bluuebunny/crossref_metadata_2025_split huggingface dataset:
A linkage disequilibrium map of the 1‐Mb 15q12 GABAA receptor subunit cluster and association to autism
Authors: McCauley Jacob L. , Olson Lana M. , Delahanty Ryan , Amin Taneem , Nurmi Erika L. , Organ Edward L. , Jacobs Michelle M. , Folstein Susan E. , Haines Jonathan L. , Sutcliffe James S. 
Published: August 2004

AbstractAutism is a complex genetic neuropsychiatric condition characterized by deficits in social interaction and language and patterns of repetitive or stereotyped behaviors and restricted interests. Chromosome 15q11.2‐q13 is a candidate region for autism susceptibility based on observations of chromosomal duplications in a small percentage of affected individuals and findings of linkage and association. We performed linkage disequilibrium (LD) mapping across a 1‐Mb interval containing a cluster of GABAA receptor subunit genes (GABRB3, GABRA5, and GABRG3) which are good positional and functional candidates. Intermarker LD was measured for 59 single nucleotide polymorphism (SNP) markers spanning this region, corresponding to an average marker spacing of 17.7 kb−1. We identified haplotype blocks, and characterized these blocks for common (>5%) haplotypes present in the study population. At this marker resolution, haplotype blocks comprise <50% of the DNA in this region, consistent with a high local recombination rate. Identification of haplotype tag SNPs reduces the overall number of markers necessary to detect all common alleles by only 12%. Individual SNPs and multi‐SNP haplotypes were examined for evidence of allelic association to autism, using a dataset of 123 multiplex autism families. Six markers individually, across GABRB3 and GABRA5, and several haplotypes inclusive of those markers, demonstrated nominally significant association. These results are positively correlated with the position of observed linkage. These studies support the existence of one or more autism risk alleles in the GABAA receptor subunit cluster on 15q12 and have implications for analysis of LD and association in regions with high local recombination. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website athttp://www.interscience.wiley.com/jpages/0148‐7299:1/suppmat/index.html. © 2004 Wiley‐Liss, Inc.
Neural connections between the hypothalamus and the liver
Authors: Uyama Naoki , Geerts Albert , Reynaert Hendrik 
Published: August 2004

AbstractAfter receiving information from afferent nerves, the hypothalamus sends signals to peripheral organs, including the liver, to keep homeostasis. There are two ways for the hypothalamus to signal to the peripheral organs: by stimulating the autonomic nerves and by releasing hormones from the pituitary gland. In order to reveal the involvement of the autonomic nervous system in liver function, we focus in this study on autonomic nerves and neuroendocrine connections between the hypothalamus and the liver. The hypothalamus consists of three major areas: lateral, medial, and periventricular. Each area has some nuclei. There are two important nuclei and one area in the hypothalamus that send out the neural autonomic information to the peripheral organs: the ventromedial hypothalamic nucleus (VMH) in the medial area, the lateral hypothalamic area (LHA), and the periventricular hypothalamic nucleus (PVN) in the periventricular area. VMH sends sympathetic signals to the liver via the celiac ganglia, the LHA sends parasympathetic signals to the liver via the vagal nerve, and the PVN integrates information from other areas of the hypothalamus and sends both autonomic signals to the liver. As for the afferent nerves, there are two pathways: a vagal afferent and a dorsal afferent nerve pathway. Vagal afferent nerves are thought to play a role as sensors in the peripheral organs and to send signals to the brain, including the hypothalamus, via nodosa ganglia of the vagal nerve. On the other hand, dorsal afferent nerves are primary sensory nerves that send signals to the brain via lower thoracic dorsal root ganglia. In the liver, many nerves contain classical neurotransmitters (noradrenaline and acetylcholine) and neuropeptides (substance P, calcitonin gene‐related peptide, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, glucagon, glucagon‐like peptide, neurotensin, serotonin, and galanin). Their distribution in the liver is species‐dependent. Some of these nerves are thought to be involved in the regulation of hepatic function as well as of hemodynamics. In addition to direct neural connections, the hypothalamus can affect metabolic functions by neuroendocrine connections: the hypothalamus‐pancreas axis, the hypothalamus‐adrenal axis, and the hypothalamus‐pituitary axis. In the hypothalamus‐pancreas axis, autonomic nerves release glucagon and insulin, which directly enter the liver and affect liver metabolism. In the hypothalamus‐adrenal axis, autonomic nerves release catecholamines such as adrenaline and noradrenaline from the adrenal medulla, which also affects liver metabolism. In the hypothalamus‐pituitary axis, release of glucocorticoids and thyroid hormones is stimulated by pituitary hormones. Both groups of hormones modulate hepatic metabolism. Taken together, the hypothalamus controls liver functions by neural and neuroendocrine connections. © 2004 Wiley‐Liss, Inc.
Anatomy and function of sensory hepatic nerves
Authors: Berthoud Hans‐Rudolf 
Published: August 2004

