bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Environmental Control on Environmental Satisfaction, Communication, and Psychological Stress
Authors: Huang Yueng-Hsiang , Robertson Michelle M. , Chang Kuo-I
Published: September 2004

The main purpose of this quasi–field experiment was to test whether an office ergonomics training program reduces employees’ psychological stress and improves their environmental control, environmental satisfaction, and communication levels. A conceptual model was developed and used to test these relationships. Preintervention and postintervention survey data were collected from 89 knowledge workers. The office ergonomics training program significantly improved workers’ self-reported perceptions of environmental control, satisfaction with the work environment, and the degree to which the environment supported communication with coworkers. However, psychological stress was unchanged. Environmental control was found to mediate the relationship between preenvironmental and postenvironmental satisfaction. Overall, the results confirm the importance of incorporating ergonomics training into office workplaces to enhance the effective use of work environments and of knowledge workers’ sense of control and environmental satisfaction.
Predicting Patronage Behaviors in a Sustainable Retail Environment
Authors: Ogle Jennifer Paff , Hyllegard Karen H. , Dunbar Brian H.
Published: September 2004

This study investigated consumer patronage (i.e., shopping and making purchases) at Recreational Equipment Inc. (REI), specifically examining consumer response to REI’s incorporation of sustainable design principles at their Denver flagship store. Data were collected using a consumer intercept survey at the Denver REI store ( n = 186). Of particular interest was the role of store atmospherics—including sustainable store design, historic preservation, and urban renewal efforts—in shaping consumers’ future intentions to patronize REI Denver. Consumers’ intentions to patronize REI were modeled using the classic belief-attitude-behavior intention model (i.e., attitude and subjective norm) based upon the theory of reasoned action, and an extended model that included variables external to the theory. Findings suggest that, when used to predict consumer patronage behaviors, the classic belief-attitudebehavior intention model should be extended to include retail characteristics, notably store atmospherics and merchandise assortment; a social context or social identity variable such as consumer lifestyle orientation; and demographics.
Syndromes with congenital brittle bones
Authors: Plotkin Horacio
Published: September 2004

Background

There is no clear definition of osteogenesis imperfecta (OI). The most widely used classification of OI divides the disease in four types, although it has been suggested that there may be at least 12 forms of OI. These forms have been named with numbers, eponyms or descriptive names. Some of these syndromes can actually be considered congenital forms of brittle bones resembling OI (SROI).

Discussion

A review of different syndromes with congenital brittle bones published in the literature is presented. Syndromes are classified in "OI" (those secondary to mutations in the type I pro-collagen genes), and "syndromes resembling OI" (those secondary to mutations other that the type I pro-collagen genes, identified or not). A definition for OI is proposed as a syndrome of congenital brittle bones secondary to mutations in the genes codifying for pro-collagen genes (COL1A1 and COL1A2).

A debate about the definition of OI and a possible clinical and prognostic classification are warranted.
Wireless local area network in a prehospital environment
Authors: Chen Dongquan , Soong Seng-jaw , Grimes Gary J , Orthner Helmuth F
Published: September 2004

Background

Wireless local area networks (WLANs) are considered the next generation of clinical data network. They open the possibility for capturing clinical data in a prehospital setting (e.g., a patient's home) using various devices, such as personal digital assistants, laptops, digital electrocardiogram (EKG) machines, and even cellular phones, and transmitting the captured data to a physician or hospital. The transmission rate is crucial to the applicability of the technology in the prehospital setting.

Methods

We created two separate WLANs to simulate a virtual local are network environment such as in a patient's home or an emergency room (ER). The effects of different methods of data transmission, number of clients, and roaming among different access points on the file transfer rate were determined.

Results

The present results suggest that it is feasible to transfer small files such as patient demographics and EKG data from the patient's home to the ER at a reasonable speed. Encryption, user control, and access control were implemented and results discussed.

Conclusions

Implementing a WLAN in a centrally managed and multiple-layer-controlled access control server is the key to ensuring its security and accessibility. Future studies should focus on product capacity, speed, compatibility, interoperability, and security management.
Regionalisation of early head ectoderm is regulated by endoderm and prepatterns the orofacial epithelium
Authors: Haworth Kim E. , Healy Christopher , Morgan Pamela , Sharpe Paul T.
Published: September 2004

The oral epithelium becomes regionalised proximodistally early in development, and this is reflected by the spatial expression of signalling molecules such as Fgf8 and Bmp4. This regionalisation is responsible for regulating the spatial expression of genes in the underlying mesenchyme. These genes are required for the spatial patterning of bone,cartilage orofacial development and, in mammals, teeth. The mechanism and timing of this important regionalisation during head epithelium development are not known. Using lipophilic dyes to fate map the oral epithelium in chick embryos, we show that the cells that will occupy the epithelium of the distal and the proximal mandible primordium already occupy different spatial locations in the developing head ectoderm prior to the formation of the first pharyngeal arch and neural crest migration. Moreover, the ectoderm cells fated to become proximal oral epithelium express Fgf8 and this expression requires the presence of endoderm. Thus, the first fundamental patterning process in jaw morphogenesis is controlled by the early separation of specific areas of ectoderm that are regulated by ectoderm-endoderm interactions, and does not involve neural crest cells.
Role of Fine‐needle Aspiration Biopsy and Frozen Section in the Management of Papillary Thyroid Carcinoma Subtypes
Authors: Furlan Julio C. , Bedard Yvan C. , Rosen Irving B.
Published: September 2004

