bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia
Authors: Elliott M. A. , Tefferi A. 
Published: January 2005

SummaryDespite decades of clinical and laboratory research, relatively little has been accomplished concerning the pathogenesis as well as the identification of risk factors for thrombosis and bleeding in myeloproliferative disorders. In polycythaemia vera, the pro‐thrombotic effect of an elevated haematocrit is well established. In contrast, thrombocytosis per se has not been similarly incriminated in essential thrombocythaemia. In both conditions, advanced age and the presence of a prior event identify thrombosis‐prone patients. There is increasing evidence to suggest an additional role by leucocytes that might partly explain the antithrombotic effects of myelosuppressive therapy. A substantial minority of affected patients display reduced levels of high molecular weight von Willebrand protein in the plasma during extreme thrombocytosis and it is believed that this might explain the bleeding diathesis of such patients. Recent controlled studies support the therapeutic value of hydroxyurea and aspirin in essential thrombocythaemia and polycythaemia vera, respectively. The current communication will address the incidence, phenotype, pathogenesis, risk factors, prevention, and treatment of both thrombosis and haemorrhage in these disorders.
The crucial role of vascular permeability factor/vascular endothelial growth factor in angiogenesis: a historical review
Authors: Ribatti Domenico 
Published: January 2005

SummaryAngiogenesis is a biological process by which new capillaries are formed and it occurs in many physiological and pathological conditions. It is controlled by the net balance between molecules that have positive and negative regulatory activity and this concept had led to the notion of the ‘angiogenic switch’, depending on an increased production of one or more of the positive regulators of angiogenesis. Numerous inducers of angiogenesis have been identified and this review offers a historical account of the relevant literature concerning the discovery of one of the best characterized angiogenic factors, namely vascular endothelial growth factor (VEGF)/vascular permeability factor. Moreover, different strategies, designed to stimulate and to inhibit VEGF production in the context of several potential therapeutical implications, are discussed.
Management of thrombosis in cancer: primary prevention and secondary prophylaxis
Authors: Lee Agnes Y. Y. 
Published: January 2005

SummaryAlthough traditional anticoagulant regimens are highly effective and safe in most patients with venous thromboembolism (VTE), the aggressive natural history of VTE and the high risk of serious bleeding in cancer patients can complicate the management of VTE. In addition, because few clinical trials have focused on the prevention and treatment of VTE in this unique patient population, many clinical questions regarding the care of cancer patients with VTE remain unanswered. Currently, low‐molecular‐weight heparins and oral vitamin K antagonists are the most commonly used agents for the primary and secondary prophylaxis of VTE in patients with or without cancer, but their use is associated with pharmacological and practical limitations. This review will provide an up‐to‐date summary of the clinical trials that have addressed the management of VTE in patients with cancer. A brief discussion of the potential application of novel anticoagulants in these clinical settings is also included.
Severe FVII deficiency caused by a new point mutation combined with a previously undetected gene deletion
Authors: Hewitt Jeff , Ballard Jennifer N. M. , Nelson Tanya N. , Smith Valerie C. , Griffiths Tanya A. M. , Pritchard Sheila , Wu John K. , Wadsworth Louis D. , Casey Brett , MacGillivray Ross T. A. 
Published: January 2005

SummaryA 3‐week‐old Caucasian female presented with severe unprovoked parenchymal cerebral haemorrhage. Her plasma factor VII (FVII) activity was <0·01 units/ml. FVII activities for her mother and sister were 0·65 units/ml and 0·51 units/ml, respectively, while her father's level was normal. These results indicated that the mother was heterozygous for a non‐functional F7 gene that had also been inherited by the proband's sister. The proband's severe FVII deficiency was caused by a new mutation in her paternal F7 gene coupled with the inheritance of the non‐functional maternal F7 gene. DNA sequence analysis revealed that the proband had apparent homozygosity for a novel single point mutation (g.3907G > A) changing the codon for Glu29 to Lys (E29K); neither parent had the E29K mutation. Because of the unlikelihood that the proband was homozygous for two identical new point mutations, the DNA sequence abnormality was more likely to have arisen from a single mutated gene on one allele and a F7 gene deletion on the other allele. Real time polymerase chain reaction (PCR) analysis confirmed that the proband had inherited a gene deletion that was present in the maternal side of the family. Subsequent clotting assays and real time PCR revealed that the maternal deletion also included the closely linked F10 gene.
Inactivation of parvovirus B19 by liquid heating incorporated in the manufacturing process of human intravenous immunoglobulin preparations
Authors: Yunoki Mikihiro , Urayama Takeru , Tsujikawa Muneo , Sasaki Yoshie , Abe Shunichi , Takechi Kazuo , Ikuta Kazuyoshi 
Published: January 2005

