bluuebunny/crossref_metadata_2025 huggingface dataset:
Down syndrome and the genes of human chromosome 21: current knowledge and future potentials
Authors: Pritchard M. , Reeves R.H. , Dierssen M. , Patterson D. , Gardiner K.J.
Published: June 2008

Down syndrome (DS), trisomy of human chromosome 21, is the most common genetic cause of intellectual disability. With an incidence in some countries as high as one in approximately 700 live births, and a complex, extensive and variably severe phenotype, Down syndrome is a significant medical and social challenge. In recent years, there has been a rapid increase in information on the functions of the genes of human chromosome 21, as well as in techniques and resources for their analysis. A recent workshop brought together experts on the molecular biology of Down syndrome and chromosome 21 with interested researchers in other fields to discuss advances and potentials for generating gene-phenotype correlations. An additional goal of the workshop was to work towards identification of targets for therapeutics that will correct features of DS. A knowledge-based approach to therapeutics also requires the correlation of chromosome 21 gene function with phenotypic features.
Recurrence of Keratocystic Odontogenic Tumor: Clinicopathological Features and Immunohistochemical Study of the Hedgehog Signaling Pathway
Authors: Yagyuu Takahiro , Kirita Tadaaki , Sasahira Tomonori , Moriwaka Yukiko , Yamamoto Kazuhiko , Kuniyasu Hiroki
Published: June 2008

Aims: Critical factors responsible for the recurrence of keratocystic odontogenic tumor (KCOT) were examined. Methods: The clinicopathological features were retrospectively studied in 74 patients with 75 sporadic KCOTs. From the 75 KCOTs, 23 were examined for the expression of Sonic Hedgehog (SHH), Patched and Smoothened (SMO) by immunohistochemistry. Results: Recurrence in multilocular lesions was more frequent than in unilocular lesions. Nine (64%) of 14 multilocular lesions recurred, in contrast to 2 (7%) of 27 unilocular lesions (p = 0.0350). The average length of recurrent lesions (62.8 ± 6.5 mm) was larger than that of nonrecurrent lesions (43.0 ± 4.0 mm; p = 0.0363). The immunoreactivity of proliferation-related SMO in KCOTs with recurrence was higher than that of those without recurrence (p = 0.0475), whereas the expressions of a ligand, SHH, and an inhibitory receptor, Patched, were not associated with KCOT recurrence. The expressions of SHH and SMO showed inverse correlation in whole KCOT (p = 0.0318). Conclusion: These findings suggest that recurrence of KCOT is associated with multilocular large lesions and high SMO expression.
Chromosomal evolution and distribution of telomeric repeats in golden moles (Chrysochloridae, Mammalia)
Authors: Gilbert C. , Maree S. , Robinson T.J.
Published: June 2008

Golden moles (Chrysochloridae) are small, subterranean mammals endemic to sub-Saharan Africa that together with tenrecs constitute one of six orders in Afrotheria. Here we present a comprehensive karyotypic comparison among six species/subspecies of golden moles based on G-banding and chromosome painting. By expanding the species representation to include a further five species recently published in a companion paper, we were able to map the distribution of telomeric repeats in ten species/subspecies that are representative of six of the nine currently recognized genera. We conclude that: (i) the monophyly of Amblysomus is supported by the amplification of heterochromatin in several pericentric regions and one intrachromosomal rearrangement; (ii) A. hottentotus meesteri groups as sister to a clade that contains A. h. hottentotus, A. h. longiceps, A. h. pondoliae and A. robustus, an association that is underpinned by a shared intrachromosomal rearrangement and the detection of telomeric sequences in the centromeres of all chromosomes of the three A. hottentotus subspecies and A. robustus but, importantly, not in those of A. h. meesteri. These findings indicate an absence of gene flow suggesting that A. h. meesteri should be elevated to specific status. We hypothesize that the lack of gene flow may, in part, reflect hybrid dysgenesis resulting from abnormal meiotic segregation as a consequence of differences in the nature of the centromeric specific satellites; (iii) chromosomes 7 and 13 of Chrysochloris asiatica are fused in both Calcochloris obtusirostris and Eremitalpa granti, but that the position of the centromere in the fused chromosome differs in each species. This suggests that rather than being indicative of common ancestry, the fusion is more likely a convergent character which has arisen independently in each lineage. Furthermore our painting data show two centromeric shifts that are probably autapomorphic for C. obtusirostris. Finally, we conclude that (iv) golden moles are characterized by strong karyotypic conservatism but in marked contrast to the constrained rates of change exhibited by most species, A. robustus is unique in that three autapomorphic fissions define its evolutionary history, and hence the more extensive reshuffling of its genome.
Arteriovenous Malformations of the Uterus: Long-Term Follow-Up
Authors: Dar Peer , Karmin Ira , Einstein Mark H.
Published: June 2008

