RUNX3 interacts with MYCN and facilitates protein degradation in neuroblastoma.

RUNX3, a runt-related transcription factor, has a crucial role in dorsal root ganglion neurogenesis. Recent studies have suggested that RUNX3 acts as a tumor suppressor in stomach, colon and breast cancer. However, the biological role of RUNX3 in neuroblastoma remains elusive. Here we report that high levels of RUNX3 expression contribute to the favorable outcome in patients with neuroblastoma, whereas low levels of RUNX3 expression result in poor outcome. Array-based analysis suggested that the allelic loss at chromosome 1p36 is one of the reasons why expression of RUNX3 is downregulated in advanced neuroblastomas. Interestingly, the several patients survived from neuroblastoma with both high mRNA expressions of MYCN and RUNX3, suggesting that RUNX3 high expression might overcome the aggressive behavior of MYCN. Exogenous expression of RUNX3 strongly inhibits cell proliferation and migration in neuroblastoma cell lines. Furthermore, RUNX3 reduces the stability of MYCN protein in MYCN-amplified neuroblastoma cell lines, and this RUNX3-mediated MYCN degradation may depend on the physical interaction between RUNX3 and MYCN. Thus, our findings provide a tumor-suppressing mechanism by which RUNX3 inhibits the MYCN activity in neuroblastoma.

Automatic detection of informative frames from wireless capsule endoscopy images.

Wireless capsule endoscopy (WCE) is a new clinical technology permitting visualization of the small bowel, the most difficult segment of the digestive tract. The major drawback of this technology is the excessive amount of time required for video diagnosis. We therefore propose a method for generating smaller videos by detecting informative frames from original WCE videos. This method isolates useless frames that are highly contaminated by turbid fluids, faecal materials and/or residual foods. These materials and fluids are presented in a wide range of colors, from brown to yellow, and/or have bubble-like texture patterns. The detection scheme therefore consists of two steps: isolating (Step-1) highly contaminated non-bubbled (HCN) frames and (Step-2) significantly bubbled (SB) frames. Two color representations, viz., local color moments in Ohta space and the HSV color histogram, are attempted to characterize HCN frames, which are isolated by a support vector machine (SVM) classifier in Step-1. The rest of the frames go to Step-2, where a Gauss Laguerre transform (GLT) based multiresolution texture feature is used to characterize the bubble structures in WCE frames. GLT uses Laguerre Gauss circular harmonic functions (LG-CHFs) to decompose WCE images into multiresolution components. An automatic method of segmentation was designed to extract bubbled regions from grayscale versions of the color images based on the local absolute energies of their CHF responses. The final informative frames were detected by using a threshold on the segmented regions. An automatic procedure for selecting features based on analyzing the consistency of the energy-contrast map is also proposed. Three experiments, two of which use 14,841 and 37,100 frames from three videos and the rest uses 66,582 frames from six videos, were conducted for justifying the proposed method. The two combinations of the proposed color and texture features showed excellent average detection accuracies (86.42% and 84.45%) with the final experiment, when compared with the same color features followed by conventional Gabor-based (78.18% and 76.29%) and discrete wavelet-based (65.43% and 63.83%) texture features. Although intra-video training-testing cases are typical choices for supervised classification in Step-1, combining a suitable number of training sets using a subset of the input videos was shown to be possible. This mixing not only reduced computation costs but also produced better detection accuracies by minimizing visual-selection errors, especially when processing large numbers of WCE videos.

Plk1 regulates liver tumor cell death by phosphorylation of TAp63.

We previously found that Plk1 inhibited the p53/p73 activity through its direct phosphorylation. In this study, we investigated the functional role of Plk1 in modulating the p53 family member TAp63, resulting in the control of apoptotic cell death in liver tumor cells. Immunoprecipitation and in vitro pull-down assay showed that p63 binds to the kinase domain of Plk1 through its DNA-binding region. in vitro kinase assay indicated that p63 is phosphorylated by Plk1 at Ser-52 of the transactivating (TA) domain. Plk1 decreased the protein stability of TAp63 by its phosphorylation and suppressed TAp63-induced cell death. Furthermore, Plk1 knockdown in p53-mutated liver tumor cells transactivated p53 family downstream effectors, PUMA, p21(Cip1/WAF1) and 14-3-3sigma, and induced apoptotic cell death. Double knockdown of Plk1/p63 attenuated Plk1 knockdown-induced apoptotic cell death and transactivation. Intriguingly, both Plk1 and p63 are highly expressed in the side population (SP) fraction of liver tumor cells compared to non-SP fraction cells, suggesting the significance of Plk1/TAp63 in the control of cell death in tumor-initiating SP fraction cells. Thus, Plk1 controls TAp63 by its phosphorylation and regulates apoptotic cell death in liver tumor cells. Plk1/TAp63 may be a suitable candidate as a molecular target of liver tumor treatments.