Since fine‐needle aspiration biopsy (FNAB) was introduced, the value of frozen section (FS) has been questioned. This study compares FNAB and FS sensitivities among the usual form of papillary thyroid cancer (uPTC) and variants of PTC such as tall cell (tcPTC), follicular (fPTC), and Hurthle cell (HcPTC). A total of 257 patients who underwent preoperative FNAB, intraoperative FS, and thyroidectomy for PTC were randomly selected from a database of a university teaching hospital in Toronto. There were 218 females (84.8%) and 39 males (15.2%), from 19 to 89 years of age (mean of 44 years), having uPTC (n = 212), fPTC (n = 24), HcPTC (n = 14), and tcPTC (n = 7). Data were analyzed using χ2 test. Sensitivities were calculated by division of true positives and by the sum of true positives and false negatives. True positives had to reflect a conclusive diagnosis of cancer. The FNAB sensitivities were uPTC (39.2%), fPTC (25%), HcPTC (42.9%), tcPTC (85.7%), similar to FS sensitivities (p = 0.497) for uPTC (44.3%), fPTC (16.7%), HcPTC (42.9%), and tcPTC (71.4%). Use of FS following FNAB increased sensitivities for uPTC to 56.1%, fPTC to 29.2%, and tcPTC to 100%. In addition, FS did not increase FNAB sensitivity in HcPTC. Combination FNAB plus FS failed in 43.9% of uPTC, 70.8% of fPTC, and 57.1% of HcPTC. We concluded that FNAB and FS sensitivity vary with PTC subtype and are still necessary for selection and treatment. The recognition of morphologic subtypes of PTC from the FNAB could optimize the selection of patients for intraoperative FS, enhance the preoperative assessment of prognosis, facilitate the surgical planning, and simplify the preparation of postoperative adjuvant therapy.
Value of Fentanyl in Flexible Sigmoidoscopy
Authors: Basu Sanjoy , Krishnamurthy Badri , Walsh Tim H.
Published: September 2004

Studies have recorded significant patient discomfort during flexible sigmoidoscopy when it is performed without sedation/analgesia. This study observed whether a single dose of 50 mcg intravenous fentanyl reduces pain, improving compliance, acceptability, and completion rates. In a prospective study, 109 consecutive patients were offered the option of 50 mcg intravenous fentanyl or no analgesia. Patient’s pre‐procedure expectations, objective pain scores, and willingness to undergo a subsequent procedure using the same technique were recorded. Endoscopist recorded the success, complications, and objective pain scores for each patient. Of the 46 patients (42%) choosing fentanyl, 9 (20%) experienced moderate/severe pain as against 26(41%) of the 63 patients (58%) opting for no analgesia (p < 0.05). Further, 52% receiving fentanyl had a significantly better experience compared to their pre‐procedure expectations as against 33% who received no analgesia (p < 0.05). No patient receiving fentanyl expressed unwillingness to undergo the procedure again using the same technique, whereas 16 (25%) of those receiving no analgesia indicated they would not (p < 0.01). Endoscopists recorded moderate/severe pain in 13 patients (12%), whereas 35 patients (32%) recorded moderate/severe pain (p < 0.001). Analgesia for endoscopy should involve patient choice. However, a single dose of 50 mcg fentanyl reduced patient discomfort and improved satisfaction. It appeared safe and likely to improve patient compliance and acceptability for flexible sigmoidoscopy.
Chromogranin A, a Marker of the Therapeutic Success of Resection of Neuroendocrine Liver Metastases: Preliminary Report
Authors: Søndenaa Karl , Sen Jon , Heinle Frank , Fjetland Lars , Gudlaugsson Einar , Syversen Unni
Published: September 2004

Recent publications indicate that life may be prolonged by surgical debulking of neuroendocrine tumors. A minimum 90% reduction of liver metastases has been suggested to alleviate symptoms of the carcinoid. We have used the tumor marker chromogranin A (CgA) to assess hepatic resection in patients with neuroendocrine metastatic tumor disease. Since 1998, seven patients (3 men) of median age 73 years (range 64–84 years) with carcinoid primary tumors in the ileum who had solitary (n = 2) or multiple (n = 5) liver metastases underwent hepatic resections. Two patients had synchronous small intestinal and liver resections; the rest had deferred hepatic resections after intestinal resection. Hormonal manifestations in the form of loose stools or diarrhea or flushing were observed in five patients, and five had abdominal symptoms from partial obstruction of the small bowel. The resection was deemed radical in five patients. Two patients with non‐radical resection needed postoperative octreotide treatment, and symptoms were alleviated or improved in the others. All seven patients are alive with an observation period from 6 to 64 months (median 36 months). Median CgA (normal < 30 ng/ml) was 292 ng/ml (range 79‐14,000 ng/ml) before liver surgery. Postoperatively, CgA became normal in three of the radically resected patients, whereas in two others, it decreased to a lowest median level of 79 ng/ml (range 52–105 ng/ml). In two palliatively resected patients, one had a near normalization to 65 ng/ml, and the last patient had a reduction from 14,000 to 2400 ng/ml following debulking surgery. A similar postoperative reduction was noted for 24 hr urinary 5‐HIAA excretion. Postoperative octreotide scintigraphy suggested residual hepatic or extrahepatic tumors in three of the patients thought radically resected, whereas two had no clear sign of disease corresponding to a normal CgA value. The CgA values, however, reflected the extent of positive scintigraphy findings. Serum CgA levels monitored the extent and short‐term course of the disease and corresponded well with scintigraphy findings and 5‐HIAA excretion, but prolonged follow‐up in more patients may be necessary before decisive conclusions are allowed to be drawn.
Surgical Management of Breast Cancer in Saudi Arabia before and after Outreach Activities
Authors: Bin Yousef Hussam M. , Al Malik Osama , Kandil Alaa , Chaudhary Mohammed A. , Sorbris Ralph
Published: September 2004