Background/Aim: Arteriovenous malformations (AVMs) of the uterus have various clinical presentations. With the advancement of and accessibility to imaging, the diagnosis of the lesions in association with less severe clinical presentations is becoming more common. Contrary to cases with severe hemorrhage, the management of these cases is not clear. The purpose of this study was to describe our experience with diagnosis, management and long-term follow-up of cases with different clinical presentations of uterine AVMs. Methods: The clinical and sonographic presentations of 8 cases diagnosed between July 2000 and July 2003 in our medical center are described. Annual sonographic follow-up was performed for a period of at least 42 months. Results: Only 3 of the 8 cases presented with heavy vaginal bleeding and 2 of them required selective embolization. Two patients had hysterectomy during the study period which was not related to a severe bleeding event. Long-term follow-up for all other cases was significant for sonographic resolution of the uterine AVM. Conclusion: Management of uterine AVMs should be influenced by the clinical and not by the sonographic findings. If clinically feasible, conservative management should be considered as the primary approach, since most of these lesions tend to spontaneously resolve.
Effect of Adlay, Buckwheat and Barley on Lipid Metabolism and Aorta Histopathology in Rats Fed an Obesogenic Diet
Authors: Son Bo Kyung , Kim Jung Yun , Lee Sang Sun
Published: June 2008

Background/Aims: The present study was carried out to evaluate the nutritional quality of adlay (AD), buckwheat (BW) and waxy barley (WB), with particular respect to their fiber components. Plasma lipid parameters, gut transit time and thickness of the aortic wall in rats fed with different grains were evaluated and compared with rats fed on white rice (WR). Methods: The rats were then raised for 4 weeks on an obesogenic diet based on the American Institute of Nutrition-93 (AIN-93 G) diets containing 1% cholesterol and 20% dietary lipids. 40 male rats were divided into 4 groups and raised for 4 weeks with a diet containing one of the following grains: WR, AD, BW, or WB. Results: Gut transit time was shortened depending on the grain, with the WB group having the shortest time, followed by the BW group and the AD group, and then the WR group. Plasma lipid profiles differed significantly according to grain combination, and the levels of triglycerides in the AD, BW and WB groups were significantly lower than that in the WR group. The BW and WB groups showed lower levels of total cholesterol and LDL-C, and higher HDL-C than the WR group, although the group fed on AD did not show such results owing to the high content of lipids and calories. Accordingly, the reduction in gut transit time resulted in decreasing levels of triglycerides, total cholesterol and LDL-C. Rats fed on WB and BW showed significantly larger aortic lumen than those fed with AD and WR. Also the wall thickness of the WB group was significantly thinner than that of the WR group. Conclusion: Consumption of BW- and WB-containing diets significantly improved several cardiovascular risk factors induced by obesity in experimental rats.
Influence of Lys656Asn Polymorphism of Leptin Receptor Gene on Leptin Response Secondary to Two Hypocaloric Diets: A Randomized Clinical Trial
Authors: de Luis D.A. , Aller R. , Izaola O. , Gonzalez Sagrado M. , Conde R.
Published: June 2008

Background: Human obesity is characterized by high levels of leptin, and it has been suggested that obese patients may be leptin-resistant. Objective: The aim of our study was to investigate the influence of Lys656Asn polymorphism in the LEPR gene on leptin response secondary to a low fat versus a low carbohydrate diet in obese patients. Design: A population of 78 obesity patients was enrolled. Before and after 2 months of two diets, a nutritional evaluation was performed. Results: 52 patients had genotype Lys656/Lys656 (wild group) and 26 patients Lys656/Asn656 or Asn656/Asn656 (mutant group). In the low fat and wild groups, BMI, weight, fat mass, glucose, total cholesterol, triglyceride, insulin, and blood pressure decreased. In mutant type (MT), BMI, weight and fat mass decreased. In wild type (WT) with low carbohydrate diet, BMI, weight, fat mass, waist circumference, waist-to-hip ratio, total cholesterol, and blood pressures decreased. In MT, BMI, weight and fat mass decreased. Only leptin concentrations have a significant decrease in WT with both diets (diet I: 30.3%; p < 0.05) and (diet II: 15.5%; p < 0.05). Conclusion: In WT patients, the changes in serum leptin concentration due to 2 months’ intervention with low fat are higher than with a low carbohydrate diet.
BCSG1 Methylation Status and BCSG1 Expression in Breast Tissues Derived from Chinese Women with Breast Cancer
Authors: Gu Yu-Mei , Tan Jian-Xin , Lu Xiao-Wei , Ding Yun , Han Xiao , Sun Yu-Jie
Published: June 2008

Objective: To investigate the role of DNA methylation in the regulation of BCSG1 gene expression in breast tissues derived from Chinese women with breast cancer. Methods: The methylation status of exon 1 of the BCSG1 gene in breast cancer, and matched non-neoplastic adjacent and benign lesion tissues was extensively examined using methylation-specific PCR analysis. Corresponding mRNA expression levels were determined by real-time PCR. Results: We found: (1) the BCSG1 gene was universally demethylated in all breast tissues regardless of the tissue state, although 50–60% of the samples displayed methylated products as well; (2) DNA methylation correlated to the expression of the BCSG1 gene in tumor tissues, but not in non-neoplastic adjacent and benign tissues; (3) breast tumor tissues expressed lower BCSG1 than non-neoplastic adjacent tissues. Conclusions: Our data revealed a unique expression pattern and methylation status of the BCSG1 gene in breast tissues derived from Chinese patients and suggested both methylation status and mechanisms underlying BCSG1 regulation might be closely related to the racial background.
Chemokine Receptor CCR7 Expression Correlates with Lymph Node Metastasis in Pancreatic Cancer
Authors: Nakata Bunzo , Fukunaga Shinya , Noda Eiji , Amano Ryosuke , Yamada Nobuya , Hirakawa Kosei
Published: June 2008

