bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Switching to Wen-Jing-Tang (Unkei-To) from Preceding Herbal Preparations Selected by Eight-Principle Pattern Identification on Endocrinological Status and Ovulatory Induction in Women with Polycystic Ovary Syndrome
Authors: Ushiroyama Takahisa , Hosotani Toshimitsu , Mori Kuniko , Yamashita Yoshiki , Ikeda Atsushi , Ueki Minoru 
Published: March 2006

The objective of this study was to investigate the effects of switching therapy to Wen-jing-tang (Unkei-to) from previous selected herbal preparations on endocrine levels and induction of ovulation in women with polycystic ovary syndrome (PCOS). Sixty-four anovulatory women diagnosed with PCOS were enrolled in the study. After Kampo diagnosis, subjects received matched Kampo preparations (43 cases: Dang-gui-shao-yao-san, 21 cases: Gui-zhi-fu-ling-wan) selected by the matching theory of eight-principle pattern identification and Kampo diagnosis based on concepts of the qi, blood, and fluids as the physiologic activity. Fifty-four women who failed to ovulate after an 8-week treatment were randomly allocated to continuation of treatment with the preceding Kampo prescription (continuation group, n = 27) or treatment with Wen-jing-tang (switching group, n = 27). Plasma FSH, LH and estradiol levels were measured and ovulation rates were determined at the beginning and after an 8-week treatment with the preceding Kampo prescription, as well as after the subsequent 8-week treatment with the same preparation or Wen-jing-tang. No decrease in mean plasma LH level was observed in the 54 women who failed to ovulate among the 64 treated with a Kampo preparation. After the 8-week treatment with Wen-jing-tang, plasma LH levels were decreased by 58.2% ( p < 0.0001) and 49.4% ( p = 0.0005) in the groups switched from Dang-gui-shao-yao-san and Gui-zhi-fu-ling-wan, respectively. In the group switched from Dang-gui-shao-yao-san, a tendency towards increase in plasma estradiol level was observed (1.51-fold, p = 0.055), which was significant compared with that in the group switched from Gui-zhi-fu-ling-wan ( p = 0.032). The ovulation rate with switching of treatment to Wen-jing-tang was significantly higher (59.3%) than that with continued use of the same preparation (7.4%, p = 0.0036). This study confirmed that Wen-jing-tang was effective in improving endocrine condition in the treatment of disturbances of ovulation in patients with PCOS without taking eight-principle pattern identification into consideration. This finding indicates that Wen-jing-tang is appropriate for use in treating PCOS in women with various constitutions (as determined by the matching theory of eight-principle pattern identification) in clinical practice and may prove to be a potent therapeutic agent with a wide therapeutic spectrum.
Characterisation of 96 mutations in 128 unrelated severe haemophilia A patients from France
Authors: Vinciguerra Christine , Zawadzki Christophe , Dargaud Yesim , Pernod Gilles , Berger Claire , Nougier Christophe , Négrier Claude 
Published: March 2006

SummaryDirect sequencing of the coding region of factor VIII (F8) gene was used to determine the mutations responsible for severe haemophilia A (FVIII<1%) in 128 unrelated haemophiliacs A, negative for intron 22 and intron 1 inversions. A mutation was found in 122/128 patients (95%). Ninety-six distinct mutations were identified in this cohort, 62 of these are novel. They consisted of deletions (7 large and 24 small deletions), insertions (n=9), associations of insertion/deletion (n=2), association of deletion/substitution (n=1), and single nucleotide substitutions (53 point mutations consisting of 31 missense, 20 nonsense, and 2 splicing mutations). Twenty-two patients had developed inhibitors, and among this subgroup 3 large deletions, 6 frameshift, 9 nonsense and 4 missense mutations were detected. For6 patients, among which one developed an anti-FVIII inhibitor, no mutations were detected in the coding and splicing regions of factor VIII gene. Different approaches of molecular modelling were performed in addition to familial linkage analysis to determine the pathophysiological responsibility of these novel missense mutations.
Homocysteine levels in amniotic fluid
Authors: Colaizzo Donatella , Vecchione Gennaro , Sciannamè Natale , Notarangelo Angelo , Croce Anna , Margaglione Maurizio , Grandone Elvira 
Published: March 2006

