bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of synteny and gene order on the homologue of chicken chromosome 7 between two passerine species and between passerines and chicken
Authors: Hale M.C. , Jensen H. , Birkhead T.R. , Burke T. , Slate J.
Published: June 2008

Wild populations of passerine birds have frequently been used in studies of ecology and evolution. However, the majority of species lack genetic linkage maps. The completion of a model avian genome sequence (the jungle fowl, Gallus gallus) has created an opportunity to advance genetic knowledge of other birds. Here we constructed genetic linkage maps of the homologue of chicken chromosome 7 for two passerine species, the zebra finch (Taeniopygia guttata) and the house sparrow (Passer domesticus). Linkage groups were constructed with a combination of SNP and microsatellite markers that were developed both in silico based on similarity to the chicken genome sequence, and de novo in the laboratory. Synteny was well conserved throughout the chromosome; however there were some gene rearrangements between chickens and passerines. This suggests that the transfer of map information from chicken to passerine and between different passerine species should not assume conserved gene order. The length of linkage maps of chromosome 7 were on average 60% that of chicken, consistent with the idea that passerines have a reduced recombination rate relative to chicken. Some evidence of heterochiasmy, i.e. a difference in the recombination rate between the sexes, was observed.
Identification of the sex-determining locus in the Thai medaka, Oryzias minutillus
Authors: Nagai T. , Takehana Y. , Hamaguchi S. , Sakaizumi M.
Published: June 2008

A sex-determining gene, DMY, which is comparable to the SRY gene in mammals, has been identified in the medaka, Oryzias latipes. Although Oryzias curvinotus, a closely related species to O. latipes also has DMY, this gene has not been found in other Oryzias fishes. It has recently been demonstrated that the sex chromosomes of Oryzias dancena and Oryzias hubbsi differ from those of O. latipes and these species have XX/XY and ZZ/ZW systems, respectively. This may suggest that Oryzias species have evolved different sex-determining genes on different sex chromosomes. In the present study, we investigated the sex determination mechanism in Oryzias minutillus, which is closely related to O. dancena and O. hubbsi. Linkage analysis using 14 isolated sex-linked DNA markers showed that this species has an XX/XY sex determination system. These sex-linked markers were located on linkage group 8 of O. latipes, suggesting that the sex chromosomes of O. minutillus are homologous to the autosomes of other Oryzias species. Furthermore, fluorescence in situ hybridization using a tightly sex-linked marker demonstrated that the XY sex chromosomes of O. minutillus and O. dancena were not homologous. These findings provide additional evidence for independent origins of sex chromosomes and sex-determining genes in these closely related species.
The 5S rDNA related repetitive sequences in the sex chromosomes of the spiny eel (Mastacembelus aculeatus)
Authors: Zhao G. , Yu Q.X. , Zhang W.W. , Zhang Y.M. , Chen J. , Long H. , Liu J.D.
Published: June 2008

The karyotype of the spiny eel (Mastacembelus aculeatus) has highly evolved heteromorphic sex chromosomes. X and Y chromosomes differ from each other in the distribution of heterochromatin blocks. To characterize the repetitive sequences in these heterochromatic regions, we microdissected the X chromosome, constructed an X chromosome library, amplified the genomic DNA using PCR and isolated a repetitive sequence DNA family by screening the library. All family members were clusters of two simple repetitive monomers, MaSRS1 and MaSRS2. We detected a conserved 5S rDNA gene sequence within monomer MaSRS2; thus, tandem-arranged MaSRS1s and MaSRS2s may co-compose 5S rDNA multigenes and NTSs in M. aculeatus. FISH analysis revealed that MaSRS1 and MaSRS2were the main components of the heterochromatic regions of the X and Y chromosomes. This finding contributes additional data about differentiation of heteromorphic sex chromosomes in lower vertebrates.
Oral Vitamin C Supplementation in Hemodialysis Patients and Its Effect on the Plasma Level of Oxidized Ascorbic Acid and Cu/Zn Superoxide Dismutase, an Oxidative Stress Marker
Authors: Washio Kazunori , Inagaki Masahiro , Tsuji Mayumi , Morio Yuri , Akiyama Shinichiro , Gotoh Hiromichi , Gotoh Tomomi , Gotoh Yoshikazu , Oguchi Katsuji
Published: June 2008

Background/Aim: Oxidative stress is known to be enhanced in hemodialysis patients, and one of its useful markers is plasma copper/zinc superoxide dismutase (Cu/Zn-SOD). The increase in plasma Cu/Zn-SOD can be inhibited by orally administered lipid-soluble vitamin E. We examined the antioxidative effects of water-soluble vitamin C administered orally on Cu/Zn-SOD levels in hemodialysis patients. Methods: Vitamin C was orally administered to 16 maintenance hemodialysis patients before each dialysis session. Doses were increased from 200 to 1,000 mg over 3 months. The levels of plasma vitamin C and Cu/Zn-SOD and its mRNA expression in leukocytes were determined 1, 2, and 3 months after the start of vitamin C administration. Furthermore, the levels of oxidized and reduced forms of plasma vitamin C were determined before the start of vitamin C administration and before and after dialysis at 1,000-mg vitamin C doses. Results: Following oral administration, the plasma levels of vitamin C and its oxidized form were increased. However, significant changes in plasma Cu/Zn-SOD or its mRNA expression in leukocytes were not observed. Conclusion: In maintenance hemodialysis patients, vitamin C administration resulted in a significant increase in the postdialysis level of the oxidized form of vitamin C, which suggested an increase in antioxidant effect. However, water-soluble vitamin C did not significantly suppress Cu/Zn-SOD expression enhancement.
Variation of Postprandial PYY3–36Response following Ingestion of Differing Macronutrient Meals in Obese Females
Authors: Helou Nancy , Obeid Omar , Azar Sami T. , Hwalla Nahla
Published: June 2008

