bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of EDHF and the role of potassium channels in the regulation of vascular tone
Authors: Ding Hong , Triggle Chris R. 
Published: March 2003

AbstractPotassium channels in both endothelial and vascular smooth muscle play an important role in the regulation of vascular tone and are therefore potential targets for new drug development. Endothelial cell potassium channels, notably small conductance and intermediate conductance calcium‐activated K channels (SKCa and IKCa, respectively), are of critical importance for the regulation of synthesis and, possibly, release of nitric oxide (NO) and prostacyclin (PGI2) as well as the elusive endothelium‐derived hyperpolarizing factor (EDHF). EDHF may represent the “third” pathway for endothelium‐dependent relaxation and, if a chemical mediator is involved, EDHF may represent a new class of K‐channel openers. Of interest also is that endothelial cell dysfunction is a common feature of cardiovascular disease and this dysfunction is often associated with a decreased availability of endothelium‐derived NO and, sometimes, an enhanced contribution of EDHF. This raises the question of the possibility that EDHF may play a pathophysiological function. A high degree of heterogeneity exists with respect to the pharmacological properties of EDHF and this may indicate that multiple EDHFs exist with some degree of vessel selectivity. Despite the heterogeneity in the properties of EDHF, a common feature is that a combination of two K‐channel toxins, apamin and charybdotoxin, which target the SKCa and IKCa channels, respectively (charybdotoxin also inhibits large‐conductance KCa, BKCa, and voltage‐gated, KV channels). The requirement for both toxins for inhibiting EDHF is suggestive that a novel K channel may exist in the vasculature; however, to date the discovery of such a channel has remained elusive. Drug Dev. Res. 58:81–89, 2003. © 2003 Wiley‐Liss, Inc.
Bioassay of endothelium‐derived hyperpolarizing factor with abolishment of nitric oxide and the role of gap junctions in the porcine coronary circulation
Authors: Yang Qin , Ge Zhi‐Dong , Yang Cheng‐Qin , Huang Yu , He Guo‐Wei 
Published: March 2003

AbstractPrevious bioassays of endothelium‐derived hyperpolarizing factor (EDHF) were partially related to the residual nitric oxide (NO) resistant to NO synthase inhibitors. Further, the role of gap junctions in EDHF is controversial. We performed a bioassay of EDHF with abolishment of NO production by using the NOS inhibitor NG‐nitro‐l‐arginine (l‐NNA) plus the NO scavenger hemoglobin (Hb) and examined the role of gap junctions/K+ channels related to EDHF in porcine coronary large and microarteries in an organ chamber/myograph. Bradykinin (BK)‐induced EDHF‐mediated relaxation and hyperpolarization (by a microelectrode) were studied with indomethacin (7 µM), l‐NNA (300 µM), and Hb (20 µM). NO concentrations ([NO]) were measured electrochemically. In large coronary arteries, BK increased [NO] (9.3±1.7 nM vs. 166.7±18.3 nM, P<0.01) that was significantly reduced by l‐NNA (49.3±7.8 nM, P<0.01) and eliminated by Hb, and hyperpolarized the downstream endothelium‐denuded artery by 9.0±1.4 mV (P<0.01) that was reduced but not abolished by l‐NNA and Hb (5.6±0.7 mV, P<0.01). In microarteries, elimination of NO decreased but did not abolish the hyperpolarization (−63.8±1.5 mV vs. −56.9±1.6 mV, P=0.01) and relaxation (70.2±5.7% vs. 42.3±4.4%, P<0.01). Charybdotoxin (0.1 µM) and apamin (0.5 µM), but neither glybenclimide (3 µM) nor gap junction inhibitors (18α‐glycyrrhetinic acid, 1‐heptanol, and gap 27) reduced the EDHF‐mediated response. We conclude that in porcine coronary arteries, with the abolishment of NO by NOS inhibitors plus the NO scavenger Hb, the non‐NO EDHF exists and is transferable from an endothelium‐intact artery to an endothelium‐denuded artery. Compared with the significant involvement of calcium‐activated K+ channels, the gap junctions may only play a minimal role in the EDHF‐mediated response even in the microcirculation of the porcine coronary artery. Drug Dev. Res. 58:99–110, 2003. © 2003 Wiley‐Liss, Inc.
Reduced sodium currents in isolated mammalian myocytes treated with chronic L‐thyroxine
Authors: Ma Yu‐Ping , Hu Hui‐Juan , Hao Xue‐Mei , Zhou Pei‐Ai , Wu Cai‐Hong , Dai De‐Zai 
Published: March 2003