SummaryHyperhomocysteinemia could playa similar role in the placenta to that played in adults at risk of thrombosis. Moreover, hyperhomocysteinemia in women is described to be associated with the birth of small for gestational age (SGA) newborns, although there are discrepancies on this issue. To date, there is no biochemical marker predictive of SGA in a given pregnancy. We verified the presence of a relationship between homocysteine in amniotic fluid at mid-pregnancy and birth-weight. Amniotic fluid was obtained from 459 healthy women undergoing midtrimester amniocentesis (17.1 ± 1.2 weeks) because of maternal age. Homocysteine levels were measured in 434 (10 twin) pregnancies. In addition, femur length (FL) and biparietal diameter (BPD) were measured. Outcome of pregnancy was recorded. 233 (53.7%) foetuses were males,201 (46.3%) females. The mean homocysteine concentration was 1.04 ± 0.72 µM, (95% C.I. 0.43–2.41). An univariate analysis showed the presence of an association with gestational age, FL, BPD. A multiple linear regression showed that homocysteine levels were significantly associated with FL (p<0.001) and BPD (p=0.011). After excluding twin pregnancies, 31 newborns (7.3%) were classified as SGA. Mean birth-weight was 2390 g in SGA, where as it was 3360 g in 393 adequate for gestational age (AGA) newborns (p<0.001).The adjusted mean level of homocysteine was significantly lower in AGA (1.01 µM; 95%CI: 0.94–1.08) than that recorded in pregnancies resulting in a SGA (1.29 µM; 95%CI: 1.05–1.51; p=0.03). In a large setting, these data provide reference values for homocysteine in amniotic fluids. Moreover, they suggest that homocysteine levels in amniotic fluids may be higher in pregnancies with a SGA newborn.
Less pronounced enhancement of thrombin-dependent inactivation of plasminogen activator inhibitor type 1 by low molecular weight heparin compared with unfractionated heparin
Authors: Nakamura Ryuta , Umemura Kazuo , Hashimmoto Hisakuni , Urano Tetsumei 
Published: March 2006

SummaryPlasminogen activator inhibitor type 1 (PAI-1), the primary inhibitor of plasminogen activators, also forms high molecular weight complexes with either thrombin or factor Xa (FXa) in the presence of heparin, resulting in the loss of mutual activities of enzyme and inhibitor.We have proposed that the inactivation of PAI-1 by these activated coagulation factors is one of the mechanisms responsible for coagulation-associated enhancement of fibrinolysis. In the present study, we compared the effects of low molecular weight (LMW)- and unfractionated-heparin on the interaction between PAI-1 and either thrombin or FXa. Both types of heparin enhanced the inhibition of thrombin activity by PAI-1 with a bell-shaped pattern, though the magnitude of the enhancement was significantly weaker with LMW-heparin. In FXa inhibition by PAI-1, only unfractionated-heparin enhanced the inhibition. In the presence of vitronectin (Vn), the inhibition of thrombin and FXa by PAI-1 was further promoted by both types of heparin but toa significantly lesser extent with LMW-heparin.We then analyzed the possible enhancing effect of heparin on tissue plasminogen activator (tPA)-induced fibrinolysis. As a consequence of thrombin-dependent inactivation of PAI-1, tPA-induced fibrin clot lysis time in the presence of PAI-1 was shortened by unfractionated-heparin as well as by LMW-heparin with lesser extent, which was further enhanced by Vn. Less pronounced enhancement of complex formation between thrombin and PAI-1 by LMW-heparin appeared to be directly related to the weaker potential of LMW-heparin in enhancing fibrinolysis and accelerating hemorrhagic tendency via neutralization of PAI-1 activity.
Home treatment of haemarthroses using a single dose regimen of recombinant activated factor VII in patients with haemophilia and inhibitors
Authors: Kavakli Khan , Makris Mike , Zulfikar Bulent , Erhardtsen Elizabeth , Abrams Zvi , Kenet Gili ,   for the NovoSeven ® trial (F7HAEM-1510) investigators
Published: March 2006

