bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical significance of granulocytic sarcoma in adult patients with acute myeloid leukemia
Authors: Shimizu Hiroaki , Saitoh Takayuki , Hatsumi Nahoko , Takada Satoru , Yokohama Akihiko , Handa Hiroshi , Jimbo Tkahiro , Sakura Toru , Tsukamoto Norifumi , Murakami Hirokazu , Miyawaki Shuichi , Nojima Yoshihisa 
Published: May 2012

To investigate the clinical significance of granulocytic sarcoma (GS) in adults with acute myeloid leukemia (AML), 434 consecutive patients with AML were analyzed retrospectively. Forty‐five patients (10.4%) with GS at diagnosis were younger (P < 0.001), presented with higher white blood cell counts (P = 0.03) and were more likely to conform to French–American–British M4 (P = 0.001) and M5 (P = 0.045) classifications than those without GS. In contrast, no significant difference in frequency of cytogenetic abnormalities was found between the GS and non‐GS groups. Treatment outcomes in 260 patients (40 with GS) who underwent intensive chemotherapy, excluding patients with acute promyelocytic leukemia, were investigated. Complete remission rates did not differ significantly between the GS and non‐GS groups (75.0% vs 79.1%; P = 0.192, respectively) or the 5‐year overall survival (OS) rates (39.9% vs 38.7%; P = 0.749, respectively). However, the GS group had a significantly higher relapse rate than the non‐GS group (74.2% vs 55.3%; P = 0.048) and a significantly lower 5‐year disease‐free survival rate (8.2% vs 25.7%, respectively; P = 0.005). When considered together with the results of multivariate analysis, which identified the presence of GS as an independent predictor for disease‐free survival time, these findings indicate that GS might identify a high‐risk subset of patients with AML. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02324.x, 2012)
Nonclonal growth of preneoplastic cells positive for glutathione S‐transferase P‐form in the rat liver
Authors: Satoh Kimihiko , Yamakawa Daishi , Kasai Kosuke , Hayakari Makoto , Uchida Koji , Miura Tomisato 
Published: May 2012

We investigated the process of induction of preneoplastic cells positive for glutathione S‐transferase P‐form (GST‐P) in the rat liver. AAF (2‐Acetylaminofluorene) mixed with normal rat chow at high concentration (0.04%) induced 517 000 ± 86 000 GST‐P+ single hepatocytes/g liver after 2 weeks followed by induction of a few foci and nodules after 4–6 weeks. Overproduction of GST‐P+ single hepatocytes was dose‐ and time‐dependent, and the induction kinetics were typical of first‐order consecutive reaction, by which induction of the positive cells was nongenetic. Quantitative analysis indicated that the estimated numbers of cells in foci and nodules at 4–6 weeks after exposure to AAF ranged from 2.7 × 104 (214.7) to 3.6 × 106 (221.7) cells, and 2.0 × 104 (214.3) to 2.7 × 106 (221.4) cells, respectively, when analyzed by using two equations. According to the initiated cell theory of Farber, foci and nodules are formed through sequential cell division of 14 to 21‐times or more within a short time period. The rapid growth exceeded the rate of cell division, indicating that the growth of preneoplastic cells is based on a nonclonal penetration mechanism. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02325.x, 2012)
Associations between substance use disorders and major depression in parents and late adolescent–emerging adult offspring: an adoption study
Authors: Marmorstein Naomi R. , Iacono William G. , McGue Matt 
Published: May 2012

