PKR is necessary for osteoclastogenesis.

Double-stranded RNA-dependent protein kinase (PKR) is involved in cell cycle progression, cell proliferation, cell differentiation, tumorgenesis, and apoptosis. We previously reported that PKR is required for differentiation and calcification in osteoblasts. TNF-α plays a key role in osteoclast differentiation. However, it is unknown about the roles of PKR in the TNF-α-induced osteoclast differentiation. The expression of PKR in osteoclast precursor RAW264.7 cells increased during TNF-α-induced osteoclastogenesis. The TNF-α-induced osteoclast differentiation in bone marrow-derived macrophages and RAW264.7 cells was markedly suppressed by the pre-treatment of PKR inhibitor, 2-aminopurine (2AP), as well as gene silencing of PKR. The expression of gene markers in the differentiated osteoclasts including TRAP, Calcitonin receptor, cathepsin K and ATP6V0d2 was also suppressed by the 2AP treatment. Bone resorption activity of TNF-α-induced osteoclasts was also supressed by 2AP treatment. Inhibition of PKR supressed the TNF-α-induced activation of NF-κB and MAPK in RAW264.7 cells. 2AP inhibited both the nuclear translocation of NF-κB and its transcriptional activity in RAW264.7 cells. 2AP inhibited the TNF-α-induced expression of NFATc1 and c-fos, master transcription factors in osteoclastogenesis. TNF-α-induced nuclear translocation of NFATc1 in mature osteoclasts was clearly inhibited by the 2AP treatment. The PKR inhibitor C16 decreased the TNF-α-induced osteoclast formation and bone resorption in mouse calvaria. The present study indicates that PKR is necessary for the TNF-α-induced osteoclast differentiation in vitro and in vivo

Morphological Alterations of the Eccrine Sweat Apparatus in Amputated Feet from Diabetes Mellitus Patients

Several physiological studies have demonstrated decreased or absent thermoregulatory sweating in the distal legs and feet of diabetes patients. Such hypohidrosis in diabetes patients is believed to be a clinical symptom of autonomic neuropathy. Thus, the present study sought to clarify the pathogenesis of structural alterations of the eccrine sweat apparatus in diabetes patients. For this study, we enrolled 17 patients with diabetic ulcers/gangrene who underwent amputation of the foot. Specimens were obtained 30mm from the ulcer/gangrene after amputation using a 6-mm trepan, with 12 normal human skin samples obtained from areas adjacent to pigmented nevi or benign skin tumors on the legs or feet to serve as controls. Numbers and morphological abnormalities of eccrine sweat glands and ducts were assessed by light microscopy. The pathogenesis of morphological alterations was examined by electron microscopy and immunoelectron microscopy of type IV collagen. Rates of disappearance of the lumen, shrunken morphology, and irregular outlines of eccrine sweat glands and ducts were significantly higher or more abundant in diabetes patients than in controls (P = 0.0002〜0.0001). Ultrastructurally, we observed prominent thickening of the basement membranes in eccrine sweat glands, admixed cell debris, and narrowing of the lumenal space. The thickened basement membranes resulted in the shrunken morphology and irregular outlines in eccrine sweat glands and ducts. Immunoelectron microscopy showed immunogold labeling for type IV collagen throughout the thickened basement membrane zone. These morphological alterations of the eccrine sweat apparatus in amputated feet from diabetes patients could be caused by diabetic and/or uremic neuropathy, and at least in part by angiopathy

Preimplant factors affecting postimplant CT-determined prostate volume and the CT/TRUS volume ratio after transperineal interstitial prostate brachytherapy with 125I free seeds