AbstractVagal and spinal afferent innervation of the portal hepatic area has not been studied as thoroughly as the innervation of other important organs. It is generally agreed that unlike noradrenergic sympathetic efferent nerve fibers, sensory nerve fibers of either vagal or dorsal root/spinal origin do not directly innervate hepatocytes, but are restricted to the stroma surrounding triades of hepatic vasculature and bile ducts, and to extrahepatic portions of the portal vein and bile ducts. For vagal afferent innervation, retrograde and anterograde tracing studies in the rat have clearly shown that only a minor portion of the common hepatic branch innervates the liver area, while the major portion descends in the gastroduodenal branch toward duodenum, pancreas, and pylorus. Hepatic paraganglia, bile ducts, and portal vein receive the densest vagal afferent innervation. Calretinin may be a relatively specific marker for vagal afferent innervation of the portal‐hepatic space. Calcitonin gene‐related peptide (CGRP) is a specific marker for dorsal root afferents, and CGRP‐immunoreactive fibers are mainly present near the intrahepatic vascular bundles and bile ducts, and in the same extrahepatic compartments that contain vagal afferents. Because of the specific anatomical organization of hepatic nerves, selective hepatic denervation, whether selective for the vagal or sympathetic division, or for efferents and afferents, is nearly impossible. Great caution is therefore necessary when interpreting functional outcomes of so‐called specific hepatic denervation studies. © 2004 Wiley‐Liss, Inc.
Innervation of the extrahepatic biliary tract
Authors: Balemba Onesmo B. , Salter Matthew J. , Mawe Gary M. 
Published: August 2004

AbstractThe extrahepatic biliary tract is innervated by dense networks of extrinsic and intrinsic nerves that regulates smooth muscle tone and epithelial cell function of extrahepatic biliary tree. Although these ganglia are derived from the same set of precursor neural crest cells that colonize the gut, they exhibit structural, neurochemical, and physiological characteristics that are distinct from the neurons of the enteric nervous system. Gallbladder neurons are relatively inexcitable, and their output is driven by vagal inputs and modulated by hormones, peptides released from sensory fibers, and inflammatory mediators. Gallbladder neurons are cholinergic and they can express a number of other neural active compounds, including substance P, galanin, nitric oxide, and vasoactive intestinal peptide. Sphincter of Oddi (SO) ganglia, which are connected to ganglia of the duodenum, appear to be comprised of distinct populations of excitatory and inhibitory neurons, based on their expression of choline acetyltransferase and substance P or nitric oxide synthase, respectively. While SO neurons likely receive vagal input and their activity is modulated by release of neuropeptides from sensory fibers, a significant source of excitatory synaptic input to these cells arise from the duodenum. This duodenum‐SO circuit is likely to play an important role in the coordination of SO tone with gallbladder motility in the process of gallbladder emptying. Now that we have gained a relatively thorough understanding of the innervation of the biliary tree under healthy conditions, the way is paved for future studies of altered neural function in biliary disease. © 2004 Wiley‐Liss, Inc.
Hepatic nervous system development
Authors: Delalande Jean‐Marie , Milla Peter J. , Burns Alan J. 
Published: August 2004

