bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Issues in the Treatment of Human Diseases by Mucosal Tolerance
Authors: WEINER HOWARD L.
Published: January 2005

Abstract: Tolerance has been defined as a lack of response to self but a more appropriate definition of tolerance is “any mechanism by which a potentially injurious immune response is prevented, suppressed, or shifted to a noninjurious class of immune response.” Thus, tolerance is related to productive self‐recognition, rather than blindness of the immune system to its autocomponents. Oral tolerance, in this sense, is of unique immunologic importance, as it is a continuous natural immunologic event driven by exogenous antigen. Because of their privileged access to the internal milieu, antigens that are continuously in contact with the mucosa are a frontier between foreign and self‐components. Thus, oral tolerance is an immunological mechanism that evolved to treat external agents that gain access to the body via a natural route as internal components that then become part of self. Given this, it would seem logical that autoimmune diseases caused by an inappropriate response to self‐antigens might ultimately be treated by presenting such autoantigens to the mucosal surface where they can be dealt with in a noninjurous (noninflammatory) immunologic environment. Furthermore, mucosal tolerance as a treatment for autoimmune diseases is an attractive concept, as antigen‐specific therapy is the most physiologic means to manipulate immune responses, and mucosal antigen is nontoxic and can be given on a chronic basis. The efficacy of mucosal tolerance has been clearly demonstrated in several animal models.
Failure to Induce Oral Tolerance in Crohn's and Ulcerative Colitis Patients: Possible Genetic Risk
Authors: KRAUS THOMAS A. , TOY LISA , CHAN LISA , CHILDS JOSEPH , CHEIFETZ ADAM , MAYER LLOYD
Published: January 2005

Abstract: It has been proposed that defective activation of suppressor or regulatory T cells is one mechanism involved in the uncontrolled inflammatory process seen in inflammatory bowel disease (IBD). Because suppressor/regulatory T cells are thought to play a role in the promotion of oral tolerance, we attempted to induce oral tolerance in normal controls (n= 21) and patients with either Crohn's disease (CD; n= 12) or ulcerative colitis (UC; n= 13). In the first study, subjects were fed the neoantigen keyhole limpet hemocyanin (KLH) on days 1 to 5 and 11 to 15. Subcutaneous immunization with KLH was performed on day 26, with a booster immunization on day 35. Blood for KLH‐induced T cell proliferation and serum for anti‐KLH antibody production was obtained at baseline, on day 26 preimmunization (postfed), on day 35 after the first immunization, and again on day 42 after the second immunization. In normal individuals, KLH feeding prior to immunization and booster resulted in reduced KLH‐specific T cell proliferation compared with the group that was not fed KLH. However, although on the same KLH‐feeding protocol, both CD and UC patients demonstrated significantly enhanced proliferation without oral tolerance induction when compared with baseline values. These data suggest that oral tolerance induction is defective in patients with IBD. This may reflect an in vivo functional defect in mucosal suppression of immune responses in IBD. Both UC and CD appear to be multigenic disorders with evidence of familial segregation. We analyzed four multiplex Crohn's and two UC families to determine whether the defect in tolerance induction was genetically regulated. In three of the four CD families at least one unaffected family member also failed to tolerize (total 5 of 14 unaffected family members). In the UC families, the defect in tolerance segregated with disease. These data suggest a genetic defect in tolerance induction in Crohn's disease.
Orally and Nasally Induced Tolerance Studies in Ocular Inflammatory Disease: Guidance for Future Interventions
Authors: NUSSENBLATT ROBERT
Published: January 2005

Abstract: The induction of both oral and nasal tolerance has been used in both experimental models of ocular disease and clinically. Initial work centered around the abrogation of experimental autoimmune uveitis using either one or two whole uveitogenic antigens. Other models of ocular disease have included a corneal transplant model, demonstrating that feeding splenocytes from the donor strain of rats enhanced corneal engraftment. Fragments of pertinent antigens have been shown to alter the expression of experimental uveitis and possibly human disease. A randomized, masked study in uveitis provided valuable information for future studies, demonstrating that single antigen feeding provided far better protection than the feeding of multiple antigens. This review will deal with animal and human studies in the treatment of ocular inflammatory disease with the goal of extracting from past experience how to construct a future study in humans.
Oral Immune Regulation toward Disease‐Associated Antigens: Results of Phase I Clinical Trials in Crohn's Disease and Chronic Hepatitis
Authors: ILAN YARON
Published: January 2005

Abstract: Oral immune regulation is an immune response toward orally administered antigens, and is a balance between several types of responses. Recent studies in animal models have shown that antiviral immunity and the immune response toward colonic proteins can be modulated by oral feeding of these antigens. The effect of oral immune regulation on the outcome of various immune‐mediated processes, including infectious, inflammatory, and neoplastic entities, has been the subject of much research and debate in recent years. Two phase I clinical trials have evaluated the effect of oral immune regulation in patients with chronic hepatitis B virus infection and Crohn's disease. Mechanisms and possible future clinical applications of this immune modulatory method are discussed.
Ingested Medium-Chain Fatty Acids Are Directly Utilized for the Acyl Modification of Ghrelin
Authors: Nishi Yoshihiro , Hiejima Hiroshi , Hosoda Hiroshi , Kaiya Hiroyuki , Mori Kenji , Fukue Yoshihiko , Yanase Toshihiko , Nawata Hajime , Kangawa Kenji , Kojima Masayasu
Published: January 2005

