tbuckley/cabot-search huggingface dataset:
Effects of single-dose zileuton on bronchial hyperresponsiveness in asthmatic patients treated with inhaled corticosteroids
Authors: PN Dekhuijzen, GP Bootsma, PL Wielders, LR van den Berg, J Festen, CL van Herwaarden
Journal: European Respiratory Journal (1997)

The aim of the study was to determine whether zileuton, an inhibitor of 5-lipoxygenase, attenuated bronchial hyperresponsiveness (BHR) in asthmatic subjects who had marked BHR during maintenance treatment with inhaled corticosteroids (ICS). In a randomized, double-blind, placebo-controlled, cross-over study, a challenge test with histamine (provocative concentration of histamine producing a 20% fall in forced expiratory volume in one second (FEV1) (PC20,Hist)) and with ultrasonically nebulized distilled water (UNDW) (provocative dose of UNDW producing a 20% fall in FEV1 (PD20,UNDW)) was performed in seven patients with asthma after intake of either 400 mg zileuton or placebo. All patients (mean age 33 yrs, mean FEV1 111% of predicted) had marked BHR, as indicated by a mean PD20,UNDW of 4.74 mL under treatment for at least 6 months with up to 800 microg ICS (mean 536 microg daily). On four different occasions, separated by at least 5 days, two UNDW and two histamine challenge tests were performed in random order 3 h after a morning dose of either zileuton or placebo. Neither zileuton nor placebo changed baseline airway calibre prior to provocation. Zileuton increased PC20,Hist from 0.99 to 5.64 mg x mL(-1) (2.1 doubling doses; p&lt;0.03 compared to placebo), and increased PD20,UNDW from 3.10 to 9.31 mL (1.3 doubling doses; p&lt;0.05 compared to placebo). In conclusion, a single dose of 400 mg zileuton attenuates bronchial hyperresponsiveness to histamine and ultrasonically nebulized distilled water in asthmatic patients with marked bronchial hyperresponsiveness during treatment with inhaled corticosteroids.
Hodgkin's disease: Correlation between causes of death at autopsy and clinical diagnosis
Authors: M. Provencio, P. España, C. Salas, F. Navarro, F. Bonilla
Journal: Annals of Oncology (2000)

The causes of mortality in Hodgkin's disease patients are insufficiently known. Autopsy study is the fundamental procedure in the investigation of these causes. The present study analyzes the autopsies performed in a series of patients diagnosed as having Hodgkin's disease, determining the cause of death in each case and comparing the premortem clinical data and the postmortem findings.A total of 486 patients diagnosed as having Hodgkin's disease between 1967 and 1996 were assessed. Autopsy was performed in 40 of the 144 deceased patients (28%). We reviewed the pathological findings, effects of treatment, discordance between the clinical diagnosis and the outcome of autopsy, and cause of death in each case.The most common clinical causes of death in those patients with autopsy study were tumor progression (37%) and infections (43%) in those patients with autopsy study. The rate of discordance between the clinical and autopsy diagnoses in this study was 43%. The most frequent location of residual Hodgkin's disease was in the lymph nodes.Autopsy study in Hodgkin's disease confirms a high rate of discrepancy between final clinical diagnosis and postmortem lesions despite advances in diagnostic methods. Autopsy revealed causes of death directly related to the treatment, as well as some lesions directly related to patient death and secondary to treatment. Infectious processes are likely to remain undetected and their symptoms can mimic tumor progression.
Chromosome 12p Deletions in<i>TEL-AML1</i>Childhood Acute Lymphoblastic Leukemia Are Associated with Retrotransposon Elements and Occur Postnatally
Authors: Joseph L. Wiemels, Jerry Hofmann, Michelle Kang, Rebecca Selzer, Roland Green, Mi Zhou, Sheng Zhong, Luoping Zhang, Martyn T. Smith, Carmen Marsit, Mignon Loh, Patricia Buffler, Ru-Fang Yeh
Journal: Cancer Research (2008)

