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1.
J Urol ; 205(6): 1710-1717, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33533636

RESUMO

PURPOSE: Ureteral stents are commonly placed after ureteroscopy. Although studies indicate that stents are associated with patient discomfort, their impact on downstream health services use is unclear. We examined patterns of stent utilization in Michigan and their association with unplanned health care encounters. MATERIALS AND METHODS: We used the Michigan Urological Surgery Improvement Collaborative's Reducing Operative Complications from Kidney Stones (MUSIC ROCKS) clinical registry to identify ureteroscopy cases between 2016 and 2019. Factors associated with stent placement were examined using bivariate and multivariable statistics. Using multivariable logistic regression, we evaluated whether stent placement was associated with emergency department visits and hospitalizations within 30 days. RESULTS: We identified 9,662 ureteroscopies and a stent was placed in 7,025 (73%) of these. Frequency of stent use across the 137 urologists varied (11%-100%, p <0.001) and was not associated with total case volume. Factors associated with stent use included age and stone size. Pre-stented cases and renal stones had a decreased odds of stent placement. On multivariable analysis after adjusting for risk factors, stent placement was associated with a 1.25 higher odds of emergency department visit (OR 1.25, 95% CI 1.01-1.54, p=0.043) but not hospitalization (OR 1.28, 95% CI 0.94-1.76, p=0.12). In a single high volume practice, 0.5% of cases that omitted a stent required urgent stenting postoperatively. CONCLUSIONS: There is substantial variation in the use of stents in Michigan, irrespective of case volume. Stent placement significantly increased the odds of an emergency department visit after surgery. Importantly, stent omission rarely required subsequent urgent stent placement.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Cálculos Renais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Stents , Ureter/cirurgia , Ureteroscopia , Adulto , Idoso , Feminino , Humanos , Masculino , Michigan , Pessoa de Meia-Idade
2.
J Appl Clin Med Phys ; 22(5): 128-138, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33811787

RESUMO

The aim of the study was to estimate and to compare effective doses in the elbow region resulting from four different x-ray imaging modalities. Absorbed organ doses were measured using 11 metal oxide field effect transistor (MOSFET) dosimeters that were placed in a custom-made anthropomorphic elbow RANDO phantom. Examinations were performed using Shimadzu FH-21 HR radiography device, Siemens Sensation Open 24-slice MSCT-device, NewTom 5G CBCT device, and Planmed Verity CBCT device, and the effective doses were calculated according to ICRP 103 recommendations. The effective dose for the conventional radiographic device was 1.5 µSv. The effective dose for the NewTom 5G CBCT ranged between 2.0 and 6.7 µSv, for the Planmed Verity CBCT device 2.6 µSv and for the Siemens Sensation MSCT device 37.4 µSv. Compared with conventional 2D radiography, this study demonstrated a 1.4-4.6 fold increase in effective dose for CBCT and 25-fold dose for standard MSCT protocols. When compared with 3D CBCT protocols, the study showed a 6-19 fold increase in effective dose using a standard MSCT protocol. CBCT devices offer a feasible low-dose alternative for elbow 3D imaging when compared to MSCT.


Assuntos
Cotovelo , Tomografia Computadorizada de Feixe Cônico Espiral , Tomografia Computadorizada de Feixe Cônico , Humanos , Imagens de Fantasmas , Doses de Radiação , Radiografia , Dosimetria Termoluminescente
3.
J Radiol Prot ; 38(4): 1371-1383, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30255853

RESUMO

Little research has been published on the radiation burden of cone beam computed tomography (CBCT) in comparison with multi-row detector computed tomography (MDCT) for extremity imaging. This manuscript reports effective doses produced by standard and reduced dose imaging protocols for a 128-slice MDCT unit and a dedicated extremity imaging device using CBCT technology. Anthropomorphic phantoms with x-ray attenuation characteristics simulating adult hand-wrist, foot-ankle, and knee areas were modified to receive optically stimulated luminescent dosimeters (OSL). Standard and lower kVp reduced dose (Lite) exposures were compared. Effective doses for four age groups (five years old to adult) were calculated following 2007 recommendations of the ICRP. Standard CBCT imaging protocols produced effective doses (1.3-21.1 µSv) that were on the order of daily US ubiquitous background radiation doses. CBCT doses were on average 90% less than comparable MDCT views of the same anatomy (9.1-204 µSv). Child doses were significantly greater than adult doses (p = 0.0001). CBCT doses could be further reduced by 36%-51% with Lite exposure protocols. These protocols can be recommended for children and in cases where increased image noise will not interfere with the diagnostic task.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Extremidades/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Doses de Radiação , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem
4.
Gen Dent ; 62(4): 34-40, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24983168

