Role of α- and ß-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease.

The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and ß-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and ß-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease. Video abstract.

Nutrient ileal digestibility evaluation of dried mealworm (Tenebrio molitor) larvae compared to three animal protein by-products in growing pigs.

OBJECTIVE: This study was to investigate the nutrient ileal digestibility of dried mealworm (Tenebrio molitor) larvae and compare with those of three animal protein by-products in growing pigs. METHODS: A total of 12 crossbred ([Landrace×Yorkshire]×Duroc) growing pigs with average body weights of 24.12±0.68 kg were surgically equipped with simple T-cannulas after being deprived of feed for 24 h according to published surgical procedures. These pigs had a recovery period of two weeks. A total of 12 pigs were assigned to individual metabolic crates and allotted to one of four treatments with 3 replicates in a fully randomized design. Dietary treatments included the following: i) Fish meal, corn-vegetable by-product basal diet+9.95% fish meal; ii) Meat meal, corn-vegetable by-product basal diet+9.95% meat meal; iii) Poultry meal, corn-vegetable by-product basal diet+9.95% poultry meal; iv) Tenebrio molitor, corn-vegetable by-product basal diet+9.95% dried Tenebrio molitor larvae. RESULTS: Results showed that the apparent ileal digestibility (AID) of Lys was higher (p<0.05) in pigs fed Tenebrio molitor diet than that in pigs fed fish meal diet. Pigs fed Tenebrio molitor diet showed increased (p<0.05) AID of His and Arg compared to pigs fed Fish meal or Meat meal diet. The AID of Cys was increased (p<0.05) in pigs fed poultry meal and Tenebrio molitor diets compared to that in pigs fish meal diet. Pigs fed meat meal, poultry meal, and Tenebrio molitor diets showed higher (p<0.05) standardized ileal digestibility (SID) of total energy compared to pigs fed fish meal diet. The SID of Arg was higher (p<0.05) in pigs fed Tenebrio molitor diet than that in pigs fed fish meal or meat meal diet. Furthermore, pigs fed poultry meal or Tenebrio molitor diets showed increased (p<0.05) SID of Cys compared to pigs fed fish meal diet. CONCLUSION: In conclusion, providing pigs with diets that contained Tenebrio molitor larvae meal improved AID and SID of nutrients as well as essential and non-essential amino acids. The digestibility of dried mealworm larvae protein and its utilization in vivo are also good. Therefore, dried mealworm larvae protein can be used as protein source at 10% level in growing pigs.

Control of interior surface materials for speech privacy in high-speed train cabins.

The effect of interior materials with various absorption coefficients on speech privacy was investigated in a 1:10 scale model of one high-speed train cabin geometry. The speech transmission index (STI) and privacy distance (rP ) were measured in the train cabin to quantify speech privacy. Measurement cases were selected for the ceiling, sidewall, and front and back walls and were classified as high-, medium- and low-absorption coefficient cases. Interior materials with high absorption coefficients yielded a low rP , and the ceiling had the largest impact on both the STI and rP among the interior elements. Combinations of the three cases were measured, and the maximum reduction in rP by the absorptive surfaces was 2.4 m, which exceeds the space between two rows of chairs in the high-speed train. Additionally, the contribution of the interior elements to speech privacy was analyzed using recorded impulse responses and a multiple regression model for rP using the equivalent absorption area. The analysis confirmed that the ceiling was the most important interior element for improving speech privacy. These results can be used to find the relative decrease in rP in the acoustic design of interior materials to improve speech privacy in train cabins.

An outbreak of lymphomas in a layer chicken flock previously infected with fowlpox virus containing integrated reticuloendotheliosis virus.

