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Significant Augmentation (significant + augmentation)
Selected AbstractsOestrogen receptor-alpha activation augments post-exercise myoblast proliferationACTA PHYSIOLOGICA, Issue 1 2010A. Thomas Abstract Aim:, Our laboratory has shown that oestrogen acts to augment myoblast (satellite cell) activation, proliferation and total number and that this may occur through an oestrogen receptor (OR)-mediated mechanism. The purpose of this study was to further investigate the mechanism of oestrogen influence on augmentation of post-exercise myoblast numbers through use of a specific OR-, agonist, propyl pyrazole triol (PPT). Methods:, Ovariectomized rats were used (n = 64) and separated into four groups: sham, oestrogen supplemented, agonist supplemented, and a combined oestrogen and agonist supplemented group. These groups were further subdivided into control (unexercised) and exercise groups. Surgical removal of white vastus and soleus muscles was performed 72 h post-exercise. Muscle samples were immunostained for the myoblast markers Pax7 and MyoD. Results:, A significant increase in total (Pax7-positive) and activated (MyoD-positive) myoblasts was found in all groups post-exercise. A further significant augmentation of total and activated myoblasts occurred in oestrogen supplemented, agonist supplemented and the combined oestrogen and agonist supplemented groups post-exercise in white vastus and soleus muscles relative to unsupplemented animals. Conclusion:, These results demonstrate that both oestrogen and the specific OR-, receptor agonist, PPT, can significantly and to similar degrees augment myoblast number and activation following exercise-induced muscle damage. This suggests that oestrogen acts through an OR-mediated mechanism to stimulate myoblast proliferation following exercise, with OR-, playing a primary role. [source] Bacterial motif DNA as an adjuvant for the breakdown of immune self-tolerance to pyruvate dehydrogenase complexHEPATOLOGY, Issue 3 2002David E. J. Jones Bacterial DNA containing unmethylated CpG dinucleotide motifs is immunostimulatory to mammals, skewing CD4+ T-cell responses toward the Th1 phenotype. Autoreactive T-cell responses seen in primary biliary cirrhosis (PBC) are typically of the Th1 phenotype, raising the possibility that bacterial DNA might play a role in the generation of pathologic autoimmunity. We therefore studied the effects of CpG motif-containing oligodeoxynucleotides (ODN) on responses to pyruvate dehydrogenase complex (PDC, the autoantigen in PBC) in a murine model. Sensitization of SJL/J mice with non,self-PDC has been shown to result in induction of autoreactive T-cell responses to PDC sharing characteristics with those seen in patients with PBC. Administration of CpG ODN to SJL/J mice at the time of sensitization with PDC resulted in a significant skewing of splenic T-cell response to self-PDC, with significant augmentation of the Th1 cytokine response (interleukin [IL] 2 and interferon [IFN] gamma) and reduction of the Th2 response (IL-4 and IL-10). In fact, CpG ODN seemed to be more effective at biasing the response phenotype and as effective at inducing liver histologic change as complete Freund's adjuvant (CFA), the standard adjuvant used for induction of Th1 responses in murine autoimmune and infectious immunity models. In conclusion, our findings raise the possibility that bacteria play a role in the development of autoimmunity (in PBC at least) through the potential of their DNA to shift the T-cell responses toward the phenotype associated with autoimmune damage. Moreover, this study suggests caution in the therapeutic use of CpG ODN as vaccine adjuvants. [source] Reproduction Phase-Related Expression of ,-Endorphin-Like Immunoreactivity in the Nucleus Lateralis Tuberis of the Female Indian Major Carp Cirrhinus mrigala: Correlation with the Luteinising Hormone Cells-Ovary AxisJOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2006A. J. Sakharkar Abstract The present study aimed to determine whether ,-endorphin immunoreactivity (bEP-ir) in the neurones of the nucleus lateralis tuberis (NLT) is linked to the seasonal cycle and shows correlation with the number of luteinising hormone (LH) cells in the pituitary gland and ovaries in the teleost, Cirrhinus mrigala. Although LH cells were moderately immunostained during the resting phase (December to January), the morphological profile suggested increased synthetic and secretory activity during the preparatory (February to April) and prespawning (May to June) phases. However, LH immunoreactivity was greatly reduced (P < 0.001) in the spawning (July to August) phase, suggesting massive discharge of the hormone; this pool was partly replenished in the postspawning (September to November) phase. The ovaries grew rapidly in the