RESUMO

The 2007 modification by the International Commission on Radiation Protection of the calculation of effective dose from ionizing radiation has renewed interest in the concept of As Low As Reasonably Achievable exposure, and the technical approaches for reducing doses. This intraoral imaging study compared effective doses from circular and rectangular collimator modalities. A total of 18-image adult and 12-image child full mouth series were exposed using a 6 cm diameter circular collimator, a universal rectangular collimator, and an enhanced rectangular device for both adult and child phantoms. Rectangular collimation significantly reduced doses for adult exposures. In the child sample, only the universal rectangular collimator achieved significant dose reduction. While dose differences were attributed to both the size of the rectangular field and the use of thyroid shielding, the results indicated that the universal rectangular collimator used alone was more effective at reducing thyroid exposure than a thyroid shield used with circular collimation.


Assuntos
Proteção Radiológica , Radiografia Dentária/efeitos adversos , Glândula Tireoide , Humanos , Doses de Radiação , Comportamento de Redução do Risco
5.
Methods Mol Biol ; 2783: 309-322, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478243

RESUMO

We have developed a hollow fiber bioreactor-based production system for manufacturing large quantities of extracellular vesicles (EVs) containing exosomes from adult human adipose-derived stromal/stem cells (ASCs). By manipulating the cellular bioreactor environment, we have found that we can alter ASC EV production, secretion, and surface protein composition. The aims of this chapter are to describe the methodology for culturing and tuning of adipose ASCs in a bioreactor, along with the collection and isolation of the EVs containing exosomes demonstrating increased HSP70 content.


Assuntos
Exossomos , Vesículas Extracelulares , Adulto , Humanos , Exossomos/metabolismo , Células Estromais , Vesículas Extracelulares/metabolismo , Adipócitos , Obesidade/metabolismo , Células-Tronco , Tecido Adiposo
6.
Am J Case Rep ; 25: e941840, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433438

RESUMO

BACKGROUND Hemiballismus is the most severe form of chorea and is a hyperkinetic disorder characterized by involuntary, high-amplitude movements of the ipsilateral arm and leg, due to lesions of the contralateral side of the central nervous system. Ischemic or hemorrhagic strokes and nonketotic hyperglycemia are predominant etiologies of hemiballismus. Case reports highlighting hemiballismus associated with temporal and parietal lobe infarcts have been published, although research of frontal lobe involvement is limited. CASE REPORT A 78-year-old woman presented to the Emergency Department with sudden-onset left-sided hemiballismus. On examination, she was alert, oriented to self and time, and able to follow commands. Her neurologic examination was notable for left-sided hemiballismus, described by the provider as periodic, uncontrolled, and involving a "flinging" motion of the left upper and lower extremities, sparing the face. She was treated with benzodiazepines in the Emergency Department and administered intravenous levetiracetam. Computed tomography of the head without contrast revealed an old left basal ganglia lacunar infarct. The patient was then admitted to the inpatient service, where magnetic resonance imaging of the brain revealed an acute punctate left superior frontal gyrus cortical infarct. Outpatient electroencephalogram revealed right anterior hemisphere dysfunction. CONCLUSIONS We describe a patient with left-sided sudden onset hemiballismus with an acute infarct of the ipsilateral superior frontal gyrus. This case highlights that brain lesions separate from the basal ganglia can induce hemiballismus, particularly within the frontal lobe, which warrants further research into precentral sulcus functioning and its role in modulating motor activity.