AbstractDuring embryonic development, the liver emerges from the foregut as a thickening of the ventral endodermal epithelium. The embryonic liver then develops into a bud of cells that proliferates and differentiates to eventually form the largest gland of the body. Prior to birth, the primary function of the liver is hematopoietic, and the organ receives little innervation during early development. Postnatally, the role of the liver changes and many different nerve types modulate its function. Although the liver shares a common embryonic origin with other foregut derivatives, such as the gallbladder and the pancreas, the development of its innervation exhibits distinct characteristics. In this review, we summarize what is known about the development of the hepatic innervation, draw comparisons with the intrinsic innervation of the gastrointestinal tract and associated organs, and discuss the potential role of molecular signals in guiding the nerves that innervate the liver. © 2004 Wiley‐Liss, Inc.
Innervation of the sinusoidal wall: Regulation of the sinusoidal diameter
Authors: Ueno Takato , Bioulac‐Sage Paulette , Balabaud Charles , Rosenbaum Jean 
Published: August 2004

AbstractIn the livers of humans, cats, guinea pigs, and tupaia, nerve endings are distributed all over the hepatic lobules. Nerve endings in the intralobular spaces are localized mainly in the Disse spaces and are oriented toward the hepatic stellate cells (HSCs), sinusoidal endothelial cells, and hepatocytes. They are especially closely related to HSCs. Various neurotransmitters such as substance P exist in the nerve endings. In addition, HSCs possess endothelin (ET) and adrenergic receptors and contract in response to the corresponding agonists. In contrast, nitric oxide (NO) inhibits the contraction of HSCs. HSCs thus appear to be involved in the regulation of hepatic sinusoidal microcirculation by contraction and relaxation. In the cirrhotic liver, intralobular innervation is decreased, but ET, ET receptors, and NO are overexpressed in the HSCs. These findings indicate that HSCs in cirrhotic liver may play an important role in the sinusoidal microcirculation through agents such as ET or NO rather than through intralobular innervation. © 2004 Wiley‐Liss, Inc.
Neural control of hepatic osmolytes and parenchymal cell hydration
Authors: Häussinger Dieter 
Published: August 2004

AbstractLiver cell function is strongly influenced by cell hydration and osmolyte content via osmosensing and osmosignaling pathways. Electrical stimulation of hepatic nerves increases the hepatocellular hydration state via an α‐adrenergic mechanism, promotes taurine release from parenchymal cells and myo‐inositol release from hepatic stellate cells. Although changes in liver cell hydration and osmolyte content are known regulators of liver cell function, the functional relevance and integration of nerve‐stimulation‐dependent alterations of liver cell volume and osmolyte content in the overall hepatic response to towards signals from the nervous system remains to be established. © 2004 Wiley‐Liss, Inc.
Neuroregulation of the neuroendocrine compartment of the liver
Authors: Roskams Tania , Cassiman David , De Vos Rita , Libbrecht Louis 
Published: August 2004

AbstractLiver progenitor cells as well as hepatic stellate cells have neuroendocrine features. Progenitor cells express chromogranin‐A and neural cell adhesion molecule, parathyroid hormone‐related peptide, S‐100 protein, neurotrophins, and neurotrophin receptors, while hepatic stellate cells express synaptophysin, glial fibrillary acidic protein, neural cell adhesion molecule, nestin, neurotrophins, and their receptors. This phenotype suggests that these cell types form a neuroendocrine compartment of the liver, which could be under the control of the central nervous system. We recently showed that the parasympathetic nervous system promotes progenitor cell expansion after liver injury, since selective vagotomy reduces the number of progenitor cells after chemical injury in the rat. Similarly, after transplantation, which surgically denervates the liver, human livers that develop hepatitis have fewer progenitor cells than native, fully innervated livers with similar degrees of liver injury. There is also accumulating experimental evidence linking the autonomic system, in particular the sympathetic nervous system (SNS), with the pathogenesis of cirrhosis and its complications. Recently, it has been shown that hepatic stellate cells themselves respond to neurotransmitters. Moreover, inhibition of the SNS reduced fibrosis in carbon tetrachloride‐induced liver injury. In view of the denervated state of transplanted livers, it is very important to unravel the neural control mechanisms of regeneration and fibrogenesis. Moreover, since there is a shortage of donor organs, a better understanding of the mechanisms of regeneration could have therapeutic possibilities, which could even obviate the need for orthotopic liver transplantation. © 2004 Wiley‐Liss, Inc.
Transplanted liver: Consequences of denervation for liver functions
Authors: Colle Isabelle , Van Vlierberghe Hans , Troisi Roberto , De Hemptinne Bernard 
Published: August 2004

