bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryopreservation reduces the concentration of detectable bacteria in contaminated peripheral blood progenitor cell products
Authors: Kipp Frank , Linnemann Elmar , Fischer Rudolf‐Josef , Sibrowski Walter , Cassens Uwe
Published: July 2004

BACKGROUND:  Microbial contamination of PBPC products PBPCPs may cause severe clinical complications. There‐fore, we investigated the influence of cryopreservation on the sensitivity to detect bacterial contaminations in PBPCPs.

STUDY DESIGN AND METHODS:  Expired PBPCPs (n = 29) were thawed, and defined concentrations of Staphylococcus epidermidis or Escherichia coli were inoculated into each bag. After 60 minutes of intermixing, a representative aliquot was drawn and cultured on Mueller‐Hinton agar for 24 hours. Then, the products were cryopreserved for 24 hours, and the procedure was repeated as mentioned above. The total numbers of CFUs were counted before and after cryopreservation.

RESULTS:  A mean concentration of 2529 CFUs per mL of S. epidermidis was determined before cryopreservation versus 2182 CFUs per mL after cryopreservation, demon‐strating a decrease of detectable colonies (p < 0.05). For E. coli, the mean numbers were 424 CFUs per mL before cryopreservation and 343 CFUs per mL after cryopreser‐vation, also showing a decrease (p < 0.05).

CONCLUSION:  The cryopreservation reduces the concentration of detectable bacteria in contaminated PBPCPs. Especially in sterility testing of PBPCPs with low bacterial contamination, this phenomenon could lead to false‐negative results with severe clinical consequences.
White particulate matter found in blood collection bags consist of platelets and leukocytes
Authors: Rentas F.J. , Macdonald V.W. , Rothwell S.W. , McFaul S.J. , Asher L.V. , Kennedy A.M. , Hmel P.J. , Meledandri C.J. , Salata J.M. , Harman R.W. , Reid T.J.
Published: July 2004

BACKGROUND:  In late January 2003, some blood centers and hospitals throughout the US voluntarily sus‐pended the use of some RBC and plasma units for trans‐fusion due to the presence of unknown white particulate matter (WPM) in these units. To better understand the WPM phenomena, a number of technologies were used to establish the nature of the particulates observed in Terumo Collection sets.

STUDY DESIGN AND METHODS:  All AS‐5 nonleuko‐reduced RBCs and plasma units were visually inspected for WPM by placing the bags on a flat counter, undisturbed, for approximately 10 minutes and then perform‐ing a visual examination for particles. Particles were isolated and placed on microscope slides or in plastic tubes for further analysis. Electron microscopy, bright field microscopy, differential interference contrast microscopy, infrared spectroscopy, and flow cytometry procedures were performed to establish the nature of the particulate matter. In addition, leukoreduction filters and blood transfusion sets were used on RBCs units with WPM.

RESULTS:  The particles were mostly composed of PLTs and WBCs, and fragments of these cells. All macroscopic WPM was removed from RBCs with leukoeduction and transfusion filters.

CONCLUSIONS:  WPM originated from PLTs and WBCs. Foreign matter (e.g., plastic) was not observed in any of the units. Leukoreduction and transfusion filters can be used to remove macroscopic WPM.
Comparison of two mononuclear cell program settings on two apheresis devices intended to collect high yields of CD14+ and CD3+ cells
Authors: Strasser Erwin F. , Dittrich Sandra , Weisbach Volker , Zimmermann Robert , Ringwald Jürgen , Achenbach Susanne , Zingsem Jürgen , Eckstein Reinhold
Published: July 2004

BACKGROUND:  In cancer and transplantation therapy apheresis devices and software of optimum standards are required for the collection of high cell yields with high purity of the desired cell fraction.

STUDY DESIGN AND METHODS:  In a paired study, 15 healthy blood donors underwent four 10‐L leukapheresis procedures (197 ± 33 min) with an inlet blood flow rate of 60 mL per minute by use of two different MNC program settings of the COBE Spectra (Gambro BCT) and the AS.TEC 204 (Fresenius Hemocare) cell separators.

RESULTS:  Use of the standard MNC program of both apheresis devices resulted in significantly higher (p < 0.01) collection efficiencies of CD14+ monocytes, CD3+ cells, CD4+ cells, CD8+ T cells, CD16+ CD56+ natural killer (NK) cells, and residual PLTs (p < 0.001), owing to higher centrifuge speed. The mean MNC purity of all components was more than 90 percent. By use of stan‐dard programs of either device, significant correlations (p < 0.01) between donor monocytes and preleukapheresis NK cell counts and the corresponding component cell yields were found.

CONCLUSION:  Compared to the program modifications with lower centrifuge velocities the standard MNC programs were significantly more efficient regarding CD14+, CD3+, and CD16+ CD56+ cells. Enhanced centrifuge speed and inlet blood flow rate in MNC programs resulted in higher, similar composed MNC concentrations of the products.
Particulate matter phenomenon: adverse event data and the effect of leukofiltration
Authors: Orton Sharyn L. , Leparc G.F. , Rossmann Susan , Lewis R.M.
Published: July 2004

BACKGROUND:  In February 2002, a multiorganizational task force investigated blood center reports of unusual particulate matter (PM) visible in packed red blood cells (RBC). A cohort study assessed increase in adverse events (AEs) related to this phenomenon, as well as the effect of post‐leukofiltration (LF) on PM.

METHODS:  Two blood centers assessed AEs in patients transfused with RBCs having visible PM (classified as normal by‐products of RBC preparation), PM RBCs subsequently LF, or RBCs without visible PM, and the effect of LF on PM removal.

