bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collagen synthesis is not altered in women with stress urinary incontinence
Authors: Chen Yu , DeSautel Michael , Anderson Ann , Badlani Gopal , Kushner Leslie 
Published: June 2004

AbstractAimsThe objective of this study was to demonstrate that weakened pelvic floor support of the lower genitourinary tract in women with stress urinary incontinence (SUI) is due, in part, to decreased collagen synthesis and secretion and/or an altered ratio of collagen III/I synthesis by the fibroblasts of the endopelvic fascia and skin compared to that of women without evidence of pelvic floor weakening.MethodsEndopelvic fascia and skin biopsies were obtained from women with SUI (n = 14) and women without evidence of SUI or genital prolapse (n = 12). Fibroblast cultures established from the biopsies were incubated with 3H‐proline in medium containing ascorbic acid for 3 hr. Conditioned medium was collected and cells were harvested. The radiolabeled collagens were precipitated and digested with collagenase. The collagen synthesized (as a percent of total protein) was determined. Collagen α1(III) was separated from collagen α1(I) and α2(I) by interrupted SDS‐PAGE and the amount of 3H‐proline in each band was determined.ResultsCollagen synthesis, expressed as percent of total protein synthesis, was not significantly different between fibroblasts obtained from women with or without SUI. The mean of collagen III/I synthesized in fibroblasts was not significantly different between fibroblasts obtained from women with or without SUI.ConclusionsThese data suggest that the lower collagen content in the endopelvic fascia and skin of women with SUI is not due to reduced collagen synthesis or selective reduction in synthesis of either collagen I or collagen III, compared to women without pelvic floor weakening. © 2004 Wiley‐Liss, Inc.
Pelvic floor maximal strength using vaginal digital assessment compared to dynamometric measurements
Authors: Morin M. , Dumoulin C. , Bourbonnais D. , Gravel D. , Lemieux M.‐C. 
Published: June 2004

AbstractAimTo compare vaginal digital assessment with dynamometric measurements for determining the maximal strength of the pelvic floor muscles (PFM).Materials and MethodsEighty‐nine women aged between 21 and 44 participated in the study. An experienced physiotherapist evaluated the maximal strength of the PFM of these women using the modified Oxford grading system (six categories, range 0–5) and dynamometric measurements. The mean maximal forces obtained for all women with the instrumented speculum for each category of digital assessment were compared using ANOVAs. Spearman's rho coefficients were calculated to assess the correlation between the dynamometric and the digital assessments.ResultsAccording to their symptoms and pad test results, 30 women were continent and 59 had stress urinary incontinence (SUI). Based on dynamometric measurements, important overlaps were observed between each category of digital assessment. The ANOVAs indicated that force values differ across categories (F = 10.08; P < 0.001), although contrast analyses revealed no differences in the mean maximal forces between adjacent digital‐assessment categories (1–2, 2–3, 3–4, 4–5). Mean force values differed significantly only between non‐adjacent levels in digital assessment, for example, between 1 and 3; 1 and 4; 1 and 5; 2 and 4; 2 and 5 (P < 0.05). Significant correlations were found between the two measurements with coefficients of r = 0.727, r = 0.450, and r = 0.564 for continent, incontinent, and all women, respectively (P < 0.01).ConclusionsEven if the dynamometric mean forces of the PFM increased across subsequent categories of digital assessment, the force values between two adjacent categories do not differ. This limitation of digital assessment should be considered by clinicians and researchers when choosing treatment orientation and evaluating treatment outcomes. © 2004 Wiley‐Liss, Inc.
Mast cell chymase is a possible mediator of neurogenic bladder fibrosis
Authors: Howard Pamela S. , Renfrow David , Schechter Norman M. , Kucich Umberto 
Published: June 2004