Visceral lymphomas occurred in a 236-day-old layer flock previously diagnosed with reticuloendotheliosis virus (REV)-integrated fowlpox virus (FPV) infection at the age of 77 days. Common pathologic lesions were multiple neoplastic nodules of homogeneous lymphocytes in the livers and spleens of all submitted chickens. All neoplastic tissues were positive for the REV envelope (env) gene by PCR. In a retrospective molecular study of FPV-infected 77-day-old chickens from the same flock, we identified nearly full-length REV provirus integrated into the genome of FPV as well as the REV env gene in trachea samples, whereas only the REV LTR region was present in the FPV strain used to vaccinate this flock. The 622-bp REV env gene nucleotide sequence derived from the trachea and neoplastic tissues was identical. Commercial ELISA of serum samples revealed that all chickens aged between 17 and 263 days in this flock were positive for REV but not for avian leukosis virus. Taken together, the evidence suggests that the visceral lymphomas were caused by a REV-integrated FPV field strain. FPV infections of commercial chickens should be followed up by careful monitoring for manifestations of REV infection, including lymphomas and immune depression, considering the ease with which the REV provirus appears to be able to integrate into the FPV genome.

Biotemplated silica and titania nanowires: synthesis, characterization and potential applications.

A simple biotemplating method for the synthesis of silica (SiO2) and titania (TiO2) nanowires was designed on a fibrillar protein (alpha-synuclein) template. The diameter of SiO2 and TiO2 nanowires could be varied, between 20-100 nm, by varying the processing conditions. The nanowires were characterized by energy dispersive spectroscopy (EDS) and electron energy loss spectroscopy (EELS). Due to their high surface area and porosity, the nanowires were tested for potential applications in enzymatic biosensor design.

Improvement of transmittance by fabricating broadband subwavelength anti-reflection structures for polycarbonate.

We report on how to increase transmittance of a 0.2 mm thick polycarbonate (PC) film by periodic subwavelength anti-reflection structures in the visible spectral range. Subwavelength anti-reflection structures like moth-eyes are fabricated into the polycarbonate substrate itself by thermal nano-imprinting lithography (TH-NIL), which uses silicon stamps that have periodic structures such as gratings (lines and spaces) and pillared dots, and are fabricated by laser interference lithography (LIL) and transformer coupled plasma etching. To increase transmittance of a polycarbonate film, we control the periods and shapes of patterns, the number of patterned surfaces, and the overlapping direction of patterns that are fabricated into its surfaces. As a result of this, we show that average transmittance improves as the pattern period gets shorter and as both surfaces of the film are patterned. We also show that the spectrum range gets larger as the pattern period gets shorter and is determined by the longer pattern period in the case of designing a film to have different pattern period on its surfaces. The maximum average transmittance of a polycarbonate film increases up to approximately 6% compared to a bare sample in the 470-800 nm spectral range.

Mandibular stability using sliding or conventional four-hole plates for fixation after bilateral sagittal split ramus osteotomy for mandibular setback.

Our aim was to compare the postoperative stability of the mandible when two different fixation methods had been used after bilateral sagittal split ramus osteotomy (BSSRO) for mandibular setback. The study included 23 patients who had two-jaw BSSRO mandibular setback at the Department of Oromaxillofacial Surgery, Korea University Guro Hospital, between January 2011 and June 2014. The first group (four-hole (control) group, n=13) comprised patients whose bony segments were fixed with conventional four-hole plates, and the second (sliding plate (experimental) group, n=10) included patients whose bone segments were fixed with sliding plates. Lateral cephalograms were taken and analysed at three time points: preoperatively (T1), and one week (T2), and 1year (T3) postoperatively. The Mann-Whitney U test was used to compare the postoperative stability of the mandible in each group. There were no significant differences between the two groups in changes in the horizontal and vertical positions of point B and pogonion postoperatively, nor were there any significant differences between them in ramal inclination and inclination of the SN plane with point B at the given time points (p=>0.05 in surgical changes in the mandible immediately after surgery and 0.397, 0.616, 0.082, 0.951, 0.901, 0.476 in postoperative changes in the mandible 1 week to 1 year after surgery). Like the conventional four-hole plate, the sliding plate can also be used to achieve stability in the fixation of mandibular bone segments after BSSRO.