AbstractAimsTo examine whether major depressive disorder (MDD) and substance use disorders [SUDs: specifically, nicotine dependence (ND), alcohol use disorders (AUDs), and cannabis use disorders (CUDs)] in parents predicted increased risk for these disorders in late adolescent–emerging adult offspring and, specifically, the extent to which the pattern of risk differed for adopted and non‐adopted youth.ParticipantsLate adolescent and emerging adult participants from the Sibling Interaction and Behavior Study (mean age = 18.8), a community‐based investigation of adopted and non‐adopted adolescents, and their parents (adoptive parents of adopted youth, biological parents of non‐adopted adolescents) were included.MeasurementsStructured interviews were used to assess these disorders.Findings(i) When the same disorder in parents and adolescents was examined, parental MDD was associated with increased risk for MDD among both adopted (P < 0.001) and non‐adopted (P < 0.01) adolescents; in contrast, SUDs were associated with increased risk for the same SUD in non‐adopted offspring (all P < 0.01). (ii) When cross‐SUD effects were examined, for the most part, each SUD was associated with increased risk for other SUDs among non‐adopted but not adopted offspring (most P < 0.05). (iii) When MDD‐SUD associations were examined, parental ND and CUDs predicted increased risk for MDD in non‐adopted (P < 0.001), but not adopted, adolescents. These effects tended to remain significant when adjusting for within‐person comorbidity (P < 0.05).ConclusionsMajor depressive disorder in parents appears to be a risk factor for late adolescent–emerging adult major depressive disorder but not substance use disorder in offspring, with this risk being environmentally mediated. Substance use disorder in parents appears, via genetic mediation, to increase risk of substance use disorder in adolescent offspring, and cannabis and nicotine use disorders in parents contribute similarly to major depressive disorder in those offspring.
Does it matter who you see to help you stop smoking? Short‐term quit rates across specialist stop smoking practitioners in England
Authors: Brose Leonie S. , McEwen Andy , West Robert 
Published: May 2012

AbstractAimsA network of Stop Smoking Services has been set up within the National Health Service (NHS) in England. The services deliver a combination of behavioural support and medication. It is important to establish the degree of variability in quit rates attributable to differences between individual practitioners, to gauge the scope for improvement by training and professional support. The aim of the present analysis was to examine how far short‐term quit rates depend on the practitioner delivering the intervention after adjusting for potential confounding variables.DesignObservational study using routinely collected data.SettingThirty‐one NHS Stop Smoking Services in England.ParticipantsData from 46 237 one‐to‐one treatment episodes (supported quit attempts) delivered by specialist practitioners.MeasurementsThree‐level logistic regression models were fitted for carbon monoxide (CO)‐validated short‐term (4‐week) quit rates. Models adjusted for age, gender, exemption from prescription charges, medication and intervention setting for each treatment episode, number of clients for each practitioner and economic deprivation at the level of the Stop Smoking Service. Secondary analyses included (i) the Heaviness‐of‐Smoking Index (HSI) as predictor and (ii) 4‐week quit rates whether or not confirmed by CO.FindingsDifferences between individual specialist practitioners explained 7.6% of the variance in CO‐verified quit rates after adjusting for client demographics, intervention characteristics and practitioner and service variables (P < 0.001). HSI had little impact on this figure; in quits not necessarily validated by CO, practitioners explained less variance.ConclusionsIndividual stop smoking practitioners appear to differ to a significant degree in effectiveness. It is important to examine what underlies these differences in order to improve selection, training and professional development.
Inhaled and systemic corticosteroid response in severe asthma assessed by alveolar nitric oxide: a randomized crossover pilot study of add‐on therapy
Authors: Williamson Peter A. , Short Philip M. , Vaidyanathan Sriram , Lipworth Brian J. 
Published: May 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Extra fine inhaled corticosteroid formulations such as HFA beclomethasone may be used to target the small airways in asthma. However, it is unclear which outcome measures may detect such small airways effects in patients with severe asthma.WHAT THIS STUDY ADDS• The alveolar fraction of exhaled nitric oxide is not a sensitive outcome measure for following effects of extra fine particle inhaled beclomethasone in severe asthma. However there were significant effects on nitric oxide fractions measured at 50 ml s−1 and bronchial flux with the extra fine formulation, which did not produce significant cortisol suppression.AIMS Alveolar nitric oxide (CANO) is a potential biomarker of small airway inflammation. We investigated effects on CANO of the addition of coarse and fine particle inhaled corticosteroids to standard therapy in severe asthma.METHODS Severe asthmatics taking ≥1600 µg day−1 budesonide or equivalent performed a randomized open‐label crossover study. Subjects with FEV1 < 80%, gas trapping and CANO≥2 ppb entered a 6 week dose‐ramp run‐in of fluticasone/salmeterol(FPSM) 250/50 µg twice daily for 3 weeks, then 500/50 µg twice daily for 3 weeks. Patients then received additional HFA‐beclomethasone diproprionate (BDP) 200 µg twice daily or FP 250 µg twice daily for 3 weeks in a crossover. Participants then received prednisolone(PRED) 25 mg day−1 for 1 week. Nitric oxide, lung function, mannitol challenge, systemic inflammatory markers and urinary cortisol were measured.RESULTS Fifteen completed per protocol: mean (SD) age 51 (12) years, FEV1 58 (13)% predicted, residual volume 193 (100)% predicted and mannitolPD10 177 (2.8) µg. There was no significant difference between FPSM and add‐on therapy for CANO. FPSM/BDP and FPSM/PRED suppressed broncial flux (JawNO) and FENO compared with FPSM alone, but there was no significant difference between FPSM/BDP and FPSM/FP. ECP, e‐selectin and ICAM‐1 were suppressed by FPSM/PRED compared with FPSM and FPSM/FP but not FPSM/BDP. Plasma cortisol was significantly suppressed by FPSM/PRED.CONCLUSION In severe asthma, CANO is insensitive to changes in dose and delivery of inhaled corticosteroids and is not suppressed by systemic corticosteroids. Additional inhaled HFA‐BDP reduced FENO and JawNO without adrenal suppression. There was a trend to reduction in FENO and JawNO with additional FP but this did not reach statistical significance. PRED reduced FENO and JawNO with suppression of systemic inflammatory markers and urinary cortisol.
Functional deficits of pertussis-specific CD4+ T cells in infants compared to adults following DTaP vaccination
Authors: Sharma S K , Pichichero M E 
Published: May 2012