AbstractAimsUrinary bladders of patients with myelomeningocele, owing to spina bifida, are often functionally impaired, fibrotic organs. Common to this condition are repeated occurrences of bladder infection and inflammation. Since mast cells have been associated with a fibrogenic response in inflammatory conditions, we investigated the role of mast cell granule product, chymase, as a mediator of myleodysplastic bladder fibrosis.MethodsHuman control and myelodysplastic bladder tissues were stained with Unna's stain and chymase antibody to determine mast cell number and localization. Cell specific localization of collagen mRNAs was determined by in situ hybridization (ISH). In vitro, normal human bladder fibroblasts were treated with recombinant chymase, heparin and inhibitors, and collagen subtype concentration was determined by enzyme linked immunosorbent assay (ELISA).ResultsMyelodysplastic bladders were characterized by increased mast cells in the detrusor muscle layer compared to control bladders, as well as mast cell degranulation and increased connective tissue deposition. Both types I and III collagen mRNA localized to fibroblasts surrounding detrusor muscle fascicles, whereas only collagen III mRNA localized to cells within connective tissue infiltrated muscle bundles in myelomeningocele bladder tissue. Chymase treatment of bladder fibroblasts, in vitro, was dose‐dependent and resulted in significant increases in both types I and III collagen. Heparin did not alter collagen protein expression, whereas heparin–chymase combination modulated type III collagen expression. Serine protease inhibitor, phenylmethylsulfonlyfluoride, did not inhibit collagen synthesis, whereas denatured chymase resulted in decreased collagenous protein levels.ConclusionsBladder fibrosis may be mediated by mast cell chymase stimulation of collagen synthesis. © 2004 Wiley‐Liss, Inc.
Oral Kohki Tea and its protective effect against in vitro ischemic damage to the bladder
Authors: Levin Robert M. , Leggett Robert E. , Whitbeck Catherine , Murakami Toshiyuki , Kambara Toshimitsu , Aikawa Ken 
Published: June 2004

AbstractAimsResults of several studies indicate that ischemia/reperfusion (I/R) is an etiological factor in the contractile dysfunctions induced by partial bladder outlet obstruction in animal models. In support of this hypothesis, pretreatment of rabbits with Kohki Tea (Engelhardtia chrysolepis), a Japanese herbal drink very high in antioxidant activity, significantly reduced the contractile dysfunctions induced by partial outlet obstruction. The current study was designed to determine if pretreating rabbits with Kohki Tea could protect the bladder against the contractile damage induced by in vitro ischemia followed by re‐oxygenation.MethodsForty‐eight New Zealand White rabbits were separated into two groups of 24; Group 1 was pretreated by oral gavage for 3 weeks with Kohki Tea and Group 2 received vehicle (water). Each rabbit was anesthetized with pentobarbital. The urinary bladder was rapidly removed and eight longitudinal muscle strips were cut from the bladder body. Each strip was mounted in a separate 15‐ml bath containing Tyrode's solution with glucose (1 mg/ml) and maintained at 37°C. All strips were equilibrated for 30 min with a gas mixture of 95% O2 and 5% CO2. At the end of this period of time, all strips were stimulated with field stimulation (FS) carbachol and KCl. After the last wash, the aeration was changed to hypoxic mixture (nitrogen–CO2) without glucose. At the end of 2 hr, the aeration was changed back to the normal 95% O2 and 5% CO2, and glucose was added to the buffer. After 1 hr of re‐oxygenation, a second set of stimulations was performed. In order to represent hyperreflexia, the strips were stimulated at 32‐Hz FS at 5‐min intervals during the hypoxic period in half of the in vitro experiments.ResultsThe results showed that Kohki Tea pretreatment protected the bladder's response to FS from the detrimental effects of repetitive stimulation and the detrimental effects of both in vitro ischemia and repetitive stimulation on the contractile responses to carbachol and KCl.ConclusionsThese data are consistent with the concept that Kohki Tea acts by protecting the bladder from cellular damage caused by hypoxia and the generation of free radicals. © 2004 Wiley‐Liss, Inc.
Changes in intracellular calcium concentration and P2X1 receptor expression in hypertrophic rat urinary bladder smooth muscle
Authors: Scott R. Sjuve , Uvelius B. , Arner A. 
Published: June 2004