We collected management information from the 1996 referral documents of 100 consecutive patients who came to us for continued treatment of breast cancer. Major deficiencies were noted with regard to clinical assessment, surgery, and pathology. Since 1997 we have intensified our personnel contacts with referring surgeons, and we have performed outreach visits. To measure the effect of our efforts, we repeated the same collection of information between March 2001 and March 2002. Correct performance of TNM (tumor, node metastasis) classification decreased from 36%–16%. The use of mammography increased from 29%–56%, application of fine needle aspiration (FNA) increased from 46%–70%, and use of core needle biopsy (CNB) increased from 0%–6%. The rate of performance of triple assessment (including correct performance of TNM) was 9% and is now 10%. The number of patients who had surgery before referral decreased from 84%–46%. A proper metastatic work‐up in the present study was performed in 10% of patients, and mammography was performed in 33% of the patients who had either modified radical mastectomy (MRM) or breast conserving therapy (BCT). Previously, 78 patients had 98 operations before referral and 75% of those needed additional surgery; now only 9 patients out of 39 who had incisional biopsy or lumpectomy needed further surgery. The median number of lymph nodes now is 10, whereas previously 42% of the axillary dissections yielded < 8 lymph nodes. Pathology reports mentioning both tumor size and surgical margins have increased from 29%–53%. These new data indicate that there is a need to join all hospitals in a national guidelines plan for the management of breast cancer.
Gasless Video‐assisted Total Thyroidectomy in the Treatment of Low Risk Intrathyroid Papillary Carcinoma
Authors: Chao Tzu‐Chieh , Lin Jen‐Der , Chen Miin‐Fu
Published: September 2004

Video‐assisted thyroidectomy, although an increasingly used method to treat benign thyroid nodules, is rarely used to treat thyroid cancer. We performed gasless video‐assisted total thyroidectomy for the treatment of papillary carcinoma of the thyroid. The patients were two men and five women with ages ranging from 29 to 52 years (median 35 years). Tumor size ranged from 0.7 to 3.8 cm (median 1.8 cm). The remnants of functional thyroid tissues were ablated with 1110 MBq of 131I following total thyroidectomy. One year after radioiodine ablation uptake of 74 MBq 131I shown by scintigraphy ranged from 0.29% to 0.70% (median 0.57%), and the serum thyroglobulin level was less than 1 µg/L. No perioperative complications occurred. The follow‐up period ranged from 1 year 5 months to 3 years 7 months (median 2 years 10 months). In conclusion, gasless video‐assisted total thyroidectomy is a feasible means for treating relatively small, noninvasive, clinically solitary, differentiated thyroid carcinomas.
Effects of Preinjury Administration of Corticosteroids on Pseudointimal Hyperplasia and Cytokine Response in a Rat Model of Balloon Aortic Injury
Authors: Nagasaki Kazuhito , Matsumoto Kenji , Kaneda Munehisa , Shintani Tsunehiro , Shibutani Shintaro , Murayama Takaya , Wakabayashi Go , Shimazu Motohide , Mukai Makio , Kitajima Masaki
Published: September 2004

Restenosis occurs in approximately one‐third of patients with coronary or peripheral vascular disease who undergo balloon angioplasty or a surgical bypass procedure primarily because of the development of pseudointimal hyperplasia (PIH). Corticosteroids were effective in suppressing PIH in several experimental studies, but no clinical studies have been reported. To resolve this discrepancy, we studied the effects of preinjury administration of several doses of methylprednisolone (MP) at targeted times in a rat model of balloon aortic injury. Rats were given either no treatment or an intravenous injection of MP (0.5, 5.0, 50, or 500 mg/kg) 2 hours before aortic injury. Four hours later interleukin‐6 (IL‐6), IL‐10, and macrophage migration inhibitory factor (MIF) concentrations in serum and tissue of injured aortas were assessed. Two weeks after injury, damaged aortas were harvested and studied histopathologically. Compared with results in controls, MP at a dose of 5 mg/kg significantly inhibited increases in plasma and tissue levels of IL‐6 and significantly reduced the pseudointimal area, pseudointimal/medial area ratio, and proliferating cell nuclear antigen index in injured vessels. Administration of MP had no significant effect on the IL‐10 or MIF level. Thus in a rat model of balloon aortic injury, preinjury administration of MP 5 mg/kg mitigated the development of PIH and cell proliferation and suppressed the postinjury increase in serum and tissue IL‐6 concentrations. These results suggest that there is an appropriate dosage as well as appropriate timing for MP administration to suppress PIH.
Cribriform‐morular variant of Papillary Thyroid Carcinoma: Clue to Early Detection of Familial Adenomatous Polyposis‐associated Colon Cancer
Authors: Tomoda Chisato , Miyauchi Akira , Uruno Takashi , Takamura Yuuki , Ito Yasuhiro , Miya Akihiro , Kobayashi Kaoru , Matsuzuka Fumio , Kuma Seiji , Kuma Kanji , Kakudo Kennichi
Published: September 2004

