bluuebunny/crossref_metadata_2025 huggingface dataset:
Both Metabolic Inhibition and Mitochondrial K
ATP
Channel Opening Are Myoprotective and Initiate a Compensatory Sarcolemmal Outward Membrane Current
Authors: Irie Hiroshi , Gao Junyuan , Gaudette Glenn R. , Cohen Ira S. , Mathias Richard T. , Saltman Adam E. , Krukenkamp Irvin B.
Published: September 2003

Background—

Blockade of oxidative phosphorylation may activate ATP sensitive mitochondrial potassium (mitoK
ATP
) channels. We examined whether both metabolic inhibition and mitoK
ATP
channel openers protect both the whole organ and isolated cells from ischemia.

Methods and Results—

Using a Langendorff preparation, one group of isolated rabbit hearts were exposed to ischemic preconditioning (IPC) via 2 episodes of flow interruption. The second group of hearts was preconditioned with 2 episodes of either the metabolic inhibitor, sodium cyanide (NaCN), or the mitoK
ATP
channel opener, diazoxide. The third group of hearts was exposed to the mitoK
ATP
channel inhibitor, 5-hydroxydecanoic acid (5-HD) prior to preconditioning with NaCN, diazoxide or IPC. Controls had no drug infused. Then, ischemia was induced in all hearts by left anterior descending coronary artery occlusion and infarct size was determined. Compared with controls (40±3%), infarct size was significantly reduced in hearts preconditioned with NaCN, diazoxide or IPC (18±3%, 26±3%, 21±2%, respectively;
P
<0.05 versus control). These reductions were reversed by 5-HD (36±3%, 33±2%, 37±2%; NaCN, diazoxide, IPC, respectively). Secondly, whole cell patch clamped isolated guinea pig ventricular myocytes were preconditioned with 2 episodes of either NaCN or diazoxide followed by Tyrodes perfusion with membrane potential set to −70 mV. Control cells were exposed to Tyrodes solution. All cells were then clamped to −20 mV and exposed to NaCN, which caused induction of an outward potassium current. Compared with controls, the average time to induction of the outward current was significantly reduced in cells preconditioned with either brief application of NaCN (11.6±1.8 versus 5.1±1.0 minutes, control versus NaCN,
P
<0.05) or diazoxide (5.5±1.4 versus 2.0±0.8 minutes, control versus diazoxide,
P
<0.05).

Conclusion—

Preconditioning protects the heart through mitoK
ATP
. This protection also alters a surface membrane current, which may be important in myocardial protection.
Failure to Prevent Progressive Dilation of Ascending Aorta by Aortic Valve Replacement in Patients With Bicuspid Aortic Valve: Comparison With Tricuspid Aortic Valve
Authors: Yasuda Hisayo , Nakatani Satoshi , Stugaard Marie , Tsujita-Kuroda Yuko , Bando Ko , Kobayashi Junjiro , Yamagishi Masakazu , Kitakaze Masafumi , Kitamura Soichiro , Miyatake Kunio
Published: September 2003

Background—

Patients with bicuspid aortic valve (BAV) have been frequently complicated with ascending aortic dilation possibly because of hemodynamic burdens by aortic stenosis (AS) or regurgitation (AR) or congenital fragility of the aortic wall.

Methods and Results—

To clarify if the aortic dilation could be prevented by aortic valve replacement (AVR) in BAV patients, we studied 13 BAV (8 AR dominant, 5 AS dominant) and 14 tricuspid aortic valve (TAV) patients (7 AR, 7 AS) by echocardiography before and after AVR (9.7±4.8 years). We also studied 18 BAV (11 AR, 7 AS) without AVR. Diameters of the sinuses of Valsalva, sinotubular junction and the proximal aorta were measured. The annual dilation rate was calculated by dividing changes of diameters during the follow-up period by the body surface area and the observation interval. We found that aortic dilation in BAV patients tended to be faster than that in TAV patients, although a significant difference was found only at the proximal aorta (0.18±0.08 versus −0.08±0.08 mm/(m
2
/year),
P
=0.03). BAV patients with and without AVR showed similar progressive dilation. AR dominant group showed tendency of more progressive dilation than AS dominant group in BAV, although it did not reach statistical significance. TAV patients did not show further aortic dilation after AVR.

Conclusions—

AVR could not prevent progressive aortic dilation in BAV. Since the aorta did not dilate in TAV, progressive aortic dilation in BAV seems mainly due to the fragility of the aortic wall rather than hemodynamic factors.
Predictors of Prosthesis Survival, Growth, and Functional Status Following Mechanical Mitral Valve Replacement in Children Aged <5 Years, a Multi-Institutional Study
Authors: Raghuveer Geetha , Caldarone Christopher A. , Hills Christine B. , Atkins Dianne L. , Belmont John M. , Moller James H.
Published: September 2003

Background—

Prosthesis survival, growth, and functional status after initial mechanical mitral valve replacement (MVR) in children <5 years of age are poorly defined.