SummarySeveral reports have suggested the possible transmission of human parvovirus B19 (B19) through the administration of plasma derivatives that had undergone virus inactivation by various types of heat treatment. However, none of the reports evaluated and discussed the inactivation of B19 by the heat treatment that is implemented in the individual manufacturing processes of such products. The present study evaluated the ability to inactivate B19 of liquid‐heat treatment at 60°C for 10 h that was incorporated in the manufacturing process of intravenous human immunoglobulin preparations. The results showed that B19 was rapidly inactivated under the conditions used for the liquid‐heat treatment.
Pre‐transfusion management of children with severe malarial anaemia: a randomised controlled trial of intravascular volume expansion
Authors: Maitland Kathryn , Pamba Allan , English Michael , Peshu N. , Levin Michael , Marsh K. , Newton Charles R.J.C. 
Published: January 2005

SummarySymptomatic severe malarial anaemia (SMA) has a high fatality rate of 30–40%; most deaths occur in children awaiting blood transfusion. Blood transfusion services in most of Africa are not capable of delivering adequate supplies of safe blood in a timely manner to critically ill children with SMA. Contrary to widely held belief, hypovolaemia, rather than heart failure, has emerged as a common complication in such children. We examined the safety of pre‐transfusion management (PTM) by volume expansion, aimed at stabilizing children and obviating the urgency for blood transfusion. Kenyan children with severe falciparum anaemia (haemoglobin < 5 g/dl) and respiratory distress were randomly assigned to 20 ml/kg of 4·5% albumin or 0·9% saline or maintenance only (control) while awaiting blood transfusion. PTM was apparently safe since it did not lead to the development of pulmonary oedema or other adverse events. There was no significant difference in the primary outcome [mean percentage reduction in base excess between admission and 8 h (95% confidence interval)] between the control group 42% (19–66%) albumin group 44% (32–57%) and saline group 36% (16–57%); adjusted analysis of variance F = 0·31, P = 0·7. However, the number of children requiring emergency interventions was significantly greater in the control group, four of 18 (22%) than the saline group 0 of 20 (P = 0·03). We have established the safety of this PTM in children with SMA whilst awaiting blood transfusion at a hospital with an adequate blood‐banking program. The impact on mortality should be assessed where blood transfusion services are unable to supply emergency transfusions.
The NFATc1 transcription factor is widely expressed in white cells and translocates from the cytoplasm to the nucleus in a subset of human lymphomas
Authors: Marafiot Teresa , Pozzobon Michela , Hansmann Martin‐Leo , Ventura Roland , Pileri Stefano A. , Roberton Helen , Gesk Stefan , Gaulard Philippe , Barth Thomas F. E. , Du Ming Q. , Leoncini Lorenzo , Möller Peter , Natkunam Yasodha , Siebert Reiner , Mason David Y. 
Published: January 2005

SummaryStimulation of lymphoid cells via their surface receptors triggers signalling pathways that terminate in the nucleus, where they induce alterations in gene transcription. Nuclear factor of activated T cells (NFAT) transcription factors, involved in a major Ca2+‐dependent signalling pathway, normally reside in the cytoplasm but re‐locate to the nucleus when activation of the pathway (e.g. following ligation of antigen receptors) leads to their dephosphorylation. This study found that one member of the NFAT family (NFATc1/NFAT2) can be detected in routine biopsy samples, where it is seen in essentially all lymphoid cells, but is absent from the great majority of non‐haematopoietic cells. An immunohistological evaluation of NFATc1 in almost 300 lymphomas showed that most neoplastic lymphoid cells also express NFATc1 as a cytoplasmic constituent, although it is absent in classical Hodgkin's disease and plasma cell proliferations. Of particular interest was the finding that NFATc1 was relocated to the nucleus in a minority of lymphoid neoplasms (usually diffuse large B‐cell lymphomas or Burkitt lymphoma), presumably reflecting activation of the NFAT pathway. It would be of interest to correlate this feature with patterns of gene expression and also with prognosis, since it may identify a subset of human lymphoma that is distinct in its molecular and clinical features.
Antiphospholipid antibodies in immune thrombocytopenic purpura tend to emerge in exacerbation and decline in remission
Authors: Bidot Carlos J. , Jy Wenche , Horstman Lawrence L. , Ahn Eugene R. , Jimenez Joaquin J. , Yaniz Miriam , Lander Gabriela , Ahn Yeon S. 
Published: January 2005

