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151.
Maija Kiuru Jason Solomon Bassem Ghali Marjolein van der Meulen Ronald G Crystal Chisa Hidaka MD 《Journal of bone and mineral research》2009,24(9):1598-1607
Bone formation and remodeling involve coordinated interactions between osteoblasts and osteoclasts through signaling networks involving a variety of molecular pathways. We hypothesized that overexpression of Sonic hedgehog (Shh), a morphogen with a crucial role in skeletal development, would stimulate osteoblastogenesis and bone formation in adult animals in vivo. Systemic administration of adenovirus expressing the N‐terminal form of Shh into adult mice resulted in a primary increase in osteoblasts and their precursors. Surprisingly, however, this was associated with altered trabecular morphology, decreased bone volume, and decreased compressive strength in the vertebrae. Whereas no change was detected in the number of osteoclast precursors, bone marrow stromal cells from Shh‐treated mice showed enhanced osteoclastogenic potential in vitro. These effects were mediated by the PTH/PTH‐related protein (PTHrP) pathway as evidenced by increased sensitivity to PTH stimulation and upregulation of the PTH/PTHrP receptor (PPR). Together, these data show that Shh has stimulatory effects on osteoprogenitors and osteoblasts in adult animals in vivo, which results in bone remodeling and reduced bone strength because of a secondary increase in osteoclastogenesis. 相似文献
152.
Bach HG Harrison H El Hassan B Kempton L Leven R Kerns JM Beddow S Gonzalez MH 《Journal of reconstructive microsurgery》2009,25(2):97-103
Preganglionic nerve root avulsion precludes sensory return, but motor regeneration is possible with sparing of motoneurons. The effect of GM-1 ganglioside treatment was studied with parallel evaluation of the autoimmune response. Rats (N=64) received injections of either GM-1 ganglioside or saline for 30 days following either C5 root avulsion or a hemilaminectomy control. The Bertelli grooming test assessed functional return. Before sacrifice at 5 months, serum was collected for enzyme-linked immunoabsorbent assay testing. Only 44% of the rats treated with ganglioside had a good functional outcome compared with 50% for controls. Although 17% of the rats developed anti GM-1 antibodies, there was no functional or histological evidence of neuropathy in any of the rats. We conclude that ganglioside treatment did not enhance recovery from peripheral nerve injury. Although an immune response was present in some rats, no overt signs of neuropathy were observed. 相似文献
153.
A skin bridge extending from the hyoid region to the sternal notch in a 3-month-old baby is reported as another form of congenital midline neck anomaly that has never been described before. Congenital midline neck anomalies are residual embryonic structures that had failed to completely disappear or mature. They can be classified into masses, clefts, and fistulas. We report this case of congenital midline cervical skin bridge. 相似文献
154.
Georgy B 《The journal of supportive oncology》2007,5(10):468; author reply 468
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157.
Microarray-based comparative genomic hybridization (array CGH) is a revolutionary platform that was recently adopted in the clinical laboratory. This technology was first developed as a research tool for the investigation of genomic alterations in cancer. It allows for a high-resolution evaluation of DNA copy number alterations associated with chromosome abnormalities. Array CGH is based on the use of differentially labeled test and reference genomic DNA samples that are simultaneously hybridized to DNA targets arrayed on a glass slide or other solid platform. In this review, we examine the technology and its transformation from a research tool into a maturing diagnostic instrument. We also evaluate the various approaches that have shaped the current platforms that are used for clinical applications. Finally, we discuss the advantages and shortcomings of "whole-genome" arrays and compare their diagnostic use to "targeted" arrays. Depending on their design, microarrays provide distinct advantages over conventional cytogenetic analysis because they have the potential to detect the majority of microscopic and submicroscopic chromosomal abnormalities. This new platform is poised to revolutionize modern cytogenetic diagnostics and to provide clinicians with a powerful tool to use in their increasingly sophisticated diagnostic capabilities. 相似文献
158.