preparatory and prespawning phases; maximal size was attained during spawning, when ovulation occurred. Thereafter, the ovaries regressed. The NLT of C. mrigala is divisible into the pars lateralis (NLTl) and medialis (NLTm). During the postspawning and resting phases, bEP-ir was readily detectable in the NLTm as well as NLTl neurones. However, a steady reduction in the immunoreactivity was observed in the NLTm neurones during the preparatory through spawning phases (P < 0.001), suggesting a negative correlation with the LH cells-ovary axis. Thus, the inhibitory influence of ,-endorphin on the gonadotrophin-releasing hormone (GnRH)-LH axis appears to be attenuated during the preparatory through spawning phases. This may be necessary for the rapid stimulation of the axis culminating in spawning. Neurones of the NLTl also showed a gradual reduction in bEP-ir during the preparatory and prespawning phases (P < 0.01) and may therefore play a similar role. However, significant augmentation of the immunoreactivity was noticed in these neurones during the spawning phase (P < 0.001), the physiological significance of which is unknown. Although the present study demonstrated a temporal correlation between the ,-endorphin in the NLT, LH cells and the ovary, we suggest that the peptide in the NLTl and NLTm may show functional duality during the spawning phase. [source] How important is stimulation of ,-adrenoceptors for melatonin production in rat pineal glands?JOURNAL OF PINEAL RESEARCH, Issue 4 2002V. A. Tobin The objective of this study was to determine the role of , -adrenoceptors in melatonin production by rat pineal gland. Pineal glands were isolated from adult male rats and maintained in organ baths. The perfusate was sampled every 5 min, stored, and later assayed for melatonin. Exposure to norepinephrine (10 ,M) or the , -adrenoceptor agonist orciprenaline (2,10 ,M) increased the glands' production of melatonin. The time courses of melatonin production in response to these agonists were unaffected by the rats' pretreatment in vivo with the , -adrenoceptor antagonist prazosin (2 mg/kg i.p., three times). Rats that had had their superior cervical ganglia removed were primed with either orciprenaline (2 mg/kg i.p) or both orciprenaline and phenylephrine (1 mg/kg i.p) 1 hr before decapitation. Exposure of the pineal glands from these rats to orciprenaline evoked melatonin release that was similar in each group. These results lend weight to the suggestion that the marked potentiation by , -adrenoceptor agonists of the stimulation of cAMP and N-acetyltransferase (NAT) by , -adrenoceptor agonists, demonstrated most readily in cultured glands or dispersed rat pinealocytes, does not carry over into significant augmentation of melatonin production in intact pineal glands. [source] Shiga toxin enhances functional tissue factor on human glomerular endothelial cells: implications for the pathophysiology of hemolytic uremic syndrome,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2005E. NESTORIDI Summary.,Background:,The pathogenesis of Shiga toxin (Stx)-mediated childhood hemolytic uremic syndrome (HUS) is not fully delineated, although current evidence implicates a prothrombotic state. We hypothesized that the tissue factor (TF) pathway plays a major role in the pathophysiology of HUS. Materials and methods:,We measured cell surface TF activity in response to tumor necrosis factor-, (TNF-,) (20 ng mL,1, 2,144 h), Stx-1 (10,11 mol L,1, 4,144 h), or their combination (TNF-, 22 h and Stx-1 for the last 0.5,4 h of TNF-, incubation) on human glomerular (microvascular) endothelial cells (HGECs) and human umbilical vein (macrovascular) endothelial cells (HUVECs). Results and conclusions:,We observed that while TNF-, caused an increase in cell surface TF activity on both cell types, the combination of TNF-, and Stx-1 differentially affected HGECs. On these cells, TF activity was increased further by 2.67 ± 0.38-fold (n = 38, P < 0.001), consistent with our parallel observation that Stx-1 binds to HGECs but not to HUVECs. Anti-TF antibody abolished functional TF while anti-tissue factor pathway inhibitor antibody enhanced TF activity. Stx-1 alone did not induce TF activity on either cell type. Measurement of TF antigen levels and quantitative real-time polymerase chain reaction demonstrated that exposure to TNF-, markedly increased TF protein and TF mRNA for HGECs, but the exposure to the combination of TNF-, and Stx-1 did not increase further the amount of either TF protein or TF mRNA. We conclude that cytokine-activated HGECs, but not HUVECs, undergo a significant augmentation of cell surface TF activity following exposure to Stx, suggesting an important role for TF in the coagulopathy observed in HUS. [source] 34 Senso-reflexory control of the gastric myoelectrical activity , effect of oral exposure to