Detecting informative frames from wireless capsule endoscopic video using color and texture features.

Despite emerging technology, wireless capsule endoscopy needs high amount of diagnosis-time due to the presence of many useless frames, created by turbid fluids, foods, and faecal materials. These materials and fluids present a wide range of colors and/or bubble-like texture patterns. We, therefore, propose a cascade method for informative frame detection, which uses local color histogram to isolate highly contaminated non-bubbled (HCN) frames, and Gauss Laguerre Transform (GLT) based multiresolution norm-1 energy feature to isolate significantly bubbled (SB) frames. Supervised support vector machine is used to classify HCN frames (Stage-1), while automatic bubble segmentation followed by threshold operation (Stage-2) is adopted to detect informative frames by isolating SB frames. An experiment with 20,558 frames from the three videos shows 97.48% average detection accuracy by the proposed method, when compared with methods adopting Gabor based-(75.52%) and discrete wavelet based features (63.15%) with the same color feature.

TAp63-dependent induction of growth differentiation factor 15 (GDF15) plays a critical role in the regulation of keratinocyte differentiation.

Since p63-deficient mice display severe defects in formation of epidermis, p63 has been considered to be a multi-isoform p53 family member essential for epidermal development. However, it is still unclear how p63 could contribute to keratinocyte differentiation. In the present study, we have found that TAp63alpha is induced in association with the upregulation and a secretion of growth differentiation factor 15 (GDF15) during the keratinocyte differentiation of HaCaT cells bearing p53 mutation. Short interference RNA-mediated knockdown of the endogenous TAp63 resulted in a remarkable reduction of GDF15. Luciferase reporter assay and reverse transcription-PCR analysis demonstrated that enforced expression of TAp63alpha significantly increases the luciferase activity driven by GDF15 promoter and the expression of GDF15. Consistent with these results, the proximal p53/p63-binding site within the GDF15 promoter region was required for the TAp63alpha-mediated transcriptional activation of GDF15, and TAp63alpha was recruited onto this site. Furthermore, siRNA-mediated knockdown of the endogenous GDF15 permitted cell growth and inhibited the expression of the differentiation markers such as keratin 10 and involucrin in response to differentiation stimuli. Taken together, our present results provide a novel insight into understanding the molecular mechanisms behind TAp63alpha-mediated keratinocyte differentiation.

A case of metastatic malignant hemangiopericytoma of the ovary: recurrence after a period of 17 years from intracranial tumor.

Hemangiopericytoma is an uncommon vascular tumor. Primary or metastatic hemangiopericytoma of the ovary is extremely rare. A 48-year-old Japanese woman had a tumor in the neck. Simultaneously, a solid ovarian tumor was detected. She had received treatment for intracranial hemangiopericytoma 17 years previously. For the ovarian tumor, she underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The left ovarian tumor weighed 1510 g and its cut surface was solid without areas of hemorrhage or necrosis. It was microscopically composed of tightly packed tumor cells outside of many vascular vessels. One or two mitotic figures were counted per 10 high power fields. Immunohistochemically, vimentin was expressed but factor-VIII-related antigen, CD 31, and CD 34 were not expressed in the tumor cells. Electron microscopy showed that the tumor cells were grown outside of the endothelium-lined vascular spaces. A discontinuous external basal lamina was also observed. We present a case of metastatic malignant hemangiopericytoma of the ovary from a primary intracranial hemangiopericytoma with a long interval of 17 years.

Tracking of a bronchoscope using epipolar geometry analysis and intensity-based image registration of real and virtual endoscopic images.