RESULTS:  There was no difference in AEs in patients transfused with PM RBCs with or without LF compared to patients transfused with RBCs without visible PM. Subsequently filtered PM RBCs had acceptable residual WBC counts and median platelet removal of 92%.

CONCLUSION:  Transfusion of RBCs with visible PM or RBCs subsequently LF does not appear to increase the risk of an AE. LF use on PM RBCs results in the PM removal without adversely affecting filter performance. The lack of evidence of an increase in AE reports does not mean that there is no effect, and there may be a baseline AE rate attributable to PM which has not been thoroughly researched.
Prevalence of viable Chlamydia pneumoniae in peripheral blood mononuclear cells of healthy blood donors
Authors: Yamaguchi Hiroyuki , Yamada Masako , Uruma Tomonori , Kanamori Masato , Goto Hajime , Yamamoto Yoshimasa , Kamiya Shigeru
Published: July 2004

BACKGROUND:  Demonstration of viable Chlamydia (Chlamydophila) pneumoniae in peripheral blood mononuclear cells (PBMNCs) is essential to understand the involvement of C. pneumoniae in atherosclerosis. Nevertheless, the prevalence of viable C. pneumoniae in the blood of healthy donors has not yet been studied.

STUDY DESIGN AND METHODS:  The presence of C. pneumoniae transcript in PBMNCs from blood of healthy human donors was assessed by real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) with primers for C. pneumoniae 16S rRNA, which is more sensitive than genomic‐DNA‐based analysis, and by the use of staining with fluorescein isothiocyanate‐conjugated chlamydia monoclonal antibody (MoAb).

RESULTS:  Thirteen of 70 donors (18.5%) showed the presence of bacterial transcript in cultured PBMNCs. The prevalence of bacterial detection and bacterial numbers was significantly increased in PBMNC cultures incubated with cycloheximide. Immunostaining of PBMNCs with antichlamydial MoAb also revealed the presence of bacterial antigen in the PBMNCs judged as positive. Nevertheless, cultivation of C. pneumoniae from all PCR‐positive donors was unsuccessful. There was no signifi‐cant correlation between the presence of chlamydia and either sex or current smoking habits. A possible age variation, however, in the presence of chlamydia in blood of healthy donors was suggested by the results obtained.

CONCLUSION:  The bacterial transcripts in PBMNCs obtained from healthy donors were detected by the RT‐PCR method. Viable C. pneumoniae may be present in healthy human PBMNCs.
Description and investigation of white particulate matter in additive solution‐1 red blood cell units
Authors: Hillyer Christopher D. , Roback John D. , Hillyer Krista L. , Josephson Cassandra D. , Page Peter L.
Published: July 2004

BACKGROUND:  In January 2003, “white particulate matter” (WPM) was transiently observed in red blood cell (RBC) units collected predominately in the southeastern US. In this report, these events, their chronology, perti‐nent observations and investigations, and summaries and conclusions associated with WPM during the 2‐week observation period are described.

CHRONOLOGY AND INVESTIGATIONS:  On January 27, 2003, WPM was first identified in RBCs; by January 31, 2003, 110 RBC units containing WPM had been identified. Elective surgeries were postponed. Approxi‐mately 400 RBC units containing WPM were inspected in the blood center and characterized into four types: I, II, III, and IV. A variety of preparations of aspirated WPM were made, including light and electron microscopic sections.

RESULTS AND CONCLUSIONS:  The rate of WPM‐containing units was 1.67 percent (1 in 60 units), whereas the background incidence was less than 0.25 percent. Investigations revealed that WPM was composed of activated and nonactivated platelets (PLTs); no toxins, infectious agents, or agents of bioterrorism were iden‐tified. WPM correlated with certain variables studied, including PLT‐rich components that had been centrifuged with a “hard spin” before leukoreduction and manu‐factured in one vendor's collection sets. Because the increased rate of appearance of WPM was a transient phenomenon, it is not clear whether this is a newly noticed or a new and different phenomenon from “aggregates” observed in the past.
Turner Syndrome: Genetic and Hormonal Factors Contributing to a Specific Learning Disability Profile
Authors: Rovet Joanne
Published: July 2004

Turner Syndrome (TS) is a genetic disorder affecting primarily females. It arises from a loss of X‐chromosome material, most usually one of the two X chromosomes. Affected individuals have a number of distinguishing somatic features, including short stature and ovarian dysgenesis. Individuals with TS show a distinct neurocognitive profile involving visuospatial deficits and selective memory and attention difficulties. They also have a number of psychosocial and behavioral problems. They are at high risk of learning disabilities and often have a need for special education. Recent research has identified some of the genetic and hormonal mechanisms contributing to their neurobehavioral profile. This article reviews the current findings on TS and shows how understanding the impact of these factors on early brain development and later brain function might advance our understanding of learning disabilities more generally. The implications of current research findings for the daily management of children with TS in the classroom are also discussed.
Cognitive Profile of Neurofibromatosis Type 1: Rethinking Nonverbal Learning Disabilities
Authors: Cutting Laurie E. , Clements Amy M. , Lightman Andrea D. , Yerby‐Hammack Pamula D. , Denckla Martha Bridge
Published: July 2004

