Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 41
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
1.
Cancer Treat Res Commun ; 17: 23-30, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30326420

RESUMO

BACKGROUND: Upper urinary tract neuroendocrine carcinoma (UUT-NEC) is extremely rare and has a poor prognosis. Although a few cases of successful treatment have been reported, no treatment has shown established efficacy. PATIENTS AND METHODS: We analyzed 70 UUT-NEC patients, including 68 with small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC) reported between 1985 and 2017 and 2 treated at our hospital. RESULTS: Median patient age was 66 years, 58.6% were men, and 60% were of Asian descent. Most UUT-NECs were SCNEC (68; 95.7%), whereas LCNEC was very rare (2; 2.9%). More than half of the patients had accompanying other histological components, the most common being urothelial carcinoma (51.5%), whereas 41.4% had NEC alone. Of the 70 patients, 27 underwent additional therapy (e.g., chemotherapy and radiotherapy) along with surgery. Median survival was 15 months. In univariate analysis, stages T1-2 disease showed better prognosis than stages T3-4 (P < 0.001). Additional treatment (e.g., chemotherapy and radiotherapy) significantly improved prognosis (P = 0.014). Moreover, platinum-based chemotherapy also was associated with improved prognosis (P = 0.017). For platinum-based chemotherapy, multicollinearity with additional treatments was strong, and, thus, these data were not included in the analysis. Multivariate analysis revealed pathological stage (T1-2 vs. T3-4; P = 0.003) and additional treatment (P = 0.028) to be independent predictors of improved prognosis. CONCLUSION: Although UUT-NEC has a poor prognosis, additional treatment along with surgery and therapeutic intervention and stage T1-2 disease are independent factors to improve prognosis.

2.
Int J Urol ; 25(5): 479-485, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29577437

RESUMO

OBJECTIVES: To assess the effect of cernitin pollen extract on serum prostate-specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure. METHODS: A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate-specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate-specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer. RESULTS: The mean change in serum prostate-specific antigen and rate of change after administration of cernitin pollen extract in all patients were -0.6 ± 1.4 ng/mL and -7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate-specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively). CONCLUSIONS: The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate-specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.

3.
Int J Urol ; 24(7): 532-537, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28503734

RESUMO

OBJECTIVES: To assess the outcomes of the tissue fixation system midurethral sling for the treatment of intrinsic sphincter deficiency. METHODS: We retrospectively studied a total of 96 intrinsic sphincter deficiency patients treated with the tissue fixation system midurethral sling at Yokohama Motomachi Women's Clinic from 2006 to 2015. We evaluated intraoperative and 1-year postoperative results. Regarding the cure rate, we divided patients into three groups: (i) patients with maximum urethral closure pressure <20 and Valsalva leak point pressure <65 combined (n = 17); (ii) patients with maximum urethral closure pressure <20 (n = 55); and (iii) patients with Valsalva leak point pressure <65 (n = 47). RESULTS: The median age was 63 years (range 38-89 years). The median operating time including local anesthesia was 24 min (range 12-55 min) and median blood loss was 5.0 mL (range 3-69 mL). All operations were day surgery under local anesthesia. Postoperative pain was minimal. All patients were discharged the same day. There were no intraoperative complications except one bladder perforation. There were no tape rejections. The 1-year postoperative cure rates were: 88.2% among patients with maximum urethral closure pressure <20 and Valsalva leak point pressure <65, 90.9% for patients with maximum urethral closure pressure <20, and 85.1% among patients with Valsalva leak point pressure <65. CONCLUSIONS: The tissue fixation system midurethral sling operation is a simple, safe and effective operation for older women with intrinsic sphincter deficiency, and it can be carried out under local anesthesia.