This paper describes a method for tracking the camera motion of a flexible endoscope, in particular a bronchoscope, using epipolar geometry analysis and intensity-based image registration. The method proposed here does not use a positional sensor attached to the endoscope. Instead, it tracks camera motion using real endoscopic (RE) video images obtained at the time of the procedure and X-ray CT images acquired before the endoscopic examination. A virtual endoscope system (VES) is used for generating virtual endoscopic (VE) images. The basic idea of this tracking method is to find the viewpoint and view direction of the VES that maximizes a similarity measure between the VE and RE images. To assist the parameter search process, camera motion is also computed directly from epipolar geometry analysis of the RE video images. The complete method consists of two steps: (a) rough estimation using epipolar geometry analysis and (b) precise estimation using intensity-based image registration. In the rough registration process, the method computes camera motion from optical flow patterns between two consecutive RE video image frames using epipolar geometry analysis. In the image registration stage, we search for the VES viewing parameters that generate the VE image that is most similar to the current RE image. The correlation coefficient and the mean square intensity difference are used for measuring image similarity. The result obtained in the rough estimation process is used for restricting the parameter search area. We applied the method to bronchoscopic video image data from three patients who had chest CT images. The method successfully tracked camera motion for about 600 consecutive frames in the best case. Visual inspection suggests that the tracking is sufficiently accurate for clinical use. Tracking results obtained by performing the method without the epipolar geometry analysis step were substantially worse. Although the method required about 20 s to process one frame, the results demonstrate the potential of image-based tracking for use in an endoscope navigation system.

Serum C4 levels in patients with systemic lupus erythematosus in remission.

Abstract Twenty-six patients with systemic lupus erythematosus (SLE) showing systemic lupus activity measure (SLAM) and SLE disease activity index (SLEDAI) scores ≤2, as well as a lower C4 concentration than the mean C4 levels of healthy controls, were selected to evaluate the C4 levels of SLE patients in remission. Serum complement (CH50), complement components (C4, C3, and B), complement split products (C4d, iC3b, and Bb), phenotypic expression of C4 allotype, C4 production by peripheral blood monocytes, peripheral blood lymphocyte subpopulation, and interferon-gamma (IFN-γ) production were examined. In patients with SLE in remission, the C4 consumption (C4d/C4) was found to increase, and this was considered to be the most important factor for determining the serum concentration of C4. However, the relevance of the C4 allotypic expression was minimal. The IFN-γ-stimulated production of C4 by peripheral blood monocytes in SLE patients in remission was also less than that of the healthy controls. The IFN-γ-stimulated production of C4 in SLE patients in remission correlated with the peripheral blood CD4-positive cells. Less IFN-γ was produced by lymphocytes of SLE in remission than by those of healthy adults. We conclude that the serum C4 levels in SLE patients in remission reflect the degree of C4 consumption as well as the disease state, rather than genetic influences such as a C4A defect.

Six cases of metastatic malignant melanoma with apparently occult primary lesions.

We report here six cases of malignant melanoma in which metastatic lesions were detected first. Of these, two cases showed some peculiar features: one exhibited widespread subcutaneous bleeding, probably due to venous rupture, and the other case had a rare primary lesion on the penis. In the Japanese literature, there have been 46 cases of malignant melanoma in which metastatic lesions were detected prior to the initial ones. The preferential site for metastasis was the lymph node (32 cases). The primary lesion was unknown in 35 patients. The outcomes were available for 36 of the 46 patients; 23 died, including 18 who died within two years.

[Three cases of occupationally induced herpetic whitlow in health care workers].

Herpetic whitlow is one of the herpes simplex virus (HSV) infections, and is known as an occupational disease. In Japan, however, there have been only a few reports of this disease. Recently, we experienced three cases of herpetic whitlow in health care workers. They presented painful vesicles on the right ring finger, the left thumb and the left index finger, respectively. All of them were considered to have been infected by HSV when they were engaged in mouth care of inpatients. We reviewed these three cases from the aspect of occupational medicine, and propose the following three points for preventing this serious nosocominal infection to health care workers: 1) re-education and enlightenment for the workers regarding hazardous behavior of HSV, 2) keeping the hands and fingers free from skin impairments, and 3) early diagnosis and treatment for herpetic whitlow of health care professionals to prevent further nosocominal infection.

Spiral, herringbone, and triple-decker silver(I) complexes of benzopyrene derivatives assembled through eta(2)-coordination.

