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1.
J Biomech Eng ; 143(11)2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34159357

RESUMO

The urinary bladder is a highly dynamic organ that undergoes large deformations several times per day. Mechanical characteristics of the tissue are crucial in determining the function and dysfunction of the organ. Yet, literature reporting on the mechanical properties of human bladder tissue is scarce and, at times, contradictory. In this study, we focused on mechanically testing tissue from both human and pig bladders using identical protocols to validate the use of pigs as a model for the human bladder. Furthermore, we tested the effect of two treatments on tissue mechanical properties. Namely, elastase to digest elastin fibers, and oxybutynin to reduce smooth muscle cell spasticity. Additionally, mechanical properties based on the anatomical direction of testing were evaluated. We implemented two different material models to aid in the interpretation of the experimental results. We found that human tissue behaves similarly to pig tissue at high deformations (collagen-dominated behavior) while we detected differences between the species at low deformations (amorphous matrix-dominated behavior). Our results also suggest that elastin could play a role in determining the behavior of the fiber network. Finally, we confirmed the anisotropy of the tissue, which reached higher stresses in the transverse direction when compared to the longitudinal direction.


Assuntos
Bexiga Urinária
2.
J Neurosci ; 35(8): 3652-62, 2015 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-25716863

RESUMO

The link between neural activity and the refinement of projections from retina to the dorsal lateral geniculate nucleus (dLGN) of thalamus is based largely on studies that disrupt presynaptic retinogeniculate activity. Postsynaptic mechanisms responsible for implementing the activity-dependent remodeling in dLGN remain unknown. We tested whether L-type Ca(2+) channel activity in the form of synaptically evoked plateau potentials in dLGN cells is needed for remodeling by using a mutant mouse that lacks the ancillary ß3 subunit and, as a consequence, has highly reduced L-type channel expression and attenuated L-type Ca(2+) currents. In the dLGNs of ß3-null mice, glutamatergic postsynaptic activity evoked by optic tract stimulation was normal, but plateau potentials were rarely observed. The few plateaus that were evoked required high rates of retinal stimulation, but were still greatly attenuated compared with those recorded in age-matched wild-type mice. While ß3-null mice exhibit normal stage II and III retinal waves, their retinogeniculate projections fail to segregate properly and dLGN cells show a high degree of retinal convergence even at late postnatal ages. These structural and functional defects were also accompanied by a reduction in CREB phosphorylation, a signaling event that has been shown to be essential for retinogeniculate axon segregation. Thus, postsynaptic L-type Ca(2+) activity plays an important role in mediating the refinement of the retinogeniculate pathway.


Assuntos
Potenciais Pós-Sinápticos Excitadores , Corpos Geniculados/fisiologia , Células Ganglionares da Retina/fisiologia , Animais , Canais de Cálcio Tipo L/genética , Canais de Cálcio Tipo L/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Feminino , Corpos Geniculados/citologia , Corpos Geniculados/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Células Ganglionares da Retina/metabolismo , Vias Visuais/citologia , Vias Visuais/metabolismo , Vias Visuais/fisiologia
3.
Can J Urol ; 22(1): 7671-3, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25694018

RESUMO

A 48-year-old man presented for evaluation of an expanding abdominal mass. Twenty years earlier, he had developed Fournier's gangrene requiring extensive debridement. He underwent augmentation cystoplasty with a catheterizable stoma due to a proximal urethral stricture. Fifteen years later, he was found to have a 14 cm x 18 cm bladder augment calculus. Simpson obstetric forceps were passed into the augment to deliver a 1110 gram stone with minimal devitalization of the colonic augmentation tissue. This is the first report of stone management with obstetric forceps in an augmented bladder. The specimen itself is among the largest stones ever reported.


