bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of tissue‐type plasminogen activator gene in mice aggravated liver fibrosis
Authors: Hsiao Yao , Zou Tie , Ling Chang‐Chun , Hu Hua , Tao Xian‐Mei , Song Hou‐Yan 
Published: October 2007

AbstractBackground and Aim:  Tissue‐type plasminogen activator (tPA) is one of the major components in the matrix proteolytic network whose role in the pathogenesis of liver fibrosis remains unknown. The aim of this study is to investigate the role of tPA in carbon tetrachloride (CCl4)‐induced liver fibrosis.Methods:  Wild‐type and tPA knockout mice (8 mice per group) were injected interperitoneumly with 25% CCl4 2 ml/kg twice per week as CCl4 administration groups and olive oil 2 ml/kg as controls. After 4 weeks, the livers of mice were removed under deep anesthesia and prepared for further studies such as histology, immunostaining, hydroxyproline assay, zymography and western blot analysis.Results:  Mice lacking tPA developed more severe morphological injury and displayed an increased deposition of collagen in the liver after CCl4 administration compared with wild‐type counterparts. Deficiency of tPA increased α‐smooth muscle actin expression in the mice livers. On the other hand, the decrease of matrix metalloproteinase‐2 (MMP‐2), matrix metalloproteinase‐9 (MMP‐9) activities, metalloproteinase‐13 (MMP‐13) expression and a marked increase of tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1) expression were found in the liver of CCl4 administrated tPA−/− mice compared with wild‐type counterparts.Conclusions:  Deficiency of tPA aggravated liver fibrosis through promoting hepatic stellate cells (HSCs) activation and inhibiting ECM degradation by decreasing MMP‐2, MMP‐9 activities and disrupting the balance between MMP‐13 and TIMP‐1.
Mycophenolate mofetil prevents lethal acute liver failure in mice induced by bacille Calmette‐Guérin and lipopolysaccharide
Authors: Yang Yong‐Feng , Tan De‐Ming , Xie Yu‐Tao , Zhao Wei , Hou Zhou‐Hua , Zhong Yan‐Dan 
Published: October 2007

AbstractBackground/Aims:  To investigate the effect of mycophenolate mofetil (MMF) on acute liver injury induced by bacille Calmette‐Guérin (BCG) and lipopolysaccharide (LPS).Methods:  Acute liver failure was induced in male Kunming strain mice by injecting the animals with BCG 2.5 mg per mouse, and LPS 10 μg per mouse 10 days later. The mice in the treatment groups were given MMF 2 h before, simultaneous with, or 2 h after administration of LPS, and the mice in the control group were given the same dose of saline. The 24‐h survival rate, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were compared. Serum levels of tumor necrosis factor alpha (TNF‐α), interferon gamma (IFN‐γ), and interleukin 6 (IL‐6) were measured and the expressions of TNF‐α, IFN‐γ, and IL‐6 mRNA in the liver tissue were determined by reverse transcription–polymerase chain reaction (RT‐PCR). Concanavalin A (Con A)–induced splenocyte proliferation were determined by methods of methyl thiazolyl tetrazolium.Results:  Injecting a small dose of LPS into BCG‐primed mice caused a lethal hepatic injury mimicking acute hepatitis, from which 16 of the 20 mice died within 24 h (20% survival rate). Massive necrosis of parenchymal hepatocytes with marked inflammatory cell infiltration was observed by histological examination. In parallel, serum ALT and TNF‐α, IFN‐γ, and IL‐6 levels were increased. Expression of TNF‐α, IFN‐γ, and IL‐6 mRNA in the liver were significantly increased also. Treatment with MMF markedly reduced the death rate in a dose‐dependent manner. It reached its maximal effect at the dosage of 150 mg per kg of body weight when pretreated 2 h before LPS injection, with improvement of histological feather and survival rate (84.2%, 16/19). MMF significantly inhibited serum levels of TNF‐α, IFN‐γ, and IL‐6, and significantly reduced TNF‐α, IFN‐γ, and IL‐6 expression in the liver, which increased after BCG and LPS injection. Moreover, splenocyte proliferation response induced by Con A was also inhibited by MMF treatment.Conclusions:  Treatment with MMF has a protective effect on endotoxin‐induced fatal liver failure by regulating the production of inflammatory cytokines and T‐cell proliferation.
Cholecystokinin receptor A gene polymorphism in gallstone disease and gallbladder cancer
Authors: Srivastava Anvesha , Pandey Sachchida Nand , Dixit Manjusha , Choudhuri Gourdas , Mittal Balraj 
Published: October 2007