AbstractWhole‐cell patch‐clamp recording techniques were applied to measure INa in isolated ventricular myocytes of guinea pigs and CA1 neurons of hippocampus of Sprague‐Dawley rats treated with L‐thyroxine (0.5 mg/kg i.p. for 8–10 days). We found that the INa densities in both hypertrophied ventricular myocytes of guinea pigs and CA1 neurons of rats were reduced significantly. The peak current of −53.2±10.8 pA/pF (n=39) which was evoked at –30mV in the hypertrophied ventricular myocytes was significantly reduced when compared with –73.8±14.7 pA/pF in control myocytes (n=45, P<0.001). The maximal INa densities (at –60 mV membrane potential) of CA1 neurons in L‐thyroxine‐treated rats were reduced from 46.0±8.5 pA/pF to 38.9±8.3 pA/pF, respectively (n=20, P<0.05). After treatment with L‐thyroxine, the decay of INa both in the ventricular myocytes of guinea pigs and CA1 neurons of rats was faster. The τ was 3.7±0.1 and 4.1±0.2 ms in the hypertrophied and control myocytes (P<0.05), respectively. The slow τ was accelerated from 3.87±1.28 in the control to 2.94±0.64 ms in the CA1 neurons of rats treated with L‐thyroxine (P<0.05). No differences were found in the steady‐state activation and inactivation and recovery kinetics in the hypertrophied ventricular myocytes. Our results indicate that impaired INa is involved in the heart and neurons in hyperthyroidism. A compromised INa for depolarization of the affected myocardium produces a slow conduction of cardiac impulses and provides a basis for uneven electrophysiological parameters. A reduced depolarizing INa combined with an impaired ion current for repolarization contribute to arrhythmogenesis of the remodeled ventricle. Drug Dev. Res. 58:111–115, 2003. © 2003 Wiley‐Liss, Inc.
L‐thyroxine affects involvement of H1, 5‐HT2, prostaglandin receptors and the endothelial NO system in allergic vascular response in guinea pigs
Authors: Hu Hui‐Juan , Dai De‐Zai 
Published: March 2003

AbstractDysfunction of the vascular system is involved in anaphylactic shock from antigen challenge. Chronic L‐thyroxine (Thy) administration induces cardiac remodeling and multiple ion channelopathies which contribute to exacerbated cardiac arrhythmias and a change in vascular responses. We measured the changes in the allergic vascular response in a Thy model. The allergic vascular response developed rapidly by exposure to antigen with two components, a peak observed at 4 min and a declining second phase. In the Thy group, the peak was reduced and the tone in the second phase increased. The H1 receptor blocker diphenhydramine (DPH) reduced the peak tension in both control and Thy groups, but increased the second phase in control and decreased the second phase in the Thy group. No effect of the H2 blocker (famotidine) was observed. The 5‐HT2 receptor antagonist ritanserin (RTS), the COX inhibitor indomethacin (IDM), and the lipoxygenase inhibitor caffeic acid (CFA) were more effective inhibitors in the Thy groups relative to the control group. Nitro‐L‐arginine (NLA), which is an NO synthase (NOS) inhibitor, enhanced peak tension in control, but not in the Thy group. The peak tension in the control group was also increased following hemoglobin (HB), which inactivates the NO pathway, by methylene blue (MTB), which suppresses cGMP formation, and by saponins, which destroy the endothelium. However, the same procedures were without effect in the Thy group. L‐Arginine, an NO donor, produced a larger reduction of peak of tension in the Thy group relative to the control group. In conclusion, suppression of allergic vascular responses by DPH, RTS, CFA, and IDM was enhanced in the Thy model and the enhancement of these responses by NLA, HB, and MTB was abolished in this group. Drug Dev. Res. 58:125–130, 2003. © 2003 Wiley‐Liss, Inc.
Changing determinants of crying termination in 6‐ to 12‐week‐old human infants
Authors: Blass Elliott M. , Camp Carole Ann 
Published: March 2003

AbstractDevelopmental change in human infant crying termination was studied in 60 infants who were 6, 9, and 12 weeks of age. They qualified by spontaneously crying for at least 30 s during the study's first minute. Infants then received either 0.8 ml sucrose (12% w/v) by syringe or sucked a pacifier dipped in the 12% solution for a total of 3.5 min. Crying was substantially reduced by pacifier‐sucking at all three ages tested. Sucrose too was effective at 6 and 9 weeks of age but did not reduce crying in 12‐week‐olds. These data suggest different schedules in the decline of sweet taste and pacifier sucking as agents of crying termination. These differential rates argue for multiple systems that govern crying reduction and argue against a single central target that changes ontogenetically in sensitivity and control. Whether the continuation of sucking effectiveness is sustained by infant sucking experience or reflects a slower rate of decline cannot be determined at present. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 42: 312–316, 2003.
Methods for introducing morpholinos into the chicken embryo
Authors: Kos Robert , Tucker Richard P. , Hall Ronelle , Duong Tuan D. , Erickson Carol A. 
Published: March 2003

