bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional analysis of apoptosis induction in acute myeloid leukaemia‐relevance of karyotype and clinical treatment response
Authors: Braess Jan , Schneiderat Peter , Schoch Claudia , Fiegl Michael , Lorenz Isolde , Hiddemann Wolfgang 
Published: July 2004

SummaryDeficiencies or structural defects of the apoptotic machinery have been postulated as a potential mechanism for a broad resistance of acute myeloid leukaemia (AML) blasts towards cytotoxic therapy comprising chemotherapeutic agents with diverse pharmacodynamic principles but also cell‐mediated cytotoxicity of the graft‐versus‐leukaemia effect, for example, in the setting of allogeneic transplantation. This hypothesis was systematically tested by functionally analysing the early, intermediate and late events of the apoptotic process in primary AML (n = 31) blasts following activation of the intrinsic and extrinsic pathway of apoptosis (etoposide and cytarabine as DNA damaging agents, FAS‐ligand as an activator of the death receptor pathway). Activation of the extrinsic pathway by FAS‐ligand did not induce apoptosis in primary AML, instead the proapoptotic signal was shown to ‘fade’, even in the early phase of the apoptotic sequence. However, activation of the intrinsic pathway induced severe cytotoxicity in all samples that showed the characteristic features of typical apoptosis, with a prominent apoptotic volume decrease (blebbing) in the early phase, significant increases in caspase 3 activity (intermediate or effector phase) and breakdown of cellular energy production in the late phase of apoptosis. These characteristics did not differ between prognostically favourable versus unfavourable AML karyotypes or between clinically responding versus refractory AML – indicating that a functional apoptotic apparatus is present even in the unfavourable AML subgroups . Our data indicate that the mechanism for a broad clinical resistance is not a dysfunctional apparatus per se but rather the consequence of anti‐apoptotic regulation impeding otherwise functional apoptotic machinery.
Haploidentical donor T cells fail to facilitate engraftment but lessen the immune response of host T cells in murine fetal transplantation
Authors: Chen Jeng‐Chang , Chang Ming‐Ling , Lee Hanmin , Muench Marcus O. 
Published: July 2004

SummaryThe effects of donor T cells, or their CD8+ subset, on engraftment and tolerance induction in fetal transplantation were evaluated using an F1‐into‐parent mouse‐model that does not permit a graft‐versus‐host effect. Gestational day 13 C57BL/6 (H‐2Kb) fetuses were transplanted with B6D2F1 (H‐2Kb/d) light density bone marrow cells (LDBMC) containing 1–2% T cells, T‐cell depleted bone marrow cells (TDBMC, <0·1% T cells), or TDBMC with enriched CD8+ T cells (CD8). Chimaerism levels in the peripheral blood, spleen and bone marrow were usually below 0·2% in all groups, indicating that T cells do not improve engraftment without a graft‐versus‐host effect. A significant, but transient, wave of donor cells was seen in the peripheral blood at 1 month of age in the CD8 and LDBMC groups. Relatively high levels of chimaerism (<17%) were sometimes detected in the peritoneal cavities of recipients. T‐cell tolerance specific to donor cells was evaluated in mixed lymphocyte cultures. The CD8 and LDBMC groups had significantly lower T‐cell responses than untransplanted controls. These findings indicate that in utero transplantation of haploidentical donor CD8+ or CD3+ cells can help to lessen the immune response of host T cells towards donor cells. The persistence of donor cells in the peritoneal cavity also correlated with tolerance induction.
Evidence of parvovirus B19 infection in patients of pre‐eclampsia and eclampsia with dyserythropoietic anaemia
Authors: Yeh Su‐Peng , Chiu Chang‐Fang , Lee Chien‐Chung , Peng Ching‐Tien , Kuan Chih‐Yu , Chow Kuan‐Chih 
Published: July 2004