The cognitive profiles of children with Neurofibromatosis Type 1 (NF‐1) have many similarities to those observed in learning disabilities in the general school population, as well as some distinct features. Approximately 30–65 percent of children with NF‐1 have learning disabilities; most commonly, they have language and reading disabilities, along with motor, visuomotor, and visuospatial deficits. Similar to learning disabilities in the general population, approximately 50 percent of children with NF‐1 have Attention Deficit Hyperactivity Disorder (ADHD). In this article, the genetic and physical characteristics, the diagnostic criteria of NF‐1, and the cognitive profile of children with NF‐1 (including relationships between neurological abnormalities and cognition) are reviewed. Additionally, the types of educational interventions that would be indicated for children with NF‐1 are discussed.
Melatonin in vivo prolongs cardiac allograft survival in rats
Authors: Jung Florian J. , Yang Lin , Härter Luc , Inci Ilhan , Schneiter Didier , Lardinois Didier , Keel Marius , Weder Walter , Korom Stephan
Published: July 2004

Abstract:  Melatonin, secreted by the pineal gland, is a multifunctional agent which (i) protects tissues from damage through free radical scavenging and attenuates ischemia/reperfusion injury in organ grafts; (ii) acts synergistically with cellular antioxidants; and (iii) displays complex, dose‐dependent immunoenhancing and suppressing effects in vitro and in vivo. We analyzed the immunomodulatory effect of melatonin on acute allograft rejection. Cardiac grafts were transplanted from LBNF1 to LEW rats and anastomosed to the abdominal great vessels. The effect of low‐dose (LD; 20 mg/kg/day) and high‐dose (HD; 200 mg/kg/day) melatonin treatment in recipients compared with untreated controls was investigated. HD melatonin therapy abrogated acute rejection, significantly prolonging allograft survival (mean survival: 12.3 ± 1 days S.D., n = 8, P < 0.0001) compared with untreated controls, which rapidly reject the transplant (6.3 ± 1 days n = 12). LD therapy did not extend survival significantly (7.3 ± 1.1 days, n = 12). Allospecific IgM showed a significant decrease in animals receiving HD therapy versus untreated recipients at days 10 and 14 post‐transplantation (P < 0.01), whereas in the LD group at day 10, a significant increase in allospecific IgM (P < 0.01) over the HD cohort was demonstrated. HD treatment markedly reduced lymphocyte proliferative capacity compared with controls and the LD group. HD melatonin treatment abrogated acute allograft rejection and significantly prolonged graft survival. Our results suggest an involvement of melatonin in humoral and cellular immune pathways following perfused organ transplantation. These findings may indicate a novel therapeutic approach, based on modulation of the neuroendocrine/immune axis through melatonin as a possible future immunosuppressant in organ transplantation.
Visualization of the antioxidative effects of melatonin at the mitochondrial level during oxidative stress‐induced apoptosis of rat brain astrocytes
Authors: Jou Mei‐Jie , Peng Tsung‐I , Reiter Russel J. , Jou Shuo‐Bin , Wu Hong‐Yueh , Wen Shiau‐Ting
Published: July 2004

Abstract:  Oxidative stress‐induced mitochondrial dysfunction has been shown to play a crucial role in the pathogenesis of a wide range of diseases. Protecting mitochondrial function, therefore, is vital for cells to survive during these disease processes. In this study, we demonstrate that melatonin, a chief secretory product of the pineal gland, readily rescued mitochondria from oxidative stress‐induced dysfunction and effectively prevented subsequent apoptotic events and death in rat brain astrocytes (RBA‐1). The early protection provided by melatonin in mitochondria of intact living cells was investigated by the application of time‐lapse conventional, confocal, and multiphoton fluorescent imaging microscopy coupled with noninvasive mitochondria‐targeted fluorescent probes. In particular, we observed that melatonin effectively prevented exogenously applied H2O2‐induced mitochondrial swelling in rat brain astrocytes at an early time point (within 10 min) and subsequently reduced apoptotic cell death (150 min later). Other early apoptotic events such as plasma membrane exposure of phosphatidyl serine and the positive YOPRO‐1 staining of the early apoptotic nucleus were also prevented by melatonin. A mechanistic study at the mitochondrial level related to the early protection provided by melatonin revealed that the indole molecule significantly reduced mitochondrial reactive oxygen species (ROS) formation induced by H2O2 stress. Melatonin also prevented mitochondrial ROS generation caused by other organic hydroperoxides including tert‐butyl hydroperoxide and cumene hydroperoxide. This antioxidative effect of melatonin is more potent than that of vitamin E. Via its ability to reduce mitochondrial ROS generation, melatonin prevented H2O2‐induced mitochondrial calcium overload, mitochondrial membrane potential depolarization, and the opening of the mitochondrial permeability transition (MPT) pore. As a result, melatonin blocked MPT‐dependent cytochrome c release, the downstream activation of caspase 3, the condensation and karyorrhexis of the nucleus and apoptotic fragmentation of nuclear DNA. Thus, the powerful mitochondrial protection provided by melatonin reinforces its therapeutic potential to combat a variety of oxidative stress‐induced mitochondrial dysfunctions as well as mitochondria‐mediated apoptosis in various diseases.
Histomorphologic correlation with routine histology and optical coherence tomography
Authors: Bechara F. G. , Gambichler T. , Stücker M. , Orlikov A. , Rotterdam S. , Altmeyer P. , Hoffmann K.
Published: July 2004

Background: Optical coherence tomography (OCT) is a new and promising diagnostic technique for investigation of skin tumours. We describe a method that makes evaluation and definition of specific morphologic structures of skin tumours via OCT more accurate.

Materials and method: We investigated three patients with basal cell carcinoma and three patients with melanocytic nevi. Three‐dimensional (3D) images were obtained from these skin tumours via OCT according to previously applied marks, which were tattooed with special histological marking dye after excision of the tumours. Corresponding to these marks, we investigated serial histological sections (haematoxylin&eosin staining).

Results: We could prove similar morphological structures both in OCT and histology. Due to tissue deformation, the compared measurements of structures like cell nests or epidermal thickness were slightly deviated. However, by this method we could prove similar tissue formations in OCT and histology.