Ghrelin, an acylated brain and gut peptide, is primarily produced by endocrine cells of the gastric mucosa for secretion into the circulation. The major active form of ghrelin is a 28-amino-acid peptide containing an n-octanoyl modification at serine that is essential for activity. Studies have identified multiple physiological functions for ghrelin, including GH release, appetite stimulation, and metabolic fuel preference. Until now, there has not been any report detailing the mechanism of ghrelin acyl modification. Here we report that ingestion of either medium-chain fatty acids (MCFAs) or medium-chain triacylglycerols (MCTs) increased the stomach concentrations of acylated ghrelin without changing the total (acyl- and des-acyl-) ghrelin amounts. After ingestion of either MCFAs or MCTs, the carbon chain lengths of the acyl groups attached to nascent ghrelin molecules corresponded to that of the ingested MCFAs or MCTs. Ghrelin peptides modified with n-butyryl or n-palmitoyl groups, however, could not be detected after ingestion of the corresponding short-chain or long-chain fatty acids, respectively. Moreover, n-heptanoyl ghrelin, an unnatural form of ghrelin, could be detected in the stomach of mice after ingestion of either n-heptanoic acid or glyceryl triheptanoate. These findings indicate that ingested medium-chain fatty acids are directly used for the acylation of ghrelin.
Genes Involved in the Adrenal Pathway of Glucocorticoid Synthesis Are Transiently Expressed in the Developing Lung
Authors: Provost Pierre R. , Tremblay Yves
Published: January 2005

We have studied the expression of genes involved in glucocorticoid synthesis in the developing lungs of male and female mouse fetuses on gestation days (GD) 15–18 (surge of surfactant, GD 17; term, GD 19). High levels of steroidogenic acute regulatory protein, cytochrome P450 cholesterol side chain cleavage, 3β-hydroxysteroid dehydrogenase type 1, 21- hydroxylase, and 11β-hydroxylase mRNAs were observed in three of the six litters studied on GD 15 and in none of the 14 litters analyzed between GD 16 and 18. Of these three litters, two showed high expression levels for these five genes in lung tissues from female fetuses only, whereas in the remaining litter, only tissues from male fetuses presented high expression of these genes. In contrast, 11β-hydroxysteroid dehydrogenase type 1 mRNA level was very low on GD 15 and presented a gradual increase between GD 15 and 18 with no sex difference. Our data indicate that, like the mature adrenal, the fetal lung expresses all genes required in glucocorticoid synthesis from cholesterol. In addition, our results demonstrate that transient expression of these genes on GD 15 in the fetal lung occurs for both male and female fetuses, 2 d before the surge of surfactant synthesis, which is stimulated by glucocorticoids.
The Distinct Agonistic Properties of the Phenylpyrazolosteroid Cortivazol Reveal Interdomain Communication within the Glucocorticoid Receptor
Authors: Yoshikawa Noritada , Yamamoto Keiko , Shimizu Noriaki , Yamada Sachiko , Morimoto Chikao , Tanaka Hirotoshi
Published: January 2005

Recent structural analyses of the nuclear receptors establish a paradigm of receptor activation, in which agonist binding induces the ligand binding domain (LBD)/activation function-2 helix to form a charge clamp for coactivator recruitment. However, these analyses have not sufficiently addressed the mechanisms for differential actions of various synthetic steroids in terms of fine tuning of multiple functions of whole receptor molecules. In the present study, we used the glucocorticoid receptor (GR)-specific agonist cortivazol (CVZ) to probe the plasticity and functional modularity of the GR. Structural docking analysis revealed that although CVZ is more bulky than other agonists, it can be accommodated in the ligand binding pocket of the GR by reorientation of several amino acid side chains but without major alterations in the active conformation of the LBD. In this induced fit model, the phenylpyrazole A-ring of CVZ establishes additional contacts with helices 3 and 5 of the LBD that may contribute to a more stable LBD configuration. Structural and functional analysis revealed that CVZ is able to compensate for the deleterious effects of a C-terminal deletion of the LBD in a manner that mimics the stabilizing influence of the F602S point mutation. CVZ-mediated productive recruitment of transcriptional intermediary factor 2 to the C-terminally deleted LBD requires the receptor’s own DNA binding domain and is positively influenced by the N-terminal regions of GR or progesterone receptor. These results support a model where ligand-dependent conformational changes in the LBD play a role in GR-mediated gene regulation via modular interaction with the DBD and activation function-1.
Multistage Epilepsy Surgery: Safety, Efficacy, and Utility of a Novel Approach in Pediatric Extratemporal Epilepsy
Authors: Bauman Joel A. , Feoli Enrique , Romanelli Pantaleo , Doyle Werner K. , Devinsky Orrin , Weiner Howard L.
Published: January 2005

OBJECTIVE:

To evaluate the safety, efficacy, and utility of a novel surgical strategy consisting of multiple (more than two) operative stages performed during the same hospital admission with subdural grid and strip electrodes in selected pediatric extratemporal epilepsy.

METHODS:

Subdural grid and strip electrodes were used for multistage chronic electroencephalographic monitoring in 15 pediatric patients (age, <19 yr) with refractory localization-related epilepsy and poor surgical prognostic factors. Initial resective surgery and/or multiple subpial transections were performed, followed by further monitoring and additional resection and/or multiple subpial transections.