AbstractBackground and Aim:  Gallbladder carcinoma (GBC) usually arises in the background of gallstone disease which may be causatively related to decreased gallbladder contractility. Cholecystokinin receptor A (CCK‐AR) mediates signals resulting in gallbladder contraction. Deteriorating gallbladder contraction promotes gallstone formation. A common genetic polymorphism of CCK‐AR may be causatively associated with the risk of gallstone and GBC. This study aimed to understand the association of CCK‐AR Pst I polymorphism in gallstone disease with gallbladder cancer.Method:  This study included 165 gallstone patients, 139 GBC patients, and 190 healthy subjects. Genotyping was done using the polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) method.Results:  The frequency of the A1A1 genotype of CCK‐AR was significantly higher in gallstone patients than healthy individuals (P = 0.008 odds ratio [OR] = 2.25, and 95% confidence interval [CI]:1.2–4.1). However, there was a significant difference in the frequency of A1A1 genotype when gallstone patients were compared to GBC patients (P = 0.041, OR = 0.49, and 95% CI: 0.3–0.9). On stratification of GBC patients according to presence or absence of gallstones, GBC patients without stones were compared to controls and GBC patients with stones were compared to stone patients; however, no significant differences in frequencies were observed.Conclusion:  The results suggest that the A1A1 genotype of CCK‐AR is an independent genetic risk factor for gallstone disease and does not modulate the susceptibility of gallbladder cancer.
Outcomes of bleeding peptic ulcers: A prospective study
Authors: Liu Nai‐Jen , Lee Ching‐Song , Tang Jui‐Hsiang , Cheng Hao‐Tsai , Chu Yin‐Yi , Sung Kai‐Feng , Lin Cheng‐Hui , Tsou Yung‐Kuan , Lien Jau‐Min , Chen Pang‐Chi , Chiu Cheng‐Tang , Cheng Chi‐Liang 
Published: October 2007

AbstractBackground and Aim:  Bleeding peptic ulcers can be due to Helicobacter pylori (H. pylori) infection, use of non‐steroidal anti‐inflammatory drugs (NSAIDs), or idiopathic causes. The aim of this prospective study was to identify the clinical outcomes of bleeding peptic ulcers related to different causes.Methods:  A total of 390 patients with bleeding ulcers were evaluated consecutively between June 2005 and August 2006. The diagnosis of H. pylori infection was made at index endoscopy, using histology and the rapid urease test. If both endoscopic diagnostic tests were not performed, a serological test was applied to detect the presence of H. pylori infection in a previously untreated patient. The prevalence and outcome of bleeding ulcers are related to H. pylori infection, NSAID use, and non‐H. pylori idiopathic causes. The outcome between patients who were admitted for ulcer bleeding (outpatient bleeder) and those who bled while hospitalized (in‐hospital bleeder) was also compared.Results:  NSAID ulcers were noted in 223 patients, H. pylori ulcers in 102, and non‐H. pylori idiopathic ulcers in 65. In total, 298 patients had outpatient bleeders, and 92 had in‐hospital bleeders. The overall 3‐day rebleeding rate was 11.8% and the mortality rate was 5.4%. Eighteen of the 21 mortality cases died of their underlying comorbid illness. Patients with non‐H. pylori idiopathic ulcers had a significantly higher mortality rate than NSAID and H. pylori ulcers (12.3% vs 4.5% vs 2.9%, P = 0.02). Patients with H. pylori ulcers had significantly favorable outcomes than patients with NSAID ulcers (less blood transfusion and a shorter hospital stay) and non‐H. pylori idiopathic ulcers (shorter hospital stay and a lower mortality). Patients with in‐hospital bleeders had an adverse outcome as compared to outpatient bleeders, including a 3‐day rebleeding rate (25.0% vs 7.7%, P < 0.0001), 30‐day rebleeding rate (32.6% vs 12.1%, P < 0.0001), and higher mortality rate (16.3% vs 2.0%, P < 0.0001).Conclusion:  This study emphasizes the role of non‐H. pylori idiopathic ulcers and in‐hospital bleeders as the determining high‐risk predictors for bleeding peptic ulcers.
Neural cadherin overexpression is a predictive marker for early postoperative recurrence in hepatocellular carcinoma patients
Authors: Seo Dong Dae , Lee Han Chu , Kim Ha Jung , Min Hyun Ju , Kim Kang Mo , Lim Young Suk , Chung Young‐Hwa , Lee Yung Sang , Suh Dong Jin , Yu Eunsil , Chun Sun Young 
Published: October 2007