Aim: This study investigated the effect of macronutrient composition of meals on postprandial peptide YY3–36 (PYY3–36) response in obese hyperinsulinemic females. Methods: Eight obese females consumed three iso-energetic meals of different macronutrient composition, high carbohydrate (HC; 60% CHO, 20% protein, 20% fat), high fat (HF; 30% CHO, 20% protein, 50% fat) and high protein (HP; 30% CHO, 50% protein, 20% fat), on three separate occasions, 1 month apart. PYY3–36, insulin and glucosewere measured before and 15, 30, 60, 120 and 180 min following each meal. Results: PYY3–36 levelsincreased significantly following the three meals, with the HC meal resulting in a sustained postprandial increase in PYY3–36 level throughout the experimental period. Comparing the three meals, the HF meal induced a significantly higher increase in postprandial PYY3–36 levels, at 15 and 30 min as compared to the HP meal (p < 0.05), whereas the postprandial increase following the HP meal became significantly higher than that following the HF meal at 120 min. Postprandial increase in PYY3–36 was highest in the first hour following the HF meal, while that following the HP meal was delayed by 1 h. Conclusion: Increasing both protein and fat content of a meal may induce an immediate and prolonged increase in PYY3–36, resulting in increased satiety and its maintenance for a longer period of time.
Effect of a Balanced Mixture of Dietary Fibers on Gastric Emptying, Intestinal Transit and Body Weight
Authors: Bortolotti Mauro , Levorato Maurizio , Lugli Andrea , Mazzero Giosuè
Published: June 2008

Background/Aims: Dietary fibers are frequently included in diets to decrease body weight, but their scarce palatability and the occurrence of meteorism prevent a long-term intake. The aim of this study was to test a mixture of dietary fibers expressly chosen to decrease their negative properties and strengthen their positive effects. Methods: In a series of 10 patients with a slight overweight, the effectiveness of a palatable dietary fibers mixture on gastric emptying and intestinal transit was tested with scintigraphic methods. Then, the effects on body weight and digestive sensations and characteristics of defecations, were evaluated for 4 weeks. Results: The intestinal transit was significantly shortened by the fiber intake, while the gastric emptying was delayed, but not significantly. The body mass index significantly and progressively decreased, whereas the sense of satiation significantly increased. No effect on abdominal bloating was referred, whereas a significant increase in number of defecations with stools of normal consistency was observed. The acceptability of the fiber mixture was good. Conclusions: The present research demonstrated that it is possible to prepare a palatable mixture of dietary fibers that maintains the property of decreasing body weight, favors the sense of satiation and accelerates the intestinal transit, with normalization of the stool consistency without the occurrence of meteorism.
Long-Term Aspiration following Treatment for Head and Neck Cancer
Authors: Nguyen Nam P. , Moltz Candace C. , Frank Cheryl , Vos Paul , Smith Herbert J. , Karlsson Ulf , Nguyen Ly M. , Rose Sue , Dutta Suresh , Nguyen Nga , Sallah Sabah
Published: June 2008

Background: Dysphagia and aspiration are long-term complications with life-threatening consequences following treatment of head and neck cancer. We would like to assess the prevalence of aspiration in patients with long-term persistence of dysphagia (1 year or more) following treatment for head and neck cancer and to identify potential risk factors of aspiration. Methods: Modified barium swallow (MBS) examinations were performed in cancer-free patients who complained of dysphagia following treatment for head and neck cancer. The severity of the dysphagia was graded on a scale of 1–7. Results: Between 1992 and 2004, 74 patients with dysphagia underwent MBS 12–152 months following treatment (median 29 months). There were 2 grade 1, 22 grade 3, 21 grade 4, 11 grade 5, 7 grade 6, and 11 grade 7 cases. Twenty-nine patients (39%) had long-term aspiration at a median follow-up of 25 months (range 12–82). Eighteen patients (24%) required permanent gastrostomy because of severe aspiration. Type of treatment and disease stage did not seem to influence long-term aspiration risk. Conclusion: Patients with long-term dysphagia after treatment for head and neck cancer are at risk of aspiration. MBS should be performed to identify these patients.
Modified CAPOX (Capecitabine plus Oxaliplatin) Regimen Every Two Weeks as Second-Line Treatment in Patients with Advanced Colorectal Cancer Previously Treated with Irinotecan-Based Frontline Therapy
Authors: Kakolyris S. , Souglakos J. , Polyzos A. , Ardavanis A. , Ziras N. , Athanasiadis A. , Varthalitis I. , Amarantidis K. , Tsousis S. , Vamvakas L. , Vardakis N. , Georgoulias V.
Published: June 2008