API5 confers cancer stem cell-like properties through the FGF2-NANOG axis.

Immune selection drives the evolution of tumor cells toward an immune-resistant and cancer stem cell (CSC)-like phenotype. We reported that apoptosis inhibitor-5 (API5) acts as an immune escape factor, which has a significant role in controlling immune resistance to antigen-specific T cells, but its functional association with CSC-like properties remains largely unknown. In this study, we demonstrated for the first time that API5 confers CSC-like properties, including NANOG expression, the frequency of CD44-positive cells and sphere-forming capacity. Critically, these CSC-like properties mediated by API5 are dependent on FGFR1 signaling, which is triggered by E2F1-dependent FGF2 expression. Furthermore, we uncovered the FGF2-NANOG molecular axis as a downstream component of API5 signaling that is conserved in cervical cancer patients. Finally, we found that the blockade of FGFR signaling is an effective strategy to control API5high human cancer. Thus, our findings reveal a crucial role of API5 in linking immune resistance and CSC-like properties, and provide the rationale for its therapeutic application for the treatment of API5+ refractory tumors.

Removal ratio of gaseous toluene and xylene transported from air to root zone via the stem by indoor plants.

This work was designed to investigate the removal efficiency as well as the ratios of toluene and xylene transported from air to root zone via the stem and by direct diffusion from the air into the medium. Indoor plants (Schefflera actinophylla and Ficus benghalensis) were placed in a sealed test chamber. Shoot or root zone were sealed with a Teflon bag, and gaseous toluene and xylene were exposed. Removal efficiency of toluene and total xylene (m, p, o) was 13.3 and 7.0 µg·m(-3)·m(-2) leaf area over a 24-h period in S. actinophylla, and was 13.0 and 7.3 µg·m(-3)·m(-2) leaf area in F. benghalensis. Gaseous toluene and xylene in a chamber were absorbed through leaf and transported via the stem, and finally reached to root zone, and also transported by direct diffusion from the air into the medium. Toluene and xylene transported via the stem was decreased with time after exposure. Xylene transported via the stem was higher than that by direct diffusion from the air into the medium over a 24-h period. The ratios of toluene transported via the stem versus direct diffusion from the air into the medium were 46.3 and 53.7% in S. actinophylla, and 46.9 and 53.1% in F. benghalensis, for an average of 47 and 53% for both species. The ratios of m,p-xylene transported over 3 to 9 h via the stem versus direct diffusion from the air into the medium was 58.5 and 41.5% in S. actinophylla, and 60.7 and 39.3% in F. benghalensis, for an average of 60 and 40% for both species, whereas the ratios of o-xylene transported via the stem versus direct diffusion from the air into the medium were 61 and 39%. Both S. actinophylla and F. benghalensis removed toluene and xylene from the air. The ratios of toluene and xylene transported from air to root zone via the stem were 47 and 60 %, respectively. This result suggests that root zone is a significant contributor to gaseous toluene and xylene removal, and transported via the stem plays an important role in this process.

Clinical impact of tumor volume reduction in rectal cancer following preoperative chemoradiation.