Abstract TEL-AML1 (ETV6-RUNX1) is the most common translocation in the childhood leukemias, and is a prenatal mutation in most children. This translocation has been detected at a high rate among newborns (∼1%); therefore, the rate-limiting event for leukemia seems to be secondary mutations. One such frequent mutation in this subtype is partial deletion of chromosome 12p, trans from the translocation. Nine del(12p) breakpoints within six leukemia cases were sequenced to explore the etiology of this genetic event, and most involved cryptic sterile translocations. Twelve of 18 del(12p) parent sequences involved in these breakpoints were located in repeat regions (8 of these in long interspersed nuclear elements). This stands in contrast with TEL-AML1, in which only 21 of 110 previously assessed breakpoints (19%) occur in DNA repeats (P = 0.0001). An exploratory assessment of archived neonatal blood cards revealed significantly more long interspersed nuclear element CpG methylations in individuals at birth who were later diagnosed with TEL-AML1 leukemia, compared with individuals who did not contract leukemia (P = 0.01). Nontemplate nucleotides were also more frequent in del(12p) than in TEL-AML1 junctions (P = 0.004), suggesting formation by terminal deoxynucleotidyl transferase. Assessment of six archived neonatal blood cards indicated that no del(12p) rearrangements backtracked to birth, although two of these patients were previously positive for TEL-AML1 using the same assay with comparable sensitivity. These data are compatible with a two-stage natural history: TEL-AML1 occurs prenatally, and del(12p) occurs postnatally in more mature cells with a structure that suggests the involvement of retrotransposon instability. [Cancer Res 2008;68(23):9935–44]
Increased Incidence of Type II Diabetes Mellitus in Mexican Americans
Authors: Steven M Haffner, Helen P Hazuda, Braxton D Mitchell, Judith K Patterson, Michael P Stern
Journal: Diabetes Care (1991)

Objective To determine whether Mexican Americans have an increased incidence of non-insulin-dependent (type II) diabetes mellitus relative to non-Hispanic whites. Currently, no study has reported on the incidence of this disorder in Mexican Americans. Research Design and Methods We determined the 8-yr incidence of type II diabetes in 617 Mexican Americans and 306 non-Hispanic whites who participated in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Forty Mexican Americans (6.5%) and 6 non-Hispanic whites (2%) developed type II diabetes, as defined by World Health Organization criteria. The age-adjusted ethnic odds ratio (OR; Mexican Americans/non-Hispanic whites) for diabetes incidence was 8.13 (95% confidence interval [C1] 1.10–59.9) in men and 3.62 (95% CI 1.37–9.55) in women. We adjusted for age, sex, ethnicity, body mass index, and level of educational attainment with multiple logistic regression analyses. Results Mexican Americans continued to show a statistically significant increase in diabetes incidence (OR 2.72, 95% CI 1.02–7.28). Obesity and age were also positively related to diabetes incidence in this analysis (P &amp;lt; 0.001). In addition, subjects with at least some college education had a lower incidence of diabetes than those with less than a high school education (OR 0.51, 95% CI 0.26–0.99). Conclusions The incidence of type II diabetes in Mexican Americans is greater than in non-Hispanic whites, a difference that is not explained by ethnic differences in obesity, age, or level of educational attainment.
Distinct Architecture of Lymphatic Vessels Induced by Chimeric Vascular Endothelial Growth Factor-C/Vascular Endothelial Growth Factor Heparin-Binding Domain Fusion Proteins
Authors: Tuomas Tammela, Yulong He, Johannes Lyytikkä, Michael Jeltsch, Johanna Markkanen, Katri Pajusola, Seppo Ylä-Herttuala, Kari Alitalo
Journal: Circulation Research (2007)

Vascular endothelial growth factor (VEGF)-C and VEGF-D are composed of the receptor-binding VEGF homology domain and a carboxy-terminal silk homology domain that requires proteolytic cleavage for growth factor activation. Here, we explored whether the C-terminal heparin-binding domain of the VEGF(165) or VEGF(189) isoform also containing neuropilin-binding sequences could substitute for the silk homology domain of VEGF-C. Such VEGF-C/VEGF-heparin-binding domain chimeras were produced and shown to activate VEGF-C receptors, and, when expressed in tissues via adenovirus or adeno-associated virus vectors, stimulated lymphangiogenesis in vivo. However, both chimeras induced a distinctly different pattern of lymphatic vessels when compared with VEGF-C. Whereas VEGF-C-induced vessels were initially a dense network of small diameter vessels, the lymphatic vessels induced by the chimeric growth factors tended to form directly along tissue borders, along basement membranes that are rich in heparan sulfate. For example, in skeletal muscle, the chimeras induced formation of lumenized lymphatic vessels more efficiently than wild-type VEGF-C. We conclude that the matrix-binding domain of VEGF can target VEGF-C activity to heparin-rich basement membrane structures. These properties may prove useful for tissue engineering and attempts to regenerate lymphatic vessels in lymphedema patients.
Ischemic Protection and Myofibrillar Cardiomyopathy
Authors: Harvey S. Hahn, Martin G. Yussman, Tsuyoshi Toyokawa, Yehia Marreez, Thomas J. Barrett, K. Chad Hilty, Hanna Osinska, Jeffrey Robbins, Gerald W. Dorn
Journal: Circulation Research (2002)