SummaryAlthough the presence of antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) has been reported, their clinical significance is not clear. The present study investigated APLA profiles in relation to the clinical stages of ITP. We studied APLA in 40 patients in three stages of ITP: exacerbation/relapse (n = 7), stable (n = 14) and remission (n = 19). Both IgG and IgM APLA to six target antigens were measured by enzyme‐linked immunosorbent assay: β2‐glycoprotein 1 (β2GP1), cardiolipin, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and factor VII/VIIa. The central finding was that APLA were common in ITP but differed significantly in disease stages, being highest in exacerbation (86% positive), intermediate in stable disease (57%) and lowest in remission (42%). In exacerbations, APLA were predominantly of IgG class, while in stable disease, IgM predominated. During remission, APLA often became undetectable. Both the frequency and titres of APLA were significantly higher during exacerbation than remission. An inverse correlation was found between platelet count and nearly all APLA (except β2GP1). Sequential study of six patients revealed that APLA tended to emerge and rise with exacerbation, concurrently with new episodes of bleeding and became undetectable during remission. These findings raise the possibility that APLA may play a role in the exacerbation and remission of ITP or they may be a consequence of platelet destruction.
Tolerance to intravenous heparin in patients with delayed‐type hypersensitivity to heparins: a prospective study
Authors: Gaigl Zeno , Pfeuffer Petra , Raith Petra , Bröcker Eva‐B. , Trautmann Axel 
Published: January 2005

SummaryDelayed‐type hypersensitivity to subcutaneously injected heparin is relatively common. Particularly, extensive cross‐reactivity between different heparins and heparinoids often occurs. Delayed‐type hypersensitivity to heparin implies the risk of a generalized eczema when heparin is administered intravenously. However, case reports demonstrated a tolerance to intravenous heparin in patients with delayed‐type hypersensitivity to subcutaneous heparin, but prospective studies have not been performed. Our study group, of 28 patients with a proven delayed‐type hypersensitivity to subcutaneous heparin, was challenged with intravenous heparin, which was well tolerated in all 28 patients. Therefore, in case of therapeutic necessity, the shift from subcutaneous to intravenous heparin administration is justified.
Gemtuzumab ozogamicin (Mylotarg) has therapeutic activity against CD33+ acute lymphoblastic leukaemias in vitro and in vivo
Authors: Golay J. , Di Gaetano N. , Amico D. , Cittera E. , Barbui A. M. , Giavazzi R. , Biondi A. , Rambaldi A. , Introna M. 
Published: January 2005

SummaryGemtuzumab ozogamicin (GO) is a humanized anti‐CD33 antibody conjugated with the cytotoxic drug calicheamicin and approved for the treatment of relapsed acute myeloid leukaemia. As approximately 18% of acute lymphoblastic leukaemias (ALL) are also CD33 positive, we have investigated the cytotoxic activity of GO on CD33+ ALL cells in vitro and in vivo. 10 ng/ml GO induced 30–95% inhibition of thymidine uptake and 30–70% cell death in four freshly isolated and one in vivo passaged CD33+ ALL‐cell cultures. Furthermore, an in vivo model of a CD33+ ALL carrying the Philadelphia chromosome [t(9;22)] was established. 5 × 106 ALL‐2 cells inoculated in the tail vein of severe combined immunodeficient mice engrafted into haematopoietic organs, reaching a mean of 70%, 61% and 69% human CD45+ cells in bone marrow, spleen and liver, respectively, at 35 d. To test the therapeutic activity of GO, 50 or 100 μg immunotoxin was inoculated i.p. on days 7, 11 and 15 following tumour‐cell inoculation. GO treatment dramatically inhibited expansion of ALL‐2 cells in all tested organs and increased survival of tumour‐injected animals by 28–41 d, relative to controls. These data demonstrated that GO is active both in vitro and in vivo against CD33+ ALL cells.
First description of somatic mosaicism in MYH9 disorders
Authors: Kunishima Shinji , Matsushita Tadashi , Yoshihara Takao , Nakase Yoko , Yokoi Kentaro , Hamaguchi Motohiro , Saito Hidehiko 
Published: January 2005