PURPOSE: The purpose of this study was to correlate tumor volumetric analysis obtained using magnetic resonance (MR) imaging with disease-free survival in patients with advanced rectal cancer who underwent preoperative chemoradiotherapy (CRT). PATIENTS AND METHODS: Institutional review board approval was obtained and patient informed consent was waived. This study included 74 patients (47 men, 27 women; mean age, 64 years±10 [SD] years) who underwent preoperative CRT and subsequent rectal surgery between January 2007 and December 2010. Two radiologists who were blinded to the clinical outcome measured tumor volume separately on two sets of MR images obtained before and after CRT. Patients were classified into two groups according to the episode of recurrence and recorded disease-free survival. To assess factors relevant to disease-free survival, univariate and multivariate Cox regression analysis were performed for tumor volume reduction ratio, circumferential resection margin, tumor regression grade, and pathologic staging. RESULTS: Tumor volume reduction ratio (P=0.009), circumferential resection margin (P=0.008) and tumor regression grade (P=0.002) were significantly associated with disease-free survival. At multivariate analysis, tumor volume reduction ratio was the single variable that was associated with disease-free survival (P=0.003). Tumor volume reduction ratio was also a reliable parameter with an excellent interobserver correlation between two readers for pre-CRT volume (ICC=0.939; 95%CI: 0.885-0.979; P<0.001) and post-CRT volume (ICC=0.889; 95%CI: 0.845-0.934; P<0.001). CONCLUSIONS: MR volumetric measurement of rectal cancer helps predict disease-free survival in patients with rectal cancer who underwent preoperative CRT.

Anti-androgen flutamide suppresses hepatocellular carcinoma cell proliferation via the aryl hydrocarbon receptor mediated induction of transforming growth factor-ß1.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and a member of the basic helix-loop-helix PER/ARNT/SIM family of chemosensors and developmental regulators. The AhR is widely known as a mediator of dioxin toxicity; however, it also suppresses cancer cell proliferation and recent findings have implicated its role as a tumor suppressor. We conducted a chemical library screen to identify nontoxic AhR ligands with anti-cancer effects and discovered flutamide (Eulexin) as a putative AhR ligand. Flutamide is an androgen receptor (AR) antagonist approved by the United States Food and Drug Administration for the treatment of prostate cancer. We found that flutamide inhibited the growth of several cancer cell lines independent of AR status, and that suppression of AhR expression reversed the anti-proliferative effects of flutamide. We investigated the AhR-dependent mechanism of action of flutamide in human hepatocellular carcinoma cells and identified that transforming growth factor-ß1 (TGF-ß1) is induced by flutamide in an AhR-dependent manner. In contrast, the potent AhR agonist 2,3,7,8-Tetrachlorodibenzo-p-dioxin had no effect on TGF-ß1 expression, indicating the ligand specificity of AhR activation. We also determined that TGF-ß1 induction is required for the AhR-dependent growth inhibitory effects of flutamide. Therefore, flutamide may be effective in AhR-positive cancers that are sensitive to TGF-ß1 signaling, such as hepatocellular carcinoma.

Mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) variants in American and Japanese populations.

M6P/IGF2R encodes a multifunctional protein involved in lysosomal enzyme trafficking, fetal organogenesis, tumor suppression, and cytotoxic T cell-induced apoptosis. M6P/IGF2R is imprinted and expressed only from the maternally inherited allele in marsupials and rodents. In contrast, humans were initially reported to differ from the imprinted mammalian orders by not having an imprinted M6P/IGF2R; however, some studies now suggest M6P/IGF2R imprinting may be a human polymorphic trait. Mutational and functional evidence are consistent with M6P/IGF2R also being a tumor suppressor in human colon, liver, lung, breast, and ovarian cancers. M6P/IGF2R expression is also pathologically downregulated following mammalian in vitro embryo culture, resulting in fetal overgrowth and "large offspring syndrome." Therefore, the M6P/IGF2R imprint status in humans is an unresolved question that critically impacts upon biological issues ranging from human cancer predisposition to evolution. Attempts to further characterize the imprint status of human M6P/IGF2R and loss of heterozygosity at this locus in cancer have been hindered by a lack of readily usable polymorphisms. To facilitate these genetic analyses, we have screened American and Japanese populations for M6P/IGF2R single nucleotide polymorphisms (SNPs). We have identified nine novel SNPs intragenic to human M6P/IGF2R, and have described experimental conditions for their optimal use. Three identified amino-acid variants in the M6P/IGF2R ligand-binding domains may be under selection in humans.

Radioprotective effect of captopril on the mouse jejunal mucosa.