To delineate the in vivo cardiac functions requiring normal δ protein kinase C (PKC) activity, we pursued loss-of-function through transgenic expression of a δPKC-specific translocation inhibitor protein fragment, δV1, in mouse hearts. Initial results using the mouse α-myosin heavy chain (αMHC) promoter resulted in a lethal heart failure phenotype. Viable δV1 mice were therefore obtained using novel attenuated mutant αMHC promoters lacking one or the other thyroid response element (TRE-1 and -2). In transgenic mouse hearts, δV1 decorated cytoskeletal elements and inhibited ischemia-induced δPKC translocation. At high levels, δV1 expression was uniformly lethal, with depressed cardiac contractile function, increased expression of fetal cardiac genes, and formation of intracardiomyocyte protein aggregates. Ultrastructural and immunoconfocal analyses of these aggregates revealed focal cytoskeletal disruptions and localized concentrations of desmin and αB-crystallin. In individual cardiomyocytes, cytoskeletal abnormalities correlated with impaired contractile function. Whereas desmin and αB-crystallin protein were increased ≈4-fold in δV1 hearts, combined overexpression of these proteins at these levels was not sufficient to cause any detectable cardiac pathology. At low levels, δV1 expression conferred striking resistance to postischemic dysfunction, with no measurable effects on basal cardiac structure, function, or gene expression. Intermediate expression of δV1 conferred modest basal contractile depression with less ischemic protection, associated with abnormal cardiac gene expression, and a histological picture of infrequent cardiomyocyte cytoskeletal deformities. These results validate an approach of δPKC inhibition to protect against myocardial ischemia, but indicate that there is a threshold level of δPKC activation that is necessary to maintain normal cardiomyocyte cytoskeletal integrity.
Contribution of outgrowth endothelial cells from human peripheral blood on in vivo vascularization of bone tissue engineered constructs based on starch polycaprolactone scaffolds
Authors: Sabine Fuchs, Shahram Ghanaati, Carina Orth, Mike Barbeck, Marlen Kolbe, Alexander Hofmann, Markus Eblenkamp, Manuela Gomes, Rui L. Reis, Charles J. Kirkpatrick
Journal: Biomaterials (2008)
Tissue doppler echocardiography detects preclinical markers of cardiac lesion in MDS patients
Authors: Cláudio César Monteiro de Castro, Carlos Bellini Gondim Gomes, Manoel Ricardo Alves Martins, Juliana Cordeiro de Sousa, Silvia MM Magalhaes, Ronald F Pinheiro
Journal: Journal of Hematology & Oncology (2012)

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder of elderly people. Cardiac dysfunction is a marker of grim prognosis in MDS. We evaluated cardiac dysfunction of MDS patients with or without transfusion dependency by tissue doppler echocardiography. We found the average values of ventricular end-systolic and end-diastolic volumes in transfusion dependency MDS group higher than others. These results were strongly correlated to hemoglobin levels. Tissue Doppler Echocardiography should be routinely performed in MDS patients to detect preclinical cardiac alterations and prevent more heart insults in this group of chronic anemic aged patients.
Low-dose inhaled corticosteroids and the risk of acute myocardial infarction in COPD
Authors: L. Huiart, P. Ernst, X. Ranouil, S. Suissa
Journal: European Respiratory Journal (2005)

Inflammation plays a major role in the development and complications of atherosclerosis. Here, the dose-related impact of inhaled corticosteroids (ICS), used for their anti-inflammatory properties, on the risk of acute myocardial infarction (AMI) is studied in a cohort of chronic obstructive pulmonary disease (COPD) patients. Saskatchewan (Canada) health services databases were used to form a population-based cohort of 5,648 patients, ≥55 yrs, who received a first treatment for COPD between 1990 and 1997. A nested case-control analysis was conducted, where 371 cases presenting with a first AMI were matched with 1,864 controls, based on the date of cohort entry and age. A conditional logistic regression was used to estimate the effect of ICS, after adjusting for use of oral corticosteroids, severity of COPD, sex, systemic hypertension, diabetes and cardiovascular disease. ICS were used in the prior year by 42.2% of cases and 46.4% of controls. Overall, current use of ICS was not associated with a significant decrease in the risk of AMI. However, a 32% reduction in the risk of AMI was observed for doses ranging 50–200 µg·day −1 . In conclusion, very low doses of inhaled corticosteroids may be associated with a reduction in the risk of acute myocardial infarction.
Field hospital in Kathmandu treated 1500 patients in two weeks
Authors: N. Jeffay
Journal: BMJ (2015)

A field hospital that helped victims of the earthquake that hit Nepal on 25 April closed this week after treating 1500 patients, carrying out lifesaving surgery on 90 people, and delivering eight babies.