SummaryThe aim was to evaluate the efficacy and safety of two recombinant factor VIIa (rFVIIa) dose regimens for treating haemarthroses in patients with congenital haemophilia A or B and inhibitors. This was a multi-centre, randomised, cross-over, double-blind trial. Patients were randomly allocated to treat a first joint bleeding episode with one 270 µg/kg rFVIIa dose followed by two doses of placebo at 3-hour intervals and a second joint bleed with three single doses of 90 µg/kg rFVIIa at 3-hour intervals, or vice versa. Efficacy was evaluated using a novel and robust treatment response-rating scale based on patient-assessment of pain and joint mobility. Outcome was rated at different timepoints, and an effective or ineffective treatment response was determined. Treatment “preference” was defined as effective treatment with one regimen and ineffective with the other. Patients with equally effective or ineffective treatments had no “preference”. Treatment was rated as effective for 65% of patients using the 270 µg/kg dose versus 70% for the 90 µg/kg ×3 regimen. An equal “preference” was noted for the two regimens (21% for each; p = 0.637); most patients (58%) had no “preference”. 37/42 bleeding episodes (88%) were successfully treated with rFVIIa; additional haemostatic medications were administered for five episodes. No safety issues were identified. Administration of rFVIIa as a single 270 µg/kg dose to treat haemarthroses in patients with haemophilia and inhibitors was at least as efficacious and safe as the 90 µg/kg ×3 regimen.
Comparison of three activated protein C resistance tests in the risk assessment of venous thrombosis in non-carriers of the factor V Leiden mutation
Authors: Guerrero Felipe , Arnaud Catherine , Nguyen Francoise , Boneu Bernard , Sié Pierre 
Published: March 2006

SummaryActivated protein C resistance (APCR), measured using the original assay described by Dahlbäck, is a risk factor for venous thrombosis independent of the factor V Leiden (FVL) mutation. This assay is based on the activated partial thromboplastin time (APTT) after plasma exposure to activated protein C (APC).As this assay was sensitive to numerous interferences, new assays have been developed for FVL screening. The objectives of the study were to investigate the association of second generation assays for APCR with venous thrombosis in FVL non-carriers. One hundred ninety-seven subjects with a history of venous thrombosis and 211 controls were explored using 3 APCR assays, the original APTT-based assay (test A), an APTT-based assay with factorV depleted plasma pre-dilution (test B) and a direct factorX activation-based assay with the same pre-dilution (test C).We found that subjects with results in the lowest quartile of the APTT-based assays are at increased risk, compared to those in the highest quartile (test A Odds Ratio = 6.39; 95%CI 3.23–12.63; test B OR=2.72; 95%CI 1.50–4.94). There was no significant risk increase associated with test C results. After adjusting for FVIII levels, the ORs of tests A and B were similar (test A OR=3.22; 95%CI 1.47–7.08; test B OR=3.10; 95%CI 1.54–6.21). In conclusion, APTT-based assays, but not direct factor X activation-based assays, effectively detect the risk for venous thrombosis independent of FVL. Pre-dilution in factor V depleted plasma is an effective way to directly assess the risk independent of FVIII levels.
Dose- and time-dependent antiplatelet effects of aspirin
Authors: Perneby Christina , Wallén N. Håkan , Rooney Cathy , Fitzgerald Desmond , Hjemdahl Paul 
Published: March 2006

SummaryAspirin is widely used, but dosages in different clinical situations and the possible importance of “aspirin resistance” are debated. We performed an open cross-over study comparing no treatment (baseline) with three aspirin dosage regimens – 37.5 mg/ day for 10 days, 320 mg/day for 7 days, and, finally, a single 640 mg dose (cumulative dose 960 mg) – in 15 healthy male volunteers. Platelet aggregability was assessed in whole blood (WB) and platelet rich plasma (PRP).The urinary excretions of stable thromboxane (TxM) and prostacyclin (PGI-M) metabolites, and bleeding time were also measured. Platelet COX inhibition was nearly complete already at 37.5 mg aspirin daily, as evidenced by >98 % suppression of serum thromboxane B2 and almost abolished arachidonic acid (AA) induced aggregation in PRP 2–6 h after dosing. Bleeding time was similarly prolonged by all dosages of as- pirin. Once daily dosing was associated with considerable recovery of AA induced platelet aggregation inWB after 24 hours, even after 960 mg aspirin. Collagen induced aggregation in WB with normal extracellular calcium levels (hirudin anticoagulated) was inhibited <40% at all dosages. TxM excretion was incompletely suppressed, and increased <24 hours after the cumulative 960 mg dose. Aspirin treatment reduced PGI-M already at the lowest dosage (by ≈25%), but PGI-M excretion and platelet aggregability were not correlated. Antiplatelet effects of aspirin are limited in WB with normal calcium levels. Since recovery of COX-dependent platelet aggregation occurred within 24 hours, once daily dosing of aspirin might be insufficient in patients with increased platelet turnover.
Hyperprothrombinaemia-induced APC resistance: Differential influence on fibrin formation and fibrinolysis
Authors: Binetti Bianca , Rotunno Crescenza , Tripodi Armando , Asti Daniela , Semeraro Fabrizio , Semeraro Nicola , Colucci Mario 
Published: March 2006