AbstractBackground and Aim:  Recent studies have disclosed alterations in neural and/or epithelial cadherin (E‐cadherin) expression in several epithelial tumors. However, the clinical relevance of these phenomena in hepatocellular carcinoma (HCC) remains to be established. In this study, we investigated the expression patterns of neural and epithelial cadherins and their clinical implications in HCC.Methods:  Immunohistochemical staining for neural and epithelial cadherins was performed on tumor and adjacent non‐tumor tissue sections of 52 HCC patients subjected to curative surgical resection. Clinical, radiological, and histopathological characteristics were analyzed, relative to the degree of neural and E‐cadherin expression.Results:  The neural cadherin (N‐cadherin) expression was upregulated in 67% of HCC tissues, compared to adjacent non‐tumoral liver tissues. Patients expressing high levels of N‐cadherin experienced more frequent tumor recurrences within 2 years (50% vs 12.5%; P = 0.01) after surgical resection. Consequently, the cumulative overall survival rate tended to be lower in patients overexpressing N‐cadherin (P = 0.08). The N‐cadherin overexpression was the only independent predictive factor for postoperative recurrence within 2 years in both univariate and multivariate analyses (odds ratio: 8.5; 95% confidence interval: 1.625–44.46; P = 0.011). No correlation was evident between E‐cadherin expression patterns and clinicopathological parameters.Conclusion:  The overexpression of N‐cadherin is significantly related to postoperative recurrence within 2 years after surgical resection in HCC. Therefore, immunohistochemical staining for N‐cadherin may be effectively applied as a predictive marker for early postoperative recurrence in HCC.
The time course of transmitter release in mouse motor nerve terminals is differentially affected by activation of muscarinic M1 or M2 receptors
Authors: Dudel J. 
Published: October 2007

AbstractAt endplates of mouse diaphragms the effects of activation of presynaptic muscarinic M1 and M2 autoreceptors on the time courses of monoquantal releases have been investigated at 20 °C. Quantal excitatory postsynaptic currents (qEPSCs) were elicited and recorded with a perfused macropatch electrode, through which control‐ and drug‐containing solutions were applied to 10 µm φ regions of a neuromuscular junction. M2 receptors were activated with muscarine, while the M1 receptors were blocked by pirenzepine. M2 activation presented a slight, but highly significant augmentation of early releases. Analogously, M1 receptors were activated with muscarine, while M2 receptors were blocked by methoctramine. M1 activation elicited a highly significant small shift of the time course of release towards longer delays. In controls, the number of late releases decayed with a time constant of 0.3 ms. This time constant did not change appreciably when methoctramine or methoctramine + muscarine were applied. However, methoctramine + muscarine reduced the amplitude of qEPSCs and shortened their decay by a partial block of postsynaptic channels. Double blocks with pirenzepine + methoctramine allowed no presynaptic effect of muscarine, showing that the blocker concentrations were sufficient. Neither the addition of methoctramine to pirenzepine, nor the further addition of muscarine changed the time constant of decay of the number of late releases. The results are very similar to that of autoreceptor activations in the glutamatergic crayfish synapse: activation of inhibitory receptors augmented early releases, and that of facilitatory receptors depressed early releases [J. Dudel (2006a) Eur. J. Neurosci., 23, 2695–2700], which may suggest a general presynaptic mechanism.
Enhancement of synaptic transmission and nociceptive behaviour in HPC‐1/syntaxin 1A knockout mice following peripheral nerve injury
Authors: Takasusuki T. , Fujiwara T. , Yamaguchi S. , Fukushima T. , Akagawa K. , Hori Y. 
Published: October 2007