Three novel silver(I) complexes with benzopyrene derivatives were synthesized and characterized in this paper. Treatment of AgClO(4)*H(2)O with 7-methylbenzo[a]pyrene (L(1)) afforded [Ag(2)(L(1))(toluene)(0.5)(ClO(4))(2)](n)() (1) which exhibits a 2-D sheet structure with double-stranded helical motifs. Reaction of AgCF(3)SO(3) with dibenzo[b,def ]chrysene (L(2)) gave rise to an unprecedented cocrystallization structure, ([Ag(2)(L(2))(CF(3)SO(3))(2)][Ag(2)(toluene)(2)(CF(3)SO(3))(2)])(n)() (2), formed by a 2-D neutral lamellar polymer and a 1-D neutral rodlike one. The ligand benzo[e]pyrene (L(3)) coordinated to silver(I) ions generating a closed triple-decker tetranuclear complex [Ag(4)(L(3))(4)(p-xylene)(ClO(4))(4)] (3) which can be regarded as a stacking polymer owing to existing intermolecular pi-pi stack interactions. The structural diversity of the silver(I) coordination polymers with polycyclic aromatic hydrocarbons is not only related to the stacking patterns of free polycyclic aromatic hydrocarbons in the crystalline state, but also the geometric shapes of the molecules for these free ligands. In addition, the coordination of solvents to metal ions plays a crucial role in the formation of the unprecedented coordination polymeric architectures. The ESR spectroscopic results, conductivity, and synthesis properties are also discussed.

[Seven cases of radiation-induced cutaneous squamous cell carcinoma].

We report 7 cases of radiation-induced skin cancer. The diagnosis was based on the history of radiotherapy for benign skin diseases (5 cases) and of occupational exposures to medical doctors (2 cases). All cases were squamous cell carcinomas which arose from chronic radiodermatitis. The estimated latent period of these tumors ranged from 6 to 64 years, with an average of 29.9 years. After surgical treatments of the lesions, no local recurrences were observed in all cases. Benign skin diseases had sometimes been treated with low-energy radiation before the 1960s. Considering the estimated latent period, the peak time point of developing risk of radiation-induced skin cancer by such treatment has been already passed, however, the danger of it should not be ignored in future. In association with multiplicity of radiation usage, occupational exposure of radiation may develop the risk of occurrence of skin cancer in future. Therefore, we should recognize that radiation-induced skin cancer is not in the past. In the cases of chronic skin diseases showing warty keratotic growth, erosion and ulcer, we should include chronic radio-dermatitis in the differential diagnosis. It is necessary to recall all patients about the history of radiotherapy or radiation exposure. Rapid histopathological examination is mandatory because of the suspicion of radiation-induced skin cancer.

Electron microscopic study of Langerhans cell histiocytosis.

Among the several forms of Langerhans cell histocytosis (LCH), Letterer-Siwe disease is the most acute disseminated multisystemic variant. The course of Letterer-Siwe disease is usually rapid and fatal. We report here a cases of Letterer-Siwe disease which showed a good response to chemotherapy. We also describe the unusual ultrastructural findings in the histiocyte-like cells in this case.

[A case of occupational contact dermatitis due to hydroxylamine].

A 36-year-old man, working in a chemical industry, had a generalized pruritic eruption. A forty-eight hour patch test revealed positivity for 1% hydroxylamine. Prevention of exposure to this chemical resulted in a dramatic improvement of the symptoms. Based on these findings, we diagnosed this case as occupational contact dermatitis due to hydroxylamine. There has been few case reports of contact dermatitis due to hydroxylamine. Histopathological examination revealed a marked spongiosis and a spongiotic bulla formation in the epidermis and follicular infundibulum, suggesting an allergic reaction.

Automated anatomical labeling of the bronchial branch and its application to the virtual bronchoscopy system.

This paper describes a method for the automated anatomical labeling of the bronchial branch extracted from a three-dimensional (3-D) chest X-ray CT image and its application to a virtual bronchoscopy system (VBS). Automated anatomical labeling is necessary for implementing an advanced computer-aided diagnosis system of 3-D medical images. This method performs the anatomical labeling of the bronchial branch using the knowledge base of the bronchial branch name. The knowledge base holds information on the bronchial branch as a set of rules for its anatomical labeling. A bronchus region is automatically extracted from a given 3-D CT image. A tree structure representing the essential structure of the extracted bronchus is recognized from the bronchus region. Anatomical labeling is performed by comparing this tree structure of the bronchus with the knowledge base. As an application, we implemented the function to automatically present the anatomical names of the branches that are shown in the currently rendered image in real time on the VBS. The result showed that the method could segment about 57% of the branches from CT images and extracted a tree structure of about 91% in branches in the segmented bronchus. The anatomical labeling method could assign the correct branch name to about 93% of the branches in the extracted tree structure. Anatomical names were appropriately displayed in the endoscopic view.