bluuebunny/crossref_metadata_2025 huggingface dataset:
A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee
Authors: Bentley G. , Biant L. C. , Carrington R. W. J. , Akmal M. , Goldberg A. , Williams A. M. , Skinner J. A. , Pringle J.
Published: March 2003

Autologous chondrocyte implantation (ACI) and mosaicplasty are both claimed to be successful for the repair of defects of the articular cartilage of the knee but there has been no comparative study of the two methods. A total of 100 patients with a mean age of 31.3 years (16 to 49) and with a symptomatic lesion of the articular cartilage in the knee which was suitable for cartilage repair was randomised to undergo either ACI or mosaicplasty; 58 patients had ACI and 42 mosaicplasty. Most lesions were post-traumatic and the mean size of the defect was 4.66 cm2. The mean duration of symptoms was 7.2 years and the mean number of previous operations, excluding arthroscopy, was 1.5. The mean follow-up was 19 months (12 to 26).

Functional assessment using the modified Cincinatti and Stanmore scores and objective clinical assessment showed that 88% had excellent or good results after ACI compared with 69% after mosaicplasty. Arthroscopy at one year demonstrated excellent or good repairs in 82% after ACI and in 34% after mosaicplasty. All five patellar mosaicplasties failed.

Our prospective, randomised, clinical trial has shown significant superiority of ACI over mosaicplasty for the repair of articular defects in the knee. The results for ACI are comparable with those in other studies, but those for mosaicplasty suggest that its continued use is of dubious value.
Enhancing Treatment of Bipolar Disorder Using the Patient's Belief System
Authors: Makela Eugene H , Griffith Robert K
Published: March 2003

OBJECTIVE:

To report a patient with bipolar disorder in whom elements of the patient's belief system were used to foster acceptance of medication treatment.

CASE SUMMARY:

A 21-year-old white man with bipolar disorder began refusing prescribed divalproex sodium treatment. On consultation, the psychiatric pharmacist identified key elements of the patient's belief system and used this information in developing a plan to foster patient acceptance of lithium carbonate treatment.

DISCUSSION:

Noncompliance with treatment for bipolar disorder is common, and reluctance to accept initial pharmacotherapeutic intervention often occurs. There are many possible reasons for this phenomenon. Patients may not believe in pharmacotherapy and/or in its benefit, fear adverse reactions, or deny that they are ill. We report a patient in denial of his illness and believing that divalproex sodium was causing adverse effects. A psychiatric pharmacist consultant identified certain patient beliefs that were ultimately important in developing a treatment plan that was acceptable to the patient. The consultant, accompanied by a colleague, used persuasive technique in proposing treatment with the natural product lithium. The patient was discharged within 1 week of accepting the lithium therapy.

CONCLUSIONS:

When a patient refuses to accept needed treatment, it is important to carefully examine the reasons for this refusal, focusing on the patient's beliefs about the illness and the therapy. Intervention strategies can be developed, using this information, to foster treatment adherence and produce positive outcomes.
Meperidine Misuse in a Patient with Sphincter of Oddi Dysfunction
Authors: Hubbard Garrick P , Wolfe Kelly R
Published: March 2003

OBJECTIVE:

To report a seizure occurring secondary to meperidine treatment despite normal renal and central nervous system (CNS) function, and to provide a review of meperidine's role in pain management, including its use in pancreatitis and sphincter of Oddi dysfunction.

CASE SUMMARY:

A 55-year-old white woman with a history of sphincter of Oddi dysfunction presented to the emergency department with severe abdominal pain. On admission to the hospital, the serum creatinine level was 0.6 mg/dL with slightly elevated aspartate aminotransferase of 56 U/L (normal range 0–31) and alanine aminotransferase of 34 U/L (0–31). The patient received repeated and escalating doses of intravenous meperidine, resulting in a generalized seizure on day 4 of hospitalization. The accumulated meperidine dose was 2125 mg. Buprenorphine was substituted in place of meperidine, and the patient had no further reported complications. She was then transferred to a tertiary-care facility for sphincter of Oddi reevaluation. An objective causality assessment revealed the adverse drug event as probable.

DISCUSSION:

Despite alternative opioids, meperidine continues to be used in pain management. Meperidine is different from other opioids because its active metabolite, normeperidine, is neurotoxic. Patients with renal insufficiency, liver failure, or CNS dysfunction are at increased risk for adverse drug reactions related to normeperidine accumulation. Due to normeperidine's extended half-life, however, accumulation of normeperidine can occur in any patient receiving repeated doses of meperidine.

CONCLUSIONS:

This case demonstrates the potential hazards that exist when using meperidine in any patient. Meperidine's inherent risks of both undertreating pain and causing adverse drug reactions should prompt clinicians and health organizations to restrict its use in pain management. This restriction should not make exceptions to meperidine's traditional use in pancreatitis or sphincter of Oddi dysfunction.
Rhabdomyolysis and Acute Renal Failure following an Ethanol and Diphenhydramine Overdose
Authors: Haas Curtis E , Magram Yanina , Mishra Archana
Published: March 2003

OBJECTIVE:

To report a case of nontraumatic rhabdomyolysis complicated by oliguric, acute renal failure following an intentional overdose of ethanol and diphenhydramine.

CASE SUMMARY:

A 21-year-old white man was admitted through the emergency department following an intentional overdose of ethanol and diphenhydramine. The patient subsequently developed acute renal failure, and a diagnosis of nontraumatic rhabdomyolysis was made. With the absence of other common causes in this case, the rhabdomyolysis was believed to be due to the combined ethanol and diphenhydramine overdose.