Summary MYH9 disorders are characterized by giant platelets, thrombocytopenia, and Döhle body‐like cytoplasmic granulocyte inclusion bodies that result from mutations in MYH9, which encodes non‐muscle myosin heavy chain‐A (NMMHCA). These disorders are known to be transmitted in an autosomal dominant manner, although about 20% of cases are considered to be sporadic. We report here the first case of a MYH9 disorder because of somatic mosaicism. The patient was the father of a male with typical May–Hegglin anomaly. The father had normal platelet counts, however, both normal‐sized and giant platelets were observed on his peripheral blood smears. In addition, 14% of neutrophils contained inclusion bodies and the rest showed a normal morphology. Quantitative fluorescent polymerase chain reaction analysis showed that only 6% of DNA from peripheral blood leucocytes harboured the mutation. The mosaicism was demonstrated at a similar rate in different tissues, buccal mucosa cells and hair bulb cells, implying that the mutation had occurred before gastrulation. Mosaicism might account for some de novo mutations in MYH9 disorders.
Thrombotic thrombocytopenic purpura in patients with retroviral infection is highly responsive to plasma infusion therapy
Authors: Novitzky Nicolas , Thomson Jacqueline , Abrahams Louise , Du Toit Cécile , McDonald Andrew 
Published: January 2005

SummaryWe prospectively studied presentation biological differences and the response to therapy in patients with thrombotic thrombocytopenic purpura (TTP) associated with, or unrelated to human immunodeficiency virus (HIV) infection. TTP patients underwent standard evaluations and were treated with prednisone 1 mg/kg in addition to infusions of fresh frozen plasma (FFP; 30 ml/kg/d) until normalization of the platelet count. Unresponsive patients were referred for plasma exchange. Compared with HIV− TTP patients (n = 23), in HIV+ subjects (n = 21) microangiopathy was dominant among Black females, who had lower presentation Hb (median 5·8 g/dl; P = 0·03), platelet count (13 × 109/l; P = 0·05) and a CD4 count of 0·096 × 109/l. HIV+ individuals responded to FFP faster than HIV− patients and none of them required apheresis. Ten HIV− TTP patients required apheresis (P = 0·03) and four died. Responses in the HIV+ and HIV− groups occurred after treatment with a median of 33 and 55 units (one unit = 320 ml) of FFP (P = 0·004) respectively. Response to this protocol was seen in 84% (95% response in HIV+ patients). Regression analysis showed that survival was associated with younger age (P = 0·001), rapid platelet (P = 0·001) and Hb (P = 0·0009) recovery, and fewer FFP units to normal lactate dehydrogenase levels (P = 0·006). We conclude that in HIV+ individuals, microangiopathy is highly responsive to plasma infusions. This observation is important particularly when apheresis is not available.
Factor V Leiden, prothrombin 20210A and the risk of venous thrombosis among cancer patients
Authors: Kennedy Margaret , Andreescu Astrid C. M. , Greenblatt Marc S. , Jiang Hongyu , Thomas Christian A. , Chassereau Laurie , Wong Cheung , Durda Peter , Cushman Mary 
Published: January 2005

SummaryCancer patients have an increased risk of venous thrombosis (VT). The association of factor V Leiden (FVL) and the prothrombin 20210A variant with VT in cancer patients is not established. We genotyped 101 cancer patients with VT and 101 cancer patients without VT for these polymorphisms. Five cases and three controls were heterozygous for FVL, yielding an odds ratio of 1·7 (95% confidence interval (CI) 0·3–10·7). Five cases and no controls were heterozygous for prothrombin 20210A, for an odds ratio of 6·7 (95% CI 0·9–infinity). Prothrombin 20210A may be associated with VT risk among cancer patients.
Molecular events associated with accelerated proliferative response in rat livers when partial hepatectomy is preceded by a sham operation
Authors: Laurent S. , Stärkel P. , Leclercq I. A. , Lambotte L. , Maiter D. , Horsmans Y. 
Published: January 2005