SummaryParvovirus B19 (PVB19) infection can induce transient anaemia in patients with increased erythropoiesis. However, the dynamic change within the bone marrow after PVB19 infection is not well understood. Increased erythropoiesis is a physiological phenomenon in puerperital women. Nevertheless, anaemia as a result of PVB19 infection in puerperital women has never been reported. We report one patient with eclampsia and two patients with pre‐eclampsia who had transient, severe anaemia during the puerperital period because of PVB19 infection. Viral genomes were detected in the peripheral blood during the anaemic period by polymerase chain reaction and became undetectable after the anaemia was resolved. Viral genomes and protein could also be detected in bone marrow by in situ hybridization and immunohistochemical staining, respectively. Serial aspiration cytology of bone marrow showed severe dysplastic change involving erythroid precursors with a few apoptotic cells at the initial onset of anaemia, markedly increased apoptotic cells that was confirmed by the increased expression of activated caspase 3, around the nadir of anaemia, and a normal marrow picture without features of apoptosis after recovery from anaemia. Our data indicates that PVB19 infection can induce transient, severe dyserythropoietic anaemia in puerperital women with pre‐eclampsia/eclampsia and the pathogenetic mechanism may probably involve the induction of apoptosis following PVB19 infection.
Increased hepcidin expression and hypoferraemia associated with an acute phase response are not affected by inactivation of HFE
Authors: Frazer David M , Wilkins Sarah J , Millard Kirstin N , McKie Andrew T , Vulpe Christopher D , Anderson Gregory J 
Published: July 2004

SummaryThe effect of HFE inactivation on iron homeostasis during an acute phase response was investigated in mice. HFE knockout, β2‐microglobulin knockout and C57BL/6J mice were injected with Freund's Complete Adjuvant to induce an acute phase response and hepatic hepcidin expression and serum transferrin saturation was determined 16 h later. Hepcidin mRNA increased in all strains in response to an acute phase stimulus when compared with untreated control animals. Hypoferraemia also occurred in all strains, indicating that both the upregulation of hepcidin and the decrease in transferrin saturation associated with an acute phase response is not dependent on HFE function.
Aberrant expression of β‐catenin discriminates acute myeloid leukaemia from acute lymphoblastic leukaemia
Authors: Serinsöz Ebru , Neusch Michael , Büsche Guntram , von Wasielewski Reinhard , Kreipe Hans , Bock Oliver 
Published: July 2004

SummaryThe role of β‐catenin in epithelial neoplasms has been widely studied whereas current knowledge regarding β‐catenin gene and protein expression in bone marrow cells derived from normal haematopoiesis and clonal haematological disorders is lacking. β‐Catenin gene expression was quantitatively investigated in bone marrow cells derived from clonal haematological disorders [acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), Philadelphia chromosome‐positive chronic myeloid leukaemia (Ph+ CML], Ph− myeloproliferative disorders, n = 96) compared with non‐neoplastic haematopoiesis (n = 33) by real‐time reverse transcription polymerase chain reaction. Cellular localization of β‐catenin protein was detected by immunocytochemistry. β‐Catenin gene expression was significantly increased in AML compared with ALL cases (P < 0·0001), Ph+ CML (P < 0·0001) and non‐neoplastic haematopoiesis (P = 0·019). Immunocytochemistry revealed that, in non‐neoplastic haematopoiesis, the granulopoietic lineage as well as megakaryocytes showed membranous and cytoplasmic staining to various degrees along with unlabelled nuclei. Besides haematopoiesis, β‐catenin prominently marked bone marrow vascularity and diverse stroma cells. β‐Catenin gene was inversely expressed in AML and ALL with a lack of protein expression in neoplastic cells in ALL. In contrast, the other haematological disorders under study, except for Ph+ CML, did not show significant alterations of overall β‐catenin gene expression compared with normal bone marrow. These data suggest different regulatory mechanisms in the expression and function of β‐catenin in haematopoietic cells.
Human cytomegalovirus persists in myeloid progenitors and is passed to the myeloid progeny in a latent form
Authors: Khaiboullina Svetlana F. , Maciejewski Jaroslaw P. , Crapnell Kirsten , Spallone Patricia A. , Dean Stock A. , Pari Gregory S. , Zanjani Esmail D. , Jeor Stephen St 
Published: July 2004