SummaryUnderstanding the immune responses that explain why infants require multiple doses of pertussis vaccine to achieve protection against infection is a high priority. The objective of this study was to compare the function and phenotypes of antigen-specific CD4+ T cells in adults (n = 12), compared to infants (n = 20), following vaccination with acellular pertussis (DTaP) vaccine. Peripheral blood mononuclear cells (PBMCs) were stimulated with pertussis toxoid (PT), pertactin (PRN) and filamentous haemagglutinin (FHA). Multi-parameter flow cytometry was used to delineate CD4+ T cell populations and phenotypes producing interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α and IL-4. Based on surface CD69 expression, infants demonstrated activation of vaccine antigen-specific CD4+ T cells similar to adults. However, among infants, Boolean combinations of gates suggested that type 1 (Th-1) CD4+ T cell responses were confined largely to TNF-α+IL-2+IFN-γ– or TNF-α+IL-2–IFN-γ–. A significantly lower percentage of polyfunctional T helper type 1 (Th1) responses (TNF-α+IFN-γ+IL-2+) and type 2 (Th2) responses (IL-4) were present in the infants compared to adults. Moreover, a significantly higher percentage of infants' functional CD4+ T cells were restricted to CD45RA–CCR7+CD27+ phenotype, consistent with early-stage differentiated pertussis-specific memory CD4+ T cells. We show for the first time that DTaP vaccination-induced CD4+ T cells in infants are functionally and phenotypically dissimilar from those of adults.
Sleep timing may modulate the effect of sleep loss on testosterone
Authors: Schmid Sebastian M. , Hallschmid Manfred , Jauch‐Chara Kamila , Lehnert Hendrik , Schultes Bernd 
Published: May 2012