The cribriform‐morular variant (CMV) of papillary thyroid carcinoma (PTC) is a rare histologic subtype of PTC that shows a combination of growth patterns including cribriform and spindle cell areas. The thyroid cancer with this unique histology was originally reported in patients with familial adenomatous polyposis (FAP), although it was later found in patients without polyposis as well. Because of its rarity, its clinical features are not clear. We reviewed seven patients with CMV‐PTC who were found among 4194 patients with PTC in our pathology files between June 1991 and March 2003. The prevalence of CMV was 0.16% among all PTCs. We invited these patients to our hospital so we could obtain a detailed family history and recommend colonoscopic examination and germline APC gene analysis. Two patients without subjective symptoms had polyposis of the colon and colon cancers. Germline APC gene mutations were found in both patients. The father of a patient who refused the invitation was revealed to have undergone surgery for colon polyposis. In the remaining four patients, neither polyposis nor APC gene mutation was found. Common clinical features included a young age (mean 25 years), predominance of females, circumscribed tumors, negative node metastasis, and no recurrence of the thyroid cancer after surgery. Two of the three patients with colon polyposis had bilateral multiple thyroid tumors, whereas the remaining four (without polyposis) had a solitary tumor. The histopathology of CMV in patients with PTC should arouse a suspicion of FAP, especially if there are multiple tumors. This finding can lead to early detection of colon cancer.
Late Pliocene volcanic island growth and flood basalt‐like lava emplacement in the Hyblean Mountains (SE Sicily)
Authors: Behncke Boris
Published: September 2004

Since ∼200 Ma, the Hyblean Mountains (southeastern Sicily) have been the site of recurrent, mainly submarine, mafic volcanism. In the upper Pliocene, large volumes of tholeiitic products were erupted in a shallow marine environment, leading to the growth of volcanic islands. The deposits of this tholeiitic episode can be grouped into two main facies associations: (1) pillow lavas and hyaloclastite tuffs erupted and deposited entirely under water, and (2) submarine pillow breccias, fed from subaerial lava flows entering the ocean and subaerial lavas, which are distinguished into a coastal lava platform facies and an inland facies. Lava flows into the ocean led to the growth of lava deltas consisting of a basal flow foot breccia and an overlying sequence of pāhoehoe flow units, the latter rarely exceeding 0.5 m in thickness. In outcrop, this facies association shows evidence for significant instability of the lava deltas during growth, indicating very similar processes to those observed during the current eruption of Kīlauea volcano, Hawaii. Away from the coast of the growing island, the inland facies is characterized by thicker (up to several meters) pāhoehoe flow units showing evidence for sheet flow inflation and limited outcrops of scoria and/or bomb deposits. Evidence for lava transport through tubes exists in the form of tumuli and multiple vesicle layers; drained tubes are absent. All tholeiitic products were emitted in a single, instantaneous, voluminous event (≥120 km3), consistent with very high effusion rates similar to those of flood basalts or the 1783 Skaftár Fires (Iceland) eruption.
Comparative study of nucleation mode aerosol particles and intermediate air ions formation events at three sites
Authors: Vana Marko , Kulmala Markku , Dal Maso Miikka , Hõrrak Urmas , Tamm Eduard
Published: September 2004

Quantitative characteristics of the formation and growth events of nucleation mode aerosol particles occurred at three stations (Hyytiälä and Värriö in Finland and Tahkuse in Estonia) have been compared. Aerosol size distributions were measured on all locations and, in addition, air ion mobility distribution at Tahkuse. Among 157 measuring days, nucleation events were identified on 62, 50, and 45 days at Hyytiälä, Värriö, and Tahkuse, respectively. Eighteen days were found when nucleation events occurred on all three locations at the same day. The concentration of condensable vapor, its source strength, the growth rate, the total condensation sink, the formation rate of 3 nm particles, the formation rate, and concentration of 1 nm particles were estimated using measured aerosol number size distributions. The estimated growth rates were in the range of 2–9 nm hr−1. The growth rates found from the measurements of air ion mobility distributions were comparable with that of nanometer particles. The condensable vapor concentrations were 1–12 × 107 cm−3, which is smaller at Hyytiälä than at Tahkuse and Värriö. At Tahkuse, source rates 6–55 × 104 cm−3s−1 were estimated, whereas at Hyytiälä and Värriö the rates were 2–14 × 104 cm−3s−1 and 1–20 × 104 cm−3s−1, respectively. The condensation sink values were usually substantially higher at Tahkuse than on the other locations. Tahkuse size distribution data showed 5–10% underestimates in the total condensation sink considering particles in the diameter range <500 nm. At Tahkuse the charged fraction of nucleation mode particles estimated through comparison of aerosol size distribution and air ion mobility distribution turned to be much higher than steady state charging probability of a single charge on the particle. Analysis of air mass trajectories and meteorological data indicated that the nucleation events are synoptic‐scale phenomenon occurring in horizontal extent more than 1000 km.
Mapping the Moho beneath the Southern Alps continent‐continent collision, New Zealand, using wide‐angle reflections
Authors: Henrys S. A. , Woodward D. J. , Okaya D. , Yu J.
Published: September 2004

A wide‐angle stack using all onshore‐offshore, and onshore seismic data from the SIGHT'96 experiment provides a direct three‐dimensional (3‐D) image of the Moho below the continental collision zone through the South Island of New Zealand. A bright reflector sequence (up to 4 s thick), the base of which coincides with the PmP modeled Moho, extends throughout most of the lower crust and bends downward asymmetrically beneath the Southern Alps. The crustal root reaches a maximum depth at ∼15 s (45 km), beneath the regional (−80 mGal) Bouguer gravity low and is flanked east and west by shallower Moho where the average crustal thickness is ∼20 km. The 3‐D structure of the crustal root in the central South island is moderately well resolved by the SIGHT'96 experiment.
Three‐dimensional ozone analyses and their use for short‐term ozone forecasts
Authors: Blond N. , Vautard R.
Published: September 2004