Kristine R Crews Varsha Gandhi Deo Kumar Srivastava Bassem I Razzouk Xin Tong Fred G Behm William Plunkett Susana C Raimondi Ching-Hon Pui Jeffrey E Rubnitz Clinton F Stewart Raul C Ribeiro 《Journal of clinical oncology》2002,20(20):4217-4224
PURPOSE: To identify the optimal schedule for infusion of cytarabine (ara-C) given with cladribine (2-CdA) to pediatric patients with acute myeloid leukemia (AML), and to compare the effects of the two schedules on the pharmacokinetics of ara-C triphosphate (ara-CTP) in leukemic cells. PATIENTS AND METHODS: Forty-nine pediatric patients with newly diagnosed primary AML received a 5-day course of ara-C 500 mg/m(2)/d and 2-CdA 9 mg/m(2)/d. They were randomly assigned to receive ara-C as either a 2-hour daily infusion (arm A) or a continuous infusion (arm B). Cellular pharmacokinetics were studied on days 1 and 2. All patients then received two courses of remission induction chemotherapy with daunorubicin, ara-C, and etoposide (DAV). RESULTS: Thirty-two percent of patients (seven of 22) in arm A and 63% (17 of 27) in arm B entered complete remission (P =.045) after ara-C and 2-CdA therapy. Coadministration of 2-CdA increased the intracellular concentration of ara-CTP in 20 of 36 patients, although we found no statistically significant difference between the treatment arms in this effect (P =.63). The incidence of toxicity did not differ significantly between the two treatment arms (P =.53). After two courses of DAV, the rate of complete remission was 91% in arm A and 96% in arm B (P =.58). CONCLUSION: Intracellular accumulation of ara-CTP is increased when 2-CdA is given with ara-C, but no schedule-dependent differences in this effect were seen. The combination of 2-CdA and ara-C seems to be effective therapy for pediatric AML. 相似文献
159.
Bidinost C Hernandez N Edward DP Al-Rajhi A Lewis RA Lupski JR Stockton DW Bejjani BA 《Investigative ophthalmology & visual science》2006,47(4):1486-1490
PURPOSE: Primary congenital glaucoma (PCG) is an autosomal recessive ocular trait caused by mutations in the gene for cytochrome P4501B1 (CYP1B1). Although PCG is often considered to be fully penetrant, the disease shows 50% penetrance in some Saudi Arabian families. The familial segregation of the nonpenetrance suggests a genetic modifier. Recently, tyrosinase (Tyr) deficiency was found to worsen the drainage structure/ocular dysgenesis phenotype of Cyp1b1-/- mice, suggesting that Tyr is a modifier of the phenotype. In the current study, tyrosinase (TYR) was investigated in human PCG. METHODS: A genome-wide screen, a single nucleotide polymorphism (SNP) analysis in the TYR chromosomal region 11q13-q21, and sequencing of the TYR gene was performed with individuals from Saudi Arabian families with multiple, clinically confirmed, molecularly proven, nonpenetrant members. RESULTS: The study outcome did not support TYR as a modifier of the PCG phenotype in this population. The sequencing data showed no TYR mutations in the nonpenetrant family members and no difference in polymorphism frequencies between nonpenetrant or fully penetrant families. CONCLUSIONS: TYR is not a modifier of the CYP1B1-associated PCG phenotype in the Saudi Arabian population. 相似文献
160.
Suematsu Y Marx GR Stoll JA DuPont PE Cleveland RO Howe RD Triedman JK Mihaljevic T Mora BN Savord BJ Salgo IS del Nido PJ 《The Journal of thoracic and cardiovascular surgery》2004,128(4):579-587
BACKGROUND: There is no current acceptable approach for intracardiac beating-heart interventions. We have adapted real-time 3-dimensional echocardiography with specialized instrumentation to facilitate beating-heart repair of atrial septal defects and mitral valve plasty to investigate the feasibility of real-time 3-dimensional echocardiography-guided cardiac surgery. METHODS: In experiment I a modified real-time 3-dimensional echocardiography system with x4 matrix transducer was compared with 2-dimensional echocardiography in the performance of common surgical tasks. Completion times, deviation from an ideal trajectory, and an echogenic target were measured. In experiment II porcine atrial septal defects were closed with an original semiautomatic suturing device (n = 4) and with a 5-mm endoscopic stapler and a pericardial or polytetrafluoroethylene patch (n = 4). In experiment III a pulsatile porcine mitral valve model was developed, and suture placement through the anterior and posterior mitral leaflets was performed (n = 8). During all experiments, the operator was blinded to the target and operated on only with ultrasonic guidance. RESULTS: In experiment I, compared with 2-dimensional echocardiographic guidance, completion times improved by 21% ( P <.01) with high-trajectory accuracy, and suture deviation was significantly smaller (2-dimensional echocardiography, 5.4 +/- 2.7 mm; 3-dimensional echocardiography, 1.7 +/- 0.7 mm; P <.05) in real-time 3-dimensional echocardiography-guided tasks. In experiments II and III in both atrial septal defect closure and mitral valve plasty, real-time 3-dimensional echocardiography provided satisfactory images and sufficient anatomic detail for suturing and patch deployment. All surgical tasks were successfully performed with accuracy. CONCLUSIONS: Real-time 3-dimensional echocardiography provides adequate imaging and anatomic detail to act as a sole guide for surgical task performance. These initial experiments demonstrate the feasibility of beating-heart direct or patch closure of atrial septal defects and mitral valve plasty without cardiopulmonary bypass. 相似文献