SummaryBackgroundSleep loss has been shown to reduce secretory activity of the pituitary–gonadal axis in men, but the determinants of this effect are unknown.ObjectiveTo discriminate the effects of sleep duration and sleep timing on serum concentrations of luteinizing hormone (LH), testosterone (T) and prolactin (PRL).MethodsFifteen young, healthy men (27·1 ± 1·3 years; BMI, 22·9 ± 0·3 kg/m2) were examined in a condition of sleep time restriction to 4 h (bedtime, 02:45 –07:00 h) for two consecutive nights and in a control condition of 8 h regular sleep (bedtime, 22:45–07:00 h). After the second night, serum concentrations of LH, T and PRL were monitored over a 15‐h period. In addition, these hormones were measured in serum samples obtained in a further experiment in eight healthy men (24·5 ± 1·1 years; BMI, 23·7 ± 0·6 kg/m2) in the morning after one night of total sleep deprivation, of 4·5 h sleep (bedtime, 22:30–03:30 h), and of regular 7 h sleep (bedtime, 22:30–06:00 h).ResultsSerum LH, T and PRL concentrations showed characteristic diurnal variations across the 15‐h period without any differences between the 4‐ and 8‐h sleep conditions. However, total sleep deprivation and 4·5 h of sleep restricted to the first night‐half markedly decreased morning T and PRL concentrations (both P ≤ 0·05).ConclusionCollectively, our data suggest that the effect of sleep restriction on pituitary–gonadal secretory activity may be modulated by sleep timing. While sleep loss in the early part of the night does not affect T and PRL, early awakening and wakefulness during the second part of the night reduces morning circulating T and PRL concentrations.
Pathophysiology of thrombosis and pregnancy morbidity in the antiphospholipid syndrome
Authors: Oku Kenji , Amengual Olga , Atsumi Tatsuya 
Published: May 2012

Eur J Clin Invest 2012; 42 (10): 1126–1135AbstractIn patients with the antiphospholipid syndrome (APS), the presence of a group of pathogenic autoantibodies called antiphospholipid antibodies causes arteriovenous thrombosis and pregnancy complications. To date, the pathogenicity of the antiphospholipid antibodies has been the focus of analysis. Recently, the antibodies were reported to be capable of direct cell activation, and research on the underlying mechanism is ongoing. The antiphospholipid antibodies bind to the membranes of vascular endothelial cells, monocytes and platelets, provoking tissue factor expression and platelet aggregation. This activation functions as intracellular signalling, independent of the cell type, to activate p38MAPK and the transcription factor NFκB. Currently, there are multiple candidates for the membrane receptors of the antiphospholipid antibodies that are being tested for potential in specific therapy. Recently, APS was reported to have significant comorbidity with complement activation, and it was proposed that this results in placental damage and cell activation and, therefore, could be the primary factor for the onset of pregnancy complications and thrombosis. The detailed mechanism of complement activation remains unknown; however, an inflammation‐inducing substance called anaphylatoxin, which appears during the activation process of the classical complement pathway, is thought to be a key molecule. Complement activation occurs in tandem, regardless of the pathology of APS or the type of antiphospholipid antibody, and it is thought that this completely new understanding of the mechanism will contribute greatly to comprehension of the pathology of APS.
Prenatal and postnatal parental effects on immunity and growth in ‘lactating’ pigeons
Authors: Jacquin Lisa , Blottière Lydie , Haussy Claudy , Perret Samuel , Gasparini Julien 
Published: May 2012