Aims: The clinical significance of chemokine receptor CCR7 expression in pancreatic ductal cancer was investigated. Methods: Immunohistochemical staining of 89 pancreatic cancers treated macroscopically with curative resection without hematogenous metastases or peritoneal dissemination were analyzed in association with clinicopathological data. Results: The positivity of CCR7 in pancreatic cancer was 32.6% (29/89). A significant correlation was detected between CCR7-positive expression and lymph node metastasis. Patients with CCR7-positive tumors had significantly shorter survival times than those with CCR7-negative tumors (median, 12.8 vs. 21.9 months, respectively; p = 0.0039). CCR7 expression was an independent prognostic factor (hazard ratio, 1.949; p = 0.0364) by multivariate survival analysis; however, it was not an indicator for any particular site of recurrence. Conclusion: The survival impact of CCR7 expression on resectable pancreatic cancer may be associated with lymphatic spread. The results from the present study should foster further investigation of treatments using an inhibitor for the CCR7 protein to improve the survival of pancreatic cancer.
MDM2SNP309 Does Not Associate with Elevated MDM2 Protein Expression or Breast Cancer Risk
Authors: Krekac Daniel , Brozkova Kristyna , Knoflickova Dana , Hrstka Roman , Muller Petr , Nenutil Rudolf , Vojtesek Borivoj
Published: June 2008

Objectives: SNP309 polymorphism (T-G) at the promoter region of MDM2 has been reported to cause increased binding affinity of transcriptional activator Sp1 followed by increased MDM2 both in mRNA and protein level. This model was proposed in vitro in the small panel of cell lines that indicated an on average 8-fold higher level of MDM2 mRNA in cells bearing the GG genotype. Methods: The incidence of SNP309 was determined in a cohort of 158 breast, 17 endometrium, 13 cervix and 45 ovarian cancer tissues by PCR-RFLP. The expression of p53 and MDM2 protein levels in the cohort was immunohistochemically investigated and statistically correlated with SNP309 polymorphism using Pearson χ2 and t test. Results: No significant difference was observed in the G allele incidence in breast cancer specimens compared to 149 noncancer controls. Furthermore, no statistically significant association of the G allele frequencies and p53 and MDM2 protein expression levels was observed. Conclusions: Our data clearly show neither association between SNP309 and cancer risk, nor the responsibility of G allele for increased MDM2 or decreased of p53 protein levels in human primary breast tumors.
PDGFRα Gene Mutation and Protein Expression in Gastrointestinal Stromal Tumors
Authors: Chang Heung Moon , Ryu Min-Hee , Lee Hyoungnam , Jang Se Jin , Lee Jae-Lyun , Kim Tae Won , Yook Jeong Hwan , Oh Sung Tae , Kim Byung Sik , Lee Jung Shin , Kang Yoon-Koo
Published: June 2008

Objective: Mutation of the PDGFRα is a potential candidate in the pathogenesis of KIT wild-type gastrointestinal tumors (GISTs). In this study, we evaluated the prevalence of PDGFRα mutations and corresponding protein expression in GISTs, to determine their usefulness in obtaining a prognosis. Methods: Genomic DNA was extracted from paraffin-embedded tumor tissues from 194 GISTs. Exons 12, 14 and 18 of the PDGFRα were amplified and sequenced. Immunohistochemical staining was performed in 179 patients. Results: Mutations in the PDGFRα were detected in 6 (3.1%) patients, and were observed solely in KIT wild-type GISTs. Among the 6 patients with PDGFRα gene mutations, 5 patients with localized GISTs showed no relapse after resection during the 19- to 80-month follow-up period. Intensity of PDGFRα expression was classified as 0 in 26 (14.5%), 1+ in 69 (38.5%), 2+ in 71 (39.7%) and 3+ in 13 (7.3%) patients. Levels of PDGFRα expression showed no correlation with relapse-free survival. Conclusion:PDGFRα mutations in GISTs were found to be rare in this Korean population. Although localized GISTs with PDGFRα mutations showed relatively good prognosis after resection, the difference was not statistically significant.
Beneficial Effects of BAY u3405, a Novel Thromboxane A2 Receptor Antagonist, in Splanchnic Artery Occlusion Shock
Authors: Canale Patrizia , Squadrito Francesco , Altavilla Domenica , Ioculano Mariapatrizia , Campo Giuseppe M. , Squadrito Giovanni , Urna Giuseppe , Sardella Aurora , Caputi Achille P.
Published: June 2008