RESULTS:

Mean patient age was 9.7 years. Mean duration of total invasive monitoring was 10.5 days (range, 8–14 d). The first monitoring period averaged 6.5 days, and the second averaged 3.9 days. Additional surgery was performed in 13 of 15 patients. Two patients who did not undergo additional surgery had a Class I outcome. Rationales for reinvestigation included incomplete localization, multifocality, and proximity to eloquent cortex. Complications were minimal, including two transfusions. There were no cases of wound infection, cerebral edema, hemorrhage, or major permanent neurological deficit. Minimum duration of follow-up was 31 months. Outcomes were 60% Engel Class I (9 of 15 patients), 27% Class III (4 of 15 patients), and 13% Class IV (2 of 15 patients).

CONCLUSION:

In a very select group of pediatric patients with poor surgical prognostic factors, the multistage approach can be beneficial. After failed epilepsy surgery, subsequent reoperation with additional intracranial investigation traditionally is used when a single residual focus is suspected. Our results, however, support the contention that multistage epilepsy surgery is safe, effective, and useful in a challenging and select pediatric population with extratemporal medically refractory epilepsy.
Multiagenten-Technologien für Ambient Intelligence (Multiagent Technologies for Ambient Intelligence)
Authors: Berger Michael , Müller Jörg P. , Seitz Christian
Published: January 2005

Der Begriff Ambient Intelligence (AmI) beschreibt die Vision, in der elektronische Umgebungen aktiv, personalisiert und kontextsensitiv auf die Wünsche der Menschen eingehen. Dieser Artikel skizziert einen möglichen Migrationspfad von Ubiquitous Computing über kontextsensitive Systeme hin zu Agenten-basierten Systemen für AmI. Anhand von zwei Projektbeispielen werden aktuelle Anwendungsmöglichkeiten und Grenzen der Forschung im Bereich AmI aufgezeigt.
Aufbau von Agentensystemen zur Unterstützung komponentenbasierter Entwicklungsprozesse (Architecture of Agent Systems Supporting Component-based Engineering Processes)
Authors: Wagner Thomas , Göhner Peter
Published: January 2005

Die aktive Unterstützung von Entwicklungsprozessen weist ein erhebliches Potenzial für den Einsatz von Agentensystemen auf. Der Architekturentwurf von Agentensystemen für diesen Einsatzbereich muss als wesentlichen Faktor das menschliche Know-how integrieren. Im folgenden Beitrag wird die grundlegende Architektur von Agentensystemen zur Unterstützung von Entwicklungsprozessen diskutiert und an Hand eines Beispiels erläutert.
Consciousness in Biogenetic Structural Theory
Authors: Laughlin Charles D.
Published: January 2005

Biogenetic structural theory takes an entrainment view of the nature of consciousness. Human consciousness is a function of the brain and is mediated by networks of living neural cells that develop from initial, neurognostic models of self and world. Models interact or "entrain" as a constantly changing field of experience. The entire population of neural models that may potentially entrain within the field of consciousness is called the "cognized environment.” The organization of the network of cells (the "conscious network") mediating consciousness operates according to a circadian cycle. Recurrent phases of consciousness are cognized and labelled. Transformations between phases of consciousness are often ritually controlled by society in order to control experiences that are in turn interpreted in terms of the society's cosmology. Recent developments in the biogenetic structural study of consciousness are summarized, including studies of transpersonal experiences, the development of consciousness in early life, and the advantages of neurophenomenology.
Witness to the Fire: Creativity and the Veil of Addiction by Linda Schierse Leonard
Authors: Clatts Michael C.
Published: January 2005

Witness to the Fire: Creativity and the Veil of Addiction. Linda Schierse Leonard. Boston: Shambhala Publications, 1989. ISBN 0‐87773‐393‐7. Cloth $19.95. Pp. xviii. 390.
Seeing White Bears That Are Not There: Inference Processes in Obsessions
Authors: Aardema Frederick , O’Connor Kieron
Published: January 2005

Meta-cognition refers to the notion of thoughts about one’s own thoughts and has been defined as knowledge and cognition about cognitive phenomena (Flavell, 1979). In recent years, meta-cognitive models have provided accounts of the maintenance of anxiety disorders (e.g., Wells, 2000). Meta-cognitive models would argue that the thoughts about the appearance and utility of otherwise normal thoughts generate anxiety. In this article we apply a meta-cognitive approach to understanding obsessions but, rather than thoughts about thoughts, we suggest that the ruminations in obsessive-compulsive disorder (OCD) without overt compulsions result largely from thoughts about thoughts that do not actually occur. Persons with obsessions thinks they might have or might have had the thoughts, and through a meta-cognitive process termed “inferential confusion,” confuse these imagined thoughts with actual thoughts. This account would explain the repetitive, compulsive yet ego-dystonic nature of obsessions. The justification, provided by patients with OCD, for treating imaginary thoughts as actual thoughts appears to be an imaginary narrative, which produces and maintains the obsessional preoccupation, and seems imposed on reality by a distorted inductive reasoning process.
Meanings of Perfectionism: A Quantitative and Qualitative Analysis
Authors: Rice Kenneth G. , Bair Callie J. , Castro Jennifer R. , Cohen Benjamin N. , Hood Camille A.
Published: January 2005