SummaryThe prothrombin gene mutation G20210A is a common risk factor for thrombosis and has been reported to cause APC resistance. However, the inhibition of thrombin formation by APC not only limits fibrin formation but also stimulates fibrinolysis by reducing TAFI activation. We evaluated the influence of prothrombin G20210A mutation on the anticoagulant and fibrinolytic activities of APC (1 µg/ml). Thirtytwo heterozygous carriers and 32 non carriers were studied. APC anticoagulant activity was assessed by aPTT prolongation whereas APC fibrinolytic activity was determined by a microplate clot lysis assay. APC-induced aPTT prolongation was markedly less pronounced in carriers than in non carriers. On the contrary, fibrinolysis time was shortened by APC to a comparable extent in both groups. Accordingly, prothrombin levels were strongly correlated with APC-induced aPTT prolongation but not with APC-induced shortening of lysis time. The addition of purified prothrombin to normal plasma (final concentration 150%) caused APC resistance in the clotting assay over the whole range of tested APC concentrations (0.125–1.5 µg/ml). In the fibrinolytic assay, instead, prothrombin supplementation made the sample resistant to low but not to high concentrations of APC (>0.5 µg/ml). Thrombin and TAFIa determination in the presence of 1 µg/ml APC revealed that hyperprothrombinemia, although capable of enhancing thrombin generation, was unable to induce detectable TAFIa formation. It is suggested that APC resistance caused by hyperprothrombinaemia does not translate in impaired fibrinolysis, at least in the presence of high APC levels, because the increase in thrombin formation is insufficient to activate the amount of TAFI required to inhibit plasminogen conversion. These data might help to better understand the relationship between thrombin formation and fibrinolysis down-regulation.
Genetic analysis of CAV1 gene in hypertension and metabolic syndrome
Authors: Grilo Antonio , Fernandez Maria , Beltrán Manuel , Ramirez-Lorca Reposo , González María , Royo Jose , Gutierrez-Tous Reyes , Morón Francisco , Couto Carmen , Serrano-Rios Manuel , Saez Maria , Ruiz Agustin , Real Luis 
Published: March 2006

SummaryRecently, we reported that the polymorphism 1132T>C (Gene-Bank: AF519768.1) of the NOS3 gene was associated with susceptibility to metabolic syndrome (MS) in hypertensive patients. This suggests that other genes such as CAV1, whose product (CAV1) regulates eNOS activity, could also be related to this phenotype.In this work we investigated the following:i) whether CAV1 is a quantitative trait locus of clustering of atherothrombotic traits associated with MS; ii) whether CVA1 is associated with hypertension or MS in hypertensive patients; and iii) whether genetic interaction between NOS3 and CAV1 is involved in the susceptibility or protection to hypertension associated with MS.To carry out the study, we genotyped 285 randomly selected individuals and 175 hypertensive patients, all of them ≤ 60 years old, with two polymorphisms of the CAV1 gene: the 22285 C>T and the 22375–22375 del AC (GeneBank AF125348), and the 1132T>C polymorphism of the NOS3 gene. To perform sample genotyping, we used pyrosequencing and FRET techniques.The 22285 C-22375–22375 del (Cd) haplotype of CAV1 gene was associated with low levels of blood pressure in the general population. Moreover, it was a genetic protection factor against MS in hypertensive patients. In addition, we found no evidence of gene-gene interaction between NOS3 and CAV1 genes with regard to that phenotype.
Biodistribution of covalent antithrombin-heparin complexes
Authors: Chindemi Paul , Klement Petr , Konecny Filip , Berry Leslie , Chan Anthony 
Published: March 2006

