tbuckley/cabot-search huggingface dataset:
Microgranular variant of acute promyelocytic leukemia in children.
Authors: A Rovelli, A Biondi, A Cantù Rajnoldi, V Conter, G Giudici, M Jankovic, A Locasciulli, C Rizzari, L Romitti, M R Rossi
Journal: Journal of Clinical Oncology (1992)

PURPOSE The microgranular variant (M3v) of acute promyelocytic leukemia (APL) rarely has been reported in a pediatric series of acute nonlymphoblastic leukemia (AnLL). We reviewed the clinical and biologic features of childhood M3v cases in our AnLL series. PATIENTS AND METHODS From January 1970 to January 1991, 11 children with M3v were admitted and treated at our center. A diagnosis was made according to French-American-British (FAB) criteria. Morphologic examination, cytochemical analysis, and immunophenotyping were performed by a single pathologist. From January 1984, the diagnosis was confirmed by cytogenetic and, subsequently, by molecular analysis on frozen material. RESULTS In our series, the overall incidence of children with APL was unusually high, 31.2% of the AnLL and M3v constituted one case in every four cases of APL. Even restriction of the analysis to the time when either cytogenetic and DNA studies confirmed the diagnosis, the incidence did not change. The immunophenotype of M3v cases was identical to that described for the hypergranular type, but an unexpected association of CD2 with M3v was shown. The onset was characterized by marked hyperleukocytosis (median WBC count, 87 x 10(9)/L) unlike classic APL. Disseminated intravascular coagulation (DIC) was always present and severe. Hyperleukocytosis and DIC were responsible for the high incidence of deaths for hemorrhagic events in the first days after onset (eight of 11 patients). CONCLUSIONS In our experience, for unknown reasons, M3v may occur in childhood more than generally was considered. The clinical course and prognosis seem worse in M3v than in typical APL cases.
Morphologic Transformation and Chromosomal Changes Induced by Chemical Carcinogens in Skin Fibroblasts From Patients With Familial Adenomatosis Coli&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: M Miyaki, N Akamatsu, T Ono, A Tonomura, J Utsunomiya
Journal: JNCI Journal of the National Cancer Institute (1982)

Skin fibroblasts from patients with familial adenomatosis coli (AC) and normal individuals were treated once with the carcinogen 4-nitroquinoline 1-oxide or N-methyl-N'-nitro-N-nitrosoguanidine and then passaged sequentially. Morphologically altered cells appeared in the cultures of carcinogen-treated AC fibroblasts at passages 6-8 (days 100-140) after treatment with the carcinogens, but carcinogen-treated normal cells and untreated AC and normal cells did not become altered even after cultivation for 25 passages. The cultures containing morphologically altered cells showed characteristics of transformed cells, such as a high frequency of colony formation in soft agarose, increased growth ability, and chromosomal abnormalities. The results suggest tha AC patients have increased susceptibility to morphologic transformation and chromosomal changes induced by chemical carcinogens.
Importance of inhalation device in asthma and COPD: A consensus using Delphi
Authors: Vincent Ninane, Guy Brusselle, Renaud Louis, Lieven Dupont, Giuseppe Liistro, Wilfried De Backer, Marc Shlesser, Walter Vincken
Journal: European Respiratory Journal (2013)

Asthma and COPD treatment guidelines give little recommendations regarding the use of inhalation devices (ID).  We performed a Delphi survey addressing the choice and interchangeability of ID, the patients’ training and the role of cost in ID selection.  A 13-items internet-based and self-administered questionnaire was developed and validated. Statistics included median and interquartile range.  50 experts in asthma and COPD participated. The level of consensus was good (G) or very good (VG) for nearly all questions after two rounds. The choice of the ID was judged as important as the active drug (VG) and should be driven by ease of use (G to VG) and teaching (VG). Other significant recommendations were oral rather than written instructions (G), systematic monitoring, predominant educational role of chest physicians and paramedics, discouraged interchangeability of ID (G), no switch without medical consultation nor by the pharmacist (VG). The cost of the ID was less important in ID selection (G) and switching by the pharmacist for cost reasons was considered unacceptable (VG).  In conclusion, the present study confirms that the ID is equally important as the active substance when selecting therapy and underscores the central place of training and monitoring.
Long-Term Faecal Continence in Infants Born with Anorectal Malformations
Authors: R Ackroyd, S Nour
Journal: Journal of the Royal Society of Medicine (1994)