DISCUSSION:

Rhabdomyolysis is a severe and life-threatening syndrome caused by various insults to skeletal muscle, including drug-induced injury. Early detection and institution of effective treatments are essential to minimizing the complications of this syndrome. A delay in establishing the diagnosis in this case likely contributed to the severity of the renal failure.

CONCLUSIONS:

Nontraumatic rhabdomyolysis is an uncommon adverse outcome of drug and toxin ingestion. Due to the potential severity of the complications of this syndrome and the importance of early recognition and treatment to prevent renal failure, clinicians should have a high index of suspicion for rhabdomyolysis following overdoses that involve alcohol or antihistamines.
Testosterone Replacement Therapy for Bone Loss Prevention in HIV-Infected Males
Authors: Clay Patrick G , Lam Amy I
Published: March 2003

OBJECTIVE:

To review the use of testosterone for the prevention of bone loss in men with HIV infection.

DATA SOURCES:

A MEDLINE search (1966–May 2002) on the use of testosterone in osteoporosis/HIV infection was performed. A reference bibliography search was also completed.

DATA SYNTHESIS:

Osteopenia/osteoporosis is reported in HIV-infected men due to a myriad of factors. Sex hormone deficiency is a frequent endocrine abnormality in this population.

CONCLUSIONS:

In HIV-negative men, testosterone may be beneficial for preventing bone loss and hastening the resolution of fractures. Testosterone's role in preventing bone loss in HIV-infected men remains to be defined.
Lecture versus Web Tutorial for Pharmacy Students' Learning of MDI Technique
Authors: Erickson Steven R , Chang Amy , Johnson Cary E , Gruppen Larry D
Published: March 2003

OBJECTIVE:

To compare pharmacy students' acquired knowledge and ability to assess metered-dose inhaler (MDI) technique after a traditional lecture versus a Web-based MDI technique tutorial.

METHODS:

All 42 third-year PharmD students completed a baseline MDI technique knowledge test and were then randomized into 1 of 3 groups. The Web group completed the tutorial on the college dispensing laboratory computers; the lecture group participated in the MDI technique excerpt of the asthma therapeutics lecture; and the control group participated in a 15-minute discussion of participants' hobbies. Afterward, participants in each group completed an identical MDI technique knowledge posttest. Students then observed a standardized mock patient perform MDI technique, documenting steps that were conducted incorrectly. MDI technique knowledge test and MDI technique evaluation test scores were compared between groups using repeated measures ANOVA.

RESULTS:

There was no significant difference in the baseline MDI technique knowledge test scores between groups. The post-MDI technique knowledge test scores for the Web and lecture groups did not differ significantly (p = 0.38), and both were significantly different from the control group (p < 0.001). MDI technique knowledge scores increased significantly for the Web and lecture groups from pre- to post-assessment, but did not change for the control group. A 2-way repeated measures ANOVA analysis demonstrated no significant interaction of subject and group characteristics. The MDI technique evaluation scores for the Web and lecture groups were not significantly different (p = 0.50), and both were significantly different from the control group (p ≤ 0.001).

CONCLUSIONS:

The Web-based MDI technique tutorial was as effective as the standard lecture format in pharmacy students acquiring knowledge of MDI technique and in evaluating a mock-patient exhibiting incorrect MDI technique. Further testing is required to assess the longitudinal effect of the program.
Cover Picture: A Powerful Combinatorial Screen to Identify High‐Affinity Terbium(III)‐Binding Peptides (ChemBioChem 4/2003)
Authors: Nitz Mark , Franz Katherine J. , Maglathlin Rebecca L. , Imperiali Barbara
Published: March 2003

The cover picture shows the chemistry and biology used to develop a new protein labeling strategy based on lanthanide‐binding peptides. Focused peptide libraries are screened to identify oligopeptide motifs of dual function: the peptides bind TbIII with remarkably high affinity and promote intense TbIII luminescence. The peptide sequences are then genetically encoded to create recombinant fusion proteins that possess a site‐specific and minimally invasive fluorophore. Further information can be found in the two articles by Imperiali and co‐workers on pp. 265–271 and pp. 272–276.
Lanthanide‐Binding Tags as Versatile Protein Coexpression Probes
Authors: Franz Katherine J. , Nitz Mark , Imperiali Barbara
Published: March 2003

Comprehensive proteomic analyses require new methodologies to accelerate the correlation of gene sequence with protein function. Key tools for such efforts include biophysical probes that integrate into the covalent architecture of proteins. Lanthanide‐binding tags (LBTs) are expressible, multitasking fusion partners that are optimized to bind lanthanide ions and have several desirable attributes, which include long‐lived luminescence, excellent X‐ray scattering power for phase determination, and magnetic properties to facilitate NMR spectroscopic structure elucidation. Herein, we present peptide sequences with a 40‐fold higher affinity for Tb3+ ions and significantly brighter luminescence intensity compared with existing peptides. Incorporation of an LBT onto ubiquitin as a prototype fusion protein allows the use of powerful protein‐visualization techniques, which include rapid luminescence detection of LBT‐tagged proteins in SDS‐PAGE gels, as well as determination of protein concentrations in complex mixtures. The LBT strategy is a new alternative for expressing fluorescent fusion proteins by routine molecular biological techniques.
On the Generation of Catalytic Antibodies by Transition State Analogues
Authors: Barbany Montserrat , Gutiérrez‐de‐Terán Hugo , Sanz Ferran , Villà‐Freixa Jordi , Warshel Arieh
Published: March 2003