AbstractBackground  When a sham operation is performed 6 h before partial hepatectomy (PH), the regenerative response is accelerated suggesting that sham operation itself contributes to cellular events leading to proliferation.Materials and methods  In order to examine the mechanisms implicated in this acceleration, we compared the activation of several factors associated with the progression through the cell cycle at various times after PH and after PH preceded by sham operation (S6 h + PH). The effect of a single sham (S) and two combined sham operations (S6 h + S) was also examined. Nonoperated rats were used as controls (C).Results  The early factors NF‐κB and Stat3 were activated after S6 h + PH and S6 h + S. C‐jun expression was increased 0·5 h and 2 h after PH and 6 h after sham. There was no further increase in S6 h + PH and S6 h + S. In contrast, c‐myc expression returned to baseline levels after S6 h and a new increase was observed 2 h after S6 h + PH but not after S6 h + S. P53 mRNA was significantly expressed 6 h after S6 h + PH, but at a level similar than that observed 6 and 12 h after PH alone. An earlier increase in c‐Ha‐ras mRNA and cyclin E protein was found in S6 h + PH, in comparison with PH alone.Conclusions  The first divergent response between the two combined models involved c‐myc expression. However, major differences related to the accelerated liver regenerative response observed after S6 h + PH were found at late time points associating an earlier expression of c‐Ha‐ras and nuclear cyclin E.
Peroxisome proliferator‐activated receptor γ: the more the merrier?
Authors: Argmann C. A. , Cock T.‐A. , Auwerx J. 
Published: January 2005

AbstractThe consequence of activating the nuclear hormone receptor, peroxisome proliferator‐activated receptor gamma (PPARγ), which coordinates adipocyte differentiation, validates the concept, ‘you are what you eat’. Excessive caloric intake leads to fat formation if the energy from these nutrients is not expended. However, this evolutionary adaptation to store energy in fat, which can be released under the form of fatty acids, potent PPARγ agonists, has become a disadvantage in today's affluent society as it results in numerous metabolic imbalances, collectively known as the metabolic syndrome. With the surge of human and genetic studies on PPARγ function, the limitations to the benefits of PPARγ signalling have been realized. It is now evident that the most effective strategy for resetting the balance of this thrifty gene is through its modulation rather than full activation, with the goal to improve glucose homeostasis while preventing adipogenesis. Finally, as more PPARγ targeted pathways are revealed such as bone homeostasis, atherosclerosis and longevity, it is most certain that the PPARγ thrifty gene hypothesis will evolve to incorporate these.
Asymmetric dimethylarginine (ADMA): the silent transition from an ‘uraemic toxin’ to a global cardiovascular risk molecule
Authors: Fliser D. 
Published: January 2005

AbstractEndothelial dysfunction as a result of reduced bioavailability of nitric oxide (NO) plays a central role in the process of atherosclerotic vascular disease. In endothelial cells NO is synthesized from the amino acidl‐arginine by the action of the NO synthase (NOS), which can be blocked by endogenous inhibitors such as asymmetric dimethylarginine (ADMA). Acute systemic administration of ADMA to healthy subjects significantly reduces NO generation, and causes an increase in systemic vascular resistance and blood pressure. Increased plasma ADMA levels as a result of reduced renal excretion have been associated with atherosclerotic complications in patients with terminal renal failure. However, a significant relationship between ADMA and traditional cardiovascular risk factors such as advanced age, high blood pressure and serum LDL‐cholesterol, has been documented even in individuals without manifest renal dysfunction. As a consequence, the metabolism of ADMA by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) has come into the focus of cardiovascular research. It has been proposed that dysregulation of DDAH with consecutive increase in plasma ADMA concentration and chronic NOS inhibition is a common pathophysiological pathway in numerous clinical conditions. Thus, ADMA has emerged as a potential mediator of atherosclerotic complications in patients with coronary heart disease, peripheral vascular disease, stroke, etc., being the culprit and not only an innocent biochemical marker of the atherosclerotic disease process.