In a retrospective study of 92 patients admitted between 1975 and 1986 with anorectal malformations, we reviewed the faecal continence according to the level of their anomaly using a scoring system taken from Pescatori et al. The results of the different operative procedures were compared. Forty-seven of the 50 patients in the low anomaly group had complete faecal continence. Two died from associated anomalies and one infant had incomplete continence. This child had an associated neural tube defect. Of eight patients in the intermediate group, three had good results while two were incontinent: three patients died from associated anomalies. There were 34 patients with high anomalies, 27 of whom showed a wide range of faecal control from complete continence to different degrees of incontinence. Seven infants died from septicaemia and/or associated anomalies. The anatomical level of the lesion and the presence or absence of any associated neurological defect were the main determinants of outcome. The sex of the child and the operative procedure employed to correct the anomaly appeared to be less important.
Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia
Authors: John C. Byrd, Joseph M. Flynn, Thomas J. Kipps, Michael Boxer, Kathryn S. Kolibaba, David J. Carlile, Guenter Fingerle-Rowson, Nicola Tyson, Jamie Hirata, Jeff P. Sharman
Journal: Blood (2015)
Abstract 90: Bendavia (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves ADP-Stimulated Mitochondrial Respiration in Cardiomyocytes Isolated From Dogs with Chronic Heart failure
Authors: Hani Sabbah, Ramesh C Gupta, Sharad Rastogi, Paula Mohyi, Kristina Szekely
Journal: Circulation Research (2014)

Background: Mitochondria (MITO) of failed human hearts and hearts of dogs with experimental heart failure (HF) manifest structural and functional abnormalities characterized by hyperplasia and reduced organelle size and reduced respiration. These abnormalities lead to reduced ATP synthesis that adversely impacts LV function. We previously showed that chronic therapy (3 months) with Bendavia (MTP-131), a novel mitochondria-targeting peptide, improves LV systolic function in dogs with heart failure (HF), reverses MITO abnormalities and normalizes mitochondria ATP synthesis in myocardium from Bendavia-treated HF dogs. In the present study we examined the direct effects of Bendavia on mitochondria ADP-stimulated state 3 respiration in freshly isolated cardiomyocytes from dogs with advanced chronic HF. Methods: Cardiomyocytes were isolated from LV free wall of 3 untreated dogs with HF produced by intracoronary microembolizations (LV ejection fraction &lt;30%). A standard collagenase-based enzymatic process was used for isolation that yielded ~70% viable rod-shaped cardiomyocytes that excluded trypan blue. Equal aliquotes of cardiomyocytes were incubated in 0, 0.01, 0.10, 1.0 and 10 μM concentration of Bendavia for one hour at 37°C. At the end of incubation, ADP-stimulated state-3 respiration was measured using a Clark electrode system and quatified in nAtom Oxygen/min/mg protein. Results: State-3 respiration in the absence of Bendavia (Vehicle-Control) was 248±9 nAtom Oxygen/min/mg protein. Compared to vehicle-control, incubation of failing cardiomyocytes with Bendavia significantly increased state-3 respiration to 303±33 at 0.01 μM, p&lt;0.05; 405±39 at 0.10 μM, p&lt;0.05; 371±28 at 1.0 μM, p&lt;0.05; and 346±29 at 10.0 μM, p&lt;0.05. Conclusions: Results of this study indicate that the effects of Bendavia on mitochondrial respiration in cardiomyocytes is direct and not a consequence of improved global LV structure or function. Furthermore, the results indicate that the improvement in mitochondrial respiration after treatment with Bendavia can occur early after initiation of therapy (within one hour) and is dose-dependent up to concentrations of 0.10 μM.
Juvenile spring eruption: an outbreak report and systematic review of the literature
Authors: S.A.G. Lava, G.D. Simonetti, M. Ragazzi, S. Guarino Gubler, M.G. Bianchetti
Journal: British Journal of Dermatology (2013)

Juvenile spring eruption of the helices of the ears is a distinctive sun-induced condition appearing on the light-exposed skin of the ears, typically in boys and young men in early spring.To determine clinical features and outcome of juvenile spring eruption of the ears.We report a new outbreak in 14 Swiss-Italian children. A systematic search of the literature was also performed.Five outbreaks in children involved a total of 203 cases (boys, 72%), and three outbreaks in young adults involved 223 male subjects. A further 54 sporadic cases were found: 41 among children (boys, 97%) and 13 among young adult males. The typical presentation included itching and diffuse erythema of both ears starting in the evening after exposure to bright sunlight during cold weather, followed within 24-48 h by papules or blisters. No other organ system was involved. The subjects recovered spontaneously without sequelae within 1-2 weeks. In New Zealand, among 162 school-aged boys, 20 developed the condition.A limitation is that the analysis was based upon the scanty available literature. Juvenile spring eruption is a self-limiting and generally easy recognizable variant of polymorphic light eruption. Outbreaks tend to appear on sunny and cold spring days. Paediatricians and general practitioners might rapidly develop the skills necessary to clinically appreciate this condition.
Declining sperm count
Authors: J. De Mouzon, A Spira, P Thonneau, L Multigner
Journal: BMJ (1996)

