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The aim of this study was to validate our laparoscopic management strategy for asymptomatic and symptomatic patients with prenatally diagnosed choledochal cysts (CCs).Thirteen prenatally diagnosed CC patients from 1997 to 2015 were included. Seven patients (1997-2008) underwent open surgery (OS group), and 6 (2009-2015) underwent laparoscopic surgery (LS group). In the asymptomatic patients, LS was performed when the patients weighed over 5 kg. When the patient had clinical manifestations, early LS was performed irrespective of body weight. A retrospective comparison was conducted between the LS and OS groups in terms of the operative time, blood loss, postoperative fasting period, hospital stay, and intra- and postoperative complications.There was no difference between the demographics of both groups. The operative time was significantly longer (380 vs. 288 min) and blood loss was significantly lower (4 vs. 30 mL) in the LS group. Additionally, the postoperative fasting period (3 vs. 6 days) and hospital stay (11 vs. 20 days) were significantly shorter in the LS group. Intraoperative events and early postoperative complications were not encountered in either group. Small bowel obstruction requiring surgery occurred in two patients, 10 and 13 years after OS, respectively.LS is as safe and feasible as OS in small children with prenatally diagnosed CC, although sufficient pediatric laparoscopic expertise is mandatory.

No previous reports have observed inside the root canal using both optical coherence tomography (OCT) and x-ray microcomputed tomography (μCT) for the same sample. The purpose of this study was to clarify both OCT and μCT image properties from observations of the same root canal after resin core build-up treatment. As OCT allows real-time observation of samples, gap formation may be able to be shown in real time. A dual-cure, one-step, self-etch adhesive system bonding agent, and dual-cure resin composite core material were used in root canals in accordance with instructions from the manufacturer. The resulting OCT images were superior for identifying gap formation at the interface, while μCT images were better to grasp the tooth form. Continuous tomographic images from real-time OCT observation allowed successful construction of a video of the resin core build-up procedure. After 10 to 12 s of light curing, a gap with a clear new signal occurred at the root-core material interface, proceeding from the coronal side (6 mm from the cemento-enamel junction) to the apical side of the root.

Pregnant rats were given 1,3-di-o-tolylguanidine (DTG) by gavage at 0, 10, 20 or 40 mg/kg bw/day on days 6-19 of pregnancy and the pregnancy outcome was determined on day 20 of pregnancy. At 40 mg/kg bw/day, deaths were observed in four out of 24 females. The incidences of females showing mydriasis at 20 and 40 mg/kg bw/day and showing decreased locomotor activity at 40 mg/kg bw/day were significantly increased. Alopecia, bradypnea, prone position and tremor were also observed at mg/kg bw/day. The maternal body weight gain at 20 and 40 mg/kg bw/day and food consumption at 40 mg/kg bw/day were significantly reduced. A significantly decreased weight of the gravid uterus, increased incidence of postimplantation loss, decreased number of live fetuses, and lowered weights of fetuses and placentae were found at 40 mg/kg bw/day. The incidences of the total number of fetuses with external malformations at 40 mg/kg bw/day and with skeletal malformations at 20 and 40 mg/kg bw/day were significantly increased. Significantly higher incidences of fetuses with brachydactyly and short tail and defects of caudal vertebrae, phalanges and metacarpals were observed at 40 mg/kg bw/day. Delayed ossification was also noted at 40 mg/kg bw/day. The data indicate that DTG is teratogenic at maternal toxic doses and the NOAELs of DTG for maternal and developmental toxicity are 10 mg/kg bw/day in rats.

The neutralization efficacy of bovine colostral antibody against verotoxin (VT) 1 and 2 was investigated. Cows were immunized with VT1 or VT2 fourteen times at 7-day intervals. A colostral antibody exhibiting high titers was obtained from immunized cows. Survival rates were evaluated in mice administered VT1 or VT2, and those infected with Escherichia coli (E. coli) O157:H7 producing VT1 or VT2. Survival rates after VT1 administration were 100% in the single-administration group, 90% in the repeat-administration group, and 78.6% in the control group. Survival rates after VT2 were 75.0% in the single-administration group, and 100% in the repeat-administration group. All mice in the control group died. Colostral antibody and fosfomycin (FOM) in the colostral antibody group and FOM and skim milk in the control group were administered three times per day for 5 days to mice infected with E. coli O157:H7 producing VT1 or VT2. Survival rates after inoculation with E. coli O157:H7 producing VT1 were 80.0% in the colostral antibody group, and 63.6% in the control group. Survival rates after inoculation with E. coli O157:H7 producing VT2 were 83.3% in the colostral antibody group, and 20.0% in the control group. The survival rate in mice without treatment following inoculation with E. coli O157:H7 producing VT2 was 88.2%. The survival rates in mice infected with E. coli O157:H7 strains producing VT1 or VT2 improved after administration of this colostral antibody, which exhibited neutralization efficacy against VT.