Conclusions: Due to the deformation by histological processing and slightly different sectioning levels, the comparison of histological pictures and OCT images seems difficult. Nevertheless, in two cases it was possible to demonstrate the same morphological structures with OCT imaging and histological investigation. Our method could play an important role for further evaluation of OCT images. We estimate better evaluation of OCT imaging using a 3D reconstruction method.
Clinical validation of an automated system for supporting the early diagnosis of melanoma
Authors: Sboner Andrea , Bauer Paolo , Zumiani Giuseppe , Eccher Claudio , Blanzieri Enrico , Forti Stefano , Cristofolini Mario
Published: July 2004

Background: Early diagnosis and surgical excision is the most effective treatment of melanoma. Well‐trained dermatologists reach a high level of diagnostic accuracy with good sensitivity and specificity. Their performances increase using some technical aids as digital epiluminescence microscopy. Several studies describe the development of computerized systems whose aim is supporting dermatologists in the early diagnosis of melanoma. In many cases, the performances of those systems were comparable to those of dermatologists. However, this cannot tell us whether a system is able to support dermatologists. Actually, the computerized system might correctly recognize the same lesions that the dermatologist does, without providing them any useful advice and therefore being useless in recognizing early malignant lesions.

Purpose: We present a novel approach to enhance dermatologists' performances in the diagnosis of early melanoma. We provide results of our evaluation of a computerized system combined with dermatologists.

Methods: A Multiple‐Classifier system was developed on a set of 152 cases and combined to a group of eight dermatologists to support them by improving their sensitivity.

Results: The eight dermatologists have average sensitivity and specificity values of 0.83 and 0.66, respectively. The Multiple‐Classifier system performs as well as the eight dermatologists (sensitivity range: 0.75–0.86; specificity range: 0.64–0.89). The combination with the dermatologists shows an average improvement of 11% (P=0.022) of dermatologists' sensitivity.

Conclusion: Our results suggest that an automated system can be effective in supporting dermatologists because it recognizes different malignant melanomas with respect to the dermatologists.
Pilot study of dermal and subcutaneous fat structures by MRI in individuals who differ in gender, BMI, and cellulite grading
Authors: Mirrashed F. , Sharp J. C. , Krause V. , Morgan J. , Tomanek B.
Published: July 2004

Background/aims: Puckered, dimply skin on the thighs, hips, and buttocks is known as cellulite. The cause of cellulite is not known, although there are a number of different hypotheses. In this study, we use magnetic resonance (MR) micro‐imaging to study cellulite skin. To the best of our knowledge, this is the first reported MR study of cellulite.

Methods: High‐resolution in vivo MR images of the postlateral thigh skin of two male groups and four female groups were obtained. Subjects were grouped according to their body mass index (BMI) and cellulite grade. A qualitative assessment of how MRI can be used to differentiate skin tissue at different levels of cellulite grading was performed.

Results: We found that changes in skin architecture with cellulite can be visualized by in vivo MR micro‐imaging. The skin fat layers beneath the dermis and down to the level of muscles are well visualized in the images. Also, the diffuse pattern of extrusion of underlying adipose tissue into dermis is clearly imaged, and was found to correlate with cellulite grading.

We also show that other skin tissue parameters such as (a) the percentile of adipose vs. connective tissue in a given volume of hypodermis and (b) the percentile of hypodermic invaginations inside the dermis are correlated with cellulite grade.

Conclusion: MR images can be interpreted to measure tissue parameters correlated with cellulite. Considering that we had only three subjects in each group, the achievements of this pilot study were highly satisfactory. We have shown that the in vivo micro‐MR is a technique able to detect the effects of cellulite and gender. This study can be extended for further investigations of drugs and/or medical devices for cellulite treatment.
On the course of the irritant reaction after irritation with sodium lauryl sulphate
Authors: Gloor Max , Senger Bettina , Langenauer Marcel , Fluhr Joachim W.
Published: July 2004

Background: The sodium lauryl sulphate (SLS) irritation test is a well‐established model for irritant contact dermatitis after the effects of surfactants.

Aim of the study: The course of changes in corneometric measurements (stratum corneum hydration), in transepidermal water loss (TEWL), in laser Doppler measurements (epidermal perfusion) and in colorimetric measurements (skin redness), after a single SLS irritation, should be studied over time.

Methods: Twenty healthy volunteers were studied. Irritation with 1% SLS solution was applied to the side of one forearm for 24 h under occlusive conditions, while the symmetrical experimental site remained untreated. Measurements were made for 9 days after completion of SLS irritation.

Results: Stratum corneum hydration was reduced immediately after irritation, and subsequently a hyper‐hydration was observed. The increase in TEWL, laser Doppler measurements and skin redness persisted for 7–9 days. With regard to skin redness, a mild blanching effect was noticeable after 9 days.

