bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic thromboembolism in children
Authors: Kuhle Stefan , Massicotte Patricia , Chan Anthony , Adams Margaret , Abdolell Mohamed , de Veber Gabrielle , Mitchell Lesley 
Published: September 2004

SummaryThromboembolism (TE) has recently been recognized as a clinical entity in children. Determining the clinical characteristics of pediatric TE is an important first step in dealing with this new disorder. The paper summarizes 1776 consecutive children with systemic TE referred to 1-800-NO-CLOTS telephone consultation service. 1-800-NO-CLOTS is a free consultation service for clinicians managing pediatric TE. Patient information was collected immediately using standardized forms. In children with systemic TE, infants under one year of age (47%) including neonates (26%) represented the largest distinct pediatric age group. Age-related differences were seen in TE locations, associated conditions, and risk factors. However, venous TE was the most frequent manifestation (74%). Neonates and children with cardiac disorders were more likely to have an arterial TE than a venous TE Beyond the neonatal period, venous TE associated with a central line is more likely to occur than arterial TE. Children with ALL were 5.7 times more likely to have a venous TE than an arterial TE. TE were infrequent in otherwise healthy children with 90% of children having at least one risk factor. Central catheters were the single most common risk factor associated with TE, present in 2/3 of children. Ultrasound was most frequently employed for diagnosis of TE. Finally, there was marked heterogeneity in treatment of children with TE. In children, neonates form the largest single group with TE. TE usually occur only in the presence of one or more risk factors with catheters being the single most important factor.
Association between the Thr715Pro P-selectin gene polymorphism and soluble P-selectin levels in a multiethnic population in South London
Authors: Kerry Sally , Dong Yanbin , Strazzullo Pasquale , Cappuccio Francesco , Miller Michelle 
Published: September 2004

SummaryThe aim was to investigate whether the Thr715Pro P-selectin polymorphism is associated with soluble P-selectin (sP-selectin) levels in individuals from different ethnic groups. Plasma sPselectin and Thr715Pro (A/C) P-selectin gene polymorphism were measured in 237 white (106 females), 177 black African origin (92 females) and 201 South Asian (94 females) individuals living in England. All were free from coronary heart disease (CHD), stroke and other cardiovascular disease, diabetes, drug therapy for hypertension or high lipids, hormone replacement therapy or oral contraceptive pill. The Thr715Pro C allele was rare in blacks (0.8%) and intermediate in South Asians (3.0%) compared to whites (11.2%; p <0.001). sP-selectin levels were significantly lower in the individuals with the AC or CC compared to the AA genotype in both whites (-25% (95% C.I. -33.3 to -16.9); p <0.001) and South Asians (-25.2% (-40.5 to -6.1); p <0.012). There was insufficient power for this analysis in blacks. In conclusion, in whites and South Asians the C allele of the Thr715Pro P-selectin polymorphism is associated with lower sP-selectin levels. Lower levels of sP-selectin were not accounted for by this polymorphism in blacks, in whom the C allele was very rare.
Contamination of coagulation factor concentrates with human parvovirus B19 genotype 1 and 2
Authors: Schneider Beate , Becker Maria , Brackmann Hans-Hermann , Eis-Hübinger Anna 
Published: September 2004

SummaryHuman parvovirus B19 (B19) DNA has frequently been detected in plasma-derived coagulation factor concentrates. Furthermore, transmission of B19 infection was observed, indicating presence of the infectious virus despite routine viral inactivation/removal procedures during the manufacturing process. Recently, human parvovirus DNA isolates, variant from B19, have been identified resulting in classification of B19 virus into three distinct genotypes, with all viruses previously classified as B19 belonging to genotype 1. So far, there is no information available on contamination of clotting factor concentrates with genotype 2. Therefore, we analysed 202 different factor concentrate lots for genotype 1 and 2 DNA by PCR. Analysis of one hundred eighty-one lots representing 13 different products, administered over the last three years, was compared to 21 lots (8 products) used until the early 1980s which had not been treated by viral inactivation procedures. Genotype 1 DNA was detected in 77/181 (42.5%) currently administered lots, and 17/21 (81%) previously used lots. The level of genotype 1 DNA contamination was similar in currently and previously administered concentrates. Genotype 2 DNA was found in 5/202 (2.5%) lots, all of which were co-contaminated with genotype 1 DNA. DNA sequence analysis showed that the PCR-double positive concentrates contained typical genotype 1 and genotype 2 DNA. Because genotype 2 appears to cause a similar spectrum of diseases as genotype 1, simultaneous detection of genotype 2 by nucleic acid amplification testing (NAT), now widely applied to plasma pools for genotype 1, would give an added level of safety to blood products.
Oxidative status of platelets in normal and thalassemic blood
Authors: Amer Johnny , Fibach Eitan 
Published: September 2004