SummaryCD34+ progenitor cells can harbour latent human cytomegalovirus (HCMV); however, the mechanisms of HCMV latency remain unclear. We have investigated the effects of the haematopoietic lineage restriction on the establishment and spread of the latent HCMV to progeny cells. In vitro‐infected and latently‐infected haematopoietic progenitor cells derived from HCMV seropositive donors were studied. The presence of HCMV DNA in bone marrow progenitor (BMP) cells was determined by single colony polymerase chain reaction and fluorescent in situ hybridization (FISH). The presence of CMV DNA was found to be restricted to myeloid progenitors and the percentage of HCMV‐infected cells was lower in naturally‐infected cells than in in vitro‐infected cells. Erythroid differentiation resulted in an abortive infection with persistence of the viral nucleic acids in red cell precursors. In BMP cells from HCMV seronegative donors, HCMV DNA was localized in the nucleus. Bone marrow progenitors in the presence of granulocyte‐macrophage colony stimulating factor (GMCSF) maintained HCMV DNA for extended periods of time. No viral production could be detected throughout the culture but the comparison of the numbers of latently‐infected cells prior to and after the culture suggests that proliferation of haematopoietic progenitor cells may lead to the expansion of latently‐infected cells.
Disturbed flow promotes deposition of leucocytes from flowing whole blood in a model of a damaged vessel wall
Authors: Skilbeck Christopher A. , Walker Peter G. , David Tim , Nash Gerard B. 
Published: July 2004

SummaryDeparture from simple laminar flow in arteries may promote the local attachment of leucocytes either to intact endothelium or platelet thrombi. We perfused blood through a chamber with a backward facing step, to observe whether adhesion from whole blood to P‐selectin was indeed localized to a region of recirculating flow, and whether platelets binding to collagen in such a region could capture leucocytes. Blood flowing over the step established a stable vortex, a reattachment point where forward and backward flow separated, and a simple laminar flow with wall shear rate c. 400/s further downstream. Fluorescently labelled leucocytes were observed to attach to P‐selectin immediately upstream or downstream of the reattachment point, and to roll back towards the step or away from it, respectively. There was negligible adhesion further downstream. When a P‐selectin‐Fc chimaera was used to coat the chamber, stable attachment occurred, again preferentially in the disturbed flow region. Numerous platelets adhered to a collagen coating throughout the chamber, although there were local maxima either side of the reattachment point. The adherent platelets captured flowing leucocytes in these regions alone. Leucocytes may adhere from flowing blood in vessels with high shear rate if the flow is disturbed. While platelets can adhere over a wider range of shear rates, their ability to capture leucocytes may be restricted to regions of disturbed flow.
HDL metabolic activities in a boy with lipoprotein lipase deficiency and his family
Authors: Brites F. , Verona J. , Fernández K. , Henriksen F. , Fruchart J. , Cesar M. , Castro G. , Wikinski R. 
Published: July 2004

AbstractBackground Lipoprotein lipase (LPL) deficiency is a rare autosomal recessively inherited disease characterized by elevated triglyceride, low total cholesterol and quantitative and qualitative alterations of high‐density lipoprotein (HDL). The aim of the present study was to explore HDL metabolic activities in a patient with LPL deficiency and in his family (n = 11).Materials and methods Subjects were divided into four groups: proband (Ser447Stop/Arg170Leu carrier), Ser447Stop carriers, Arg170Leu carriers and silent mutation/wild‐type carriers (controls). Cholesterol efflux from Fu5AH cells, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), paraoxonase 1 (PON1) and platelet‐activating factor acetylhydrolase (PAF‐AH) activities were evaluated.Results Comparison between the proband and the control group revealed that the boy had significantly reduced cholesterol efflux (P < 0·001), conserved LCAT activity (P > 0·05) and increased CETP activity (P < 0·001). As regards antioxidant enzymes, while PON1 activity was higher in the proband than in the controls (P < 0·0001), PAF‐AH activity was reduced (P < 0·05). The other groups did not show relevant differences in comparison with controls.Conclusions The presence of one mutation was not enough to introduce important modifications in HDL functions. Markedly reduced HDL levels can keep certain normal enzymatic activities, which probably tend to counteract the deleterious effects of LPL deficiency.
Selenium supplementation decreases nuclear factor‐kappa B activity in peripheral blood mononuclear cells from type 2 diabetic patients
Authors: Faure P. , Ramon O. , Favier A. , Halimi S. 
Published: July 2004