Assuntos
Discinesias , Feminino , Humanos , Idoso , Discinesias/etiologia , Sistema Nervoso Central , Encéfalo , Administração Intravenosa , Infarto
7.
Artigo em Inglês | MEDLINE | ID: mdl-37914543

RESUMO

OBJECTIVES: We compared the effective dose (E) and thyroid equivalent dose of 2 extraoral bitewing (EOBW) units and compared E with their respective panoramic (PAN) modes and with intraoral bitewing radiography (IOBW). STUDY DESIGN: Child and adult anthropomorphic phantoms with dosimeters were used to evaluate Orthophos SL, Rayscan α+, and 1 intraoral unit using rectangular and circular collimation. Extraoral bitewing thyroid equivalent dose was assessed without and with thyroid shielding. RESULTS: Child and adult E values of EOBW were lower with Orthophos (3.6 and 8.6 µSv) than with Rayscan (28.1 and 30.2 µSv). For IOBW, E was lower with rectangular vs circular collimation for child (7.0 vs 11.8 µSv) and adult (4.6 vs 14.2 µSv). E values of EOBW were lower than PAN for Orthophos. The IOBW E was lower than Rayscan EOBW for child (≤11.8 vs 28.1 µSv) and adult (≤14.2 vs 30.2 µSv). Adult E for rectangular IOBW (4.6 µSv) was lower than EOBW with Orthophos (8.6 µSv) and Rayscan (30.2 µSv). Thyroid shielding reduced EOBW thyroid equivalent dose with Rayscan in the adult from 190.7 to 89.0 µSv. CONCLUSION: Orthophos provides significantly lower EOBW E than Rayscan, thus EOBW recommendations must be unit specific. For children, Orthophos EOBW could be an alternative to IOBW, for which rectangular collimation is recommended. Thyroid shielding reduced adult Rayscan equivalent dose but added imaging artifacts.


Assuntos
Proteção Radiológica , Adulto , Criança , Humanos , Radiografia Panorâmica , Radiografia Interproximal , Doses de Radiação , Glândula Tireoide/diagnóstico por imagem , Imagens de Fantasmas
8.
J Exp Med ; 204(8): 1973-87, 2007 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-17664288

RESUMO

Human hepatic stem cells (hHpSCs), which are pluripotent precursors of hepatoblasts and thence of hepatocytic and biliary epithelia, are located in ductal plates in fetal livers and in Canals of Hering in adult livers. They can be isolated by immunoselection for epithelial cell adhesion molecule-positive (EpCAM+) cells, and they constitute approximately 0.5-2.5% of liver parenchyma of all donor ages. The self-renewal capacity of hHpSCs is indicated by phenotypic stability after expansion for >150 population doublings in a serum-free, defined medium and with a doubling time of approximately 36 h. Survival and proliferation of hHpSCs require paracrine signaling by hepatic stellate cells and/or angioblasts that coisolate with them. The hHpSCs are approximately 9 microm in diameter, express cytokeratins 8, 18, and 19, CD133/1, telomerase, CD44H, claudin 3, and albumin (weakly). They are negative for alpha-fetoprotein (AFP), intercellular adhesion molecule (ICAM) 1, and for markers of adult liver cells (cytochrome P450s), hemopoietic cells (CD45), and mesenchymal cells (vascular endothelial growth factor receptor and desmin). If transferred to STO feeders, hHpSCs give rise to hepatoblasts, which are recognizable by cordlike colony morphology and up-regulation of AFP, P4503A7, and ICAM1. Transplantation of freshly isolated EpCAM+ cells or of hHpSCs expanded in culture into NOD/SCID mice results in mature liver tissue expressing human-specific proteins. The hHpSCs are candidates for liver cell therapies.


Assuntos
Técnicas de Cultura de Células/métodos , Fígado/citologia , Fígado/embriologia , Células-Tronco/citologia , Adesão Celular , Membrana Celular/metabolismo , Meios de Cultura Livres de Soro/metabolismo , Células Epiteliais/citologia , Células-Tronco Hematopoéticas/metabolismo , Hepatócitos/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Antígenos Comuns de Leucócito/biossíntese , Fígado/metabolismo , Mesoderma/metabolismo , Transdução de Sinais , alfa-Fetoproteínas/metabolismo
9.
Am J Orthod Dentofacial Orthop ; 144(6): 802-17, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24286904