Methods and Results—

The experience of the Pediatric Cardiac Care Consortium (45 centers, 1982 to 1999), which included 102 survivors after initial MVR, was analyzed. Median follow-up: 6.0 years (interquartile range: 3.0 to 10.6 years; 96% complete). Twenty-nine survivors had undergone a second MVR at an interval of 4.8±3.8 years after initial MVR. Reasons for second MVR were prosthetic valve stenosis 24 (83%), thrombosis 4 (14%), and endocarditis 1 (3%). For those who had second MVR, prosthesis sizes were: first MVR 19±2 mm and second MVR 22±3 mm, and their body weight increased from 7.4±2.8 kg to 16.8±10.5 kg. To identify risk factors for having a second MVR, the 29 second MVR survivors were compared with the 73 who did not have a second MVR on first-MVR demographic and perioperative variables. By univariate analysis, patients with shorter prosthesis survival were younger, weighed less, had smaller prostheses, greater ratio of prosthesis size:body weight, were less likely to have a St. Jude prosthesis and more likely to have Shone’s syndrome. By multivariate analysis prosthesis survival was predicted only by first MVR age: odds ratio (OR) 7.7 (95% confidence interval [CI] 2.6–22.7) and prosthesis size: OR 6.8 (95% CI 2.6–18.2). High risk patients (age <2 years and prosthesis <20 mm at first MVR) had an OR=46.3 compared with low-risk patients (age ≥2 years and prosthesis ≥20 mm at first MVR) over similar follow-up intervals. Using first-MVR weight-matched controls, body weight increased similarly for patients <2 years old who had a second MVR versus those who did not. Prosthesis size, however, differed significantly, with second MVR patients having smaller prostheses at first MVR (18.7±0.8 mm versus 22.4±3.6 mm,
P
=0.017). An estimate of current New York Heart Association (NYHA) functional status was class 1 in 76%, class 2 in 22%, and classes 3 or 4 in 2%.

Conclusion—

Prosthesis survival can be predicted based on first MVR age and prosthesis size. Somatic growth is comparable regardless of the need for second MVR. There is an increment in prosthesis size at second MVR, suggesting continued annular growth. Significant limitation of function after MVR is uncommon. MVR may be an appropriate strategy for children <5 years old despite the risk of second MVR in the youngest patients in whom the smallest prostheses are used.
Endoscopic Exposure and Stabilization of Posterior and Inferior Branches Using the Endo-Starfish Cardiac Positioner and the Endo-Octopus Stabilizer for Closed-Chest Beating Heart Multivessel CABG: Hemodynamic Changes in the Pig
Authors: Gründeman Paul F. , Budde Ricardo , Beck Hendricus Mansvelt , van Boven Wim-Jan , Borst Cornelius
Published: September 2003

Background—

Closed-chest, off-pump, multivessel CABG requires modified instruments to expose and stabilize posterior and inferior coronary branches. Using three new prototype devices, we explored the feasibility of endoscopic bypass grafting on these branches and assessed cardiac function during cardiac displacement.

Methods—

Eight pigs (75 to 85 kg) were instrumented for hemodynamics and paced at 80 to 100 bpm. After closure of the sternotomy wound, the Da Vinci endoscope was inserted subxiphoidally. A sternal hook was used to hoist the sternum ventrally by 5 cm. The articulating EndoStarfish cardiac positioner was placed through a trocar (Ø12 mm). The positioner was fixed to the apex using −400 mm Hg suction and the heart was displaced anteriorly to 90 degrees. In 12 other pigs (75 to 85 kg), both internal mammary arteries (IMA) were harvested and the sternal wound was closed. Five trocar ports were placed for instrumentation (Ø12 mm, two in left chest, two in right chest, and one subxiphoidally). For coronary stabilization, a novel deployable EndoOctopus cardiac stabilizer was employed (suction −400 mm Hg). The Da Vinci robot-telemanipulator system was used for endoscopic grafting of the left and right IMA on posterior and inferior branches (16 anastomoses).

Results—

When circumflex arteries were fully exposed and accessible for coronary surgery, stroke volume decreased by 18%±3 versus baseline (
P
=0.02) and mean arterial pressure decreased by 27%±6 (
P
=0.001). Additional 10 degrees Trendelenburg head-down positioning normalized stroke volume and arterial pressure. In the displaced heart, obtuse marginal branches (OM) and the ramus descending posterior (RDP) of the right coronary artery became fully exposed with a mean arterial pressure >70 mm Hg during grafting. No accidental detachment occurred. Coronary target motion was restrained to approximately 1×1 mm. In two test cases, five sham distal anastomoses were created (grafts sewn to epicardium, left IMA to OM2 jump to OM3, right IMA to RDP, and composite graft from left IMA jump to diagonal branch). In 10 animals, 16 successfully completed anastomoses to RPD and OM branches of Ø1.75 to 2.5 mm required 25 to 60 minutes each to construct. At sacrifice, all anastomoses were patent.

Conclusion—

In the closed-chest pig in Trendelenburg position and during lifting of the sternum, the EndoStarfish and EndoOctopus enabled IMA grafting of posterior and inferior branches on the beating heart without mean arterial pressure dropping below 70 mm Hg.
Trends in Surgery and Chemotherapy for Women Diagnosed With Ovarian Cancer in the United States
Authors: Harlan Linda C. , Clegg Limin X. , Trimble Edward L.
Published: September 2003

Purpose: We examined patterns of care in a population-based sample of 601 ovarian cancer patients diagnosed in 1991, and a sample of 566 women was selected in 1996 to examine trends in care.

Patients and Methods: Patient cases were sampled from within the Surveillance, Epidemiology, and End Results program. Medical records were reabstracted, and treatment data were verified with the treating physician.