For almost a fortnight an open area next to Kathmandu’s large military hospital was transformed into a fully functioning hospital with …
Advances in the Genetics of High-Risk Childhood B-Progenitor Acute Lymphoblastic Leukemia and Juvenile Myelomonocytic Leukemia: Implications for Therapy
Authors: Mignon L. Loh, Charles G. Mullighan
Journal: Clinical Cancer Research (2012)

Hematologic malignancies of childhood comprise the most common childhood cancers. These neoplasms derive from the pathologic clonal expansion of an abnormal cancer-initiating cell and span a diverse spectrum of phenotypes, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and myelodysplastic syndromes (MDS). Expansion of immature lymphoid or myeloid blasts with suppression of normal hematopoiesis is the hallmark of ALL and AML, whereas MPN is associated with proliferation of 1 or more lineages that retain the ability to differentiate, and MDS is characterized by abnormal hematopoiesis and cytopenias. The outcomes for children with the most common childhood cancer, B-progenitor ALL (B-ALL), in general, is quite favorable, in contrast to children affected by myeloid malignancies. The advent of highly sensitive genomic technologies reveals the remarkable genetic complexity of multiple subsets of high-risk B-progenitor ALL, in contrast to a somewhat simpler model of myeloid neoplasms, although a number of recently discovered alterations displayed by both types of malignancies may lead to common therapeutic approaches. This review outlines recent advances in our understanding of the genetic underpinnings of high-risk B-ALL and juvenile myelomonocytic leukemia, an overlap MPN/MDS found exclusively in children, and we also discuss novel therapeutic approaches that are currently being tested in clinical trials. Recent insights into the clonal heterogeneity of leukemic samples and the implications for diagnostic and therapeutic approaches are also discussed.
Tri-layered elastomeric scaffolds for engineering heart valve leaflets
Authors: Nafiseh Masoumi, Nasim Annabi, Alexander Assmann, Benjamin L. Larson, Jesper Hjortnaes, Neslihan Alemdar, Mahshid Kharaziha, Keefe B. Manning, John E. Mayer, Ali Khademhosseini
Journal: Biomaterials (2014)
Effect of the Silybin-Phosphatidylcholine Complex (IdB 1016) on the Development of Mammary Tumors in HER-2/neu Transgenic Mice
Authors: Mauro Provinciali, Francesca Papalini, Fiorenza Orlando, Sara Pierpaoli, Alessia Donnini, Paolo Morazzoni, Antonella Riva, Arianna Smorlesi
Journal: Cancer Research (2007)

Abstract Silybin, a main component of the milk thistle of Silybum marianum, has been reported to possess anticancer activity. We investigated the effects of IdB 1016, a complex of silybin with phosphatidylcholine, on the development of mammary tumors appearing spontaneously in HER-2/neu transgenic mice. The mechanisms involved in the antitumor effect of IdB 1016 were evaluated by studying the apoptosis, senescent-like growth arrest, intratumoral leukocyte infiltrate, and the expression of HER-2/neu and p53 in tumoral mammary glands from transgenic mice and in human breast SKBR3 tumor cells. The administration of IdB 1016 delayed the development of spontaneous mammary tumors, reduced the number and size of mammary tumor masses, and diminished lung metastasization in HER-2/neu transgenic mice. In tumoral mammary glands from IdB 1016–treated mice, a down-regulation of HER-2/neu gene expression was associated with an increased senescent-like growth arrest of tumor cells, and an increased infiltrate of neutrophils, CD4, and CD8 T cells. Both senescent-like growth arrest and apoptosis were significantly increased and were associated with a reduced p185HER-2/neu protein and an increased p53 mRNA in SKBR3 in vitro treated with IdB 1016 in comparison with control cells. The results show the antitumor effect of IdB 1016 in the development of spontaneous mammary tumors in HER-2/neu transgenic mice. The effect of IdB 1016 might be related to the down-regulation of HER-2/neu expression and the induction of senescent-like growth arrest and apoptosis through a p53-mediated pathway in tumor cells. [Cancer Res 2007;67(5):2022–9]
Chemokines and alcoholic hepatitis: are chemokines good therapeutic targets?
Authors: Bin Gao, Mingjiang Xu
Journal: Gut (2014)