Background: To evaluate the efficacy and tolerance of capecitabine (CAP) given every other week and biweekly oxaliplatin (OX; modified CAPOX regimen) in patients with advanced colorectal cancer previously treated with irinote- can-based frontline chemotherapy. Methods: Sixty-seven patients were enrolled; the median age was 62 years and 62 (92.5%) had a performance status (ECOG) of 0–1. OX and CAP were administered at the dose of 100 mg/m2 on day 1 and 2,000 mg/m2 on days 1–7, respectively, every 2 weeks. Results: A total of 429 treatment cycles were administered. Grade 3/4 neutropenia and thrombocytopenia were observed in 4 (6%) and 2 (3%) patients, respectively. Febrile neutropenia complicated 1 treatment cycle. The main nonhematologic toxicities were grade 2/3 peripheral sensory neurotoxicity (10% of patients) and grade 3/4 diarrhea (7%). In an intention-to-treat analysis, 3 (4.5%) complete and 13 (19.4%) partial responses (overall response rate 24%) were observed. Seventeen (24.5%) patients had stable and 27 (40.3%) progressive disease. The median time to tumor progression and overall survival were 5 months and 11.3 months, respectively. Conclusions: The results indicate that the modified CAPOX regimen is safe and effective as salvage treatment in patients with advanced colorectal cancer who were previously treated with irinotecan-based frontline therapy.
Phase II Study of a Combination of S-1 and Paclitaxel in Patients with Unresectable or Metastatic Gastric Cancer
Authors: Narahara Hiroyuki , Fujitani Kazumasa , Takiuchi Hiroya , Sugimoto Naotoshi , Inoue Kentaro , Uedo Noriya , Tsukuma Hideaki , Tsujinaka Toshimasa , Furukawa Hiroshi , Taguchi Tetsuo
Published: June 2008

Objectives: A phase II study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to evaluate the efficacy and tolerability in unresectable or metastatic gastric cancer. Patients and Methods: Twenty-nine patients with unresectable and/or metastatic gastric cancer were enrolled in the study. Paclitaxel 50 mg/m2 was administered on days 1 and 8. S-1 was administered orally at 40 mg/m2 b.i.d. for 14 consecutive days, followed by a 1-week rest. The primary endpoint was the response rate. Secondary endpoints were safety and overall survival. Results: The overall response rate in 29 patients was 48.3%, differentiated 36.4% and undifferentiated 55.6%. The median survival time was 13.9 months. Grade 3 or higher toxicity was observed in neutropenia (3.4%), diarrhea (3.4%), bilirubin (3.4%) and neuropathy (3.4%). Conclusions: Combination chemotherapy of weekly paclitaxel and S-1 demonstrated tolerable toxicity and efficacy. This regimen will be one of the initial treatment options for unresectable or metastatic gastric cancer.
Squamous Cell Carcinoma Antigen in Patients with Locally Advanced Cervical Carcinoma Undergoing Preoperative Radiochemotherapy: Association with Pathological Response to Treatment and Clinical Outcome
Authors: Ferrandina Gabriella , Macchia Gabriella , Legge Francesco , Deodato Francesco , Forni Franca , Digesù Cinzia , Carone Vito , Morganti Alessio G. , Scambia Giovanni
Published: June 2008

Objective: We investigated the role of squamous cell carcinoma (SCC) at presentation (pre-SCC) and after treatment (post-SCC) as predictor of pathological response and outcome in locally advanced cervical cancer (LACC) patients undergoing preoperative chemoradiation. Methods: One hundred and twenty-three consecutive LACC patients underwent preoperative chemoradiation including cisplatin and 5-fluorouracil plus external radiotherapy to the whole pelvic region. Clinical responders underwent radical surgery. SCC levels were expressed in nanograms/milliliter. Results: Ninety-five of 123 (77.2%) and 15/113 (13.3%) cases were classified as having high pre-SCC and high post-SCC levels. Complete pathological response was documented in 51 cases (41.5%), while persistence of microscopic foci was shown in 40 cases (32.5%). In the univariate analysis, FIGO (International Federation of Gynecology and Obstetrics) stage, clinical response to treatment and post-SCC levels were associated with pathological response to chemoradiation. In the multivariate analysis, only clinical response to treatment and post-SCC levels retained an independent role as predictors of pathological response to treatment. Cases with high post-SCC status had a shorter disease-free survival than cases with low post-SCC levels (p = 0.028). In the multivariate analysis, lack of a pathological complete response/persistence of microscopic foci to treatment retained an independent negative prognostic role for disease-free survival. Conclusions: Post-SCC identifies LACC patients with a poor chance of pathological response to chemoradiation and an unfavorable outcome.
Identification of Genes Targeted by CpG Island Methylator Phenotype in Neuroblastomas, and Their Possible Integrative Involvement in Poor Prognosis
Authors: Abe Masanobu , Watanabe Naoko , McDonell Nathalie , Takato Tsuyoshi , Ohira Miki , Nakagawara Akira , Ushijima Toshikazu
Published: June 2008