Splanchnic artery occlusion shock was induced in male anaesthetized rats by clamping the splanchnic artery for 45 min. The arteries were then released and survival rate, mean survival time, mean arterial blood pressure, plasma levels of thromboxane B2 and 6-keto-PGFlα, macrophage phagocytosis activity and plasma levels of myocardial depressant factor were evaluated. In addition, the neutrophilic infiltrate was quantified in the ileum and lung using a myeloperoxidase (MPO) assay. Sham splanchnic-artery-occlusion-shocked rats were used as controls. Splanchnic-artery-occlusion-shocked rats died within 93 ± 7 min, while all sham-shocked animals survived more than 3 h. Splanchnic artery occlusion shock caused changes in mean arterial blood pressure, significantly increased the plasma levels of thromboxane B2 (7.5 ± 1.3 ng/ ml; p < 0.001 vs. sham), 6-keto-PGFlα (8.9 ± 1.7 ng/ml; p < 0.001 vs. sham) and myocardial depressant factor (114 ± 11 U/ml), and reduced macrophage phagocytosis. Furthermore, MPO activity was significantly elevated (0.12 ± 0.03 × 10-3 and 1.8 ± 0.5 × 10∼3 U/g protein in the ileum and lung, respectively) 70 min after starting reperfusion. Administration of BAY u3405, a novel thromboxane A2 receptor antagonist (30 mg/kg i.v., 30 min before occlusion), significantly increased survival time (187 ± 3.7 min) and survival rate, improved mean arterial blood pressure, reduced the plasma levels of myocardial depressant factor (54 ± 3 U/ml), partially restored macrophage phagocytosis and lowered MPO activity in both the ileum and the lung. Our data are consistent with an involvement of thromboxane A2 in splanchnic artery occlusion shock and suggest that BAY u3405 might be of benefit in low-flow states such as circulatory shock.
Increased platelet sensitivity among individuals with aspirin resistance – Platelet aggregation to submaximal concentration of arachidonic acid predicts response to antiplatelet therapy
Authors: Guthikonda Sasidhar , Mangalpally Kirankumar , Patel Rajnikant , DeLao Timothy , Bergeron Angela L. , Dong Jing-Fei , Lev Eli I. , Vaduganathan Muthiah , Kleiman Neal S.
Published: June 2008

Aspirin ‘resistance’ (AR) is a phenomenon of uncertain etiology describing decreased platelet inhibition by aspirin. We studied whether (i) platelets inAR demonstrate increased basal sensitivity to a lower degree of stimulation and (ii) platelet aggregation with submaximal stimulation could predict responses to aspirin. Serum thromboxane B2 (TxB2) levels and platelet aggregation with light transmission aggregometry (LTA ) were measured at baseline and 24 hours after 325 mg aspirin administration in 58 healthy subjects. AR was defined as the upper sixth of LTA (≥ 12%) to 1.5 mM AA. Baseline platelet aggregation with sub-maximal concentrations of agonists [ADP 2 µM, arachidonic acid (AA) 0.75 mM, collagen 0.375 and 0.5 µg/ml] was greater in AR subjects compared with non-AR subjects, but not with higher concentrations (ADP 5 µM and 20 µM, AA 1.5 mM and collagen 1 µg/ml). Post-aspirin platelet aggregation was elevated in AR subjects with both submaximal and maximal stimulation. Baseline and post-aspirin serumTxB2 were higher inAR subjects and decreased further with ex-vivo COX -1 inhibition, suggesting incompletely suppressed COX -1 activity. Pre-aspirin platelet aggregation to 0.75 AA demonstrated a dichotomous response with 29/58 subjects having aggregation ≤15% and 29/58 subjects having aggregation ≥75%. In the high aggregation group 28% had AR compared to 6% in the non-AR group (p=0.04). In conclusion, platelets in AR subjects demonstrate increased basal sensitivity to submaximal stimulation, which could predict responses to antiplatelet therapy.
Absolute risk of venous and arterial thromboembolism in thrombophilic families is not increased by high thrombin-activatable fibrinolysis inhibitor (TAFI) levels
Authors: Coppens Michiel , veeger Nic J. G. M. , Bom Victor J. J. , Middeldorp Saskia , Hamulyak Karly , Prins Martin H. , Büller Harry R. , van der Meer Jan , Folkeringa Nienke
Published: June 2008

High levels of thrombin-activatable fibrinolysis inhibitor (TAFI) are a supposed risk factor for thrombosis. However, results from previous studies are conflicting. We assessed the absolute risk of venous and arterial thromboembolism in subjects with high TAFI levels (>126 U/dl) versus subjects with normal levels, and the contribution of other concomitant thrombophilic defects. Relatives from four identical cohort studies in families with either deficiencies of antithrombin, protein C or protein S, prothrombin 20210A, high factor VIII levels, or hyperhomocysteinemia were pooled. Probands were excluded. Of 1,940 relatives, 187 had high TAFI levels. Annual incidences of venous thromboembolism were 0.23% in relatives with high TAFI levels versus 0.26% in relatives with normal TAFI levels (adjusted relative risk [RR] 0.8; 95% confidence interval [CI], 0.5–1.3). For arterial thrombosis these were 0.31% versus 0.23% (adjusted RR 1.4; 95% CI, 0.9–2.2). High levels of factor VIII, IX and XI were observed more frequently in relatives with high TAFI levels. Only high factor VIII levels were associated with an increased risk of venous and arterial thrombosis, independently of TAFI levels. None of these concomitant defects showed interaction with high TAFI levels. High TAFI levels were not associated with an increased risk of venous and arterial thromboembolism in thrombophilic families.
Formation of tissue factor-factor VIIa-factor Xa complex induces activation of the mTOR pathway which regulates migration of human breast cancer cells
Authors: Jiang Xiaofeng , Zhu Shimei , Panetti Tracee S. , Bromberg Michael E.
Published: June 2008

