bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease
Authors: Allen Irving C. , Pace Amy J. , Jania Leigh A. , Ledford Julie G. , Latour Anne M. , Snouwaert John N. , Bernier Virginie , Stocco Rino , Therien Alex G. , Koller Beverly H.
Published: July 2006

A genetic contribution to asthma susceptibility is well recognized, and linkage studies have identified a large number of genes associated with asthma pathogenesis. Recently, a locus encoding a seven-transmembrane protein was shown to be associated with asthma in founder populations. The expression of the protein GPRA (G protein-coupled receptor for asthma susceptibility) in human airway epithelia and smooth muscle, and its increased expression in a mouse model of asthma, suggested that a gain-of-function mutation in this gene increased the disease risk. However, we report here that the development of allergic lung disease in GPRA-deficient mice is unaltered. A possible explanation for this finding became apparent upon reexamination of the expression of this gene. In contrast to initial studies, our analyses failed to detect expression of GPRA in human lung tissue or in mice with allergic lung disease. We identify a single parameter that distinguishes GPRA-deficient and wild-type mice. Whereas the change in airway resistance in response to methacholine was identical in control and GPRA-deficient mice, the mutant animals showed an attenuated response to thromboxane, a cholinergic receptor-dependent bronchoconstricting agent. Together, our studies fail to support a direct contribution of GPRA to asthma pathogenesis. However, our data suggest that GPRA may contribute to the asthmatic phenotype by altering the activity of other pathways, such as neurally mediated mechanisms, that contribute to disease. This interpretation is supported by high levels of GPRA expression in the brain and its recent identification as the neuropeptide S receptor.
Functional expression of the GABAB receptor in human airway smooth muscle
Authors: Osawa Yoko , Xu Dingbang , Sternberg David , Sonett Joshua R. , D’Armiento Jeanine , Panettieri Reynold A. , Emala Charles W.
Published: July 2006

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABAA/GABAC) and metabotropic (GABAB) receptors (R). In addition to their location on neurons, GABA and functional GABAB receptors have been detected in nonneuronal cells in peripheral tissue. Although the GABABR has been shown to function as a prejunctional inhibitory receptor on parasympathetic nerves in the lung, the expression and functional coupling of GABAB receptors to Gi in airway smooth muscle itself have never been described. We detected the mRNA encoding multiple-splice variants of the GABABR1 and GABABR2 in total RNA isolated from native human and guinea pig airway smooth muscle and from RNA isolated from cultured human airway smooth muscle (HASM) cells. Immunoblots identified the GABABR1 and GABABR2 proteins in human native and cultured airway smooth muscle. The GABABR1 protein was immunohistochemically localized to airway smooth muscle in guinea pig tracheal rings. Baclofen, a GABABR agonist, elicited a concentration-dependent stimulation of [35S]GTPγS binding in HASM homogenates that was abrogated by the GABABR antagonist CGP-35348. Baclofen also inhibited adenylyl cyclase activity and induced ERK phosphorylation in HASM. Another GABABR agonist, SKF-97541, mimicked while pertussis toxin blocked baclofen’s effect on ERK phosphorylation, implicating Gi protein coupling. Functional GABAB receptors are expressed in HASM. GABA may modulate an uncharacterized signaling cascade via GABAB receptors coupled to the Gi protein in airway smooth muscle.
Battered Women Who Kill Their Abusers
Authors: Huss Matthew T. , Tomkins Alan J. , Garbin Calvin P. , Schopp Robert F. , Kilian Allen
Published: July 2006

It has been argued that battered women who kill their abusers represent a special class of defendants being unfairly treated in the legal system. As a result, commentators have argued for reforms to permit the judicial system to respond more fairly. Researchers have investigated the influences of these prescribed legal modifications and the possible influence of various demographic and psychological factors on legal reforms. However, social scientists have not yet asked some fundamental, psychological questions. Is the law consistent with what society believes is right and just? Is there a commonsense notion of justice in these cases? What factors constitute cognitive decision rules and influence judgments in cases of battered women who kill their abusers? This study uses a basic, psychological method to identify psychological factors that are important in judgments regarding battered women who kill and to better understand commonsense notions of justice in these cases.
Childhood Sexual Abuse and Multiple Dimensions of Self-Concept
Authors: Murthi Meera , Servaty-Seib Heather L. , Elliott Ann N.
Published: July 2006

The purpose of this investigation was to examine the relationship between child sexual abuse (CSA) and self-concept in a nonclinical sample of female college students. Participants with a history of CSA had lower scores than participants without a history of CSA on four domains of self-concept: familial, affect, competence, and physical. History of CSA was not associated with lower self-concept in the social and academic domains. The primary conclusions to be drawn from this study are that CSA may be differentially associated with various domains of self-concept, and thus multidimensional assessment of self-concept can yield useful information that cannot be gathered from global measures which yield a single composite score.
Offender Characteristics in Lethal Violence With Special Reference to Antisocial and Autistic Personality Traits
Authors: Wahlund Katarina , Kristiansson Marianne
Published: July 2006