The objective of this study was to evaluate the developmental toxicity of 1-butanol in rats. Pregnant rats were given drinking water containing 1-butanol at 0.2%, 1.0% or 5.0% (316, 1454 or 5654 mg/kg/day) on days 0-20 of pregnancy. A significant decrease in maternal body weight gain accompanied by reduced food and water consumption was found at 5.0%. No significant increase in the incidence of pre- and postimplantation embryonic loss was observed in any groups treated with 1-butanol. Fetal weight was significantly lowered at 5.0%. Although a significant increase in the incidence of fetuses with skeletal variations and decreased degree of ossification was found at 5.0%, no increase in the incidence of fetuses with external, skeletal and internal abnormalities was detected in any groups treated with 1-butanol. The data demonstrate that 1-butanol is developmental toxic only at maternal toxic doses. No evidence for teratogenicity of 1-butanol was noted in rats. Based on the significant decreases in maternal body weight gain and fetal weight, it is concluded that the no observed adverse effect levels (NOAELs) of 1-butanol for both dams and fetuses are 1.0% (1454 mg/kg/day) in rats.

Objective: The aim of the present study is to examine the outcome of middle ear surgery in terms of hearing functions, graft take rate, complications, prognoses, and safety of same day middle ear surgery with 3-day admission.Design: Prospective cohort study in consecutive middle ear surgery patients.Setting: University-affiliated municipal oto-rhino-laryngological surgi-center.Methods: We prospectively analyzed the surgical outcome of 209 consecutive cases of middle ear surgery (176 patients) with regard to postoperative hearing functions, graft take rate, complications including infections, prognoses, and safety.Results: There were 198 tympanoplasties (Type I: 131, Type III: 46, Type IV: 10, and Type 0: 11) and 11 other operations. In the 198 tympanoplasties, the rate of reperforation of the eardrum was 4.5% in Type I, 2.2% in Type III, and 0% in Type IV and Type 0 tympanoplasties. There were two occurrences of post-operative ear infection in chronic otitis media (tympanoplasty I), and the infection rate for all middle ear procedures was 1.0%. Analysis of the results revealed that hearing functions and graft take rates of tympanoplasties, and the incidence of complications were comparable to the results of previous studies in outpatient settings.Conclusions: This study provided an appropriate characterization of the outcomes of middle ear surgery, and this information will be useful in the areas of informed consent, patient counseling, surgical treatment decisions, and cost analysis. This study confirms the safety of same-day middle ear surgery during 3-day admission even in Type III and Type IV tympanoplasty with mastoid obliteration.

Metal parts in a target object sometimes cause metal artifacts and beam hardening effects in an x-ray tomographic image. In this paper, we proposed a new method to extract a region of metals by finding a change of an energy spectrum in the projection data measured with an energy discriminating photon counting detector. The change in the energy spectrum was calculated using two parameters; RAI (relative attenuation index) and SDI (spectrum deformation index), that were defined to the projection data measured with different energy windows. And a scatter plot (SDI vs. RAI) was used for the extraction of pixels including metals in the projection data. The feasibility of our method was evaluated with Monte Carlo simulations with a numerical phantom and experiments with two human teeth phantoms. The results of the simulations and experiments showed that pixels including metals and those without metals were separated from each other, making it possible to easily separate regions including metals in the projection data. The accuracy of extracting metal parts depended on its atomic number, however, pixels including metals with a large atomic number such as copper and silver could be easily separated.

Hydroquinone (HQ) is used in skin bleaching agents, hair dyes, and finger nail treatments. Many skin-lightening cosmetics that contain HQ are currently marketed in Japan. Concerns have been expressed regarding health risks to the general population because the carcinogenicity of HQ was previously suggested in animal studies. HQ induced hepatocellular adenomas and forestomach hyperplasias in mice and renal tubular cell adenomas in male rats. In the present study, the lacZ transgenic mutation assay was conducted according to OECD test guideline 488 to determine whether mutagenic mechanisms were involved in HQ-induced carcinogenesis. Male Muta™ mice were repeatedly administered HQ orally at dosages of 0, 25, 50, 100, or 200mg/kg bw/day for 28 days. Body weight gain was decreased in all treatment groups. No significant differences were observed in mutant frequencies in the liver, stomach, lung, or kidney between HQ-treated mice and the concurrent negative controls, whereas the significant induction of mutations was noted in the positive control, N-ethyl-N-nitrosourea. These results suggest that a mutagenic mechanism is not responsible for HQ-induced carcinogenesis.