AbstractOur previous analysis of HPC‐1/syntaxin 1A knockout (KO) mice indicated that HPC‐1/syntaxin 1A plays an important role in the synaptic plasticity of the hippocampus in vitro and learning behaviour in vivo. In order to gain further insights into the physiological functions of HPC‐1/syntaxin 1A, we studied the changes in the plasticity of synaptic transmission in the superficial dorsal horn of the spinal cord following a peripheral nerve injury in HPC‐1/syntaxin 1A KO and wild‐type (WT) mice. The von Frey filament test revealed that partial ligation of the sciatic nerve caused neuropathic pain in both WT and KO mice. However, KO mice showed significant enhancement of mechanical allodynia as compared with WT mice. Tight‐seal whole‐cell recordings were obtained from neurons in the superficial dorsal horn of the spinal cord slices. Electrical stimulus‐evoked excitatory postsynaptic currents (EPSCs), asynchronous EPSCs (aEPSCs) in the presence of strontium, and spontaneously occurring miniature EPSCs (mEPSCs) were analysed. Prior to peripheral nerve ligation, no significant differences were observed in the properties of evoked EPSCs, aEPSCs and mEPSCs in KO and WT mice. Seven−14 days after partial ligation, the amplitude of evoked EPSCs and the frequency of aEPSCs and mEPSCs in KO mice were significantly greater than those in WT mice; however, the amplitude of aEPSCs and mEPSCs remained unchanged in both groups. Enhanced allodynia behaviour and significant enhancement of excitatory synaptic transmission following peripheral nerve ligation in KO mice suggest that HPC‐1/syntaxin 1A might play a role in synaptic plasticity in the nociceptive pathway.
Pre‐ and postsynaptic excitation and inhibition at octopus optic lobe photoreceptor terminals; implications for the function of the ‘presynaptic bags’
Authors: Piscopo Stefania , Moccia Francesco , Di Cristo Carlo , Caputi Luigi , Di Cosmo Anna , Brown Euan R. 
Published: October 2007

AbstractSynaptic transmission was examined in the plexiform zone of Octopus vulgaris optic lobes using field‐potential recording from optic lobe slices. Stimulation of the optic nerve produced pre‐ and postsynaptic field potentials. Transmission was abolished in calcium‐free seawater, L‐ glutamate or the AMPA/Kainate receptor blocker CNQX (EC50, 40 µm), leaving an intact presynaptic field potential. ACh markedly reduced or blocked and d‐tubocurarine augmented both pre‐ and postsynaptic field potentials, while α‐bungarotoxin and atropine were without effect. Paired‐pulse stimulation showed short‐term depression of pre‐ and postsynaptic components with a half‐time of recovery of ∼ 500 ms. The depression was partially relieved in the presence of d‐tubocurarine (half‐time of recovery, 350 ms). No long‐term changes in synaptic strength were induced by repetitive stimulation. A polyclonal antibody raised against a squid glutamate receptor produced positive staining in the third radial layer of the plexiform zone. No positive staining was observed in the other layers. Taking into account previous morphological data and our results, we propose that the excitatory terminations of the photoreceptors are in the innermost layer of the plexiform zone where the transmitter is likely to be glutamate and postsynaptic receptors are AMPA/kainate‐like. Thus, the function of the terminal bags is to provide a location for a presynaptic cholinergic inhibitory shunt. The results imply that this arrangement provides a temporal filter for visual processing and enhances the perception of moving vs. stationary objects.
The formation of trajectories during goal‐oriented locomotion in humans. I. A stereotyped behaviour
Authors: Hicheur Halim , Pham Quang‐Cuong , Arechavaleta Gustavo , Laumond Jean‐Paul , Berthoz Alain 
Published: October 2007

AbstractHuman locomotion was investigated in a goal‐oriented task where subjects had to walk to and through a doorway starting from a fixed position and orientation in space. The door was located at different positions and orientations in space, resulting in a total of 40 targets. While no specific constraint was provided to subjects in terms of the path they were to follow or the expected walking speeds, all of them generated very similar trajectories in terms of both path geometry and velocity profiles. These results are reminiscent of the stereotyped properties of the hand trajectories observed in arm reaching movements in studies over the last 20 years. This observation supports the hypothesis that common constraining mechanisms govern the generation of segmental and whole‐body trajectories. In contrast, we observed that the subjects placed their feet at different spatial positions across repetitions, making unlikely the hypothesis that goal‐oriented locomotion is planned as a succession of steps. Rather, our results suggest that common planning and/or control strategies underlie the formation of the whole locomotor trajectory during a spatially oriented task.
Translin‐associated factor‐X (Trax) is a molecular switch of growth‐associated protein (GAP)‐43 that controls axonal regeneration
Authors: Schröer Uwe , Volk Gerd Fabian , Liedtke Tomas , Thanos Solon 
Published: October 2007