Discussion: The evidence of very short‐term exsiccation of the stratum corneum with persistent barrier damage, as well as reactive hyper‐hydration and blanching of the skin, is remarkable. These first findings suggest that exsiccation of the stratum corneum is not caused by a damage to barrier lipids.
Effect of compression on blood flow in lower limb wounds
Authors: Oduncu Hakan , Clark Michael , Williams Robert J
Published: July 2004

Blood flow is believed to be a key parameter in the formation and management of lower limb wounds. Patients with venous leg ulcers (VLUs) have high venous pressures, due to the partial or complete failure of calf muscle pump, which in turn disturbs the local blood flow within the lower limb. Compression has currently been the mainstay for treatment of VLUs and is thought to restore valvular competence and reduce or suppress superficial and deep venous reflux. Efficacy and assessment of compression therapy can be understood in a better way by measuring blood flow in lower limbs. Publications applicable to the effects of compression on lower limb blood flow parameters are summarised. However, they have shown varying results due to the different methodology and assessment techniques used. This article seeks to explore the methods of assessment of blood flow in the lower limb associated with wound management and compression in particular and provides suggestions for future explorations.
Diabetic foot infections: stepwise medical and surgical management
Authors: Armstrong David G , Lipsky Benjamin A
Published: July 2004

Foot complications are common among diabetic patients; foot ulcers are among the more serious consequences. These ulcers frequently become infected, with potentially disastrous progression to deeper spaces and tissues. If not treated promptly and appropriately, diabetic foot infections can become incurable or even lead to septic gangrene, which may require foot amputation. Diagnosing infection in a diabetic foot ulcer is based on clinical signs and symptoms of inflammation. Properly culturing an infected lesion can disclose the pathogens and provide their antibiotic susceptibilities. Specimens for culture should be obtained after wound debridement to avoid contamination and optimise identification of pathogens. Staphylococcus aureus is the most common isolate in these infections; the increasing incidence of methicillin‐resistant S. aureus over the past two decades has further complicated antibiotic treatment. While chronic infections are often polymicrobial, many acute infections in patients not previously treated with antibiotics are caused by a single pathogen, usually a gram‐positive coccus. We offer a stepwise approach to treating diabetic foot infections. Most patients must first be medically stabilised and any metabolic aberrations should be addressed. Antibiotic therapy is not required for uninfected wounds but should be carefully selected for all infected lesions. Initial therapy is usually empirical but may be modified according to the culture and sensitivity results and the patient's clinical response. Surgical intervention is usually required in cases of retained purulence or advancing infection despite optimal medical therapy. Possible additional indications for surgical procedures include incision and drainage of an abscess, debridement of necrotic material, removal of any foreign bodies, arterial revascularisation and, when needed, amputation. Most foot ulcers occur on the plantar surface of the foot, thus requiring a plantar incision for any drainage procedure.
Effects of the Calcitonin Gene‐Related Peptide (CGRP) Receptor Antagonist BIBN4096BS on α‐CGRP‐Induced Regional Haemodynamic Changes in Anaesthetised Rats
Authors: Arulmani Udayasankar , Schuijt Martin P. , Heiligers Schuijt , Willems Heiligers , Villalón Carlos M. , Saxena Pramod R.
Published: July 2004

Abstract: Several studies suggest that a calcitonin gene‐related peptide (CGRP) receptor antagonist may have antimigraine properties, most probably via the inhibition of CGRP‐induced cranial vasodilatation. We recently showed that the novel selective CGRP receptor antagonist, BIBN4096BS (1‐piperidinecarboxamide, ‐N‐[2‐[[5‐amino‐1‐[[4‐(4‐pyridinyl)‐1‐piperazinyl] carbonyl] pentyl]amino]‐1‐[(3,5‐dibromo‐4‐hydroxyphenyl) methyl]‐2‐oxoethyl]‐4‐(1,4‐dihydro‐2‐oxo‐3(2H)‐quinazolinyl)‐, [[R‐(R,(R*,S*)]), attenuated the CGRP‐induced porcine carotid vasodilatation in a model predictive of antimigraine activity. In order to evaluate the potential safety of BIBN4096BS in migraine therapy, this study was designed to investigate the effects of intravenous BIBN4096BS on α‐CGRP‐induced systemic and regional haemodynamic changes in anaesthetised rats, using radioactive microspheres. In vehicle‐pretreated animals, consecutive intravenous infusions of α‐CGRP (0.25, 0.5 and 1 μg kg−1 min.−1) dose‐dependently decreased mean arterial blood pressure with an accompanying increase in heart rate and systemic vascular conductance whereas cardiac output remained unchanged. α‐CGRP also increased the vascular conductance to the heart, brain, gastrointestinal tract, adrenals, skeletal muscles and skin, whilst that to the kidneys, spleen, mesentery/pancreas and liver remained unaltered. The above systemic and regional haemodynamic responses to α‐CGRP were clearly attenuated in BIBN4096BS (3 mg kg−1 intravenously)‐pretreated animals. These results indicate that exogenously administered α‐CGRP dilates regional vascular beds via CGRP receptors on the basis of the antagonism produced by BIBN4096BS. Moreover, the fact that BIBN4096BS did not alter baseline haemodynamics suggests that endogenously produced CGRP does not play an important role in regulating the systemic and regional haemodynamics under resting conditions.
Glutamate Receptor Antagonists
Authors: Bigal Marcelo E.
Published: July 2004

GLUR5 Antagonists as Novel Migraine Therapies

BACKGROUND: L‐glutamate activates neurons in the trigeminal nucleus caudalis (TNC). Furthermore, non‐NMDA ionotropic glutamate receptors such as GluR5 are expressed in rat trigeminal ganglion (TG), and GluR5 receptors play an important role in central sensitization (CS). CS is implicated in, and the trigeminal system is at the core of, migraine. Therefore, we hypothesized that GluR5 receptor antagonists would be effective in preclinical models of migraine.

OBJECTIVES: 1) To test the potency and efficacy of GluR5 antagonists with varying degrees of affinity and selectivity for the GluR5/kainate receptor in the dural plasma protein extravasation (PPE) and the c‐fos models of migraine. 2) To test these GluR5 receptor antagonists for their ability to contract the rabbit saphenous vein (RSV) in vitro.

