Effectiveness of a radiation protective device for anesthesiologists and transesophageal echocardiography operators in structural heart disease interventions.

In structural heart disease (SHD) interventions, the exposure of staff other than the first operator such as anesthesiologists and transesophageal echocardiography (TEE) operators to the radiation can also pose the risks of cancer and cataracts in the long term. This study was conducted to test our new radiation protective device (RPD) for anesthesiologists and TEE operators in SHD interventions. The RPD, which consists of a head side shield and a cradle shield, was mounted on a 0.25 mm Pb-equivalent unleaded radiation protection sheet on a self-made J-shaped acrylic table, and it was placed on the head side and cradle on the operating table. A CT human body phantom was placed on the operating table, and the C-arm was set in five directions: posteroanterior, right anterior oblique 30°, left anterior oblique 30°, caudal 30°, and cranial 30°. The ambient dose equivalent rate at the usual positions of the anesthesiologist and TEE operator were measured under a fluoroscopic sequence with and without the RPD, and the dose reduction rate was obtained. The height of each measurement point was set to 100, 130 or 160 cm. The reduction rates at the positions of the anesthesiologist and the TEE operator were 82.6-86.4% and 77.9-89.5% at the height of 100 cm, 48.5-68.4% and 83.3-91.0% at 130 cm, and 23.6-62.9% and 72.9-86.1% at 160 cm, respectively. The newly developed RPD can thus effectively reduce the radiation exposure of anesthesiologists and TEE operators during SHD interventions.

[Reduction of Operator Exposure Radiation Dose and Evaluation of Image Quality Using Half Scan in CT Fluoroscopy].

In recent years, the number of examinations and treatments using computed tomography fluoroscopy (CTF) has been increasing, and there is concern about an increase in the exposure radiation dose of the operator. Use of half scan CTF can be expected to reduce the exposure radiation dose, but there is no report. The purpose of this study was to evaluate the exposure radiation dose at the operator's position and image quality when using a half scan CTF. The left side facing the gantry was the operator's position, and the ambient dose equivalent at 160 cm, 130 cm, and 100 cm from the floor was measured using an ionization chamber survey meter. The absorbed dose at the forceps holding position of the operator was measured using a fluorescent glass dosimeter with the forceps holding position 15 cm caudal from the scan center. The imaging conditions used a tube voltage of 120 kV and a tube current of 50 mA. Half scan CTF was performed by changing the center angle of the half scan on the console every 45°. As a result, the set angles were 135°and 90°at the operator's position, and 135°at the operator's forceps holding position. In addition, we evaluated the effect of half scan CTF on image quality. CTF images were collected with a cryogenic needle used for cryotherapy punctured in a water-equivalent self-made phantom. The profile curves of the obtained images were drawn and compared using analysis software to evaluate the effects of artifacts. Then, the SD of the CT value of the region of interest with and without the artifact was measured, and the relative artifact index was calculated and evaluated. Using the same image, CT value and SD were tested to evaluate noise. Half scan CTF had no effect on the image quality due to artifacts and noise.

The sodium phosphate cotransporter family and nicotinamide phosphoribosyltransferase contribute to the daily oscillation of plasma inorganic phosphate concentration.

Circulating inorganic phosphate exhibits a remarkable daily oscillation based on food intake. In humans and rodents, the daily oscillation in response to food intake may be coordinated to control the intestinal absorption, renal excretion, cellular shifts, and extracellular concentration of inorganic phosphate. However, mechanisms regulating the resulting oscillation are unknown. Here we investigated the roles of the sodium phosphate cotransporter SLC34 (Npt2) family and nicotinamide phosphoribosyltransferase (Nampt) in the daily oscillation of plasma inorganic phosphate levels. First, it is roughly linked to urinary inorganic phosphate excretion. Second, expression of renal Npt2a and Npt2c, and intestinal Npt2b proteins also exhibit a dynamic daily oscillation. Analyses of Npt2a, Npt2b, and Npt2c knockout mice revealed the importance of renal inorganic phosphate reabsorption and cellular inorganic phosphate shifts in the daily oscillation. Third, experiments in which nicotinamide and a specific Nampt inhibitor (FK866) were administered in the active and rest phases revealed that the Nampt/NAD+ system is involved in renal inorganic phosphate excretion. Additionally, for cellular shifts, liver-specific Nampt deletion disturbed the daily oscillation of plasma phosphate during the rest but not the active phase. In systemic Nampt+/- mice, NAD levels were significantly reduced in the liver, kidney, and intestine, and the daily oscillation (active and rest phases) of the plasma phosphate concentration was attenuated. Thus, the Nampt/NAD+ system for Npt2 regulation and cellular shifts to tissues such as the liver play an important role in generating daily oscillation of plasma inorganic phosphate levels.