Tissue factor (TF) is a transmembrane glycoprotein that initiates blood coagulation when complexed with activated factor VII (FVIIa).TF is constitutively expressed in a variety of tumor cells and has been implicated in cellular signaling, angiogenesis, and tumor progression. Formation of TF-FVIIa complex and generation of downstream coagulation proteases, including activated factor X (FXa) and thrombin, initiate signaling by activation of protease-activated receptors (PARs).We have previously shown thatTFFVIIa-Xa complex formation promotes phosphorylation of p44/42 mitogen-activated protein kinase and Akt/protein kinase B in human breast cancer cells. In the present study, we show that formation of TF-FVIIa-FXa complex induces phosphorylation of mammalian target of rapamycin (mTOR) and p70 S6 kinase in a human breast cancer cell line, Adr-MCF-7. Activation of the mTOR pathway, which is probably mediated by PAR1 and/or PAR2, was associated with enhanced cell migration, a key step in the metastatic cascade. Inhibition of this pathway with the specific mTOR inhibitor, rapamycin, markedly decreased cell migration induced by formation of TFFVIIa-FXa complex. These studies suggest thatTFFVIIa-mediated signaling modulates mTOR pathway activation, which regulates in part breast cancer cell migration. Targeting the TF-mediated cell signaling pathway might represent a novel strategy for the treatment of breast cancer.
An observational study of sucrose-formulated recombinant factor VIII for Japanese patients with haemophilia A
Authors: Ikegawa Chiho , koyama ChisatoYo , Haupt Verena , Delumeau Jean-Christophe
Published: June 2008

The safety and efficacy of sucrose-formulated recombinant factor VIII (rFVIII-FS; Kogenate® FS) under usual clinical practice were evaluated for 12 months in an observational, postmarketing surveillance study conducted at 214 treatment centres throughout Japan. The study included 631 patients with haemophilia A, 80% of whom had severe or moderately-severe disease (≤2% FVIII:C).Most patients (n=477;75.6%) had >100 prior exposure days (EDs), but the study also included 62 (9.8%) patients with <20 EDs who were at high risk for inhibitor development. A total of 71,240 infusions were administered during the observation (mean, 113 ± 108 per patient). Physicians rated efficacy and tolerability of rFVIII-FS as “very good” or “good” in >99% of patients. FVIII inhibitors were observed in seven patients (5 de novo; 1 persistent/fluctuating; 1 recurrent).The overall de novo inhibitor incidence was 0.8% (5/631; or 5/599 among the subgroup of patients with negative baseline titre and no known inhibitor history).De novo cases represented 3.2% (2/62) of patients with <20 EDs at enrollment (2/57 in the no inhibitor subgroup) and 0.2 % (1/477) of patients pretreated with >100 EDs (1/452 in the no inhibitor subgroup) at enrollment. The results of this large observational study demonstrate that rFVIII-FS is both safe and efficacious as used in the usual clinical setting for the treatment of Japanese patients with mild to severe haemophiliaA. This study supports the efficacy of rFVIII-FS with an incidence of inhibitor formation no greater than in a comparable European study or previous phase III clinical studies.
Immune complex-mediated glomerulonephritis is ameliorated by thrombin-activatable fibrinolysis inhibitor deficiency
Authors: Bruno Nelson E. , Yano Yutaka , Takei Yoshiyuki , Qin Liqiang , Suzuki Toshinari , Morser John , D’Alessandro-Gabazza Corina N. , Mizoguchi Akira , Suzuki Koji , Taguchi Osamu , Sumida Yasuhiro , Gabazza Esteban C.
Published: June 2008

The activity of plasmin plays a critical role in the development of chronic glomerulonephritis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a potent inhibitor of plasmin generation. We hypothesized thatTAFI is involved in the pathogenesis of glomerulonephritis because it inhibits plasmin generation. To demonstrate this hypothesis, we compared the development of immune complex-mediated glomerulonephritis in wild-type and TAFI-deficient mice. After six weeks of treatment with horse spleen apoferritin and lipoplysaccharide to induce glomerulonephritis, mice deficient in TAFI had significantly better renal function as shown by lower concentrations of albumin in urine and blood urea nitrogen compared to wild-type mice. In addition, the activity of plasmin and matrix metalloproteinases was significantly increased, and mesangial matrix expansion and the deposition of collagen and fibrin in kidney tissues were significantly decreased in TAFI-knockout mice as compared to their wildtype counterparts. Depletion of fibrinogen by batroxobin (Defibrase) treatment led to equalization of the renal function and the amount of collagen deposition in the kidneys of TAFI-knockout and wild-type mice with immune complex-mediated glomerulonephritis. Together these observations suggest that TAFI-mediated inhibition of plasmin generation plays a role in the pathogenesis of glomerulonephritis, and that it may constitute a novel molecular target for the therapy of this disease.
Baseline platelet activity and response after clopidogrel in 257 diabetics among 822 patients with coronary artery disease
Authors: Pokov Ilya , Kuliczkowski Wiktor , Chesebro James , Badimon Juan , Serebruany Victor
Published: June 2008