METHODS: GluR5 antagonists were synthesized in the Lilly Research Laboratories. Ligand binding studies using recombinant human non‐NMDA receptors expressed in HEK293 cell membranes were used to determine compound affinity. We evaluated parenterally administered compounds in the PPE and the c‐fos models induced by electrical stimulation of male rats TG. Fos protein in the TNC was measured in the c‐fos experiment. Ring preparations of RSV were suspended in tissue baths and isometric contractions were recorded following incremental increases in the concentration of the test compound. Sumatriptan was used as a positive control for the RSV studies.

RESULTS: LY293558, LY382884 and LY435735 dose‐dependently blocked protein extravasation in the PPE model. The rank order of potency correlated with affinity for GluR5. In contrast, LY300168, a potent and selective AMPA antagonist, did not block protein extravasation, even at relatively high doses. LY293558 and LY435735 also blocked c‐fos expression in the TNC. LY293558 and LY382884 did not contract the tissue in the RSV assay at concentrations up to 100 mM.

CONCLUSIONS: The inhibitory effects of GluR5 antagonists in the PPE and c‐fos preclinical models of migraine suggest a novel role for GluR5 antagonism in migraine therapy. The lack of efficacy of the selective AMPA antagonist LY300168 in PPE does not support a role for this mechanism in migraine. The lack of activity of these compounds in the RSV provides a therapeutic advantage of GluR5 antagonists over current vasoactive migraine therapies. These pharmacological properties of GluR5 antagonists suggest that they could be used in the treatment of acute migraine without a cardiovascular liability.
Correlating growth conditions with photoluminescence and lasing properties of mid-IR antimonide type II “W” structures
Authors: Canedy C. L. , Boishin G. I. , Bewley W. W. , Kim C. S. , Vurgaftman I. , Kim M. , Lindle J. R. , Meyer J. R. , Whitman L. J.
Published: July 2004

We explored the evolution of the photoluminescence (PL) properties versus molecular beam epitaxy growth conditions for a series of type II “W” quantum well [InAs/GaInSb/InAs/AlAsSb] structures. The highest PL intensities are obtained when the quantum wells are grown in a temperature range between 487 and 507 °C. Cross-sectional scanning tunneling microscopy was used to explain the temperature evolution of the PL. AlAs clustering within the AlAsSb barrier was observed at low growth temperature. The PL intensity decrease at high temperature was related to In clustering in the GaInSb layer. Laser structures grown at both 425 and 500 °C displayed lower lasing thresholds, lower internal losses, and longer Shockley–Read lifetimes than any similar structures grown previously at NRL. A thicker optical cladding layer of 3.5 μm suppressed mode leakage into the substrate and reduced the internal loss to 2.1 cm−1 at 78 K.
Development of field emission displays
Authors: Itoh Shigeo , Tanaka Mitsuru , Tonegawa Takeshi
Published: July 2004

Field emission displays (FED) are drawing attention as one of the most promising flat panel displays. Currently, the development stage of Spindt-type FEDs with Mo emitter is close to an end. The monocolor Spindt-type FEDs are being supplied to the market, and the color FEDs are ready for mass production. FED is also expected as a low power consumed display device, because the power, in principle, is consuming at the light emitting part only. The present status of FEDs with Spindt type and nanocarbon emitters are reported in this article.
Fresnel diffraction mask for focus monitoring
Authors: Yuito Takashi , Watanabe Hisashi
Published: July 2004

A focus monitoring method has been developed by using oblique propagation of a light beam and a binary mask. Oblique propagation of the light intensity was generated by using the main space pattern and asymmetric assist patterns. This method achieves a sensitive focus monitoring with a binary mask instead of a phase shift mask. The Fresnel diffraction image of asymmetric space patterns is formed near the mask and is reconstructed on the wafer with a projection lens at the defocus condition. We can obtain the focal value by measuring the lateral position shift of the Fresnel diffraction image. To measure the lateral pattern shift efficiently, we use bar-in-bar marks, which consist of asymmetric space patterns because the relative displacement of the inner and outer bars can be measured with a commercially available overlay measurement system.
Correlation between nanostructure and electron emission characteristics of a ballistic electron surface-emitting device
Authors: Ichihara Tsutomu , Baba Toru , Komoda Takuya , Koshida Nobuyoshi
Published: July 2004

The mechanism of ballistic electron emission from nanocrystalline silicon diodes has been studied for nanocrystallized polysilicon (NPS) based devices. The electron emission characteristics of two devices with NPS layers prepared under different conditions are compared in relation to the nanostructural analyses by transmission electron microscope (TEM) and energy-dispersive x-ray microanalyzer (EDX). In the sample where a chainlike nanocrystalline silicon (nc-Si) structure is produced along columnar poly-Si grains, a sufficient electron emission current density of 3.0 mA/cm2 was observed with a high emission efficiency (2.8%) and stability. The surface and interfacial oxidation of nc-Si particles is another important factor for efficient emission. The results indicate that control of interconnected nc-Si structures is a key issue for the efficient ballistic electron emission.
Growth and characterization of compressive-strain GaInAsP/InP multiple-quantum-well laser diodes with the tensile-strain GaInP quantum barrier
Authors: Wu Ming-Yuan , Lei Po-Hsun , Tsai Chia-Lung , Yang Chi-Da , Huang Yin-Hsun , Ho Wen-Jeng , Wu Meng-Chyi
Published: July 2004