a sweet or a bitter taste on a multichannel electrogastrogramNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2006M DZIELICKI Aim:, To examine the effect of sensory stimulation with a sweet or a bitter taste on the interdigestive gastric myoelectrical activity (GMA) in humans. Methods:, Eighteen healthy subjects (10F, 8M) underwent on two separate days four-channel electrogastrographic recordings comprising three consecutive 35 min periods: (i) basal fasted, (ii) a stimulation epoch while a subject was chewing an agar cube soaked with a taste-delivering substance (saccharose for the sweet taste, quinine hydrochloride for the bitter taste), (iii) a post-stimulatory (recovery) epoch. An electrocardiogram was simultaneously registered for the purpose of the heart rate variability (HRV) analysis. Results:, Exposure to the sweet taste brought about an increase in the power of the high frequency (HF: 0.15,0.4 Hz) band of the power spectrum-analyzed HRV data. The bitter taste had no effect on the HRV. During the stimulation and the recovery epoch a statistically significant augmentation in the relative time share of tachy- and bradygastria within the multichannel electrogastrogram was found either with the sweet or the bitter taste. Whereas no any other modifications of the GMA were elicited by the sweet taste, the exposure to the bitter taste resulted in a statistically significant decrease in the relative time share of normogastria, a decline in the dominant frequency and the dominant power of the gastric slow waves, as well as a reduction in the percentage of the slow wave coupling. Conclusions:, (i) Exposure to the sweet taste elicits a vagal arousal expressed by an increase in the HF power, whereas the bitter taste does not affect the equilibrium between the parasympathetic and the sympathetic component of the autonomous nervous system; (ii) The increased relative time contribution of tachy- and bradygastria within the electrogastrogram during both the stimulation and the recovery epoch should be considered an unspecific phenomenon because it accompanied stimulation either with the sweet or the bitter taste; (iii) The inhibitory effect of the bitter taste on the GMA, reflected by a diminution in the dominant frequency and the dominant power of the gastric slow waves, as well as their reduced coupling, may be indicative of an evolutionary archetype of a warning reaction of the human (mammalian) organism towards this taste. [source] Retroviral vector-producing mesenchymal stem cells for targeted suicide cancer gene therapyTHE JOURNAL OF GENE MEDICINE, Issue 5 2009Ryosuke Uchibori Abstract Background Mesenchymal stem cells (MSCs) are a promising vehicle for targeted cancer gene therapy because of their potential of tumor tropism. For efficient therapeutic application, we developed retroviral vector-producing MSCs that enhance tumor transduction via progeny vector production. Methods Rat bone marrow-derived MSCs were nucleofected with the proviral plasmids (vesicular stomatitis virus-G protein-pseudotyped retroviral vector components) (VP-MSCs) or pLTR plasmid alone (non-VP-MSCs). The luciferase-based in vivo imaging system was used to assess gene expression periodically. To evaluate the anticancer effects, we administered MSCs expressing herpes simplex virus-thymidine kinase (HSV- tk) into the left ventricular cavity of nude mice engrafted with 9L glioma cells subcutaneously. Results In vivo imaging revealed that administration of luciferase-expressing non-VP-MSCs enhanced the bioluminescence signal at the inoculation sites of 9L cells, whereas no accumulation was observed in mice at the site of the control Rat-1 fibroblasts. Compared to non-VP-MSCs, the administration of VP-MSCs resulted in significant augmentation of the signal with an increase in transgene copy number. Immunohistochemical analysis showed marked luciferase expression at the tumor periphery in mice injected with VP-MSCs, whereas little expression was detected in those injected with non-VP-MSCs. Under the continuous infusion of ganciclovir, systemic administration of VP-MSCs expressing HSV- tk suppressed tumor growth more effectively than non-VP-MSC administration, whereas no anticancer effect was observed without ganciclovir treatment. Furthermore, VP-MSC administration caused no transgene transduction in the normal tissues and organs. Conclusions VP-MSCs accumulated at the site of tumors after intravascular injection in tumor-bearing mice, followed by in situ gene transfer to tumors without transduction of normal organs. When applied to the HSV- tk/ganciclovir suicide gene therapy, more efficient tumor growth suppression was observed using VP-MSCs compared to non-VP-MSCs. This VP-MSC-based system has great potential for improved cancer gene therapy. Copyright © 2009 John Wiley & Sons, Ltd. [source] | |||||||||||||