Quantitative and qualitative analysis is used in this article to explore the meaning of perfectionism. The defining feature of perfectionism appears to be high personal standards. The distinction between having high standards and the affective, intrapersonal, and interpersonal responses to living up to those standards distinguish adaptive from maladaptive perfectionists. Adaptive perfectionists seem to be less distressed when high standards are not achieved whereas maladaptive perfectionists experience considerable distress. Individual interviews with perfectionists and non-perfectionists refined the meaning of perfectionism as one thatgenerallyencompasses elements of distress andtypicallyemphasizes the desire to perform well. Other typical features of perfectionism also emerged and yielded several implications for psychotherapy and future research.
Electrocatalytic proton reduction by zinc phthalocyanine in nafion and poly(4-vinylpyridine-co-styrene) matrices
Authors: ZHAO FENG , ZHANG JIAN , WÖHRLE DIETER , KANEKO MASAO
Published: January 2005

Electrochemical proton reduction was catalysed by zinc phthalocyanine ( ZnPc ) incorporated in a Nafion or poly(4-vinylpyridine-co-styrene) (P(VP-St)) film coated on a graphite electrode. The turnover number (TN) of the complex to catalyse H 2 evolution was 104 h-1. The TN of Nafion[ ZnPc ] was about two times higher than that of P(VP-St)[ ZnPc ]. The difference was ascribed to the electron propagation in the film influenced by the interaction of the complex with the matrix and by the counterion migration between the matrix and the electrolyte solution. The electron transfer in the reduction of the ZnPc complex in the matrix was concluded to be the rate-determining step for the proton reduction. The TN was independent of the ZnPc concentration in the matrix at low concentrations although H 2 formation was regarded to be a bimolecular reaction process, which was explained by the electron transfer through the matrix via a monomolecular diffusion which was the rate-determining step.
Mechanism of charge transport by redox metal complexes confined in polymer matrices
Authors: ZHANG JIAN , ZHAO FENG , KANEKO MASAO
Published: January 2005

The mechanism of charge transport by metal complexes confined in polymer matrices is reviewed. There are two possibilities, one where the charge propagates in the matrix by diffusion of redox center molecules, and the other where the charge propagates by hopping between redox center molecules. The mechanism can be decided by investigating the dependence of the charge propagation rate on the redox center concentration, since in the diffusion mechanism the rate is first-order with respect to the concentration, while in the hopping mechanism it is second-order. In the hopping mechanism the charge-hopping distance can be analyzed by assuming a random distribution of the redox center in the matrix. The mechanism of charge transport by typical redox centers such as metal porphyrins, metal phthalocyanines, [Formula: see text] and methylviologen confined in a polymer membrane is presented and the charge-hopping distance is determined.
High-valent iron porphyrins
Authors: GOLD AVRAM , WEISS RAYMOND
Published: January 2005

The term ‘high-valent’ refers to iron complexes of porphyrins and related macrocycles in which the oxidation state of the iron center exceeds III. High-valent iron porphyrins and chlorins are important biological transients whose intermediacy has been demonstrated in numerous peroxidase and catalase enzymes. Two species, compounds I and II, are spectroscopically detectable upon stoichiometric addition of monooxygen donors to resting ferric enzymes. Compounds I and II are formally two and one oxidizing equivalents respectively above the ferric state. In compound II the oxidizing equivalent has been shown by spectroscopic studies to be located on iron as an oxoiron(IV) unit. The spectroscopic and magnetic properties of compound I support the structural assignment of an S = 1 oxoiron(IV) unit magnetically coupled to a heme π-cation radical (S = 1/2). Studies on model hemes have contributed much to the understanding of protein chemistry. Much work has been accomplished with meso-tetaarylporphyrins and, more recently, with physiologically congruent meso-unsubstituted pyrrole β-substituted complexes. Compounds I of both proteins and synthetic models have been characterized by a wide array of spectroscopic methods, including UV-vis, NMR, resonance Raman, EPR, variable-temperature/variable-field magnetic Mössbauer, magnetic circular dichroism and extended X-ray absorption fine structure spectroscopy. Results of these studies are summarized. Recent developments, which promise to yield a detailed picture of electronic structure, are variable-temperature magnetic circular dichroism, studies in the pre-K-edge region and L-edge X-ray absorption spectroscopy. Time-resolved X-ray diffraction techniques have been applied to obtain the first structural data on the protein forms of compound I.
Reactivity and mechanisms of metalloporphyrin-catalyzed oxidations
Authors: GROVES JOHN T.
Published: January 2005

Effective systems for the catalytic oxygenation of hydrocarbons have been developed based on metalloporphyrins containing iron, manganese and ruthenium. These metalloporphyrin catalysts were inspired by studies of the mechanism of the heme oxygenase cytochrome P450 and related enzymes. Oxometalloporphyrins, which have now been spectroscopically characterized, have very high reactivity as oxygen transfer agents. A combination of experimental and computational methods has begun to provide an understanding of the structure and reactivity of these oxometalloporphyrin complexes and the mechanisms of oxygen transfer reactions they catalyze.
Molecular recognition
Authors: MAIYA BHASKAR G.
Published: January 2005

The ‘marriage’ between porphyrin chemistry and the newly emerging molecular recognition science has opened up novel research opportunities leading to many biological and abiological applications. An overview of this fascinating research area is presented here.
Psychological benefit of diagnostic certainty for mothers of children with disabilities: Lessons from Down syndrome
Authors: Lenhard W. , Breitenbach E. , Ebert H. , Schindelhauer‐Deutscher H.J. , Henn W.
Published: January 2005