In this article, we report on the growth of 1.3-μm-compressive-strain GaInAsP/InP multiple-quantum-well laser diodes (CS-MQW LDs) with a tensile-strain GaInP quantum barrier (GaInP-QB) in the separate-confinement-heterostructure (SCH) regions. Observed via the photoluminescence (PL) spectra, the optimum Ga composition of GaxIn1−xP-QB, GaInP-QB thickness, and pair number of the GaxIn1−xP-QB are 0.09, 5 nm thick and one pair, respectively. The optimum GaInP-QB structure in the p-side SCH region exhibits the narrowest PL full width at half maximum of 43.1 meV, the lowest threshold current of 23 mA, and the highest characteristic temperature of 52 K for the as-cleaved LDs with a 600-μm-cavity length and a 3.5-μm-wide ridge stripe. This low threshold current is better than that of the LDs with GaInP-QB in the n-side SCH region and that of the conventional LDs without GaInP-QB.
Double-gate field emitters with planar carbon-nanoparticle cathodes: Simulation studies
Authors: Bae Sungil , Seo Woo Jong , Choi Seungho , Lee Soonil , Koh Ken Ha
Published: July 2004

Simulation studies for the field electron emission from double-gate emitters with planar cathodes were carried out using the finite-element method, the Fowler–Nordheim field-emission equation, and the equation of motion for electrons. We systematically investigated radial position dependence of electric field, radial distribution of emission current, and trajectories of emitted electrons for various double-gate geometries and bias configurations. In particular, we studied the simplest operation mode of double-gate emitters, grounding both the cathode and the second gate adjacent to it, and the dependence of emission-electron focusing on the vertical position and the negative biasing of the second gate in detail. The flexibility in double-gate-emitter operation due to the separate control of electron emission and focusing was also discussed.
Investigation of Ge profile on SiGe islands by scanning photoelectron microscopy
Authors: Cho M.-H. , Cho Y. J. , Lee M. K. , Park S. A. , Roh Y. S. , Kim Y. K. , Jeong K. , Kang S. K. , Ko D.-H. , Shin H. J. , Kwon K. W.
Published: July 2004

The effect of annealing on SiGe films was investigated using scanning photoelectron spectroscopy (SPEM). Films annealed at a temperature above 950 °C in N2 ambient show a drastic morphological change. The difference in the chemical state between an islandlike surface and flat surface is dependent on the Si and Ge contents. In addition, the chemical state of the flat surface is closely related to differences in Si and Ge content, resulting in a donutlike shape. The oxidation of Ge is suppressed during the annealing process because of the lower heat of formation of GeO2 than for SiO2. Thus, differences in content and the extent of oxidation are major determinants of the chemical state in the islandlike shape. The characteristic donutlike shape reflects kinetic changes in the SiGe content during the annealing process.
Incorporation efficiency of carbon in GaAs using carbon tetrabromide in solid source molecular beam epitaxy
Authors: Sun Z. Z. , Yoon S. F. , Tan K. H. , Zhang R. , Jiang J.
Published: July 2004

The incorporation efficiency of carbon in GaAs using carbon tetrabromide (CBr4) was studied. A series of carbon-doped GaAs samples were grown at different CBr4 pressures and V/III ratios using solid source molecular beam epitaxy (SSMBE). The results showed a high carbon incorporation efficiency of ∼30% within the CBr4 pressure range up to 2×10−7 Torr, which resulted in carbon doping concentration of up to 2×1020 cm−3. However, an increase in V/III ratio was found to reduce the carbon incorporation efficiency. Based on our experimental results, a kinetic model was developed to explain the effect of carbon incorporation in GaAs from CBr4 in SSMBE growth. The model incorporates the effects of different CBr4 decomposition rates on the As-covered and Ga-covered surface.
Conduction and trapping mechanisms in SiO2 films grown near room temperature by multipolar electron cyclotron resonance plasma enhanced chemical vapor deposition
Authors: Isai Gratiela I. , Holleman Jisk , Wallinga Hans , Woerlee Pierre H.
Published: July 2004

Silicon dioxide layers with stoichiometric composition and excellent electrical properties were deposited at a substrate temperature of 60 °C with an electron cyclotron resonance plasma source. This work is focused on determining the electrical conduction and trapping mechanisms of the deposited films. From the temperature dependence of current density–electric field characteristics, Fowler–Nordheim tunneling was found to be the dominant conduction mechanism in SiO2 films obtained with low silane flow and at low pressure. For layers deposited with higher silane flows and higher pressures, the current at low biases is highly dependent on temperature. Positive charge was measured at the Si/SiO2 interface during low electric stress, while electrons were trapped at the interface for electric fields higher than 7 MV/cm. Constant current stress measurements confirmed that low silane flow and low total pressure are suitable deposition conditions for obtaining a film comparable to thermally grown oxide from the reliability point of view.
Planar metal–insulator–semiconductor type field emitter fabricated on an epitaxial Al/Al2O3/Si (111) structure
Authors: Kim Jang-Seop , Hoshi Tomohiro , Sawada Kazuaki , Ishida Makoto
Published: July 2004

A planar metal–insulator–semiconductor (MIS)-type field emitter using epitaxial γ-Al2O3 (111)/Si (111) structure was successively fabricated and field-emission phenomena were observed. Planar MIS-type field emitters using epitaxially grown Al2O3 were fabricated by molecular beam epitaxy (MBE) method and characteristics of these emitters were evaluated. It was confirmed that the Al2O3 possessed good crystalline quality and surface morphology. The breakdown field of the epitaxial Al2O3 layer was able to increase in situ annealing at the substrate temperature of 750 °C. From experimental measurements of diode current, conduction band offset (ΔEc) value between the epitaxial γ-Al2O3 and Si (111) substrate was calculated to be 2.5 eV. Fowler–Nordheim (F–N) tunneling was observed from the 8-nm-thick epitaxial Al2O3 film. Emission characteristics were obtained from the 10-nm-thick epitaxial Al2O3 insulator with a 20-nm-thick Al gate electrode. The maximum transfer ratio of emission current was confirmed to be 1%.
Field-emission characteristics from carbon nanotube field emitter arrays grown on silicon emitters
Authors: Yoshimoto Tomomi , Kamimaru Dai , Iwasaki Hideo , Iwata Tatsuo , Matsumoto Kazuhiko
Published: July 2004