Results: Across these two time periods, the percentage of women with presumptive stage I, II, and IV disease who received lymph node dissection increased. However, a significant number still were not precisely staged. More than 65% of women with ovarian cancer were given cyclophosphamide in 1991 compared with about 14% in 1996. Paclitaxel increased from 1% to 62% during that time. After adjusting for age, race or ethnicity, registry, income, insurance status, Charlson score, residency training program, and marital status, women with early-stage disease were significantly more often given National Institutes of Health Consensus Development Conference guideline therapy in 1996 than in 1991. However, for women with stage III and IV disease, the use of guideline therapy did not significantly increase. Older women and minorities consistently received less guideline therapy, and the lack of private insurance was an impediment for both Hispanic and non-Hispanic black women.

Conclusion: Despite guidelines presented by several organizations, significant numbers of women with ovarian cancer are not being provided with appropriate care. This is particularly true for older and minority women, especially those without private insurance. Educational strategies must be devised to increase the number of women receiving guideline therapy and decrease disparities across population groups.
Addition of Either Lonidamine or Granulocyte Colony-Stimulating Factor Does Not Improve Survival in Early Breast Cancer Patients Treated With High-Dose Epirubicin and Cyclophosphamide
Authors: Papaldo Paola , Lopez Massimo , Cortesi Enrico , Cammilluzzi Eugenio , Antimi Mauro , Terzoli Edmondo , Lepidini Giuseppe , Vici Patrizia , Barone Carlo , Ferretti Gianluigi , Di Cosimo Serena , Nisticò Cecilia , Carlini Paolo , Conti Francesca , Di Lauro Luigi , Botti Claudio , Vitucci Carlo , Fabi Alessandra , Giannarelli Diana , Marolla Paolo
Published: September 2003

Purpose: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity.

Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients).

Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non–G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non–G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively).

Conclusion: EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.
Long-Term Event-Free Survival After Intensive Chemotherapy for Ewing’s Family of Tumors in Children and Young Adults
Authors: Kolb E. Anders , Kushner Brian H. , Gorlick Richard , Laverdiere Caroline , Healey John H. , LaQuaglia Michael P. , Huvos Andrew G. , Qin Jing , Vu Ha Thanh , Wexler Leonard , Wolden Suzanne , Meyers Paul A.
Published: September 2003

Purpose: To improve the long-term event-free survival of patients with Ewing’s family of tumors (EFTs) using high-dose, short-term chemotherapy.

Patients and Methods: P6 was a prospective study of previously untreated patients with newly diagnosed EFTs. Patients received seven cycles of chemotherapy. Cycles 1, 2, 3, and 6 consisted of cyclophosphamide 2,100 mg/m2/d on days 1 and 2, and a 72-hour continuous infusion of doxorubicin 75 mg/m2 and vincristine 2 mg/m2 starting day 1. Cycles 4, 5, and 7 consisted of 5 consecutive days of ifosfamide 1,800 mg/m2/d and etoposide 100 mg/m2/d.

Results: Sixty-eight patients were enrolled from 1991 to 2001 (median age, 18.7 years; range, 3.7 to 39.9 years). At diagnosis, 44 patients had local-regional disease, and 24 had distant metastases. The 4-year event-free survival (EFS) rate for patients with local-regional disease is 82%; overall survival (OS) is 89%. The 4-year EFS rate for patients with distant metastases is 12%; the OS rate is 17.8%. All events occurred within 51 months of diagnosis. Four patients with distant metastases had progressive disease during therapy, and no patient with local-regional disease experienced disease progression during therapy.

Conclusion: Sustained EFS and OS can be achieved with intensive chemotherapy in children and young adults with local-regional EFTs. This therapy is relatively ineffective in the treatment of metastatic EFTs.
Cisplatin in Combination With Either Gemcitabine or Irinotecan in Carcinomas of Unknown Primary Site: Results of a Randomized Phase II Study—Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01)
Authors: Culine Stéphane , Lortholary Alain , Voigt Jean-Jacques , Bugat Roland , Théodore Christine , Priou Frank , Kaminsky Marie-Christine , Lesimple Thierry , Pivot Xavier , Coudert Bruno , Douillard Jean-Yves , Merrouche Yacine , Allouache Jelila , Goupil Alain , Négrier Sylvie , Viala Juliette , Petrow Peter , Bouzy Jeannine , Laplanche Agnès , Fizazi Karim
Published: September 2003

Purpose: To evaluate the efficacy and toxicity of novel chemotherapy combinations including cisplatin with gemcitabine (GC) or irinotecan (IC) for patients with carcinomas of an unknown primary site.

Patients and Methods: Eighty patients were randomly assigned to receive GC or IC. In the GC arm, chemotherapy consisted of cycles combining gemcitabine 1,250 mg/m2 intravenously (IV) on days 1 and 8, and cisplatin 100 mg/m2 IV on day 1 at 3-week intervals. Patients in the IC arm originally received 3-week cycles of irinotecan 200 mg/m2 IV on day 1 and cisplatin 80 mg/m2 IV on day 1. After the inclusion of 15 patients in that arm, the toxicity profile required the irinotecan doses to be reduced to 150 mg/m2 per cycle. Independent histologic and radiologic reviews were done.

Results: A total of 78 patients were assessable for efficacy and toxicity. The median number of cycles was four in each arm. Objective responses were observed in 21 patients (55%) in the GC arm (95% CI, 34% to 66%) and in 15 patients (38%) in the IC arm (95% CI, 23% to 54%). Treatment had to be stopped because of toxicity in seven patients in the GC arm and in eight patients in the IC arm. With a median follow-up of 22 months, the median survivals were 8 and 6 months in the GC and IC arms, respectively.

Conclusion: This study demonstrates the activity of both the GC and IC regimens. There was toxicity associated with both regimens. Additional studies of combination chemotherapy regimens are required.
Beyond the Development of Health-Related Quality-of-Life (HRQOL) Measures: A Checklist for Evaluating HRQOL Outcomes in Cancer Clinical Trials—Does HRQOL Evaluation in Prostate Cancer Research Inform Clinical Decision Making?
Authors: Efficace Fabio , Bottomley Andrew , Osoba David , Gotay Carolyn , Flechtner Henning , D’haese Sven , Zurlo Alfredo
Published: September 2003

Purpose: The aim of this study was to evaluate whether the inclusion of health-related quality of life (HRQOL), as a part of the trial design in a randomized controlled trial (RCT) setting, has supported clinical decision making for the planning of future medical treatments in prostate cancer.

Materials and Methods: A minimum standard checklist for evaluating HRQOL outcomes in cancer clinical trials was devised to assess the quality of the HRQOL reporting and to classify the studies on the grounds of their robustness. It comprises 11 key HRQOL issues grouped into four broader sections: conceptual, measurement, methodology, and interpretation. Relevant studies were identified in a number of databases, including MEDLINE and the Cochrane Controlled Trials Register. Both their HRQOL and traditional clinical reported outcomes were systematically analyzed to evaluate their consistency and their relevance for supporting clinical decision making.

Results: Although 54% of the identified studies did not show any differences in traditional clinical end points between treatment arms and 17% showed a difference in overall survival, 74% of the studies showed some difference in terms of HRQOL outcomes. One third of the RCTs provided a comprehensive picture of the whole treatment including HRQOL outcomes to support their conclusions.

Conclusion: A minimum set of criteria for assessing the reported outcomes in cancer clinical trials is necessary to make informed decisions in clinical practice. Using a checklist developed for this study, it was found that HRQOL is a valuable source of information in RCTs of treatment in metastatic prostate cancer.
Dysadherin: Expression and Clinical Significance in Thyroid Carcinoma
Authors: Sato Haruhiro , Ino Yoshinori , Miura Ayaka , Abe Yoshifumi , Sakai Hideto , Ito Koichi , Hirohashi Setsuo
Published: September 2003

Dysadherin is a cancer-associated cell membrane glycoprotein. Its cDNA encodes 178 amino acids, including a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Dysadherin is believed to down-regulate the expression of E-cadherin, the prime mediator of cell-cell adhesion in epithelial cells, by a posttranscriptional mechanism and promote the metastasis of carcinoma cells. To evaluate the association between dysadherin expression and E-cadherin expression in thyroid carcinoma, immunostaining for dysadherin and E-cadherin was performed in 51 papillary, 10 follicular, and 31 undifferentiated carcinomas. Immunoreactivity for dysadherin, localized at cell-cell boundaries, was detected in 39 of the 51 papillary carcinomas and all 31 undifferentiated carcinomas but not in the follicular carcinomas or normal thyroid tissue controls. Dysadherin expression was significantly higher in undifferentiated carcinoma than in papillary carcinoma and follicular carcinoma and showed significant negative correlation with E-cadherin expression. The degree of dysadherin expression was significantly associated with the prognosis, occurrence of secondary undifferentiated carcinomas, size of the primary tumor, and metastasis to the regional lymph nodes and lungs. In conclusion, a process involving increased dysadherin expression may lead to an adverse clinical outcome.
Effects of Short-Term Detraining on Postprandial Metabolism, Endothelial Function, and Inflammation in Endurance-Trained Men: Dissociation between Changes in Triglyceride Metabolism and Endothelial Function
Authors: Gill Jason M. R. , Caslake Muriel J. , McAllister Craig , Tsofliou Fotini , Ferrell William R. , Packard Chris J. , Malkova Dalia
Published: September 2003

Endurance-trained athletes experience a low level of postprandial lipaemia, but this rapidly increases with detraining. We sought to determine whether detraining-induced changes to postprandial metabolism influenced endothelial function and inflammation. Eight endurance-trained men each undertook two oral fat tolerance tests [blood taken fasted and for 6 h following a high-fat test meal (80 g fat, 80 g carbohydrate)]: one during a period of their normal training (trained) and one after 1 wk of no exercise (detrained). Endothelial function in the cutaneous microcirculation was assessed using laser Doppler imaging with iontophoresis in the fasted state and 4 h postprandially during each test. Fasting plasma triglyceride (TG) concentrations increased by 35% with detraining (P = 0.002), as did postprandial plasma (by 53%, P = 0.002), chylomicron (by 68%, P = 0.02) and very low-density lipoprotein (by 51%, P = 0.005) TG concentrations. Endothelial function decreased postprandially in both the trained (by 17%, P = 0.03) and detrained (by 22%, P = 0.03) conditions but did not differ significantly between the trained and detrained conditions in either the fasted or the postprandial states. These results suggest that, although fat ingestion induces endothelial dysfunction, interventions that alter postprandial TG metabolism will not necessarily concomitantly influence endothelial function.
RIN3: a novel Rab5 GEF interacting with amphiphysin II involved in the early endocytic pathway
Authors: Kajiho Hiroaki , Saito Kota , Tsujita Kyoko , Kontani Kenji , Araki Yasuhiro , Kurosu Hiroshi , Katada Toshiaki
Published: September 2003

The small GTPase Rab5, which cycles between active (GTP-bound) and inactive (GDP-bound) states, plays essential roles in membrane budding and trafficking in the early endocytic pathway. However, the molecular mechanisms underlying the Rab5-regulated processes are not fully understood other than the targeting event to early endosomes. Here, we report a novel Rab5-binding protein, RIN3, that contains many functional domains shared with other RIN members and additional Pro-rich domains. RIN3 displays the same biochemical properties as RIN2, the stimulator and stabilizer of GTP-Rab5. In addition, RIN3 exhibits its unique intracellular localization. RIN3 expressed in HeLa cells localized to cytoplasmic vesicles and the RIN3-positive vesicles contained Rab5 but not the early endosomal marker EEA1. Transferrin appeared to be transported partly through the RIN3-positive vesicles to early endosomes. RIN3 was also capable of interacting via its Pro-rich domain with amphiphysin II, which contains SH3 domain and participates in receptor-mediated endocytosis. Interestingly, cytoplasmic amphiphysin II was translocated into the RIN3- and Rab5-positive vesicles when co-expressed with RIN3. These results indicate that RIN3 biochemically characterized as the stimulator and stabilizer for GTP-Rab5 plays an important role in the transport pathway from plasma membrane to early endosomes.
Irradiation of dystrophic host tissue prior to myoblast transfer therapy enhances initial (but not long-term) survival of donor myoblasts
Authors: Hodgetts Stuart I. , Grounds Miranda D.
Published: September 2003

There is a massive and rapid death of donor myoblasts (<20% surviving) within hours after intramuscular injection in myoblast transfer therapy (MTT), due to host immune cells, especially natural killer (NK) cells. To investigate the role of host immune cells in the dramatic death of donor myoblasts, MTT experiments were performed in irradiated host mice. Cultured normal C57BL/10ScSn male donor myoblasts were injected into muscles of female C57BL/10ScSn-Dmdmdx host mice after one of three treatments: whole body irradiation (WBI) to eliminate all circulating leukocytes, WBI and bone marrow reconstitution (BMR), or local irradiation (or protection) of one limb. Similar experiments were performed in host mice after antibody depletion of NK cells. Numbers of male donor myoblasts were quantified using a Y-chromosome-specific (male) probe following total DNA extraction of injected muscles. WBI prior to MTT resulted in dramatically enhanced survival (∼80%) of donor myoblasts at 1 hour after MTT, supporting a central role for host inflammatory cells in the initial death of donor myoblasts seen in untreated host mice. BMR restored the massive and rapid loss (∼25% surviving) of donor myoblasts at 1 hour after MTT. Local pre-irradiation also resulted in increased donor myoblast numbers (∼35-40%) compared with untreated controls (∼10%) at 3 weeks after MTT. Preirradiation of host muscle with 10 Gy did not significantly stimulate proliferation of the injected donor myoblasts. Serum protein levels of TNFα, IL-1β, IL-6 and IL-12 fluctuated following irradiation treatments. These combined results strongly reinforce a major role for host immune cells in the rapid death of injected cultured donor myoblasts.
Mechanical behaviour of powders using a medium pressure flexible boundary cubical triaxial tester
Authors: Li F , Puri V M
Published: September 2003

A medium pressure (<21 MPa) flexible boundary cubical triaxial tester was designed to measure the true three-dimensional response of powders. In this study, compression behaviour and strength of a microcrystalline cellulose powder (Avicel® PH102), a spray-dried alumina powder (A16SG), and a fluid-bed-granulated silicon nitride based powder (KY3500) were measured. To characterize the mechanical behaviour, three types of triaxial stress paths, that is, the hydrostatic triaxial compression (HTC), the conventional triaxial compression (CTC), and the constant mean pressure triaxial compression (CMPTC) tests were performed. The HTC test measured the volumetric response of the test powders under isostatic pressure from 0 to 13.79MPa, during which the three powders underwent a maximum volumetric strain of 40.8 per cent for Avicel® PH102, 30.5 per cent for A16SG, and 33.0 per cent for KY3500. The bulk modulus values increased 6.4-fold from 57 to 367MPa for Avicel® PH102, 3.7-fold from 174 to 637 MPa for A16SG, and 8.1-fold from 74 to 597MPa for KY3500, when the isotropic stress increased from 0.69 to 13.79 MPa. The CTC and CMPTC tests measured the shear response of the three powders. From 0.035 to 3.45MPa confining pressure, the shear modulus increased 28.7-fold from 1.6 to 45.9MPa for Avicel® PH102, 35-fold from 1.7 to 60.5MPa for A16SG, and 28.5-fold from 1.5 to 42.8MPa for KY3500. In addition, the failure stresses of the three powders increased from 0.129 to 4.41 MPa for Avicel® PH102, 0.082 to 3.62 MPa for A16SG, and 0.090 to 4.66MPa for KY3500, respectively, when consolidation pressure increased from 0.035 to 3.45MPa. In addition, the shear modulus and failure stress values determined from the CTC test at 2.07, 2.76, and 3.45MPa confining pressures are consistently greater than those from the CMPTC test at the same constant mean pressures. This observation demonstrates the influence of stress paths on material properties. The CTT is a useful tool for characterizing the three-dimensional response of powders and powder mixtures.
Bearing defect diagnosis and acoustic emission
Authors: Morhain A , Mba D
Published: September 2003

Acoustic emission (AE) was originally developed for non-destructive testing of static structures, but over the years its application has been extended to health monitoring of rotating machines and bearings. It offers the advantage of earlier defect detection in comparison with vibration analysis. However, limitations in the successful application of the AE technique for monitoring bearings have been partly due to the difficulty in processing, interpreting and classifying the acquired data. The investigation reported in this paper was centred on the application of standard AE characteristic parameters on a radially loaded bearing. An experimental test rig was modified such that defects could be seeded onto the inner and outer races of a test bearing. As the test rig was adapted for this purpose, it offered high background acoustic emission noise providing a realistic test for fault diagnosis. In addition to a review of current diagnostic methods for applying AE to bearing diagnosis, the results of this investigation validated the use of r. m. s., amplitude, energy and AE counts for diagnosis. Furthermore, this study determined the most appropriate threshold level for AE count diagnosis, the first known attempt.
Transient elastohydrodynamic point contact analysis using a new coupled differential deflection method Part 1: Theory and validation
Authors: Holmes M. J. A. , Evans H. P. , Hughes T. G. , Snidle R. W.
Published: September 2003

The paper presents a transient analysis technique for point contact elastohydrodynamic (EHL) lubrication problems using coupled elastic and hydrodynamic equations. Full coupling is made possible by use of a novel differential deflection formulation. The way in which the differential deflection is incorporated into the overall solution method for a point contact is discussed. A range of spatial and temporal discretization methods are incorporated and compared. The method is validated under transient conditions by a detailed comparison with published work produced using a different, independent method incorporating a moving roughness feature.

A comparison of the results with different discretization methods leads to the conclusion that spatial central differencing with a Crank-Nicolson temporal discretization is the most effective finite difference scheme, and this is generally equivalent to the finite element discretization given in detail in the paper. A comparison of the results produced for moving rough surfaces suggests that the finite element formulation is preferred.
The sensitivity of numerical simulations to initial modifications of potential vorticity—a case‐study
Authors: RøSting B. , Kristjánsson J. E. , Sunde J.
Published: September 2003

Modifications of numerical potential vorticity (PV) fields according to features in water vapour (WV) images are combined with singular‐vector dynamics in an attempt to improve the numerical analysis in the study of a severe winter storm. The apparent mismatch between features in the WV images and upper‐level PV anomalies in the numerical analysis is corrected at levels indicated as sensitive by the fastest growing singular vectors. Model re‐runs, based on the inverted PV fields, are then carried out. Though numerical weather prediction (NWP) re‐runs are highly successful in improving the simulation of the storm, they produce a degraded simulation of a second wave which followed rapidly in the wake of the first one. Some success is achieved by enhancing its associated upper‐level PV anomaly at sensitive levels. The impact on the large‐scale flow arising from localized PV modifications is discussed and may point to a reason why the NWP runs based on PV modification occasionally fail to improve the simulation, e.g. the second wave in this case. Copyright © 2003 Royal Meteorological Society
Four‐dimensional variational data assimilation: A new formulation of the background‐error covariance matrix based on a potential‐vorticity representation
Authors: Cullen M. J. P.
Published: September 2003

All variational data assimilation schemes use some form of mass–wind coupling in their definitions of the control variables used in the minimization of the cost function. At the European Centre for Medium‐Range Weather Forecasts, the statistical coupling developed by Parrish and Derber (1992) is used. This is simple and robust. The robustness is obtained by calculating the mass–wind correlations from a dataset representing short‐range forecast errors. A potential disadvantage of this method is that, if the calibration dataset is not well balanced, there will be little mass–wind coupling in the analysis procedure. An alternative procedure is to assume that the balanced part of the errors, represented in this case by potential‐vorticity errors, is uncorrelated with the unbalanced part of the error. This would be natural for a linear model. A simple potential‐vorticity based method is developed and tested. It is shown that the strong scale dependence of the gravity‐wave speed introduces significant numerical difficulties. However, with care, good results can be obtained. Copyright © 2003 Royal Meteorological Society
Total ozone observations prior to the IGY. II: Data and quality
Authors: Brönnimann S. , Cain J. C. , Staehelin J. , Farmer S. F. G.
Published: September 2003

This paper is the second part of a systematic compilation of total ozone observations prior to the International Geophysical Year (IGY), July 1957 to June 1958. The first part provides an overview of the locations, instruments, observers and type of observations. For this second part, 17 data series were selected for further evaluation and quality assessment. We present daily observations from 13 Dobson‐stations in Europe (1952–57), from College, Alaska (1952–54, 1957), New York (1941–44) and Zi‐Ka‐Wei in China (1932–36) as well as monthly mean values for Århus, Denmark (1940–44) and Zi‐Ka‐Wei (1937–42). The data were mostly re‐evaluated using statistical techniques because original instrument readings and calibration information were not available in most cases. The quality was assessed by comparisons with meteorological variables (local 100 hPa temperature and 300 hPa geopotential height) and neighbouring total ozone series. Unreliable values were flagged, and corrections are proposed in some cases. The quality assessment shows that about half of the series can be used for scientific applications. They cannot be used, however, for trend analysis. © Royal Meteorological Society, 2003. S. F. G. Farmer's contribution is Crown copyright
Model study of the North Atlantic region atmospheric response to autumn tropical Atlantic sea‐surface‐temperature anomalies
Authors: Dréevillon Marie , Cassou Christophe , Terray Laurent
Published: September 2003