SummaryChronic platelet activation may be involved in thromboembolic complications, a leading cause of morbidity and mortality in β-thalassemia. Oxidative stress, with the generation of reactive oxygen species (ROS), is suspected to play a role in the pathophysiology of thalassemia and cardiovascular disorders. In the present study, we adapted flow cytometric techniques to measure oxidative state markers, ROS generation and reduced glutathione (GSH) content in platelets. Our results show that platelets obtained from β-thalassemic patients contain higher ROS and lower GSH levels than do platelets from normal donors, indicating a state of oxidative stress. In the absence of any known inherent abnormality in thalassemia platelets, this may be attributed to continuous exposure to oxidative insults from extra-platelet sources. We found that exposure of platelets to oxidants such as hydrogen peroxide and tertbutylhydroperoxide or to the platelet activators thrombin, calcium ionophore or phorbol myristate acetate stimulated the platelets’ oxidative stress.This was also increased by plasma of thalassemia patients, and decreased following treatment of the plasma with the iron-chelator Desferoxamin. Iron and hemin, the levels of which are augmented in plasma of thalassemia patients, stimulated the platelets’ oxidative stress.The oxidative status of the platelets was also affected by red blood cells (RBC); it was higher in normal platelets incubated with thalassemic RBC than with normal RBC. Normal RBC stimulated with hydrogen peroxide had a greater effect on platelets than did unstimulated RBC.The platelets’ oxidative stress was ameliorated by antioxidants such as N-acetyl-L-cysteine and vitamin C. Our findings indicate that in thalassemia, platelets undergo a state of oxidative stress, leading to their activation and potentially to thromboembolic consequences, and suggest that this hypercoagulable state might be treated with antioxidants.
Amino acid mutagenesis within ligand-binding loops in αv confers loss-of-function or gain-of-function phenotype on integrin αvβ3
Authors: Honda Shigenori , Kashiwagi Hirokazu , Kiyoi Teruo , Kato Hisashi , Kosugi Satoru , Shiraga Masamichi , Kurata Yoshiyuki , Tomiyama Yoshiaki 
Published: September 2004

SummaryThe crystal structure of αvβ3 in complex with a cyclic RGDcontaining ligand has recently been demonstrated. However, the functional significance of each residue within ligand binding loops has not been fully elucidated. Here, by employing alaninescanning mutagenesis, we have examined the functional role of ligand contact residues in αv. Tyr178 –> Ala substitution (Tyr178Ala) and Asp218Ala abolished a monovalent ligand, WOW-1 Fab binding as well as soluble fibrinogen binding, which is in perfect agreement with the crystallography. However, Asp150Ala showed no or only a modest inhibition of ligand binding. In contrast, Tyr substitution at Ala215 (Ala215Tyr) increased WOW-1 Fab binding, suggesting that the substitution increased the integrin affinity. The adhesion assay to immobilized fibrinogen showed essentially the same data as obtained using soluble ligands. Our present data indicate that Tyr178 and Asp218, but not Asp150 in αv is critically involved in ligand-binding and that Ala215 could regulate the affinity of αvβ3.
Platelets from Munc18c heterozygous mice exhibit normal stimulus-induced release
Authors: Schraw Todd , Crawford Garland , Ren Qiansheng , Choi Wangsun , Debbie C. , Pessin Jeffery , Whiteheart Sidney 
Published: September 2004