<p>Abstract</p> <p>Background</p> <p>The aim was to identify preimplant factors affecting postimplant prostate volume and the increase in prostate volume after transperineal interstitial prostate brachytherapy with ¹²⁵I free seeds.</p> <p>Methods</p> <p>We reviewed the records of 180 patients who underwent prostate brachytherapy with ¹²⁵I free seeds for clinical T1/T2 prostate cancer. Eighty-one (45%) of the 180 patients underwent neoadjuvant hormonal therapy. No patient received supplemental external beam radiotherapy. Postimplant computed tomography was undertaken, and postimplant dosimetric analysis was performed. Univariate and multivariate analyses were performed to identify preimplant factors affecting postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.</p> <p>Results</p> <p>Preimplant prostate volume by transrectal ultrasound, serum prostate-specific antigen, number of needles, and number of seeds implanted were significantly correlated with postimplant prostate volume by computed tomography. The increase in prostate volume after implantation was significantly higher in patients with neoadjuvant hormonal therapy than in those without. Preimplant prostate volume by transrectal ultrasound, number of needles, and number of seeds implanted were significantly correlated with the increase in prostate volume after implantation. Stepwise multiple linear regression analysis showed that preimplant prostate volume by transrectal ultrasound and neoadjuvant hormonal therapy were significant independent factors affecting both postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.</p> <p>Conclusions</p> <p>The results of the present study show that preimplant prostate volume by transrectal ultrasound and neoadjuvant hormonal therapy are significant preimplant factors affecting both postimplant prostate volume by computed tomography and the increase in prostate volume after implantation.</p

Incidence of seed migration to the chest, abdomen, and pelvis after transperineal interstitial prostate brachytherapy with loose 125I seeds

<p>Abstract</p> <p>Background</p> <p>The aim was to determine the incidence of seed migration not only to the chest, but also to the abdomen and pelvis after transperineal interstitial prostate brachytherapy with loose ¹²⁵I seeds.</p> <p>Methods</p> <p>We reviewed the records of 267 patients who underwent prostate brachytherapy with loose ¹²⁵I seeds. After seed implantation, orthogonal chest radiographs, an abdominal radiograph, and a pelvic radiograph were undertaken routinely to document the occurrence and sites of seed migration. The incidence of seed migration to the chest, abdomen, and pelvis was calculated. All patients who had seed migration to the abdomen and pelvis subsequently underwent a computed tomography scan to identify the exact location of the migrated seeds. Postimplant dosimetric analysis was undertaken, and dosimetric results were compared between patients with and without seed migration.</p> <p>Results</p> <p>A total of 19,236 seeds were implanted in 267 patients. Overall, 91 of 19,236 (0.47%) seeds migrated in 66 of 267 (24.7%) patients. Sixty-nine (0.36%) seeds migrated to the chest in 54 (20.2%) patients. Seven (0.036%) seeds migrated to the abdomen in six (2.2%) patients. Fifteen (0.078%) seeds migrated to the pelvis in 15 (5.6%) patients. Seed migration occurred predominantly within two weeks after seed implantation. None of the 66 patients had symptoms related to the migrated seeds. Postimplant prostate D90 was not significantly different between patients with and without seed migration.</p> <p>Conclusion</p> <p>We showed the incidence of seed migration to the chest, abdomen and pelvis. Seed migration did not have a significant effect on postimplant prostate D90.</p

Depressive psychosis: clinical usefulness of MR spectroscopy data in predicting prognosis

PURPOSE: To prospectively assess the usefulness of magnetic resonance (MR) spectroscopy data acquired before the initiation of medical therapy in predicting prognosis in patients with depressive psychosis. MATERIALS AND METHODS: All subjects gave written informed consent to an institutional committee for clinical research-approved study protocol. The clinical course after medication in 52 patients with depressive psychosis (age range, 52-78 years; 21 men, 31 women) was investigated. In all patients, MR spectroscopy was performed with a 1.5-T MR imaging unit before the initiation of medical therapy. Cerebrovascular lesions (CVLs), which appear as high-signal-intensity areas on T2-weighted MR images, were evaluated by using the Fazekas rating scale. Patients were classified into two groups on the basis of the ratio of N-acetylaspartate (NAA) to creatine and phosphocreatine (Cr): Patients in group A had an NAA/Cr ratio greater than 1.91, and patients in group B had an NAA/Cr ratio of 1.91 or less. To assess the response of the patients to medication, standard psychiatric tests--the Verbal Associative Fluency Test (VAFT), the Digit Symbol Test (DST), the Mini-Mental State Examination (MMSE), and the Hamilton Depression Rating Scale (HAM-D)--were administered before and after medical therapy was initiated. Mean test scores before and after medication were compared with paired t testing. P < .05 was considered to indicate a significant difference. RESULTS: There were 25 patients in group A and 27 in group B. In group A, the mean VAFT and DST scores increased and the mean HAM-D score decreased after medication. There was no significant difference in mean MMSE scores before and after medication (P = .945 for group A and P = .934 for group B). In group B, there were no significant differences in any of the psychiatric test scores before and after medication. The high-signal-intensity area score in group B was significantly higher than that in group A (P = .004). CONCLUSION: MR spectroscopy data obtained before the initiation of medical therapy were useful in predicting prognosis in patients with depressive psychosis; this suggests that the combined burden of all CVLs may affect the response to antidepressant medication