AbstractThe ability of neurons to form axons requires the choreographed assembly of growth cones. We show that there is a time window from postnatal day 14 (P14) until P21/22 when axons of rat retinal ganglion cells will regenerate under serum‐free culture conditions. In contrast, no outgrowth occurred before P13, and growth declined from P22 and ceased after P30. Using proteomics, we have identified translin‐associated factor X (Trax), a DNA‐binding factor that is expressed during this period of postnatal development. Trax is shown to coexpress with growth‐associated protein GAP‐43. Small interfering RNA‐mediated inhibition of Trax expression resulted in downregulation of both Trax and GAP‐43 transcripts and protein both before and during the period of regeneration (P8) and (P16). In contrast, silencing of Trax at P30 resulted in significant upregulation of the GAP‐43 transcript and protein and induced outgrowth of axons. These data suggest that Trax regulates GAP‐43 transcription and regeneration‐promoting effects during the postnatal maturation period. Trax may represent a new potent therapeutic target gene for optic nerve and spinal cord injuries.
Audition differently activates the visual system in neonatally enucleated mice compared with anophthalmic mutants
Authors: Chabot Nicole , Robert Stéphane , Tremblay Robin , Miceli Dom , Boire Denis , Bronchti Gilles 
Published: October 2007

AbstractThe occipital cortex, normally visual, can be activated by auditory or somatosensory tasks in the blind. This cross‐modal compensation appears after early or late onset of blindness with differences in activation between early and late blind. This could support the hypothesis of a reorganization of sensory pathways in the early blind that does not occur in later onset blindness. Using immunohistochemistry of the c‐Fos protein following a white noise stimulus and injections of the anterograde tracer dextran‐biotin in the inferior colliculus, we studied how the occurrence of blindness influences cross‐modal compensation in the mutant anophthalmic mouse strain and in C57BL/6 mice enucleated at birth. We observed, in mutant mice, immunolabeled nuclei in the visual thalamus – the dorsal lateral geniculate nucleus – in the primary visual area (V1) and a few labeled nuclei in the secondary visual area (V2). In enucleated mice, we observed auditory activity mainly in V2 but also sparsely in V1. No labeled cells could be found in the visual thalamus. Tracing studies confirmed the difference between anophthalmic and birth‐enucleated mice: whereas the first group showed inferior colliculus projections entering both the dorsal lateral geniculate and the latero‐posterior nuclei, in the second, auditory fibers were found only within the latero‐posterior thalamic nucleus. None was found in controls with intact eyes. We suggest that the prenatal period of spontaneous retinal activity shapes the differences of the sensory reorganization in mice.
Role of the corticotropin‐releasing factor receptor type 2 in the control of food intake in mice: a meal pattern analysis
Authors: Tabarin A. , Diz‐Chaves Y. , Consoli D. , Monsaingeon M. , Bale T. L. , Culler M. D. , Datta R. , Drago F. , Vale W. W. , Koob G. F. , Zorrilla E. P. , Contarino A. 
Published: October 2007

AbstractThe actions of corticotropin‐releasing factor (CRF) and related peptides are mediated by two receptors (CRF1and CRF2). The respective role of each subtype in the control of food intake remains poorly known. In the present study, we examined the quantity and microstructure of ingestive behavior of knockout (KO) mice lacking CRF2receptors and their wild‐type (WT) littermates. Under basal conditions, CRF2KO mice showed increased nocturnal food intake, evident as an increased zenith in circadian cosinor analysis of food intake. Microstructure analysis revealed that this greater food intake reflected increased meal size, rather than meal frequency, suggesting a decreased satiating value of food. Following acute restraint stress, CRF2KO mice showed an intact immediate anorectic response with increased latency to eat and decreased meal size. However, CRF2deletion abolished the prolonged phase of restraint‐induced anorexia. CRF2KO mice did not differ from WT controls in feeding responses to food deprivation or injection of ghrelin receptor agonists. Independent of genotype, food deprivation increased food intake, with dramatic changes in meal size, meal frequency, water : food ratio and eating rate. Acyl‐ghrelin or BIM‐28131, a potent ghrelin analog, dose‐dependently stimulated food intake by increasing meal size (ghrelin, BIM‐28131) and meal number (BIM‐28131), while slowing the average eating rate (BIM‐28131) similarly in WT and KO mice. These results suggest that the CRF2receptor is involved in the control of meal size during the active phase of eating and following acute exposure to stress.