PURPOSE: Captopril, an inhibitor of angiotensin I converting enzyme, has been shown to modify radiation damage and prevent radiation injury of normal tissue in rats and pigs. The present study was carried out to determine whether captopril would reduce radiation changes in the proximal small bowel in mice. METHODS AND MATERIALS: Mice were subjected to whole body irradiation with 9 Gy or 15 Gy. Captopril was administered in drinking water at a regimen of 62.5 mg/kg/day (captopril group I) and 125 mg/kg/day (captopril group II), continuously from 7 days before irradiation to the end of each designed experiment. The jejunal damage was evaluated microscopically by crypt count per circumference and by histologic damage grading. RESULTS: Crypt number in the sham-irradiated control was 133 +/- 6.8/circumference. In both captopril group I and II, crypt numbers and histologic scores were not significantly different from those in the normal group. The 9 Gy and 15 Gy radiation alone groups showed significantly lower crypt counts and histologic scores compared with the sham-irradiated control group (p < 0.05). The groups exposed to 9 Gy radiation plus captopril I and II showed significantly higher crypt counts and lower histologic damage scores on the third day, and lower histologic damage scores on the fifth day compared with the 9 Gy radiation alone group (p < 0.05). The 15 Gy radiation plus captopril I and II groups had significantly higher crypt counts and lower histologic damage scores on the third day than those of the 15 Gy radiation alone group (p < 0.05). All mice of the 15 Gy radiation group succumbed to intestinal radiation death. CONCLUSION: Our results suggest that captopril provides protection from acute radiation damage to the jejunal mucosa in mice.

Clinical results of 24 pituitary macroadenomas with linac-based stereotactic radiosurgery.

PURPOSE: To determine the impact of stereotactic radiosurgery (SRS) on the clinical course, hormonal status, and follow-up CT/MRI scan of pituitary macroadenomas. METHODS AND MATERIALS: From July 1988 to March 1996, 24 pituitary macroadenomas had been treated using 6 MV linear accelerator based SRS. They consisted of 11 (45.8%) prolactinomas, 2 (8.3%) growth hormone (GH)-secreting tumors, 1 (4.2%) Cushing's disease, 8 (33.3%) nonsecreting (nonfunctioning: NF) tumors, and 2 (8.3%) mixed prolactin-growth hormone (PRL-GH)-secreting tumors (M:F = 12:12; aged 21-61 years). Postoperative irradiation was performed in all cases except for the instance of Cushing's disease. The prescribed dose to tumor center varied from 10 to 27 Gy (mean 21.1 Gy) using a collimator size of 0.5 to 2.5 cm. The follow-up duration ranged from 13 to 89 months (mean 49.2 months). Results from these patients were compared to our results using conventional radiation. RESULTS: Visual acuity and field defect were improved or became normal in 19 (79.2%) cases. Four (16.7%) remained unchanged after the treatment. One (4.1%) progressed 6 years after SRS and subsequently had repeat surgery with conventional boost irradiation. Of the 13 (46.4%) prolactinomas, including two mixed PRL-GH secreting tumors, 11 (84.1%) revealed normal hormonal levels within 1 year after SRS. In contrast, it took 2 years to become normal after conventional radiation therapy. In four GH-secreting tumors including two mixed PRL-GH secreting tumors, SRS and conventional methods showed similar responses. On follow-up imagings of the 21 patients, the mass was completely resolved in 4 (16.7%), including 3 PRLs and one NF, decreased in 11 (45.8%), and unchanged in 5 (16.7%) with central necrosis or cysts. One (4.2%) progressed and was reoperated 6 years after treatment. The complications related to SRS were comparable to those from conventional method. CONCLUSION: Radiosurgery can be used effectively in patients with pituitary adenoma. In this study, a more rapid hormonal and clinical response was achieved with radiosurgery than with conventional pituitary irradiation treatment.

DNA-mediated immunization of glycoprotein 350 of Epstein-Barr virus induces the effective humoral and cellular immune responses against the antigen.

