Melanocortin is the downstream mediator of leptin signaling and absence of leptin signaling in ob/ob and db/db mice revealed the enhancement of bone formation through the central regulation. While alpha-melanocyte-stimulating hormone (alphaMSH) inhibits the secretion of interleukin-1alpha and tumor necrosis factor-alpha from the inflammatory cells, alphaMSH can also enhance clonal expansion of pro B cells linked to stimulation of osteoclastogenesis. Therefore, we tested the effect of melanocortin on bones. alphaMSH analogues [(6)His]alphaMSH-ND and [(6)Asn]alphaMSH-ND were synthesized and the radio-ligand receptor binding- and cyclic AMP generating activity were analyzed in China Hamster Ovary cell line over- expressing melanocortin receptors. The EC(50) of [(6)His]alphaMSH-ND measured from melanocortin-1, 3, 4 and 5 receptors were 0.008 +/- 0.0045, 1.523 +/- 0.707, 0.780 +/- 0.405, and 250.320 +/- 42.234 nM, respectively, and the EC(50) of [(6)Asn]alphaMSH-ND were 16.8 +/- 6.94, 271.8 +/- 21.95, 8.0 +/- 1.21, and 1132.5 +/- 635.46 nM, respectively. Four weeks after the subcutaneous injection of the analogues, the body weights in the [(6)His]alphaMSH-ND and the [(6)Asn]alphaMSH-ND treated groups (346.0 +/- 20.63 g vs. 350.0 +/- 13.57 g) were lower than that of the vehicle treated group (375.8 +/- 17.31 g, p < 0.05). There was no difference in the total femoral BMD measured by dual x-ray absorptiometry among the three groups. Among the three groups, there were no differences in the total numbers of crystal violet positive- or alkaline phosphatase positive colonies, in the expression of Receptor Activator of Nuclear Factor Kappa-B ligand on the tibia and the total number of multinucleated osteoclast-like cells differentiated from primary cultured bone marrow cells. From the above results, no evidence of bone gain or loss was found after treatment of the alphaMSH analogues peripherally. 相似文献
PURPOSE: Constitutive mutational activation of c-kit has been found to be associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of c-kit mutations, however, is still controversial. EXPERIMENTAL DESIGN: We examined 86 patients curatively resected for localized GIST. Genomic DNA was extracted from paraffin-embedded tumor tissues. Exons 9, 11, 13, and 17 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations in exon 11 were detected in 61 tumors, and mutations in exon 9 were observed in three tumors, whereas no mutations were detected in exons 13 or 17. The overall c-kit mutation frequency was 74%. Amino acid alterations in the 61 tumors with exon 11 mutations were deletion in 33 tumors, substitution in 20, both deletion and substitution in 4, insertion in 1, and duplication in 3. Histologically, tumors with c-kit mutations showed higher mitotic counts and higher cellularity. The 5-year relapse-free survival (RFS) in patients having GISTs with c-kit mutations was 21%, compared with 60% in those without c-kit mutations. Significantly higher RFS rates were observed in patients with tumors having mitotic counts < 5 mitoses/50 high power field, spindle-cell histology, tumor size < 5 cm, or gastric GISTs. Multivariate analyses indicated association of poorer RFS with a higher mitotic count > or = 5 of 50 high power fields; odds ratio (OR) = 3.0], presence of c-kit mutations (OR = 5.6), and a larger tumor size (> or = 5 cm; OR = 4.2). CONCLUSIONS: The presence of c-kit mutation, along with high mitotic count and larger tumor size, was an independent factor for poor prognosis in patients with localized GISTs. 相似文献
Rationale:Traumatic arteriovenous fistulas (AVFs) of the pelvis are uncommon and present with a variety of clinical manifestations; their detection may be difficult. An endovascular approach is usually the first choice of treatment, because surgical intervention is complicated due to the location of the lesions.Patient concerns:A 68-year-old man was admitted with severe pelvic pain following a fall.Diagnosis:A pelvic bone fracture (Young and Burgess Classification, lateral compression type II) was revealed on pelvic computed tomography (CT), while a pelvic sidewall hematoma, unaccompanied by any vascular injury, was detected on multidetector CT.Interventions:Pelvic