RESUMO

INTRODUCTION: The increasing use of cone-beam computed tomography in orthodontics has been coupled with heightened concern about the long-term risks of x-ray exposure in orthodontic populations. An industry response to this has been to offer low-exposure alternative scanning options in newer cone-beam computed tomography models. METHODS: Effective doses resulting from various combinations of field of view size and field location comparing child and adult anthropomorphic phantoms with the recently introduced i-CAT FLX cone-beam computed tomography unit (Imaging Sciences, Hatfield, Pa) were measured with optical stimulated dosimetry using previously validated protocols. Scan protocols included high resolution (360° rotation, 600 image frames, 120 kV[p], 5 mA, 7.4 seconds), standard (360°, 300 frames, 120 kV[p], 5 mA, 3.7 seconds), QuickScan (180°, 160 frames, 120 kV[p], 5 mA, 2 seconds), and QuickScan+ (180°, 160 frames, 90 kV[p], 3 mA, 2 seconds). Contrast-to-noise ratio was calculated as a quantitative measure of image quality for the various exposure options using the QUART DVT phantom. RESULTS: Child phantom doses were on average 36% greater than adult phantom doses. QuickScan+ protocols resulted in significantly lower doses than standard protocols for the child (P = 0.0167) and adult (P = 0.0055) phantoms. The 13 × 16-cm cephalometric fields of view ranged from 11 to 85 µSv in the adult phantom and 18 to 120 µSv in the child phantom for the QuickScan+ and standard protocols, respectively. The contrast-to-noise ratio was reduced by approximately two thirds when comparing QuickScan+ with standard exposure parameters. CONCLUSIONS: QuickScan+ effective doses are comparable with conventional panoramic examinations. Significant dose reductions are accompanied by significant reductions in image quality. However, this trade-off might be acceptable for certain diagnostic tasks such as interim assessment of treatment results.


Assuntos
Tomografia Computadorizada de Feixe Cônico/instrumentação , Ortodontia/instrumentação , Imagens de Fantasmas , Doses de Radiação , Radiometria/métodos , Adulto , Análise de Variância , Cefalometria , Criança , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Ortodontia/métodos
10.
Artigo em Inglês | MEDLINE | ID: mdl-37236876

RESUMO

OBJECTIVE: This study measured effective (E) and equivalent doses from adult and child 3-dimensional (3D) and 2D posterior bitewing (PBW) examinations using the PORTRAY stationary-intraoral tomosynthesis radiography system. STUDY DESIGN: Adult and child phantoms and optically stimulated luminescent dosimeters were used to measure doses for adult-4 and child-2 projection PBW examinations acquired without (W/O) and with (W) a direct digital sensor in the beam path. Child doses without and with thyroid shielding were measured. RESULTS: Three-dimensional examination E values (µSv) W/O and W were 16.7 and 7.3 for adult, 9.2 and 3.5 for child, and 8.7 and 3.0 with thyroid shielding, respectively. Two-dimensional examination E values W/O and W were 4.3 and 1.5 for adult, 2.1 and 0.6 for child, and 2.0 and 0.5 with shielding, respectively. Sensor presence reduced E for all adult and child examinations (P = .0001). Child E was reduced compared with adult E for both sensor conditions in 3D (P < .0001) and 2D (P ≤ .0043) imaging. Adult and child 3D W/O and W equivalent thyroid doses did not differ (P ≥ .9996). However, child 2D W/O and W doses were lower (P ≤ .0002). Shielding produced no reduction (P ≥ .1128) for either 3D condition or 2D with the sensor (P = .6615) but reduced child 2D dose without the sensor. CONCLUSIONS: Inclusion of a sensor yielded significant reductions in adult and child E. Sensor presence impacted thyroid dose reduction more than shielding.


Assuntos
Radiografia Interproximal , Adulto , Humanos , Doses de Radiação , Radiografia , Imagens de Fantasmas
11.
Birth Defects Res C Embryo Today ; 96(1): 30-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22457175

RESUMO

Multiple methodological approaches are currently under active development for application in tissue engineering and regenerative medicine of tubular and solid organs. Most recently, developmental engineering (TE/RM), or the leveraging of embryonic and morphological paradigms to recapitulate aspects of organ development, has been proposed as a strategy for the sequential, iterative de novo assembly of tissues and organs as discrete developmental modules ex vivo, prior to implantation in vivo. In this article, we focus on the kidney to highlight in detail how principles of developmental biology are impacting approaches to TE of this complex solid organ. Ultimately, such methodologies may facilitate the establishment of clinically relevant therapeutic strategies for regeneration of renal structure and function, greatly impacting treatment regimens for chronic kidney disease.