SummaryA critical aspect of hemostasis is the release of clot-forming components from the three intra-platelet stores: dense core granules, α-granules and lysosomes. Exocytosis from these granules is mediated by soluble (SNAPs and NSF) and integralmembrane proteins (v- and t-SNAREs).Three SM (Sec1/Munc18) proteins are present in mouse platelets (Munc18a, 18b and 18c) and each potentially regulates exocytosis via modulation of their cognate syntaxin binding partner. To define the molecular machinery required for platelet exocytosis, we analyzed platelets from Munc18c heterozygous knockout mice. These platelets show a decrease in Munc18c but no apparent reduction in other secretory machinery components. No differences in the rates of aggregation or of secretion of [3H]-5HT (dense core granules), platelet factor 4 (α-granules), or hexosaminidase (lysosomes) were detected between platelets from Munc18c heterozygous knockout or wild-type mice. The platelets also show normal morphology. Contrary to a predicted requirement for Munc18c in platelet secretion, data reported here show that reducing Munc18c levels does not substantially alter platelet function. These data show that despite Munc18c’s role in platelet secretion, the lack of a secretion defect may be attributed to compensation by other Munc18 isoforms or that one allele is sufficient to maintain secretion under standard conditions.
Increased shear stress- and ristocetin-induced binding of von Willebrand factor to platelets in cord compared with adult plasma
Authors: Rehak Thomas , Cvirn Gerhard , Gallistl Siegfried , Leschnik Bettina , Köstenberger Martin , Katzer Helga , Ribitsch Volker , Muntean Wolfgang 
Published: September 2004

SummaryMultiple indications do exist that the extensive neonatal platelet adhesion and aggregation, and the shorter closure time of neonatal compared with adult whole blood in the platelet function analyzer 100 are attributable to the physiological high plasma concentrations and high concentrations of unusually large von Willebrand factor (vWf) multimers in neonates. However, to date the direct experimental evidence is lacking. Therefore, we compared in the present study the ability of neonatal vWf to bind to platelets to that of adult vWf. Platelet-poor plasma of neonatal or adult origin, containing antibody-stained vWf, was incubated with neonatal or adult platelet suspension. Subsequently, vWf-platelet interaction was induced by exposing the mixture to shear stress by means of a cone/plate measuring system or by incubating the mixture with ristocetin. Finally, samples were analyzed in a FAC Scan flow cytometer. Detected fluorescence intensities directly correlate with the amount of vWf attached to the platelet surface. We found that significantly higher amounts of neonatal vWf were attached to platelets in the presence of shear stress or ristocetin.This efficient neonatal vWf-platelet interaction is an effect intrinsic to the neonatal vWf, and not to the neonatal platelet: the amount of neonatal vWf attached to neonatal platelets was not different from the amount of neonatal vWf attached to adult platelets. Furthermore, decreasing the vWf content in cord plasma to adult level resulted in significantly suppressed vWf-platelet attachment in the presence of ristocetin, indicating that the high neonatal vWf level contributes to the efficient vWf-platelet binding in neonates.
The factor VII activating protease G511E (Marburg) variant and cardiovascular risk
Authors: Miller George , E.Webb Karen , Cooper Jackie , Humphries Steve , Ireland Helen 
Published: September 2004

SummaryA previous study had shown a strong relationship between a variant in factor VII activating protease (FSAP G511E) and advanced carotid atheroma. In-vitro, the variant has reduced fibrinolytic but normal pro-coagulant activity, which may constitute a prothrombotic state. The current study has addressed risk for coronary heart disease in a prospective study of cardio-vascular disorders (Northwick Park Heart Study II). An interactive effect upon risk was found between the 511E allele and elevated levels of cholesterol and triglyceride. Fibrinogen could substitute for triglyceride levels in this risk-interaction analysis. The findings support the proposal that the FSAP 511E allele exacerbates atherosclerosis or its clinical sequelae.
Parallel Robots with Adaptronic Components
Authors: Rose M. , Keimer R. , Breitbach E. J. , Campanile L. F. 
Published: September 2004

Performance in high-speed mechanisms can be increased by means of a lightweight design. But, quite often, the resulting structures have the drawback of being susceptible to vibrations. This can be overcome by applying a smart-structures technology. In this work, an application to parallel mechanisms is presented, in which undesired vibrations are reduced by integrated piezoceramic (PZT) actuators and sensors, which are driven by a proper control system. As a basis for the development of suitable control laws, a proper simulation approach is to be used which is capable to model the mechanism’s dynamic behavior correctly, taking into account large motions. The multibody approach fulfills these requisites. The paper deals with the development of a fast C++-coded S-function in MATLAB/SIMULINK for a “five revolute joint” mechanism chosen as a test platform. This routine incorporates a multibody model with changing states. The flexibility of the bodies is taken into account in a modal form. The corresponding parameters are read from data files which can be generated by suitable preprocessors of proprietary multibody software packages like SIMPACK. The created model is compared with an equivalent SIMPACK-model and an interpolation-based control strategy is discussed.
Splenic lymphoma with villous lymphocytes, associated with type II cryoglobulinemia and HCV infection: a new entity?
Authors: Saadoun David , Suarez Felipe , Lefrere François , Valensi Françoise , Mariette Xavier , Aouba Achille , Besson Caroline , Varet Bruno , Troussard Xavier , Cacoub Patrice , Hermine Oliver 
Published: September 2004