4.
Int Urogynecol J ; 28(11): 1733-1738, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28500515

RESUMO

INTRODUCTION: To evaluate the clinical effectiveness and quality of life (QOL) of outpatient mid-urethral tissue fixation system sling (TFS) procedures for urodynamic stress urinary incontinence (SUI) at 3-year follow-up. METHODS: We analyzed 50 mid-urethral TFS sling operations between 2007 and 2012 at Yokohama Motomachi Women's Clinic LUNA. The primary outcome was success defined as a negative 24-h pad test, negative cough and Valsalva stress test, and no re-treatment for SUI. Secondary outcome was improvement in quality of life, which was assessed using the Incontinence Questionnaire-Short Form (ICIQ-SF) and the Incontinence Impact Questionnaire Short Form (IIQ-7). The 3-year postoperative scores were compared with baseline scores using the Wilcoxon signed rank test. A 5% two-sided significance level was used for all statistical testing. RESULTS: All operations were carried out on an outpatient basis with no intraoperative complications. The primary cure rate result at 3-year follow-up was 90%. Median total ICIQ-SF score changed from 12 (6-20) to 0 (0-14) and median total IIQ-7 score changed from 156 (0-300) to 0 (0.00-16.7) at 3-year follow-up. CONCLUSIONS: Results show that the TFS mid-urethral sling operation is a simple, safe, effective procedure that may be done without difficulty at a freestanding clinic on an outpatient basis and favorably improves subjective QOL of the patient.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/instrumentação , Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Local , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Qualidade de Vida
5.
ACS Comb Sci ; 18(6): 320-9, 2016 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-27053324

RESUMO

Identifying "druggable" targets and their corresponding therapeutic agents are two fundamental challenges in drug discovery research. The one-bead-one-compound (OBOC) combinatorial library method has been developed to discover peptides or small molecules that bind to a specific target protein or elicit a specific cellular response. The phage display cDNA expression proteome library method has been employed to identify target proteins that interact with specific compounds. Here, we combined these two high-throughput approaches, efficiently interrogated approximately 10(13) possible molecular interactions, and identified 91 small molecule compound beads that interacted strongly with the phage library. Of 19 compounds resynthesized, 4 were cytotoxic against cancer cells; one of these compounds was found to interact with EIF5B and inhibit protein translation. As more binding pairs are confirmed and evaluated, the "library-against-library" screening approach and the resulting small molecule-protein domain interaction database may serve as a valuable tool for basic research and drug development.


Assuntos
Descoberta de Drogas/métodos , Biblioteca de Peptídeos , Proteômica/métodos , Bibliotecas de Moléculas Pequenas , Antineoplásicos/farmacologia , Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Ciclo Celular , Linhagem Celular , Técnicas de Química Combinatória/métodos , DNA Complementar/biossíntese , DNA Complementar/genética , Ensaios de Seleção de Medicamentos Antitumorais , Ensaios de Triagem em Larga Escala , Humanos , Células Jurkat , Ligantes , Metionina/metabolismo
6.
Langmuir ; 31(26): 7251-63, 2015 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-26035074

RESUMO

The aim of this work is to derive formulas for numerical calculations of the orientation-dependent London-van der Waals (vdW) interaction energy (V(A)) between two rectangular bodies with arbitrary dimensions, arranged at arbitrary relative angles (θ) and separations in twisted and coplanar rotational modes. The formulation is made using a simple volume-element-integration method in the framework of the microscopic approach, in which V(A) is the sum of the local vdW energy (Vp) between body 1 and each thin plate constituting body 2. Examples of the calculation results are the following: (1) The θ values that give maximal and minimal values of V(A) depend on their shapes and relative positions. (2) As the bodies come close to each other, the variations of V(A) with θ and thus vdW dispersion torques generated are drastically intensified. (3) Upon increasing the length of crossing rods in twisted configurations, the V(A) values become constant beyond a critical length (depending on θ and separation), where the length effect on V(A) disappears. (4) The distribution curves of Vp show that the region in body 2 which interacts effectively with body 1 (i.e., the effective interaction region) is more sharply localized in the vicinity of the surface (closest to body 1) as the separation is decreased.