Declining sperm countSemen quality has declined among men born in France since 1950 EDrroR,-Several recent papers have reported a possible decrease in sperm counts.`15Three of them were based on data collected in single laboratories, from a relatively low number of fertile men (between 302 and 1351).`-3Their conclu- sions were in favour of a decline related to the year of birth1 or to the year of the measurement3 or of no change.2The two other papers were reviews of the same published papers, the first concluding that sperm counts had decreased and
Involvement and functional impairment of the CD34+CD38−Thy-1+ hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8
Authors: Lars Nilsson, Ingbritt Åstrand-Grundström, Kristina Anderson, Ingrid Arvidsson, Peter Hokland, David Bryder, Lars Kjeldsen, Bertil Johansson, Eva Hellström-Lindberg, Robert Hast, Sten Eirik W. Jacobsen
Journal: Blood (2002)
Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies.
Authors: S A Giralt, C F LeMaistre, H M Vriesendorp, B S Andersson, M Dimopoulos, J Gajewski, K Van Besien, R Mehra, D Przepiorka, I Khouri
Journal: Journal of Clinical Oncology (1994)

To determine the efficacy and toxicity of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) as the conditioning regimen for allogeneic bone marrow transplantation (BMT) in patients with hematologic malignancies.Seventy-nine patients underwent BMT from a human leukocyte antigen (HLA)-identical sibling using cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis. Thirty-four patients had early leukemia (acute leukemia or lymphoblastic lymphoma in first remission, chronic myelogenous leukemia [CML], or refractory anemia [RA]), and 45 patients had more advanced disease. Patients received etoposide 1,500 mg/m2 on day -8, followed by cyclophosphamide 60 mg/kg/d on days -7 and -6, and 10.2 Gy of TBI administered in six fractions of 1.7 Gy given twice daily for 3 days from day -3 to -1. Donor bone marrow was harvested and infused on day 0.Patients with early leukemia had a disease-free survival rate of 53% +/- 9% and an overall survival rate of 57% +/- 10% at 3 years. Patients with advanced disease had a disease-free survival rate of 15% +/- 5% and overall survival rate of 17% +/- 5%. The actuarial relapse rate for the early-leukemia group is 33% +/- 9% versus 69% +/- 9% for patients with more advanced disease. Severe toxicity was most frequently manifested as pulmonary hemorrhage followed by multiorgan failure and death. The 100-day mortality rate for the early-leukemia group was 10% versus 50% for patients with more advanced disease.The combination of cyclophosphamide, etoposide, and TBI is a relatively safe and effective preparative regimen for patients with early hematologic malignancies. Controlled trials are needed to evaluate critically this combination versus other standard preparative regimens. Greater toxicity was observed in patients with advanced disease, and this program does not appear to offer any advantage over other regimens.
Late-breaking abstract: Azithromycin plays an important role in treating diffuse panbronchiolitis by specific inhibition of CXCL-2/MIP-2 and IL-17A in T cells
Authors: Huiping Li
Journal: European Respiratory Journal (2014)

Background: Azithromycin (AZM), is a novel macrolide antibiotic that is effective at treating diffuse panbronchiolitis (DPB), although the underlying mechanism remains unclear. Herein, we have studied the effects of AZM on the expression of chemokine (C-X-C motif) ligand 2/macrophage inflammatory protein 2 (CXCL-2/MIP-2) and interleukin-17A (IL-17A) in Jurkat T cells and human DPB-derived peripheral blood lymphocytes (PBLs) in vitro.  Methods: Human Jurkat T cells were dose-dependently treated with AZM, or erythromycin (EM) as a positive control. In addition, 40 DPB patients and 12 healthy subjects were enrolled, and their PBLs treated with optimal doses of AZM and EM. As a negative control, cells were treated with an equal volume of dimethylsulfoxide(DMSO). After 24 h, relative mRNA expression levels of IL-17A and CXCL-2 were analyzed. Eight of the DPB patients were treated for 1 wk with AZM, and their PBLs were stimulated with AZM or EM prior to determining mRNA and protein expression levels of IL-17A and CXCL-2.  Results: AZM significantly inhibited mRNA and protein levels of CXCL-2 and IL-17A (P   Conclusions: Both IL-17A and CXCL-2 were highly expressed in PBLs of DPB patients. Moreover, the inhibitory effects on AZM the transcriptional and protein expression of CXCL-2 and/or IL-17A, has revealed a previously under-appreciated mechanism of action of of low-dose AZM in DPB.
Targeting TGR5 in cholangiocyte proliferation: default topic
Authors: Cecília M P Rodrigues, Han Moshage
Journal: Gut (2015)