Objective: A blunt costophrenic (CP) angle in chest radiographs is known as a sign of pleural effusion, but is also observed in pulmonary emphysema. However, healthy young adult subjects with a blunt CP angle were often encountered in company annual medical examinations. The goal of the study was to evaluate radiographic measurements, spirometry, and cough symptoms in such subjects with a stable blunt CP angle obtained in a company medical check to clarify the underlining condition. Methods: Radiographic measurements were made for the diameter of the main bronchus (MB), the tracheal width (TR), and the lung area (LA) estimated from the product of the height of the right lung and internal chest diameter in posteroanterior chest radiographs. The MB/LA and TR/LA ratios were calculated as markers of dysanapsis. An interview was performed to obtain information on cough symptoms. Results: The MB/LA and TR/LA ratios were both significantly lower in subjects with a blunt CP angle than in controls without blunt CP angles. Spirometry in the subjects with blunt CP angles indicated that 57.2% of parameters, including FEF25-75%, FEF75%, FEF50%, PEF, and FEV1/FVC, were subnormal and 84.1% of the subjects had a concave maximal expiratory flow-volume curve. These spirometric findings suggest the presence of airflow limitation involving the small airways. In correlation analyses, the MB/LA ratio was significantly associated with FEF25-75%/FVC, PEF, and FEF50%; and the TR/LA ratio was positively correlated with FEF25-75%/FVC and FEF50%. In interviews, 62% of subjects with a blunt CP angles stated that they had experienced cough symptoms in recent years or in the past. Conclusion: A stable blunt CP angle is associated with dysanapsis and airflow limitation. These changes may explain the high rate of cough among subjects with a stable blunt CP angle.

A sensitive enzyme linked immunosorbent assay (ELISA) using horseradish peroxidase as a label enzyme and a simple dip-strip test using this ELISA which enable the monitoring of bacitracin (BC) in chicken plasma are described. The anti-BC antiserum which was raised against the antigenic BC-bovine gamma globulin conjugate in rabbit possessed an excellent specificity for BC, exhibiting no cross-reactivity with other antibiotics used as animal feed additives and veterinary drugs. The detection limit of BC by the ELISA was estimated to be 0.1 μg l−1 (equivalent to 1 ng of BC per 1 ml of chicken plasma). The recoveries of BC from chicken plasma ranged from 97% to 103%. The dip-strip using an anti-BC IgG dotted nitrocellulose membrane was prepared and a simple and rapid test for monitoring BC in chicken plasma was developed. Using this test, 50 ng of BC in 1 ml of plasma could be distinguished from that of control (blank) plasma.

Perfluoroalkyl carboxylic acids (PFCAs) are a series of environmental contaminants that have received attention because of their possible adverse effects on wildlife and human health. Although many toxicological studies have been performed on perfluorooctanoic acid with carbon chain length C8, available toxicity data on PFCAs with longer chains are still insufficient to evaluate their hazard. A combined repeated dose and reproductive/developmental toxicity screening study for perfluorododecanoic acid (PFDoA; C12) was conducted in accordance with OECD guideline 422 to fill these toxicity data gaps. PFDoA was administered by gavage to male and female rats at 0.1, 0.5, or 2.5 mg/kg/day. The administration of PFDoA at 0.5 and 2.5 mg/kg/day for 42-47 days mainly affected the liver, in which hypertrophy, necrosis, and inflammatory cholestasis were noted. Body weight gain was markedly inhibited in the 2.5 mg/kg/day group, and a decrease in hematopoiesis in the bone marrow and atrophic changes in the spleen, thymus, and adrenal gland were also observed. Regarding reproductive/developmental toxicity, various histopathological changes, including decreased spermatid and spermatozoa counts, were observed in the male reproductive organs, while continuous diestrous was observed in the females of the 2.5 mg/kg/day group. Seven of twelve females receiving 2.5 mg/kg/day died during late pregnancy while four other females in this group did not deliver live pups. No reproductive or developmental parameters changed at 0.1 or 0.5 mg/kg/day. Based on these results, the NOAELs of PFDoA were concluded to be 0.1 mg/kg/day for repeated dose toxicity and 0.5 mg/kg/day for reproductive/developmental toxicity.

The development of a pixilated semiconductor detector such as CdTe or CdZnTe, which is available for x-ray imaging, has been pursued by many researchers. In the case of x-ray imaging, the photon flux is very high, and thus conventional CT systems adopt energy integration detectors. On the other hand, the reduction of patient dose becomes one of the major issues in state-of-art CT systems. Thus, detectors require high sensitivity and signal to noise ratio in low flux, and we developed a new CdTe semiconductor detector with a dedicated application-specific integration circuits (ASICs) for a photon counting mode. In this paper, we compared our detector with a conventional energy integration detector by evaluating CT images reconstructed with the projection data that were acquired by each detector. Especially, we evaluated these detectors in terms of the effects on the CT images in the very low x-ray flux. The results showed that no significant differences on CT images between the two detectors were observed except for streak artifacts in the images with the energy integration detector. Our previous research confirmed that the signal to noise ratio of our detector was slightly better than that of the energy integration detector in the very low flux. The results showed that a high signal to noise ratio contributed to the reduction of artifacts in CT images with very low x-ray flux.