Assuntos
Falência Renal Crônica/patologia , Rim/patologia , Regeneração/fisiologia , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Animais , Humanos , Rim/crescimento & desenvolvimento , Falência Renal Crônica/terapia , Modelos Animais , Transplante de Células-Tronco
12.
Cells Tissues Organs ; 196(4): 374-84, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22584161

RESUMO

Dedifferentiation and proliferation of resident tubular epithelial cells is a mechanism of action potentially contributing to repair and regeneration in kidneys presenting with ischemic or chronic disease. To more efficiently develop cell and tissue engineering technologies for the kidney, we have developed molecular assays to evaluate the acquisition of a pluripotent state associated with stem/progenitor cell phenotype during induction of a regenerative response within the kidneys of rats with chronic kidney disease (CKD) following therapeutic intervention. Intrarenal delivery of selected bioactive renal cells leads to significant upregulation of pluripotency-associated SOX2 mRNA within the diseased kidney tissue from 1 to 24 weeks after treatment. The overall regenerative response index was assessed by quantitative composite expression of CD24, NODAL and LEFTY1 proteins, which were induced within 1 week of cell treatment and peaked at 12 weeks after treatment, reaching statistical significance (p < 0.05) compared to untreated CKD controls. Molecular assays that incorporate the assessment of SOX2 and the regenerative response index may prove to be valuable tools for the detection and monitoring of the tissue response after the delivery of regenerative treatments for CKD, thereby significantly shortening the developmental timelines associated with such therapies.


Assuntos
Transplante de Células/métodos , Nefropatias/terapia , Rim/fisiologia , Medicina Regenerativa/métodos , Animais , Doença Crônica , Modelos Animais de Doenças , Rim/citologia , Rim/metabolismo , Nefropatias/metabolismo , Masculino , Ratos , Ratos Endogâmicos Lew , Regeneração/fisiologia , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Engenharia Tecidual
13.
Clin Oral Implants Res ; 23(11): 1261-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22092929

RESUMO

OBJECTIVE: To evaluate the type and prevalence of incidental findings from cone beam computed tomography (CBCT) of the maxillofacial region. Findings are divided into those that require (i) intervention/referral, (ii) monitoring, and (iii) no further evaluation. METHODS: Three hundred consecutive CBCT scans conducted in the University of North Carolina School of Dentistry Oral and Maxillofacial Radiology Clinic from January 1 to August 31, 2008 were retrospectively reviewed. Findings were categorized into airway, soft tissue calcifications, bone, temporomandibular joint (TMJ), endodontic, dental developmental, and pathological findings. RESULTS: A total of 272 scans revealed 881 incidental findings (3.2 findings/scan). The most prevalent was airway findings (35%) followed by soft tissue calcifications (20%), bone (17.5%), TMJ (15.4%), endodontic (11.3%), dental developmental (0.7%), and pathological (0.1%). 16.1% required intervention/referral, 15.6% required monitoring, and the remainder (68.3%) required neither. CONCLUSION: This study underscores the need to thoroughly examine all CBCT volumes for clinically significant findings within and beyond the region of interest.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Achados Incidentais , Radiografia Dentária/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Software
14.
Kidney Int Rep ; 7(7): 1619-1629, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35812284

RESUMO

Introduction: Chronic kidney disease (CKD) is a worldwide disease without cure. Selected renal cells (SRCs) can augment kidney function in animal models. This study correlates the phenotypical characteristics of autologous homologous SRCs (formulated product called Renal Autologous Cell Therapy [REACT]) injected into patients' kidneys with advanced type 2 diabetes-related CKD (D-CKD) to clinical and laboratory findings. Methods: A total of 22 adults with type 2 D-CKD underwent a kidney biopsy followed by 2 subcortical injections of SRCs, 7 ± 3 months apart. There were 2 patients who had only 1 injection. We compared annualized estimated glomerular filtration rate (eGFR) slopes pre- and post-REACT injection using the 2009 CKD-EPI formula for serum creatinine (sCr) and the 2012 CKD-EPI Creatinine-Cystatin C equation and report clinical/laboratory changes. Fluorescent Activated Cell Sorting (FACS) Analysis for renal progenitor lineages in REACT and donor vascular endothelial growth factor A (VEGF-A) analysis were performed. Longitudinal parameter changes were analyzed with longitudinal linear mixed effects model. Results: At baseline, the mean diabetes duration was 18.4 ± 8.80 years, glycated hemoglobin (Hgb) was 7.0 ± 1.05, and eGFR was 40.3 ± 9.35 ml/min per 1.73 m2 using the 2012 CKD-EPI cystatin C and sCr formulas. The annualized eGFR slope (2012 CKD-EPI) was -4.63 ml/min per 1.73 m2 per year pre-injection and improved to -1.69 ml/min per 1.73 m2 per year post-injection (P = 0.015). There were 7 patients who had an eGFR slope of >0 ml/min per 1.73 m2 postinjection. SRCs were found to have cell markers of ureteric bud, mesenchyme cap, and podocyte sources and positive VEGF. There were 2 patients who had remote fatal adverse events determined as unrelated with the biopsies/injections or the REACT product. Conclusion: Our cell marker analysis suggests that SRCs may enable REACT to stabilize and improve kidney function, possibly halting type 2 D-CKD progression.