AP-1-mediated expression of brain-specific class IVa ß-tubulin in P19 embryonal carcinoma cells.

Expression of brain-specific phenotypes increased in all trans retinoic acid (ATRA)-induced neural differentiation of mouse P19 embryonal carcinoma cells. Among these phenotypes, expression of class IVa ß-tubulin isotype (TUBB4a) was particularly enhanced in neural differentiation. Transient transfection assays employing a reporter construct found that ATRA-mediated regulatory region of the TUBB4a gene lay in the region from -83 nt to +137 nt relative to the +1 transcription start site. Site-directed mutagenesis in the AP-1 binding site at -29/-17 suggested that the AP-1 binding site was a critical region for ATRA-mediated TUBB4a expression. Chromatin immunoprecipitation experiments suggested participation of JunD and activating transcription factor-2 (ATF2) in TUBB4a expression. Additionally, exogenous induction of the dominant-negative (dn) type of JunD canceled ATRA-induced upregulation of TUBB4a, and the dn type of ATF2 suppressed even the basal activity. Further immunoblot study revealed an ATRA-mediated increase in JunD protein, while a significant amount of ATF2 protein was constantly produced. These results suggest that differentiation-mediated activation of JunD results in enhanced TUBB4a expression.

[Inspection of dose reduction in patients during percutaneous coronary intervention and catheter ablation procedures].

With an increasing number of interventional radiology (IVR) procedures, it is a critical issue to control and reduce the radiation dose for patients by radiological technologists. In our study, we analyzed the usefulness of a provision for radiation reduction on catheter ablation and percutaneous coronary intervention (PCI) procedures based on the data from radiation information system (RIS). With regard to catheter ablation, 50% reduction was enabled with decreasing fluoroscopic and radiographic conditions regardless of each technique. Radiation reduction enabled a decrease in the fluoroscopic dose during PCI procedure. However, note that excessive radiation reduction does not show positive results of the radiation dose reduction. Moreover it leads to an increase in fluoroscopic time.

Rab27b regulates c-kit expression by controlling the secretion of stem cell factor.

Rab27b, a subfamily of Rab27 small GTPases, was originally identified in platelets. However, the role of Rab27b in megakaryocytic lineage cells remains unknown. Here, using a human megakaryoblastic cell line, CMK, we show that Rab27b negatively regulates c-kit-expression. We found that transfection of shRNA-Rab27b into CMK cells led to specific increase in the amount of the receptor-type tyrosine kinase c-kit. To elucidate the molecular mechanisms by which Rab27b regulates c-kit expression, we analyzed the dynamics of c-kit by the stimulation with its ligand, stem cell factor (SCF). We found that cell surface expression of c-kit was promptly reduced and rapidly degraded in both CMK and Rab27b-knockdown CMK cells. Pretreatment with a lysosome inhibitor bafilomycin suppressed the degradation of c-kit, indicating that c-kit expression is controlled by SCF-induced endolysosomal degradation system. We therefore focused on the potential involvement of SCF in Rab27b-mediated effects on c-kit expression levels. We found that autocrine secretion of SCF was downregulated in Rab27b-knockdown cells as compared with parental CMK cells. These results suggest that Rab27b negatively regulates the cell surface expression of c-kit via secretion of SCF and that ligation of SCF leads to the endolysosomal degradation system of c-kit.

ATP-induced osteoclast function: the formation of sealing-zone like structure and the secretion of lytic granules via microtubule-deacetylation under the control of Syk.

Osteoclasts are bone-resorbing cells which play an exclusive role in bone remodeling, but the molecular mechanisms of osteolysis, how osteoclasts are activated and how the lytic granules are finally released towards the bone matrix are poorly understood. Here we show that an energy molecule ATP induces osteolysis via P2X(7)-nucleotide receptor and that deacetylation of alpha-tubulin is essential for the whole process of osteolysis under the control of a tyrosine kinase Syk. By developing a traceable and reproducible in vitro analyzing system for osteoclast function, we found that ATP-signaling gives rise to two events simultaneously (i) cytoskeletal reorganization for the formation of sealing zones, ring-like adhesion structures which delimit the contact surface, and (ii) the delivery and secretion of lytic granules towards the delimited site on the matrix. We further found that deacetylation of alpha-tubulin is a critical reaction for osteoclast function. Pharmacological inhibition of alpha-tubulin deacetylation resulted in (i) failure of the sealing-zone like structure formation and (ii) ceased secretion of lytic granules. Additionally, kinetics of deacetylation was found to be regulated by Syk. These data suggest a novel P2X(7) microtubular regulation pathway related to Syk for a therapeutic target in osteolytic diseases.

Effects of peripheral cannabinoid receptor ligands on motility and polarization in neutrophil-like HL60 cells and human neutrophils.

The possible role of the peripheral cannabinoid receptor (CB2) in neutrophil migration was investigated by using human promyelocytic HL60 cells differentiated into neutrophil-like cells and human neutrophils isolated from whole blood. Cell surface expression of CB2 on HL60 cells, on neutrophil-like HL60 cells, and on human neutrophils was confirmed by flow cytometry. Upon stimulation with either of the CB2 ligands JWH015 and 2-arachidonoylglycerol (2-AG), neutrophil-like HL60 cells rapidly extended and retracted one or more pseudopods containing F-actin in different directions instead of developing front/rear polarity typically exhibited by migrating leukocytes. Activity of the Rho-GTPase RhoA decreased in response to CB2 stimulation, whereas Rac1, Rac2, and Cdc42 activity increased. Moreover, treatment of cells with RhoA-dependent protein kinase (p160-ROCK) inhibitor Y27632 yielded cytoskeletal organization similar to that of CB2-stimulated cells. In human neutrophils, neither JWH015 nor 2-AG induced motility or morphologic alterations. However, pretreatment of neutrophils with these ligands disrupted N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced front/rear polarization and migration and also substantially suppressed fMLP-induced RhoA activity. These results suggest that CB2 might play a role in regulating excessive inflammatory response by controlling RhoA activation, thereby suppressing neutrophil migration.

[Optimization of the chest exposure condition with a contrast-detail phantom: evaluation of the flat-panel versus computed radiography systems].

In this study, we evaluated the performance of a digital chest imaging system using a contrast-detail (C-D) phantom. In the initial step, 76 sample images of the C-D phantom were produced by changing the doses from 0.5, 0.75, 1.0, 1.25, 1.5, to 2.0 times the dose for a screen-film (S/F) system. The sample images were analyzed by five radiological technologists and two medical physicists, and the image quality figure (IQF) was determined. The quality of each image was examined, and appropriate doses were determined from the calculated IQF to obtain the same image quality for other digital chest imaging systems. The method of determining IQF from C-D phantom analysis was very useful for comparing image quality and determining radiographic techniques.

[Study of improvement in X-ray computed tomography images with a radiation treatment planning system: image noise and slice thickness].

In radiotherapy, dose distribution and calculation of dose monitor units (DMU) are generally performed by a radiation treatment planning system using CT images. Therefore, differences in calculation can arise as a result of the quality of the CT image data. The quality of CT images involves contrast resolution, resolution, noise, slice thickness, and other factors. Among these factors, we examined noise and slice thicknesses. Results demonstrated that, even if noise increased, CT value did not change, and, therefore, did not influence DMU. Examination of slice thickness showed that, when the radiation field was rectangular, it was not influenced by slice thickness. However, when a multi-leaf collimator (MLC) was used, if slice thickness was thicker than the size of the MLC, a difference arose in the position of the MLC, and, therefore, some difference arose in dose. Therefore, slice thickness should be thinner than the size of the MLC.

[Low contrast detectability of a new CR system with two-sided reading].

A new imaging plate (IP) with a transparent support and reading system that can detect emissions from both sides of the IP has been developed and has already been introduced in some facilities. In this study, low contrast threshold detectability was investigated experimentally for a CR system with a two-sided reading system (new CR) and for a conventional CR system. Images of a Contrast-Detail phantom were obtained with the new and conventional CR systems at dose levels corresponding to 26%, 49%, 82%, 103%, and 164% of the dose used for the screen-film system. Using an observer performance study of Contrast-Detail phantom images, the threshold contrast of disk-shaped objects ranging from 0.3 mm to 4.0 mm in diameter was determined. We also calculated image quality figure (IQF) from the results of observation. The new CR system showed significantly better contrast detectability than the conventional CR system. The use of a new CR system provided a reduction of approximately 25% in radiographic dose while providing comparable IQF.

A case of multiple keratoacanthoma centrifugum marginatum: response to oral etretinate.

The patient was a 48-year-old man who had a history of colonic polyps. About 18 months before, a dark reddish nodule had appeared on his right forearm. By peripheral growth, this lesion had formed a crateriform prominence with central healing. Similar symptoms multiplied and expanded, the largest being about the size of a child's head. Given both the clinical and histologic evidence, a diagnosis of keratoacanthoma centrifugum marginatum (KCM) was made. Oral etretinate was administered, and an involution of verrucous plaque began after 4 weeks. After 8 weeks, the lesions faded, leaving pigmentation in some areas. This is a rare disorder, only 30 such cases having been reported worldwide, and the present case was the third in which oral etretinate was found to be effective.