Assuntos
Estruturas Criadas Cirurgicamente/efeitos adversos , Cálculos da Bexiga Urinária/cirurgia , Bexiga Urinária/cirurgia , Procedimentos Cirúrgicos Urológicos/instrumentação , Cistostomia , Humanos , Masculino , Pessoa de Meia-Idade , Cálculos da Bexiga Urinária/etiologia
4.
Dis Model Mech ; 16(7)2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37293698

RESUMO

Little is known about the distal excretory component of the urinary tract in Danio rerio (zebrafish). This component is affected by many human diseases and disorders of development. Here, we have undertaken multi-level analyses to determine the structure and composition of the distal urinary tract in the zebrafish. In silico searches identified uroplakin 1a (ukp1a), uroplakin 2 (upk2) and uroplakin 3b (upk3b) genes in the zebrafish genome (orthologues to genes that encode urothelium-specific proteins in humans). In situ hybridization demonstrated ukp1a expression in the zebrafish pronephros and cloaca from 96 h post-fertilization. Haematoxylin and Eosin staining of adult zebrafish demonstrated two mesonephric ducts uniting into a urinary bladder that leads to a distinct urethral opening. Immunohistochemistry identified Uroplakin 1a, Uroplakin 2 and GATA3 expression in zebrafish urinary bladder cell layers that match human urothelial expression. Fluorescent dye injections demonstrated zebrafish urinary bladder function, including urine storage and intermittent micturition, and a urethral orifice separate from the larger anal canal and rectum. Our findings reveal homology between the urinary tracts of zebrafish and humans, and offer the former as a model system to study disease.


Assuntos
Glicoproteínas de Membrana , Peixe-Zebra , Animais , Humanos , Adulto , Peixe-Zebra/metabolismo , Glicoproteínas de Membrana/metabolismo , Uroplaquina Ia/metabolismo , Uroplaquina II/metabolismo , Bexiga Urinária/metabolismo
5.
J Neurosci ; 31(2): 575-86, 2011 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-21228166

RESUMO

Development of visual system circuitry requires the formation of precise synaptic connections between neurons in the retina and brain. For example, axons from retinal ganglion cells (RGCs) form synapses onto neurons within subnuclei of the lateral geniculate nucleus (LGN) [i.e., the dorsal LGN (dLGN), ventral LGN (vLGN), and intergeniculate leaflet (IGL)]. Distinct classes of RGCs project to these subnuclei: the dLGN is innervated by image-forming RGCs, whereas the vLGN and IGL are innervated by non-image-forming RGCs. To explore potential mechanisms regulating class-specific LGN targeting, we sought to identify differentially expressed targeting molecules in these LGN subnuclei. One candidate targeting molecule enriched in the vLGN and IGL during retinogeniculate circuit formation was the extracellular matrix molecule reelin. Anterograde labeling of RGC axons in mutant mice lacking functional reelin (reln(rl/rl)) revealed reduced patterns of vLGN and IGL innervation and misrouted RGC axons in adjacent non-retino-recipient thalamic nuclei. Using genetic reporter mice, we further demonstrated that mistargeted axons were from non-image-forming, intrinsically photosensitive RGCs (ipRGCs). In contrast to mistargeted ipRGC axons, axons arising from image-forming RGCs and layer VI cortical neurons correctly targeted the dLGN in reln(rl/rl) mutants. Together, these data reveal that reelin is essential for the targeting of LGN subnuclei by functionally distinct classes of RGCs.


Assuntos
Moléculas de Adesão Celular Neuronais/fisiologia , Proteínas da Matriz Extracelular/fisiologia , Corpos Geniculados/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Células Ganglionares da Retina/fisiologia , Serina Endopeptidases/fisiologia , Animais , Axônios/fisiologia , Moléculas de Adesão Celular Neuronais/genética , Córtex Cerebral/fisiologia , Proteínas da Matriz Extracelular/genética , Camundongos , Camundongos Mutantes , Proteínas do Tecido Nervoso/genética , Proteína Reelina , Serina Endopeptidases/genética , Transdução de Sinais
6.
Tissue Eng Part A ; 27(1-2): 103-116, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32460641