7.
J Neurosci ; 35(12): 5007-22, 2015 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-25810530

RESUMO

Genetic or pharmacological activation of canonical Wnt/ß-catenin signaling inhibits oligodendrocyte differentiation. Transcription factor 7-like 2 (TCF7l2), also known as TCF4, is a Wnt effector induced transiently in the oligodendroglial lineage. A well accepted dogma is that TCF7l2 inhibits oligodendrocyte differentiation through activation of Wnt/ß-catenin signaling. We report that TCF7l2 is upregulated transiently in postmitotic, newly differentiated oligodendrocytes. Using in vivo gene conditional ablation, we found surprisingly that TCF7l2 positively regulates neonatal and postnatal mouse oligodendrocyte differentiation during developmental myelination and remyelination in a manner independent of the Wnt/ß-catenin signaling pathway. We also reveal a novel role of TCF7l2 in repressing a bone morphogenetic protein signaling pathway that is known to inhibit oligodendrocyte differentiation. Thus, our study provides novel data justifying therapeutic attempts to enhance, rather than inhibit, TCF7l2 signaling to overcome arrested oligodendroglial differentiation in multiple sclerosis and other demyelinating diseases.


Assuntos
Diferenciação Celular/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Oligodendroglia/citologia , Oligodendroglia/fisiologia , Proteína 2 Semelhante ao Fator 7 de Transcrição/fisiologia , Via de Sinalização Wnt/fisiologia , beta Catenina , Animais , Proteínas Morfogenéticas Ósseas/fisiologia , Diferenciação Celular/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Técnicas de Silenciamento de Genes , Camundongos , Camundongos Transgênicos , Bainha de Mielina/genética , Bainha de Mielina/fisiologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Via de Sinalização Wnt/genética , beta Catenina/metabolismo
8.
Int J Urol ; 22(3): 306-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25403926

RESUMO

OBJECTIVES: To examine the efficacy and safety of onabotulinumtoxinA (Botox) injection into the bladder wall for the treatment of neurogenic detrusor overactivity secondary to spinal cord injury in Japanese patients. METHODS: We enrolled Japanese spinal cord injury patients with cystometrically confirmed neurogenic detrusor overactivity who experienced urinary incontinence at least once a week either because they were refractory to anticholinergics or had to discontinue treatment because of adverse events. Patients received 200 units of onabotulinumtoxinA injected into the bladder wall after a 2-week washout of anticholinergics, and urodynamic variables were assessed before and 1 month after injection. Catheterization and urinary incontinence data, as well as International Consultation on Incontinence Questionnaire-Short Form scores, were assessed before injection and every month thereafter until the cessation of treatment effects. RESULTS: The study enrolled 19 patients (13 men, six women, age range 22-67 years). One month after injection, the mean number of urinary incontinence episodes decreased from 4.3 to 1.5 times/day (P = 0.004), and the maximum cystometric capacity increased from 100 mL to 296 mL (P = 0.0004). The rate of effective cases whose daily urinary incontinence frequency was decreased to less than 50% was 74%. The duration of efficacy without anticholinergic medication ranged from 3 to 12 months (median 8.5 months). Clinically significant adverse events were not observed. CONCLUSIONS: The present findings show the efficacy and tolerability of onabotulinumtoxinA injection for the treatment of neurogenic detrusor overactivity in Japanese spinal cord injury patients.


Assuntos
Inibidores da Liberação da Acetilcolina/administração & dosagem , Toxinas Botulínicas Tipo A/administração & dosagem , Traumatismos da Medula Espinal/complicações , Bexiga Urinária Hiperativa/tratamento farmacológico , Incontinência Urinária/tratamento farmacológico , Inibidores da Liberação da Acetilcolina/efeitos adversos , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Toxinas Botulínicas Tipo A/efeitos adversos , Feminino , Humanos , Injeções Intramusculares , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária Hiperativa/etiologia , Urodinâmica , Adulto Jovem
9.
PLoS One ; 9(3): e92808, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24667894