15.
Elife ; 112022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36454035

RESUMO

Background: MicroRNAs (miRNA) and other components contained in extracellular vesicles may reflect the presence of a disease. Lung tissue, sputum, and sera of individuals with idiopathic pulmonary fibrosis (IPF) show alterations in miRNA expression. We designed this study to test whether urine and/or tissue derived exosomal miRNAs from individuals with IPF carry cargo that can promote fibrosis. Methods: Exosomes were isolated from urine (U-IPFexo), lung tissue myofibroblasts (MF-IPFexo), serum from individuals with IPF (n=16) and age/sex-matched controls without lung disease (n=10). We analyzed microRNA expression of isolated exosomes and their in vivo bio-distribution. We investigated the effect on ex vivo skin wound healing and in in vivo mouse lung models. Results: U-IPFexo or MF-IPFexo expressed miR-let-7d, miR-29a-5p, miR-181b-3p and miR-199a-3p consistent with previous reports of miRNA expression obtained from lung tissue/sera from patients with IPF. In vivo bio-distribution experiments detected bioluminescent exosomes in the lung of normal C57Bl6 mice within 5 min after intravenous infusion, followed by distribution to other organs irrespective of exosome source. Exosomes labeled with gold nanoparticles and imaged by transmission electron microscopy were visualized in alveolar epithelial type I and type II cells. Treatment of human and mouse lung punches obtained from control, non-fibrotic lungs with either U-IPFexo or MF-IPFexo produced a fibrotic phenotype. A fibrotic phenotype was also induced in a human ex vivo skin model and in in vivo lung models. Conclusions: Our results provide evidence of a systemic feature of IPF whereby exosomes contain pro-fibrotic miRNAs when obtained from a fibrotic source and interfere with response to tissue injury as measured in skin and lung models. Funding: This work was supported in part by Lester and Sue Smith Foundation and The Samrick Family Foundation and NIH grants R21 AG060338 (SE and MKG), U01 DK119085 (IP, RS, MTC).


Assuntos
Exossomos , Fibrose Pulmonar Idiopática , Nanopartículas Metálicas , MicroRNAs , Animais , Camundongos , Humanos , Ouro , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Fibrose
16.
J Cell Physiol ; 226(10): 2702-11, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21792927

RESUMO

Myocardin (MYOCD) is a smooth and cardiac muscle-specific transcriptional coactivator that is required for the proper expression of contraction-related genes. Through its function to transactivate effector genes, MYOCD plays an essential role in mediating the switch between contractile and non-contractile phenotypes, particularly in smooth muscle cells (SMC). There are at least two known transcript variants of MYOCD that are expressed in SMC, differing only by the presence (+) or absence (Δ) of Exon 11. To date, no functional role has been assigned to the domain encoded by Exon 11, nor have any notable differences between the ability of each isoform to activate contraction-related genes been observed. In this study we compared sequences for Exon 11 among several mammalian species and identified a highly conserved, putative target sequence for glycogen synthase kinase 3 (GSK3) phosphorylation, suggesting a regulatory role for Exon 11 that can be modulated by alternative splicing. The function of Exon 11 was investigated by altering MYOCD splice selection in cultured porcine SMC with small interfering RNAs (siRNA) and specific chemical inhibitors, resulting in a relative increase in expression of ΔExon 11 variants in the endogenous pool of MYOCD mRNA. The relative increase in ΔExon 11 mRNAs correlated with a reduction of contractile phenotype in the porcine SMC as evidenced by morphological assessment and molecular analysis of effector genes. Together, these data suggest that MYOCD ΔExon 11 may participate in modulating SMC phenotype, potentially acting as a dominant-negative repressor of contraction-related genes.