Background/Aims: CpG island (CGI) methylator phenotype (CIMP) is strongly associated with poor prognosis in neuroblastomas (NBLs; hazard ratios 7–22). Methylation of nonpromoter CGIs is useful to detect the presence of the CIMP, while the poor prognosis is considered to be caused by gene silencing due to promoter methylation. Here, promoter CGIs targeted by the CIMP were searched for. Methods: A genome-wide screening was performed by methylation-sensitive representational difference analysis of CIMP(+) and CIMP(–) NBLs. Results: Promoter CGIs of 9 genes were methylated in CIMP(+) NBL cell lines and caused silencing of their downstream genes. On analysis of 90 clinical specimens, CYP26C1,FERD3L (N-TWIST), CRYBA2 and PCDHGC4 were methylated at significantly higher incidences in CIMP(+) NBLs than CIMP(–) NBLs, while the difference was unclear for NPY, SPAG6, DDIT4L, CHR3SYT and C6Orf141. Methylation of CYP26C1 and FERD3L was significantly associated with poor prognosis, but weaker than the presence of the CIMP. Treatment of an NBL cell line with a demethylating agent caused demethylation of multiple promoter CGIs, and enhanced 13-cis-retinoic acid-induced neuronal differentiation. Conclusion: Our results indicate that the CIMP causes poor prognosis of NBLs by inducing methylation of multiple promoter CGIs with various incidences.
Clinical Significance of Insulin-Like Growth Factor Type 1 Receptor and Epidermal Growth Factor Receptor in Patients with Advanced Gastric Cancer
Authors: Matsubara Junichi , Yamada Yasuhide , Nakajima Takako E. , Kato Ken , Hamaguchi Tetsuya , Shirao Kuniaki , Shimada Yasuhiro , Shimoda Tadakazu
Published: June 2008

Objective: To better understand the clinical implications of insulin-like growth factor type 1 receptor (IGF-1R), epidermal growth factor receptor (EGFR) and HER2 expressions in gastric cancer (GC). Methods: The study group comprised 86 patients who received first-line chemotherapy for advanced GC at the National Cancer Center Hospital. Using laser-captured microdissection and a real-time RT-PCR assay, we quantitatively evaluated mRNA levels of IGF-1R, EGFR and HER2 in paraffin-embedded cancer specimens of surgically removed primary tumors. Results: In univariate analysis of the study group as a whole, patients with low expression of both IGF-1R and EGFR (n = 13) had a significantly longer overall survival than the other patients (n = 51; median, 24.6 vs. 12.8 months; log-rank p = 0.013). Multivariate survival analysis demonstrated that high EGFR expression [hazard ratio, HR: 2.94 (95% confidence interval, CI: 1.40–6.17), p = 0.004] and poor performance status [HR: 1.96 (95% CI: 1.12–3.42), p = 0.018] were significant predictors of poor survival. In patients given first-line S-1 monotherapy (n = 29), low IGF-1R (p = 0.002) and low EGFR (p = 0.035) gene expression correlated with a better response, without a significant prolongation of survival. Conclusion: Our data warrant further investigations on the strategy of co-targeting IGF-1R and EGFR in GC.
Epoetin β Once-Weekly Therapy in Anemic Patients with Solid Tumors and Non-Myeloid Hematological Malignancies Receiving Chemotherapy
Authors: Spaëth Dominique , Desablens Bernard , Rodon Philippe , Mennecier Bertrand , Oudard Stéphane , Moullet Isabelle , Ghomari Kamel , Bergougnoux Loïc , Bleuzen Pascal , Jenabian Arash , Ifrah Norbert
Published: June 2008

Objectives: This study aimed to provide further clinical evidence for the efficacy and safety of epoetin β once weekly across a wide range of cancer types. Methods: This was a multicenter, open-label, prospective, single-arm study in patients with either a solid tumor or non-myeloid hematological malignancy, receiving or scheduled to receive further chemotherapy. Patients received epoetin β 30,000 IU subcutaneously once weekly for 16 weeks. The primary efficacy endpoint was the change in hemoglobin (Hb) level according to the patient’s baseline Hb level. Results: A total of 691 patients were included in the intent-to-treat population. Epoetin β effectively increased Hb levels (a mean increase from baseline of 1.1 g/dl by week 4 and 2.2 g/dl by week 12). Hb response was achieved in 60.4% of all patients and 61.2% of those with baseline Hb <11 g/dl. Hb response was similar in patients with solid tumors (60.5%) and non-myeloid hematological malignancies (60.2%). Type of chemotherapy and baseline platelet count were independent predictive factors for response. Epoetin β treatment was well tolerated. Conclusions: Epoetin β 30,000 IU once weekly effectively increases Hb levels, is well tolerated and has similar efficacy in anemic patients with solid tumors or non-myeloid hematological malignancies.
Metabolic and Respiratory Variables during Pressure Support versus Synchronized Intermittent Mandatory Ventilation
Authors: El-Khatib Mohamad , Bou-Khalil Pierre , Zeineldine Salah , Kanj Nadim , Abi-Saad George , Jamaleddine Ghassan
Published: June 2008

Background: Mechanically ventilated patients interact and respond differently to different modes of ventilatory support. Objectives: To assess changes in metabolic and respiratory variables during equivalent changes with either pressure support ventilation (PSV) or volume-cycled synchronized intermittent mandatory ventilation (SIMV) in non-tracheostomized patients without known obstructive pulmonary disease receiving short-term mechanical ventilation in the intensive care unit. Methods: Fourteen patients receiving volume-cycled SIMV at 12 breaths/min (SIMV100%) were included in the study. The PSV level (PSV100%) resulting in a minute volume and respiratory rate equivalent to that during SIMV100% was determined for each patient. Then each patient underwent trials at 66% and 33% of initial ventilator support with volume-cycled SIMV (SIMV66% and SIMV33%) and PSV (PSV66% and PSV33%) in random order. At the end of each trial, oxygen consumption (v̇O2), carbon dioxide production (v̇CO2), measured energy expenditures (MEE), peak inspiratory flow, total respiratory frequency, tidal volume, minute ventilation, occlusion pressure (P0.1) and inspiratory duty cycle (Ti/Ttot) were measured. Results: There were smaller changes in v̇O2, v̇CO2 and MEE when equivalent changes were applied with PSV (15.7 ± 4.4; 12.5 ± 2.2 and 15 ± 3.5%) compared with volume-cycled SIMV (32.7 ± 7.7; 23 ± 5.2 and 30.7 ± 6.8%; p < 0.05). P0.1 and Ti/Ttot were significantly smaller during PSV (2.64 ± 0.28 and 0.38 ± 0.03 cm H2O) than volume-cycled SIMV (4.01 ± 0.21 and 0.43 ± 0.02 cm H2O; p < 0.05). Conclusions: Changes in the level of PSV resulted in smaller changes in metabolic and respiratory variables compared with equivalent changes in the level of volume-cycled SIMV support. PSV may be more suitable for progressive respiratory muscle reloading.
Regular Exercise in the Elderly Is Effective to Preserve the Speed of Voluntary Stepping under Single-Task Condition but Not under Dual-Task Condition
Authors: Melzer Itshak , Marx Roni , Kurz Ilan
Published: June 2008