Lead–lag Maximum Covariance Analysis (MCA) between National Centers for Environmental Prediction re‐analysis sea surface temperature (SST) and 500 hPa geopotential‐height fields shows that autumn tropical Atlantic SST anomalies are significantly linked with the following‐winter North Atlantic Oscillation (NAO). The ability of the Météo‐France atmospheric general circulation model ARPEGE to reproduce this relationship is tested, by forcing it with autumn tropical SST anomalies derived from lead–lag MCA analysis results. The autumn SST forcing induces a strong wave‐like simultaneous response in October and November. The occurrence of the autumn weather regimes is also affected, in agreement with the significant spatial correlation of the midlatitude part of the wave response with the NAO pattern. By coupling the model with a slab ocean in midlatitudes, we show that the thermal coupling between the ocean and the atmosphere allows a better representation of the midlatitude part of the response. A negative autumn tropical SST anomaly triggers an interaction between the midlatitude SST, the low‐frequency circulation and the storm‐track activity, which reinforces and maintains a positive phase of the NAO until winter. Copyright © 2003 Royal Meteorological Society
Propagation properties of inertia–gravity waves through a barotropic shear layer and application to the Antarctic polar vortex
Authors: Öllers M. C. , Kamp L. P. J. , Lott F. , Velthoven P. F. J. VAN , Kelder H. M. , Sluijter F. W.
Published: September 2003

The propagation of inertia–gravity waves (IGWs) through a dynamical transport barrier, such as the Antarctic polar vortex edge is investigated using a linear wave model. The model is based on the linearized, inviscid hydrostatic equations on an f‐plane. Typical values for the parameters that are appropriate to the Antarctic polar vortex are given. The background flow U is assumed to be barotropic and its horizontal shear is represented by a hyperbolic tangent background wind profile. The wave equation that describes the latitudinal structure of a monochromatic disturbance contains two singularities. The first corresponds to the occurrence of a critical level where the intrinsic wave frequency Ω=ω−kU becomes zero. ω is the absolute wave frequency and k its longitudinal wave number in the direction of U. The second is an apparent singularity and does not give rise to singular wave behaviour. It becomes zero whenever the square of the intrinsic wave frequency Ω2=f(f−Uy), f being the Coriolis frequency and Uy the horizontal shear of the flow. The wave equation is solved numerically for different values of the angles of incidence of the wave upon the background flow, of the wave frequency, of the horizontal wave number and of the Rossby number. Reflection (|R|) and transmission (|T|) coefficients are determined as a function of these parameters. The results depend on whether the flow is inertially stable or not. They also depend on the presence and location of the turning levels, where the wave becomes evanescent, with respect to the location of the Ω‐critical levels. For inertially stable flows, the wave totally reflects at the turning level and never reaches the critical level. If the background flow is inertially unstable, turning levels can disappear and the wave can now reach the critical level. Then over‐reflection, over‐transmission and absorption can occur. Copyright © 2003 Royal Meteorological Society
Our neighborhood: Using entertaining children's television to promote interethnic understanding in Macedonia
Authors: Shochat Lisa
Published: September 2003

Nashe Maalo (Our Neighborhood in Macedonian) is a television series designed to encourage mutual respect
and understanding among ethnic Albanian, Macedonian, Roma, and Turkish youths ages seven to twelve. Grounded in the belief that entertaining media
programming can play an important role in conflict transformation, Nashe Maalo's research results show that the series is popular,
that children understand what they watch, and that the series holds significant potential to affect children's attitudes and behavior.
System identification on the seismic behavior of an isolated bridge
Authors: Lee Zheng‐Kuan , Wu Tzu‐Hsiu , Loh Chin‐Hsiung
Published: September 2003

Seismic isolation devices and technology have been developed in the last two decades and the first seismic‐isolated bridge, Bai‐Ho Bridge, in Taiwan was completed in 1999. This bridge was equipped with a seismic monitoring system under the Taiwan Strong Motion Instrumentation Program (TSMIP). On 22 October 1999, a moderate earthquake took place and struck the bridge. The seismic monitoring sensors were normally triggered and produced an intact time history for the health monitoring of the bridge system. The data set provided valuable records about the seismic response of the isolation bridge structure. This paper uses this data to explore the vibration mechanism of Bai‐Ho Bridge. The analysis includes (1) the global dynamic behavior identification and (2) the local component mechanism of the bridge such as the LRB and boundary condition between the deck and the abutments. Both the EMD+HHT method and the non‐linear parametric model were used to identify the model of the bridge structure. Copyright © 2003 John Wiley & Sons, Ltd.
Land degradation in Bronze Age Germany: Archaeological, pedological, and chronometrical evidence from a hilltop settlement on the Frauenberg, Niederbayern
Authors: Lang Andreas , Niller Hans‐Peter , Rind Michael M.
Published: September 2003

This paper examines the effects of early agriculture and land use in the vicinity of a Bronze Age fortress at Weltenburg, Germany. Sediments and soils found below archaeological structures are compared with sediments and soils surrounding these structures. A chronology is established using relative archaeological dating,14C dating of charcoal fragments, TL dating of heated objects, and OSL dating of sediments. Results demonstrate dramatic environmental changes that occurred as early as the Bronze Age. Erosion resulting from agriculture stripped away most Holocene soils and Pleistocene sediments, transforming the natural landscape into a severely degraded cultural landscape. Since the Bronze Age, only minor changes have occurred because agriculture is limited on the degraded soils and the clay‐rich soil remnants are resistant to further erosion. © 2003 Wiley Periodicals, Inc.
Neurite‐localized estrogen receptor‐α mediates rapid signaling by estrogen
Authors: Xu Yun , Traystman Richard J. , Hurn Patricia D. , Wang Michael M.
Published: September 2003