Summary1. Parental effects can have profound consequences on offspring phenotype. Still, little is known about the relative influence of prenatal versus postnatal parental effects of parasite exposure of parents on offspring traits.2. In this study, we investigated the respective role of a prenatal and a postnatal immune challenge of parent feral pigeons (Columba livia) on offspring humoral immunity, growth and survival. We used a cross‐fostering design and antigen injections in biological and foster parents. Feral pigeons are particularly suitable for studying the effects of parental immune challenges because they can affect the phenotype of their young through the transmission of prenatal antibodies in the egg and postnatal antibodies in the ‘crop milk’, a substance produced in the crop of both parents.3. Results show that a prenatal immune challenge of biological parents with keyhole limpet haemocyanin (KLH) antigen decreased the humoral response against KLH of nestlings injected at 14 days of age. In contrast, a postnatal immune challenge of foster parents with KLH enhanced the humoral response of 1‐year‐old juveniles exposed to a second KLH injection, but only when these juveniles had received their first injection at 3 days of age.4. No effect on nestling and juvenile response to another antigen (NDV) was observed, indicating that the changes in humoral responses were specific to the KLH injected in parents. In addition to this, prenatal and postnatal parental immune challenges had an interaction effect on fledging body mass, but no effect on juvenile survival.5. This study shows that pre‐ and postnatal exposure to antigens in parents has contrasted effects on offspring humoral response and growth. Moreover, it shows that the timing of an early exposure to antigens in nestlings has important effects on their specific humoral response.6. This study thus suggests that pre‐ and postnatal parental effects have distinct roles in shaping the phenotype of the offspring on different time scales and calls for further investigations on the potential adaptive role of combined parental effects. Moreover, it suggests that pigeon milk has positive effects on offspring humoral immunity and thus could potentially have a similar immune role as mammalian milk.
Discovered on gastrointestinal stromal tumours 1 (DOG1) expression in non‐gastrointestinal stromal tumour (GIST) neoplasms
Authors: Hemminger Jessica , Iwenofu O Hans 
Published: May 2012

Hemminger J & Iwenofu O H  (2012) Histopathology 61, 170–177Discovered on gastrointestinal stromal tumours 1 (DOG1) expression in non‐gastrointestinal stromal tumour (GIST) neoplasmsAims:  To further characterize discovered on GIST1 (DOG1) antibody clone K9 expression in a broad range of mesenchymal and epithelial tumours.Methods and results:  Formalin‐fixed paraffin‐embedded sections of various tumours were stained with the anti‐DOG1 monoclonal antibody clone K9. The tumours (n = 187) included: gastrointestinal stromal tumours (GISTs) (n = 20); malignant melanoma (n = 19); schwannoma (n = 10); neurofibroma (n = 10); leiomyosarcoma (n = 10); low‐grade fibromyxoid sarcoma (n = 5); angiosarcoma, (n = 10); epithelioid sarcoma (n = 5); clear cell sarcoma (n = 3); synovial sarcoma (n = 10); malignant peripheral nerve sheath tumour (MPNST) (n = 12); alveolar soft part sarcoma (n = 3); chordoma (n = 5); pleomorphic undifferentiated sarcoma (n = 5); perineurioma (n = 4); granular cell tumour (n = 6); acinic cell carcinoma (n = 5); adenocarcinoma, lung (n = 5), colon (n = 10), endometrioid (n = 10), prostate (n = 10) and renal cell (n = 10). Nineteen of 20 GISTs expressed DOG‐1 and 12 of 20 were diffusely positive (≥95%) with moderate to strong intensity. There was focal, predominantly luminal staining of colorectal (three of 10), endometrioid (four of 10) and acinic cell carcinomas (four of five). One case each of spindle cell/desmoplastic melanoma (2+), schwannoma (trace) and MPNST (2+) showed DOG‐1 expression.Conclusions:  Our study supports that DOG‐1 is a highly sensitive and specific marker for GISTs and also highlights hitherto unrecognized and unusual patterns of expression in non‐mesenchymal neoplasms.
Hepatic sinusoidal obstruction syndrome (SOS) reduces the effect of oxaliplatin in colorectal liver metastases
Authors: Vreuls Celien P H , Van Den Broek Maartje A , Winstanley Alison , Koek Ger H , Wisse Eddie , Dejong Cornelis H , Olde Damink Steven W M , Bosman Fred T , Driessen Ann 
Published: May 2012

Vreuls C P H, Van Den Broek M A, Winstanley A, Koek G H, Wisse E, Dejong C H, Olde Damink S W M, Bosman F T & Driessen A  (2012) Histopathology 61, 314–318Hepatic sinusoidal obstruction syndrome (SOS) reduces the effect of oxaliplatin in colorectal liver metastasesAims:  Oxaliplatin is an important chemotherapeutic agent used to reduce hepatic colorectal metastases, resulting in tumour reduction and permitting surgical resection. This treatment has significant side effects, as oxaliplatin can induce sinusoidal obstruction syndrome (SOS) in the non‐tumour‐bearing liver, resulting in increased morbidity. We hypothesized that SOS might impede hepatic perfusion, thereby interfering with the tumour environment and attenuate the response to the chemotherapy.Methods and results:  From the prospective database of the Maastricht University Medical Centre we collected 50 patients with hepatic colorectal carcinoma metastases. All patients received neo‐adjuvant oxaliplatin followed by partial hepatectomy. Metastases and non‐tumour‐bearing liver were studied histopathologically. Thirty‐two of 50 (64%) patients showed SOS lesions, classified as mild (26%) and moderate–severe (38%). The response to treatment, as expressed in the tumour regression grade (TRG), was grade 1 (10%); grade 2 (14%); grade 3 (28%); grade 4 (32%) and grade 5 (16%). Statistical analysis showed that a higher grade of SOS was associated with a higher grade of TRG (P = 0.016).Conclusion:  Developing SOS is associated with a lower tumour response to neo‐adjuvant oxaliplatin treatment. Hepatic hypoperfusion due to sinusoidal obstruction syndrome might induce hepatic hypoxia, diminishing the response to chemotherapy.
Involvement of α‐ and β‐catenins and E‐cadherin in the development of mammary phyllodes tumours
Authors: Tsang Julia Y S , Mendoza Paulo , Lam Christopher C F , Yu Alex M C , Putti Thomas C , Karim Rooshdiya Z , Scolyer Richard A , Lee Cheok Soon , Tan Puay Hoon , Tse Gary M 
Published: May 2012

Tsang J Y S, Mendoza P, Lam C C F, Yu A M C, Putti T C, Karim R Z, Scolyer R A, Lee C S, Tan P H & Tse G M  (2012) Histopathology 61, 667–674Involvement of α‐ and β‐catenins and E‐cadherin in the development of mammary phyllodes tumoursAims:  Phyllodes tumours (PT) are rare but clinically important fibroepithelial tumours of the breast. β‐Catenin, a key component in Wnt signalling, has been shown to be important in the development of PT. It also functions as a component of the cadherin complex, which may therefore be implicated in PT pathogenesis. By assessing stromal α‐catenin, β‐catenin and E‐cadherin expression in 158 PT cases using immunohistochemistry and examining associations with clinicopathological features, we aimed to determine the role of these proteins in PT pathogenesis.Methods and results:  Cytoplasmic β‐catenin correlated with α‐catenin expression. A significantly higher expression of both markers was observed in borderline than in benign PT (P = 0.003 and <0.001, respectively), but a lower level was found in malignant PT. Cytoplasmic E‐cadherin expression was significantly higher in borderline and malignant than in benign PT (P = 0.001 and 0.012, respectively), but was not correlated with other markers. Both E‐cadherin and α‐catenin showed stronger correlations with histological parameters than β‐catenin. α‐Catenin showed a significant correlation with recurrence (P = 0.005 and 0.016, respectively).Conclusions:  α‐ and β‐catenins may be important in the early stages of PT development, while E‐cadherin may be required for malignant development. The correlation of α‐catenin expression with tumour recurrence may be relevant in predicting PT behaviour.