[show abstract][hide abstract] ABSTRACT: This study applied advanced machine learning techniques, widely considered as the most successful method to produce objective to an inferential problem of recurrent cervical cancer. Traditionally, clinical diagnosis of recurrent cervical cancer was based on physician’s clinical experience with various risk factors. Since the risk factors are broad categories, years of clinical study and experience have tried to identify key risk factors for recurrence. In this study, three machine learning approaches including support vector machine, C5.0 and extreme learning machine were considered to find important risk factors to predict the recurrence-proneness for cervical cancer. The medical records and pathology were accessible by the Chung Shan Medical University Hospital Tumor Registry. Experimental results illustrate that C5.0 model is the most useful approach to the discovery of recurrence-proneness factors. Our findings suggest that four most important recurrence-proneness factors were Pathologic Stage, Pathologic T, Cell Type and RT Target Summary. In particular, Pathologic Stage and Pathologic T were important and independent prognostic factor. To study the benefit of adjuvant therapy, clinical trials should randomize patients stratified by these prognostic factors, and to improve surveillance after treatment might lead to earlier detection of relapse, and precise assessment of recurrent status could improve outcome.
Neural Computing and Applications 01/2014; · 1.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients with inflammatory gynecological/obstetrical problems often complain of irritable bowel syndrome. The authors examined whether acute uterus irritation reflexively provokes colonic motility in rat preparations.
A modified colon manometry and striated abdominal muscle electromyogram activity in response to mustard oil (MO) instillation into the uterine horn were continuously recorded in anesthetized rats. The lumbosacral (L6-S1) dorsal horn was dissected to assess the level and the cellular location of phosphorylated NR2B subunit using Western blotting and immunofluorescence analysis, respectively. Finally, the uterine transient receptor potential A1 or spinal NR2B subunit was pharmacologically blocked to elucidate its roles.
MO (0.1%, 0.2 ml) injected into the lower uterine horn dramatically provoked colonic hypermotility characterized by rhythmic colonic contractions (about 3-4 contractions per 10 min, n = 7) accompanied by synchronized electromyogram firing in the abdominal muscle (about 4-5 folds of control, n = 7). In addition to provoking colonic hypermotility, MO administration also up-regulated phosphorylated (about 2-3 folds of control, n = 7), but not total, NR2B expression in the dorsal horn neurons. Both intrathecal Ro 25-6981 (a selective NR2B subunit antagonist; 10 μM, 10 μl) and intrauterine HC-030031 (a selective transient receptor potential A1 receptor antagonist; 30 mg/kg, 0.2 ml) injected before the MO instillation attenuated the MO-induced colonic hypermotility and spinal NR2B phosphorylation.
The comorbidity of gynecological/obstetrical and gastrointestinal problems is not coincidental but rather causal in nature, and clinicians should investigate for gynecological/urological diseases in the setting of bowel problems with no known pathological etiology.
[show abstract][hide abstract] ABSTRACT: Mesh-augmented vaginal surgery for treatment of pelvic organ prolapse (POP) does not meet patients' needs. This study aims to test the hypothesis that fascia tissue engineering using adipose-derived stem cells (ADSCs) might be a potential therapeutic strategy for reconstructing the pelvic floor.
Human ADSCs were isolated, differentiated, and characterized in vitro. Both ADSCs and fibroblastic-differentiated ADSCs were used to fabricate tissue-engineered fascia equivalents, which were then transplanted under the back skin of experimental nude mice.
ADSCs prepared in our laboratory were characterized as a group of mesenchymal stem cells. In vitro fibroblastic differentiation of ADSCs showed significantly increased gene expression of cellular collagen type I and elastin (p < 0.05) concomitantly with morphological changes. By contrast, ADSCs cultured in control medium did not demonstrate these changes. Both of the engrafted fascia equivalents could be traced up to 12 weeks after transplantation in the subsequent animal study. Furthermore, the histological outcomes differed with a thin (111.0 ± 19.8 μm) lamellar connective tissue or a thick (414.3 ± 114.9 μm) adhesive fibrous tissue formation between the transplantation of ADSCs and fibroblastic-differentiated ADSCs, respectively. Nonetheless, the implantation of a scaffold without cell seeding (the control group) resulted in a thin (102.0 ± 17.1 μm) fibrotic band and tissue contracture.