Assuntos
Processamento Alternativo/fisiologia , Miócitos de Músculo Liso/fisiologia , Proteínas Nucleares/genética , Transativadores/genética , Sequência de Aminoácidos , Animais , Aorta/citologia , Artérias Carótidas/citologia , Sequência Conservada , Variação Genética , Técnicas In Vitro , Dados de Sequência Molecular , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Fenótipo , Suínos , Transativadores/química , Transativadores/metabolismo , Bexiga Urinária/citologia
17.
Nat Med ; 8(9): 1033-6, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12185363

RESUMO

Analysis of the viability, differentiation, clonogenicity and function of human stem/progenitor cells requires suitable xenograft models. However, the identification of transplanted cells has been generally difficult. Fluorescence in situ hybridization is a tedious method for analyzing tissues, and localization of transplanted cells with X or Y chromosome probes is limited by the sparse signals produced. Therefore, we examined the possibility of generating either pan-nuclear signals with a total human DNA probe or multiple nuclear signals with a pan-centromeric human DNA probe. The probes were labeled with digoxigenin to make reaction products visible by light microscopy and to allow the use of immunohistochemistry methods incorporating various color schemes to demonstrate specific properties of transplanted cells. The ability to localize all types of nucleated human cells with such probes will facilitate studies of stem cell biology and cell and gene therapy, as well as the development of new animal models.


Assuntos
Bioquímica/métodos , Sondas de DNA/química , Hibridização In Situ , Fígado/citologia , Transplante Heterólogo , Animais , Diferenciação Celular , Enzimas/química , Humanos , Transplante de Fígado , Masculino , Camundongos , Camundongos SCID
18.
Lipids Health Dis ; 10: 171, 2011 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-21957910

RESUMO

BACKGROUND: Therapeutically bioactive cell populations are currently understood to promote regenerative outcomes in vivo by leveraging mechanisms of action including secretion of growth factors, site specific engraftment and directed differentiation. Constitutive cellular populations undoubtedly participate in the regenerative process. Adipose tissue represents a source of therapeutically bioactive cell populations. The potential of these cells to participate in various aspects of the regenerative process has been demonstrated broadly. However, organ association of secretory and developmental markers to specific peri-organ adipose depots has not been investigated. To characterize this topographical association, we explored the potential of cells isolated from the stromal vascular fraction (SVF) of kidney sourced adipose to express key renal associated factors. RESULTS: We report that renal adipose tissue is a novel reservoir for EPO expressing cells. Kidney sourced adipose stromal cells demonstrate hypoxia regulated expression of EPO and VEGF transcripts. Using iso-electric focusing, we demonstrate that kidney and non-kidney sourced adipose stromal cells present unique patterns of EPO post-translational modification, consistent with the idea that renal and non-renal sources are functionally distinct adipose depots. In addition, kidney sourced adipose stromal cells specifically express the key renal developmental transcription factor WT1. CONCLUSIONS: Taken together, these data are consistent with the notion that kidney sourced adipose stromal (KiSAS) cells may be primed to recreate a regenerative micro-environment within the kidney. These findings open the possibility of isolating solid-organ associated adipose derived cell populations for therapeutic applications in organ-specific regenerative medicine products.


Assuntos
Adipócitos Brancos/metabolismo , Regulação da Expressão Gênica , Gordura Intra-Abdominal/citologia , Rim/citologia , Medicina Regenerativa/métodos , Adipócitos Brancos/citologia , Animais , Biomarcadores , Hipóxia Celular , Separação Celular , Células Cultivadas , Eritropoetina/genética , Eritropoetina/metabolismo , Humanos , Gordura Intra-Abdominal/metabolismo , Rim/metabolismo , Masculino , Especificidade de Órgãos , Processamento de Proteína Pós-Traducional , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew , Fatores de Crescimento do Endotélio Vascular/genética , Fatores de Crescimento do Endotélio Vascular/metabolismo , Proteínas WT1/genética , Proteínas WT1/metabolismo
19.
Am J Orthod Dentofacial Orthop ; 139(1): 126-32, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21195286