RESUMO

Surgical reconstruction of tubular esophageal defects with autologous gastrointestinal segments is the gold standard treatment to replace damaged or diseased esophageal tissues. Unfortunately, this approach is associated with adverse complications, including dysphagia, donor-site morbidity, and in some cases patient death. Bilayer silk fibroin (BLSF) scaffolds were investigated as alternative, acellular grafts for tubular esophagoplasty in a porcine defect model for 3 months of implantation. Adult Yucatan mini-swine (n = 5) were subjected to esophageal reconstruction with tubular BLSF grafts (2 cm in length) in combination with transient esophageal stenting for 2 months followed by a 1-month period, where the graft site was unstented. All animals receiving BLSF grafts survived and were capable of solid food consumption, however strictures were noted at graft regions in 60% of the experimental cohort between 2 and 3 months postop and required balloon dilation. In addition, fluoroscopic analysis showed peristaltic function in only 1/5 neotissues. Following swine harvest at 3 months, ex vivo tissue bath evaluations revealed that neoconduits exhibited contractile responses to carbachol, electric field stimulation, and KCl, whereas sodium nitroprusside and isoproterenol induced relaxation effects. Histological (Masson's Trichrome) and immunohistochemical analyses of regenerated tissue conduits showed a stratified, squamous epithelium expressing pan-cytokeratins buttressed by a vascularized lamina propria containing a smooth muscle-rich muscularis mucosa surrounded by a muscularis externa. Neuronal density, characterized by the presence of synaptophysin-positive boutons, was significantly lower in neotissues in comparison to nonsurgical controls. BLSF scaffolds represent a promising platform for the repair of tubular esophageal defects, however improvements in scaffold design are needed to reduce the rate of complications and improve the extent of constructive tissue remodeling. Impact statement The search for a superior "off-the-shelf" scaffold capable of repairing tubularesophageal defects as well as overcoming limitations associated with conventional autologous gastrointestinal segments remains elusive. The purpose of this study was to investigate the performance of an acellular, bilayer silk fibroin graft (BLSF) for tubular esophagoplasty in a porcine model. Our results demonstrated that BLSF scaffolds supported the formation of tubular neotissues with innervated, vascularized epithelial and muscular components capable of contractile and relaxation responses. BLSF scaffolds represent a promising platform for esophageal tissue engineering.


Assuntos
Esofagoplastia , Fibroínas , Animais , Fibroínas/farmacologia , Regeneração , Seda , Suínos , Engenharia Tecidual , Alicerces Teciduais
7.
Sci Rep ; 11(1): 7086, 2021 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782465

RESUMO

Constructive remodeling of focal esophageal defects with biodegradable acellular grafts relies on the ability of host progenitor cell populations to repopulate implant regions and facilitate growth of de novo functional tissue. Intrinsic molecular mechanisms governing esophageal repair processes following biomaterial-based, surgical reconstruction is largely unknown. In the present study, we utilized mass spectrometry-based quantitative proteomics and in silico pathway evaluations to identify signaling cascades which were significantly activated during neoepithelial formation in a Sprague Dawley rat model of onlay esophagoplasty with acellular silk fibroin scaffolds. Pharmacologic inhibitor and rescue experiments revealed that epithelialization of neotissues is significantly dependent in part on pro-survival stimuli capable of suppressing caspase activity in epithelial progenitors via activation of hepatocyte growth factor receptor (c-MET), tropomyosin receptor kinase A (TrkA), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) signaling mechanisms. These data highlight the molecular machinery involved in esophageal epithelial regeneration following surgical repair with acellular implants.


Assuntos
Esôfago/citologia , Fibroínas/administração & dosagem , Procedimentos de Cirurgia Plástica/métodos , Animais , Células Epiteliais/citologia , Esôfago/cirurgia , Humanos , Ratos Sprague-Dawley , Regeneração , Transdução de Sinais
8.
J Endourol ; 32(4): 290-295, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29239225