Patterns of Interstitial Lung Disease During Everolimus Treatment in Patients with Metastatic Renal Cell Carcinoma

Objective: To elucidate the patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma, we reviewed seven cases of everolimus-induced interstitial lung disease. Methods: Seven patients with metastatic renal cell carcinoma, which continued to progress despite treatment with sunitinib or sorafenib, developed interstitial lung disease after treat-ment with everolimus. Results: Chest X-ray demonstrated diffuse infiltrates in lung fields, and chest computed tom-ography showed bilateral reticular and ground-glass opacities. Serum levels of lactate de-hydrogenase (7/7), C-reactive protein (6/7), pulmonary surfactant associated protein D (1/7) and Krebs von den Lungen 6 (5/7) were elevated. The bronchoalveolar lavage fluid obtained from four patients with Grade 3 interstitial lung disease showed lymphocytosis. The transbron-chial lung biopsy specimens showed interstitial lymphocytic infiltration and septal thickening of alveolar walls. In two cases with mild interstitial lung disease, the everolimus therapy was successfully continued. In four cases with Grade 3 interstitial lung disease, the drug was dis-continued and steroid therapy was initiated. Pulmonary symptoms and radiological abnormal

Boiling Heat Transfer Characteristics of Vertical Water Jet Impinging on Horizontally Moving Hot Plate

This study investigates the heat transfer characteristics of a circular jet pointing upward that impinges on a moving hot steel sheet by using a laboratory-scale setup. The test liquid was water at 17°C, and the volumetric flow rate of the coolant was set to 450, 960, and 1480 mL/min. The test solid was 0.3 mm thick stainless steel (SUS430) with an initial temperature in the range 300–700°C. The moving velocity of the solid was set to 0.5, 1.0, and 1.5 m/s, and its temperature profile was measured by an infrared camera. The results showed that a region of high heat flux appeared in the area impacted by the jet. The heat transfer characteristics relied heavily on the initial temperature of the solid associated with the boiling patterns—namely, nucleate, transition, and film boiling. Along the boundary between the strong nucleate and the transition boiling regimes, the heat flux took peak values. The local minimum values of heat flux obtained between the transition and the film boiling regimes. The initial temperatures of the solid exhibiting these values were influenced by its moving velocity and the jet impact velocity. Moreover, the heat fluxes in the jet impact region for upward-impinging jets were compared with reported data for downward-impinging jets under the condition whereby the jet impact velocity and diameter in the two cases were nearly identical prior to impact. The two sets of results showed very similar trends, although the flow motions of water varied because of the effect of gravit

Growth of membrane nanostructures on W co-deposition layer

Large-scale mm thick fiberform nanostructures are grown when materials are subjected to high flux helium ions with tungsten particles (ions and neutrals) precipitation. Observations of the large-scale fiberform nanostructures (LFNs) were conducted by scanning electron microscope (SEM) and transmission electron microscope (TEM) analyses. In particular, this study focuses on membrane nanostructures. Membranes that contain He bubbles were always observed when LFNs covered the surface. We discuss the growth process of the membrane structures based on detailed observations. Keywords: Nanostructures, Helium, Tungsten, Transmission electron microscop

Microstructure and Retention in He-W Co-Deposition Layer

A tungsten (W) deposition layer is formed while a sample is exposed to a helium (He) plasma at the surface temperature of 473 or 573 K. The formed He-W co-deposition layer was composed of fine grains, the size of which increased with the surface temperature. The samples with the co-deposition layer was exposed to a deuterium (D2) plasma, and the D retention was investigated using thermal desorption spectroscopy. It was found that the co-deposition layer has quite different D retention characteristics compared with bulk W