The fluctuation of the emission current from carbon nanotube field emitter arrays (CNT FEAs) grown on silicon emitters was investigated as a function of total emission current and ambient pressure. The ratio of amplitude of short-term fluctuation ΔI and average emission current Iave strongly depended on Iave. The relationship ΔI/Iave∝Iave−1/2 was found. This relationship showed that the average emission current Iave is proportional to the number of active carbon nanotube emitters. The effect of vacuum pressure on the emission properties was examined by adjusting the pumping speed of the turbomolecular pump. The emission current at fixed voltage was affected by the adsorption of gas species and amounts.
Polarization control of vertical cavity surface emitting laser structure by using self-organized quantum wires grown on (775)B-oriented GaAs substrate by molecular beam epitaxy
Authors: Ohno Yasuhide , Shimomura Satoshi , Hiyamizu Satoshi , Takasuka Yasuyuki , Ogura Mutsuo , Komori Kazuhiro
Published: July 2004

Vertical cavity surface emitting laser (VCSEL) structures with self-organized InGaAs quantum wires (QWRs) in their active region were grown on (775)B-oriented GaAs substrate by molecular beam epitaxy. The (775)B self-organized InGaAs QWRs have a regularly corrugated AlAs-on-InGaAs upper interface with average lateral period of 40 nm and vertical amplitude of 1.5 nm and a flat InGaAs-on-AlAs lower interface. The (775)B VCSEL structure was optically pumped and showed room temperature lasing action for wavelength of around 830 nm. The light output was linearly polarized and the polarization direction was fixed to the QWR direction. This is the first demonstration of polarization control of VCSELs by self-organized QWRs in their active region.
Alkylation of nanoporous silica thin films by high density plasma chemical vapor deposition of a-SiC:H
Authors: Pan F. M. , Wu B. W. , Cho A. T. , Tsai K. C. , Tsai T. G. , Chao K. J. , Chen J. Y. , Chang L.
Published: July 2004

Film stacks of a-SiC:H and molecularly templated nanoporous silica thin films have been prepared, and alkylation of pore surfaces of the nanoporous silica layer by the a-SiC:H layer was studied. The a-SiC:H thin films were deposited by high-density plasma chemical vapor deposition (HDP-CVD) using trimethylsilane (3MS) as the precursor. Carbon is found to uniformly distribute in the thin nanoporous silica film, and the carbon content in the nanoporous film decreases with increasing the a-SiC:H deposition temperature. We used the modified Sanderson formalism to estimate the corresponding Si(2p) and C(1s) electron energies in x-ray photoelectron spectra (XPS) for possible terminal species on pore surfaces in the nanoporous silica layer. According to the XPS analysis and thermal desorption mass spectroscopy, the terminal species are probably in the chemical form of alkoxyl structures. The alkoxyl terminal groups introduced into the nanoporous silica thin film are believed to stem from hydrocarbons trapped in microvoids in the a-SiC:H film, which are formed during the HDP-CVD deposition. The terminal alkoxyl groups in the nanoporous silica layer can greatly enhance the hydrophobicity of the nanoporous silica dielectric, and hence improve the dielectric property of the film stack of a-SiC:H/nanoporous silica. An effective dielectric constant smaller than 1.7 can be obtained for the film stacks.
Development of an advanced high efficiency electro-emission device
Authors: Sakemura Kazuto , Negishi Nobuyasu , Yamada Takashi , Satoh Hideo , Watanabe Atsushi , Yoshikawa Takamasa , Ogasawara Kiyohide , Koshida Nobuyoshi
Published: July 2004

In this article, we describe the improvement in cold emission characteristics of a device termed HEED (high efficiency electro-emission device) by optimizing the emission site structures. The advanced HEED consists of a bottom electrode, a Si layer, a SiOx layer, a top electrode, and a carbon layer. The electron emission properties were significantly improved by appropriately arranging emission sites of “dimplelike” forms with a diameter of 1 μm on the device surface. The applied voltage was significantly lowered to 20 V (1/5 of that in the previously reported HEED), and a high emission current density of 1.8 mA/cm2 was obtained at a applied voltage of 20 V with an electron emission efficiency of 1% under a pulse operation. The energy distribution measurement of emitted electrons showed that the device emits considerably high-energy electrons as compared with conventional field emitters. Using this emitter as an excitation source, a 4 in. prototype flat display panel has been fabricated with a vacuum spacing of 9 mm between glass substrates. The panel operates well at a practical brightness of 2000 cd/m2.
Molecular beam epitaxial growth of mid-infrared InGaAsSb laser diodes on indium-free GaSb substrates
Authors: Pei C. W. , Héroux J. B. , Wang W. I.
Published: July 2004

It was experimentally observed that the presence of indium solder between the backside of GaSb substrates and the molybdenum block has a significant effect on the molecular beam epitaxial (MBE) growth of antimony compounds. X-ray diffraction and photoluminescence characterization results show that material quality was substantially improved when a custom-made substrate holder with which to avoid indium solder between GaSb substrate and molybdenum block for mounting was used. Strain compensated InGaAsSb/AlGaAsSb laser diode devices were grown by MBE. A 2.82 μm emission wavelength and a 660 A/cm2 threshold current density were obtained in the pulsed mode at room temperature.