The effective design of catalytic antibodies represents a major conceptual and practical challenge. It is implicitly assumed that a proper transition state analogue (TSA) can elicit a catalytic antibody (CA) that will catalyze the given reaction in a similar way to an enzyme that would evolve (or was evolved) to catalyze this reaction. However, in most cases it was found that the TSA used produced CAs with relatively low rate enhancement as compared to the corresponding enzymes, when these exist. The present work explores the origin of this problem, by developing two approaches that examine the similarity of the TSA and the corresponding transition state (TS). These analyses are used to assess the proficiency of the CA generated by the given TSA. Both approaches focus on electrostatic effects that have been found to play a major role in enzymatic reactions. The first method uses molecular interaction potentials to look for the similarity between the TSA and the TS and, in principle, to help in designing new haptens by using 3D quantitative struture–activity relationships. The second and more quantitative approach generates a grid of Langevin dipoles, which are polarized by the TSA, and then uses the grid to bind the TS. Comparison of the resulting binding energy with the binding energy of the TS to the grid that was polarized by the TS provides an estimate of the proficiency of the given CA. Our methods are used in examining the origin of the difference between the catalytic power of the 1F7 CA and chorismate mutase. It is demonstrated that the relatively small changes in charge and structure between the TS and TSA are sufficient to account for the difference in proficiency between the CA and the enzyme. Apparently the environment that was preorganized to stabilize the TSA charge distribution does not provide a sufficient stabilization to the TS. The general implications of our findings and the difficulties in designing a perfect TSA are discussed. Finally, the possible use of our approach in screening for an optimal TSA is pointed out.
Nuclear Localisation Sequence Templated Nonviral Gene Delivery Vectors: Investigation of Intracellular Trafficking Events of LMD and LD Vector Systems
Authors: Keller Michael , Harbottle Richard P. , Perouzel Eric , Colin Morvane , Shah Imran , Rahim Ahad , Vaysse Laurence , Bergau Anna , Moritz Sylviane , Brahimi‐Horn Christiane , Coutelle Charles , Miller Andrew D.
Published: March 2003

The impact of a peptide that contains a nuclear localisation sequence (NLS) on intracellular DNA trafficking was studied. We used the adenoviral core peptide mu and an SV40 NLS peptide to condense plasmid DNA (pDNA) prior to formulation with 3β‐[N‐(N′, N′‐dimethylaminoethane)carbamoyl]cholesterol/dioleoyl‐L‐α‐phosphatidyl ethanolamine (DC‐Chol/DOPE) liposomes to give LMD and LND vectors, respectively. Fluorescent‐labelled lipid and peptides plus dye‐labelled pDNA components were used to investigate gene delivery in dividing and S‐phase growth‐arrested cells. Confocal microscopic analyses reveal little difference in intracellular trafficking events. Strikingly, mu peptide associates with nuclei and nucleoli of cells within less than 15 mins incubation of LMD with cells, which suggests that mu peptide has an NLS function. These NLS properties were confirmed by cloning of a mu‐β‐galactosidase fusion protein that localises in the nuclei of cells after cytosolic translation. In dividing cells both LMD and LND deliver pDNA(Cy3) to nuclei within 30–45 min incubation with cells. By contrast, pDNA is detected only in the cytoplasm in growth‐arrested cells over the period of time investigated, and not in the nuclei. LD systems prepared from DC‐Chol/DOPE cationic liposomes and pDNA(Cy3) behave similarly to LMD systems, which suggests that mu peptide is unable to influence trafficking events in this current LMD formulation, in spite of its strong NLS capacity. We further describe the effect of polyethyleneglycol (PEG) on cellular uptake. “Stealth” systems obtained by post‐coating LMD particles with fluorescent‐labelled PEG molecules (0.5, 5 and 10 mol % fluorescein‐PEG5000‐N‐hydroxysuccinimide) were prepared and shown to be internalised rapidly (mins) by cells, without detectable transgene expression. This result indicates that PEG blocks intracellular trafficking of pDNA.
Solitary fibrous tumor of the thyroid: Cytopathologic findings and differential diagnosis
Authors: Parwani Anil V. , Galindo Rene , Steinberg David M. , Zeiger Martha A. , Westra William H. , Ali Syed Z.
Published: March 2003

Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm that arises primarily from the pleura. Extrapleural occurrences are rare. To our knowledge, there is no published account of this entity in the thyroid in the cytopathology literature. We report the case of a 61‐yr‐old man who was evaluated at The Johns Hopkins Hospital for a slow‐growing thyroid mass that was present for 2 yr despite thyroid hormone suppression. Thyroid‐stimulating hormone (TSH) was within normal limits. The patient underwent ultrasound‐guided fine‐needle aspiration (FNA), which showed predominantly discohesive slender spindle‐shaped cells and fragments of collagenized stromal tissue. After the FNA diagnosis of “thyroid neoplasm” was made, the patient underwent a near‐total thyroidectomy, which revealed a SFT. Differential diagnosis of spindle cell lesions in thyroid is also presented. Diagn. Cytopathol. 2003;28:213–216. © 2003 Wiley‐Liss, Inc.
Endoscopic bile duct brushing of malignant pancreatic biliary strictures: Retrospective study with comparison of conventional smear and ThinPrep® techniques
Authors: Ylagan Lourdes R. , Liu Lucy H. , Maluf Horacio M.
Published: March 2003