Our results suggest the ADSC-seeded implant is better than the implant alone in enhancing tissue regeneration after transplantation. ADSCs with or without fibroblastic differentiation might have a potential but different role in fascia tissue engineering to repair POP in the future.
Journal of the Formosan Medical Association 06/2013; · 1.00 Impact Factor
[show abstract][hide abstract] ABSTRACT: The coupling of the spinal postsynaptic density-95 (PSD-95) with the glutamatergic N-methyl-d-aspartate receptor NR2B subunit and the subsequent NR2B phosphorylation contribute to pain-related plasticity. Increasing evidence reveals that kalirin, a Rho-guanine nucleotide exchange factor, modulates PSD-95-NR2B-dependent neuroplasticity. Our laboratory recently demonstrated that serum-inducible and glucocorticoid-inducible kinase 1 (SGK1) participates in inflammation-associated pain hypersensitivity by modulating spinal glutamatergic neurotransmission. Because kalirin is one of the proteins in PSD that is highly phosphorylated by various kinases, we tested whether kalirin could be a downstream target of spinal SGK1 that participates in neuropathic pain development via regulation of the PSD-95-NR2B coupling-dependent phosphorylation of NR2B. We observed that spinal nerve ligation (SNL, L5) in male Sprague Dawley rats resulted in behavioral allodynia, which was associated with phosphorylated SGK1 (pSGK1), kalirin, and phosphorylated NR2B (pNR2B) expression and an increase in pSGK1-kalirin-PSD-95-pNR2B coprecipitation in the ipsilateral dorsal horn (L4-L5). SNL-enhanced kalirin immunofluorescence was coincident with pSGK1, PSD-95, and pNR2B immunoreactivity. Small-interfering RNA (siRNA) that targeted spinal kalirin mRNA expression (10 μg, 10 μl; i.t.) reduced SNL-induced allodynia, kalirin and pNR2B expression, as well as kalirin-PSD-95 and PSD-95-pNR2B coupling and costaining without affecting SGK1 phosphorylation. Daily administration of GSK-650394 (an SGK1 antagonist; 100 nm, 10 μl, i.t.) not only exhibited effects similar to the kalirin mRNA-targeting siRNA but also attenuated pSGK1-kalirin costaining and SGK1-kalirin coupling. We suggest that nerve injury could induce spinal SGK1 phosphorylation that subsequently interacts with and upregulates kalirin to participate in neuropathic pain development via PSD-95-NR2B coupling-dependent NR2B phosphorylation.
Journal of Neuroscience 03/2013; 33(12):5227-5240. · 6.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: Unexpected environmental and social stimuli could trigger stress. Although coping with stress is essential for survival, long-term stress impacts visceral functions, and therefore, it plays a role in the development and exacerbation of symptoms of gastrointestinal/urogenital disorders. The aim of this study is to characterize the role of corticosterone in stress-sensitized colon-bladder cross-talk, a phenomenon presumed to underlie the comorbidity of functional bowel and bladder disorders. Cystometry and protein/mRNA expression in the lumbosacral dorsal horn (L6-S1) in response to intracolonic mustard oil (MO) instillation were analyzed in female Wistar-Kyoto rats subjected to water avoidance stress (WAS; 1 h/day for 10 days) or sham stress (WAsham). Whereas it had no effect on baseline-voiding function, chronic stress upregulated plasma corticosterone concentration and dorsal horn spinal p90 ribosomal S6 kinase 2 (RSK2) protein/mRNA levels, and RSK2 immunoreactivity colocalized with NeuN-positive neurons. Intracolonic MO dose-dependently decreased intrercontraction intervals and threshold pressure, provoked spinal RSK2 and NR2B phosphorylation, and enhanced PSD-95-RSK2 and PSD-95-NR2B coupling. Intrathecal kaempferol (a RSK2 activation antagonist; 30 min before MO instillation), bilateral adrenalectomy (7 days prior the stress paradigm), and subcutaneous RU-38486 (a glucocorticoid receptor antagonist; 30 min daily before stress sessions), but not RU-28318 (a mineralocorticoid receptor antagonist), attenuated MO-induced bladder hyperactivity, protein phosphorylation, and protein-protein interactions in the WAS group. Our results suggest that stress-associated glucocorticoid release mediates WAS-dependent sensitization of colon-bladder cross-talk via the spinal RSK2/PSD-95/NR2B cascade and offer a possibility for developing pharmacological strategies for the treatment of stress-related pelvic pain.