angiography revealed an AVF between the internal iliac artery and vein, which was undetected by MDCT. The AVF was successfully treated using transcatheter arterial embolization (TAE) with n-butyl cyanoacrylate (NBCA).Outcomes:The patient recovered well and was discharged 4 weeks later. No complications were noted at the 8-month follow-up.Lessons:AVF may occur as a complication of blunt pelvic bone fracture. A high index of suspicion, angiography, and prompt diagnosis resulted in the successful management of our patient who presented with risk factors. Furthermore, TAE using NBCA enables a minimally invasive and effective treatment of traumatic pelvic AVF. 相似文献
Bias temperature stress stabilities of thin-film transistors (TFTs) using In–Ga–Zn–O (IGZO) channels prepared by the atomic layer deposition process were investigated with varying channel thicknesses (10 and 6 nm). Even when the IGZO channel thickness was reduced to 6 nm, the device exhibited good characteristics with a high saturation mobility of 15.1 cm2 V−1 s−1 and low sub-threshold swing of 0.12 V dec−1. Excellent positive and negative bias stress stabilities were also obtained. When positive bias temperature stress (PBTS) stability was tested from 40 to 80 °C for 104 s, the threshold voltages (VTH) of the device using the 6 nm-thick IGZO channel shifted negatively, and the VTH shifts increased from −0.5 to −6.9 V with the increasing temperature. Time-dependent PBTS instabilities could be explained by a stretched-exponential equation, representing a charge-trapping mechanism.Bias temperature stress stabilities of thin-film transistors (TFTs) using In–Ga–Zn–O (IGZO) channels prepared by the atomic layer deposition process were investigated with varying channel thicknesses (10 and 6 nm). 相似文献
For hearing support devices, it is important to minimize the negative effect of ambient noises for speech recognition but also, at the same time, supply natural ambient sounds to the hearing‐impaired person. However, conventional fixed bilateral asymmetric directional microphone (DM) algorithms cannot perform in such a way when the DM‐mode device and a dominant noise (DN) source are placed on the same lateral hemisphere. In this study, a new binaural asymmetric DM algorithm that can overcome the defects of conventional algorithms is proposed. The proposed algorithm can estimate the position of a specific DN in the 90°–270° range and switch directional‐ and omnidirectional‐mode devices automatically if the DM‐mode device and the DN are placed in opposite lateral hemispheres. Computer simulation and KEMAR mannequin recording tests demonstrated that the performance of the conventional algorithm deteriorated when the DM‐mode device and the DN were placed in the opposite hemisphere; in contrast, the performance of the proposed algorithm was consistently maintained regardless of directional variations in the DN. Based on these experimental results, the proposed algorithm may be able to improve speech quality and intelligibility for hearing‐impaired persons who have similar degrees of hearing impairment in both ears. 相似文献
Aim: Chondroblastoma is a rare, benign bone tumor that accounts for approximately 1% of all primary bone tumors. Chondroblastoma that occurs at the temporomandibular joint can exhibit symptoms similar to those associated with other temporomandibular disorders. This case study aims to present an eight-year followup of chondroblastoma occurring at the temporomandibular joint.
Methodology: The patient presented swelling in the left temporomandibular joint and trismus. Based oncomputed tomography and magnetic resonance imaging findings, a provisional diagnosis of synovial chondromatosis was made. Complete excision of the lesion was performed under general anesthesia.
Results: After histopathological examination, the lesion was finally diagnosed as chondroblastoma. Currently, 8 years after the operation, the patient has not experienced any symptoms or any notable complications.
Conclusions: Although chondroblastoma is a benign tumor, it shows aggressive characteristics with bone invasion. Therefore, precise diagnosis and proper treatment planning is crucial for successful treatment of chondroblastoma. 相似文献