RESUMO

BACKGROUND: The gender-specific influences of various confounding factors, including apnea, age, BMI, and cigarette consumption, on the function of the parasympathetic nerve system (PNS) during sleep in OSA patients has never been investigated. METHODS: One hundred ninety-seven males and 63 females with OSA were subjected to full PSG examinations including assessment of R-R intervals (RRIs) during an overnight ECG. The PNS-derived modulatory effect on the RRIs and the variability of this effect were quantified during REM and NREM using instantaneous time-frequency analysis with complex demodulation. The spectral domain with the maximum instantaneous amplitude in the high-frequency band between 0.15 and 0.4 Hz was defined as the main HF peak and used as a surrogate marker of PNS discharge. Based on density-spectrum-array maps of the main HF peaks (HF-DSA map), shifts in the central frequency of the main HF peak over time were continuously observed. When the main HF peaks on the HF-DSA maps maintained the same central frequency for more than 20 sec or 5 min, the PNS functions were considered to be "stable" or "very stable", respectively. RESULTS: Apneas enhanced PNS-derived cardiac-modulation during REM in males, but more importantly, they made PNS-function unstable during both REM and NREM in males and during NREM in females. Aging blunted the PNS-derived cardiac-modulation during both REM and NREM regardless of gender, but aging had no impact on the stability of PNS-function. BMI blunted PNS-eliciting cardiac-modulation during REM in males and during NREM in both males and females. BMI made the PNS unstable during REM in females. Neither height nor cigarette consumption influenced any PNS-related parameter. CONCLUSIONS: The PNS-derived cardiac-modulation was generally inhibited by aging and obesity, in which the effect of obesity was gender-specific. The PNS instability at nighttime was mainly induced by apneas but by obesity particularly during REM in females.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Caracteres Sexuais , Apneia Obstrutiva do Sono/fisiopatologia , Sono REM , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doenças do Sistema Nervoso Autônomo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Apneia Obstrutiva do Sono/patologia , Fumar/efeitos adversos
11.
Sleep Med ; 15(1): 33-41, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24342227

RESUMO

BACKGROUND AND OBJECTIVES: The pathophysiologic aspects of parasympathetic nerve (PN) function during sleep in patients with obstructive sleep apnea (OSA) studied by classical power spectrum analysis on heart rate variability (HRV) are highly controversial. The controversy is attributed to methodologic concerns, such as poor time resolution involved in power spectrum analysis. We aimed to establish the appropriate method for the investigation of PN function in OSA patients with apneas and hypopneas using instantaneous time-frequency analysis with complex demodulation (CD) and sufficient time resolution. METHODS: A total of 30 patients with PSG-confirmed mild to severe OSA were recruited for the analysis of frequency spectra contained in R-R intervals (RRI) of overnight electrocardiograph (ECG) tracings. High-frequency (HF) domains ranging between 0.15 and 0.40 Hz were selected for analysis. Among these domains, the HF domain with the maximum instantaneous amplitude was defined as the main HF peak and was used as the surrogate marker of PN discharge. Based on density spectrum array (DSA) map for main HF peak constructed with a time scale of 1s and a frequency resolution of 0.002 Hz (HF-DSA map), the shift in central frequency (CF) of main HF peak over time was continuously monitored. When the main HF peak with the same CF lasted for more than 20 s or 5 min on HF-DSA map, the PN function was considered to be stable or very stable. The measurements were then repeated after continuous positive airway pressure (CPAP) treatment. RESULTS: The extent of PN-evoked modulation of RRI was enhanced in nonrapid eye movement (NREM) sleep, though the stability was reduced in both NREM and rapid eye movement (REM) sleep. These peculiar behaviors of PN function were reversed by CPAP treatment. CONCLUSION: We found that instantaneous time-frequency analysis allowed estimation of transitional changes in PN function during sleep in OSA patients.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Pressão Positiva Contínua nas Vias Aéreas , Sistema Nervoso Parassimpático/fisiologia , Polissonografia/métodos , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Idoso , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa Respiratória/fisiologia , Processamento de Sinais Assistido por Computador , Fases do Sono/fisiologia
12.
Int Urogynecol J ; 25(6): 783-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24318563