Classically, estrogen acts on cells by directly activating gene transcription driven by ligand‐bound nuclear estrogen receptors (ER). Accumulating evidence demonstrates that estrogen acts on neurons by utilizing diverse molecular mechanisms, including rapid signaling by proteins localized to the plasma membrane. Recent studies showing that ERα localizes to axons and dendrites of hippocampal neurons suggest that nonnuclear stores of the receptor may transduce estrogen signaling. Here, we have studied the subcellular localization, dynamic regulation, and function of ERα in mouse cortical neurons. Estrogen‐stimulated mouse cortical neurons activate both estrogen response element (ERE) stimulated transcription and rapid activation of p44/42 mitogen‐activated protein kinases (MAPK). We demonstrate that green fluorescent protein (GFP)‐tagged ERα localizes to neurites in cultured cortical neurons and that the expression within neurites can be down‐regulated by estrogen or up‐regulated by antiestrogen administered during synthesis. Neurite ERα appears to be directed to neurites directly from its site of translation and not from nuclear stores. By using confocal microscopy, we show that ERα within neurites stimulates local activation of p44/42 MAP kinases in response to estrogen. We conclude that hormonal status alters subcellular ERα targeting in cortical neurons and that neurite‐expressed ERα is important in the activation of local MAPK signaling. © 2003 Wiley‐Liss, Inc.
Protective effects of sesamin and sesamolin on hypoxic neuronal and PC12 cells
Authors: Hou Rolis Chien‐Wei , Huang Hsueh‐Meei , Tzen Jason T.C. , Jeng Kee‐Ching G.
Published: September 2003

Reactive oxygen species (ROS) are important mediators of a variety of pathological processes, including inflammation and ischemic injury. The neuroprotective effects of sesame antioxidants, sesamin and sesamolin, against hypoxia or H2O2‐induced cell injury were evaluated by cell viability or lactate dehydrogenase (LDH) activity. Sesamin and sesamolin reduced LDH release of PC12 cells under hypoxia or H2O2‐stress in a dose‐dependent manner. Dichlorofluorescein (DCF)‐sensitive ROS production was induced in PC12 cells by hypoxia or H2O2‐stress but was diminished in the presence of sesamin and sesamolin. We evaluated further the role of mitogen‐activated protein kinases (MAPKs) and caspase‐3 in hypoxia‐induced PC12 cell death. Extracellular signal‐regulated protein kinase (ERK) 1, c‐jun N‐terminal kinase (JNK), and p38 MAPKs of signaling pathways were activated during hypoxia. We found that the inhibition of MAPKs and caspase‐3 by sesamin and sesamolin correlated well with the reduction in LDH release under hypoxia. Furthermore, the hypoxia‐induced apoptotic‐like cell death in cultured cortical cells as detected by a fluorescent DNA binding dye was reduced significantly by sesamin and sesamolin. Taken together, these results suggest that the protective effect of sesamin and sesamolin on hypoxic neuronal and PC12 cells might be related to suppression of ROS generation and MAPK activation. © 2003 Wiley‐Liss, Inc.
Novel putative nonprotein‐coding RNA gene from 11q14 displays decreased expression in brains of patients with schizophrenia
Authors: Polesskaya Oxana O. , Haroutunian Vahram , Davis Kenneth L. , Hernandez Ivan , Sokolov Boris P.
Published: September 2003

A modified method of differential display was employed to identify a novel gene (namedPSZA11q14), the expression of which was reduced in brains from patients with schizophrenia. Decreased expression ofPSZA11q14was identified initially in Brodmann's area (BA) 21 from a small group of patients with schizophrenia (n= 4) and normal controls (n= 6) and was confirmed subsequently using independent RT‐PCR assay in BA 21, 22, and 9, and in hippocampus from a larger group of patients with schizophrenia (n= 36) and controls (n= 35).PSZA11q14is located on chromosome 11q14, an area shown previously to co‐segregate with schizophrenia and related disorders in several families. Decreased expression ofPSZA11q14in patients with schizophrenia and its location on 11q14 provide converging lines of evidence indicating thatPSZA11q14may be involved in at least some cases of schizophrenia.PSZA11q14shows no significant homology with any known gene. It has no introns and produces two RNA transcripts of ∼4.5 and ∼7.0 kb. The largest open reading frame (ORF) in thePSZA11q14transcripts may potentially encode for a short polypeptide of 71 amino acids. High frequency of rare codons, the short size of this ORF, and low homology with mouse sequences, however, indicate thatPSZA11q14may instead represent a novel member of a family of nonprotein‐coding RNA genes that are not translated and that function at the RNA level.PSZA11q14is located within the first intron of theDLG‐2gene and transcribed in the opposite direction toDLG‐2. These results suggest thatPSZA11q14may be considered a candidate gene for schizophrenia acting as an antisense regulator ofDLG‐2, which controls assembling functionalN‐methyl‐D‐aspartate (NMDA) receptors. © 2003 Wiley‐Liss, Inc.