Diagnostic and prognostic uncertainty is one of the major psychological stressors for patients in acute and chronic illness, as well as for parents of children with disabilities or chronic disease. Whereas the parents' feeling of uncertainty is undoubtedly very strong shortly after the birth of a child with disabilities, the long‐term effects on the parents of having or not having a precise genetic diagnosis, in terms of emotional stress, remain unclear. In this study, mothers of non‐disabled children are compared to mothers of children with Down syndrome, and to mothers of children with a diagnostically unassigned mental retardation with regard to the level of anxiety, feelings of guilt, and emotional burden. While the mothers of children with Down syndrome score comparably to the mothers of non‐disabled children, the results show broad psychoemotional disadvantages for mothers of children with a mental retardation of unknown etiology. Consequently, the value of genetic diagnosis of infantile disabilities encompasses, beyond clinical considerations like therapy planning and assignment of the recurrence risk for siblings, significant and long‐lasting emotional relief for the parents. © 2005 Wiley‐Liss, Inc.
Time–temperature dependency of mode II fracture toughness for bisphenol A type epoxy resin
Authors: Araki Wakako , Asahi Daisuke , Adachi Tadaharu , Yamaji Akihiko
Published: January 2005

We investigated the mode II fracture toughness (KIIc) with time and temperature dependence of the bisphenol A type of epoxy resin. We performed an asymmetric four‐point bending test under various conditions of temperature and displacement rate. We found that KIIc strongly depended on the displacement rate and the temperature, even at room temperature. Moreover, it was governed by the time–temperature equivalence principle in regard to the fracture time. The time–temperature dependency of KIIc was similar to that of the loss modulus (E″), and the transition of brittle to ductile fractures occurred nearly simultaneously when E″ peaked. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 51–55, 2005
Wood‐fiber/high‐density‐polyethylene composites: Coupling agent performance
Authors: Lu John Z. , Wu Qinglin , Negulescu Ioan I.
Published: January 2005

The coupling efficiency of seven coupling agents in wood–polymer composites (WPC) was investigated in this study. The improvement on the interfacial bonding strength, flexural modulus, and other mechanical properties of the resultant wood fiber/high‐density polyethylene (HDPE) composites was mainly related to the coupling agent type, function groups, molecular weight, concentration, and chain structure. As a coupling agent, maleated polyethylene (MAPE) had a better performance in WPC than oxidized polyethylene (OPE) and pure polyethylene (PPE) because of its stronger interfacial bonding. A combination of the acid number, molecular weight, and concentration of coupling agents had a significant effect on the interfacial bonding in WPC. The coupling agents with a high molecular weight, moderate acid number, and low concentration level were preferred to improve interfacial adhesion in WPC. The backbone structure of coupling agents also affected the interfacial bonding strength. Compared with the untreated composites, modified composites improved the interfacial bonding strength by 140% on maximum and the flexural storage modulus by 29%. According to the statistical analysis, 226D and 100D were the best of the seven coupling agents. The coupling agent performance was illustrated with the brush, switch, and amorphous structures. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 93–102, 2005
Effects of cysteine on the pharmacokinetics of intravenous chlorzoxazone in rats with protein–calorie malnutrition
Authors: Kim Yoon G. , Cho Min K. , Kwon Jong W. , Kim Sang G. , Chung Suk J. , Shim Chang‐K. , Lee Myung G.
Published: January 2005

The effects of cysteine on the pharmacokinetics of chlorzoxazone (CZX) and one of its metabolites, 6‐hydroxychlorzoxazone (OH‐CZX), were investigated after intravenous administration of CZX, 25 mg/kg, to control rats (4‐week fed on 23% casein diet) and rats with PCM (4‐week fed on 5% casein diet) and PCMC (PCM with oral cysteine supplementation, 250 mg/kg, twice daily during the fourth week). In rats with PCM, the area under the plasma concentration–time curve from time zero to time infinity (AUC) of OH‐CZX (436 compared with 972 μg min/ml) and the percentages of intravenous dose of CZX excreted in 8‐h urine as OH‐CZX (20.2 compared with 38.5%) were significantly smaller than those in control rats. The above data indicated that the formation of OH‐CZX from CZX decreased significantly in rats with PCM due to a significant decrease in chlorzoxazone‐6‐hydroxylase activity (328 compared with 895 pmol/min/mg protein) in the rats. The results were expected since in rats with PCM, hepatic CYP2E1 expression and its mRNA levels decreased significantly as compared to control, and CZX was metabolized to OH‐CZX primarily by CYP2E1 in rats. By cysteine supplementation (rats with PCMC), some pharmacokinetic parameters restored fully (hepatic microsomal chlorzoxazone 6‐hydroxylation activity based on both mg protein and nmol CYP450) or partially (total body clearance and apparent volume of distribution at steady state of CZX, and AUC, terminal half‐life and 8‐h urinary excretion of OH‐CZX) to control levels. Copyright © 2002 John Wiley & Sons, Ltd.
Evaluation and treatment of covert stereotypy
Authors: Ringdahl Joel E. , Andelman Marc S. , Kitsukawa Kana , Winborn Lisa C. , Barretto Anjali , Wacker David P.
Published: January 2005