The objective was to describe the indices of platelet aggregation and activation in a large cohort of diabetic patients with coronary artery disease (CAD). Recently, a number of observations have indicated that patients with diabetes mellitus (DM) exhibit persistent platelet activation, and low response after antiplatelet therapy, although no randomized data exist. We sought to define the baseline platelet biomarkers, and the patterns of response to aspirin and clopidogrel therapy in DM versus non-diabetic patients. Secondary post-hoc analyses were made of platelet activity biomarkers in the dataset which consisted of patients with documented CAD (n=822), including those with DM (n=257). Patients with DM exhibited higher baseline platelet activity by adenosine diphosphate (ADP)- (p=0.0002), and collagen-induced (p=0.03) aggregometry; Ultegra- (p=0.0001), and PFA-100 (p=0.02) analyzers; and expression of platelet/endothelial cell adhesion molecule-1 (PECAM-1) (p=0.01), glycoprotein (GP) IIb/IIIa antigen (p=0.001), and activity (p=0.02), vitronectin receptor (p=0.03), P selectin (p=0.02), and intact epitope of PAR-1 thrombin receptor (p=0.02). Antiplatelet response after clopidogrel in diabetics was impaired when compared with non-diabetics. In conclusion, diabetic patients exhibit high pretreatment platelet activity, and do not respond well to the available antiplatelet regimens when compared with similar patients without DM. The clinical implications of these findings are unknown but are potentially important. Considering worsened outcomes in this high-risk population, clinical trials in DM are urgently needed in order to define the optimal degree of platelet inhibition and suitability for more aggressive antiplatelet regimens.
An evaluation of methods for determining reference intervals for light transmission platelet aggregation tests on samples with normal or reduced platelet counts
Authors: Moffat Karen A. , Pai Menaka , Liu Yang , Seecharan Jodi , McKay Heather , Webert Kathryn E. , Cook Richard J. , Heddle Nancy M. , Hayward Catherine P. M.
Published: June 2008

Light transmission platelet aggregation tests are important for diagnosing platelet function defects. However, uncertainties exist about the best procedures to determine aggregation reference intervals. We investigated methods for determining reference intervals for light transmission aggregation tests, using the % maximal aggregation values for prospectively collected data on healthy control samples. Reference intervals for samples tested at 250 x 109 platelets/l were determined by mean ± 2 standard deviations and non-parametric analyses. To establish reference intervals for tests on thrombocytopenic subjects, regression analyses were used to estimate 95% confidence limits for % maximal aggregation, according to sample platelet counts, using data for control samples diluted to match the platelet count of undiluted thrombocytopenic patient platelet-rich plasma samples. For samples tested at 250 x 109 platelets/l, non-parametric analyses described 95% of data for healthy control samples better than mean ± 2 standard deviations. For samples tested at lower counts, to match thrombocytopenic samples, the % maximal aggregation was influenced by platelet count and derived limits were wider at very low platelet counts for almost all agonists. With ristocetin, it proved feasible to test samples with very low platelet counts to exclude Bernard-Soulier syndrome and type 2B von Willebrand disease. Non-parametric analyses should be the preferred method to establish light transmission aggregation reference intervals for samples tested at normal platelet counts. The derived limits for thrombocytopenic samples provide guidance for evaluating thrombocytopenic platelet function disorders, including which agonists to test, based on the sample platelet count.
Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry
Authors: Ruíz-Giménez Nuria , Suárez Carmen , González Rocío , Nieto José , Todolí José , Samperiz Ángel , Monreal Manuel ,   and the RIETE Investigators
Published: June 2008

A score that can accurately determine the risk of major bleeding during anticoagulant therapy may help to make decisions on anticoagulant use. RIETE is an ongoing registry of consecutive patients with acute venous thromboembolism (VTE). We composed a score to predict the risk for major bleeding within three months of anticoagulant therapy. Of 19,274 patients enrolled, 13,057 (67%) were randomly assigned to the derivation sample, 6,572 to the validation sample. In the derivation sample 314 (2.4%) patients bled (fatal bleeding, 105). On multivariate analysis, age >75 years, recent bleeding, cancer, creatinine levels >1.2 mg/dl, anemia, or pulmonary embolism at baseline were independently associated with an increased risk for major bleeding. A score was composed assigning 2 points to recent bleeding, 1.5 to abnormal creatinine levels or anemia, 1 point to the remaining variables. In the derivation sample 2,654 (20%) patients scored 0 points (low risk); 9,645 (74%) 1–4 points (intermediate); 758 (5.8%) >4 points (high risk). The incidences of major bleeding were: 0.3% (95% confidence interval [CI]: 0.1–0.6), 2.6% (95% CI: 2.3–2.9), and 7.3% (95% CI: 5.6–9.3), respectively. The likelihood ratio test was:0.14 (95% CI:0.07–0.27) for patients at low risk;2.96 (95% CI:2.18–4.02) for those at high risk. In the validation sample the incidence of major bleeding was:0.1%,2.8%,and 6.2%,respectively. In conclusion, a risk score based on six variables documented at entry can identify VTE patients at low, intermediate, or high risk for major bleeding during the first three months of therapy.
Aristotle on Natural Slavery
Authors: Heath Malcolm
Published: June 2008

Aristotle's claim that natural slaves do not possess autonomous rationality (Pol. 1.5, 1254b20-23) cannot plausibly be interpreted in an unrestricted sense, since this would conflict with what Aristotle knew about non-Greek societies. Aristotle's argument requires only a lack of autonomous practical rationality. An impairment of the capacity for integrated practical deliberation, resulting from an environmentally induced excess or deficiency in thumos (Pol. 7.7, 1327b18-31), would be sufficient to make natural slaves incapable of eudaimonia without being obtrusively implausible relative to what Aristotle is likely to have believed about non-Greeks. Since Aristotle seems to have believed that the existence of people who can be enslaved without injustice is a hypothetical necessity, if those capable of eudaimonia are to achieve it, the existence of natural slaves has implications for our understanding of Aristotle's natural teleology.
Attitudes of Parents and Physicians Toward Febrile Seizures
Authors: Yilmaz Deniz , Arhan Ebru , Yuksel Deniz , Özçelik Aysima , Senbil Nesrin , Serdaroglu Ayse , Gurer Y.K. Yavuz
Published: June 2008

Objectives Although febrile seizures are common in children, attitudes may change among parents. The management of a child may differ depending on the specialty of the attending physician. This study was carried out to analyze attitudes of Turkish parents and physicians toward febrile seizures.