AbstractAimsContractile responses to purinergic activation in the urinary bladder are altered in outflow obstruction (O). We determined if the lowered contractile response to adenosine triphosphate (ATP) in obstructed rat urinary bladder was due to changes in calcium handling or in P2X1 purinoceptor density.Materials and MethodsO was created in rat by partial ligature of the urethra, with non‐obstructed rats as controls (C). Force and intracellular calcium were measured in bladder strips activated with ATP. Tissue was sectioned for light and electron microscopy and analyzed with Western blot using a P2X1 antibody.ResultsBladder weight increased from 66 ± 3 (C) to 206 ± 17 mg (O) (n = 6). ATP gave a transient contractile response which was decreased in the obstructed strips (C: 161 ± 20; O: 63 ± 16% of high‐K+ force). Intracellular calcium concentration after ATP activation in the obstructed bladder muscle was about 50% of that in the control preparations (C: 669 ± 110; O: 335 ± 59 nM). Half‐time for calcium influx was increased in the O group. P2X1 immunoreactivity per unit bladder weight was similar in the two groups. Cell membrane area per unit wet weight was decreased in the O group.ConclusionsAttenuated contractile responses to ATP in obstructed rat urinary bladder are due to a lowered rate of calcium influx and maximal peak calcium concentration. This change in Ca2+ transients is not due to a decrease in P2X1 receptor density in the smooth muscle cell membranes. Possibly, the increase in cell volume buffers the rapid and transient influx of Ca2+ following purinoceptor activation in the obstructed bladder. © 2004 Wiley‐Liss, Inc.
Basic science and translational research in female pelvic floor disorders: Proceedings of an NIH‐sponsored meeting
Authors: Weber Anne M. , Buchsbaum Gunhilde M. , Chen Bertha , Clark Amanda L. , Damaser Margot S. , Daneshgari Firouz , Davis Gary , DeLancey John , Kenton Kimberly , Weidner Alison C. , Word R. Ann 
Published: June 2004

AbstractAimsTo report the findings of a multidisciplinary group of scientists focusing on issues in basic science and translational research related to female pelvic floor disorders, and to produce recommendations for a research agenda for investigators studying female pelvic floor disorders.MethodsA National Institutes of Health (NIH)‐sponsored meeting was held on November 14–15, 2002, bringing together scientists in diverse fields including obstetrics, gynecology, urogynecology, urology, gastroenterology, biomechanical engineering, neuroscience, endocrinology, and molecular biology. Recent and ongoing studies were presented and discussed, key gaps in knowledge were identified, and recommendations were made for research that would have the highest impact in making advances in the field of female pelvic floor disorders.ResultsThe meeting included presentations and discussion on the use of animal models to better understand physiology and pathophysiology; neuromuscular injury (such as at childbirth) as a possible pathogenetic factor and mechanisms for recovery of function after injury; the use of biomechanical concepts and imaging to better understand the relationship between structure and function; and molecular and biochemical mechanisms that may underlie the development of female pelvic floor disorders.ConclusionsWhile the findings of current research will help elucidate the pathophysiologic pathways leading to the development of female pelvic floor disorders, much more research is needed for full understanding that will result in better care for patients through specific rather than empiric therapy, and lead to the potential for prevention on primary and secondary levels. © 2004 Wiley‐Liss, Inc.
Constitutive expression of p21H‐rasVal12 in pyramidal neurons results in reorganization of mouse neocortical afferents
Authors: Alpár Alán , Gärtner Ulrich , Seeger Gudrun , Härtig Wolfgang , Brauer Kurt , Arendt Thomas 
Published: June 2004

AbstractThe effect of constitutive expression of p21H‐rasVal12 in pyramidal neurons upon the establishment of afferent input has been investigated in the primary somatosensory cortex of transgenic mice. In these animals, relevant transgene expression is confined to cortical pyramidal neurons and starts postnatally at a period when neuronal morphogenesis has been largely completed. We have shown recently that overexpression of p21H‐rasVal12 in these cells results in considerable enlargement of their size and consequently in expansion of the cortex. In the present study we demonstrate that the density of terminals representing intra‐ or interhemispheric afferents within cortical layers II/III, however, is only slightly decreased. The density of thalamocortical boutons within layer IV is even higher and the number of afferent contacts to transgenic pyramidal neurons is significantly increased compared to the wild‐type. The number of catecholaminergic and cholinergic terminals is augmented proportionally to cortical size or even overproportionally, respectively. Along intercortical and striatal fibers arising from p21H‐rasVal12‐expressing pyramidal neurons, frequency of varicosities is significantly increased, but remains unchanged on cortical cholinergic and catecholaminergic axons originating from “nontransgenic” neurons. Additionally, a higher number of multiple synaptic bodies are found in transgenic mice, suggesting subtle effects on synaptic plasticity. It is concluded that the enlargement of pyramidal neurons due to transgenic expression of p21H‐rasVal12 is paralleled by significant changes in the quantity and pattern of afferent connections. Moreover, expression of p21H‐rasVal12 in pyramidal cells induces an enhanced establishment of efferent boutons. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 263–274, 2004
Repetitive exposures to nicotine induce a hyper‐responsiveness via the cAMP/PKA/CREB signal pathway in Drosophila
Authors: Hou Jiamei , Kuromi Hiroshi , Fukasawa Yohko , Ueno Kohei , Sakai Takaomi , Kidokoro Yoshiaki 
Published: June 2004