The treatment of behavior maintained by automatic reinforcement (e.g. stereotypy) can present a unique challenge if practitioners cannot control delivery of the maintaining reinforcer. Further, some individuals might engage in stereotypy only when care providers are absent. In the current evaluation, an adolescent boy's hand flapping was demonstrated to occur in the absence of social contingencies and care providers. To reduce the behavior, two treatment strategies were assessed. In the first approach, verbal reminders to refrain from hand flapping were delivered on time‐based schedules. In the second approach (differential reinforcement of other behavior, DRO), we provided access to a preferred item contingent on prespecified time lengths with no hand flapping when the participant was alone in a room. Results of the investigation indicated that the verbal reminders were unsuccessful, whereas the DRO program resulted in near‐zero levels of stereotypy. Copyright © 2002 John Wiley & Sons, Ltd.
The effect of providing choices on skill acquisition and competing behavior of children with autism during discrete trial instruction
Authors: Newman Bobby , Needelman Meredith , Reinecke Dana R. , Robek Adrienne
Published: January 2005

Discrete trial instruction was carried out for three students with autism. An alternating treatments design was implemented. In one condition, teachers chose the reinforcers to be used and the order in which programs were conducted. In a second condition, students chose the order of programs and the reinforcers to be used. Speed of skill acquisition and the presence of competing behavior such as tantrums, aggression, escape attempts or idiosyncratic noncompliance responses were measured. Speed of skill acquisition did not differ between the two conditions, but competing behavior was markedly reduced during student choice conditions. Copyright © 2002 John Wiley & Sons, Ltd.
Simultaneous detection of two verotoxin genes using dual‐label time‐resolved fluorescence immunoassay with duplex PCR
Authors: Watanabe Kazuyuki , Arakawa Hidetoshi , Maeda Masako
Published: January 2005

Verotoxin (VT) produced by several Escherichia coli serotypes causes haemorrhagic colitis and has been associated with haemolytic uraemic syndrome in humans. Two types of verotoxin are known. Conventional diagnosis of verotoxin‐producing Escherichia coli (VTEC) is conducted after isolation of bacteria from clinical specimens, followed by serological determination and identification of VTs. This method is complicated and time‐consuming. Recently, rapid, direct immunological methods for identification of VTEC, i.e. immunochromatography and latex agglutination, have been developed. However, these techniques continue to suffer from limited sensitivity and a lack of specificity. These difficulties arise from the fact that the antibody used in these procedures reacts exclusively with the O157 antigen; moreover, VTEC strains with non‐O157 antigens, such as O26, O103 and O111 antigens, exist. These VTEC groups did not react with anti‐O157 antibody. Consequently, it is necessary to diagnose the VT gene in these bacteria. Therefore, we have designed a sensitive and specific method for the detection of two VT genes simultaneously, utilizing duplex PCR with time‐resolved fluorescence immunoassay (TRFIA). Copyright © 2002 John Wiley & Sons, Ltd.
Depressed humoral immunity after weight reduction in competitive judoists
Authors: Ohta Seikou , Nakaji Shigeyuki , Suzuki Katsuhiko , Totsuka Manabu , Umeda Takashi , Sugawara Kazuo
Published: January 2005

We studied changes in serum opsonic activity (SOA) in male judoists who were engaged in active weight reduction. Serum immunoglobulins, complements and SOA, measured by neutrophil‐associated chemiluminescence responses, were investigated 20 days, 7 days and 1 day before a competition and 5 days after the competition. In addition, muscle strength and anaerobic work capacity, as well as body composition, were also determined. A dietary survey was conducted daily during the observation period. Body weight decreased by 4.2 kg over 19 days. SOA significantly decreased 5 days after the competition, as well as the concentrations of serum immunoglobulins, complements and total proteins. These trends were noted in the marked weight reduction group (i.e. reduction weight of body fat/body fat weight before weight reduction ≧25%) more than the slight reduction group (<25%). Depressed SOA was closely correlated with the decreased concentrations of immunoglobulins and complements. These results suggest that the decrease in immunoglobulins and complements following weight reduction is associated with reduced SOA, which might cause susceptibility to infections. This study demonstrated that such immunosuppression appeared in the recovery period after the competition rather than immediately before the competition. Copyright © 2002 John Wiley & Sons, Ltd.
Stochastic‐based descriptors studying biopolymers biological properties: Extended MARCH‐INSIDE methodology describing antibacterial activity of lactoferricin derivatives
Authors: Ramos de Armas Ronal , Díaz Humberto González , Molina Reinaldo , Uriarte Eugenio
Published: January 2005