AbstractFollowing liver transplantation, all hepatic nerves are transected; thus, liver allografts are completely isolated from neural control of their hosts. Despite this absolute denervation, liver allograft function does not appear to be significantly impaired after successful transplantation. In experimental animal models, hepatic denervation has no major effects on bile acid production and biotransformation, while it increases blood pressure and salt retention; decreases the number of hepatic progenitor cells, cholangiocyte proliferation, and liver regeneration; and influences the hepatic microcirculation, diet behavior, and glycemic control. In humans, hepatic denervation after liver transplantation has no major deleterious effects on bile secretion, liver regeneration, and hepatic blood flow. Insulin resistance and postprandial hyperglycemia, changes in ingestion behavior, and reduced stimulation of hepatic progenitor cells in the canals of Hering are the major side effects of absent liver innervation. Despite these abnormalities, patients can lead a new life with improved quality of life. © 2004 Wiley‐Liss, Inc.
When is “enough” enough? Modeling the information‐seeking and stopping behavior of senior arts administrators
Authors: Zach Lisl 
Published: August 2004

AbstractAmong managers, those who are responsible for nonprofit organizations in general and arts organizations in particular have been an understudied group. These managers have much in common with their for‐profit counterparts, but their environment also differs in significant ways. The goal of this exploratory research effort was to identify how senior administrators in fine arts museums and symphony orchestras go about identifying and acquiring the information they want to complete a range of management tasks. Deciding when and where to look for information, obtaining the “right” information at the time it is needed, evaluating its credibility and utility, and determining when “enough” information has been collected are challenges facing this group of information users every day. A multiple‐case studies design involving a replication strategy was selected to structure the research process. Data were collected from 12 arts administrators using a pretested interview protocol that included the Critical Incident Technique. Patterns in the data were identified, and the data were further reviewed for disconfirming evidence. The study resulted in a list of the types and sources of information that arts administrators use as well as a list of the factors or “stopping criteria” that influence them to end their information‐seeking process. A model describing the way in which arts administrators go about acquiring the information they want was also developed. The main findings of the study are (a) arts administrators do not consider information seeking to be a discrete management task, (b) they rely heavily on direct personal experience to fill their information‐seeking needs, and (c) they are “satisficers” when it comes to seeking information. Based on Simon's alternative to rational choice theory, satisficers are people who are willing to pursue a “good enough” option rather than the best possible option (maximizers) (Simon, 1956). Since arts administrators have not been studied in the context of LIS research before, understanding more about where they go for information, what factors influence the level of effort they are willing to invest in seeking information, and how they decide when they have “enough” information provides insights into the information‐seeking behavior of a new user group. Furthermore, although this research effort is focused on specific users in a specific field, the results from this study may be compared to what we already know about other user groups to confirm and expand existing models of information‐seeking behavior.
Pharmacokinetics and safety of oral almotriptan in healthy male volunteers
Authors: McEwen J. , Salva M. , Jansat J.M. , Cabarrocas X. 
Published: August 2004

AbstractAlmotriptan (LAS 31416) is a new, oral, specific 5‐hydroxytryptamine1B/1D receptor agonist for the treatment of migraine. The pharmacokinetics and safety of a range of oral doses were assessed in 23 healthy male volunteers. Peak plasma concentrations were reached between 1.5 and 4 h after dosing. The maximum plasma concentration and area under the curve showed dose proportionality over the dose range 5–200 mg. The elimination half‐life was constant at approximately 3 h across all dose levels. A substantial proportion of the initial dose was excreted in urine (27%–39%) during 12 h post‐dose and the main excretory product was unchanged drug. Three major urinary metabolites were detected, all of which were pharmacologically inactive. The most common events following almotriptan administration were headache, tiredness and mild nausea. Nine events (18%) were classed as probably related to almotriptan and these were all at the highest dose level of 200 mg. The maximum tolerated dose of almotriptan was, therefore, determined as 150 mg. In conclusion, almotriptan is well tolerated following single, oral doses up to 150 mg and has predictable pharmacokinetics. Copyright © 2004 John Wiley & Sons, Ltd.
Enhancement of tyrosinase inhibition of the extract of Veratrum patulum using cellulase
Authors: Kim Dong Hyun , Kim Jin Hee , Baek Seung Hwa , Seo Jin Ho , Kho Yung Hee , Oh Tae Kwang , Lee Choong Hwan 
Published: August 2004