RESUMO

INTRODUCTION AND HYPOTHESIS: In 2005, a new minimally invasive procedure, the tissue fixation system (TFS) was reported. Like TVT (tension-free vaginal tape), the TFS works by creating a foreign body collagenous tissue reaction that reinforces a weakened pelvic ligament. The objective was to assess the effectiveness and perioperative safety of TFS in a day surgery clinic for the treatment of pelvic organ prolapse (POP). METHODS: The TFS tape was applied in a tunnel adjacent to natural ligaments to repair the anterior cervical ring and cardinal ligament, paravaginal tissues and uterosacral ligaments under local anesthesia/sedation. We prospectively studied 60 patients, mean age 67, between October 2008 and February 2010 at Women's Clinic LUNA. Levels of POP were grade 2 (n = 20; 7 %), grade 3 (n = 30; 55 %), and grade 4 (n = 4; 7 %) according to the ICS POPQ classification. Fifty-four patients (90 %) who underwent a total of 162 POP operations presented for review. Follow-up was performed at 12 months. We defined surgical failure according to the ICS POPQ classification. We used prolapse quality of life (P-QOL) questions for QOL measurement. RESULTS: Ninety-eight percent of patients were discharged on the day of surgery. Of the 162 TFS operations reviewed, 157 were successful and 5 failed. The 5 failed operations comprised 4 cystoceles and 1 rectocele. Two patients developed cervical protrusions at the introitus at 6 months with no prolapse of the uterine body. We found 5 cases of erosion in 162 tape insertions. The total number of patients who had no complications, no surgical failures, no erosions, no sensation of bulging, and no cervical protrusions was 47 (87 %). CONCLUSIONS: The TFS uses the same surgical principle for repair as the TVT; this principle vastly minimizes the volume of mesh used, erosions, and other complications.


Assuntos
Anestesia Local , Ligamentos/cirurgia , Prolapso de Órgão Pélvico/cirurgia , Idoso , Procedimentos Cirúrgicos Ambulatórios , Desenho de Equipamento , Feminino , Procedimentos Cirúrgicos em Ginecologia/instrumentação , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Estudos Prospectivos , Indução de Remissão , Telas Cirúrgicas , Fatores de Tempo
13.
Langmuir ; 29(33): 10529-38, 2013 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-23876087

RESUMO

Monodispersed colloidal rods of ß-FeOOH with sizes ranging from 270 to 580 nm in length and 50 to 80 nm in width were synthesized. Narrow wedgelike gaps (0 to 700 nm in height) were formed around the inner bottom edge of the suspension glass cells. Optical microscopic observations revealed the formation of stringlike clusters of the rods and smectic sheets (by spontaneous side-by-side clustering of the strings) in the isotropic phase of the rod suspensions confined in narrow gaps; the electrolyte (HCl) concentrations of the suspensions are 5-40 mM, at which inter-rod interactions are attractive. The strings exhibit different colors that were used to investigate the structures of the strings with the help of interference color theory for thin films. The results are as follows. (1) The rods, lying flat on the gap bottom, are connected side-by-side and stacked upward to form stringlike clusters with different thicknesses depending on the gap height. (2) The stacking numbers (N(sr)) of the rods are estimated to be 1-5. With N(sr) increasing from 2 to 5, the volume fractions (ϕ) of the rods in the strings increased typically from 0.25-0.3 to 0.35-0.42 to reach limiting values (close to the ϕ values of the rods in the bulk smectic phase). (3) Unexpected low-ϕ strings are found in regions with an intermediate height in the gaps. These behaviors of ϕ may be caused by thermal fluctuations of the strings.