A statistical interpolation method is evaluated for routine production of ozone three‐dimensional fields over western Europe. These fields are used for initializing short‐term ozone forecasts issued from a chemistry‐transport model. We mainly address two questions: (1) To what extent can the use of surface ozone observation data improve the description of ozone fields relative to raw simulations? (2) Does the use of ozone analysis improve short‐term forecasts of the troposphere's chemical composition? The method consists of combining ozone simulations with surface ozone measurements. The resulting analyses are compared with independent observations in a statistical way over a long period of time (four consecutive summers). The improvement of the root‐mean‐square (RMS) error of the analyses relative to the raw simulations is ∼30%. The short‐term (1–2 days in advance) ozone forecasts are improved on average (by ∼1 ppb of RMS error) if ozone analyses are used for initialization. The improvement is almost lost after a lead time of 36 hours. However, in cases where a model error propagates throughout the model domain, the improvement can be much larger (∼10 ppb). We analyze one such case.
Diagnosis of medium‐range predictability enhancement during anomalous winter zonal flows over western North America
Authors: Byerle Lee A. , Paegle Jan
Published: September 2004

This investigation analyzes medium‐range predictability enhancement during winter cases of anomalous, upper troposphere zonal flows over western North America. Time correlations based upon a 50‐year record of reanalyses suggest that winters with anomalously strong zonal winds are wetter over the region, while years with anomalously weak zonal winds are relatively drier. Forecasts are selected based upon anomalously weak and strong zonal flows during January. Results from 15‐day simulations using a variety of operational and research global model configurations are presented to diagnose the predictability of precipitation and large‐scale features. Model forecasts of precipitation accumulation delineate qualitatively between wet and dry events at both 5 and 10 days. Anomaly correlations of the geopotential height field reveal useful predictability for some ensembles extending to 9.5 days. Uniform resolution forecasts are compared with two model configurations that employ rotated, variable resolution. Uniform and variable resolution forecasts maintain representative precipitation into the second week over the western United States. The rotated variable resolution simulations provide more precipitation detail. Diagnostics and model simulations of a small number of extreme events suggest that flow modifications associated with ambient flows exist over the orography during the winter season and that a predictable regional response may be present to ∼10 days. The persistence of the anomalies may also contribute to the improved model performance in certain cases. Improved performance may be related to the large inertia of the flow in wet events and to the persistence and increased predictability of initial, large‐scale anomalies in both wet and dry events. Present conclusions are limited by the small case sampling, which will be expanded in future investigations.
Sodium–calcium exchanger contributes to membrane hyperpolarization of intact endothelial cells from rat aorta during acetylcholine stimulation
Authors: Bondarenko Alexander
Published: September 2004

The role of sodium–calcium exchanger in acetylcholine (Ach)‐induced hyperpolarization of intact endothelial cells was studied in excised rat aorta. The membrane potential was recorded using perforated patch‐clamp technique.

The mean resting potential of endothelial cells was −44.1±1.4 mV. A selective inhibitor of sodium–calcium exchanger benzamil (100 μM) had no significant effect on resting membrane potential, but reversibly decreased the amplitude of sustained Ach‐induced endothelial hyperpolarization from 20.9±1.4 to 5.7±1.1 mV when applied during the plateau phase.

The blocker of reversed mode of the exchanger KB‐R7943 (2‐[2‐[4‐(4‐nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate, 20 μM) reversibly decreased the amplitude of sustained Ach‐induced hyperpolarization from 20.5±2.9 to 7.5±1.8 mV.

Introduction of tetraethylammonium (10 mM) in the continuous presence of Ach decreased the sustained phase of hyperpolarization from 17.9±1.5 by 12.9±0.9 mV. Subsequent addition of 20 μM KB‐R7943 further depolarized endothelial cells by 4.8±1.1 mV.

Substituting external sodium with N‐methyl D‐glucamine during the plateau phase of Ach‐evoked hyperpolarization reversibly decreased the hyperpolarization from −61.8±2.7 to −54.2±1.9 mV. In the majority of preparations, the initial response to removal of external sodium was a transient further rise in the membrane potential of several mV. Sodium ionophore monensin hyperpolarized endothelium by 10.3±0.7 mV.

The inhibitory effect of benzamil on Ach‐induced endothelial sustained hyperpolarization was observed in endothelium mechanically isolated from smooth muscle.

These results suggest that the sodium–calcium exchanger of intact endothelial cells is able to operate in reverse following stimulation by Ach, contributing to sustained hyperpolarization. Myoendothelial electrical communications do not mediate the effect of blockers of sodium–calcium exchanger.

British Journal of Pharmacology (2004) 143, 9–18. doi:10.1038/sj.bjp.0705866
Aspirin induces nitric oxide release from vascular endothelium: a novel mechanism of action
Authors: Taubert D , Berkels R , Grosser N , Schröder H , Gründemann D , Schömig E
Published: September 2004

The study was designed to test the hypothesis that aspirin may stimulate nitric oxide (NO) release from vascular endothelium, a pivotal factor for maintenance of vascular homeostasis.

Clinical evidence suggests that low‐dose aspirin may improve vascular endothelial function. Since other cyclooxygenase (COX) inhibitors showed no beneficial vascular effects, aspirin may exhibit a vasculoprotective, COX‐independent mechanism.

Luminal NO release was monitored in real time on dissected porcine coronary arteries (PCA) by an amperometric, NO‐selective sensor. Additionally, endothelial NO synthase (eNOS) activity was measured in EA.hy 926 cell homogenates by an L‐[3H]citrulline/L‐[3H]arginine conversion assay. Superoxide scavenging capacity was assessed by lucigenin‐enhanced luminescence.