AbstractNicotine, in addition to acute effects, has long‐lasting effects on mammalian behaviors, such as those leading to addiction. Here we present genetic and pharmacological evidence in Drosophila suggesting that repetitive exposures to nicotine induce a hyper‐responsiveness through synthesis of new protein(s) via CREB‐mediated gene transcription. Single exposure to volatilized nicotine dose‐dependently inhibited the startle‐induced climbing response. Compared with this effect of nicotine in wild‐type flies, it was stronger in dunce, which has defective phosphodiesterase, and in wild‐type flies treated with a phosphodiesterase inhibitor, whereas it was weaker in DC0, which has defective protein kinase A (PKA), and in wild‐type flies treated with a PKA blocker. Thus, the effect of nicotine is enhanced by a mechanism involving the cAMP/PKA cascade. However, in wild‐type flies, an increase in head cAMP was not detected within 2 min after single exposure to nicotine, during which the nicotine effect on the behavior was maximal. In wild‐type flies, after repetitive exposures to nicotine, the nicotine effect was significantly enhanced and the head cAMP was elevated. The responsiveness to nicotine at second exposure increased with a 4 h interval but not with a 2 h interval, suggesting that the observed hyper‐responsiveness was not due to accumulation of residual nicotine. Both enhancement of the nicotine effect and elevation of cAMP during repetitive exposures to nicotine were blocked by a protein synthesis inhibitor. Induction of a dominant negative CREB transgene also blocked the enhancement, suggesting that CREB‐mediated gene transcription is required for the hyper‐responsiveness. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 249–261, 2004
Hedgehog and Fgf signaling pathways regulate the development of tphR‐expressing serotonergic raphe neurons in zebrafish embryos
Authors: Teraoka H. , Russell C. , Regan J. , Chandrasekhar A. , Concha M. L. , Yokoyama R. , Higashi K. , Take‐uchi M. , Dong W. , Hiraga T. , Holder N. , Wilson S. W. 
Published: June 2004

AbstractSerotonin (5HT) plays major roles in the physiological regulation of many behavioral processes, including sleep, feeding, and mood, but the genetic mechanisms by which serotonergic neurons arise during development are poorly understood. In the present study, we have investigated the development of serotonergic neurons in the zebrafish. Neurons exhibiting 5HT‐immunoreactivity (5HT‐IR) are detected from 45 h postfertilization (hpf) in the ventral hindbrain raphe, the hypothalamus, pineal organ, and pretectal area. Tryptophan hydroxylases encode rate‐limiting enzymes that function in the synthesis of 5HT. As part of this study, we cloned and analyzed a novel zebrafish tph gene named tphR. Unlike two other zebrafish tph genes (tphD1 and tphD2), tphR is expressed in serotonergic raphe neurons, similar to tph genes in mammalian species. tphR is also expressed in the pineal organ where it is likely to be involved in the pathway leading to synthesis of melatonin. To better understand the signaling pathways involved in the induction of the serotonergic phenotype, we analyzed tphR expression and 5HT‐IR in embryos in which either Hh or Fgf signals are abrogated. Hindbrain 5HT neurons are severely reduced in mutants lacking activity of either Ace/Fgf8 or the transcription factor Noi/Pax2.1, which regulates expression of ace/fgf8, and probably other genes encoding signaling proteins. Similarly, serotonergic raphe neurons are absent in embryos lacking Hh activity confirming a conserved role for Hh signals in the induction of these cells. Conversely, over‐activation of the Hh pathway increases the number of serotonergic neurons. As in mammals, our results are consistent with the transcription factors Nk2.2 and Gata3 acting downstream of Hh activity in the development of serotonergic raphe neurons. Our results show that the pathways involved in induction of hindbrain serotonergic neurons are likely to be conserved in all vertebrates and help establish the zebrafish as a model system to study this important neuronal class. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 275–288, 2004
Chronic stress alters dendritic morphology in rat medial prefrontal cortex
Authors: Cook Susan C. , Wellman Cara L. 
Published: June 2004