Abstract
Hepatitis C virus (HCV) has been associated with the development of B-cell non-Hodgkin lymphomas. We recently reported the regression of splenic lymphoma with villous lymphocytes (SLVL) in patients with HCV after antiviral treatment, demonstrating a direct role of HCV in lymphomagenesis. This study expands our previous results in 18 patients with chronic HCV and SLVL. Mixed cryoglobulinemia (MC) was present in all cases and was symptomatic in 13 (72%). All patients were treated with interferon alone or in association with ribavirin. Hematologic and virologic responses were correlated. Fourteen (78%) patients achieved a sustained complete hematologic response after clearance of HCV RNA. Two patients had a virologic partial response and achieved a complete hematologic response. Two virologic nonresponders achieved partial hematologic response. Regardless of the response, monoclonal immunoglobulin gene rearrangement persisted after treatment. This study underscores the role of HCV in the lymphomagenesis and the benefit of antiviral treatment for patients presenting with HCV-driven lymphoproliferations.
Artificial neural network approach for selection of susceptible single nucleotide polymorphisms and construction of prediction model on childhood allergic asthma
Authors: Tomita Yasuyuki , Tomida Shuta , Hasegawa Yuko , Suzuki Yoichi , Shirakawa Taro , Kobayashi Takeshi , Honda Hiroyuki 
Published: September 2004

Abstract
Background
Screening of various gene markers such as single nucleotide polymorphism (SNP) and correlation between these markers and development of multifactorial disease have previously been studied. Here, we propose a susceptible marker-selectable artificial neural network (ANN) for predicting development of allergic disease.

Results
To predict development of childhood allergic asthma (CAA) and select susceptible SNPs, we used an ANN with a parameter decreasing method (PDM) to analyze 25 SNPs of 17 genes in 344 Japanese people, and select 10 susceptible SNPs of CAA. The accuracy of the ANN model with 10 SNPs was 97.7% for learning data and 74.4% for evaluation data. Important combinations were determined by effective combination value (ECV) defined in the present paper. Effective 2-SNP or 3-SNP combinations were found to be concentrated among the 10 selected SNPs.

Conclusion
ANN can reliably select SNP combinations that are associated with CAA. Thus, the ANN can be used to characterize development of complex diseases caused by multiple factors. This is the first report of automatic selection of SNPs related to development of multifactorial disease from SNP data of more than 300 patients.
Most of the extant mtDNA boundaries in South and Southwest Asia were likely shaped during the initial settlement of Eurasia by anatomically modern humans
Authors: Metspalu Mait , Kivisild Toomas , Metspalu Ene , Parik Jüri , Hudjashov Georgi , Kaldma Katrin , Serk Piia , Karmin Monika , Behar Doron M , Gilbert M Thomas P , Endicott Phillip , Mastana Sarabjit , Papiha Surinder S , Skorecki Karl , Torroni Antonio , Villems Richard 
Published: September 2004

Abstract
Background
Recent advances in the understanding of the maternal and paternal heritage of south and southwest Asian populations have highlighted their role in the colonization of Eurasia by anatomically modern humans. Further understanding requires a deeper insight into the topology of the branches of the Indian mtDNA phylogenetic tree, which should be contextualized within the phylogeography of the neighboring regional mtDNA variation. Accordingly, we have analyzed mtDNA control and coding region variation in 796 Indian (including both tribal and caste populations from different parts of India) and 436 Iranian mtDNAs. The results were integrated and analyzed together with published data from South, Southeast Asia and West Eurasia.

Results
Four new Indian-specific haplogroup M sub-clades were defined. These, in combination with two previously described haplogroups, encompass approximately one third of the haplogroup M mtDNAs in India. Their phylogeography and spread among different linguistic phyla and social strata was investigated in detail. Furthermore, the analysis of the Iranian mtDNA pool revealed patterns of limited reciprocal gene flow between Iran and the Indian sub-continent and allowed the identification of different assemblies of shared mtDNA sub-clades.