RESUMO

INTRODUCTION: Orthodontists assess mesiodistal root angulations before, during, and after orthodontic treatment as an aid in establishing proper root position. Panoramic imaging has been useful for this purpose and is a valuable screening tool in diagnosis and planning treatment of orthodontic patients. Cone-beam computed tomography (CBCT) for imaging of the craniofacial complex creates the opportunity to evaluate 3-dimensional images compared with traditional 2-dimensional images. The purpose of this project was to compare mesiodistal root angulations by using posttreatment panoramic radiographic images and CBCT scans. METHODS: Mesiodistal root angulations from panoramic images and CBCT scans of 35 orthognathic surgery patients after orthodontic treatment were compared. The panoramic images were measured by using VixWin (Gendex Dental Systems, Des Plaines, Ill), and the CBCT scans by using InvivoDental 3D (version 4.1, Anatomage, San Jose, Calif). The mesiodistal root angulation of each maxillary and mandibular tooth was measured by using the occlusal plane as the reference line. With an intercept-only linear regression for correlated data (with an unstructured covariance structure), the global test of whether the mean vector of all differences for the teeth is zero was performed separately for the 2 arches. RESULTS: The global test for both arches was statistically significant (P <0.001), indicating an overall difference in root angulation between measurements from panoramic and CBCT images. There was no discernible pattern in the average differences between panoramic and CBCT measurements. CONCLUSIONS: The assessment of mesiodistal tooth angulation with panoramic radiography should be approached with caution and reinforced by a thorough clinical examination of the dentition.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Má Oclusão/terapia , Radiografia Panorâmica , Raiz Dentária/diagnóstico por imagem , Dente Pré-Molar/diagnóstico por imagem , Dente Canino/diagnóstico por imagem , Arco Dental/diagnóstico por imagem , Oclusão Dentária , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Incisivo/diagnóstico por imagem , Masculino , Má Oclusão/diagnóstico por imagem , Mandíbula/diagnóstico por imagem , Maxila/diagnóstico por imagem , Dente Molar/diagnóstico por imagem , Ortodontia Corretiva , Procedimentos Cirúrgicos Ortognáticos , Estudos Prospectivos , Ápice Dentário/diagnóstico por imagem , Adulto Jovem
20.
Urology ; 158: 57-65, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34480941

RESUMO

OBJECTIVES: To evaluate patient factors associated with post-ureteroscopy opioid prescriptions, provider-level variation in opioid prescribing, and the relationship between opioid-free discharges and ED visits. METHODS: This is a retrospective analysis of a prospective cohort study of adults age 18 years and older who underwent primary ureteroscopy for urinary stones from June 2016 to September 2019 within the Michigan Urological Surgery Improvement Collaborative (MUSIC) Reducing Operative Complications from Kidney Stones (ROCKS) quality improvement initiative. Postoperative opioid prescription trends and variation among practices and surgeons were examined. Multivariable logistic regression models defined risk factors for receipt of opioid prescriptions. The association among opioid prescriptions and postoperative ED visits within 30 days of surgery was assessed among complete case and propensity matched cohorts, matched on all measured characteristics other than opioid receipt. RESULTS: 13,143 patients underwent ureteroscopy with 157 urologists across 28 practices. Post-ureteroscopy opioid prescriptions and ED visits declined (86% to 39%, P<.001; 10% to 6%, P<.001, respectively). Practice and surgeon-level opioid prescribing varied from 8% to 98%, and 0% to 98%, respectively. Patient-related factors associated with opioid receipt included male, younger age, and history of chronic pain. Procedure-related factors associated with opioid receipt included pre- and post-ureteroscopy ureteral stenting and access sheath use. An opioid-free discharge was not associated with increased odds of an ED visit (OR 0.77, 95% CI 0.62-0.95, P=.014). CONCLUSIONS: There was no increase in ED utilization among those not prescribed an opioid after ureteroscopy, suggesting their routine use may not be necessary in this setting.


Assuntos
Analgésicos Opioides/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Dor Pós-Operatória/tratamento farmacológico , Alta do Paciente , Readmissão do Paciente/estatística & dados numéricos , Melhoria de Qualidade , Ureteroscopia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
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