RESUMO

INTRODUCTION AND OBJECTIVE: Recently there has been interest in a dusting technique for lithotripsy during ureteroscopy (URS) utilizing high-frequency and low-pulse energy (HiFr-LoPE) settings. We assessed a 120-W holmium laser that permits high-frequency (>50 Hz) dusting. MATERIALS AND METHODS: Consecutive URS cases performed by a single surgeon using the P120H (Lumenis, San Jose, CA) were reviewed. Lithotripsy was performed using HiFr-LoPE settings (50-80 Hz/0.2-0.5 J [10-40 W]). Residual fragments (RFs) were determined on postoperative radiography, ultrasonography, or CT. Complications were classified using the Clavien-Dindo grade. RESULTS: URS was performed on 82 renal units (71 patients). Renal stones constituted the majority (73%), including four partial staghorn stones. Mean stone size and density (HU) were 12.5 mm (SD 8.7; range 5.0-50.0) and 993 (SD 353; range 230-1580), respectively. Ureteral access sheath was used in 15 (21%) patients. Mean total laser energy per case was 5.2 kJ (range 0.1-42.1). Dusting was exclusively performed in 84% of cases. Postoperative stents were placed in 91% (41% string). Zero-fragment and ≤2 mm RF rates were 62.1% and 74.2%, respectively. There were 11 complications (13%) (grade 1 = 5, grade 2 = 6). The emergency department visit rate was 5.6%. There were no hospitalizations or reinterventions. CONCLUSIONS: Refinements in laser technology have expanded methods to ablate urinary stones. Outcomes utilizing a dusting technique demonstrated acceptable RF and complication rates. However, not all stones are amenable to dusting, and further study is needed to define the optimal role of this technique during laser lithotripsy.


Assuntos
Cálculos Renais/cirurgia , Lasers de Estado Sólido , Litotripsia a Laser/métodos , Ureteroscopia/métodos , Adulto , Idoso , Coleta de Dados , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização , Humanos , Cálculos Renais/diagnóstico por imagem , Litotripsia a Laser/efeitos adversos , Masculino , Pessoa de Meia-Idade , Radiografia , Cálculos Coraliformes/diagnóstico por imagem , Cálculos Coraliformes/cirurgia , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto Jovem
9.
Urology ; 116: 41-46, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29545043

RESUMO

OBJECTIVE: To evaluate the association of clinical factors on outcomes in patients with spinal cord injury (SCI) undergoing ureteroscopy. Immobility, recurrent urinary tract infection, and lower urinary tract dysfunction contribute to renal stone formation in patients with SCI. Ureteroscopy is a commonly utilized treatment modality; however, surgical complication rates and outcomes have been poorly defined. Evidence guiding safe and effective treatment of stones in this cohort remains scarce. METHODS: Records were retrospectively reviewed for patients with SCI who underwent ureteroscopy for kidney stones from 1996 to 2014 at a single institution. Multivariate relationships were evaluated using a general estimating equation model. RESULTS: Forty-six patients with SCI underwent a total of 95 ureteroscopic procedures. After treatment, stone-free rate was 17% and 20% with <2-mm fragments. The complication rate was 21%. On multivariate analysis, SCI in cervical (C) levels was associated with higher risk of complications (C3: odds ratio [OR] 3.83, 95% confidence interval [CI] 2.17-6.98; C6: OR 3.83, 95% CI 1.08-13.53). American Spinal Injury Association Scale A classification was associated with a lower probability of stone-free status (OR 0.16, 95% CI 0.03-0.82). Patients averaged 2.2 procedures yet more procedures were associated with lower stone-free status (OR 0.83, 95% CI 0.03-0.32). Chronic obstructive pulmonary disease and bladder management modality were not associated with stone-free status or complications. CONCLUSION: In patients with SCI, higher injury level and complete SCI were associated with worse stone clearance and more complications. Stone-free rate was 17%. Overall, flexible ureteroscopy is a relatively safe procedure in this population. Alternative strategies should be considered after failed ureteroscopy.