The transmembrane G protein-coupled receptor TGR5 binds to and is activated by bile acids.1 ,2 TGR5 is widely distributed, in animals and humans, in the gallbladder, liver, brown adipose tissue, muscle, intestine, kidney, placenta and brain. In the liver, TGR5 appears in sinusoidal endothelial cells, bile duct epithelial cells and Kupffer cells. Interestingly, the ubiquitous TGR5 expression positions previously unsuspected tissues such as muscle, brain and adipose tissue, and cells such as macrophages and endothelial cells, as potential targets of bile acid signalling. Bile acid binding to TGR5 activates multiple signalling routes involved in a multitude of processes thus potentially affecting metabolism, inflammation, fibrosis and carcinogenesis. Lithocholic acid is the strongest natural ligand of TGR5,1 ,2 while INT-777 is a semisynthetic TGR5 agonist.3 Further development of semisynthetic bile acid analogues that target TGR5 or intracellular nuclear receptors, such as the Farnesoid X receptor (FXR), holds great expectations to treat chronic liver disease, hepatocellular cancer and extrahepatic inflammatory and metabolic diseases. Randomised, placebo controlled clinical trials for the treatment of non-alcoholic steatohepatitis and primary biliary cirrhosis with FXR agonist obeticholic acid are the first initiated trials.

Cholangiocarcinoma (CCA) is the second most common primary liver tumour and accounts for ∼3% of all …
Cysteine‐Mediated Redox Regulation of Cell Signaling in Chondrocytes Stimulated With Fibronectin Fragments
Authors: Scott T. Wood, David L. Long, Julie A. Reisz, Raghunatha R. Yammani, Elizabeth A. Burke, Chananat Klomsiri, Leslie B. Poole, Cristina M. Furdui, Richard F. Loeser
Journal: Arthritis & Rheumatology (2015)

Objective Oxidative posttranslational modifications of intracellular proteins can potentially regulate signaling pathways relevant to cartilage destruction in arthritis. In this study, oxidation of cysteine residues to form sulfenic acid (S‐sulfenylation) was examined in osteoarthritic (OA) chondrocytes and investigated in normal chondrocytes as a mechanism by which fragments of fibronectin (FN‐f) stimulate chondrocyte catabolic signaling. Methods Chondrocytes isolated from OA and normal human articular cartilage were analyzed using analogs of dimedone that specifically and irreversibly react with protein S‐sulfenylated cysteines. Global S‐sulfenylation was measured in cell lysates with and without FN‐f stimulation by immunoblotting and in fixed cells by confocal microscopy. S‐sulfenylation in specific proteins was identified by mass spectroscopy and confirmed by immunoblotting. Src activity was measured in live cells using a fluorescence resonance energy transfer biosensor. Results Proteins in chondrocytes isolated from OA cartilage were found to have elevated basal levels of S‐sulfenylation relative to those of chondrocytes from normal cartilage. Treatment of normal chondrocytes with FN‐f induced increased levels of S‐sulfenylation in multiple proteins, including the tyrosine kinase Src. FN‐f treatment also increased the levels of Src activity. Pretreatment with dimedone to alter S‐sulfenylation function or with Src kinase inhibitors inhibited FN‐f–induced production of matrix metalloproteinase 13. Conclusion These results demonstrate for the first time the presence of oxidative posttranslational modification of proteins in human articular chondrocytes by S‐sulfenylation. Due to the ability to regulate the activity of a number of cell signaling pathways, including catabolic mediators induced by fibronectin fragments, S‐sulfenylation may contribute to cartilage destruction in OA and warrants further investigation.
Temporal Trends and Sex Differences in Revascularization and Outcomes of ST-Segment Elevation Myocardial Infarction in Younger Adults in the United States
Authors: Sahil Khera, Dhaval Kolte, Tanush Gupta, Kathir Selvan Subramanian, Neel Khanna, Wilbert S. Aronow, Chul Ahn, Robert J. Timmermans, Howard A. Cooper, Gregg C. Fonarow, William H. Frishman, Julio A. Panza, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2015)
Interleukin-2 therapy in patients with metastatic malignant melanoma: a phase II study.
Authors: D R Parkinson, J S Abrams, P H Wiernik, A A Rayner, K A Margolin, D A Van Echo, M Sznol, J P Dutcher, F R Aronson, J H Doroshow
Journal: Journal of Clinical Oncology (1990)