AbstractThe use of antisense morpholino oligos to inhibit the translation of a target transcript has been applied recently to studies of the chicken embryo. In contrast to other developmental systems such as in frog, sea urchin, and zebrafish that permit the direct microinjection of morpholinos into a blastomere, square pulse electroporation is used to introduce fluorescently tagged morpholinos into specific populations of chick embryo cells in ovo. This article reviews the methods that have proven successful, the types of controls that are necessary when performing knockdowns of gene expression in the chick embryo, and discusses the limitations of the current technique, as well as directions for further research. Developmental Dynamics 226:000–000, 2003. © 2003 Wiley‐Liss, Inc.
Differentially expressed nucleolar TGF‐β1 target (DENTT) in mouse development
Authors: Ozbun Laurent L. , Martínez Alfredo , Angdisen Jerry , Umphress Sarah , Kang Yang , Wang Min , You Ming , Jakowlew Sonia B. 
Published: March 2003

AbstractDifferentially expressed nucleolar TGF‐β1 target (DENTT) is a recently identified gene whose mRNA is differentially affected by TGF‐β1 in TGF‐β1–responsive human lung cancer cells and who is a new member of the TSPY/TSPY‐like/SET/NAP‐1 (TTSN) protein superfamily. Here, we report that mouse DENTT mRNA contains a 2031‐bp open reading frame that encodes a predicted polypeptide of 677‐amino acids with a relative molecular mass of 77,671 Da. The mouse and human DENTT sequences show 77% and 78% homology at the nucleotide and amino acid level, respectively. Mouse DENTT is predicted to be a nuclear protein with two nuclear localization signals (NLS), two coiled‐coil regions, and a domain that shows significant identity to a region that defines the TTSN superfamily. Green fluorescent protein (GFP)‐tagged full‐length mouse DENTT transfected into COS‐7 cells showed localization predominantly in the nucleolus. Reverse transcription‐polymerase chain reaction amplification, Northern hybridization, and Western blot analyses showed expression of mouse DENTT mRNA and protein throughout mouse embryogenesis. Immunohistochemical staining analysis showed that DENTT is expressed in multiple tissues in a defined spatiotemporal pattern during mouse embryogenesis. The heart and primitive brain were the first organs of the embryo that showed immunoreactivity for the DENTT antibody by day 8 of development (E8). In the developing mouse brain, the choroid plexus was intensely stained for DENTT in all stages of development. The spinal cord and dorsal root ganglia were also positive for DENTT staining beginning in the 11‐day‐old embryo (E11), where homogeneous immunostaining was observed throughout the developing neurons. By day 16 of development (E16), only a small subset of the neuronal population in the spinal cord and dorsal root ganglia was positively stained for DENTT. DENTT immunoreactivity increased steadily with maturation as the differentiation of cartilage and osteoblasts proceeded and reached a maximum in the growth plate during endochondral ossification. DENTT expression was also detected in multiple rodent cell types in vitro, including mouse F9 embryonal carcinoma (EC) cells. Addition of retinoic acid or sodium butyrate to F9 EC cells showed a rapid decrease in expression of DENTT protein occurring by 1 hr that continued to decrease to almost undetectable levels after 24 hr. Cotransfection of full‐length mouse DENTT expression plasmid with 3TPLux or COL7A1Luc Luciferase reporter plasmids into F9 EC cells significantly increased the level of 3TPLux reporter transcription while decreasing the level of COL7A1Luc reporter transcription, suggesting that DENTT may play multiple roles in modulating transcriptional responses. These findings suggest new roles for the TTSN superfamily during embryogenesis and differentiation Developmental Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Brain dopamine is associated with eating behaviors in humans
Authors: Volkow Nora D. , Wang Gene‐Jack , Maynard Laurence , Jayne Millard , Fowler Joanna S. , Zhu Wei , Logan Jean , Gatley S. John , Ding Yu‐Shin , Wong Christopher , Pappas Naomi 
Published: March 2003

AbstractObjectiveEating behavior in humans is influenced by variables other than just hunger‐satiety including cognitive restraint, emotional distress, and sensitivity to food stimuli. We investigate the role of dopamine (DA), a neurotransmitter involved with food motivation, in these variables.MethodsWe used the Dutch Eating Behavior Questionnaire (DEBQ) to measure Restraint, Emotionality, and Externality in 10 subjects. We correlated DEBQ scores with brain DA levels. Positron emission tomography and {11C}raclopride uptake were used to measure baseline D2 receptors (neutral stimulation) and to assess changes in extracellular DA to food stimulation (display of food).ResultsRestraint was correlated with DA changes with food stimulation (higher restraint, greater responsivity), emotionality was negatively correlated with baseline D2 receptors (higher emotionality, lower D2 receptors), whereas externality was not. These correlations were significant in the dorsal but not in the ventral striatum.DiscussionThese results provide evidence that DA in the dorsal striatum is involved with the restraint and emotionality components regulating eating behavior and that these two dimensions reflect different neurobiologic processes. © 2003 by Wiley Periodicals, Inc.Int J Eat Disord 33: 136–142, 2003.
Causes and recovery in anorexia nervosa: The patient's perspective
Authors: Tozzi Federica , Sullivan Patrick F. , Fear Jennifer L. , McKenzie Jan , Bulik Cynthia M. 
Published: March 2003

AbstractObjectiveWe explored anorexic patients' subjective accounts of the causes of their anorexia and of the factors that fostered recovery. Subjective accounts could assist in understanding this complicated and often intractable disorder.MethodAll female new referrals to an eating disorders service underwent extensive interviews including open‐ended questions about their beliefs concerning the causes of their anorexia nervosa and factors that led to recovery. Responses were categorized by two independent raters.ResultsThe most commonly mentioned perceived causes were dysfunctional families, weight loss and dieting, and stressful experiences and perceived pressure. The three most commonly cited factors contributing to recovery were supportive nonfamilial relationships, therapy, and maturation.DiscussionIndividuals with anorexia nervosa perceive both external (family environment) and personal factors (dieting and stress) as contributory to their disorders. The results underscore the importance of interpersonal factors in recovery from anorexia nervosa and suggest that attention to this area in treatment may be beneficial. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 33: 143–154, 2003.
Olanzapine treatment of anorexia nervosa: A retrospective study
Authors: Malina Amanda , Gaskill Jill , McConaha Claire , Frank Guido K. , LaVia Maria , Scholar Lisa , Kaye Walter H. 
Published: March 2003

AbstractBackgroundRecent reports raise the possibility that olanzapine, which commonly causes weight gain in non–eating‐disordered subjects, assisted weight gain and mood during refeeding in anorexia nervosa (AN) patients.MethodsEighteen AN subjects who engaged in open treatment with olanzapine were retrospectively questioned about their response.ResultsSubjects reported a significant reduction in anxiety, difficulty eating, and core eating disorder symptoms after taking olanzapine.DiscussionThese data lend support to the possibility that olanzapine may be useful in AN patients.ConclusionA controlled trial is necessary to prove that olanzapine is efficacious. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 33: 234–237, 2003.
Six‐month open trial of haloperidol as an adjunctive treatment for anorexia nervosa: A preliminary report
Authors: Cassano Giovanni B. , Miniati Mario , Pini Stefano , Rotondo Alessandro , Banti Susanna , Borri Chiara , Camilleri Valeria , Mauri and Mauro 
Published: March 2003

AbstractObjectiveTo evaluate the effectiveness of haloperidoll as an adjunctive treatment for resistant anorexia nervosa restricting subtype (AN‐R).MethodThirteen outpatients with treatment‐resistant AN‐R were treated for 6 months with haloperidol in addition to standard treatment. Treatment resistance was defined as persistent and resistant anorectic symptoms despite multiple standard therapies. Assessments were carried out at baseline and after 1, 3, and 6 months with the Eating Disorder Inventory (EAT), the Eating Attitude Test (EAT), and the Clinical Global Impression and Improvement Scale (CGI‐I).ResultsSignificant change from baseline to end point was observed on EDI total score (p = .02) and on the subscales Drive for Thinness (p = .009), Bulimia (p = .01), and Interoceptive Awareness (p = .02), as well as on the EAT (p = .009) and CGI scores (p = .001). Body mass index changed significantly from baseline (15.7 ± 1.9) to end point (18.1 ± 2.5; p = .03).DiscussionThese preliminary data suggest that low doses of haloperidol might be effective as an adjunctive treatment for patients with severe AN‐R. Larger controlled studies are warranted to confirm these data. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 33: 172–177, 2003.
Human fractalkine mediates leukocyte adhesion but not capture under physiological shear conditions; a mechanism for selective monocyte recruitment
Authors: Kerfoot Steven M. , Lord Sarah E. , Bell Robert B. , Gill Varinder , Robbins Stephen M. , Kubes Paul 
Published: March 2003

AbstractFractalkine is a unique chemokine possessing a long mucin‐like stalk and a transmembrane region that has been proposed to act as an adhesion molecule. We investigated the ability of fractalkine to recruit leukocytes from whole blood, using an immobilized fractalkine fusion protein in the parallel‐plate flow‐chamber assay. Significant adhesion of leukocytes to fractalkine peaked at 2 dynes/cm2 but was minimal at 10 dynes/cm2. In contrast, VCAM‐1 could recruit cells from whole blood at 10 dynes/cm2. Co‐immobilization of fractalkine and VCAM‐1 at 10 dynes/cm2 resulted in a twofold increase in adherent cells compared with VCAM‐1 alone, suggesting that fractalkine can mediate adhesion at high shear if combined with a molecule that can mediate leukocyte tethering. Pretreatment of blood with pertussis toxin eliminated this increase in adhesion, implicating intracellular signaling in fractalkine‐mediated mechanisms of adhesion to co‐immobilized fractalkine/VCAM‐1. Analysis of the cell types recruited to fractalkine alone at low shear, or to fractalkine and VCAM‐1 at 10 dynes/cm2, revealed that monocytes were recruited to fractalkine with the highest specificity. In conclusion, fractalkine is unlikely to act alone at shear forces found in most vascular beds where it most likely co‐operates with tethering molecules, e.g. VCAM‐1, in the recruitment of monocytes.
Efficient expansion of regulatory T cells in vitro and in vivo with a CD28 superagonist
Authors: Lin Chia‐Huey , Hünig Thomas 
Published: March 2003

AbstractCD4+CD25+ T cells play a central role in the suppression of autoimmunity and inflammation, making their in vivo expansion a highly attractive therapeutic target. By phenotyping with a novel rat CTL antigen‐4 (CTLA‐4)‐specific monoclonal antibody (mAb) and functional in vitro assays, we here first establish that rat CD4+CD25+ T cells correspond to the regulatory T cells (Treg cells) described in mice and humans: they constitutively express CTLA‐4, produce IL‐10 but not IL‐2, and are able to suppress the proliferation of costimulated CD25‐negative indicator cells. Furthermore, we show that rat Treg cells respond less well than CD25– T cells to conventional costimulation, but are readily expanded in vitro with "superagonistic" CD28‐specific mAb which are potent mitogens for all T cells without the need for TCR engagement. In vivo, functional Treg cells are preferentially expanded by CD28 stimulation over other T cell subsets, leading to a 20‐fold increase within 3 days in response to a single antibody dose. These data suggest that CD28‐driven activation of Treg cells may be highly effective in the treatment of inflammatory and autoimmune diseases.
Immune evasion of Borrelia burgdorferi: mapping of a complement‐inhibitor factor H‐binding site of BbCRASP‐3, a novel member of the Erp protein family
Authors: Kraiczy Peter , Hellwage Jens , Skerka Christine , Kirschfink Michael , Brade Volker , Zipfel Peter F. , Wallich Reinhard 
Published: March 2003

AbstractThe causative agents of Lyme disease, Borrelia burgdorferi s.s., B. garinii, and B. afzelii, differ in their susceptibility to complement‐mediated lysis. This phenomenon apparently depends on the expression of proteins termed complement regulator‐acquiring surface proteins (CRASP) and their binding to the inhibitory plasma proteins factor H and FHL‐1. To characterize these bacterial proteins in more detail we have now isolated from a B. burgdorferi expression library a novel factor H‐binding protein. In accordance with our previous studies this protein was termed BbCRASP‐3 and represents a novel member of the polymorphic Erp (OspE/F‐related) protein family. On the basis of protease accessibility assays using intact spirochetes, BbCRASP‐3 isidentified as a surface‐exposed protein and binds the C‐terminal short consensus repeats of factor H. Applying deletion mutants of BbCRASP‐3, the factor H‐binding site was mapped to the nine‐amino‐acid motif LEVLKKNLK localized at the C‐terminal end of BbCRASP‐3. Factor H bound to BbCRASP‐3 maintains its cofactor activity in factor I‐mediated C3b inactivation. Binding of BbCRASP‐3 to factor H can be inhibited by heparin, a physiological ligand of the complement regulator factor H. Blocking of factor‐H‐binding by soluble BbCRASP‐3 leads to an increase of complement deposition on intermediate serum‐resistant strain ZS7. In conclusion, BbCRASP‐3 has been identified as a novel factor H‐binding protein on B. burgdorferi which by conferring complement resistance to the pathogen may contribute to its persistence in the mammalian host.