AbstractObjective  The role of selenium in preventing cardiovascular diseases has been largely described. Oxidative stress and the subsequent activation of nuclear factor‐kappa B (NF‐κB) have been linked to the development of vascular complications. We investigated the effects of selenium supplementation in type 2 diabetic patients on several oxidative stress parameters and NF‐κB activity.Methods  We enrolled 56 type 2 diabetic patients with similar glycaemic control: 21 were supplemented by selenium (960 µg d−1, 3 months) and 27 received a placebo, and 10 nondiabetic subjects formed the control group. To determine NF‐κB activation, we used an electrophoretic mobility shift assay followed by a semi‐quantitative determination of NF‐κB in peripheral blood mononuclear cells.Results  Selenium treatment resulted in a significant increase in plasma selenium and red‐cell Se GSH px activity. It had no effect on lipid peroxidation measured by malone‐dialdehyde (MDA) or on red‐cell Cu/Zn SOD. NF‐κB activity was increased by 80% in diabetic patients. In patients receiving selenium supplementation, selenium NF‐κB activity was significantly reduced, reaching the same level as the nondiabetic control group.Conclusion  In type 2 diabetic patients, activation of NF‐κB measured in peripheral blood monocytes can be reduced by selenium supplementation, confirming its importance in the prevention of cardiovascular diseases.
Cholecystokinin‐1 receptor protein up‐regulation during pancreatic regeneration after acute haemorrhagic pancreatitis in rats
Authors: Yoshikawa H. , Nakamura H. , Tashiro M. , Yamaguchi T. , Taguchi M. , Fukumitsu K. , Otsuki M. 
Published: July 2004

AbstractBackground  Cholecystokinin (CCK) plays an important role in regeneration after acute pancreatitis in rats. The present study was aimed to elucidate the role of CCK‐1 receptor (CCK‐1R) in acute pancreatitis. We investigated the serial changes in CCK‐1R mRNA and protein levels and their immunolocalization after acute haemorrhagic pancreatitis induced in male Wistar rats by retrograde intraductal infusion of 4% sodium taurocholate (100 µL 100 g−1 body weight).Methods  Histological changes were evaluated by haematoxylin and eosin staining. Pancreatic CCK‐1R mRNA was determined by Northern blot analysis. Pancreatic CCK‐1R protein was evaluated by immunoblot analysis and immunohistochemistry with a polyclonal antibody against rat CCK‐1R protein.Results  Histological findings revealed that newly formed acinar cells were detected at the periphery of tubular complexes on day 14, and normal architecture of lobules was observed focally on day 21. Pancreatic CCK‐1R mRNA peaked on day 3 and thereafter gradually decreased. Cholecystokinin‐1R protein rapidly increased after induction of pancreatitits, reaching a maximal level on day 3. On day 3, intense immunoreactivity for CCK‐1R protein was observed in both the cytoplasm of vacuolized acinar cells and the tubular complexes. In the regenerative process after acute haemorrhagic pancreatitis in rats, the expression of pancreatic CCK‐1R mRNA and protein increased, and intense immunoreactivity for CCK‐1R protein was observed in tubular complexes in the cytoplasm of regenerated acinar cells.Conclusion  These results suggest that CCK‐1R contributes to pancreatic regeneration after acute haemorrhagic pancreatitis and that tubular complexes are involved in the process of acinar cell regeneration following pancreatic injury.
Effects of low‐dose dopamine on ventilation in patients with chronic obstructive pulmonary disease
Authors: Ciarka A. , Rimacchi R. , Vincent J.‐L. , Velez‐Roa S. , Dumonceaux M. , Leeman M. , Van De Borne P. 
Published: July 2004

AbstractBackground  Dopamine plays an important role in the regulation of respiration and low‐dose dopamine infusion is associated with a decreased respiratory drive response to hypoxia in animals and humans. The effects of dopamine on ventilation in patients with chronic obstructive pulmonary disease (COPD) is unknown. We tested the hypothesis that dopamine inhibits ventilation in patients with COPD.Materials and methods  In a double‐blinded, cross‐over, placebo‐controlled, randomized study we studied nine patients with decompensated COPD, ventilated in the pressure support mode in the intensive care unit (ICU) and five ambulatory patients with stable COPD. All patients received 5 µg kg−1 min−1 of dopamine or an equivalent volume of 5% glucose solution.Results  In the mechanically ventilated COPD patients, there was no difference in the effects of dopamine compared with placebo on blood pressure, heart rate, minute ventilation (−0·5 ± 1·1 vs. −0·2 ± 0·9 L min−1, P = 0·46, respectively), respiratory rate (−0·4 ± 2·7 vs. −0·3 ± 2·1 min−1, P = 0·96), PaO2 (−5 ± 4 vs. −5 ± 10 mmHg, P = 0·90, respectively), or PaCO2 (−0·7 ± 1·4 vs. −1·0 ± 3·4 mmHg, P = 0·83, respectively). In spontaneously breathing stable patients, dopamine increased systolic blood pressure (P = 0·02) but did not influence other haemodynamic and respiratory variables.Conclusion  Although low‐dose dopamine has been shown to depress ventilation in a variety of conditions, it does not compromise ventilation in COPD patients either breathing spontaneously or when weaned using pressure support ventilation.
8‐isoprostane increases scavenger receptor A and matrix metalloproteinase activity in THP‐1 macrophages, resulting in long‐lived foam cells
Authors: Scholz H. , Aukrust P. , Damås J. K. , Tonstad S. , Sagen E. L. , Kolset S. O. , Hall C. , Yndestad A. , Halvorsen B. 
Published: July 2004