Aspirin induced an immediate concentration‐dependent NO release from PCA with an EC50 of 50 nM and potentiated the NO stimulation by the receptor‐dependent agonist substance P. These effects were independent of an increase in intracellular calcium and could be mimicked by stimulation with acetylating aspirin derivatives. The aspirin metabolite salicylic acid or the reversible cyclooxygenase inhibitor indomethacin failed to modulate NO release. Incubation of soluble eNOS for 15 min with 100 μM aspirin or acetylating aspirin analogues increased the L‐[3H]citrulline yield by 40–80%, while salicylic acid had no effect. Aspirin and salicylic acid showed a similar, but only modest, magnitude and velocity of superoxide scavenging.

Our findings demonstrate that therapeutically relevant concentrations of aspirin elicit NO release from vascular endothelium. This effect appears to be due to a direct acetylation of the eNOS protein, but is independent of COX inhibition or inhibition of superoxide‐mediated NO degradation.

British Journal of Pharmacology (2004) 143, 159–165. doi:10.1038/sj.bjp.0705907
GEA 3162 decomposes to co‐generate nitric oxide and superoxide and induces apoptosis in human neutrophils via a peroxynitrite‐dependent mechanism
Authors: Taylor Emma L , Rossi Adriano G , Shaw Catherine A , Dal Rio Francesco P , Haslett Christopher , Megson Ian L
Published: September 2004

GEA 3162 (1,2,3,4,‐oxatriazolium, 5‐amino‐3‐(3,4‐dichlorophenyl)‐chloride), has powerful effects on neutrophil function and apoptosis, but the underlying mechanisms are unclear, particularly with respect to the possible roles of nitric oxide (NO) and/or peroxynitrite (ONOO−).

Our hypothesis was that GEA 3162 is a generator of ONOO− and that its biological effects on neutrophil apoptosis differ from those of a conventional NO donor. The effects of GEA 3162 were compared to those of the established ONOO− donor, 3‐morpholinosydnonimine (SIN‐1), and the NO donor, diethylamine diazeniumdiolate (DEA/NO) in neutrophils from healthy volunteers. Electrochemical detection and electron paramagnetic resonance were used to define the NO‐related species generated from these agents.

GEA 3162 and SIN‐1 influence neutrophil apoptosis differently from DEA/NO. All three compounds induced morphological neutrophil apoptosis. However, both GEA 3162 and SIN‐1 paradoxically inhibited internucleosomal DNA fragmentation, whereas DEA/NO induced fragmentation compared to control.

In contrast to DEA/NO, generation of free NO was not detectable in solutions of GEA 3162 or SIN‐1 (100 μM). However, Cu/Zn superoxide dismutase (SOD; 50–750 U ml−1) unmasked NO generated from these compounds in a concentration‐dependent manner. GEA 3162 and SIN‐1 oxidised the O2−‐ and ONOO−‐sensitive dye, dihydrorhodamine 123 (DHR 123; 1 μM), suggesting that ONOO− released from these compounds is responsible for oxidation of DHR 123.

We conclude that GEA 3162 is an ONOO− donor with pro‐apoptotic properties that more closely resemble SIN‐1 than the NO donor, DEA/NO. Moreover, unlike NO, ONOO− induces apoptosis in neutrophils via a mechanism that does not require DNA fragmentation.

British Journal of Pharmacology (2004) 143, 179–185. doi:10.1038/sj.bjp.0705909
Preclinical characterisation of 111In‐DTPA‐trastuzumab
Authors: Lub‐de Hooge Marjolijn N , Kosterink Jos G W , Perik Patrick J , Nijnuis Hugo , Tran Ly , Bart Joost , Suurmeijer Albert J H , de Jong Steven , Jager Pieter L , de Vries Elisabeth G E
Published: September 2004

Trastuzumab (Herceptin®) is a recombinant humanised IgG1 monoclonal antibody against the human epidermal growth factor receptor 2 (HER2), used for metastatic breast cancer treatment. Radiolabelled trastuzumab may have several future applications for diagnostic use. The aim of the present study was to develop clinical grade 111Indium (111In) radiolabelled trastuzumab, to evaluate the stability and immunoreactivity of the tracer and to perform a biodistribution study in human tumour‐bearing mice. Trastuzumab was radiolabelled with 111In using DTPA as a chelator. 111In‐DTPA‐trastuzumab (labelling yield 92.3±2.3%, radiochemical purity 97.0±1.5%) is stable in PBS when stored at 4°C for more than 14 days. The immunoreactive fraction determined by cell‐binding assays, using the HER2‐overexpressing human ovarian SK‐OV‐3 tumour cell line, was 0.87±0.06. Biodistribution and tumour targeting were studied in HER2 receptor‐positive and ‐negative tumour‐bearing athymic mice. The HER2‐positive tumour showed (9.77±1.14% injected dose per gram (ID g−1)) substantial uptake of the labelled antibody already after 5 h. The difference in uptake between HER2‐positive versus ‐negative tumours was even more pronounced 3 days after injection (16.30±0.64% ID g−1), and was visualised by radioimmunoscintigraphy. Liver, spleen and kidney showed marked tracer uptake. In summary, trastuzumab can be efficiently radiolabelled with 111In with high labelling yields and high stability. 111In‐DTPA‐trastuzumab selectively binds to the human HER2 receptor both in vitro and in vivo in animals. Therefore, 111In‐DTPA‐trastuzumab appears suitable for clinical use.

