT PROPERTIES IN DOGS WITH ATRIAL TACHYCARDIA REMODELING
Authors: Hiroyuki Motoda, Akiko Shiroshita-Takeshita, Tomoko Morikawa, Kazuhiko Sekine, Shinya Abe, Masaru Suzuki, Shingo Hori, Satoshi Ogawa
Journal: Journal of the American College of Cardiology (2010)
The Lack of Cyclin Kinase Inhibitor p27Kip1 Ameliorates Progression of Diabetic Nephropathy
Authors: Midori Awazu, Sayu Omori, Kenji Ishikura, Mariko Hida, Hisayo Fujita
Journal: Journal of the American Society of Nephrology (2003)

Cyclin kinase inhibitor p27(Kip(1)) (p27) has been shown to be upregulated in glomeruli of diabetic animals and mesangial cells cultured under high glucose. This study was an investigation of the role of p27 in the progression of diabetic nephropathy. Mice deficient in p27 (p27 -/-) and wild-type mice (p27 +/+) were studied 12 wk after diabetes induction by streptozotocin. Blood glucose and BP were comparable between diabetic p27 +/+ and p27 -/- mice. The kidney weight to body weight ratio and glomerular volume increased in diabetic p27 +/+ mice. In contrast, these parameters did not change in diabetic p27 -/- mice. Similarly, albuminuria developed in diabetic p27 +/+ mice but not in diabetic p27 -/- mice. The mesangial expansion was significantly milder in diabetic p27 -/- mice than that in diabetic p27 +/+ mice. These changes were associated with a similar increase in glomerular TGF-beta expression in diabetic p27 +/+ and p27 -/- mice. However, glomerular protein expression of fibronectin, a target of TGF-beta, increased only in diabetic p27 +/+ mice. In mesangial cells cultured from p27 +/+ mice, exposure to high glucose caused significant increases in total protein content and [(3)H]-leucine incorporation. On the other hand, high glucose caused a significant reduction in these parameters in cells from p27 -/- mice. Phosphorylation of 4E-BP1, the translation inhibitor, increased after exposure to high glucose in p27 +/+ cells. In p27 -/- cells, the level of phosphorylated 4E-BP1 was higher than that in control p27 +/+ cells and decreased under high glucose conditions. In conclusion, renal hypertrophy, glomerular hypertrophy, and albuminuria did not develop, and mesangial expansion was milder in diabetic p27 -/- mice despite glomerular TGF-beta upregulation. These results suggest that controlling p27 function may ameliorate diabetic nephropathy.
Incidence of non-Hodgkin's lymphoma among individuals with chronic hepatitis B virus infection
Authors: Marianne Ulcickas Yood, Charles P. Quesenberry, Dianlin Guo, Cary Caldwell, Karen Wells, Jun Shan, Lynn Sanders, Mary Lou Skovron, Uchenna Iloeje, Michele M. Manos
Journal: Hepatology (2007)

Although hepatitis C virus (HCV) infection has been shown to be associated with development of non-Hodgkin's lymphoma (NHL), few studies have investigated the association between chronic HBV infection and NHL. The purpose of this study was to compare the incidence of NHL between patients with and without chronic hepatitis B virus (HBV) infection. Using automated laboratory result and clinical data from two United States health systems, we identified individuals with chronic HBV infection from January 1, 1995 through December 31, 2001. Using each health system's population-based tumor registry, we identified all cases of NHL diagnosed through December 31, 2002. We excluded any individual with a history of NHL or human immunodeficiency virus (HIV). We fit Cox proportional hazards models to calculate hazard ratios comparing the incidence of NHL between chronic HBV-infected patients (N = 3,888) and patients without HBV (N = 205,203) drawn from the source populations. We identified 8 NHL cases in the chronic HBV infection cohort and 111 cases in the comparison cohort. Patients with chronic HBV infection were 2.8 times more likely to develop NHL than matched comparison patients (adjusted hazard ratio = 2.80, 95% confidence interval = 1.16-6.75), after controlling for age, race, sex, income, Charlson comorbidity index, study site, and HCV infection.chronic HBV-infected patients were nearly 3 times more likely to develop NHL than comparison patients.