14.
J Neurosci ; 33(7): 3113-30, 2013 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-23407966

RESUMO

The expression of the gut tumor suppressor gene adenomatous polyposis coli (Apc) and its role in the oligodendroglial lineage are poorly understood. We found that immunoreactive APC is transiently induced in the oligodendroglial lineage during both normal myelination and remyelination following toxin-induced, genetic, or autoimmune demyelination murine models. Using the Cre/loxP system to conditionally ablate APC from the oligodendroglial lineage, we determined that APC enhances proliferation of oligodendroglial progenitor cells (OPCs) and is essential for oligodendrocyte differentiation in a cell-autonomous manner. Biallelic Apc disruption caused translocation of ß-catenin into the nucleus and upregulated ß-catenin-mediated Wnt signaling in early postnatal but not adult oligodendroglial lineage cells. The results of conditional ablation of Apc or Ctnnb1 (the gene encoding ß-catenin) and of simultaneous conditional ablation of Apc and Ctnnb1 revealed that ß-catenin is dispensable for postnatal oligodendroglial differentiation, that Apc one-allele deficiency is not sufficient to dysregulate ß-catenin-mediated Wnt signaling in oligodendroglial lineage cells, and that APC regulates oligodendrocyte differentiation through ß-catenin-independent, as well as ß-catenin-dependent, mechanisms. Gene ontology analysis of microarray data suggested that the ß-catenin-independent mechanism involves APC regulation of the cytoskeleton, a result compatible with established APC functions in neural precursors and with our observation that Apc-deleted OPCs develop fewer, shorter processes in vivo. Together, our data support the hypothesis that APC regulates oligodendrocyte differentiation through both ß-catenin-dependent and additional ß-catenin-independent mechanisms.


Assuntos
Proteína da Polipose Adenomatosa do Colo/fisiologia , Oligodendroglia/fisiologia , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/imunologia , Animais , Anticorpos , Western Blotting , Diferenciação Celular/fisiologia , Linhagem da Célula/fisiologia , Células Cultivadas , Antagonistas de Estrogênios/farmacologia , Imunoprecipitação , Hibridização In Situ , Camundongos , Camundongos Knockout , Análise em Microsséries , Microscopia Confocal , Glicoproteína Associada a Mielina/biossíntese , Regeneração Nervosa/fisiologia , RNA/biossíntese , RNA/isolamento & purificação , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Células-Tronco/fisiologia , Tamoxifeno/farmacologia , beta Catenina/fisiologia
15.
Low Urin Tract Symptoms ; 5(2): 55-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-26663370

RESUMO

OBJECTIVE: The aim of the present study was to assess the effects of onabotulinumtoxinA injection for refractory non-neurogenic overactive bladder (OAB) for 12 months. METHODS: For patients with persistent urgency urinary incontinence (UUI) more than once a week despite taking anti-cholinergic agents or incapability to continue the agents because of adverse effects, 100 units of onabotulinumtoxinA was injected at 30 sites in the sub-epithelial bladder wall. Efficacy was assessed every month up to 12 months after injection, using a three-day frequency-volume chart (FVC) and postvoid residual urine (PVR), three questionnaires, and a simple score of Global Response Assessment (GRA). Failure was defined as when GRA was negative and additional treatment was administered. RESULTS: Nine men and eight women aged 67 ± 12 years were included. On FVC, frequencies of urgency, UUI and daytime urination significantly decreased up to the 11th month. PVR significantly increased at the first and second months but no patient required catheterization. The total scores of Overactive Bladder Symptom Score and International Consultation on Incontinence Questionnaire Short Form were significantly decreased for 10 and eight months, respectively. The score of GRA was significantly improved for eight months. The median time to failure was 11.0 months. CONCLUSION: This study suggests that onabotulinumtoxinA submucosal injection is promising for refractory non-neurogenic OAB. It is anticipated that the treatment is effective for eight to nine months and approximately 40% of the patients do not require anticholinergics at the 12th month postoperatively.

16.
J Neurosci ; 32(2): 639-45, 2012 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-22238099

RESUMO

Pharmacological studies have suggested that oligodendroglial NMDA glutamate receptors (NMDARs) mediate white matter injury in a variety of CNS diseases, including multiple sclerosis (MS). We tested this hypothesis in experimental autoimmune encephalomyelitis (EAE), a model of human MS, by timed conditional disruption of oligodendroglial NR1, an essential subunit of functional NMDARs, using an inducible proteolipid protein (Plp) promoter-driven Cre-loxP recombination system. We found that selective ablation of oligodendroglial NR1 did not alter the clinical severity of EAE elicited in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG-peptide), nor were there significant differences between the oligodendroglial NR1 KO and non-KO mice in numbers of axons lost in spinal cord dorsal funiculi or severity of spinal cord demyelination. Similarly, constitutive deletion of NR3A, a modulatory subunit of oligodendroglial NMDARs, did not alter the course of MOG-peptide EAE. Furthermore, conditional and constitutive ablation of NR1 in neonatal oligodendrocyte progenitor cells did not interrupt their normal maturation and differentiation. Collectively, our data suggest that oligodendroglial lineage NMDARs are neither required for timely postnatal development of the oligodendroglial lineage, nor significant participants in the pathophysiology of MOG-peptide EAE.