SummaryWe have developed a covalent antithrombin-heparin (ATH) complex with advantages compared to non-covalent antithrombin: heparin (AT:H) mixtures. In addition to increased activity, ATH has a longer intravenous half-life that is partly due to reduced plasma protein binding. Given ATH’s altered clearance, we investigated biodistribution of ATH in vivo. ATH made from either human plasma-derived AT (pATH) or recombinant human (produced in goats) AT (rhATH) was studied. 125I-ATH + unlabeled carrier was injected into rabbits at different doses. 131Ilabeled albumin was administered just before sacrifice as a marker for trapped blood in tissues. Immediately after sacrifice, animal components were removed, weighed, and subsamples were counted for gamma-radioactivity. Percent recoveries of ATH in various organs/compartments at different time points were calculated, and kinetic distribution plots generated. At saturating doses, early disappearance of rhATH from the circulation was much faster than pATH. Co-incident with clearance, 26 ± 3 % of dose for rhATH was liver-associated compared to only 3.7 ± 0.5 % for pATH by 20 min. Also, at early time periods, > 60% of all extravascular ATH was liver-associated. Analysis of the vena cava and aorta suggested that vessel wall binding might also account for initial plasma loss of rhATH. By 24 h, most of pATH and rhATH were present as urinary degradation products (51 ±3 % and 63 ±8 %, respectively). In summary, systemic elimination of ATH is greatly influenced by the form of AT in the complex, with liver uptake and degradation playing a major role.
Anti-angiogenesis mediated by angiostatin K1–3, K1–4 and K1–4.5
Authors: Chen Ya-Huey , Wu Hua-Lin , Li Ching , Huang Yi-Hsien , Chiang Chi-Wu , Wu Ming-Ping , Wu Li-Wha 
Published: March 2006

SummaryThe molecular mechanism mediated by multiple forms of angiostatin via acting on proliferating vascular endothelium remains elusive. To address whether three forms of angiostatin, K1-3, K1-4 or K1-4.5, utilized similar or distinct pathways to mediate anti-angiogenesis, we adopted an adenoviral expression system to express secretable angiostatin molecules for CM collection. The anti-angiogenic activity of K1-3, K1-4 or K1-4.5 was confirmed by using proliferation, migration, tube formation and apoptotic assays of human endothelial cells. These angiostatin molecules at comparable expression level inhibited various in vitro angiogenesis assays with some variations. Furthermore, K1-3, K1-4 or K1-4.5 increased the expression of p53 protein and its downstream effectors, enhanced FasL-mediated signaling pathways, and decreased activation of AKT. At least three different receptors, Fas, integrin αvβ3 and ATP synthase, were involved in the anti-angiogenic action of angiostatin molecules. Besides, the expression of 189 genes at mRNA level was significantly altered by K1-3, K1-4 or K1-4.5. More than 70% of these genes participate in growth, inflammation, apoptosis, migration and extracellular matrix. Taken together, K1-3, K1-4 and K1-4.5, regardless of the number of kringles in the angiostatin molecules, mediated anti-angiogenesis via mostly similar pathways. We are the first to demonstrate the involvement of DAPK1 in the mediation of anti-angiogenesis by angiostatin.
Analysis of SAGE data in human platelets: Features of the transcriptome in an anucleate cell
Authors: Dittrich Marcus , Birschmann Ingvild , Pfrang Julia , Herterich Sabine , Smolenski Albert , Walter Ulrich , Dandekar Thomas 
Published: March 2006

SummaryA comprehensive SAGE (serial analysis of gene expression) library of purified human platelets was established. Twenty-five thousand (25,000) tags were sequenced, and after removal of mitochondrial tags, 12,609 (51%) non-mitochondrial-derived tags remained, corresponding to 2,300 different transcripts with expression levels of up to 30,000 tags per million. This new, highly purified SAGE library of platelets is enriched in specific transcripts.The complexity in terms of tag distribution is similar to cells that are still able to replenish their mRNA pool by transcription.We show that our SAGE data are consistent with recently published microarray data but show further details of the platelet transcriptome, including (i) longer UTR regions and more stable folding in the enriched mRNAs, (ii) biologically interesting new candidate mRNAs that show regulatory elements, including elements for RNA stabilization or for translational control, and (iii) significant enrichment of specific, highly transcribed mRNAs compared to a battery of SAGE libraries from other tissues. Among several regulatory mRNA elements known to be involved in mRNA localization and translational control, CPE elements are in particular enriched in the platelet transcriptome. mRNAs previously reported to be translationally regulated were found to be present in the library and were validated by real-time PCR. Furthermore, specific molecular functions such as signal transduction activity were found to be significantly enriched in the platelet transcriptome.These findings emphasize the richness and diversity of the platelet transcriptome.