Epstein-Barr virus (EBV) is a human pathogen that is involved in numerous diseases and tumors. Since the EBV infection occurs in the early ages of life, and most of the population is subsequently exposed to EBV, the conventional method of vaccination to induce the prophylactic immunity cannot be considered effective in coping with the virus infection. In this study, we tested whether the injection of a plasmid vector that contained the gene for glycoprotein 350 (gp350), which had been identified as a ligand for virus' adsorption and a target for virus neutralizing antibodies, could induce effective immune responses against the antigen. As a result, the injection of the constructed plasmid vector into mice induced the production of gp350-specific antibodies. A major isotype of the gp350-specific antibodies was IgG1. The antibodies efficiently mediated the antibody-dependent cellular cytotoxicity against the cells expressing the gp350 antigen. In addition, the injection of the constructed plasmid vector stimulated the precursor T cell population that was specific to the gp350 antigen. In addition, gp350-specific cytotoxic T lymphocytes were efficiently stimulated by the injection of the constructed plasmid vector. These results suggested that the injection of the plasmid vector, containing the gp350 gene of Epstein-Barr virus, could be one of the most effective ways to induce both prophylactic and therapeutic vaccinations against the virus infection.

Cloning and analysis of the Epstein-Barr virus glycoprotein 350 genes.

Membrane glycoprotein 350 (gp350) of the Epstein-Barr virus (EBV) is considered as a major target for vaccine development, since the gp350 has been identified as the virus' mediator for receptor interaction and as an inducer of specific in vitro virus-neutralizing antibodies. In an initial attempt to develop an effective DNA vaccine against an EBV infection, gp350 genes were isolated from SNU-20 and SNU-1103 which are the EBV-infected lymphoblastoid cell lines established in Korea. In addition, the nucleotide sequences of the gp350 genes were determined and compared with those of other EBV strains such as B95-8, P3HR-1/AG876 and M81. Sequence analysis showed that similar high degrees of homology between 2 EBV strains derived from African Burkitt's lymphoma, P3HR-1 and AG876, was shown between the gp350 genes isolated from 2 EBV-infected lymphoblastoid cell lines established in Korea. Furthermore, these 2 Korean and 2 African strains displayed nearly identical patterns of sequence variations from B95-8. In addition, the sequence of the isolated gp350 genes, which have been reported to be associated with the biology of EBV infection, is analyzed.

Fluoroscopy-aided thoracoscopic resection of pulmonary nodule localized with contrast media.

BACKGROUND: The pulmonary nodules have become the major indication of video-assisted thoracic surgery (VATS). Recently, several preoperative or intraoperative techniques for identifying small or deeply seated pulmonary nodules have facilitated thoracoscopic resection. We describe the new technique for detecting difficult lesions. METHODS: Preoperatively, we marked the visceral pleura near the pulmonary nodules with dye, simultaneously injected contrast media (1 water-soluble Optiray [Mallinckrodt Medical Inc, Quebec, Canada], 18 barium sulfate, 11 Lipiodol [Laboratoire Guerbet, Aulnay-sous-Bois, France]) into or around the nodule under computed tomography (CT) guidance. During VATS, we were able to easily and accurately detect and resect all the nodules localized with contrast media, of which the radiopacity was visualized on the portable fluoroscopic monitor. RESULTS: Between February 1996 and December 1998, we thoracoscopically resected 30 nodules in 28 patients (13 were women; age, 53 +/- 14 years). The resected nodules were 17 +/- 7.6 mm (range; 4 to 32 mm) in size, and 8.9 +/- 8 mm (range, 2 to 34 mm) in depth. The pathologic diagnosis of the nodules was benign in 20 and malignant in 10 (six primary cancers of lung and four metastatic cancers). There were only minor complications related CT localization. CONCLUSIONS: This new technique can help the surgeons detect and resect the difficult lesions with safety and rapidity by VATS without thoracotomy.