Lactoferricin are a number of related peptides derived from the enzymatic cleavage of lactoferrin, an iron‐binding protein. These peptides, and other peptides derived from them by simple amino acid substitutions, have shown interesting antibacterial activity. In this paper we applied the MARCH‐INSIDE methodology extended to peptide and proteins, to a QSAR study related to antibacterial activity of 31 derivatives of lactoffericin against E. Coli and S. Aureus by means of Linear Discriminant (LDA) and Multiple Linear Regression Analysis (MLR). In the case of LDA we obtained models that classify correctly more than 80% of all cases (85.7% for E. Coli antibacterial activity and 83.9 for S. Aureus). With the application of a Leave‐One‐Out Cross Validation Procedure, the percentage of good classification of both classification models remained near the above reported values (87.1% for E. Coli antibacterial activity and 83.9 for S. Aureus). We obtained several linear regression models taking into account total and local descriptors. The inclusion of those local descriptors improved the correlation parameters, the statistical quality, and the predictive power of the former model obtained only with total descriptors. The best models explained more than 80% of the experimental variance in the antimicrobial activity of those compounds. These results are comparable with those reported previously by Strom (Strom, M. B.; Rekdal, O.; Svendesen, J. S. J Peptide Res 2001, 57, 127–139.) and Tore‐Lejon (Lejon, T.; Strom, M.; Svendsen, S. J Protein Sci 2001, 7, 74–78.; Lejon, T.; Svendsen J. S.; Haug, B. E. J Peptide Sci 2002, 8, 302–306.) in a smaller dataset applying Z‐scales and volume‐based descriptors and PLS as statistical techniques. © 2005 Wiley Periodicals, Inc. Biopolymers, 2005
Specific 3′‐Terminal Modification of DNA with a Novel Nucleoside Analogue that Allows a Covalent Linkage of a Nuclear Localization Signal and Enhancement of DNA Stability
Authors: Ikeda Yutaka , Kawahara Shun‐ichi , Yoshinari Koichi , Fujita Satoshi , Taira Kazunari
Published: January 2005

We report a straightforward method for the site‐specific modification of long double‐stranded DNA by using a maleimide adduct of deoxycytidine. This novel nucleoside analogue was efficiently incorporated at the 3′‐termini of DNA by terminal deoxynucleotidyl transferase (TdT). Thiol‐containing compounds can be covalently linked to the maleimide moieties. We added a nuclear localization signal peptide to the 3′‐terminal of a 350 bp‐long DNA that encoded short‐hairpin RNA, and these modifications resulted in the enhancement of silencing activity by RNA interference. This enhancement is mainly attributed to increased stability of the template DNA.
Asprich: A Novel Aspartic Acid‐Rich Protein Family from the Prismatic Shell Matrix of the Bivalve Atrina rigida
Authors: Gotliv Bat‐Ami , Kessler Naama , Sumerel Jan L. , Morse Daniel E. , Tuross Noreen , Addadi Lia , Weiner Steve
Published: January 2005

Almost all mineralized tissues contain proteins that are unusually acidic. As they are also often intimately associated with the mineral phase, they are thought to fulfill important functions in controlling mineral formation. Relatively little is known about these important proteins, because their acidic nature causes technical difficulties during purification and characterization procedures. Much effort has been made to overcome these problems, particularly in the study of mollusk‐shell formation. To date about 16 proteins from mollusk‐shell organic matrices have been sequenced, but only two are unusually rich in aspartic and glutamic acids. Here we screened a cDNA library made from the mRNA of the shell‐forming cells of a bivalve, Atrina rigida, using probes for short Asp‐containing repeat sequences, and identified ten different proteins. Using more specific probes designed from one subgroup of conserved sequences, we obtained the full sequences of a family of seven aspartic acid‐rich proteins, which we named “Asprich”; a subfamily of the unusually acidic shell‐matrix proteins. Polyclonal antibodies raised against a synthetic peptide of the conserved acidic1 domain of these proteins reacted specifically with the matrix components of the calcitic prismatic layer, but not with those of the aragonitic nacreous layer. Thus the Asprich proteins are constituents of the prismatic layer shell matrix. We can identify different domains within these sequences, including a signal peptide characteristic of proteins destined for extracellular secretion, a conserved domain rich in aspartic acid that contains a sequence very similar to the calcium‐binding domain of Calsequestrin, and another domain rich in aspartic acid, that varies between the seven sequences. We also identified a domain with DEAD repeats that may have Mg‐binding capabilities. Although we do not know, as yet, the function of these proteins, their generally conserved sequences do indicate that they might well fulfill basic functions in shell formation.
Multivalent HSA Conjugates of 3′‐Sialyllactose are Potent Inhibitors of Adenoviral Cell Attachment and Infection
Authors: Johansson Susanne M. C. , Arnberg Niklas , Elofsson Mikael , Wadell Göran , Kihlberg Jan
Published: January 2005

Adenoviruses of serotypes 8, 19 and 37 are the major cause of the severe eye infection EKC (epidemic keratoconjunctivitis). In general, all adenoviruses interact with their cellular receptors through the fibre proteins, which extend from the virus particle. Recently, adenovirus type 37 (Ad37) was found to bind and infect human corneal cells through attachment to carbohydrate structures that carry terminal α‐(2–3)‐linked sialic acids. Herein we present a synthetic route to a 3′‐sialyllactose derivative and corresponding multivalent HSA conjugates with varying orders of valency. The potential of these compounds as inhibitors of EKC‐causing adenovirus of serotype Ad37, was studied with both a binding assay and an infectivity assay. The results revealed that these compounds effectively prevent Ad37 from binding to and infecting human corneal epithelial (HCE) cells. Moreover, the inhibition is significantly increased with higher orders of multivalency.
Cover Picture: A New Chemical Probe for Proteomics of Carbohydrate‐Binding Proteins (ChemBioChem 2/2005)
Authors: Ballell Lluis , Alink Kirstin J. , Slijper Monique , Versluis Cees , Liskamp Rob M. J. , Pieters Roland J.
Published: January 2005