Conclusions
Since the initial peopling of South and West Asia by anatomically modern humans, when this region may well have provided the initial settlers who colonized much of the rest of Eurasia, the gene flow in and out of India of the maternally transmitted mtDNA has been surprisingly limited. Specifically, our analysis of the mtDNA haplogroups, which are shared between Indian and Iranian populations and exhibit coalescence ages corresponding to around the early Upper Paleolithic, indicates that they are present in India largely as Indian-specific sub-lineages. In contrast, other ancient Indian-specific variants of M and R are very rare outside the sub-continent.
Effects of age and leg length upon central loop of the Gastrocnemius-soleus H-reflex latency
Authors: Sadeghi Shahram , Ghavanini Mohammadrezaalavian , Ashraf Alireza , Jafari Peyman 
Published: September 2004

Abstract
Background
central loop of the gastrocnemius-soleus H-reflex latency (Tc) that looks promising in the diagnosis of S1 radiculopathy; has been investigated in a few studies and only two of them have focused on the constitutional factors affecting it. Although leg length has been shown to contribute to the Tc, the role of age is controversial. More confusing, none of the previously performed studies have used strict criteria to rule out subclinical neuropathy, so the results could be misleading. This study has been performed to determine the influence of leg length and age on Tc among a carefully selected group of healthy volunteers.

Methods
after screening forty six volunteers by taking history, physical examination and a brief electrophysiologic study; forty of them were selected to enroll into the study. Tc was obtained in all the study subjects and leg length and age were recorded for correlational analyses.

Results
this group was consisted of 26 males (65%) and 14 females (35%) with the age range of 19–65 years (Mean ± SD: 37 ± 10.7) and leg length range of 29.5–43 centimeters (36.4 ± 3.4).
Mean ± SD for Tc was 6.78 ± 0.3. We found a significant correlation between Tc and leg length (p value= 0.003, r = 0.49 and confidence interval 95% = 0.59–0.88), no significant correlation was found between age and Tc (p value= 0.48, r = 0.11), also we obtained the regression equation as: Tc = 0.04L + 5.28

Conclusions
in contrast to leg length, age was not correlated with Tc. Future studies are required to delineate other contributing factors to Tc.
Lactobacillus caseistrain GG in the treatment of infants with acute watery diarrhea: A randomized, double-blind, placebo controlled clinical trial [ISRCTN67363048]
Authors: Salazar-Lindo Eduardo , Miranda-Langschwager Percy , Campos-Sanchez Miguel , Chea-Woo Elsa , Sack R Bradley 
Published: September 2004

Abstract
Background
Adjuvant therapy to ORT with probiotic bacteria for infants with acute watery diarrhea has been under active investigation. Most studies have been done in the developed world showing benefit only for viral mild gastroenteritis. We evaluated the effect of a milk formula containing one billion (109) cfu/ml of Lactobacillus casei strain GG (LGG) upon duration and severity of diarrhea in infants in an environment with more severe acute diarrhea, where etiologic agents other than rotavirus are involved more frequently, and where mixed infections are more prevalent.

Methods
Male infants aged 3–36 months brought for treatment of acute watery diarrhea of less than 48 hours were eligible. After rehydration was completed with the WHO's oral rehydration solution, patients were randomly assigned to receive a milk formula either containing LGG or not. Stool volume was periodically measured using a devise suited to collect stools separate from urine. Duration of diarrhea was estimated based on stools physical characteristics.

Results
Eighty nine patients received the placebo milk formula and ninety received the LGG containing formula. Both groups were comparable in their baseline characteristics. Total stool output was significantly larger (p = 0.047) in the LGG group (247.8 ml/kg) than in the placebo group (195.0 ml/kg). No significant differences were found in duration of diarrhea (58.5 hours with LGG vs. 50.4 hours with placebo), rate of treatment failure (21.1% with LGG vs. 18.0% with placebo), and proportion of patients with unresolved diarrhea after 120 hours (12.2% with LGG vs. 12.5% with placebo). The rate of stools with reducing substances after 24 hours of treatment increased significantly in both groups (from 41.4% to 72.2% with LGG and from 45.9% to 68.0% with placebo).

Conclusion
This study did not show a positive effect of LGG on the clinical course of acute watery diarrhea. Positive beneficial effects of LGG, as had been reported elsewhere, could have been masked in our study by worsening diarrhea due to transient lactose malabsorption. Further studies with low-lactose or non-lactose conveyors of LGG are desirable.