Background: Stepping response may be considered the most important postural reaction to prevent a fall because it is the inability to respond effectively to a loss of balance that ultimately determines whether a fall occurs. However, very little has been studied on the effect of exercising on step execution behavior in the elderly. Objectives: To explore whether older persons who exercise regularly have faster voluntary stepping times than sedentary elderly persons. Additionally, we investigated the association between step execution behavior, self-reported physical function, and balance performance. Methods: Case-control study of 48 elderly adults aged 65–91 years who live independently in retirement homes. Participants were classified as 24 exercisers (reporting >2 exercise training activities/week) and 24 age- and gender-matched inactive elderly individuals (who do not exercise regularly). The Voluntary Step Execution Test was performed as a reaction time task while standing on a force platform under single-task and dual-task conditions. Step initiation phase, foot off time, foot contact time, preparatory, and swing phases were extracted from center of pressure and ground reaction force data. Self-reported function was examined using Late-Life Function and Disability Instrument; Berg Balance Test was also performed. Results: Exercisers had significantly faster voluntary step times in single-task condition (959 vs. 1,158 ms) but not during dual-task condition (1,170 vs. 1,303 ms). Exercisers had a significantly higher Berg Balance Test (53.7 ±3.6 vs. 49.8 ±5.3), consumed less medication (3.3 ±2.3 vs. 5.6 ±2.9), and their lower extremity function scores were higher (88.61 ±2.3 vs. 73.1 ±2.7) than those of inactive subjects. Conclusion: Exercising regularly protects from physical functioning loss in older persons and against a decrease in voluntary step execution times during single-task but not during dual-task conditions. Lack of specificity (dual-task exercises) during the training may be the cause of insignificant differences in dual-task stepping performance. Thus, adding dual-task training may improve dual-task performance in the elderly.
Effects of von Willebrand factor concentration and platelet collision on shear-induced platelet activation
Authors: Gao Zhenyue , Liu Fang , Yu Ziqiang , Bai Xia , Zhuang Fengyuan , Yang Chun , Ruan Changgeng
Published: June 2008

The binding of plasma von Willebrand factor (vWF) to platelet glycoprotein (GP) Ibα in a high shear stress field, and subsequent integrin-GPIIb/IIIa-vWF conjunction induces platelet aggregation (SIPA). However, the specific biomechanical mechanism of the vWF-GPIb interaction still remains to be elucidated. A parallel-plate rectangular flow chamber was built to simulate a stenopeic artery flow pattern. Using the flow chamber, we examined shear- induced platelet activation (SIPAct) at different vWF concentrations (5–25 µg/ml) and several simulated stenotic high shear rates. P-selectin expression on the platelets and annexin V binding to the platelets were used as two markers of platelet activation. At different localized shear rates (3,000 s-1–9,500 s-1), the percentage of annexin V and P-selectin positive cells increased from 8.3 ± 0.4% to 22.3 ± 1.8% ( p 0.05) and from 17.4 ± 0.5% to 33.5 ± 2.5% (p 0.05),respectively. As the vWF concentration increased from 5 µg/ml to 25 µg/ml, the annexinV binding rate increased from 7.2 ± 0.6% to 53.4 ± 3.8% (p 0.05), and P-selectin expression increased from 16.5 ± 1.2% to 65.9 ± 5.2% (p 0.05). A test in a uniform shear field using cone-plate viscometer rheometry showed that the platelet activation rate was proportional to the platelet concentration. This result suggests that platelet collision is one of the impact factors of SIPAct.
Salsolinol, an endogenous neurotoxin, enhances platelet aggregation and thrombus formation
Authors: Lim Kyung-Min , Noh Ji-Yoon , Chung Seung-Min , Kim Keunyoung , Hong Suyoung , Shin Sue , on Jong-HyunYo , Bae Ok-Nam , Kim Young-Dae , Chung Jin-Ho
Published: June 2008