Assuntos
Cálculos Renais/cirurgia , Litotripsia a Laser/métodos , Traumatismos da Medula Espinal/complicações , Ureteroscopia , Adulto , Idoso , Apatitas/análise , Doenças Cardiovasculares/epidemiologia , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Cálculos Renais/química , Cálculos Renais/epidemiologia , Cálculos Renais/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Doenças Respiratórias/epidemiologia , Traumatismos da Medula Espinal/epidemiologia , Estruvita/análise , Resultado do Tratamento , Bexiga Urinaria Neurogênica/complicações , Infecções Urinárias/complicações , Infecções Urinárias/epidemiologia
10.
Urol Pract ; 5(5): 405-410, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37312365

RESUMO

INTRODUCTION: Paging is a critical modality for urgent hospital communication. We sought to improve overnight nurse paging practices to reduce noncritical pages, improve resident sleep practices and create a team approach to patient care between residents and overnight nursing staff. METHODS: Residents, overnight urology nurses and a communications liaison met during 2 overnight sessions in October 2014 to develop a training curriculum for overnight paging, which consisted of a paging protocol based on page urgency, and batching nonurgent communication into a cluster page. Overnight (11 p.m. to 7 a.m.) pages per night were assessed from March 2014 to March 2015. Nurses and residents categorized page messages for perceived urgency. Pre-training and post-training surveys examined physician-nurse opinion after collaboration. RESULTS: Before training the nurses and residents had variable agreement across all urgency categories (Cohen's kappa=0.25 indicating poor agreement, sample size 132 pages). On trained floors average nightly pages decreased from 2.6 during training to 1.6 after training (November to January, Mann-Whitney p=0.007). This reduction was stable 5 months after training (1.8 pages per night, p=0.994 compared to after training). There was also a paging decrease on untrained floors (7.9 from 9.8 pages per night, p=0.005) but the decrease was lost at 5 months (6.29 pages per night, p=0.0493). Paging frequency from trained floors was proportionally lower (50% reduction) than from untrained floors (29% reduction). The post-training survey demonstrated that new paging practices improved overnight communication, physician response and mutual respect. CONCLUSIONS: This nurse-physician training collaborative produced a lasting reduction in overnight pages, an improved resident response to urgent pages and an enhanced culture of mutual respect.

11.
Urology ; 106: 39-44, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28502597

RESUMO

OBJECTIVE: To demonstrate that commercial activity monitoring devices (CAMDs) are practical for monitoring resident sleep while on call. Studies that have directly monitored resident sleep are limited, likely owing to both cost and difficulty in study interpretation. The advent of wearable CAMDs that estimate sleep presents the opportunity to more readily evaluate resident sleep in physically active settings and "home call," a coverage arrangement familiar to urology programs. METHODS: Twelve urology residents were outfitted with Fitbit Flex devices during "home call" for a total of 57 (out of 64, or 89%) call or post-call night pairs. Residents were surveyed with the Stanford Sleepiness Scale (SSS), a single-question alertness survey. Time in bed (TIB) was "time to bed" to "rise for day." Fitbit accelerometers register activity as follows: (1) not moving; (2) minimal movement or restless; or (3) above threshold for accelerometer to register steps. Total sleep time (TST) was the number of minutes in level 1 activity during TIB. Sleep efficiency (SE) was defined as TST divided by TIB. RESULTS: While on call, 10 responding (of 12 available, 83%) residents on average reported TIB as 347 minutes, TST as 165 minutes, and had an SE of 47%. Interestingly, SSS responses did not correlate with sleep parameters. Post-call sleep demonstrated increases in TIB, SE, and TST (+23%, +15%, and +44%, respectively) while sleepiness was reduced by 22%. CONCLUSION: We demonstrate that urologic residents can consistently wear CAMDs while on home call. SSS did not correlate with Fitbit-estimated sleep duration. Further study with such devices may enhance sleep deprivation recognition to improve resident sleep.