AbstractChronic stress produces deficits in cognition accompanied by alterations in neural chemistry and morphology. Medial prefrontal cortex is a target for glucocorticoids involved in the stress response. We have previously demonstrated that 3 weeks of daily corticosterone injections result in dendritic reorganization in pyramidal neurons in layer II–III of medial prefrontal cortex. To determine if similar morphological changes occur in response to chronic stress, we assessed the effects of daily restraint stress on dendritic morphology in medial prefrontal cortex. Male rats were exposed to either 3 h of restraint stress daily for 3 weeks or left unhandled except for weighing during this period. On the last day of restraint, animals were overdosed and brains were stained using a Golgi‐Cox procedure. Pyramidal neurons in lamina II–III of medial prefrontal cortex were drawn in three dimensions, and the morphology of apical and basilar arbors was quantified. Sholl analyses demonstrated a significant alteration of apical dendrites in stressed animals: overall, the number and length of apical dendritic branches was reduced by 18 and 32%, respectively. The reduction in apical dendritic arbor was restricted to distal and higher‐order branches, and may reflect atrophy of terminal branches: terminal branch number and length were reduced by 19 and 35%. On the other hand, basilar dendrites were not affected. This pattern of dendritic reorganization is similar to that seen after daily corticosterone injections. This reorganization likely reflects functional changes in prefrontal cortex and may contribute to stress‐induced changes in cognition. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 236–248, 2004
RhoA/ROCK and Cdc42 regulate cell‐cell contact and N‐cadherin protein level during neurodetermination of P19 embryonal stem cells
Authors: Laplante Isabel , Béliveau Richard , Paquin Joanne 
Published: June 2004

AbstractRhoGTPases regulate actin‐based signaling cascades and cellular contacts. In neurogenesis, their action modulates cell migration, neuritogenesis, and synaptogenesis. Murine P19 embryonal stem cells differentiate to neurons upon aggregation in the presence of retinoic acid, and we previously showed that RhoA and Cdc42 RhoGTPases are sequentially up‐regulated during neuroinduction, suggesting a role at this very early developmental stage. In this work, incubation of differentiating P19 cells with C3 toxin resulted in decreased aggregate cohesion and cadherin protein level. In contrast, C3 effects were not observed in cells overexpressing recombinant dominant active RhoA. On the other hand, C3 did not affect cadherin in uninduced cells and their postmitotic neuronal derivatives, respectively expressing E‐ and N‐cadherin. RhoA is thus influential on cell aggregation and cadherin expression during a sensitive time window that corresponds to the switch of E‐ to N‐cadherin. Cell treatment with Y27632 inhibitor of Rho‐associated‐kinase ROCK, or advanced overexpression of Cdc42 by gene transfer of a constitutively active form of the protein reproduced C3 effects. RhoA‐antisense RNA also reduced cadherin level and the size of cell aggregates, and increased the generation of fibroblast‐like cells relative to neurons following neuroinduction. Colchicin, a microtubule disrupter, but not cytochalasin B actin poison, importantly decreased cadherin in neurodifferentiating cells. Overall, our results indicate that the RhoA/ROCK pathway regulates cadherin protein level and cell‐cell interactions during neurodetermination, with an impact on the efficiency of the process. The effect on cadherin seems to involve microtubules. The importance of correct timing of RhoA and Cdc42 functional expression in neurogenesis is also raised. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 289–307, 2004
Updated Lagrangian free surface flow simulations with natural neighbour Galerkin methods
Authors: Martínez M. A. , Cueto E. , Alfaro I. , Doblaré M. , Chinesta F. 
Published: June 2004

AbstractIn this paper, a new method to simulate free surface fluid flows within an updated Lagrangian framework is described. It is based on the use of a meshless technique coined as natural element method (NEM) or, more recently, as natural neighbour Galerkin method. The position of the flow front or the geometry of the fluid domain is handled by invoking the geometrical concept of α‐shape of the cloud of points, thus avoiding the explicit definition of the boundary of the domain as it evolves. This method also avoids the traditional need of remeshing typical in finite element simulations of this kind of processes. Three types of fluid behaviour have been considered, namely a purely Newtonian fluid, a non‐Newtonian short fibre‐reinforced thermoplastic, and finally a Norton–Hoff viscoplastic behaviour. Benchmark examples showing the performance of the technique are included in the paper. Copyright © 2004 John Wiley & Sons, Ltd.