Long-term use of preservatives on rat nasal respiratory mucosa: effects of benzalkonium chloride and potassium sorbate.

OBJECTIVES: The preservatives benzalkonium chloride (BZC) and potassium sorbate (PS) are widely used, not only for nasal drops, but also for eyedrops and cosmetics. However, there have been many case reports that consider lesions such as dermatitis or conjunctivitis to be the results of irritation induced by BZC or PS. METHODS: We evaluated the histological changes after the long-term administration of BZC or PS on rat nasal respiratory mucosa. Forty rats were used for the BZC group and 40 rats for PS group. Animals in each group were divided into four subgroups The first subgroup received a low-concentration preservative solution that was commonly used for nasal sprays. The second subgroup received a high-concentration preservative solution that was reported to induce dermatitis in humans. The third and fourth subgroups received a steroid mixed preservative solution of low and high concentrations, respectively. The control group was administrated normal saline. After each group received 1, 2, and 4 weeks of topical administration, the symptomatic and histological changes on H&E stain were observed. RESULTS: Sneezing and nasal rubbing with forelegs were observed in almost all subgroups by the seventh day of treatment. The preservatives induced nasal lesions, including intraepithelial glandular formation, inflammatory cell infiltration, vascular hyperplasia, and edematous change. The symptomatic and histological changes were pronounced with the prolonged duration of administration. Similar results were observed in the steroid mixed-solution groups. In the PS steroid mixed-solution group, however, symptoms and nasal lesions were reduced with the prolonged duration of administration. CONCLUSION: It is our finding that even a low-concentration solution of preservative can lead to nasal lesion. Hence there is a strong need to develop both a preservative that can be safely and widely used and a nasal spray without preservatives.

Ultrasound attenuation estimation using the LMSE filters and the median filter.

The ultrasound attenuation coefficient in known to increase with frequency in soft biological tissue within the diagnostic frequency range. The frequency dependent attenuation coefficient is an important parameter in clinical tissue characterization, especially in liver, and in ultrasonic quantitative B-scan imaging. But, because of the random spatial variation in the backscattered signal amplitude, the estimator variance becomes very large, making it difficult to estimate the attenuation slope from the backscattered ultrasound signal. In this paper we suggest a new ultrasound attenuation estimator based on the calibrated log spectral difference. The proposed estimation process consists of Wiener filtering, Kalman filtering, and median filtering in this order. The simulation results and experimental results with tissue equivalent (TE) phantoms show that combination of the above filterings yields a considerably reduced estimator variance compared with the conventional estimators.

Administration of multiple cytokine genes with anti-tumor activity inhibits both tumor incidence and tumor growth.

The finding of reporter gene expression in muscle cells after intramuscular injection of a reporter gene containing DNA has suggested that injection of a certain gene in its naked form could induce an expression of the injected gene. The result proposed the concept, namely DNA or genetic vaccine technology, that injection of an antigen gene could induce a specific immune response against the antigen. Although the concept was initially applied to vaccination technology, the result also means that administration of cytokine genes with anti-tumor activity could exert their functions when they are applied as a naked form of DNA. To test the possibility, plasmid vector containing granulocyte macrophage-colony stimulation factor (GM-CSF) and interleukin-12 (IL-12) genes, which are known as one of the most potent anti-tumor cytokines, were constructed and injected into mice together with syngeneic tumor cells. When the cytokine gene containing plasmid was injected on the same day of tumor cell injection, a tumor mass developed in 4 out of 5 mice tested. Even among the 4 mice, the tumor mass of a mouse disappeared 2 weeks after tumor development. In addition, tumor generation was significantly delayed in cytokine gene injected mice and the average tumor size was about 51.5% that of vector control injected mice. These results suggested that tumor treatment through the injection of multiple cytokine genes with potent anti-tumor activity significantly inhibits tumor development and growth, and that the method could be considered as one of the tools for efficient tumor treatment.