Assuntos
Acelerometria , Internato e Residência , Polissonografia , Sono , Urologia/educação , Fadiga , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Autorrelato , Fatores de Tempo , Tolerância ao Trabalho Programado
12.
Cancer Res ; 63(14): 4021-7, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12874001

RESUMO

Therapeutic irradiation of the brain is associated with a number of adverse effects, including cognitive impairment. Although the pathogenesis of radiation-induced cognitive injury is unknown, it may involve loss of neural precursor cells from the subgranular zone (SGZ) of the hippocampal dentate gyrus and alterations in new cell production (neurogenesis). Young adult male C57BL mice received whole brain irradiation, and 6-48 h later, hippocampal tissue was assessed using immunohistochemistry for detection of apoptosis and numbers of proliferating cells and immature neurons. Apoptosis peaked 12 h after irradiation, and its extent was dose dependent. Forty-eight h after irradiation, proliferating SGZ cells were reduced by 93-96%; immature neurons were decreased from 40 to 60% in a dose-dependent fashion. To determine whether acute cell sensitivity translated into long-term changes, we quantified neurogenesis 2 months after irradiation with 0, 2, 5, or 10 Gy. Multiple injections of BrdUrd were given to label proliferating cells, and 3 weeks later, confocal microscopy was used to determine the percentage of BrdUrd-labeled cells that showed mature cell phenotypes. The production of new neurons was significantly reduced by X-rays; that change was dose dependent. In contrast, there were no apparent effects on the production of new astrocytes or oligodendrocytes. Measures of activated microglia indicated that changes in neurogenesis were associated with a significant inflammatory response. Given the known effects of radiation on cognitive function and the relationship between hippocampal neurogenesis and associated memory formation, our data suggest that precursor cell radiation response and altered neurogenesis may play a contributory if not causative role in radiation-induced cognitive impairment.


Assuntos
Giro Denteado/efeitos da radiação , Neurônios/efeitos da radiação , Animais , Apoptose/efeitos da radiação , Divisão Celular/efeitos da radiação , Giro Denteado/crescimento & desenvolvimento , Relação Dose-Resposta à Radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia
13.
Urol Case Rep ; 7: 20-22, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34703770

RESUMO

Crossed-fused renal ectopy is an uncommon abnormality of the genitourinary tract that results from errors during embryological development. Ureteral herniation represents another rare anatomic event and can often occur from spontaneous, postoperative, and congenital causes (Allam, Johnson, Grewal & Johnson 2015; Pollack, Popky & Blumberg 1975). Here, we discuss the complex clinical course of a patient with crossed-fused renal ectopia who presents with symptoms due to ureteroinguinal herniation and provide a brief overview of the literature. We highlight the clinical considerations in the management of this patient and provide a potential anatomical and embryological explanation for his presentation.

14.
Radiat Res ; 162(1): 39-47, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15222778

RESUMO

During treatment of brain tumors, some head and neck tumors, and other diseases, like arteriovenous malformations, the normal brain is exposed to ionizing radiation. While high radiation doses can cause severe tissue destruction, lower doses can induce cognitive impairments without signs of overt tissue damage. The underlying pathogenesis of these impairments is not well understood but may involve the neural precursor cells in the dentate gyrus of the hippocampus. To assess the effects of radiation on cognitive function, 2-month-old mice received either sham treatment (controls) or localized X irradiation (10 Gy) to the hippocampus/cortex and were tested behaviorally 3 months later. Compared to controls, X-irradiated mice showed hippocampal-dependent spatial learning and memory impairments in the Barnes maze but not the Morris water maze. No nonspatial learning and memory impairments were detected. The cognitive impairments were associated with reductions in proliferating Ki-67-positive cells and Doublecortin-positive immature neurons in the subgranular zone (SGZ) of the dentate gyrus. This study shows significant cognitive impairments after a modest dose of radiation and demonstrates that the Barnes maze is particularly sensitive for the detection of radiation-induced cognitive deficits in young adult mice. The significant loss of proliferating SGZ cells and their progeny suggests a contributory role of reduced neurogenesis in the pathogenesis of radiation-induced cognitive impairments.