<h3>Background</h3> Fibromyalgia syndrome (FMS) is a common chronic musculoskeletal disorder characterized by the presence of widespread pain and multiple tender points on physical examination. Deficiency of vitamin D can cause similar musculoskeletal symptoms. Studies regarding vitamin D and FMS relationship have been done in the recent years. Although some studies determined this relationship, other have failed to do so. <h3>Objectives</h3> We aimed to evaluate the relationship between serum vitamin D and parathyroid hormone (PTH) levels and clinical findings in premenopausal FMS patients. <h3>Methods</h3> 77 patients diagnosed with FMS according to new criteria and 60 healthy women were included in this study. We did not include smokers and obese patients. Both groups were questioned for age, height, weight, BMI, education level, working status, number of children, menarche age, living condition (urban, rural), dressing style and sun exposure. Both groups were checked for serum calcium, phosphor, alkaline phosphatase, vitamin D, and PTH levels. FMS new diagnosis criteria scoring, sleep symptom scale, SF-36, Beck depression scale, BASDAI, VAS, revised fibromyalgia impact (FIQR) questionnaires were done to the patient group, and scores were recorded. Serum vitamin D deficiency was described as ≤20 ng/mL, insufficient vitamin D as 21-29 ng/mL and adequate vitamin D as ≥30 ng/mL. <h3>Results</h3> Mean age was 38,68±5,196 and 38,12±4.939 years for patient and control group, respectively. No significant difference was found between the groups for age, height, weight, BMI, education level, working status, number of children, menarche age, living condition (urban, rural), dressing style and sun exposure (p&gt;0.05). Hemoglobin, calcium, phosphor, and alkaline phosphatase were similar in both groups. Serum vitamin D levels were found lower in the patient group when compared with controls (p=0.000). Parathyroid hormone levels were significantly higher in the patient group (p=0.000). Vitamin D levels were ≤20 ng/mL for 32 (42.7%), 21-29 ng/mL for 14 (18.7%) and &gt;30 ng/mL for 29 (38.7) patients. No significant difference between scores were found when patients who had serum vitamin D levels ≤20 ng/mL and &gt;20 ng/mL compared. SF-36, new diagnosis criteria score and FIQR scores were correlated. Patient serum PTH levels and serum vitamin D levels showed negative correlation, and it was significantly higher than in the control group (p=0.000). <h3>Conclusions</h3> We determined an increase in vitamin D deficiency and insufficiency in FMS patients. However, pain and quality of life scores did now show any significant difference when patient who had vitamin D deficiency and patients who did not have were compared. We highly think that receptor inactivity must be investigated before stating that vitamin D levels and FMS disease scores do not show any correlation. <h3>Disclosure of Interest</h3> None Declared
Timing of Initial Cereal Exposure in Infancy and Risk of Islet Autoimmunity
Authors: Jill M. Norris
Journal: JAMA (2003)

Dietary exposures in infancy have been implicated, albeit inconsistently, in the etiology of type 1 diabetes mellitus (DM).To examine the association between cereal exposures in the infant diet and appearance of islet autoimmunity (IA).Birth cohort study conducted from 1994 to 2002 with a mean follow-up of 4 years.Newborn screening for HLA was done at St Joseph's Hospital in Denver, Colo. First-degree relatives of type 1 DM individuals were recruited from the Denver metropolitan area.We enrolled 1183 children at increased type 1 DM risk, defined as either HLA genotype or having a first-degree relative with type 1 DM, at birth and followed them prospectively. We obtained exposure and outcome measures for 76% of enrolled children. Participants had variable lengths of follow-up (9 months to 9 years).Blood draws for the detection of insulin autoantibody, glutamic acid decarboxylase autoantibody, or IA-2 autoantibody were performed at 9, 15, and 24 months and annually thereafter. Children with IA (n = 34) were defined as those testing positive for at least 1 of the autoantibodies on 2 or more consecutive visits and who tested positive or had diabetes on their most recent visit.Children initially exposed to cereals between ages 0 and 3 months (hazard ratio [HR], 4.32; 95% confidence interval [CI], 2.0-9.35) and those who were exposed at 7 months or older (HR, 5.36; 95% CI, 2.08-13.8) had increased hazard of IA compared with those who were exposed during the fourth through sixth month, after adjustment for HLA genotype, family history of type 1 DM, ethnicity, and maternal age. In children who were positive for the HLA-DRB1*03/04,DQB8 genotype, adjusted HRs were 5.55 (95% CI, 1.92-16.03) and 12.53 (95% CI, 3.19-49.23) for initial cereal exposure between ages 0 to 3 months and at 7 months or older, respectively.There may be a window of exposure to cereals in infancy outside which initial exposure increases IA risk in susceptible children.