The objective of the study is to assess the relationships between personality traits, lifetime psychosocial functioning, and crime scene behavior. Thirty-five male offenders referred for forensic psychiatric assessment in Sweden (1996-2001) and assigned a main diagnosis of either antisocial personality disorder (APD) or autism spectrum disorder (AUT) were retrospectively studied. APD were subcategorized into impulsive (APDi) and controlled (APDc). Those in the AUT group were less intoxicated at the time of the crime and did not often use knives or guns compared to the APD group. Males in the APDi group were older and had a higher proportion of abuse of alcohol and drugs in biological parents, physical abuse during childhood, psychiatric contacts, and suicide attempts compared to the APDc group. In the APDi group, knives were used in the homicide compared to the use of guns in the APDc group. The results suggest differences in psychosocial functioning and crime scene characteristics related to personality traits.
Impact of Stress and Mitigating Information on Evaluations, Attributions, Affect, Disciplinary Choices, and Expectations of Compliance in Mothers at High and Low Risk for Child Physical Abuse
Authors: De Paúl Joaquín , Asla Nagore , Pérez-Albéniz Alicia , De Cádiz Bárbara Torres-Gómez
Published: July 2006

The objective is to know if high-risk mothers for child physical abuse differ in their evaluations, attributions, negative affect, disciplinary choices for children's behavior, and expectations of compliance. The effect of a stressor and the introduction of mitigating information are analyzed. Forty-seven high-risk and 48 matched low-risk mothers participated in the study. Mothers' information processing and disciplinary choices were examined using six vignettes depicting a child engaging in different transgressions. A four-factor design with repeated measures on the last two factors was used. High-risk mothers reported more hostile intent, global and internal attributions, more use of power assertion discipline, and less induction. A risk group by child transgression interaction and a risk group by mitigating information interaction were found. Results support the social information–processing model of child physical abuse, which suggests that high-risk mothers process childrelated information differently and use more power assertive and less inductive disciplinary techniques.
AP-1-directed human T cell leukemia virus type 1 viral gene expression during monocytic differentiation
Authors: Grant Christian , Jain Pooja , Nonnemacher Michael , Flaig Katherine E , Irish Bryan , Ahuja Jaya , Alexaki Aikaterini , Alefantis Timothy , Wigdahl Brian
Published: July 2006

Human T cell leukemia virus type 1 (HTLV-1) has previously been shown to infect antigen-presenting cells and their precursors in vivo. However, the role these important cell populations play in the pathogenesis of HTLV-1-associated myelopathy/tropical spastic paraparesis or adult T cell leukemia remains unresolved. To better understand how HTLV-1 infection of these important cell populations may potentially impact disease progression, the regulation of HTLV-1 viral gene expression in established monocytic cell lines was examined. U-937 promonocytic cells transiently transfected with a HTLV-1 long-terminal repeat (LTR) luciferase construct were treated with phorbol 12-myristate 13-acetate (PMA) to induce cellular differentiation. PMA-induced cellular differentiation resulted in activation of basal and Tax-mediated transactivation of the HTLV-1 LTR. In addition, electrophoretic mobility shift analyses demonstrated that PMA-induced cellular differentiation induced DNA-binding activity of cellular transcription factors to Tax-responsive element 1 (TRE-1) repeat II. Supershift analyses revealed that factors belonging to the activator protein 1 (AP-1) family of basic region/leucine zipper proteins (Fra-1, Fra-2, JunB, and JunD) were induced to bind to TRE-1 repeat II during cellular differentiation. Inhibition of AP-1 DNA-binding activity by overexpression of a dominant-negative c-Fos mutant (A-Fos) in transient expression analyses resulted in severely decreased levels of HTLV-1 LTR activation in PMA-induced U-937 cells. These results have suggested that following infection of peripheral blood monocytes, HTLV-1 viral gene expression may become up-regulated by AP-1 during differentiation into macrophages or dendritic cells.
Hypoxia and HIF‐1α in Chondrogenesis
Authors: SCHIPANI ERNESTINA
Published: July 2006

Abstract:  In endochondral bone development chondrocytes undergo proliferation, hypertrophic differentiation, mineralization of the surrounding matrix, death, blood vessel invasion, and finally replacement of cartilage with bone. The chondrocytic growth plate is a unique mesenchymal tissue, as it is avascular but it requires blood vessel invasion in order to be replaced by bone. We have recently provided evidence that the growth plate is hypoxic during fetal development. Adaptation to hypoxia is a critical event in numerous pathological settings, such as tumor progression and survival of tissues in which blood flow has been suddenly interrupted. One of the hallmarks of the response to hypoxia is activation of the transcription factor HIF‐1α. The von Hippel–Lindau (VHL) tumor suppressor protein is a component of a ubiquitin ligase promoting proteolysis of HIF‐1α. By using a genetic approach, we have demonstrated that VHL and HIF‐1α are critical regulators of endochondral bone development.
Reactions with 2(1H)-Quinolinone and Coumarine Derivatives: New Routes to Polysubstituted 2(1H)-Quinolinone and Coumarine Derivatives
Authors: El-Taweel Fathy Mohamed Abdel Aziz , Sowellim Salah Zaki Ahmed , Elagamey Abdel Ghani Ali
Published: July 2006