Assuntos
Cognição/efeitos da radiação , Hipocampo/efeitos da radiação , Neurônios/efeitos da radiação , Animais , Cognição/fisiologia , Transtornos Cognitivos/etiologia , Hipocampo/fisiologia , Antígeno Ki-67/análise , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia
15.
J Child Neurol ; 29(3): 412-4, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23334079

RESUMO

The hypothesis that the presence of macrocephaly might vary with the specific growth chart used was tested by using the Nellahus, CDC, and recent Rollins et al revision head circumference charts to plot the head circumferences of 253 children with neurodevelopmental disorders and with ages between 12 to 36 months; of these children, 59 had a diagnosis of autism spectrum disorder. The CDC and Rollins et al head circumference charts identified more cases of macrocephaly and fewer cases of microcephaly than did the older Nellhaus chart but did not significantly differ in their identification of macrocephaly in children with autism.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/complicações , Megalencefalia/complicações , Microcefalia/complicações , Cefalometria , Transtornos Globais do Desenvolvimento Infantil/patologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Megalencefalia/patologia , Microcefalia/patologia , Tamanho do Órgão
16.
Urology ; 106: 43-44, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28622877
17.
Neural Dev ; 6: 8, 2011 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-21418557

RESUMO

BACKGROUND: Most retinal ganglion cells (RGCs) convey contrast and motion information to visual brain centers. Approximately 2% of RGCs are intrinsically photosensitive (ipRGCs), express melanopsin and are necessary for light to modulate specific physiological processes in mice. The ipRGCs directly target the suprachiasmatic nucleus (SCN) to photoentrain circadian rhythms, and the olivary pretectal nucleus (OPN) to mediate the pupillary light response. How and when this ipRGC circuitry develops is unknown. RESULTS: Here, we show that some ipRGCs follow a delayed developmental time course relative to other image-forming RGCs. Specifically, ipRGC neurogenesis extends beyond that of other RGCs, and ipRGCs begin innervating the SCN at postnatal ages, unlike most RGCs, which innervate their image-forming targets embryonically. Moreover, the appearance of ipRGC axons in the OPN coincides precisely with the onset of the pupillary light response. CONCLUSIONS: Some ipRGCs differ not only functionally but also developmentally from RGCs that mediate pattern-forming vision.


Assuntos
Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/fisiologia , Vias Visuais/crescimento & desenvolvimento , Vias Visuais/fisiologia , Fosfatase Alcalina/metabolismo , Animais , Axônios/fisiologia , Feminino , Imuno-Histoquímica , Injeções Intravítreas , Luz , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/fisiologia , Células Fotorreceptoras de Vertebrados , Gravidez , Pupila/fisiologia , Reflexo Pupilar/fisiologia , Retina/crescimento & desenvolvimento , Células Ganglionares da Retina/metabolismo , Opsinas de Bastonetes/biossíntese , Núcleo Supraquiasmático/crescimento & desenvolvimento , Núcleo Supraquiasmático/fisiologia
18.
Invest Ophthalmol Vis Sci ; 51(2): 686-93, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19797210

RESUMO

PURPOSE: In the Gbeta5(-/-) mouse, the electroretinogram (ERG) b-wave is absent, and the R7 subfamily of regulators of G protein signaling (RGS), which includes RGS6, -7, -9, and -11, is downregulated. Mutant mouse strains deficient in RGS7 or -11 were characterized, and the SG711 strain which is deficient in both proteins was examined, to learn whether the loss of some of these RGS proteins causes the absence of the ERG b-wave. METHODS: Antibodies to RGS7 and -11 were generated to determine their expression levels and localizations in retinas with various genetic backgrounds by Western blot analysis and immunohistochemistry, respectively. The implicit times and amplitudes of ERG a- and b-waves were analyzed to examine photoreceptor and bipolar cell functions. RESULTS: RGS7 and -11 co-localized to the dendritic tips of the ON-bipolar cells. In the RGS11(-/-) mouse, the level of RGS7 protein increased. However, the level of RGS11 protein remained unchanged in the RGS7 mutant mouse, where a truncated RGS7 protein was expressed due to the deletion of exon 10. In the SG711 mouse retina, the Gbeta5-S protein level was reduced. The ERG b-wave of SG711 mice was markedly delayed. In contrast, RGS11(-/-) mice showed a moderately delayed b-wave, whereas the RGS7 mutant mice showed normal ERG responses. CONCLUSIONS: The data demonstrate the presence of a delayed ERG b-wave in SG711 mice and a functionally redundant role for RGS11 and -7 at the tips of ON-bipolar cell dendrites. These results suggest that RGS11 or -7 works as the major physiological GAP (GTPase acceleration protein) for Galphao1 in ON-bipolar cells.


