bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic alterations and gene expression in primary diffuse large B‐cell lymphomas of immune‐privileged sites: the importance of apoptosis and immunomodulatory pathways
Authors: Booman M , Szuhai K , Rosenwald A , Hartmann E , Kluin‐Nelemans HC , de Jong D , Schuuring E , Kluin PM 
Published: July 2008

AbstractPrimary diffuse large B‐cell lymphomas of different immune‐privileged sites (IP‐DLBCLs) share many clinical and biological features, such as a relatively poor prognosis, preferential dissemination to other immune‐privileged sites, and deletion of the HLA region, which suggests that IP‐DLBCL represents a separate entity. To further investigate the nature of IP‐DLBCL, we investigated site‐specific genomic aberrations in 16 testicular, nine central nervous system (CNS), and 15 nodal DLBCLs using array CGH. We also determined minimal common regions of gain and loss. Using robust algorithms including multiple testing procedures and the ACE‐it script, which is specifically designed for this task, the array CGH data were combined with gene expression data to explore pathways deregulated by chromosomal aberrations. Loss of 6p21.32–p25.3, including the HLA genes, was associated with both types of IP‐DLBCL, whereas gain of 2p16.1–p25.3 was associated with nodal DLBCL. Gain of 12q15–q21.1 and 12q24.32–q24.33 was associated with CNS DLBCL and gain of 19q13.12–q13.43 with testicular DLBCL. Analysis of candidate genes in site‐specific regions and minimal common regions revealed two major groups of genes: one involved in the immune response, including regulation of HLA expression, and the other involved in apoptosis, including the p53 pathway. Many of these genes were also involved in homozygous deletions or high‐level gains. The presence of both shared and site‐specific aberrations in CNS and testicular DLBCLs underlines the concept of IP‐DLBCL but also indicates that IP‐DLBCLs of the CNS and testis do not form a single entity. The observed aberrations emphasize the importance of the deregulation of anti‐tumour immune response and apoptosis pathways. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Dynamics of immune granuloma formation in a Leishmania braziliensis‐induced self‐limiting cutaneous infection in the primate Macaca mulatta
Authors: Souza‐Lemos C , de‐Campos SN , Teva A , Côrte‐Real S , Fonseca EC , Porrozzi R , Grimaldi Jr G 
Published: July 2008

AbstractIn order to unravel the physiopathology of leishmaniasis in humans, it is necessary to better understand how Leismania are able to survive for years within immunologically active granulomas. In the present study, we used a macaque (Macaca mulatta) model of infection with Leishmania braziliensis as a means of assessing the usefulness of this primate system. This model more closely mirrors human protective immunity to Leishmania than the murine model; therefore, we used it to study the host inflammatory granulomatous response involved in the control of cutaneous leishmaniasis. Infected primates developed localized long‐term skin ulcerations, but complete spontaneous clinical healing occurred in all infected animals. The infection induced the recruitment and activation of inflammatory mast cells, granulocytes, mononuclear phagocytes, and lymphocytes at the site of infection. During the acute reaction, polymorphonuclear leukocytes were more prominent than other cell types and apparently destroyed many parasites; macrophages then rapidly engulfed dying neutrophils together with their parasitic cargo. In the chronic phase, persisting parasites induced a typical T helper (Th) cytokine, type 1‐mediated, immunity‐induced granulomatous reaction. By this time, more or less differentiated macrophage accumulations were found, and these evolved to become mature tissue granulomas consisting of all the specific cell types found within human granulomas. In the healing stage, fibroblasts proliferated at the periphery and finally invaded the granulomas with fibrotic substitution. These findings point to the feasibility of using this model to elucidate the potentially disabling Th1‐cell mechanisms that may eventually render the host granulomatous response inadequate for fighting L. braziliensis infections. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Beneficial effects of prolonged systemic administration of PlGF on late outcome of post‐ischaemic myocardial performance
Authors: Roncal C , Buysschaert I , Chorianopoulos EK , Georgiadou M , Meilhac O , Demol M , Michel J‐B , Vinckier S , Moons L , Carmeliet P 
Published: July 2008

AbstractRecent evidence indicates that an imbalance between cardiomyocyte hypertrophy and blood vessel growth in the remote myocardium may contribute to heart failure in ischaemic heart disease. It remains, however, largely unknown which angiogenic factors are capable of stimulating vessel growth in the remote myocardium after myocardial infarction (MI) and whether systemic, rather than local, administration of such factors suffices to ameliorate post‐MI cardiac recovery. We therefore analysed the effect of systemic placental growth factor (PlGF) delivery on myocardial recovery post‐MI in mice. MI was induced by permanent ligation of the left anterior descending coronary (LAD) artery in C57Bl6/J mice, followed by systemic injection of a PlGF adenovirus, resulting in elevated circulating levels of PlGF for 4 weeks. Functional and morphological analysis revealed that PlGF treatment induced cardiomyocyte hypertrophy and improved cardiac recovery at day 28 post‐MI. PlGF stimulated angiogenesis in the infarct border and vessel enlargement in the remote myocardium. In this mouse model, capillary‐to‐cardiomyocyte ratios in the remote myocardium were maintained post‐MI, but PlGF increased the vascular perfusion area in balance with the cardiomyocyte hypertrophy. Overall, systemic delivery of PlGF improves cardiac performance and promotes adaptive remodelling of the post‐MI heart. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
MYC translocation‐negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation
Authors: Leucci E , Cocco M , Onnis A , De Falco G , van Cleef P , Bellan C , van Rijk A , Nyagol J , Byakika B , Lazzi S , Tosi P , van Krieken H , Leoncini L 
Published: July 2008

AbstractThe molecular feature of Burkitt lymphoma (BL) is the translocation that places c‐Myc under the control of immunoglobulin gene regulatory elements. However, there is accumulating evidence that some cases may lack an identifiable MYC translocation. In addition, during the EUROFISH project, aiming at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split‐signal as well as a dual‐fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c‐Myc, in BL cases, to clarify whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post‐transcriptional level. Several studies have reported their involvement in cancer and their association with fragile sites in the genome. They have also been shown to control cell growth, differentiation, and apoptosis, suggesting that these molecules could act as tumour suppressors or oncogenes. Our results demonstrated a modulation of specific miRNAs. In particular, down‐regulation of hsa‐let‐7c was observed in BL cases, compared to normal controls. More interestingly, hsa‐mir‐34b was found to be down‐regulated only in BL cases that were negative for MYC translocation, suggesting that this event might be responsible for c‐Myc deregulation in such cases. This hypothesis was further confirmed by our in vitro experiments, which demonstrated that increasing doses of synthetic hsa‐mir‐34b were able to modulate c‐Myc expression. These results indicate for the first time that hsa‐mir‐34b may influence c‐Myc expression in Burkitt lymphoma as the more common aberrant control exercised by the immunoglobulin enhancer locus. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Amyloid fibril composition is related to the phenotype of hereditary transthyretin V30M amyloidosis
Authors: Ihse E , Ybo A , Suhr OB , Lindqvist P , Backman C , Westermark P 
Published: July 2008

AbstractSwedish familial systemic amyloidosis with polyneuropathy (FAP) depends on a mutation leading to a methionine‐for‐valine substitution in transthyretin. The disease appears with different clinical manifestations, including age of onset and involvement of the heart. Liver transplantation is currently the only curative treatment, but progressive cardiomyopathy may occur post‐transplant. Two amyloid deposition patterns have previously been described in the heart. In one, the amyloid consists partially of transthyretin fragments and is weakly stainable by Congo red, while in the other, only full‐length molecules are found and the fibrils have a strong affinity for Congo red. The present study aimed to see whether these morphological and biochemical variations have clinical implications. Subcutaneous adipose tissue biopsies were taken from 33 patients with Val30Met FAP and examined by microscopy, electrophoresis and western blot. Clinical data included age, sex, duration of disease and echocardiographic determination of the interventricular septum (IVS) thickness. It was found that fibrils composed of only full‐length transthyretin were associated with early age of onset (44.8 ± 12.9 years), no clinical cardiac involvement and a strong affinity for Congo red. In contrast, presence of transthyretin fragments in the amyloid was associated with late age of onset (67.3 ± 7.0 years), signs of cardiac involvement and weak Congo red staining. For each individual, the same molecular type of amyloid was found in different organs. This is the first report showing that variations in clinical appearance of familial ATTR amyloidosis are associated with specific structural differences in the amyloid fibrils, and therefore may have a molecular cause. The molecular type of amyloid can be determined from a subcutaneous fat tissue biopsy. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Stellenwert der Phytotherapie beim benignen Prostatasyndrom. Pflanzlich definierte Prostatamedikamente verlangen nach Anerkennung
Authors: Popa Gerd 
Published: July 2008

AbstractWissenschaftlich nachgewiesene Wirksamkeit, Nebenwirkungsarmut und weiter bestehende Preiswürdigkeit, sowie die bekannt hohe Einnahmetreue (Compliance) der Patienten sprechen trotz aller aufgezeigten Widrigkeiten für eine positive Zukunftsperspektive dieser Präparategruppe.
Neuropsychological sequelae in patients with neurodegenerative Langerhans cell histiocytosis
Authors: van't Hooft Ingrid , Gavhed Désirée , Laurencikas Evaldas , Henter Jan‐Inge 
Published: July 2008

AbstractBackgroundPatients with Langerhans cell histiocytosis (LCH) may develop neurodegeneration and significant CNS sequelae, affecting a significant proportion of the patients. We here aimed to investigate the neuropsychological consequences in more detail.MethodsUsing an extensive neuropsychological test battery, we evaluated nine LCH patients, 6–20 years old, with radiological signs indicative of neurodegeneration.ResultsAltogether 3/9 patients performed below 1 SD of normal for age on full IQ. Detailed analysis revealed that 4/9 had deficient performance IQ, whereas 1/9 had subnormal verbal IQ (defined as below 1 SD). Furthermore, 3/8 patients showed slow speed of performance for age. Notably, 8/9 (89%) had deficient verbal working memory and 7/8 (88%) performed below normal on visual‐spatial working memory.ConclusionsThe results indicate a specific, uneven neuropsychological profile in patients affected by CNS‐LCH, with a decline particularly on perceptual tasks whereas the verbal performance was not as negatively influenced. Furthermore, verbal and visual‐spatial working memory functions were below normal for age in all but one patient studied. LCH may easily be misdiagnosed, but it is important that individuals affected by CNS‐LCH are diagnosed to provide advice and support. It remains a challenge to find a treatment reducing this unfortunate neurodegeneration. Pediatr Blood Cancer 2008;51:669–674. © 2008 Wiley‐Liss, Inc.
Myocardial iron overload in transfusion‐dependent pediatric patients with acute leukemia
Authors: Lutz K. , von Komorowski G. , Dürken M. , Engelhardt R. , Dinter D.J. 
Published: July 2008

AbstractFor patients who regularly receive blood transfusions, cardiac failure is the major cause of death. This is most alarming because it progresses rapidly and is difficult to manage. We present three pediatric patients with acute leukemia whose therapy‐induced anemia was treated with different amounts of red blood cell concentrates (RCC). In all patients, a liver iron overload was measured by super‐conducting interference device (SQUID) biosusceptometry and magnetic resonance imaging (MRI). MRI is a rapid, noninvasive, and widely available method of determining early myocardial iron overload caused by multiple blood transfusion due to anemia during polychemotherapy. Pediatr Blood Cancer 2008;51:691–693. © 2008 Wiley‐Liss, Inc.
Parental perceptions of being told their child has cancer
Authors: Parker Torrey M. , Johnston Donna L. 
Published: July 2008

AbstractBackgroundFinding out that your child has cancer is a devastating experience. How this information is communicated can have a lasting impression on parents receiving the news. The purpose of this study was to assess how well parents recall discussing the diagnosis of cancer and to summarize suggestions for improvement.MethodsA questionnaire was developed with input from several parents of children previously diagnosed with cancer. All parents of children <18 years of age with a diagnosis of cancer who were >1 month post‐diagnosis at our children's hospital were asked to participate. The patient sample was identified through the in‐ and outpatient clinics from June to August 2006.ResultsOne‐hundred sixteen parents (mothers and fathers) completed the questionnaire, with only two parents refusing (1.7%). The moment of disclosure of the diagnosis was remembered vividly in 77%, well in 20%, and somewhat, vaguely or not at all in 1% each. Parental reaction to the disclosure was viewed as a positive experience 79% of the time and a negative experience 21% of the time. Parents also provided a number of suggestions for future disclosure.ConclusionsThe majority of parents recall receiving the diagnosis and the discussions that ensued about their child's diagnosis of cancer. Most parents were satisfied with their experience with receiving the diagnosis. Suggestions for improvement can be incorporated into future educational indicatives for front line healthcare providers to improve communication of sensitive diagnoses with parents. Pediatr Blood Cancer 2008;51:531–534. © 2008 Wiley‐Liss, Inc.
The morbidity and mortality of pediatric oncology patients presenting to the intensive care unit with septic shock
Authors: Pound Catherine M. , Johnston Donna L. , Armstrong Rachel , Gaboury Isabelle , Menon Kusum 
Published: July 2008

AbstractBackgroundChildren with an underlying diagnosis of malignancy are at high risk for developing serious infections. Previous studies, although very limited in number, suggest a particularly poor outcome for these patients if admitted to an intensive care unit with septic shock.ProcedureA review of all oncology patients admitted to the pediatric intensive care unit (PICU) at a tertiary care Children's Hospital over an 11‐year period with a diagnosis of septic shock was performed. Patients were age and gender‐matched with non‐oncology patients also admitted to the PICU with septic shock during the same time period. Mortality and morbidity rates were compared, and risk factors for poor outcome were examined.ResultsThe charts of 69 oncology patients and 69 control patients were reviewed. Mortality rate at PICU discharge was not significantly different between the two groups (15.9% in the oncology group, versus 11.6% in the control group, P = 0.607). Organ dysfunction was higher in the oncology group (P = 0.005), although length of PICU stay was shorter (P = 0.036). There was no difference in ventilator days or vasopressor use.ConclusionThis review found that the survival of oncology patients admitted to the PICU with septic shock was not significantly different from control patients, and was significantly higher than previous reports. Aggressive management of these children is warranted as their long term prognosis may be much more favorable than originally thought. Pediatr Blood Cancer 2008;51:584–588. © 2008 Wiley‐Liss, Inc.
Improved growth velocity during thyroid hormone therapy in children with Fanconi anemia and borderline thyroid function
Authors: Eyal Ori , Blum Samantha , Mueller Robin , Smith Franklin O. , Rose Susan R. 
Published: July 2008

AbstractBackgroundChildren with Fanconi anemia (FA) tend to have short stature, mild thyrotropin (TSH) elevation, and borderline low free thyroxine (FT4). Objective was to examine whether thyroid hormone therapy improves linear growth in children with FA and borderline thyroid function testsProcedureThyroid function tests were performed in 63 children with FA. Eight subjects participated in a random order, double‐blind, cross‐over treatment for 7 months with levothyroxine and for 7 months with placebo. Monitoring included growth measurements and laboratory assays at 1, 4 and 7 months of each phase. A 1 month lead in/wash out period was excluded from analysis of each treatment phase.ResultsThe majority (63%) of FA children had borderline thyroid function tests. All eight FA subjects enrolled in the treatment study had FT4 in the lowest third of the normal range of 0.8–1.8 ng/dL (10.3–23.2 pmol/L) [FT4 0.9 ± 0.1 ng/dL (mean ± SD), range 0.8–1.2 ng/dL (10.3–15.4 pmol/L)]. TSH (optimal range 0.5–3 mU/L) was borderline elevated in six of eight subjects (4.0 ± 1.5 mU/L, 1.9–7.3 mU/L). Growth velocity was slow at baseline and improved significantly during the thyroid phase compared to the placebo phase (2.1 ± 1.2 cm/year vs. 5.4 ± 1.7 cm/year, P < 0.05).ConclusionsThyroid hormone therapy is safe and may improve linear growth velocity in children with FA who have borderline thyroid function. Subtle hypothyroidism has importance for growth in children. Whether thyroid hormone treatment improves adult height in these children remains to be elucidated. Pediatr Blood Cancer 2008;51:652–656. © 2008 Wiley‐Liss, Inc.
A critical assessment of transcranial doppler screening rates in a large pediatric sickle cell center: Opportunities to improve healthcare quality
Authors: Raphael Jean L. , Shetty Priya B. , Liu Hao , Mahoney Donald H. , Mueller Brigitta U. 
Published: July 2008

AbstractBackgroundTranscranial Doppler ultrasound (TCD) has been demonstrated to be a powerful predictor of stroke risk due to sickle cell disease (SCD) in pediatric populations. Little is known about how this healthcare innovation has disseminated into preventive care for SCD. The objective of this study was to determine TCD screening rates and modifiable patient barriers in children with SCD.ProcedureWe retrospectively assessed the screening of 207 children with SCD at the Texas Children's Sickle Cell Center over a 3‐year period (2004–2006). Demographics, adherence to comprehensive care visits, severity of disease, and distance from the sickle cell center were obtained from computerized medical record databases. Screenings cancelled or missed by patients were extracted from a computerized order entry system.ResultsThe average yearly screening rate for eligible patients was 45%. The average yearly cancellation rate by patients was 20%. Patient with private insurance were three times more likely to be compliant with ordered screenings than patients with Medicaid (P = 0.0077). Patients adherent to hematology comprehensive care visits more likely underwent ordered screenings than those who were not (P = 0.0386). When given at least one opportunity per year, providers, on average, ordered TCD screening 74% of the time when it was indicated.ConclusionsDespite evidence that routine screening to assess stroke risk is vital to the preventive care of SCD, implementation of this healthcare technology may be slow to disseminate due to patient and provider related factors. Pediatr Blood Cancer 2008;51:647–651. © 2008 Wiley‐Liss, Inc.
Congenital Ewing sarcoma in retroperitoneum with multiple metastases
Authors: Saito Yusuke , Matsuzaki Akinobu , Suminoe Aiko , Koga Yuhki , Kurata Hiroaki , Oda Yoshinao , Tsuneyoshi Masazumi , Hara Toshiro 
Published: July 2008

AbstractA 7‐day‐old Japanese female showed the absence of spontaneous movement in her both legs. MRI revealed tumors in the retroperitoneum invading into the spinal canal, the left cerebral hemisphere and the right eyeball. Histological examination of retroperitoneal tumor revealed the sheets of undifferentiated small round cells with hyperchromatic nuclei and scanty cytoplasm. EWS‐FLI1 fusion gene was detected by RT‐PCR, indicating Ewing sarcoma. She received chemo‐radiotherapy and survived for 2 years and 10 months despite the multiple metastases at initial presentation. Pediatr Blood Cancer 2008;51:698–701. © 2008 Wiley‐Liss, Inc.
Congenital anomaly and childhood cancer: A population‐based, record linkage study
Authors: Rankin Judith , Silf Kirstin A. , Pearce Mark S. , Parker Louise , Ward Platt Martin 
Published: July 2008

AbstractBackgroundThe cause of the majority of childhood malignancies is unknown. Association with the presence of congenital anomalies has been noted in some studies. In this study, we describe and quantify the association between congenital anomalies and childhood cancer.ProcedureCases from the Northern Congenital Abnormality Survey (NorCAS) and the Northern Region Young Persons Malignant Disease Registry (NRYPMDR) were matched using four key variables: surname at birth, date of birth, postcode at birth, and infant gender. All potential matches were checked manually. A second match was performed for children with matched birth dates, postcodes and gender but different surnames, to identify children whose surname at diagnosis was not the same as at birth.ResultsThirty‐nine children with a congenital anomaly and a diagnosis of cancer were identified from a cohort of 599,290 children born during 1985–2001. There was an almost threefold overall increased risk of malignancy among these children (RR = 2.9; 95% CI 2.1, 3.9), particularly of acute lymphoblastic leukaemia (RR = 2.7; 95% CI 1.5, 5.0), acute myeloblastic leukaemia (RR = 22.0; 95% CI 12.1, 40.0), other leukaemia (RR = 7.5; 95% CI 1.3, 43.6) and lymphomas (RR = 5.3; 95% CI 2.4, 12.0). This increased rate remained when children with Down syndrome were excluded (RR = 1.8, 95% CI 1.2, 2.7).ConclusionOur findings suggest that children born with congenital anomalies are at increased risk of certain types of cancer. Further linkage studies between high quality registers, may provide insights into the origins of such malignancies. Pediatr Blood Cancer 2008;51:608–612. © 2008 Wiley‐Liss, Inc.