British Journal of Pharmacology (2004) 143, 99–106. doi:10.1038/sj.bjp.0705915
P2X2 and P2Y1 immunofluorescence in rat neostriatal medium‐spiny projection neurones and cholinergic interneurones is not linked to respective purinergic receptor function
Authors: Scheibler Peter , Pesic Mihail , Franke Heike , Reinhardt Robert , Wirkner Kerstin , Illes Peter , Nörenberg Wolfgang
Published: September 2004

The presence of ionotropic P2X receptors, targets of ATP in fast synaptic transmission, as well as metabotropic P2Y receptors, known to activate K+ currents in cultured neostriatal neurones, was investigated in medium‐spiny neurones and cholinergic interneurones contained in neostriatal brain slices from 5–26‐day‐old rats.

In these cells, adenosine‐5′‐triphosphate (ATP) (100–1000 μM), 2‐methylthioadenosine‐5′‐triphosphate (2MeSATP), α,β‐methyleneadenosine‐5′‐triphosphate (α,βmeATP, 30–300 μM, each) and adenosine‐5′‐O‐(3‐thiotriphosphate (ATPγS) (100 μM) failed to evoke P2X receptor currents even when 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX, 0.1 μM), apyrase (10 U ml−1) or intracellular Cs+ was used to prevent occluding effects of the ATP breakdown product adenosine, desensitisation of P2X receptors by endogenous ATP and an interference with the activation of K+ channels, respectively. P2X receptor agonists were also ineffective in outside‐out patches withdrawn from the brain slice tissue. Muscimol (10 μM) evoked GABAA receptor‐mediated currents under all these conditions.

When used as a control, locus coeruleus neurones responded with P2X receptor‐mediated currents to ATP (300 μM), 2MeSATP and α,βmeATP (100 μM, each).

ATP and adenosine‐5′‐diphosphate (ADP) (100 μM, each) did not activate K+ currents in the neostriatal neurones.

Despite the observed lack of function, P2X2 and P2Y1 immunofluorescence was found in roughly 50% of the medium‐spiny neurones and cholinergic interneurones.

A role of ATP in synaptic transmission to striatal medium‐spiny neurones and cholinergic interneurones appears unlikely, however, the otherwise silent P2X and P2Y receptors may gain functionality under certain yet unknown conditions.

British Journal of Pharmacology (2004) 143, 119–131. doi:10.1038/sj.bjp.0705916
Inhibitory pathways in the circular muscle of rat jejunum
Authors: Vanneste Gwen , Robberecht Patrick , Lefebvre Romain A
Published: September 2004

Conflicting data have been reported on the contribution of nitric oxide (NO) to inhibitory neurotransmission in rat jejunum. Therefore, the mechanism of relaxation and contribution to inhibitory neurotransmission of NO, adenosine 5′‐triphosphate (ATP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating peptide (PACAP) was examined in the circular muscle of Wistar–Han rat jejunum.

Mucosa‐free circular muscle strips were precontracted with methacholine in the presence of guanethidine and exposed to electrical field stimulation (EFS) and exogenous NO, ATP, VIP and PACAP. All stimuli induced reduction of tone and inhibition of phasic motility. Only electrically induced responses were sensitive to tetrodotoxin (3 × 10−6M).

NO (10−6–10−4M)‐induced concentration‐dependent relaxations that were inhibited by the soluble guanylyl cyclase inhibitor 1H‐[1,2,4]‐oxadiazolo‐[4,3‐a]‐quinoxalin‐1‐one (ODQ; 10−5M) and the small conductance Ca2+‐activated K+‐channel blocker apamin (APA; 3 × 10−8M).

Relaxations elicited by exogenous ATP (10−4–10−3M) were inhibited by the P2Y purinoceptor antagonist reactive blue 2 (RB2; 3 × 10−4M), but not by APA and ODQ.

The inhibitory responses evoked by 10−7M VIP and 3 × 10−8M PACAP were decreased by the selective PAC1 receptor antagonist PACAP6–38 (3 × 10−6M) and APA. The VPAC2 receptor antagonist PG99‐465 (3 × 10−7M) reduced relaxations caused by VIP, but not those by PACAP, while the VPAC1 receptor antagonist PG97‐269 (3 × 10−7M) had no influence.

EFS‐induced relaxations were inhibited by the NO‐synthase inhibitor Nω‐nitro‐L‐arginine methyl ester (3 × 10−4M), ODQ and APA, but not by RB2, PG97‐269, PG99‐465 and PACAP6–38.

These results suggest that NO is the main inhibitory neurotransmitter in the circular muscle of Wistar–Han rat jejunum acting through a rise in cyclic guanosine monophosphate levels and activation of small conductance Ca2+‐dependent K+ channels.

British Journal of Pharmacology (2004) 143, 107–118. doi:10.1038/sj.bjp.0705918
Ouabain‐induced hypertension alters the participation of endothelial factors in α‐adrenergic responses differently in rat resistance and conductance mesenteric arteries
Authors: Xavier Fabiano E , Rossoni Luciana V , Alonso María J , Balfagón Gloria , Vassallo Dalton V , Salaices Mercedes
Published: September 2004

This study compares the role of endothelial factors in α‐adrenoceptor contractile responses in mesenteric resistance (MRA) and superior (SMA) mesenteric arteries from ouabain‐treated (8.0 μg day−1, 5 weeks) and untreated rats. The role of the renin–angiotensin system was also evaluated.

Ouabain treatment increased systolic blood pressure. In addition, ouabain reduced the phenylephrine response in SMA but did not alter noradrenaline responses in MRA.