AJP Endocrinology and Metabolism 11/2012; 303(9):E1094-106. · 4.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: The elusiveness of the mechanism underlying pain is a major impediment in developing effective clinical treatments. We examined whether the phosphorylation of spinal serum- and glucocorticoid-inducible kinase 1 (SGK1) and downstream glutamate receptor interacting protein (GRIP)-associated protein-1 (GRASP-1)/Rab4-dependent GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) recycling play a role in inflammatory pain. After intraplantar injection of complete Freund's adjuvant (CFA), we assessed thermal hyperalgesia using the Hargreaves test and analyzed dorsal horn samples (L4-5) using Western blotting, coprecipitation, and immunofluorescence. CFA administration provoked behavioral hyperalgesia along with SGK1 phosphorylation, GluR1 trafficking from the cytosol to the membrane, and phosphorylated SGK1 (pSGK1)-GRASP-1, GRASP-1-Rab4, and Rab4-GluR1 coprecipitation in the ipsilateral dorsal horn. In the dorsal horns of hyperalgesic rats, CFA-enhanced pSGK1 was demonstrated to be colocalized with NeuN, GRASP-1, Rab4, and GluR1 by immunofluorescence. GSK-650394 (an SGK1 activation antagonist, 1, 10, and 30μM, 10μL/rat, intrathecally) dose-dependently prevented CFA-induced pain behavior and the associated SGK1 phosphorylation, GluR1 trafficking, and protein-protein interactions at 1day after CFA administration. Intrathecal 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, an AMPAR antagonist, 1, 3, and 10μM, 10μL/rat) attenuated the hyperalgesia and GluR1 trafficking caused by CFA; however, it had no effect on SGK1 phosphorylation. Small interfering RNA targeting Rab4 hindered the CFA-induced hyperalgesia and the associated GluR1 trafficking and Rab4-GluR1 coprecipitation. Our results suggest that spinal SGK1 phosphorylation, which subsequently triggers the GRASP-1/Rab4 cascade, plays a pivotal role in CFA-induced inflammatory pain by regulating GluR1-containing AMPAR recycling in the dorsal horn.
[show abstract][hide abstract] ABSTRACT: The objective of this study was to demonstrate the diversity of urodynamic findings and temporal effects on bladder dysfunction in diabetes as well as to evaluate the predisposing factors that attenuate the storage and voiding function of diabetic women.
In this prospective study, 181 women with type 2 diabetes mellitus (DM) and lower urinary tract dysfunction underwent complete urogynecological evaluations and urodynamic studies. The patients' histories of DM and the treatment agents used were documented from chart records and interviews. The urodynamic diagnoses were recategorized into two groups for comparison, namely overactive detrusor (detrusor overactivity and/or increased bladder sensation as well as mixed incontinence) and voiding dysfunction (detrusor hyperactivity with insufficient contractility and detrusor underactivity with poor voiding efficiency) in order to evaluate the temporal effect of DM on diabetic bladder dysfunction.
The development of bladder dysfunction showed a trend involving time-dependent progression, beginning with storage problems (i.e. advancing from urodynamic stress incontinence to detrusor overactivity and/or increased bladder sensation) and eventually led to impaired voiding function. The duration of DM relative to the urodynamic diagnoses of these women was longer in women with voiding dysfunction (6.8 ± 2.8 years with urodynamic stress incontinence, 7.3 ± 6.5 years with detrusor overactivity and/or increased bladder sensation, and 10.4 ± 8.3 years with women with voiding dysfunction). Notwithstanding these findings, stepwise logistic regression analysis indicated that age and recurrent urinary tract infections were the two independent factors associated with developing voiding dysfunction.
The urodynamic study revealed a temporal effect on bladder function, and women with diabetic voiding dysfunction were found to have had a longer duration of DM than women with an overactive detrusor. However, aging and recurrent urinary tract infections are the two independent factors that contribute to impaired voiding function and diabetic bladder dysfunction.
Taiwanese journal of obstetrics & gynecology 09/2012; 51(3):381-6.
[show abstract][hide abstract] ABSTRACT: To evaluate the prevalence and associated risk factors of pelvic organ prolapse (POP) and lower urinary tract symptoms (LUTS) among women seeking healthcare services in 3 discrete rural areas in Nepal.
A cross-sectional study was conducted using a Nepalese-specific questionnaire to obtain demographic and personal information. Urinary symptoms were examined using the Urogenital Distress Inventory Short form questionnaire, while POP severity was staged according to the POP-Q system. The χ(2) test and multivariate logistic regression analysis were used to determine POP risk factors.
Of the 174 women included in the analysis, 106 (60.9%) had stage II POP or greater. In all, 93 women (53.4%) had cystocele, 63 (36.2%) had rectocele, and 37 (21.3%) had uterine prolapse. Univariate analysis identified high parity; young age at first delivery; menopause; squatting or standing position during delivery; and early return to work after delivery as risk factors for POP. Multivariate logistic regression revealed that delivery in a lying position presented a lower risk for cystocele than squatting or standing (odds ratio 0.34; P<0.01).
Both LUTS and POP are common among women in rural Nepal. Cystocele is the most frequent, advanced, and symptomatic form of POP observed in this population.
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 08/2012; 119(2):185-8. · 1.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: INTRODUCTION AND HYPOTHESIS: Dimethyl sulfoxide (DMSO) bladder instillation is a standard therapy for interstitial cystitis (IC); however, there are varying degrees of success. We hypothesize that first-line intravesical therapy with a DMSO cocktail will optimize treatment outcome. METHODS: Ninety women with newly diagnosed IC were enrolled consecutively for the treatment. The IC symptom and problem index was used as an outcome measure. RESULTS: Six (6.7%) patients dropped out of the treatment due to intolerable bladder irritation. Fifty-five (65.5%) of the remaining 84 patients, who completed the treatment, experienced ≧50% symptomatic improvement. After a regression analysis, three clinical variables were found to affect treatment adversely, i.e., the presence of advanced cystoscopic glomerulations, microscopic hematuria, and urodynamic detrusor underactivity, respectively. CONCLUSIONS: Our results suggest bladder instillation with a DMSO cocktail may well be considered as first-line therapy for IC patients. However, there exists a subgroup of nonresponders who may have severe disease.
International Urogynecology Journal 03/2012; · 2.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: The fact that neuropathic pain mechanisms are not well understood is a major impediment in the development of effective clinical treatments. We examined whether the interaction between signal regulatory protein alpha 1 (SIRPα1) and Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2), and the downstream spinal SHP2/postsynaptic density 95 (PSD-95)/N-methyl-d-aspartate receptor NR2B subunit signaling cascade play a role in neuropathic pain. Following spinal nerve ligation (L5), we assessed tactile allodynia using the von Frey filament test and analyzed dorsal horn samples (L4-5) by Western blotting, reverse transcription polymerase chain reaction, coimmunoprecipitation, and immunofluorescence. Nerve ligation induced allodynia, SIRPα1, SHP2, phosphorylated SHP2 (pSHP2), and phosphorylated NR2B (pNR2B) expression, and SHP2-PSD-95, pSHP2-PSD-95, PSD-95-NR2B, and PSD-95-pNR2B coimmunoprecipitation in the ipsilateral dorsal horn. In allodynic rats, injury-induced SHP2 immunoreactivity was localized in the ipsilateral dorsal horn neurons and coincident with PSD-95 and NR2B immunoreactivity. SIRPα1 silencing using small interfering RNA (siRNA; 1, 3, or 5μg/rat for 7days) prevented injury-induced allodynia and the associated changes in protein expression, phosphorylation, and coimmunoprecipitation. Intrathecal administration of NSC-87877 (an SHP2 antagonist; 1, 10, or 100μM/rat) and SIRPα1-neutralizing antibodies (1, 10, or 30μg/rat) suppressed spinal nerve ligation-induced allodynia, spinal SHP2 and NR2B phosphorylation, and SHP2/phosphorylated SHP2-PSD-95 and PSD-95-NR2B/phosphorylated NR2B coprecipitation. SHP2 siRNA led to similar effects as the NSC-87877 and SIRPα1 antibody treatments, except it prevented the allodynia-associated spinal SHP2 expression. In conclusion, our results suggest that a spinal SIRPα1-SHP2 interaction exists that subsequently triggers SHP2/PSD-95/NR2B signaling, thereby playing a role in neuropathic pain development.
[show abstract][hide abstract] ABSTRACT: We reviewed articles in the PubMed database which describe the results and outcome of a repeat midurethral synthetic sling
(MUS), known as tension-free vaginal tape (TVT), or transobturator tape/tension-free vaginal tape obturator for prior MUS
failure in patients who presented with persistent or recurrent stress urinary incontinence (SUI). We combined or separated
the keywords “TVT,” “failure,” “repeat TVT,” and “recurrent/persistent SUI.” The search was limited by publication data from
2000 to 2010, humans, female, and English text. A repeat TVT procedure treating prior TVT failure showed success rates ranging
from 70% to 90%. The outcomes showed no significant differences between a repeat retropubic route or transobturator route.
A repeat MUS procedure for persistent or recurrent stress urinary incontinence is a reliable option for patients with prior
[show abstract][hide abstract] ABSTRACT: To investigate blood pressure (BP) and pulse rate (PR) changes during urodynamic (UD) examinations in patients with suprasacral spinal cord injury (SCI).
A case control study.
Tertiary hospital affiliated with a medical university.
Control subjects (n=22) and patients with suprasacral SCI (n=120).
Systolic (SBP) and diastolic BP (DBP) and PR before and during UD studies.
Healthy subjects had an average SBP change of 9.7 ± 10.6 mm Hg and a maximal SBP increase of 21 mm Hg. Autonomic dysreflexia (AD) was defined as an SBP increase of 20mm Hg or more, and incidence rates were 36.7% overall, 42.6% in patients with injury level at or above T6, and 15.4% in patients with lesions below T6. Both SBP and DBP changes in patients with SCI showed significant negative correlations with injury levels (r=-.383 and -.315; P<.05). The BP increase was more significant in patients with SCI who had detrusor sphincter dyssynergia (DSD), especially the continuous type, or severely impaired bladder compliance than in those who did not. Most patients (75%) had no significant PR changes (within 10 beats/min) during AD responses and only 22.7% had a decrease of 10 beats/min or more. Patients younger than 50 years had a greater PR decrease than those 50 years or older (-7.1 ± 9.0 vs 0.7 ± 11.4 beats/min; P<.05).
AD occurred not only in patients with lesions above T6, but also in those with lower lesion levels. Patients with higher injury level, continuous DSD, or a poorly compliant bladder had greater SBP changes during UD studies. During AD reactions, younger patients tended to have a greater PR decrease than older patients.
Archives of physical medicine and rehabilitation 09/2011; 92(9):1450-4. · 2.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to compare the results of a transrectal ultrasound-guided botulinum toxin injection with those of a cystoscopy-guided method to the external urethral sphincter in treating detrusor external sphincter dyssynergia.
A total of 18 suprasacral spinal cord-injured patients with detrusor external sphincter dyssynergia were included in the present study. A single dose of 100 IU botulinum toxin A was applied into the external urethral sphincter via a transrectal ultrasound-guided transperineal route. We retrospectively compared the outcome measurements with 20 suprasacral spinal cord-injured patients previously treated with the same dose of botulinum toxin through a cystoscopy-guided procedure.
There were significant reductions in integrated electromyography and urethral pressure but not in detrusor pressure and leak point pressure after treatment. Postvoiding residuals were significantly decreased in the first, second, and third months in the cystoscopy group and in the first and second months in the transrectal ultrasound group. There were no significant differences between the groups in all of the outcome measures.
This study demonstrates that transrectal ultrasound-guided transperineal botulinum toxin injection may be an alternative for a cystoscopy-guided injection. This alternative procedure provides clinicians with an innovative and less invasive method that is performed without requiring anesthesia or cystoscopy.
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists 05/2011; 90(9):723-30. · 1.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recently, the role of EphB receptor (EphBR) tyrosine kinase and their ephrinB ligands in pain-related neural plasticity at the spinal cord level have been identified. To test whether Src-family tyrosine kinase-dependent glutamatergic N-methyl-d-aspartate receptor NR2B subunit phosphorylation underlies lumbosacral spinal EphBR activation to mediate pelvic-urethra reflex potentiation, we recorded external urethra sphincter electromyogram reflex activity and analyzed protein expression in the lumbosacral (L(6)-S(2)) dorsal horn in response to intrathecal ephrinB2 injections. When compared with vehicle solution, exogenous ephrinB2 (5 μg/rat it)-induced reflex potentiation, in associated with phosphorylation of EphB1/2, Src-family kinase, NR2B Y1336 and Y1472 tyrosine residues. Both intrathecal EphB1 and EphB2 immunoglobulin fusion protein (both 10 μg/rat it) prevented ephrinB2-dependent reflex potentiation, as well as protein phosphorylation. Pretreatment with PP2 (50 μM, 10 μl it), an Src-family kinase antagonist, reversed the reflex potentiation, as well as Src kinase and NR2B phosphorylation. Together, these results suggest the ephrinB2-dependent EphBR activation, which subsequently provokes Src kinase-mediated N-methyl-d-aspartate receptor NR2B phosphorylation in the lumbosacral dorsal horn, is crucial for the induction of spinal reflex potentiation contributing to the development of visceral pain and/or hyperalgesia in the pelvic area.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to develop a mathematical equation to predict the birth weight during the second trimester at 20-24 weeks of gestation.
In a university hospital, 110 healthy pregnant women were eligible for inclusion at 20-24 weeks of gestation. We recorded the maternal weight (pre-pregnancy, mid-pregnancy, and at delivery) and body mass index (BMI), newborn birth weight, time period from ultrasound examination to term delivery, and also the fetal biometrics sonographically at 20-24 weeks of gestation. Pearson's correlation was used to verify the extent of the relationship between all the above measurements and the newborn birth weight. Multiple regressions with the stepwise method were used to analyze maternal weight factors, fetal biometrical factors, and pregnancy interval. An equation for term birth weight estimation during the second trimester was determined.
Maternal BMI at mid-pregnancy, time interval from mid-pregnancy to term, and abdominal circumference had the highest correlation with newborn birth weight (r = 0.388, 0.341, and 0.315, respectively, p < 0.05). Using the stepwise regression analysis, an optimal formula with variance of 0.303 was derived: estimated birth weight = -700 + 49.766 × (mid-pregnancy BMI [kg/m2]) + 13.362 × (time interval from mid-pregnancy to term delivery [days]) + 68.696 × (abdominal circumference [cm]).
We propose an accurate, simple, and easy formula to better assess the newborn birth weight at mid-pregnancy for the Asian population. Mid-pregnancy BMI was a more significant factor for birth weight estimation than other maternal weight factors in this study.
Taiwanese journal of obstetrics & gynecology 09/2010; 49(3):285-90.
[show abstract][hide abstract] ABSTRACT: To clarify the role of descending dopaminergic innervation in reflexive urethral closure, the impacts of dopaminergic D2 receptor (DR2)-selective agonists and antagonists on repetitive stimulation-induced pelvic-to-urethra spinal reflex potentiation (SRP) were tested using in vivo rat preparations. Pelvic afferent nerve test stimulation (TS; 1 pulse/30 s for 30 min) evoked baseline reflex activity with single spikes in the external urethral sphincter electromyogram (EUSE), whereas, repetitive stimulation (RS; 1 pulse/s for 30 min) induced SRP. Intrathecal application of quinelorane dihydrochloride (Q110; 10, 30, and 100 nM, 10 microl, a selective DR2 agonist) dose dependently inhibited the RS-induced SRP. Pretreatment with L135 (100 nM, 10 microL it, a selective DR2 antagonist) antagonized the Q110-dependent inhibition (100 nM, 10 microl it). Intrathecal AMPA (10 microM, 10 microl, a selective glutamatergic AMPA receptor agonist), and NMDA (10 microM, 10 microl, a selective glutamatergic NMDA receptor agonist) reversed the Q110-dependent inhibition. Intrathecal forskolin (100 nM, 10 microl, a PKA activator) prevented the Q110-dependent inhibition that was reversed by CNQX (10 microM, 10 microl it, a selective glutamate AMPA receptor antagonist) and APV (10 microM, 10 microl it , a selective glutamate NMDA receptor antagonist). Our results suggest that DR2 activation, which inactivates intracellular PKA, may be involved in descending dopaminergic inhibition of NMDA/AMPA receptor-dependent SRP at the lumbosacral spinal cord, which is thought to be involved in reflexive urethral closure.
[show abstract][hide abstract] ABSTRACT: Mesh-augmented reconstructive surgery for pelvic organ prolapse (POP) does not meet clinical expectations. A tissue-engineered fascia equivalent needs to be developed.
Human vaginal fibroblasts (HVFs) from 10 patients were characterized in vitro. Eligible HVFs and a biodegradable scaffold were used to fabricate a fascia equivalent, which was then transplanted in vivo.
The cultured HVFs were divided into high (n = 6) or low (n = 4) collagen I/III ratio groups. Cells of the high-ratio group exhibited significantly higher proliferation potential than those of the low-ratio group (P < 0.05). A fascia equivalent was made with HVFs of the high-ratio group. In the subsequent animal study, a well-organized neo-fascia formation containing HVFs could be traced up to 12 weeks after transplantation.
Our results suggest that a tissue-engineered fascia could be developed from HVFs in vitro and in vivo, which might be an effective treatment for POP in the future.
International Urogynecology Journal 09/2010; 21(9):1085-93. · 2.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study was performed to define the roles of actin-binding proteins in the regulation of actin filament assembly associated with cellular signal transduction pathways in stromal cell proliferation. Genistein, a tyrosine protein kinase inhibitor, decreased the intracellular Ca(2+) and attenuated cell proliferation and DNA synthesis through the beta-catenin and cyclin D1 pathway in human umbilical CD105-positive cells. Immunoprecipitation studies using anti-beta-actin antibody revealed that several actin-binding proteins implicated in cells include formin-2 (FMN-2), caldesmon (CaD), tropomyosin (Tm), and profilin. Protein levels of these proteins in whole cell lysates were not significantly changed by genistein. Three Tm isoforms, Tm-1, Tm-2, and Tm-4, were found to be present in cells. Genistein caused a reduction in levels of mRNAs coding for Tm-1 and Tm-4, but had no significant effect on Tm-2 mRNA levels. Immunofluorescence confocal scanning microscopy indicated that changes in the subcellular distribution of Tm and CaD, in which the diffuse cytosolic staining was shifted to show colocalization with actin stress fibers. In contrast, genistein-induced accumulation of FMN-2 and profilin in the peri-nuclear area. Silencing of FMN-2 by small interfering RNA resulted in increases of intracellular Ca(2+) and rendered genistein resistance in decreasing intracellular Ca(2+) in cells. These results provide the novel findings that genistein acts by modulating the cellular distribution of actin-binding proteins in association with alterations of cellular signal transduction pathways in human stromal cell proliferation.
Journal of Cellular Physiology 05/2010; 223(2):423-34. · 4.22 Impact Factor