AbstractInhibitors of melanin biosynthesis were screened by using three different methods. The extract of Veratrum patulum contains hydroxystilbene compounds that are potent tyrosinase inhibitors. We evaluated the enzyme inhibitory property on the mushroom tyrosinase of hydroxystilbene compounds including resveratrol, oxyresveratrol, and their analogs. Biotransformation using cellulase of the whole extract brought about an increase in the inhibitory activity of the products on mushroom tyrosinase. The enhancement of tyrosinase inhibition is supposed to increase the concentration of aglycon, which has superior inhibitory activity to its glycoside. Eventually, melanin biosynthesis was inhibited by the enhanced tyrosinase inhibitory activity of the extract. This result indicated that deglycosylation of stilbene compounds has exerted more effective inhibition on the enzyme than that of the unprocessed plant extract. © 2004 Wiley Periodicals, Inc.
Thermodynamic analysis of product formation in mesophilic acidogenesis of lactose
Authors: Yu Han‐Qing , Mu Yang , Fang Herbert H. P. 
Published: August 2004

AbstractThermodynamic analysis on the acidogenesis of lactose was performed to evaluate the different acidogenic patterns and mechanisms by using Gibbs free energy calculation. Batch acidogenesis of lactose was investigated by using an enriched culture at 37°C, pH 5.5 and varied substrate levels. In addition to usual acidogenic products, i‐butyrate, valerate, i‐valerate, caproate, and propanol were also produced at a significant level. Thermodynamic analysis shows that valerate might be formed through the reaction requiring hydrogen as electron donor and consuming of propionate and carbon dioxide. Caproate was most likely produced directly from butyrate, hydrogen, and carbon dioxide. The minimum amount of Gibbs free energies needed to sustain isomerization of butyrate and valerate were approximately 5.7–5.8 and 4.5–4.6 kJ/mol, respectively. Propanol was produced from acetate, hydrogen, and carbon dioxide with a minimum amount of Gibbs free energy of 41.8–42.0 kJ/mol. Formation of butanol was controlled more by substrate level or population dynamics than by thermodynamics. © 2004 Wiley Periodicals, Inc.
Real‐time detection of 13C NMR labeling kinetics in perfused EMT6 mouse mammary tumor cells and βHC9 mouse insulinomas
Authors: Mancuso A. , Beardsley N.J. , Wehrli S. , Pickup S. , Matschinsky F.M. , Glickson J.D. 
Published: August 2004

AbstractA method was developed for obtaining high signal‐to‐noise 13C NMR spectra of intracellular compounds in metabolically active cultured cells. The method allows TCA cycle labeling kinetics to be determined in real time without significant oxygen transport limitations. Cells were immobilized on the surface of nonporous microcarriers that were either uncoated or coated with polypeptides and used in a 12‐cm3 packed bed. The methods were tested with two EMT6 mouse mammary tumor cell lines, one strongly adherent and the other moderately adherent, and a weakly adherent mouse insulinoma line (βHC9). For both EMT6 lines, NTP and oxygen consumption measurements indicated that the number of cells in the spectrometer ranged from 6 × 108 to 1 × 109. During infusion of [1‐13C]glucose, labeling in C‐4 glutamate (indicative of flux into the first half of the TCA cycle) could be detected with 15‐min resolution. However, labeling for C‐3 and C‐2 glutamate (indicative of complete TCA cycle activity) was fivefold lower and difficult to quantify. To increase TCA cycle labeling, cells were infused with medium containing [1,6‐13C2]glucose. A 2.5‐fold increase was observed in C‐4 glutamate labeling and C‐3 and C‐2 glutamate labeling could be monitored with 30‐min resolution. Citrate synthase activity was indirectly detected in real time, as [3,4‐13C2]glutamate was formed from [2‐13C]oxaloacetate and [2‐13C]acetate (of acetyl‐CoA). Cell mass levels observed with βHC9 cells were somewhat lower. However, the 13C S/N was sufficient to allow real‐time monitoring of the response of intracellular metabolite labeling to a step change in glucose and a combined glutamine/serum pulse. © 2004 Wiley Periodicals, Inc.