Endothelium removal or the nitric oxide synthase (NOS) inhibitor (L‐NAME, 100 μM) increased the responses to α‐adrenergic agonists in both vessels. After ouabain treatment, both endothelial modulation and the L‐NAME effect were increased in SMA, while only the L‐NAME effect was increased in MRA. Endothelial NOS expression remained unaltered after ouabain treatment.

Indomethacin (10 μM) similarly reduced the noradrenaline contraction in MRA from both groups; in contrast, in SMA, indomethacin only reduced phenylephrine‐induced contractions in segments from untreated rats. Co‐incubation of L‐NAME and indomethacin leftward shifted the concentration–response curves for noradrenaline more in MRA from ouabain‐treated rats; tetraethylammonium (2 mM) shifted the noradrenaline curves further leftward only in MRA from untreated rats.

Losartan treatment prevents the development of hypertension but not all vascular changes observed after ouabain treatment.

In conclusion, a rise in endothelial NO and impaired prostanoid participation might explain the reduction in phenylephrine‐induced contraction in SMA after ouabain treatment. An increase in the modulatory effect of endothelial NO and impairment of endothelium‐dependent hyperpolarizing factor effect might explain why the ouabain treatment had no effect on noradrenaline responses in MRA.

British Journal of Pharmacology (2004) 143, 215–225. doi:10.1038/sj.bjp.0705919
Surface chemical modification of InN for sensor applications
Authors: Lu Hai , Schaff William J. , Eastman Lester F.
Published: September 2004

The effect of chemical exposures on the InN surface is reported. InN surface shows a fast capture, slow release, responsivity, and selectivity to certain solvent exposures, such as methanol and water. Enhancement in sheet carrier density as large as 7×1012cm−2 with a simultaneous increase in Hall mobility of thin InN films was determined by Hall measurements. A corresponding reduction in sheet resistance of more than 30% was measured on a 20nm InN film. The added electrons are likely to be surface carriers whose density decays after the solvent fully evaporates. This study shows the promise of using the sensitive InN surface for sensor applications.
O
2
(
Δ
1
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production in He∕O2 mixtures in flowing low pressure plasmas
Authors: Stafford D. Shane , Kushner Mark J.
Published: September 2004

Chemical oxygen-iodine lasers (COIL) are attractive for diverse industrial applications because they are capable of high efficiency, high power operation, and because the 1.315μm wavelength can be transmitted through fiber optics and couples efficiently with most metals. Conventional COILs are pumped with O2(Δ1) that is generated by reaction of Cl2 in a basic H2O2 solution. Current trends in pumping COILs involve producing the O2(Δ1) in electric discharges, thereby circumventing the hazards, complexity, and weight associated with pumping and storing caustic liquids. In this work, we have investigated the scaling of O2(Δ1) yields with specific energy deposition in He∕O2 mixtures in flowing radio frequency (rf) discharges at pressures of a few to tens of Torr using a global plasma kinetics model. We found that O2(Δ1) yield increases nearly linearly with specific energy deposition in O2 molecules up to a few eV per molecule, with yields peaking around 30% by 5–8eV. Further increases in specific energy deposition serve only to increase O2 dissociation and gas heating, thereby reducing the O2(Δ1) yield. We also found that variations in peak yields at a given specific energy deposition are caused by secondary effects resulting from dilution, pressure, and power level. We show that these secondary effects alter the O2(Δ1) yield by shifting the O2(Σ1)∕O2(Δ1) ratio.
Conductivity of DNA probed by conducting–atomic force microscopy: Effects of contact electrode, DNA structure, and surface interactions
Authors: Heim Thomas , Deresmes Dominique , Vuillaume Dominique
Published: September 2004

We studied the electrical conductivity of DNA molecules with conducting–atomic force microscopy as a function of the chemical nature of the substrate surfaces, the nature of the electrical contact, and the number of DNA molecules (from a few molecules to ropes and large fibers containing up to ∼106 molecules). Independent of the chemical nature of the surface (hydrophobic or hydrophilic, electrically neutral or charged), we find that DNA is highly resistive. From a large number of current-voltage curves measured at several distances along the DNA, we estimate a conductivity of about 10−6–10−5Scm−1 per DNA molecule. For single DNA molecules, this highly resistive behavior is correlated with its flattened conformation on the surface (reduced thickness, ∼0.5–1.5nm, compared to its nominal value, ∼2.4nm). We find that intercalating an organic semiconductor buffer film between the DNA and the metal electrode improves the reliability of the contact, while direct metal evaporation usually destroys the DNA and prevents any current measurements. After long exposure under vacuum or dry nitrogen, the conductivity strongly decreases, leading to the conclusion that water molecules and ions in the hydration shell of the DNA play a major role.
Electro-optical properties of a nematic liquid crystal cell by double-side fringe-field switching
Authors: Xiang C. Y. , Sun X. W.
Published: September 2004

The electro-optical and response properties of a nematic liquid crystal cell driven by double-side fringe-field switching [C. Y. Xiang, X. W. Sun, and X. J. Yin, Appl. Phys. Lett. 83, 5154 (2003)] have been studied. The transmission-voltage curve of the double-side fringe-field cell can be modeled by the change of the maximum twist angle. It is shown that the liquid crystal layer is linearly twisted before the transmission reaches the maximum. The threshold voltage of double-side fringe-field switching is the same as that of single-side fringe-field switching. The turn-on and turn-off response times, showing four time improvement over the single-side fringe-field switching, have been derived. The experimental turn-off times of the double-sides fringe-field switching and single-side fringe-field switching cell match with the theoretical prediction. The experimental turn-on time of the double-side fringe-field switching cell shows four times improvement over the single-side fringe-field one as predicted by the theoretical analysis.