Assuntos
Linhagem da Célula/fisiologia , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Oligodendroglia/metabolismo , Receptores de N-Metil-D-Aspartato/deficiência , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Suscetibilidade a Doenças , Encefalomielite Autoimune Experimental/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oligodendroglia/patologia , Oligodendroglia/fisiologia , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo
17.
J Neurosci ; 31(33): 11914-28, 2011 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-21849552

RESUMO

Accumulations of hypertrophic, intensely glial fibrillary acidic protein-positive (GFAP(+)) astroglia, which also express immunoreactive nestin and vimentin, are prominent features of multiple sclerosis lesions. The issues of the cellular origin of hypertrophic GFAP(+)/vimentin(+)/nestin(+) "reactive" astroglia and also the plasticities and lineage relationships among three macroglial progenitor populations-oligodendrocyte progenitor cells (OPCs), astrocytes and ependymal cells-during multiple sclerosis and other CNS diseases remain controversial. We used genetic fate-mappings with a battery of inducible Cre drivers (Olig2-Cre-ER(T2), GFAP-Cre-ER(T2), FoxJ1-Cre-ER(T2) and Nestin-Cre-ER(T2)) to explore these issues in adult mice with myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis (EAE). The proliferative rate of spinal cord OPCs rose fivefold above control levels during EAE, and numbers of oligodendroglia increased as well, but astrogenesis from OPCs was rare. Spinal cord ependymal cells, previously reported to be multipotent, did not augment their low proliferative rate, nor give rise to astroglia or OPCs. Instead, the hypertrophic, vimentin(+)/nestin(+), reactive astroglia that accumulated in spinal cord in this multiple sclerosis model were derived by proliferation and phenotypic transformation of fibrous astroglia in white matter, and solely by phenotypic transformation of protoplasmic astroglia in gray matter. This comprehensive analysis of macroglial plasticity in EAE helps to clarify the origins of astrogliosis in CNS inflammatory demyelinative disorders.


Assuntos
Astrócitos/patologia , Encefalomielite Autoimune Experimental/patologia , Plasticidade Neuronal/fisiologia , Oligodendroglia/patologia , Animais , Astrócitos/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Oligodendroglia/fisiologia , Medula Espinal/citologia , Medula Espinal/fisiologia
18.
Vet Immunol Immunopathol ; 143(1-2): 11-9, 2011 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-21722969

RESUMO

There is a need to develop novel targeted imaging and therapeutic agents that can aid in early diagnosis, detection of metastasis and treatment of melanoma. Alpha-3 integrin is overexpressed in 82% of metastatic melanomas in humans and may be a potential target for peptide ligands carrying therapeutic agents. Five melanoma cell lines were generated from canine primary oral and metastatic canine tumors, grown in mice, and validated with melanoma markers Melan A, S-100, Micropthalmia transcription factor (MITF), Tyrosinase, and MART-1. The melanoma cell lines were tested for binding affinity to previously published alpha-3 integrin-binding peptides containing the cdGXGXXc motif. Fluorescent conjugates of the alpha-3 integrin binding OA02 peptide were used to quantify receptor affinity in the cell lines, a specimen of canine primary oral melanoma, and melanoma xenografts. Alpha-3 integrin was expressed by all 5 canine melanoma cell lines. Four of the 5 lines as well as the primary canine tumor showed affinity to alpha-3 integrin binding peptides with the cdGXGXXc motif. Optical imaging of canine melanoma xenografts in nude mice indicates rapid, strong uptake of the optical tracer in the tumor with an average persistence of approximately 48 h. Ex vivo images showed high tumor-to-background ratio, with tumor signals more than twice that of the kidney and other vital organs. We propose that integrin alpha-3 integrin binding ligands could potentially become useful probes for imaging and delivery of cytotoxic agents for the treatment of melanoma.