Whereas 2H-pyrano[3,2-c]quinoline-2,5(6H)-dione (2a) or 3-acetyl-1-methyl-2(1H)-quinolinone (3a) reacted with the benzylidenenitriles 1a—f or a mixture of either malononitrile or ethyl cyanoacetate and aromatic aldehydes in ethanol/piperidine to give 4H-pyran derivatives 8, the reaction of 2b,c or 3b,c with the same reagents afforded 4,6-dihydro-5H-pyrano[3,2-c]quinolin-5-ones 11. Compounds 11 were also prepared from 1a—f and 3d,e,f. Reaction of pyrano[3,2-c]coumarin 2d with 1a yielded 6H,11H-[2]benzopyrano[4,3-c][1]benzopyran-6,11-dione (15). Treatment of 17 with aqueous potassium cyanide or hydroxylamine afforded the 2(1H)-quinolinone derivatives 19 and 20 respectively.
Rhodium(I)- and Palladium(0)-Catalyzed Carbonylation of Triarylbismuthines with Carbon Monoxide via a Possible Oxidative Addition of a Carbon–Bismuth Bond to Rhodium(I) and Palladium(0)
Authors: Cho Chan Sik , Yoshimori Yasuharu , Uemura Sakae
Published: July 2006

Triarylbismuthines react with carbon monoxide (CO) at atmospheric pressure in acetonitrile at 25 °C in the presence of a catalytic amount of a rhodium compound such as [RhCl(CO)2]2, RhCl3·3H2O, and [RhCl(COD)]2 to give the corresponding diaryl ketones in high yields. If methanol is used as the solvent, methyl benzoates are also produced. When similar reactions are carried out in methanol in the presence of a catalytic amount of palladium(II) acetate together with potassium carbonate in place of the rhodium compound, methyl benzoates are formed as the sole carbonylation products. The oxidative addition of a carbon–bismuth bond to rhodium(I) and palladium(0) is proposed as the key step of these carbonylation reactions.
Incorporating Satisfaction into Customer Value Analysis: Optimal Investment in Lifetime Value
Authors: Ho Teck-Hua , Park Young-Hoon , Zhou Yong-Pin
Published: July 2006

We extend the Schmittlein et al. model (1987) of customer lifetime value to include satisfaction. Customer purchases are modeled as Poisson events, and their rates of occurrence depend on the satisfaction of the most recent purchase encounter. Customers purchase at a higher rate when they are satisfied than when they are dissatisfied. A closed-form formula is derived for predicting total expected dollar spending from a customer base over a time period (0, T]. This formula reveals that approximating the mixture arrival processes by a single aggregate Poisson process can systematically underestimate the total number of purchases and revenue.

Interestingly, the total revenue is increasing and convex in satisfaction. If the cost is sufficiently convex, our model reveals that the aggregate model leads to an overinvestment in customer satisfaction. The model is further extended to include three other benefits of customer satisfaction: (1) satisfied customers are likely to spend more per trip on average than dissatisfied customers, (2) satisfied customers are less likely to leave the customer base than dissatisfied customers, and (3) previously satisfied customers can be more (or less) likely to be satisfied in the current visit than previously dissatisfied customers. We show that all the main results carry through to these general settings.
An Integrated Choice Model Incorporating Alternative Mechanisms for Consumers’ Reactions to In-Store Display and Feature Advertising
Authors: Zhang Jie
Published: July 2006

The marketing literature has suggested two prominent decision mechanisms through which in-store display and feature advertising can affect brand choice, which I call the price-cut proxy effect and the consideration set formation effect. The primary objective of this study is to propose an integrated brand choice model that incorporates these two possible behavioral mechanisms, which have been shown to work by previous research. The model allows consumers to use various combinations of the decision mechanisms with different probabilities and thus enables one to jointly assess the extent to which each effect might occur in actual purchase data and to investigate how consumers might differ in their tendencies to engage in these decision processes. By incorporating these likely behavioral mechanisms, the proposed model alleviates the problems caused by multicollinearity and produces sensible parameter estimates for the joint effects of promotion vehicles (in-store display, feature ad, and price discount), which contributes to better managerial decision making.
Optimal Data Interval for Estimating Advertising Response
Authors: Tellis Gerard J. , Franses Philip Hans
Published: July 2006

The abundance of highly disaggregate data (e.g., at five-second intervals) raises the question of the optimal data interval to estimate advertising carryover. The literature assumes that (1) the optimal data interval is the interpurchase time, (2) too disaggregate data causes a disaggregation bias, and (3) recovery of true parameters requires assumption of the underlying advertising process. In contrast, we show that (1) the optimal data interval is what we call unit exposure time, (2) too disaggregate data does not cause any disaggregation bias, and (3) recovery of true parameters does not require assumption of the advertising process but only data at the unit exposure time. These results hold for any linear dynamic model linking sales with current and past advertising.
On the Profitability of Firms in a Differentiated Industry
Authors: Jing Bing
Published: July 2006

In a model of vertical differentiation, the principal concern of this paper is to identify sufficient conditions for producing a higher- or lower-quality good to be more profitable (in terms of profits and profit margin). Our basic model considers a short-run scenario where the firms’ quality levels are fixed and they engage in price competition. Here, our results are three. First, we develop the notion of relative cost efficiency and show that its (increasing or decreasing) monotonicity in product quality implies that of firm profitability in equilibrium. A firm’s relative cost efficiency refers to its quality-adjusted cost (dis)advantage relative to its immediate competitors, for a given distribution of consumer tastes. Second, selling a higher-quality good is more profitable when absolute cost efficiency (defined as the ratio between a firm’s quality and unit cost) is increasing in quality. Third, we also establish a set of lower and upper bounds on each firm’s profitability.

The basic model is then extended in two directions. We examine unit cost functions that demonstrate monotone profitability, even when both quality and price are endogenous variables. We also show that the spirit of relative cost efficiency and its associated sufficient condition hold valid for a logconcave consumer distribution.
Biologisch aktive Moleküle mit “Lichtschalter”
Authors: Mayer Günter , Heckel Alexander
Published: July 2006

Biologisch aktive Verbindungen, die auf Licht reagieren, bieten experimentelle Möglichkeiten, die sonst nur sehr schwierig zu realisieren sind. Da Licht z. B. mit Lasern und (konfokalen) Mikroskopen punktgenau eingesetzt werden kann, sind schnelle Konzentrationssprünge der aktiven Form von Molekülen mit exakter räumlicher, zeitlicher und dosierungsbezogener Steuerung möglich. Die Entwicklung derartiger Strategien reicht bis in die 70er Jahre zurück. Dieser Aufsatz fasst neue Entwicklungen der letzten fünf Jahre zusammen und behandelt “kleine Moleküle”, Proteine und Nucleinsäuren, die entweder durch Licht irreversibel aktiviert werden (“photoaktivierbare Verbindungen”) oder reversibel zwischen einem aktiven und einem inaktiven Zustand geschaltet werden.
Novel formulation of the quadrupole equation for potential stellar gravitational‐wave power estimation
Authors: Baker R. M. L.
Published: July 2006

A novel formulation of the quadrupole equation for potential stellar gravitational‐wave power estimation is derived. The derivation commences with the classical Einstein quadrupole formalism and then utilizes Newton's second law to establish a simplified formulation involving the radius of gyration of a mass or system of masses involving a pair of massive stars either on orbit about one another, or otherwise separated, or a star with a dumbbell‐like or aspherical mass distribution and an impulsive force acting on the mass or masses in order to estimate the power of a gravitational wave that is generated. A numerical example, based upon the well‐known gravitational‐wave power observed to be generated by PSR 1913+16, is utilized to test the formulation. Potential applications to stellar jets, including stellar‐black‐hole produced jets, are cited as examples of the potential applications of the novel quadrupole formulation. It is suggested that the gravitational waves, generated by the applications suggested, might be detected by the proposed space‐based Laser Interferometer Space Antenna or LISA. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Challenges in optics for Extremely Large Telescope instrumentation
Authors: Spanò P. , Zerbi F. M. , Norrie C. J. , Cunningham C. R. , Strassmeier K. G. , Bianco A. , Blanche P. A. , Bougoin M. , Ghigo M. , Hartmann P. , Zago L. , Atad‐Ettedgui E. , Delabre B. , Dekker H. , Melozzi M. , Snÿders B. , Takke R. , Walker D. D.
Published: July 2006

We describe and summarize the optical challenges for future instrumentation for Extremely Large Telescopes (ELTs). Knowing the complex instrumental requirements is crucial for the successful design of 30–60 m aperture telescopes. After all, the success of ELTs will heavily rely on its instrumentation and this, in turn, will depend on the ability to produce large and ultra‐precise optical components like light‐weight mirrors, aspheric lenses, segmented filters, and large gratings. New materials and manufacturing processes are currently under study, both at research institutes and in industry. In the present paper, we report on its progress with particular emphasize on volume‐phase‐holographic gratings, photochromic materials, sintered silicon‐carbide mirrors, ion‐beam figuring, ultra‐precision surfaces, and free‐form optics. All are promising technologies opening new degrees of freedom to optical designers. New optronic‐mechanical systems will enable efficient use of the very large focal planes. We also provide exploratory descriptions of “old” and “new” optical technologies together with suggestions to instrument designers to overcome some of the challenges placed by ELT instrumentation. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Cancelling magnetic feature and filament activation
Authors: Contarino L. , Romano P. , Zuccarello F.
Published: July 2006

We report in this paper the analysis of the evolution of a magnetic fragment observed in NOAA 9445 on 5 May, 2001. This magnetic fragment emerged laterally to a filament which later split into two parts. The bifurcation site coincided with the magnetic fragment location and the part of the filament which split was later destabilized and a flare occurred. The magnetic flux variations in the magnetic fragment and in the surrounding area were analyzed and, considering their trends and other observational signatures (Hα brightenings and associated plasma motions), we could infer that it was a cancelling magnetic feature (CMF).We determined some geometrical and physical parameters of the CMF (area, magnetic flux variation, cancellation speed and flux cancellation rate) using high resolution magnetograms taken by BBSO. We compared the observed parameters of the CMF with the parameters of low‐lying reconnection current sheets given in the model proposed by Litvinenko (1999) and found good agreement between observed and theoretical values. Therefore, we conclude that a low‐lying magnetic reconnection process might be the cause of the filament activation. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Epstein–Barr virus in breast cancer: artefact or aetiological agent?
Authors: Murray PG
Published: July 2006

The Epstein–Barr virus (EBV) has been reported to be associated with a variety of different tumours; for some of these malignancies, including breast cancer, the association remains controversial. This might be due in part to differences in the methodologies used to detect EBV in tissue samples. One approach favoured by many groups is to use immunohistochemistry to detect an EBV protein, EBNA1, which is essential for the maintenance of viral latency in infected cells and therefore should be a good marker for the presence of the virus. However, in this issue of the Journal of Pathology, Hennard and colleagues report that one of the antibodies frequently employed to detect EBNA1 in tissue samples cross‐reacts with the MAGE4 protein, a cancer testis antigen expressed in many cancer types. Their observation suggests that reports documenting an EBV association on the basis of reactivity with this antibody must be considered unreliable. It also re‐opens the debate about whether breast cancer is an EBV‐associated disease. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Influence of blend miscibility on the proton conductivity and methanol permeability of polymer electrolyte blends
Authors: Gasa Jeffrey V. , Weiss R. A. , Shaw Montgomery T.
Published: July 2006

The influence of miscibility on the transport properties of polymer electrolyte blends composed of a proton conductor and an insulator was investigated. The proton‐conductive component in the blends was sulfonated poly(ether ketone ketone) (SPEKK), while the nonconductive component was either poly(ether imide) (PEI) or poly(ether sulfone) (PES). The phase behavior of PEI‐SPEKK blends was strongly influenced by the sulfonation level of the SPEKK. At low sulfonation levels (ion‐exchange capacity (IEC) = 0.8 meq/g), the blends were miscible, while at a slightly higher level (IEC = 1.1 meq/g), they were only partially miscible and for IEC ≥ 1.4 meq/g they were effectively immiscible over the entire composition range. The PES‐SPEKK blends were miscible over the entire range of SPEKK IEC considered in this study (0.8–2.2 meq/g). At high IEC (2.2 meq/g) and at low mass fractions of SPEKK (<0.5), the miscible blends (PES‐SPEKK) had higher proton conductivities and methanol permeabilities than the immiscible ones (PEI‐SPEKK). The opposite relationship was observed for high mass fractions of SPEKK (>0.5). This behavior was explained by the differences in morphology between these two blend systems. At low IEC of SPEKK (0.8 meq/g), where both PEI‐SPEKK and PES‐SPEKK blend systems exhibited miscibility, the transport properties were not significantly different. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 2253–2266, 2006
Mechanical and transport property modifications of perfluorosulfonate ionomer membranes prepared with mixed organic and inorganic counterions
Authors: Phillips Alan K. , Moore Robert B.
Published: July 2006

Preparation of solution‐processed perfluorosulfonate ionomer membranes containing both small alkali metal and large alkylammonium counterions has been shown to have a profound impact on the mechanical and transport properties of the resulting acidified ionomer. The use of mixed counterions is shown to be an effective means of tailoring the thermomechanical properties of the membrane as evidenced by compositionally dependent relaxations in dynamic mechanical analysis. In agreement with our recent assignments, the α‐relaxation is found to be systematically dependent on the strength of electrostatic interactions, whereas theTgof Nafion® (i.e., the β‐relaxation) is susceptible to plasticization. Investigations of ionic aggregation using solid‐state23Na NMR and small‐angle X‐ray scattering provided information suggesting the presence of mixed aggregates containing populations of both sodium and tetrabutylammonium ions. In contrast to the general perception that proton conductivity tracks with water content, membranes prepared at a 50:50 sodium/tetrabutylammonium counterion composition, followed by conversion to the H+‐form, showed a minimum in water content yet relatively high proton conductivity. This behavior suggests that specific interactions during processing affect the organization of the ionic domains and yield persistent structures that can significantly influence membrane transport properties. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 2267–2277, 2006
A Study of the Subvesical Bile Duct (Duct of Luschka) in Resected Liver Specimens
Authors: Ko Kenju , Kamiya Junichi , Nagino Masato , Oda Koji , Yuasa Norihiro , Arai Toshiyuki , Nishio Hideki , Nimura Yuji
Published: July 2006

Background

Injury to the duct of Luschka is associated with biliary fistula from the gallbladder bed after cholecystectomy. However, few studies have reported on the detailed anatomy. We elucidated the anatomy and frequency of the duct of Luschka

Methods

A total of 128 specimens from patients who underwent right hepatectomy or more extensive right‐sided liver resection between February 1992 and December 2003 were examined. Specimens were fixed in formalin, and serial sections were prepared to trace the course of the bile ducts from the subsegmental branch level.

Results

The duct of Luschka was observed in 6 (4.6%) specimens. The sites of confluence were as follows: right anterior inferior dorsal branch (2 patients), right anterior branch (2 patients), right hepatic duct (1 patient), and common hepatic duct (1 patient). The upstream end was located in the liver parenchyma of the right anterior inferior dorsal subsegment (5b) and connective tissue of the gallbladder bed in 4 and 2 specimens, respectively.

Conclusions

The duct of Luschka never crosses the segmental (5b) border. Therefore, its upstream region may not be injured by segmentectomy or more extensive liver resection. However, it is possible to injure the duct of Luschka at the common hepatic duct, even if right‐sided hepatectomy is performed, as the sites of confluence included the common hepatic duct.
Preoperative Enteral Immunonutrition Improves Postoperative Outcome in Patients with Gastrointestinal Cancer
Authors: Xu Jianmin , Zhong Yunshi , Jing Dayong , Wu Zhaohan
Published: July 2006

Objectives

The purpose of this study was to evaluate the effect of preoperative immunonutrition pharmaceutics (IMPACT) diet versus standard enteral nutrition (EN) on the nutritional status and immunity of patients with colorectal or gastrointestinal (GI) cancer and to evaluate whether it influences the incidence of postoperative complication.

Methods

Sixty patients with GI cancer were randomly divided into 2 groups, immunonutrition (IM) and control diet (CT), each of which was fed with IMPACT and conventional diet, respectively, for 7 days before surgical procedures. Variables of nutritional status and immunity, postoperative complications, infections, and the days of postoperative hospitalization were measured.

Results

There were no significant differences in the immunological and nutritional variables between the 2 groups preoperatively. The incidence of postoperative complications was significantly lower and the days of postoperative hospitalization were significantly decreased in the IM group. Serum concentrations of both prealbumin (PALB) and transferrin (TRF) were lower in the IM than in the CT group on postoperative day 3 (P < 0.01). TRF continued to be significantly lower in the CT group than in the IM group between day 4 and day 7. However, PALB was significantly lower than before operation in the IM group on postoperative day 3 and TRF was significantly higher in the IM than the CT group on postoperative day 3 (P < 0.05). Both PALB and TRF were significantly higher in the IM than the CT group on postoperative day 7 (P < 0.05). Postoperative immunoglobulin G (IgG) level in the IM group was higher than that in the CT group (13.35 ± 2.06 g/l vs. 9.59 ± 2.23 g/l, P < 0.05). CD4/CD8 ratio was significantly higher in the IM group (2.10 ± 0.51 vs. 1.62 ± 0.52, P < 0.05).

Conclusions

Preoperative enteral IM in patients with GI cancer improves nutritional status and immunity and decreases the incidence of postoperative complications and infections.
Homozygosity for the double D409H+H255Q allele in type II Gaucher disease
Authors: Michelakakis Helen , Moraitou Marina , Dimitriou Evagelia , Santamaria Raul , Sanchez Gessami , Gort Laura , Chabas Amparo , Grinberg Daniel , Dassopoulou Maria , Fotopoulos Spyros , Vilageliu Lluisa
Published: July 2006

Homozygosity for D409H has been associated with a unique type III subtype of the disease with a phenotype dominated by severe cardiovascular involvement, whereas neurological findings, if present, are restricted to oculomotor apraxia and features such as visceromegaly are either minimal or absent. Using PCR amplification followed by restriction enzyme analysis, 3 patients (1 Greek, 2 Albanians) were IDentified with the D409H/D409H genotype. All shared a very severe early‐onset neurological phenotype that classified them as type II. Amplification and sequencing of the full coding region of the GBA gene revealed that all three patients were homozygous not only for D409H but also for H255Q. Both mutations were present on the same allele, as shown by analysis of the parental DNA. The double D409H+H255Q allele was found in heterozygosity in Greek, Bulgarian and Argentinian patients but was not IDentified in any Spanish patients carrying the D409H mutation.
Improved angiogenic response in pig heart following ischaemic injury using human skeletal myoblast simultaneously expressing VEGF165 and angiopoietin‐1
Authors: Ye Lei , Haider Husnain Kh. , Jiang Shujia , Tan Ru San , Ge Ruowen , Law Peter K. , Sim Eugene K.W.
Published: July 2006

Objective

To achieve angiogenic interaction between VEGF165 and angiopoietin‐1 (Ang‐1) using a novel adenoviral bicistronic vector (Ad‐Bic) encoding the two factors and delivered ex vivo using sex‐mismatched human skeletal myoblasts.

Methods and results:

A myocardial infarction model was developed in 29 female pigs; randomised into four groups: DMEM (group‐1, n=6); Adenovirus null (Ad‐null) vector‐myoblast (group‐2, n=5); Ad‐Ang‐1 myoblast (group 3, n=7) and Ad‐Bic‐myoblast (group‐4, n=11). Three weeks later, 5 ml DMEM without myoblasts or containing 3 × 108 myoblasts carrying lac‐z gene and transduced with Ad‐null, Ad‐Ang‐1 or Ad‐Bic were injected intra‐myocardially in and around the infarct. 2D‐echocardiography and fluorescent microsphere studies 6‐ and 12‐weeks post‐treatment revealed significantly improved cardiac performance and regional blood flow in groups 3 and 4. Histological studies and Y‐chromosome analysis revealed extensive survival of lac‐z positive myoblasts staining positive for human proteins in the pig heart. ELISA, immunostaining and RT‐PCR revealed that Ad‐Bic transduced myoblasts concomitantly but transiently expressed hVEGF165 and Ang‐1 both in vitro and in vivo. Double fluorescent immunostaining of the tissue sections for vWFactor‐III and smooth muscle actin showed significantly higher vascular density of mature blood vessels per low power microscopic field in groups 3 and 4 at 6‐ and 12‐weeks.

Conclusion:

Our combined approach led to enhanced angiogenesis with a greater percentage of functionally mature blood vessels in a porcine heart.
Duration of the haemodynamic action of a 24‐h infusion of levosimendan in patients with congestive heart failure
Authors: Lilleberg J. , Laine M. , Palkama T. , Kivikko M. , Pohjanjousi P. , Kupari M.
Published: July 2006

Aims:

To determine the duration of haemodynamic and neurohormonal action of a 24‐h infusion of levosimendan in heart failure.

Methods and results:

This was a double‐blind, parallel group study in patients with New York Heart Association class II to IV heart failure. Twenty‐two patients, with left ventricular ejection fraction <35% and pulmonary capillary wedge pressure (PCWP) above 12 mmHg, were randomised to receive either levosimendan (12 μg/kg followed by a continuous infusion of 0.1–0.2 μg/min) or placebo. Invasively measured cardiac output (CO) increased from 4.3 l/min to 5.4 l/min in the levosimendan group at 6 h. PCWP decreased from 20 mmHg to 15 mmHg in response to levosimendan. Echocardiographically measured maximal effect on PCWP occurred after 6 h, whereas CO reached its highest value at 24 h. The estimated duration of the decrease in PCWP was 7–9 days, and in CO was 12–13 days. Plasma NT‐proANP and NT‐proBNP levels reached their lowest values at days 3 and 2, and the treatment effect was estimated to last 16 and 12 days, respectively. The long‐acting haemodynamic responses reflect levels of the active metabolites OR‐1896 and OR‐1855, maximal metabolite levels occurred at day 3.

Conclusions:

Levosimendan infusion achieved a rapid improvement in haemodynamic parameters in patients with congestive heart failure with maximal effects occurring 1–3 days after starting the infusion, effects were sustained for up to at least a week.
Post‐infarction treatment with simvastatin reduces myocardial no‐reflow by opening of the KATP channel
Authors: Yang Yue‐Jin , Zhao Jing‐Lin , You Shi‐Jie , Wu Yong‐Jian , Jing Zhi‐Cheng , Gao Run‐Lin , Chen Zai‐Jia
Published: July 2006

Simvastatin can prevent cardiac remodelling after myocardial infarction, though the exact mechanisms are uncertain. Myocardial no‐reflow is associated with progressive cardiac remodelling. However, it remains unknown whether post‐infarction treatment with simvastatin can also reduce myocardial no‐reflow for which suppression of adenosine triphosphate‐sensitive K+ (KATP) channel opening is an important mechanism.

Methods:

Area at risk and the area of no‐reflow were determined by myocardial contrast echocardiography (MCE) and by pathology in 45 mini‐swine randomised into 5 groups: 10 control, 9 simvastatin, 9 glibenclamide, 9 simvastatin plus glibenclamide and 8 sham‐operated. A myocardial infarction and reperfusion model was created by 3‐h occlusion of the coronary artery followed by 4 weeks of reperfusion.

Results:

Compared with the control group, simvastatin significantly increased coronary blood volume (P<0.01) and decreased the area of no‐reflow measured by MCE (78.5±4.5% to 43.7±4.3%) and pathological evaluation (82.3±1.9% to 45.2±3.8%) of area at risk (P<0.01). Simvastatin also increased the levels of KATP channel proteins (SUR2 and Kir6.2) (P<0.05), but had no effect on necrosis area. The combination of simvastatin and glibenclamide had no significant effect on the above parameters.

Conclusions:

Post‐infarction treatment with simvastatin can reduce myocardial no‐reflow. This beneficial effect is due to activation of the KATP channel.
Changes in connexin 43, metalloproteinase and tissue inhibitor of metalloproteinase during tachycardia‐induced cardiomyopathy in dogs
Authors: Zhong Jing‐quan , Zhang Wei , Gao Haiqing , Li Yan , Zhong Ming , Li Duoling , Zhang Cheng , Zhang Yun
Published: July 2006

Objective:

To study changes in connexin, metalloproteinase and tissue inhibitor of metalloproteinase levels during tachycardia‐induced cardiomyopathy (TIC).

Methods:

Canine models of TIC were established by rapid right atrial pacing at 350–400 beats per min for 8 weeks in 11 dogs, six dogs acted as a sham operation group. Echocardiography, left ventricular pressure and its first derivation with time (positive and negative maximum, dp/dtmax, –dp/dtmax), and intracardiac electrograms were recorded before and after rapid pacing at 1, 4 and 8 weeks. Data were acquired in sinus rhythm. Ultrastructural changes in left ventricular tissue were observed by transmission electron microscope. Connexin 43 (Cx43) levels in the left ventricular myocardium were measured by confocal laser microscopy. The relative abundance of matrix metalloproteinase (MMP‐2) and tissue inhibitor of metalloproteinase (TIMP‐2) were studied by immunoblotting.

Result and conclusions:

(1) Ventricular dilatation and systolic dysfunction occurred after 1 week of rapid right atrial pacing. (2) There was structural damage to the myofibrils, mitochondria, and the sarcoplasmic reticulum with intercalated disk discontinuity. (3) Levels of Cx43 decreased significantly and gap junction remodelling occurred during TIC. (4) TIC may result from several mechanisms, such as ultrastructural changes or gap junction and matrix remodelling.
Disease management programs for heart failure: Not just for the ‘sick’ heart failure population
Authors: McDonald Ken , Conlon Carmel , Ledwidge Mark
Published: July 2006

The development of disease management programs has been a major advance in heart failure care, bringing about significant improvements for the heart failure population, with reduction in readmission, better use of guideline therapy and improved survival. However, at present, the majority of such programs focus their attention only on the sicker segment of this population, with little application of this important service to the broader heart failure population, where potentially benefits may be even more impressive. This has led to an imbalance in the care of patients with heart failure, where aspects of management such as regular structured review and education are preferentially given to the group at the later stages of the natural history of the syndrome. This paper argues for a far wider application of the disease management program concept in heart failure care so as to bring the benefits of specialist care, patient education and follow‐up to patients at an earlier stage in the natural history of heart failure.
Hypothesis: Correction of low vitamin D status among Arab women will prevent heart failure and improve cardiac function in established heart failure
Authors: Saadi Hussein F. , Kazzam Elsadig , Ghurbana Bahlul A. , Nicholls M. Gary
Published: July 2006

Vitamin D deficiency is common in Arab countries particularly among women. This is the result of a low dietary intake of the vitamin, limited exposure to sunlight (a paradox in view of the high sunshine figures), skin colour, obesity and high parity. Apart from its adverse effects on bone in women and their offspring, vitamin D deficiency has the potential to cause or exacerbate heart failure through a number of mechanisms including activation of the renin–angiotensin system and increased arterial pressure. Accordingly, we propose that ensuring adequate vitamin D levels in Arab women will have a much greater impact on health than just the prevention of bone disease. In particular, we suggest that prevention and correction of vitamin D deficiency will reduce the incidence of heart failure and, for Arab women with established heart failure and vitamin D deficiency, improve cardiac function.
Tako‐Tsubo‐like syndrome during anaphylactic reaction
Authors: Vultaggio Alessandra , Matucci Andrea , Del Pace Stefano , Simonetti Ignazio , Parronchi Paola , Rossi Oliviero , Maggi Enrico , Gensini Gianfranco , Romagnani Sergio
Published: July 2006

Tako‐Tsubo's syndrome (apical ballooning or broken heart syndrome) is a reversible left ventricular dysfunction due to apical asynergy that occurs typically after sudden emotional stress in a subject without coronary disease. It is characterized by acute onset of chest pain or dyspnoea or both and is associated with electrocardiographic changes such as ST segment elevation and/or T wave inversion. Myocardial biomarkers may be normal or slightly elevated.

Anaphylaxis is a severe, life‐threatening, generalized hypersensitivity reaction, most often starting with urticaria and/or angioedema, that may involve cardiovascular and respiratory systems. Cardiovascular symptoms, including hypotension, cardiac arrhythmia and chest pain, are presumably linked to cardiac mast cell mediator release. We describe the case of a young woman who experienced a profound reversible cardiomyopathy with typical features of Tako‐Tsubo's syndrome during an anaphylactic reaction.
Do care patterns change over time in a newly established mental health service? A report from the UK700 trial
Authors: Fiander M. , Burns T. , Ukoumunne O.C. , Fahy T. , Creed F. , Tyrer P. , Byford S.
Published: July 2006

Purpose.

Data on the process of mental health care is scant. Most studies focus on services at their inception when activity may be atypical and then usually present data only mean values for the reported variables over the whole study period. We aimed to test whether care delivery changes over time, and to describe any changes at the individual patient and team levels.

Methods.

Process data on 272 patients in three new intensive case management (ICM) teams were collected over 2 years. Interventions were prospectively recorded using clinician-derived categories. Changes over time are described at both patient and team level.

Results.

The number of contacts and the proportion of face-to-face activity were remarkably constant after the first month at the patient level. The proportion of ‘psychiatric’ interventions (main focus on medication or a specific ‘mental health’ intervention performed) increased greatly after the first 6 months. The care activity received by individual patients varied considerably. Overall, teams varied significantly in the extent to which their activity rates were sustained over time.

Conclusions.

New ICM teams deliver highly individualised care with more marked differences in treatment patterns between patients in the same team than mean differences between teams. The early ‘engagement’ period is marked by a greater focus on social care. There is evidence of differences in sustainability of the services by site.
In vitro self‐propagation of recombinant PrPSc‐like conformation generated in the yeast cytoplasm
Authors: Yang Wenbin , Yang Huaiyi , Tien Po
Published: July 2006

Self‐propagation is characteristic property for a prion conformation. Previous studies revealed that prion protein expressed in the cytoplasm gained a PrPSc‐like conformation. However, it remains unclear whether the PrPSc‐like conformation has the self‐propagating property. We found that PrP partially purified from yeast cytoplasm formed amyloid fiber like structures, and we found that the PrPSc‐like conformation is able to convert normal PrPC in the brain homogenate to a proteinase K‐resistant conformation. These results suggest that yeast cytoplasm expressed recombinant PrPSc‐like conformation has the characteristic self‐propagating property of a prion, which may have implications in the pathogenesis of sporadic and inherited prion diseases.
Impacts of two point mutations of RPE65 from Leber's congenital amaurosis on the stability, subcellular localization and isomerohydrolase activity of RPE65
Authors: Chen Ying , Moiseyev Gennadiy , Takahashi Yusuke , Ma Jian-xing
Published: July 2006

RPE65, a membrane‐associated protein in the retinal pigment epithelium, is the isomerohydrolase essential for regenerating 11‐cis retinal, the chromophore for visual pigments. RPE65 mutations are associated with inherited retinal dystrophies. Here we report that single point mutations of RPE65, Y144D and P363T, identified in patients with Leber's congenital amaurosis (LCA), significantly decreased the stability of RPE65. Moreover, these mutations altered subcellular localization of RPE65 and abolished its isomerohydrolase activity. These observations suggest that the decreased protein stability and altered subcellular localization of RPE65 may represent a mechanism for these mutations to lead to vision loss in LCA patients.
cAMP controls oxygen metabolism in mammalian cells
Authors: Piccoli Claudia , Scacco Salvatore , Bellomo Francesco , Signorile Anna , Iuso Arcangela , Boffoli Domenico , Scrima Rosella , Capitanio Nazzareno , Papa Sergio
Published: July 2006

The impact of cAMP on ROS‐balance in human and mammalian cell cultures was studied. cAMP reduced accumulation of ROS induced by serum‐limitation, under conditions in which there was no significant change in the activity of scavenger systems. This effect was associated with cAMP‐dependent activation of the NADH‐ubiquinone oxidoreductase activity of complex I. In fibroblasts from a patient a genetic defect in the 75 kDa FeS‐protein subunit of complex I resulted in inhibition of the activity of the complex and enhanced ROS production, which were reversed by cAMP. A missense genetic defect in the NDUFS4 subunit, putative substrate of PKA, suppressed, on the other hand, the activity of the complex and prevented ROS production.