Salsolinol, an endogenous neurotoxin, is known to be involved in the neuropathy of Parkinson’s disease and chronic alcoholism. In these diseases, increased thrombotic events are also commonly reported, yet the mechanism underlying remains poorly understood. Here we report that salsolinol can enhance agonist-induced platelet aggregation and granular secretion, which is essential in the thrombus formation. In rat and human platelets, agonist-induced platelet aggregation was significantly increased by salsolinol in a concentration-dependent manner. Agonist-induced granular secretions of serotonin and concomitant P-selectin expression were also augmented by salsolinol. α2-adrenergic blockers attenuated the salsolinol-enhanced aggregation and the inhibition of cyclic AMP generation was found, suggesting the involvement of α2-adrenergic receptor-mediated pathways in these events. In accord with the in-vitro results, in an arterial and venous thrombosis model in vivo in the rat, salsolinol shortened vessel occlusion time and increased thrombus formation, respectively. In conclusion, we demonstrated that sal-solinol can enhance agonist-induced aggregation and granular secretion in platelets through α2-adrenergic receptor activation, which resulted in the increased thrombus formation in vivo.These results suggest that salsolinol-enhanced platelet aggregation could be a possible contributing factor to the thrombotic events observed in Parkinson’s disease and alcoholism.
The biphasic transmittance waveform: An early marker of sepsis in patients with neutropenia
Authors: Hussain Nazia , Hodson Dan , Marcus Robert , Baglin Trevor , Luddington Roger
Published: June 2008

Transmittance waveform (TW) analysis has been proposed as a method of both prediction and monitoring of non-overt and overt disseminated intravascular coagulation. This study assessed the use of the rapid TW of the activated partial thromboplastin time in the detection of sepsis in 49 consecutive neutropenic haemato-oncology patients. A slope 1 cut-off value of –0.050 was found to be optimum giving 85% sensitivity with 92% specificity and positive and negative predictive values of 62% and 98%, respectively. Furthermore a worsening slope 1 value at 24 hours was indicative of a 60% increase in mortality risk. Haemato-oncology patients have a significantly increased risk of developing sepsis during intensive chemotherapy, exacerbated by the resultant neutopenia. This sepsis may progress extremely rapidly and is associated with a high mortality. Early diagnosis is therefore critical and is currently made on a predominantly clinical basis with supporting microbiological evidence 2–3 days later. This study showed that TW offers an early marker, predictive of sepsis in neutropenic patients. It correlates with subsequent microbiological results and may identify patients at greater risk of clinical deterioration who may require more intensive early therapy or observation. It may also provide a useful marker to monitor the effects of treatment.
Potential protective role of apoprotein J (clusterin) in atherogenesis: Binding to enzymatically modified low-density lipoprotein reduces fatty acid-mediated cytotoxicity
Authors: Lux Cornelia A. , Paprotka Kerstin , Torzewski Michael , Dersch Katrin , Koch-Brandt Claudia , Husmann Matthias , Schwarz Margarethe , Spath Lena , Bhakdi Sucharit
Published: June 2008

Following entrapment in the arterial intima, low-density lipoprotein (LDL) can be modified by hydrolytic enzymes to yield a lipoprotein derivative that binds C-reactive protein, activates complement, and is rapidly taken up by monocytes/macrophages. Free fatty acids contained in enzymatically modified LDL (E-LDL) render the lipoprotein cytotoxic due to their capacity to trigger programmed cell death. Apoprotein J (ApoJ) alias clusterin is a multifunctional glycoprotein with cytoprotective and anti-inflammatory properties. It interacts with diverse substrates, is present in the intima and the media of arteries with atherosclerotic lesions and is also synthesized by smooth muscle cells during development of atherosclerosis. We report that ApoJ binds to E-LDL but not to native LDL. Binding resulted in marked reduction of cytotoxicity of E-LDL on smooth muscle cells, as revealed by determination of caspase activity, annexin binding, and cellular ATP. ApoJ was detected immunohistochemically in early atherosclerotic lesions, where it was found to colocalize with E-LDL. In atherosclerotic lesions, ApoJ may thus subserve protective functions through its capacity to inactivate C5b-9 complement complexes and by reducing the cytotoxic effects of modified LDL on cells that gain contact with the lipoprotein.
Possible mechanisms contributing to oxidative inactivation of activated protein C: Molecular dynamics study
Authors: Nalian Armen , Iakhiaev Alexei V.
Published: June 2008

Activated protein C (APC) is a serine protease, an effector enzyme of the natural anticoagulant pathway. APC is approved for treatment of severe sepsis characterized by the increased concentrations of H2O2 and hypochlorite. We found that treatment of APC with these oxidants markedly inhibits the cleavage of the APC-specific chromogenic substrate, suggesting that oxidants can induce changes in the structure of the active site of APC. Resistance of oxidant-treated APC to chemical digestion with cyanogen bromide (CNBr) implies that methionine oxidation can at least in part be responsible for inhibition of APC. Since methionine residues, the main targets of oxidants in APC, are not included in the active site, we hypothesize that oxidation induces allosteric changes in the architecture of the catalytic triad of APC. Using molecular dynamics (MD) simulations we found that methionine oxidation alters the distance between cSer 195Oγ and cHis57 Nε2 atoms placing them in positions unfavorable for the catalysis. At the same time, neither distances between Cα atoms of the catalytic triad cAsp102-cHis57-cSer195, nor the overall structure of APC changed significantly after oxidation of the methionine residues. Disruption of the H-bond between Nδ1 of cHis57 and carboxyl group of cAsp 102, which can take place during the hypochlorite-induced modification of cHis57,dramatically changed the architecture of the catalytic triad in oxidized APC. This mechanism could contribute to APC inactivation by hypochlorite concurrently with methionine oxidation. These are novel findings, which describe potentially pathophysiologically relevant changes in the functional stability of APC exposed to the oxidative stress.
Phenotypic heterogeneity in the gray platelet syndrome extends to the expression of TREM family member, TLT-1
Authors: Bermejo Emilsé , Combrié Robert , McVicar Daniel W. , Washington A.Valance , Nurden Alan T. , Nurden Paquita
Published: June 2008