Assuntos
Dendritos/fisiologia , Proteínas RGS/fisiologia , Células Bipolares da Retina/fisiologia , Animais , Western Blotting , Eletrorretinografia , Técnica Indireta de Fluorescência para Anticorpo , Subunidades beta da Proteína de Ligação ao GTP/genética , Proteínas Ativadoras de GTPase/metabolismo , Genótipo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Mutantes , Estimulação Luminosa , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima , Visão Ocular/fisiologia
19.
Prog Mol Biol Transl Sci ; 86: 229-48, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20374718

RESUMO

Recent advances in our understanding of R7RGS proteins have benefited from studies involving the fifth member of the Gß family (Gß5) that is found throughout the visual system. Unlike conventional Gßsthat form dimers with Gγ, Gß5 partners with R7RGS proteins, which contain the G-protein gamma-like (GGL) domain, to act as a GTPase accelerating protein (GAP) complex on certain Gα subunits. Recent studies in the retina underscore the necessity of Gß5 for normal recovery in photoreceptors and light responses in ON-bipolar cells. Gß5 may also be important for the generation and propagation of spontaneous retinal waves in retina and proper synapse formation in lateral geniculate nucleus (LGN). Here, we review these findings and discuss future investigative directions concerning Gß5's function in vision.


Assuntos
Subunidades beta da Proteína de Ligação ao GTP/metabolismo , Visão Ocular/fisiologia , Animais , Humanos , Transdução de Sinal Luminoso , Proteínas RGS/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Células Bipolares da Retina/metabolismo
20.
Exp Neurol ; 202(1): 189-99, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16876159

RESUMO

Clinical and experimental data show that traumatic brain injury (TBI)-induced cognitive changes are often manifest as deficits in hippocampal-dependent functions of spatial information processing. The underlying mechanisms for these effects have remained elusive, although recent studies have suggested that the changes in neuronal precursor cells in the dentate subgranular zone (SGZ) of the hippocampus might be involved. Here, we assessed the effects of unilateral controlled cortical impact on neurogenic cell populations in the SGZ in 2-month-old male C57BL6 mice by quantifying numbers of dying cells (TUNEL), proliferating cells (Ki-67) and immature neurons (Doublecortin, Dcx) up to 14 days after TBI. Dying cells were seen 6 h after injury, peaked at 24 h and returned to control levels at 14 days. Proliferating cells were decreased on the ipsilateral and contralateral sides at all the time points studied except 48 h after injury when a transient increase was seen. Simultaneously, immature neurons were reduced up to 84% relative to controls on the ipsilateral side. In the first week post-TBI, reduced numbers of Dcx-positive cells were also seen in the contralateral side; a return to control levels occurred at 14 days. To determine if these changes translated into longer-term effects, BrdU was administered 1 week post-injury and 3 weeks later the phenotypes of the newly born cells were assessed. TBI induced decreases in the numbers of BrdU-positive cells and new neurons (BrdU/NeuN) on the ipsilateral side without apparent changes on the contralateral side, whereas astrocytes (BrdU/GFAP) were increased on the ipsilateral side and activated microglia (BrdU/CD68) were increased on both ipsi- and contralateral sides. No differences were noted in oligodendrocytes (BrdU/NG2). Taken together, these data demonstrate that TBI alters both neurogenesis and gliogenesis. Such alterations may play a contributory role in TBI-induced cognitive impairment.


Assuntos
Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Hipocampo/patologia , Neurônios/fisiologia , Organogênese/fisiologia , Animais , Bromodesoxiuridina/metabolismo , Morte Celular/fisiologia , Proliferação de Células , Modelos Animais de Doenças , Proteína Duplacortina , Lateralidade Funcional , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica/métodos , Marcação In Situ das Extremidades Cortadas/métodos , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores CCR2 , Receptores de Quimiocinas/metabolismo , Células-Tronco/patologia , Fatores de Tempo
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