Assuntos
Doenças do Cão/metabolismo , Integrina alfa3/metabolismo , Melanoma/veterinária , Animais , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Cães , Corantes Fluorescentes , Humanos , Ligantes , Melanoma/metabolismo , Melanoma Amelanótico/metabolismo , Melanoma Amelanótico/veterinária , Camundongos , Camundongos Nus , Neoplasias Bucais/metabolismo , Neoplasias Bucais/veterinária , Pesquisa Médica Translacional , Transplante Heterólogo
19.
Masui ; 60(6): 728-32, 2011 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-21710774

RESUMO

We described a case of ventricular fibrillation in patients with Brugada type electrocardiogram (ECG) during surgery. A 63-year-old man underwent lung lobectomy under combined general and epidural anesthesia. His preoperative ECG showed Brugada type, but he was asymptomatic and did not have a family history of sudden death. Anesthesia was induced using propofol, vecuronium and fentanyl, and maintained using propofol and lidocaine via epidural catheter. One hour into operation, ventricular fibrillation developed. After cardiac compression in a few seconds, sinus rhythm was restored and blood pressure was elevated. When the wound was sutured, ventricular fibrillation occurred again. Defibrillation was attempted immediately and sinus rhythm was restored. We diagnosed coronary spastic angina after acetylcholine challenge test. Previous report describes that the incidence of vasospasm in Brugada type ECG cases is relatively higher than those with the normal ECG. In addition, ventricular fibrillation might be induced by local anesthetics because these agents were administrated 10 minutes before the few events and balance of autonomic nervous system was changed. We conclude that strict monitoring and immediate treatment for ventricular fibrillation are important for anesthetic management in asymptomatic patient with Brugada type ECG.


Assuntos
Síndrome de Brugada/induzido quimicamente , Eletrocardiografia , Complicações Intraoperatórias/induzido quimicamente , Fibrilação Ventricular/induzido quimicamente , Acetilcolina , Anestesia Epidural , Anestesia Geral , Anestésicos Locais/efeitos adversos , Vasoespasmo Coronário/induzido quimicamente , Vasoespasmo Coronário/diagnóstico , Humanos , Complicações Intraoperatórias/terapia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Pneumonectomia , Fibrilação Ventricular/terapia
20.
ACS Comb Sci ; 13(3): 259-64, 2011 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-21302937

RESUMO

The one-bead-one-compound (OBOC) technology enables one to generate thousands to millions of chemical molecules on resin beads (90 µm diameter) such that each bead displays 10(13) copies of the same chemical entity. Whole-cell binding assays have been developed to screen OBOC combinatorial libraries for ligands that bind to specific cell surface receptors. While very powerful, this screening method does not address the downstream cell signaling properties of the binding ligand. We have modified the OBOC technology by introducing a fixed known cell adhesion ligand to the outer layer of each bead. This one-bead-two-compound (OB2C) library configuration allows the bound cells to interact with the random immobilized chemical molecules on each bead. The bound cells can then be probed for specific cellular responses such as apoptosis and activation or inhibition of a specific cell signaling pathway. To validate this concept, an OB2C combinatorial library was created such that a random hexapeptide plus a high affinity lymphoma targeting ligand LLP2A were displayed on each bead. This LLP2A-X(6) OB2C library was then screened with human T-cell leukemia cells (Molt-4) for cell death responses. After 5 days of incubation, propidium iodide was added to the bead library to stain dead cells. Beads coated by red fluorescent cells were isolated for sequence analysis. Two ligands identified by this method, when added to the lymphoid cancer cells, were able to induce cell death.


Assuntos
Técnicas de Química Combinatória , Leucemia de Células T/patologia , Linhagem Celular Tumoral , Humanos , Ligantes
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA