Preparation of Flattened Cross-Linked Hollow Particles by Suspension Polymerization in a Solid Dispersion Medium.

Flattened cross-linked hollow poly(divinylbenzene) (PDVB) particles with encapsulated n-hexadecane (HD) were successfully prepared through suspension polymerization using the self-assembling of phase-separated polymer (SaPSeP) method, in which the solid dispersion medium was gelled by gellan gum and compressed. The solid phase induced by gellan gum can be easily changed to a liquid state by heating, allowing the obtained particles to be easily recovered after polymerization. When the polymerization was conducted in the solid dispersion medium without compression, spherical hollow PDVB/HD composite particles were obtained. In contrast, when the polymerization was conducted with the compression of the solid dispersion medium, flattened hollow PDVB/HD composite particles were obtained. The shape of the flattened hollow polymer particles was controlled by changing the compression ratio of the solid phase, and the size could also be controlled by changing the DVB/HD droplet size using the Shirasu porous glass membrane-emulsification technique. Furthermore, flattened hollow particles larger than 20 µm in size were obtained, but it was difficult to obtain spherical hollow particles of such large size using the SaPSeP method.

The antitumor effects of methyl-ß-cyclodextrin against primary effusion lymphoma via the depletion of cholesterol from lipid rafts.

Primary effusion lymphoma (PEL) is a subtype of aggressive and chemotherapy-resistant non-Hodgkin lymphoma that occurs predominantly in patients with advanced AIDS. In this study, we examined the antitumor activity of methyl-ß-cyclodextrin (M-ß-CyD) in vitro and in vivo. M-ß-CyD quickly induced caspase-dependent apoptosis in PEL cells via cholesterol depletion from the plasma membrane. In a PEL xenograft mouse model, M-ß-CyD significantly inhibited the growth and invasion of PEL cells without apparent adverse effects. These results strongly suggest that M-ß-CyD has the potential to be an effective antitumor agent against PEL.

A position-adaptive noise-reduction method using a deep denoising filter bank for dedicated breast positron emission tomography images.

Dedicated breast positron emission tomography (db-PET) is more sensitive than whole-body positron emission tomography and is thus expected to detect early stage breast cancer and determine treatment efficacy. However, it is challenging to decrease the sensitivity of the chest wall side at the edge of the detector, resulting in a relative increase in noise and a decrease in detectability. Longer acquisition times and injection of larger amounts of tracer improve image quality but increase the burden on the patient. Therefore, this study aimed to improve image quality via reconstruction with shorter acquisition time data using deep learning, which has recently been widely used as a noise reduction technique. In our proposed method, a multi-adaptive denoising filter bank structure was introduced by training the training data separately for each detector area because the noise characteristics of db-PET images vary at different locations. Input and ideal images were reconstructed based on 1- and 7-min collection data, respectively, using list mode data. The deep learning model used residual learning with an encoder-decoder structure. The image quality of the proposed method was superior to that of existing noise reduction filters such as Gaussian filters and nonlocal mean filters. Furthermore, there was no significant difference between the maximum standardized uptake values before and after filtering using the proposed method. Taken together, the proposed method is useful as a noise reduction filter for db-PET images, as it can reduce the patient burden, scan time, and radiotracer amount in db-PET examinations.

[A case of neuromyelitis optica presenting ileus as a neurologic finding].

PURPOSE: To report an atypical case of neuromyelitis optica (NMO) with Sjögren syndrome that presented only ileus as a neurologic finding. CASE: A thirty two-year-old woman was hospitalized for abnormal abdominal symptoms, and was diagnosed as having paralytic ileus. Dry eye symptoms due to Sjogren syndrome were also observed, and visual acuity OU decreased suddenly 10 days after hospitalization. The best corrected visual acuity was 0.04 OD and 0.6 OS, and the optic discs OU were swollen and red. Although no neurologic signs were found, pleocytosis and abnormal MRI findings suggested NMO. Steroid pulse therapy was performed, and after three cycles, the ileus symptoms disappeared, and the disturbed visual acuity OU returned to normal. Because the anti-aquaporin 4 antibody was positive and no abnormal abdominal findings that might have caused ileus were found, we diagnosed NMO presenting only paralytic ileus as a neurologic finding. CONCLUSIONS: Differential diagnosis is important for NMO initiated by ileus as the only neurologic sign.

Interleukin-19 downregulates interleukin-4-induced eotaxin production in human nasal fibroblasts.

BACKGROUND: Interleukin-19 (IL-19), a member of the IL-10 family, is characterized as the cytokine suppressing the release and function of several proinflammatory cytokines. For regulation of local reaction in allergic rhinitis (AR), IL-19 might play an especially important role. METHODS: We examined effects of IL-19 on IL-4-induced eotaxin production by human nasal fibroblasts. Early receptor-mediated events (expression of the suppressors of cytokine signaling (SOCS) and phosphorylation of signal transducer and activator of transcription 6 [STAT6]) by IL-19 was examined. Knockdown methods by RNAi were administered to investigate the involvement of those signal transductions. RESULTS: Pretreatment with IL-19 downregulates IL-4-induced eotaxin production, but not interferon-γ(IFN-γ)-induced RANTES. Pretreatment with IL-19 suppressed the IL-4-induced STAT6 phosphorylation. The IL-19 induced SOCS-1, but not SOCS-3 or SOCS-5. The SOCS-1 knockdown by RNAi diminished pretreatment with IL-19-induced down-regulation of eotaxin production. CONCLUSIONS: These results suggest that IL-19 down-regulates IL-4-induced eotaxin production via SOCS-1 in human nasal fibroblasts. In non-hematopoietic cells in AR, IL-19 might be an immunosuppressive factor.

Platelet derived endothelial cell growth factor/thymidine phosphorylase enhanced human IgE production.

BACKGROUND: Angiogenesis is one pathogenesis of allergic airway disease. METHODS: A potent angiogenic factor is platelet-derived endothelial cell growth factor (PD-ECGF), also known as thymidine phosphorylase (TP) in the field of cancer-associated research. Vascular endothelial growth factor (VEGF) is another representative angiogenic factor. Both factors were added to the culture system of human peripheral blood mononuclear cells (PBMC) with IL-4 and anti-CD40 monoclonal antibody (mAb). Total IgE levels in the supernatants and signal transduction of stimulated PBMC were evaluated. RESULTS: Addition of PD-ECGF enhances in vitro IgE production by PBMC in the presence of IL-4 and anti-CD40 mAb, but VEGF does not enhance IgE production. Although PD-ECGF catalyzes the reversible phosphorolysis of thymidine to 2-deoxy-D-ribose-1-phosphate (2DDR), treatment of 2DDR has no effect on IgE production by human PBMC. Both IL-4 and anti-CD40 mAb induce PD-ECGF by human PBMC. Thymidine phosphorylase inhibitor (TPI), 5-chloro-6-[1- (2-iminopyrrolidinyl) methyl] uracil hydrochloride reduce IgE production via blocking of STAT6- phosphorylation. CONCLUSIONS: Taken together, these results suggest TP involvement in the enhancement of IgE production and suggest that TPI is a novel strategy against IgE-related allergic disease.

On-chip optical interconnection by using integrated III-V laser diode and photodetector with silicon waveguide.

On-chip integration of III-V laser diodes and photodetectors with silicon nanowire waveguides is demonstrated. Through flip-chip bonding of GaInNAs/GaAs laser diodes directly onto the silicon substrate, efficient heat dissipation was realized and characteristic temperatures as high as 132K were achieved. Spot-size converters for the laser-to-waveguide coupling were used, with efficiencies greater than 60%. The photodetectors were fabricated by bonding of InGaAs/InP wafers directly to silicon waveguides and formation of metal-semiconductor-metal structures, giving responsivities as high as 0.74 A/W. Both laser diode and the photodetector were integrated with a single silicon waveguide to demonstrate a complete on-chip optical transmission link.

Prevalence of allergic rhinitis and sensitization to common aeroallergens in a Japanese population.

BACKGROUND: Allergic rhinitis (AR) is recognized as a major health problem worldwide, and its prevalence depends on the age range of the subjects. The aims of this study were to determine the current prevalence of AR, effects of age on the prevalence of IgE sensitization to inhalant allergens, and serum total IgE levels in Japanese subjects. METHODS: We conducted a survey of 1,540 subjects between 20 and 49 years of age in 2006 and 2007 and examined the prevalence of AR and sensitization to 7 common aeroallergens. We measured serum total IgE and specific IgE to 7 aeroallergens. AR was determined based on symptoms, predominantly in the nose and eyes, caused by aeroallergens as mentioned in a questionnaire and sensitization to any of the 7 aeroallergens as assessed by measurement of serum specific IgE. RESULTS: The prevalence of AR was 44.2% (681 of the 1,540 subjects) and there was no difference among age decades. Of the 1,540 subjects, 1,073 (69.7%) were sensitized to at least 1 of the 7 aeroallergens. The most common allergen in AR was Japanese cedar pollen (89.6%, 610 of the 681 with AR) in all the age decades examined. The sensitization rate to mites was significantly higher in the younger subjects. CONCLUSION: Our data suggest that the prevalence of AR between 20 and 49 years of age has increased by nearly 10% during the last 10 years. Cedar pollen and mites were predominant allergen sources among the 7 aeroallergens in the Japanese population.

Bax-gene transfer enhances apoptosis by steroid treatment in human nasal fibroblasts.

Gene therapy has become a focus not only in the study of cancer but also lifestyle-related diseases. In case of chronic rhinosinusitis with nasal polyps and aspirin-induced asthma, nasal polyps poorly respond to a local administration of steroid. The Bax and Bcl-2 proteins play important roles in the regulation of apoptosis. The treatment of steroid (prednisone) induced apoptosis in the fibroblast. The Bax accelerates apoptosis. Apoptosis is very important in the anti-inflammatory mechanism. In this study, we investigated whether the overexpression of Bax in human fibroblasts influences apoptosis by treatment with a steroid (prednisolone) in vitro. Human nasal fibroblasts were isolated from small pieces of nasal polyp and were transfected with a bax gene-bearing mammalian expression vector. Human nasal fibroblasts were transiently transfected with the expression vector hBaxpcDNA3 (Bax-NF) or native pcDNA3 (Neo-NF). Both transfectants (Bax-NF, Neo-NF) and wild-type-nasal fibroblast (wt-NF) were cultured in conditioning medium and treated with each concentration of prednisolone for 72 h. Prednisolone at a concentration of 10 ng/ml decreased the viability of Bax-NF compared to that of Bax-NF in the absence of prednisolone. The cytotoxicity of prednisolone to Bax-NF was significantly higher than that to Neo-NF or wt-NF (p < 0.01) and the susceptibility of Bax-NF to prednisolone was about 1,000 times that of Neo-NF or wt-NF. We found that the transfer of the exogenous bax gene enhanced the induction of apoptosis by steroid-treatment in human nasal fibroblasts. Therefore, we suggest that exogenous Bax protein expression by gene transfer might be useful for the treatment of nasal polyps. We will further the preclinical study in improving steroids dose and in adopting to transfer bax gene to the nasal polyps by intranasal injection, thus providing a more effective and safer way for the nasal polyps that poorly respond to a local administration of steroids.

Kiss1R Identification and Biodistribution Analysis Employing a Western Ligand Blot and Ligand-Derivative Stain with a FITC-Kisspeptin Derivative.

It is not always easy to establish specific antibodies against receptors. Most receptors are hydrophobic and have complicated three-dimensional structures, making them difficult to use as immunogens. Thus, we developed receptor detection methods with a fluorescein-labeled ligand as an antibody alternative, which we referred to as a western ligand blot (WLB) and ligand derivative stain (LDS). Kisspeptin receptor (Kiss1R) was detected by its ligand. Kiss1R expression was confirmed in eight human cell lines by the WLB and in four pathological tissues by the LDS. Next, Kiss1R was stained by LDS in organs, revealing Kiss1R expression by [67 Ga]Ga-DOTA-kisspeptin 10 accumulation. As a result, Kiss1R-expressing cells in each organ could be stained with fluorescein-labeled kisspeptin 14 instead of an antibody and observed by light microscopy. The combination of the WLB and LDS allows identification of receptors in tissues, which can be readily applied to target receptor detection by a synthetic ligand derivative.

Organometal halide perovskites as visible-light sensitizers for photovoltaic cells.

Two organolead halide perovskite nanocrystals, CH(3)NH(3)PbBr(3) and CH(3)NH(3)PbI(3), were found to efficiently sensitize TiO(2) for visible-light conversion in photoelectrochemical cells. When self-assembled on mesoporous TiO(2) films, the nanocrystalline perovskites exhibit strong band-gap absorptions as semiconductors. The CH(3)NH(3)PbI(3)-based photocell with spectral sensitivity of up to 800 nm yielded a solar energy conversion efficiency of 3.8%. The CH(3)NH(3)PbBr(3)-based cell showed a high photovoltage of 0.96 V with an external quantum conversion efficiency of 65%.

Benign cystic teratoma of the parotid gland: a case report.

BACKGROUND: Mature cystic teratomas of the major salivary glands are rare. This report describes a case of a mature cystic teratoma of the left parotid gland, including the cytologic and histopathologic findings. CASE: A 17-year-old young woman presented with a slow-growing left parotid mass that had been present for 4 years. Preoperative fine needle aspiration cytology showed the presence of acinar and ductal cells, foamy cells and multinucleated giant cells. Imprint cytology of the surgical material showed the presence of some squamous cells and sebaceous gland-like cells with hair shafts. Cellular atypia was inconspicuous. Grossly, the 3-cm lesion was unicystic and embedded within the parotid gland parenchyma. Microscopically, the inner surface of the cyst was lined with keratinized squamous epithelium. The cyst wall contained skin adnexa such as sebaceous, eccrine and apocrine glands, as well as hair follicles. Some mature cartilage tissue was also detected. Foreign body granulomatous change was seen focally. No immature tissue or malignant transformation was found. CONCLUSION: There is no previous report describing the cytologic findings of a mature cystic teratoma of the parotid gland. Mature cystic teratomas should therefore be considered in the differential diagnosis of a cystic lesion of the parotid

Monte Carlo simulation of energy spectra for (123)I imaging.

(123)I is a radionuclide frequently used in nuclear medicine imaging. The image formed by the 159 keV photopeak includes a considerable scatter component due to high energy gamma-ray emission. In order to evaluate the fraction of scattered photons, a Monte Carlo simulation of a scintillation camera used for (123)I imaging was undertaken. The Monte Carlo code consists of two modules, the HEXAGON code modelled the collimator with a complex hexagonal geometry and the NAI code modelled the NaI detector system including the back compartment. The simulation was carried out for various types of collimators under two separate conditions of the source locations in air and in water. Energy spectra of (123)I for every pixel (matrix size = 256 x 256) were obtained by separating the unscattered from the scattered and the penetrated photons. The calculated energy spectra (cps MBq(-1) keV(-1)) agreed with the measured spectra with approximately 20% deviations for three different collimators. The difference of the sensitivities (cps MBq(-1)) for the window of 143-175 keV was less than 10% between the simulation and the experiment. The partial sensitivities for the scattered and the unscattered components were obtained. The simulated fraction of the unscattered photons to the total photons were 0.46 for LEHR, 0.54 for LEGP and 0.90 for MEGP for the 'in air' set-up, and 0.35, 0.40 and 0.68 for the 'in water' set-up, respectively. The Monte Carlo simulation presented in this work enabled us to investigate the design of a new collimator optimum for (123)I scintigraphy.

[A paper sheet phantom for scintigraphic planar imaging: usefulness of pouch-laminated paper source].

In order to perform experimental measurements for evaluation of imaging device's performance, data acquisition technique, and clinical images on scintigraphic imaging, many kinds of phantoms are employed. However, since these materials are acrylic and plastic, the thickness and quality of those materials cause attenuation and scatter in itself. We developed a paper sheet phantom sealed with a pouch laminator, which can be a true radioactive source in air. In this study, the paper sheet phantom was compared to the acrylic liver phantom, with the thickness of 2 cm, which is commercially available. The results showed that although some scatter counts were contained within the image of the acrylic liver phantom, there were few scattered photons in the paper sheet phantom image. Furthermore, this laminated paper sheet phantom made handling of the source and its waste easier. If the paper sheet phantom will be designed more sophisticatedly, it becomes a useful tool for planar imaging experiments.

Development of a collimator blurring compensation method using fine angular sampling projection data in SPECT.

Due to the collimator aperture, spatial resolution of SPECT data varies with source-to-detector distance. Since the radius of detector rotation is bigger when scanning larger patients, spatial resolution is degraded in these cases. Emitted gamma rays travel not only along the central axis of the collimator hole but also off-axis due to the collimator aperture. However, an off-axis ray at one angle would be a central-axis ray at another angle; therefore, raw projection data at one angle can be thought of as an ensemble of central-axis rays collected from a small arc equal to the collimator aperture. Thus, fine angular sampling can compensate for collimator blurring. By using a sampling pitch of less than half the collimator aperture angle, compensation was performed by subtracting the weighted sum of the projection data from the raw projection data. Collimator geometry and detector rotation radius determined the weighting function. Cylindrical phantom with four different-sized rods and torso phantom for Tl-201 cardiac SPECT simulation were used for evaluation. Aperture angle of the collimator was 7 degrees. Projection sampling pitch was 2 degrees. In both phantom studies, the proposed method showed improvement in contrast and reduction of partial volume effect, thereby indicating that the proposed method can compensate adequately for image blurring caused by the collimator aperture.

Oral and oropharyngeal squamous cell carcinomas expressing CCR7 have poor prognoses.

OBJECTIVE AND METHODS: Tumor cell migration and metastasis have many similarities with leukocyte trafficking regulated by chemokines and their receptors. In this study, we investigated the expression of CC chemokine receptor 7 (CCR7) in oral and oropharyngeal squamous cell carcinomas (SCCs) using an immunohistochemical approach. RESULTS: Among 90 cases of oral and oropharyngeal SCCs, 54 cases (60%) were positive for CCR7. The CCR7-positive group had a significantly lower incidence of being disease-free and an overall lower survival rate than the CCR7-negative group (p<0.01 and p<0.01, respectively). Among the 35 patients who died of cancer, 28 patients (80%) were positive for CCR7. The expression of CCR7 was significantly associated with five clinical factors. SCCs expressing CCR7 tend to have large, lymph node metastases, progressive stages, local recurrences and cancer death. The CCR7 expression of metastatic SCCs in draining lymph nodes was detected, and the staining score of CCR7 between primary SCCs and metastatic SCCs were significantly correlated (p<0.01). CONCLUSIONS: The investigation of CCR7 expression in oral and oropharyngeal SCCs may be useful to predict patients prognoses.

Hybrid Light Imaging Using Cerenkov Luminescence and Liquid Scintillation for Preclinical Optical Imaging In Vivo.

PURPOSE: Cerenkov luminescence imaging (CLI) has recently emerged as a molecular imaging modality for radionuclides emitting ß-particles. The aim of this study was to develop a hybrid light imaging (HLI) technique using a liquid scintillator to assist CLI by increasing the optical signal intensity from both ß-particle and γ-ray emitting radionuclides located at deep regions in vivo. PROCEDURES: A commercial optical imaging system was employed to collect all images by HLI and CLI. To investigate the performance characteristics of HLI with a commercially available liquid scintillator (Emulsifier-safe), phantom experiments were conducted for two typical ß-particle and γ-ray emitters, sodium iodide (Na[(131)I]I) and 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG), respectively. To evaluate the feasibility of HLI for in vivo imaging, HLI was applied to a Na[(131)I]I injected nu/nu mouse and an [(18)F]FDG injected Balb-c mouse and compared with CLI alone. RESULTS: Measured HLI wavelength spectra with Emulsifier-safe showed higher signal intensities than for CLI at 500-600 nm. For material preventing light transmission of 12-mm thickness, CLI imaging provided quite low intensity and obscure signals of the source. However, despite degraded spatial resolution, HLI imaging provided sustained visualization of the source shape, with signal intensities 10-14 times higher than for CLI at 10-mm thickness. Furthermore, at 0, 4, and 8-mm material thicknesses, HLI showed a strong correlation between Na[(131)I]I or [(18)F]FDG radioactivity and signal intensity, as for CLI. In vivo studies also demonstrated that HLI could successfully visualize Na[(131)I]I uptake in the mouse thyroid gland in the prone position and [(18)F]FDG accumulation in the heart in the supine position, which were not observed with CLI. CONCLUSION: Our preliminary studies suggest that HLI can provide enhanced imaging of a ß-particle probe emitting together with γ-rays at deep tissue locations. HLI may be a promising imaging technique to assist with preclinical in vivo imaging using CLI.

Iodine-131 imaging using 284 keV photons with a small animal CZT-SPECT system dedicated to low-medium-energy photon detection.

OBJECTIVE: Iodine-131 is widely used for radionuclide therapy because of its ß-particle and for diagnostic imaging employing its principal gamma ray. Since that principal gamma ray has the relatively high energy of 364 keV, small animal single-photon emission computed tomography (SPECT) imaging systems may be required to possess the ability to image such higher energy photons. The aim of this study was to investigate the possibility of imaging I-131 using its 284 keV photons instead of its 364 keV photons in a small animal SPECT imaging system dedicated to the detection of low-medium-energy photons (below 300 keV). METHODS: The imaging system used was a commercially available preclinical SPECT instrument with CZT detectors that was equipped with multi-pinhole collimators and was accompanied by a CT imager. An energy window for I-131 imaging was set to a photopeak of 284 keV with a low abundance compared with 364 keV photons. Small line sources and two mice, one of each of two types, that were injected with NaI-131 were scanned. RESULTS: Although higher counts occurred at the peripheral region of the reconstructed images due to the collimator penetration by the 364 keV photons, the shape of the small line sources could be well visualized. The measured spatial resolution was relatively poor (~1.9 mm for full width at half maximum and ~3.9 mm for full width at tenth maximum). However, a good linear correlation between SPECT values and the level of I-131 radioactivity was observed. Furthermore, the uptake of NaI-131 to the thyroid gland for the two mice was clearly identified in the 3D-SPECT image fused with the X-ray CT image. CONCLUSION: We conclude that the use of an energy window set on the photopeak of 284 keV and the multi-pinhole collimator may permit I-131 imaging for a preclinical CZT-SPECT system that does not have the ability to acquire images using the 364 keV photons.

Optimum energy window setting on Hg-201 x-rays photopeak for effective Tl-201 imaging.

For more effective Tl-201 imaging, the location and width of the energy window set on the Hg-201 x-rays photopeak was investigated using Monte Carlo simulation and phantom experiments. We calculated energy spectra and investigated the amount of primary and scattered photons within various energy windows set on the x-rays photopeak. The energy resolution (ER) at 71 keV (the peak of the x-rays photopeak) was changed to 10%, 12%, 14% and 16%. The relationships between the energy window and the primary counts rate or the scatter fraction (= scattered counts/primary counts, SF) were obtained. By compromise between the primary counts rate and the SF for ER = 12%, the optimum energy window was determined as a wider off-peak window, 77 keV +/- 14.3% (66-88 keV). This off-peak window increased the primary counts rate by 12.5% and decreased the SF by -17% as compared with the conventional on-peak energy window (71 keV +/- 10%, 64-78 keV). When this off-peak widow acquisition was compared with the conventional on-peak window one on a gamma camera, planar and SPECT images using the off-peak widow clearly showed superior results qualitatively and quantitatively.