Endoscopic bile duct brushing (EBDB) is carried out to differentiate benign from malignant biliary strictures in patients who have pancreaticobiliary disease. The sensitivity of this method for the diagnosis of malignancy is relatively low. The aim of this study is to analyze the cytomorphologic features that are helpful in increasing the sensitivity of detecting these lesions on cytologic samples. These features are compared with slides prepared with the ThinPrep® technique. The study included 142 patients with bile duct obstruction or pancreatic mass who underwent EBDB and follow‐up surgery or biopsy between 1997 to 2000. Twenty‐five (18%) of these cases were positive for malignancy in both EBDB and follow‐up surgical biopsy; 20 of these cases were used as positive controls (PC). Sixty‐one (43%) were negative in both EBDB and follow‐up surgical biopsy specimens, and 21 of those cases were used as negative controls (NC). Fifty‐six (39%) cases were negative/atypical in EBDB cytology but were suspicious or positive in the surgical or biopsy specimens (false‐negative). We identified the cytologic criteria that were helpful in differentiating our positive and negative control groups and applied these criteria to our false‐negative group to see whether our sensitivity could be increased, using well‐defined cytologic criteria alone. Of the 56 false‐negative cases, 9 (16%) were upgraded to suspicious/positive based on the presence of the following features: three‐dimensional (3D) micropapillae (95% PC vs 19% NC, P < 0.0001), anisonucleosis (90% PC vs 5% NC, P < 0.0001), high nuclear‐to‐cytoplasmic (N/C) ratio (95% PC vs 9% NC, P < 0.0001), nuclear contour irregularity (65% PC vs 24% NC, P = 0.0079), and prominent nucleoli (70% PC vs 38% NC, P = 0.0406). Cytomorphologic features which were not helpful in distinguishing positive and negative cases were: single naked nuclei (50% PC vs 28% NC, P = 0.1597), chromatin granularity (50% PC vs 62% NC, P = 0.54), and necrosis (10% PC vs 5% NC, P = 0.5197). Improvement in diagnostic sensitivity for carcinoma of pancreaticobiliary tract in EBDB samples may be achieved by identifying the key malignant cytomorphologic features: 3D micropapillae, anisonucleosis, nuclear contour irregularity, prominent nucleoli, and high N/C ratio. The sensitivity in detecting malignant biliary strictures increased from 31% to 42% based on these criteria in our current study. Diagn. Cytopathol. 2003;28:196–204. © 2003 Wiley‐Liss, Inc.
Pharmacology, toxicology, and radiation dosimetry evaluation of [123I]5‐I‐A‐85380, a radioligand for in vivo imaging of cerebral neuronal nicotinic acetylcholine receptors in humans
Authors: Vaupel D. Bruce , Tella Srihari R. , Huso David L. , Mukhin Alexey G. , Baum Ira , Wagner Valentine O. , Horti Andrew G. , London Edythe D. , Koren Andrei O. , Kimes Alane S.
Published: March 2003

[123I]5‐I‐A‐85380, which selectively binds to α4β2 nicotinic acetylcholine receptors, may be a suitable single photon emission computed tomography (SPECT) ligand for imaging nicotinic receptors in the human brain. In a mutagenicity study, 5‐I‐A‐85380 produced positive effects in one of five bacterial strains in the bacterial reverse mutation assay only with metabolic activation. The ED50 for 5‐I‐A‐85380 to elicit tonic‐clonic convulsions in mice, 7.1 µmol/kg, i.v., was five times that of nicotine (ED50=1.4 µmol/kg, i.v.). A 2‐day acute toxicity study (0.03–150 nmol/kg, i.v.) and a 14‐day chronic toxicity study (0.3–30 nmol/kg, s.c.) in mice revealed no evidence of gross pathology or histopathological changes. Biodistribution and dosimetry studies revealed that the urinary bladder wall and the thyroid gland were the critical organs with respect to radiation exposure. In unanesthetized rats, 5‐I‐A‐85380 (5.2–174 nmol/kg, i.v.) and nicotine (20–400 nmol/kg, i.v.) produced similar increases in systolic and diastolic blood pressure, heart rate, and locomotor activity. Doses of 5‐I‐A‐85380 that elevated blood pressure and heart rate by 10% ranged from 5–10 nmol/kg, i.v. The highest doses tested, which produced near maximal increases in blood pressure and heart rate, did not affect the PR, QRS, or QTc intervals of the electrocardiogram. Based on these preclinical data, initial SPECT imaging studies in humans (Fujita et al. [2002] Eur J Nucl Med 29:183–190) used a mass dose of 8.6 pmol/kg [123I]5‐I‐A‐8380, estimated to be 1/580th of the dose that elevates blood pressure and heart rate by 10%. Importantly, no clinical pharmacological effects were observed. Drug Dev. Res. 58:149–168, 2003. Published 2003 Wiley‐Liss, Inc.
Solubilized candida cell Wall β‐glucan, CSBG, is an epitope of natural human antibody
Authors: Masuzawa Shinya , Yoshida Masaharu , Ishibashi Ken‐ichi , Saito Nakaya , Akashi Masakazu , Yoshikawa Noriko , Suzuki Tatsuya , Nameda Sachiko , Miura Noriko N. , Adachi Yoshiyuki , Ohno Naohito
Published: March 2003

We have recently developed a protocol to obtain a soluble Candida spp. β1, 3‐glucan (CSBG) by sodium hypochlorite (NaClO) oxidation and subsequent dimethyl sulfoxide (DMSO) extraction. CSBG is composed mainly of β‐1,3 and β‐1,6‐glucosidic linkages with a small amount of branching. Antibody to β‐glucan is generally difficult to produce. In the present study, the specificity of the human sera to CSBG was examined by ELISA. Using CSBG‐coated plates, sera from normal human volunteers showed high reactivity that was neutralized by adding soluble CSBG as a competitor. However, the reactivity could not be neutralized by a β‐1,6 branched β‐1,3‐glucan, grifolan. Similar specificity of the immunoglobulin (Ig) was detected in commercially available γ‐globulin prepared from pooled human sera. Comparing various standard glucans, a major epitope was present on β‐1,6 glucan segment. Drug Dev. Res. 58:179–189, 2003. © 2003 Wiley‐Liss, Inc.
Antithrombotic effects of YM466, a synthesized direct inhibitor of factor Xa, in an arterio‐venous shunt thrombosis model in squirrel monkeys
Authors: Iwatsuki Yoshiyuki , Kaku Seiji , Moritani Yumiko , Taniuchi Yuta , Hirayama Fukushi , Koshio Hiroyuki , Matsumoto Yuzo , Mano Yuji , Kawasaki Tomihisa
Published: March 2003

The antithrombotic effects of YM466, a synthetic direct inhibitor of human factor Xa (FXa), were evaluated in an arterio‐venous shunt thrombosis model in squirrel monkeys. YM466 significantly inhibited thrombus formation after continuous IV zx infusion at doses of 3–30 µg/kg/h. Although prothrombin time (PT) was significantly prolonged at doses of 10 and 30 µg/kg/h, this effect was small (1.2‐ and 1.4‐fold of the control, respectively). Furthermore, YM466 had no effect on template bleeding time and activated partial thromboplastin time at any dose. Plasma anti‐FXa activity increased in a dose‐dependent manner correlating with the antithrombotic effect of YM466. Thrombin‐antithrombin III complex levels decreased to less than normal levels at 30 µg/kg/h of YM466. Mean plasma concentrations of YM466 measured by LC/MS/MS were 2.5, 10.5, 27.4, and 75.5 ng/ml at doses of 1, 3, 10, and 30 µg/kg/h, respectively. These results suggest that YM466 is a safe antithrombotic agent with low bleeding risk, and that plasma anti‐FXa activity may be a suitable parameter for monitoring its antithrombotic effect. Drug Dev. Res. 58:190–195, 2003. © 2003 Wiley‐Liss, Inc.
Mechanism of carvedilol‐induced block of delayed rectifier K+ current in the NG108‐15 neuronal cell line
Authors: Liu Chun‐Peng , Chiang Hung‐Ting , Jan Chung‐Ren , Wu Sheng‐Nan
Published: March 2003

The effects of the β‐adrenoceptor antagonist carvedilol on delayed rectifier K+ current (IK (DR)) were examined in NG108‐15 neuronal cells. Carvedilol (1–100µM) reversibly blocked IK (DR) with an IC50 value of 5 µM. IK (DR) in response to depolarizing pulses was sensitive to inhibition by quinidine or dendrotoxin, but not by iberiotoxin, 5‐hydroxydecanoate sodium, or linopiridine. The carvedilol‐induced inhibition of IK (DR) could not be reversed by further application of t‐butyl hydroperoxide or diazoxide. The inhibition of IK (DR) by carvedilol could still be observed in cells preincubated with t‐butyl hydroperoxide (1 mM), ruthenium red (30 µM), or carbonyl cyanide m‐chlorophenyl hydrazone (10 µM). The presence of carvedilol enhanced both the rate and extent of IK (DR) inactivation. Recovery from block by carvedilol (3 µM) could be fitted by a single exponential with a value of 1.64 s. Crossover of tail currents in the presence of carvedilol was also observed. Cell‐attached single‐channel recordings revealed that carvedilol suppressed channel activity without altering single‐channel amplitude. With the aid of the binding scheme, a quantitative description of the carvedilol actions on IK (DR) was also developed that clearly showed that in addition to being an antioxidative agent, carvedilol can block delayed rectifying K+ channel of neurons in an open‐ and state‐dependent manner. Drug Dev. Res. 58:196–208, 2003. © 2003 Wiley‐Liss, Inc.
Haptic intramodal comparison of texture in human neonates
Authors: Molina Michèle , Jouen François
Published: March 2003

We investigated neonates' capacity to haptically compare objects varying in texture property. Right‐hand manual activity, assessed by holding time and hand‐pressure frequency, was recorded for objects in the presence (test period) or absence (pretest and post‐test periods) of an object simultaneously held in the left hand. Thirty‐two babies were assigned to four experimental conditions according to the texture density of the object held in each hand: Objects had either the same (matching conditions) or different (non‐matching conditions) texture density. Although holding time decreased during test period in both conditions, hand‐pressure frequency changed according to the matching and non‐matching conditions. In the matching condition, hand‐pressure frequency of the right hand did not differ from hand‐pressure frequency of the left hand. In the non‐matching condition, hand‐pressure frequency recorded from the right hand was significantly higher than hand‐pressure frequency recorded from the left hand. These results point to neonates' capacity to compare information between simultaneously held objects. These results are interpreted in relation to existing data on the early capacity for intermodal exploration of objects. © 2003 Wiley‐Liss, Inc. Dev Psychobiol 42: 378–385, 2003.
Rat pups reduce ultrasonic vocalization after exposure to an adult male rat
Authors: Wiedenmayer Christoph P. , Lyo Donggon , Barr Gordon A.
Published: March 2003

We examined how the experience of a threatening stimulus alters subsequent behavior in a situation where the immediate threat is absent. A small huddle of 12‐day‐old rats was exposed to a potentially infanticidal adult male rat for 5 min. During male exposure, pups were significantly more immobile than control pups. Thirty, 60, and 180 min after male exposure, the pups were isolated for 5 min from litter and dam in an unfamiliar environment. When isolated, pups that had been previously exposed to the male emitted significantly fewer ultrasonic vocalizations than controls, but did not differ in immobility. Low levels of vocalization were apparent 30 and 60 min after male exposure and were not evident at 180 min. The pups seemed to have adjusted their behavior to a potential male threat in a different context for a limited period of time. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 42: 386–391, 2003.
A study of the flywheel capacity of the power compensator for the wind turbine generator
Authors: Nakamura Hirokazu , Koyanagi Akihiro , Suzuki Yasunori , Eguchi Naoya , Sato Yoshihisa , Shimada Ryuichi
Published: March 2003

Nowadays, the Wind Turbine Generator (WTG) system is remarkably increasing as a renewable energy resource in Japan. But in the WTG, the power fluctuations caused by the wind speed fluctuation are the most crucial issue in providing their energy to the utility. It was found that a power compensation system (PCS) of suitable capacity is not yet available. In this paper, the time range and standardized wind speed including fluctuations are discussed. We estimated the storage capacity of PCS at different wind profiles by standardization of wind speed and verified the validity of their capacities using a computer simulation. In this way we determined the suitable capacity of the power compensation system. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 64–71, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10122
Voltage stability preventive and emergency‐preventive control using VIPI sensitivity
Authors: Takehara Arisa , Tanaka Yoshiyuki , Iwamoto Shinichi
Published: March 2003

Recently, power systems have become larger and more complicated, and the rate of occurrence of constant power loads has increased. Under a situation like this, concerns about voltage instability phenomena have been raised. Therefore, in addition to the conventional local voltage control, the necessity of a global on‐line voltage control scheme has risen.

In this paper, we propose a method of on‐line voltage stability control including preventive and emergency‐preventive controls to retain voltage stability even if a severe fault occurs. According to the result of contingency analysis for severe faults, we consider operation of control equipment as preventive control. And in the case that the fault seems severe still after preventive control, we consider load curtailment as emergency‐preventive control. When we select the control equipment and loads to curtail, we use voltage stability index VIPI sensitivity. And we determine the amount of control and load curtailment using Optimal Power Flow calculation. The effectiveness of the proposed method is verified by simulations using a 28‐bus system. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 22–30, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10128
Proposal of a high‐performance solid oxide fuel cell combined power generation system with carbon dioxide recovery
Authors: Inui Yoshitaka , Yanagisawa Shin , Ishida Taichi
Published: March 2003

A new fossil‐fuel‐utilized high‐performance combined power generation system with liquefaction recovery of carbon dioxide is proposed. In the system, pure oxygen is used as the oxidant gas to prevent the mixture of nitrogen in the exhaust gas and to make the liquefaction recovery of carbon dioxide possible. Solid oxide fuel cell is selected as the topping cycle. The exhaust fuel gas of the solid oxide fuel cell is afterburned with its exhaust oxidant gas of pure oxygen and the heat of the combustion gas is utilized in the bottoming cycle. Nonequilibrium MHD/noble gas turbine cycle is selected as the bottoming cycle because the temperature of the combustion gas reaches about 2300 K. It is made clear through detailed examination of energy balance that the total thermal efficiency of the system using natural gas (methane) as the fuel reaches 63.24% (HHV) or 70.18% (LHV). This efficiency is very high as for the system with carbon dioxide recovery. The proposed system, therefore, has excellent performance, and further research and development is warranted. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 12–21, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10146
Facial identification system based on a high‐speed matching algorithm for isodensity lines
Authors: Hirano Teruaki , Ikeda Misuzu , Nakamura Osamu
Published: March 2003

In this paper, a high‐speed personal identification system which is adaptable for slant faces is presented.

In the proposed method, the 25 facial images which are taken with different angles are registered in the database as reference images. The similarity of an input image is first examined between all registered images and the three facial images, which are similar to the input image, are then extracted as the candidate facial images. The isodensity map, which is expected to have the maximum similarity to the input image, is created by the interpolation between two candidate images and the input facial image is judged identical or not with the interpolated images.

A template matching is adopted to obtain a similarity between two isodensity lines. In general, template matching requires a lot of time to obtain maximum similarity, while on the other hand it is very simple to use. To reduce the processing time for the matching efficiently, the techniques which are suited for the line pictures and the Sequential Similarity Detection Algorithm (SSDA) are adopted.

Computer simulation using 50 people shows an accuracy of 95.2% correct discrimination. In addition, processing time is reduced to approximately 1/12. From the experimental results, the prospects of using this method are very encouraging. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 31–41, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10147
A method of gene selection that decreases the number of fitness value calculations
Authors: Yamaguchi Satoshi , Itakura Hidekiyo
Published: March 2003

This paper proposes a new selection method of a gene from a population for reducing the number of fitness value calculations in genetic algorithms. The proposed method effectively reduces the computation time required to search for a solution to the optimization of a process involving a large number of such calculations as in robot behavior decisions and neural network learnings. In the proposed method, the use of a special buffer for storing a gene and its associated fitness value is introduced. The gene in the buffer is used as a candidate for the solution to the optimization problem. This gene is compared with a gene selected from the population, and one of the values is used in the next generation depending on the results of the comparison. The proportion of suitable genes in the population is increased in the possible shortest time. The convergence speed of our buffer depends on the population topology, which is introduced for choosing a gene from the population to compare with the buffer gene. Three kinds of topology are applied to our algorithm and they are compared and evaluated. The proposed method is applied to a robot control problem to demonstrate the validity of the technique. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 42–49, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10148
Rosmarinic acid inhibits TCR‐induced T cell activation and proliferation in an Lck‐dependent manner
Authors: Won Jonghwa , Hur Yun‐Gyoung , Hur Eun Mi , Park See‐Hyoung , Kang Mi‐Ae , Choi Youngbong , Park Changwon , Lee Keun‐Hyeung , Yun Yungdae
Published: March 2003

Lck is a T cell‐restricted Src family protein tyrosine kinase that plays pivotal roles in TCR‐mediated signaling. We aimed to identify novel agents that could disrupt the molecular interactionof the Src homology 2‐domain of Lck (Lck SH2) with its binding partners, with the expectation that this would impair TCR signaling and generate immunosuppression. Large‐scale screening of plant extracts indicated that rosmarinic acid (RosA) in extracts of Prunella vulgaris consistently inhibits the interaction between Lck SH2 and a peptide containing its consensus binding sequence (pYEEI). The inhibitory effect of RosA was specific for SH2 domains of Src family protein tyrosine kinase. RosA inhibited TCR‐induced‐Ca2+ mobilization and IL‐2 promoter activation but not phorbol 12‐myristate 13‐acetate/ionomycin‐induced IL‐2 promoter activation, indicating its point of inhibition at the membrane proximal site of TCR signaling. Furthermore, RosA inhibited TCR‐induced splenocyte proliferation as well as one‐way MLR at an IC50 of 25–50 μM and inhibited cytokine expression such as IL‐2 and IFN‐γ. Here, we first report RosA as an inhibitor of TCR‐signaling and subsequent T cell proliferation.
Activity of human monocytes in IgE antibody‐dependent surveillance and killing of ovarian tumor cells
Authors: Karagiannis Sophia N. , Wang Qin , East Nick , Burke Frances , Riffard Stephane , Bracher Marguerite G. , Thompson Richard G. , Durham Stephen R. , Schwartz Lawrence B. , Balkwill Frances R. , Gould Hannah J.
Published: March 2003

We have previously shown that a chimeric IgE antibody against the folic acid receptor (MOv18 IgE) inhibits tumor growth in a SCID mouse model of ovarian carcinoma. MOv18 IgE gave greater protection than the corresponding chimeric MOv18 IgG1. We have now confirmed these effects in a nude‐mouse model of ovarian carcinoma and have demonstrated for the first time that human monocytes are active in IgE antibody‐dependent cell‐mediated cytotoxicity. Injection of tumor‐bearing mice with PBMC and MOv18 IgE led to infiltration of monocytes into the tumors and prolonged survival of the mice.Incubation of PBMC or purified monocytes and MOv18 IgE with ovarian tumor cells in vitro resulted in tumor cell killing proportional to the expression of unoccupied FcϵRI on monocytes.We observed phagocytosis of tumor cells by the monocytes in vitro. Our results suggest that tumor‐specific IgE antibodies may be exploited for immunotherapy of cancer.
Signaling through HLA‐DR induces PKCβ‐dependent B cell death outside rafts
Authors: Guo Wenyan , Castaigne Jean‐Gabriel , Mooney Nuala , Charron Dominique , Al‐Daccak Reem
Published: March 2003

Signals through HLA‐DR molecules contribute to optimal activation of antigen‐presenting cells (APC) during T cell/APC interactions participating in the generation of productive interactions, and to the induction of APC death, which has been postulated to play a role in the termination of the immune response. To understand how these molecules accommodate both cellular responses, we studied the not yet well‐defined signaling events and the biochemical requirements for HLA‐DR‐mediated death. We demonstrate that in B cells the HLA‐DR‐activated protein kinase C (PKC) β is required for HLA‐DR‐mediated death whereas the HLA‐DR‐activated Src family of PTK is redundant. In contrast to HLA‐DR‐mediated activation of Src kinase Lyn, the aggregation of HLA‐DR molecules in lipid rafts is not required for HLA‐DR‐mediated PKCβ activation nor for the induction of cell death. Indeed, the bulk of HLA‐DR‐activated PKCβ reside outside rafts. This is the first report showing that HLA‐DR‐induced PKCβ activation is essential for the induction of B cell death via HLA‐DR, and that these HLA‐DR‐mediated events do not require the integrity of rafts.
The CD4‐related molecule, LAG‐3 (CD223), regulates the expansion of activated T cells
Authors: Workman Creg J. , Vignali Dario A. A.
Published: March 2003

The lymphocyte activation gene‐3 (LAG‐3, CD223) is a CD4‐related, activation‐induced cell surface molecule that binds to MHC class II with high affinity. The function of murine LAG‐3 on T cells is unclear. Here, we show that Vβ7/8+LAG‐3–/– T cells expand poorly following staphylococcal enterotoxin B (SEB) stimulation in vitro. LAG‐3–/– T cells proliferate at a normal rate, but exhibit increased cell death. Similar observations were made with LAG‐3–/–CD4+OT‐II TCR transgenic T cells following peptide stimulation. Despite reduced T cell expansion and increased cell death, LAG‐3–/–OT‐II+ T cells secrete more IL‐2 and IFN‐γ following stimulation. Antigen‐driven expansion of LAG‐3–/– T cells was restored by constitutive expression of LAG‐3 via retroviral‐mediated stem cell gene transfer. We further show that LAG‐3 function is mediated via its cytoplasmic domain, for which a conserved ‘KIEELE’ motif is essential. Our data support a role for LAG‐3 in regulating the expansion of activated T cells.
IL‐10 is crucial for the transition from acute to chronic disease state during infection of mice with Schistosoma mansoni
Authors: Sadler Clare H. , Rutitzky Laura I. , Stadecker Miguel J. , Wilson R. Alan
Published: March 2003

After infection of mice with Schistosoma mansoni, deposition of eggs in the walls of the intestine and liver provokes an intense (acute) T cell response that peaks at week 8 and, thereafter, down‐modulates as the disease becomes chronic. Egg antigen‐stimulated proliferation of mesenteric lymph node and spleen cells in vitro was intense at week 8 in both IL‐10–/– and wild‐type (WT) mice, while proliferative responses were markedly reduced at week 15 in WT mice, but undiminished in IL‐10–/– animals. Moreover, in the absence of IL‐10 production, levels of both IFN‐γ and IL‐4 remained elevated at week 15. Granulomas around eggs embolized in the livers of WT mice were significantly smaller at week 15 than week 8, whereas those in IL‐10–/ animals were larger at week 8, showed no reduction in size at week 15, and were less sharply demarcated by peripheral collagen. There was also a greater leukocytic infiltration and necrosis of the hepatic parenchyma. These data suggest that in mice IL‐10 regulates not only the intensity of hepatic inflammation, but also granuloma organization and cohesiveness. It is a crucial agent in the down‐modulation of immune responses and immunopathology that defines the transition from acute to chronic disease.
A common site within factor H SCR 7 responsible for binding heparin, C‐reactive protein and streptococcal M protein
Authors: Giannakis Eleni , Jokiranta T. Sakari , Male Dean A. , Ranganathan Shoba , Ormsby Rebecca J. , Fischetti Vince A. , Mold Carolyn , Gordon David L.
Published: March 2003

The complement inhibitor factor H (fH) interacts via its seventh short consensus repeat (SCR) domain with multiple ligands including heparin, streptococcal M protein and C‐reactive protein (CRP). The aim of this study was to localize the residues in SCR 7 required for these interactions. We initially built a homology model of fH SCR 6–7 using the averaged NMR structures of fH SCR 15–16 and vaccinia control protein SCR 3–4 as templates. Electrostatic potentials of the model's surface demonstrated a co‐localization of three clusters of positively charged residues on SCR 7, labeled site A (R369 and K370), site B (R386 and K387) and site C (K392). These residues, localized to the linker region preceding SCR 7 and to the end of a "hypervariable loop" in SCR 7, were systematically replaced with uncharged alanine residues in an fH construct containing SCR 1–7. The resulting proteins were expressed in the methylotrophic yeast, Pichia pastoris. By ELISA analysis we demonstrated: first, that substituting site A inhibited heparin and CRP binding; secondly, that substituting site B inhibited binding to heparin, CRP and M protein; and thirdly, that substituting site C clearly inhibited only heparin binding.
B lymphocyte life span, rate of division and differentiation are regulated by total cell number
Authors: Agenès Fabien
Published: March 2003

I analyzed how B cell survival, the rate of B cell division and the rate of B cell activation may be affected in mice with different numbers of peripheral B cells. For this purpose, I created bone marrow (BM) chimeras with different BM B cell production; I analyzed peripheral B cell dynamics in these animals and studied the fate of carboxyfluorescein succinimidyl ester‐labeled lymph node B cells transferred into these mice. I found that in lymphopenic mice, B cell life span is shortened and the rates of terminal B cell differentiation and cell death increased. As a consequence, I did not observe accumulation of B cells in mice with reduced but constant B‐cell‐poiesis. These results suggest that peripheral B cell survival relies not only on the number of competitors, as previously shown, but also on the rate of throughput of cells in a particular compartment.
KIR enrichment at the effector‐target cell interface is more sensitive than signaling to the strength of ligand binding
Authors: Borszcz Peter D. , Peterson Mary , Standeven Leah , Kirwan Sheryl , Sandusky Mina , Shaw Andrew , Long Eric O. , Burshtyn Deborah N.
Published: March 2003

Target cell lysis by natural killer cells is inhibited by killer cell immunoglobulin‐like receptors (KIR) that bind major histocompatibility complex class I molecules. Many lymphocyte receptors, including KIR, become enriched at the interface with ligand‐bearing cells. The contribution of the enrichment to inhibitory signaling has not been determined. We now describe a KIR variant with enhanced green fluorescent protein (EGFP) at the N terminus that can mediate inhibitory signaling, but its enrichment is markedly reduced. This receptor is only slightly weaker at inhibiting lysis than the same KIR tagged with EGFP in the cytoplasmic tail, even though the latter enriched as extensively as wild‐type KIR. A slight defect was also detected in the ability of the receptor to reduce adhesion to target cells and for binding of a soluble counterpart to cell surface HLA‐C. Our findings suggest that the strength of the interaction required to readily detect receptor enrichment exceeds that required for signaling.
Accumulation of type 2 cytokine+ T cells: differentiation‐independent proliferation of pre‐existing type 2 T cells
Authors: Loza Matthew J. , Perussia Bice
Published: March 2003

Analysis of proliferation and cytokine production at the single‐cell level indicated that proliferation of pre‐existing type 2 cytokine+ human peripheral naive T cells (CD4+ and CD8+) accounts for the accumulation of type 2 T cells in lymphocytes cultured with IL‐2, with or without IL‐4, and independently from TCR‐mediated stimulation. This is because: firstly,the number of cells progenitor to the type 2 cytokine+ T cells accumulated in culture is lower than that of the original cytokine+ cells; secondly, percentages and numbers of the accumulated type 2 cytokine+ T cells depend on those in the original lymphocyte population; thirdly, no accumulation occurs in cultures of lymphocytes experimentally depleted of type 2 cells; and fourthly, naive T cells do not require proliferation before producing type 2 cytokines. In contrast, accumulation of IFN‐γ+ T cells in cultures with IL‐12 can not be explained with induced proliferation of pre‐existing IFN‐γ+ cells, but depends on differentiation from more‐immature cells. These novel insights into the regulation of type 2 and type 1 cytokine+ T cells provide a new understanding of the cellular bases for the regulation of immune responses and for manipulating the immune system in clinical settings.