Material and Methods 308 children with febrile seizure who were admitted to the Department of Pediatric Neurology at Dr Sami Ulus Children's Hospital and Gazi University in Turkey between January 2006 and March 2007 were enrolled.

Results Prior to seizure, approximately half of the parents took appropriate steps in reducing fever. The data also showed that there was a wide variation of treatment practice depending on the specialty of the attending physician.

Discussion Educational level and economic status are important variables affecting attitudes of parents toward fever and febrile seizure. The management of the child with a febrile seizure differs even within the same specialty in Turkish physicians.
Interdistrict Disparity in Sentencing in Three U.S. District Courts
Authors: Wu Jawjeong , Spohn Cassia
Published: June 2008

Research examining disparities in sentencing outcomes under federal sentencing guidelines has focused almost exclusively on aggregate national data. Although these studies contribute considerably to the criminological literature on sentencing disparity, their findings may have masked contextual variation in relation to case processing across jurisdictions. With data from the U.S. District Courts for Minnesota, Nebraska, and Southern Iowa for 1998 through 2000, this article assesses whether interdistrict variations in sentence outcomes exist and whether the factors that affect these outcomes vary across jurisdictions. It also attempts to determine whether disparities in sentence outcomes can be attributed to downward departures. The findings raise questions about the validity of the assumption of uniformity in the federal sentencing process and the use of aggregate data to study federal sentence outcomes.
The Risks and Opportunities of the IEP Requirements Under IDEA '97
Authors: Huefner Dixie Snow
Published: June 2008

The new Individualized Education Program (IEP) requirements in the 1997 Amendments to the Individuals with Disabilities Education Act (IDEA '97) have significant implications for both general and special education teachers. Although they create increased opportunities for collaboration, they also create new risks of backlash. The micromanagement by the federal government reflected in them is problematic. Whether the expectations of the new requirements can be realized depends on many factors, including the energy and good will of IEP team members. This article analyzes the IEP changes and their implications for the effective delivery of special education and related services.
Litigating a Free Appropriate Public Education
Authors: Yell Mitchell L. , Drasgow Erik
Published: June 2008

Between 1993 and 1998 there were 45 published due process hearings and court cases in which parents of children with autism challenged the appropriateness of a school district's educational program for their child. These hearings and cases involved parental requests for school districts to provide, fund, or reimburse them for the Lovaas treatment program for their young children. The purpose of this article is to examine how these hearings and cases affect the definition of "appropriate" special education programs. First, we review previous legislative and litigative definitions of a free appropriate public education (FAPE). Next, we analyze the Lovaas treatment hearings and cases to identify factors associated with winning and losing decisions. Finally, we discuss the implications of these decisions to provide guidance to schools in adhering to the procedural and substantive requirements of a FAPE.
Medical Services
Authors: Bartlett Larry
Published: June 2008

The Supreme Court agreed for a second time to review a lower court decision based on legal questions regarding the medical and health services components of related services required under IDEA, and has recently rendered a decision. This article traces the legal history behind the issue presented before the Court, discusses the decision, and discusses the likely educational implications of its decision.
Idea '97
Authors: Osborne Allan G. , Russo Charles J. , DiMattia Philip
Published: June 2008

This article analyzes the provisions of IDEA '97 as they pertain to students in private schools. More specifically, the article reviews implementing regulations and relevant case law, issues concerning the extent to which services must be provided and the manner in which they are provided, and the quality of services that are provided. Finally, the article examines guidelines for implementing the new provisions and suggestions for how to avoid violating the establishment clause when one is providing services to students who attend sectarian schools.
Legal Perspectives on School Outcomes Assessment for Students with Disabilities
Authors: Shriner James G.
Published: June 2008

Assessment of educational results for students with disabilities has been an element of nearly all recent reform, policy, and legislative activities. IDEA '97 includes specific provisions regarding the participation of students with disabilities in general education assessment of student progress at both the district and state levels. Historically, when legal issues regarding the relationship between students with disabilities and outcomes assessments have arisen, courts have said such assessments (e.g., minimum competency, exit exams) are allowable provided the student is provided (a) appropriate accommodations to demonstrate his or her skills and (b) adequate opportunity to learn the subject matter measured by such tests. As newer assessments of progress toward higher learning standards are adopted by districts and states, these issues are likely to be revisited. Additionally, IDEA '97 creates both opportunities and challenges regarding students with disabilities' partial participation in general state assessments, as well as alternate assessments of educational outcomes when appropriate. Policies regarding assessment of students with disabilities, seemingly, have outpaced practices and, perhaps, legal interpretations of their appropriateness when stakes are attached to student participation and performance.
Disciplining Students in Special Education
Authors: Hartwig Eric P. , Ruesch Gary M.
Published: June 2008