The cover picture shows how galectins are selected from a mixture of proteins by a novel probe. The probe noncovalently binds the medicinally relevant galectins, and its photoaffinity label covalently captures the protein. The captured protein is visualized by a fluorescent dye that is introduced by chemoselective 1,2,3‐triazole formation or "click" chemistry. The methodology represents a step towards comparative quantification of the galectin amounts in proteomes, which is relevant, for example, for prognosis with respect to the malignancy of tissues. Despite the low affinities in protein–carbohydrate interactions, the probe shown is able to select the galectins from a mixture of four proteins. For more information, see the article by R. J. Pieters et al on p. 291 ff.
Cover Picture: A Modular Approach to DNA‐Programmed Self‐Assembly of Macromolecular Nanostructures (Chem. Eur. J. 4/2005)
Authors: Gothelf Kurt V. , Brown Raymond S.
Published: January 2005

DNA‐programmed self‐assembly: K. V. Gothelf and R. S. Brown describe new and powerful tools for assembling chemical compounds into predetermined complex structures by using DNA‐programmed organic reactions in their Concepts article on page 1062 ff. This approach is particular efficient for the selection and covalent coupling of multiple components. DNA‐templated synthesis is used for polymerization of PNA tetramers and for copying of the connectivity information in DNA. Direct DNA‐programmed multicomponent coupling of custom designed organic modules is described. The macromolecular structures obtained are highly conjugated potentially conducting nanoscaffolds.
Predicting winds and air quality within the Las Vegas Valley
Authors: Carrington David B. , Pepper Darrell W.
Published: January 2005

A finite element model that employs local mesh adaptation is used to calculate wind fields and pollutant transport within the Las Vegas Valley. Meteorological data collected from various country, city, and government agencies are used to generate diagnostic flow fields, which subsequently provide initial conditions for the prognostic solution of the time‐dependent equations of motion and species transport. Copyright © 2002 John Wiley & Sons, Ltd.
Direct intralymphatic injection of peptide vaccines enhances immunogenicity
Authors: Johansen P. , Häffner A. C. , Koch F. , Zepter K. , Erdmann I. , Maloy K. , Simard J. J. , Storni T. , Senti G. , Bot A. , Wüthrich B. , Kündig T. M.
Published: January 2005

Research to enhance the efficiency of vaccines focuses mainly on improving either the adjuvant or the type and form of the antigen. This study evaluates the influence of the administration route on the efficiency of a peptide‐based vaccine. Peptide vaccines are generally administered subcutaneously or intradermally, from where they must reach secondary lymphatic organs to induce an immune response. We analyzed the efficacy of peptide vaccines administered directly into a lymph node. Using a MHC class I‐binding peptide from lymphocytic choriomeningitis virus, we found that intralymphatic injection enhanced immunogenicity by as much as 106 times when compared to subcutaneous and intradermal vaccination. Intralymphatic administration induced CD8 T cell responses with strong cytotoxic activity and IFN‐γ production that conferred long‐term protection against viral infections and tumors. These results should have immediate implications for clinical immunotherapy of infectious disease and cancer.
Survival versus neglect: redefining thymocyte subsets based on expression of NKG2D ligand(s) and MHC class I
Authors: Li Jennifer , Rabinovich Brian A. , Hurren Rose , Cosman David , Miller Richard G.
Published: January 2005

BALB/c thymocytes can be divided into three distinct subsets according to the expression of a ligand for the NK activation receptor NKG2D (NKG2D‐L) and the expression of MHC class I (MHC‐I). The first subset (MHC‐Imid/NKG2D‐Lhigh or “N+”) is predominately CD4+CD8+ double positive (DP), comprises ∼35% of thymocytes in a 6–8‐week‐old adult and contains uncommitted cells that have neither undergone selection nor are committed to death by neglect. The second subset (MHC‐Ilow/NKG2D‐Llow or “M–”), also mostly DP cells, comprises ∼50% of thymocytes and consists of cells committed to death by apoptosis, likely due to neglect. By contrast, the third subset (MHC‐Ihigh/NKG2D‐Llow or “M+”) is largely single positive (SP), represents ∼15% of thymocytes and mostly contains more mature cells that have undergone successful positive selection. The major advantage of the analysis is that it splits DP cells into two subpopulations, one committed to death by apoptosis and the other subjected to selection. The analysis also suggests that NKG2D‐L may play a role in thymocyte development.
Distinct temporal programming of naive CD4+ T cells for cell division versus TCR‐dependent death susceptibility by antigen‐presenting macrophages
Authors: Schrum Adam G. , Palmer Ed , Turka Laurence A.
Published: January 2005

Naive T cells become programmed for clonal expansion and contraction during the early hours of antigenic signaling. Recent studies support an ‘autopilot’ model, wherein the commitment to proliferate and the magnitude of the proliferative response are simultaneously determined during a single, brief period of antigen exposure. Here, we have examined whether the proliferation of naive CD4+ T cells must occur on ‘autopilot’, or whether extended periods of antigenic signaling can impact primary proliferative responses to antigen‐presenting macrophages (macrophage APC). We found that a single exposure to antigen (18 h) simultaneously committed T cells to (1) up‐regulate surface TCR above the level expressed on naive T cells, (2) undergo minimal cell division, and (3) acquire susceptibility to TCR‐dependent activation‐induced cell death. However, continued antigenic signaling between 18 and 72 h was required to amplify the number of daughter cells derived from the already committed T cells. Thus, a discrete commitment time was followed by a ‘tuning’ period, where extended antigenic signaling determined the volume of the proliferative response. We conclude that T cell commitment to full clonal expansion versus TCR‐dependent death susceptibility represent two separate programming events whose timing can be segregated by macrophage APC.