Forty-seven patients with metastatic malignant melanoma were treated with two 5-day cycles of 100,000 U/kg recombinant interleukin-2 (IL-2) intravenously (IV) every 4 hours separated by 1 week. This dose and schedule of IL-2 were identical to those used in a previous combined IL-2 and lymphokine-activated killer (LAK) cell phase II clinical trial of the IL-2/LAK Working Group. Patient eligibility criteria, and clinical management guidelines were similar to those used in the previous trial. Forty-six patients were assessable for response. Objective responses were observed in 10 of 46 patients (two complete responses [CRs], eight partial responses [PRs]) or 22% with responses occurring in lung and liver as well as lymph nodes and subcutaneous sites. The median response duration was 8 months. Toxicity was significant; three patients developed myocardial infarction, and one patient died during therapy. Overall the toxicity and response rate for single-agent IL-2 are similar to that observed with IL-2 administered in combination with LAK cells in the previous trial. These results suggest that single-agent therapy with IL-2 when administered in this schedule has significant antimelanoma activity in humans, and that LAK cells generated from peripheral blood add little to the antimelanoma activity of this dose and schedule of IL-2.
Transplantation Antigens (H-2) on Virally and Chemically Transformed BALB/3T3 Fibroblasts in Culture2
Authors: Evangelia Tsakraklides, Clark Smith, John H. Kersey, Robert A. Good
Journal: JNCI Journal of the National Cancer Institute (1974)

Quantitative absorptions of monospecific and oligospecific H-2d antisera were used to test differences in concentration of histocompatibility antigens on nontransformed BALB/3T3 (clone A31) mouse fibroblasts; on A31 fibroblasts transformed by Kirsten murine sarcoma virus (MSV), simian virus 40 (SV40), and 3-methylcholanthrene; and on spontaneously transformed A31 fibroblasts. Cells transformed spontaneously and by MSV showed increased H-2 concentration, whereas those transformed chemically and by SV40 had decreased H-2 antigen specificities. The findings correlated with the lower in vivo immunogenicity of cells transformed spontaneously and by MSV and with the higher immunogenicity of cells transformed chemically and by SV40. An inverse relationship between tumor-associated and histocompatibility antigens was suggested.
Mitotic Circadian Rhythm in a Fast-Growing and a Slow-Growing Hepatoma: Mitotic Rhythm in Hepatomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Julian M. Echave Llanos, Rosa E. Nash
Journal: JNCI Journal of the National Cancer Institute (1970)

A circadian rhythm is reported in the mitotic activity of a fast-growing hepatoma (SS1K) and a slow-growing hepatoma (SS1H). These tumors are 2 different sublines of a spontaneous hepatoma transplanted in 1949 by J. W. Wilson, Brown University, Providence, Rhode Island, into C3H/StWi strain. Significantly higher values in mitotic activity were observed during light periods than during dark periods. The SS1K hepatoma presented higher values than the SS1H hepatoma during the dark period, but the values for both hepatomas were not different during the light period. The variation was significantly higher in the slow-growing hepatoma and approached that of the immature liver.
Impact of diabetes in patients admitted with acute exacerbation of COPD
Authors: Rosalind Benson, Nosheen Kazmi, Anne Pocock, Syed Huq, Sanjeev Agarwal
Journal: European Respiratory Journal (2012)

Background  In patients admitted with acute exacerbation of COPD (AECOPD), the presence of concomitant diabetes has been shown to prolong the length of stay (LOS) and increase the risk of death. However, it is not clear if this impacts on readmission rates.  Methods  A retrospective study of consecutive patients admitted with AECOPD in an acute teaching hospital.  Results  67 patients (45% male) with a mean (SD) age of 72 (12) years and % predicted FEV1 of 55 (20) were included in the study. 15 (22%) of them had concomitant diabetes with a mean (SD) HbA1C of 6.8 (1.3).  No significant difference in LOS or mortality within one year was noted between the two groups. However, there was a trend for increased readmission rates in the following year in patients admitted with AECOPD and concomitant diabetes.  Conclusions  Our study suggests that the presence of DM might have an impact on readmission rates following a hospital admission with AECOPD. Prospective studies with larger sample size are needed to evaluate this further.