Congress reauthorized the Individuals with Disabilities Education Act of 1990 in the spring of 1997. The Department of Education adopted the final regulations on March 12, 1999, and they became effective on May 11, 1999. This article addresses the substantial changes that Congress made in the legislation regarding the discipline of students with disabilities. We analyze both the procedural and substantive requirements relating to suspending students, expelling students, and conducting functional behavioral assessments and manifestation determinations.
College Students and Disability Law
Authors: Thomas Stephen B.
Published: June 2008

This article briefly reviews Section 504 and the Americans with Disabilities Act of 1990 and identifies the criteria that are used to determine whether a student is both "disabled" and "qualified." Then, specific areas of admission, accommodation, and dismissal are examined. Finally, guidelines are presented that may be used by professors and administrators in their efforts to provide qualified students with disabilities with nondiscriminatory access to higher education.
Leveling the Playing Field or Leveling the Players?
Authors: Sullivan Kathleen A. , Lantz Patricia J. , Zirkel Perry A.
Published: June 2008

Schools are faced with a growing body of case law outlining the legal limits regulating the participation of students with disabilities in interscholastic sports. This article provides a systematic synthesis, including jurisdictional differences, of the agency and court rulings that apply Section 504, the Americans with Disabilities Act, and the Individuals with Disabilities Education Act to interscholastic athletics. This comprehensive framework also provides insight into how these federal statutes likely pertain to the participation of students with disabilities in other extracurricular activities. The article concludes with recommendations for prudent professional practice.
Designing High-Quality Research in Special Education
Authors: Gersten Russell , Baker Scott , Lloyd John Wills
Published: June 2008

This article discusses critical issues related to conducting high-quality intervention research using experimental and quasi-experimental group designs. As researchers have learned more about teaching and learning, intervention studies have become more complex. The research community is struggling with ways to sensibly negotiate a balance between rigorous research designs that satisfy traditional laboratory standards of quality and interventions that are complex and flexible enough for conducting research in the real world of classrooms and schools. Rather than organizing the discussion around a list of resolute research standards, we weigh the pros and cons of making the many difficult choices involved in conducting intervention research. Our goal is to convey the sense that good designs must involve a series of balances and compromises that defy easily categorized solutions. Among the controversial areas discussed are the importance of defining the nature of the independent variable, the value of measuring implementation, and the improvement of the quality of quasi-experiments.
The Effects of Cooperative Learning on Students with Learning Difficulties in the Lower Elementary School
Authors: Gillies Robyn M. , Ashman Adrian F.
Published: June 2008

This study investigated the behaviors, interactions, and learning outcomes of children with learning difficulties who participated in structured and unstructured group activities. Of the 152 Grade 3 children who worked in four-person, gender-balanced groups, 22 children were identified as having learning difficulties requiring up to 3 hours of specialist teacher support for their learning each week. The children worked in their groups for one 6-week social studies unit of work each term for three school terms. The results showed that the children in the structured groups were more involved in group activities and provided more directions and help to other group members than their peers in the unstructured groups. Furthermore, children in the structured groups obtained a significantly higher performance on the comprehension questionnaire than children in the unstructured groups (effect size = +1.43 standard deviations). Reasons for these differences are discussed.
Struggling First-Grade Readers
Authors: Chard David J. , Kameenui Edward J.
Published: June 2008

First-grade struggling readers' oral reading was observed during primary reading instructional time. Participants were 65 first-graders experiencing difficulties in beginning reading and nominated by their teacher as at risk for reading failure. Each participant was observed three times over a 12-week period in the spring of the first-grade year. Observers collected frequency data on participants' oral reading at three levels of complexity: letter-sound, word-word part, and sentence-paragraph. Measures of student reading progress were also collected throughout the observation period. The findings revealed that most instruction for struggling readers may not be aligned with recent research on preventing reading difficulties, and even struggling readers receiving reading instruction aligned with best practices may be only making minimal progress.
State-Level Accountability for the Performance of Students with Disabilities
Authors: Elliott Judy L. , Erickson Ron N. , Thurlow Martha L. , Shriner Jim G.
Published: June 2008

Along with the dramatic expansion of assessment activities during this decade, there has been increased use of state-level assessments as accountability tools. The extent to which students with disabilities have been included in state-level accountability, however, is questionable. This study examined changes that have taken place over 5 years in four aspects of state accountability practices involving students with disabilities: (a) the number of states using data on students with disabilities for state-level accountability and the nature of their accountability systems, (b) the existence of state policies on allowable accommodations and adaptations in assessments, (c) information on the rates of participation of students with disabilities in state-level assessments, and (d) the availability of data on students with disabilities in state-level accountability systems. Information was collected from all 50 states, plus the 9 educational units whose special education students were supported by the U.S. Office of Special Education Programs (e.g., Bureau of Indian Affairs, District of Columbia, Marshall Islands, Puerto Rico) in both 1991 and 1995. The results indicated that there have been dramatic increases in the number of states that indicate they use data from students with disabilities on school participation, exit, and achievement in their state accountability systems and in the number of states with written guidelines on the use of accommodations in state assessments. In contrast, states seem to have changed little in their specific knowledge about the participation rates of students with disabilities in assessments, although it appears that, when students are included in assessments, their data now are more likely to be accessible than 5 years ago. The implications of these findings for future efforts to include students with disabilities in state accountability systems are explored.