The Gray platelet syndrome (GPS) is a rare inherited disorder linked to undefined molecular abnormalities that prevent the formation and maturation of α-granules. Here, we report studies on two patients from unrelated families that confirm phenotypic heterogeneity in the disease. First we used immunoelectron microscopy (I-EM) to confirm that TREM-like transcript-1 (TLT-1) is mostly localized to α-granule membranes of normal platelets. Then we performed Western blotting (WB) and flow cytometry with permeabilized platelets to show that TLT - 1 is selectively reduced in the platelets of patient 1, previously noted to be deficient in glycoprotein (GP)VI (Nurden et al., Blood 2004; 104: 107–114).Yet both TLT - 1 and GPVI were normally expressed in platelets of patient 2. Usual levels of JAM-C and claudin-5, also members of the immunoglobulin receptor family, were detected in platelets of both patients. In contrast, P-selectin was markedly decreased for patient 1 but not patient 2.Two metalloproteases, MMP-2 and MMP-9 were normally present. As predicted, platelets of patient 1 showed little labelling for TLT - 1 in I-EM, whereas residual Fg was seen in small vesicular structures and P-selectin lining vacuoles or channels of what may be elements of the surface-connected canalicular system. Our results identify TLT - 1 as a glycoprotein potentially targeted in platelets of GPS patients, while decreases in at least three membrane glycoproteins suggest that an unidentified proteolytic activity may contribute to the phenotype in some patients with this rare disease.
Protease activated receptor 1 (PAR-1) activation by thrombin is protective in human pulmonary artery endothelial cells if endothelial protein C receptor is occupied by its natural ligand
Authors: Bae Jong-Sup , Rezaie Alireza R.
Published: June 2008

We recently demonstrated that the occupancy of endothelial protein C receptor (EPCR) by its natural ligand activated protein C (APC)/protein C switches the protease activated receptor 1 (PAR-1)-dependent signaling specificity of thrombin from a disruptive to a protective effect in cultured human umbilical vein endothelial cells. Given the phenotypic differences between endothelial cells in venular and arterial beds, in this study we evaluated the signaling function of thrombin in human pulmonary artery endothelial cells (HPAECs) before and after treating them with PC-S195A which lacks catalytic activity but exhibits a normal affinity for EPCR. As expected, both thrombin and thrombin receptor agonist peptide (TRAP) enhanced the permeability barrier of HPA ECs; however, both PAR-1 agonists exhibited a potent barrier protective effect when the cells were treated with PC-S195A prior to stimulation by the agonists. Interestingly, similar toAPC, thrombin exhibited a potent cytoprotective activity in the LPS-induced permeability and TNF-α-induced apoptosis and adhesion assays in the PC-S195A treated HPAECs. Treatment of HPAECs with the cholesterol depleting molecule methyl-β-cyclodextrin eliminated the protective effect of both APC and thrombin. These results suggest that the occupancy of EPCR by its natural ligand recruits PA R-1 to a protective signaling pathway within lipid rafts of HPAECs. Based on these results we conclude that the activation of PAR-1 by thrombin would initiate a protective response in intact arterial vascular cells expressing EPCR. These findings may have important ramifications for understanding the mechanism of the participation of the vascular PAR-1 in pathophysiology of the inflammatory disorders.
The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid
Authors: van Oijen Martijn G. H. , Sundaresan Santosh , Brouwer Marc A. , te Morsche Rene H. M. , Keuper Wessel , Peters Wilbert H. M. , Drenth Joost P . H. , Verheugt Freek W. A. , Clappers Nick
Published: June 2008

Aspirin prevents thrombotic events by inhibiting platelet cyclooxygenase-1 (COX-1), thus reducing thromboxane A2 formation and platelet aggregation. The C50T polymorphism of COX-1 is associated with an impaired inhibition of both thromboxane production and in-vitro platelet aggregation by aspirin. We studied whether this polymorphism is also associated with the risk of clinical thrombotic events in patients using aspirin. We included 496 patients admitted to our Coronary Care Unit for various indications treated with aspirin 80 mg daily. Genotyping for the C50T polymorphism demonstrated that 86.7% of the patients had the common genotype, and 13.3% had the variant (12.5% heterozygous, 0.8% homozygous). Baseline variables were well balanced, except that patients with the common genotype more frequently used aspirin prior to admission compared to those patients with the variant genotype. The composite primary endpoint of myocardial infarction, stroke, and/or cardiovascular death occurred in 98 patients (19.8%). Myocardial infarction occurred in 9.6% of patients, stroke in 1.6%, and cardiovascular death in 12.1%.The unadjusted hazard ratio (95% CI) for the primary endpoint for patients with the variant versus the common genotype was 1.07 (0.62–1.85), p=0.8.The adjusted hazard ratio was 0.86 (0.49–1.50), p=0.6. In prior laboratory studies the COX-1 C50T polymorphism was associated with an impaired inhibitory effect of aspirin on thromboxane production and platelet function. However, in this cohort of patients using low-dose aspirin for secondary prevention the polymorphism was not associated with a higher risk of atherothrombotic events.
Forging Buddhist Credentials as a Tool of Legitimacy and Ethnic Identity: A Study of Arakan's Subjection in Nineteenth-Century Burma
Authors: Leider Jacques
Published: June 2008