AbstractBackground  Oxidative stress is a key factor in atherogenesis, in which it is closely associated with the inflammation and formation of bioactive lipids. Although 8‐isoprostane is regarded as a reliable marker of oxidative stress in vivo, the pathogenic role of this F2‐isoprostane in atherogenesis is far from clear. Based on the important role of foam cells in the initiation and progression of atherosclerosis we hereby examined the ability of 8‐isoprostane to modulate oxidized (ox)LDL‐induced foam cell formation and the function of these cells, particularly focusing on the effect on matrix degradation.Methods and results  8‐isoprostane (10 µM) augmented the oxLDL‐induced (20 µg mL−1) lipid accumulation of THP‐1 macrophages evaluated by Oil‐Red‐O staining and lipid mass quantification (colourimetric assay). Additionally, 8‐isoprostane induced the expression of the scavenger receptor A type 1 (MSR‐1) [mRNA and protein level], assessed by RT‐PCR and Western blotting, respectively. Moreover, 8‐isoprostane counteracted the oxLDL‐induced apoptosis of these cells, involving both mitochondrial‐protective and caspase‐suppressive mechanisms. Along with these changes, 8‐isoprostane increased the oxLDL‐induced gene expression of matrix metalloproteinase (MMP)‐9 and its endogenous inhibitor [i.e. tissue inhibitor of MMP (TIMP)‐1] accompanied by enhanced total MMP activity.Conclusions  We show that 8‐isoprostane increases foam cell formation at least partly by enhancing MSR‐1 expression and by inhibiting apoptosis of these cells, inducing long‐lived foam cells with enhanced matrix degrading capacity. Our findings further support a role for 8‐isoprostane not only as a marker of oxidative stress in patients with atherosclerotic disorders, but also as a mediator in atherogenesis and plaque destabilization.
Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxide
Authors: Borke W. B. , Munkeby B. H. , Halvorsen B. , Bjornland K. , Tunheim S. H. , Borge G. I. A. , Thaulow E. , Saugstad O. D. 
Published: July 2004

AbstractBackground  Perinatal asphyxia is associated with cardiac dysfunction, and it is important to prevent further tissue injury during resuscitation. There is increasing evidence that myocardial matrix metalloproteinases (MMPs) are involved in myocardial hypoxaemia–reoxygenation injury.Objective  To assess MMPs and antioxidant capacity in newborn pigs after global ischaemia and subsequent resuscitation with ambient air or 100% O2 at different PaCO2‐levels.Methods  Newborn pigs (12–36 h of age) were resuscitated for 30 min by ventilation with 21% or 100% O2 at different PaCO2 levels after a hypoxic insult, and thereafter observed for 150 min. In myocardial tissue extracts, MMPs were analyzed by gelatin zymography and broad matrix‐degrading capacity (total MMP). Total endogenous antioxidant capacity in myocardial tissue extracts was measured by the oxygen radical absorbance capacity (ORAC) assay.Results  Matrix metalloproteinase‐2 more than doubled from baseline values (P < 0·001), and was higher in piglets resuscitated with 100% O2 than with ambient air (P = 0·012). The ORAC value was considerably decreased (P < 0·001). In piglets with elevated PaCO2, total MMP‐activity in the right ventricle was more increased than in the left ventricle (P = 0·008). In the left ventricle, total MMPactivity was higher in the piglets with low PaCO2 than in the piglets with elevated PaCO2 (P = 0·013).Conclusion  In hypoxaemia‐reoxygenation injury the MMP‐2 level was highly increased and was most elevated in the piglets resuscitated with 100% O2. Antioxidant capacity was considerably decreased. Assessed by total MMP‐activity, elevated PaCO2 during resuscitation might protect the left ventricle, and probably increase right ventricle injury of the myocardium.