The kingdom of Arakan was conquered by the Burmese in 1785 and annexed by the British after the first Anglo-Burmese War (1824-6). Resistance to the occupation was followed by campaigns of pacification that entailed social disruption. Starting with an analysis of the religious motives for King Bodawphaya's quest to conquer Arakan, this article focuses on the use of local religious traditions to bolster ethnic self-identification and resist the process of integration. Based on little explored indigenous and Western primary sources, this essay attempts to make a contribution to the social history of Buddhism in Arakan. Le royaume d'Arakan fut conquis en 1785 par les Birmans. Après la première guerre anglobirmane (1824-6), il fut annexé par les Anglais. La résistance arakanaise aux occupants provoqua des campagnes d'oppression qui eurent un impact considérable sur la société. L'article que voici propose une analyse des motifs religieux qui sous-tendent la conquête par le roi Bodawphaya (1781-1819). L'attention se porte ensuite sur le recours aux traditions locales qui étayaient l'identité communautaire et permettaient de résister au processus d'intégration. Cette enquête fondée sur des sources primaires indigènes et occidentales offre ainsi une contribution à l'histoire sociale du bouddhisme en Arakan.
Individuation, particularisation et détermination selon Plotin
Authors: Aubry Gwenaëlle
Published: June 2008

Plotinus' formulation of the problem of the individual should not be reduced to the question of whether or not one can accept Forms of Individuals. First, if Plotinus does indeed posit an intelligible foundation of individuality, there are no grounds to identify this foundation with a Form: it must rather be considered a logos. Second, we must, in addition to this intelligible “principle of distinction”, allow for a sensible “principle of individuation”: the living body. Finally, we have to distinguish a third level: that of the hêmeis, the individual as a person, capable of freedom and consciousness. This latter's compatibility with the other two seems problematic, so that the real difficulty may lie in this tension, in Plotinus' thought, between an ontological and an ethical concept of the individual.
Creating Comparability Differently: Disassembling Ethnographic Comparison in Law-in-Action
Authors: Scheffer Thomas
Published: June 2008

Ethnographic comparison identifies and analyses core mechanisms which integrate and drive various ethnographic fields. This is exemplified here by what we term, following Luhmann, "the binding mechanism" – which we identify in criminal cases from England, the United States and Germany. By choosing criminal cases as the dynamic frames of "their" (participants') activity and "our" (observers') analysis, thick comparison questions the sources of stability found in structural comparisons of legal doctrines, namely fixed items, definite meaning, and detached contexts. This paper discusses how these features of structural comparison are replaced by more dynamic components, such as becomings, involvements, and formations.
Multi-Sited Comparison of "Doing Regulation"
Authors: Sørensen Estrid
Published: June 2008

George Marcus (1995) emphasizes that multi-sited ethnography embodies within itself a comparative dimension. For our general understanding of comparison, however, multi-sited ethnography lacks a crucial component: a grounding or tertium comparationis. This article proposes a multi-sited comparison which does not take as its point of departure any tertium comparationis but instead identifies this as an outcome. The method of comparison was developed amidst a multisited ethnography of "doing regulation," here with reference to computer games and the regulatory purpose of protecting minors from harmful media content.
Gaining Insight from Incomparability: Exploratory Comparison in Studies of Social Practices
Authors: Schmidt Robert
Published: June 2008

This paper suggests an experimental approach to comparison. It is argued that comparing should be detached from the question of adequacy in order to regain it as an analytical and explorative tool. This approach is put to work by comparing boxing to computer programming. Drawing on comparisons of sports practices to other social practices by Mead and Bourdieu, the paper deploys sports comparison quite similarly. In a comparative perspective the practice of writing code for software is depicted by using means and modes of description developed from an ethnography of boxing. This serves for illuminating and understanding programming's gestural and embodied logic.
Landslide Risk Analysis using a New Constitutive Relationship for Granular Flow
Authors: Ren Diandong , Leslie Lance M. , Karoly David
Published: June 2008

In this study, landslide potential is investigated, using a new constitutive relationship for granular flow in a numerical model. Unique to this study is an original relationship between soil moisture and the inertial number for soil particles. This numerical model can be applied to arbitrary soil slab profile configurations and to the analysis of natural disasters, such as mudslides, glacier creeping, avalanches, landslips, and other pyroclastic flows. Here the focus is on mudslides.

The authors examine the effects of bed slope and soil slab thickness, soil layered profile configuration, soil moisture content, basal sliding, and the growth of vegetation, and show that increased soil moisture enhances instability primarily by decreasing soil strength, together with increasing loading. Moreover, clay soils generally require a smaller relative saturation than sandy soils for sliding to commence. For a stable configuration, such as a small slope and/or dry soil, the basal sliding is absorbed if the perturbation magnitude is small. However, large perturbations can trigger significant-scale mudslides by liquefying the soil slab.

The role of vegetation depends on the wet soil thickness and the spacing between vegetation roots. The thinner the saturated soil layer, the slower the flow, giving the vegetation additional time to extract soil moisture and slow down the flow. By analyzing the effect of the root system on the stress distribution, it is shown that closer tree spacing increases the drag effects on the velocity field, provided that the root system is deeper than the shearing zone.

Finally, the authors investigated a two-layer soil profile, namely, sand above clay. A significant stress jump occurs at the interface of the two media.