The development of photon counting detectors enables us to decompose materials in x-ray CT images. The photon counting detection can measure a linear attenuation coefficient of a given energy range, thereby contributing to the material decomposition or identification. In this detection, measured photon counts were affected by statistical noise, making it difficult to obtain accurate measurements of material concentration. To calculate this concentration ratio the principal component analysis is sometimes used, although the results are much affected by the noise included in the measured data. In this paper we evaluate the performance of the singular value decomposition (SVD) method for the purpose of material decomposition using the numerical simulation phantom and Monte Carlo simulation. The materials used were water, calcium, Au-colloid, and gadolinium solution. The results of simulations showed that the accuracy strongly depended on the setting of energy windows and the energy resolution of the detector.

The purpose of our research is to measure the amount of contrast agents used in x-ray CT accurately. The use of contrast agents such as gold nano-particles enables molecular imaging with the x-ray CT system. To realize an energy discriminating measurement, we have developed a photon counting detector with a CdTe semiconductor that is able to measure x-rays with the count rate of 107 cps/mm2 with four energy windows. In order to measure the concentration ratio of the contrast agent, we used a k-edge imaging technique. The materials used in this experiment were Au-colloid, Pt-colloid and gadolinium solution. The results of experiments showed linearity between the linear attenuation coefficients of k-edge images that were calculated using the two energy bins near each k-edge, and the concentration ratios of the contrast agents. For Au-colloid, the measurement error was less than 4 %, while for the gadolinium agent, the accuracy depended on the window width. This was caused by the electrical noise in the lower energy window and the beam-hardening effect in the measured data.

To provide speech prostheses for individuals with severe communication impairments, we investigated a classification method for brain computer interfaces (BCIs) using silent speech. Event-related potentials (ERPs) obtained when four subjects imagined the vocalization of Japanese vowels, /a/, /i/, /u/, /e/, and /o/ in order and in random order while the subjects remained silent and immobilized were recorded using 111 scalp electrodes and 3 reference electrodes. Regarding detection of the imagined voice, some problems occurred by which the related brain geometries and suitable electrodes for classifications differed between subjects. To overcome these problems, we used an adaptive collection that divided ERP data into small elements, performed evaluation relative to the elements, and selected better elements for classification. In earlier reports of studies using the common spatial patterns (CSPs) filter and support vector machines (SVMs), the classification accuracies (CAs) were 56-72% for the pairwise classification /a/ vs. /u/ in the case of 63 channel EEG measurement. In this study, the CA was improved to 73-92% using the adaptive collection. According to the CA, 19 channel measurements were worse than 111 channel measurements, but 63 channel measurements were slightly worse that 111 channel measurements. Using 63 channel measurements, 73% of CA was achieved for all pairwise combinations of the five vowels. The average of the CAs was 85%. These results show that the proposed method exhibited great potential for use in classification of imagined voice for a speech prosthesis controller.

Phthalate esters are widely used as plasticizers in polyvinyl chloride products. Because of human health concerns, regulatory authorities in Japan, US, Europe and other countries control the use of di(2-ethylhexyl) phthalate, diisononyl phthalate, di-n-butyl phthalate, butylbenzyl phthalate, diisodecyl phthalate and di-n-octyl phthalate for the toys that can be put directly in infants' mouths. While these regulatory actions will likely reduce the usage of phthalate esters, there is concern that other plasticizers that have not been sufficiently evaluated for safety will be used more frequently. We therefore collected and evaluated the toxicological information on di(2-ethylhexyl) terephthalate (DEHT), 1,2-cyclohexanedicarboxylic acid, diisononyl ester (DINCH), diisononyl adipate (DINA), 2,2,4-trimetyl-1,3-pentanediol diisobutyrate (TXIB), tri-n-butyl citrate (TBC) and acetyl tri-n-butyl citrate (ATBC) which were detected at a relatively high frequency in toys. The collected data have shown that chronic exposure to DEHT affects the eye and nasal turbinate, and DINCH exerts effects on the thyroid and kidney in rats. DINA and TXIB have been reported to have hepatic and renal effects in dogs or rats, and ATBC slightly affected the liver in rats. The NOAELs for repeated dose toxicity are relatively low for DINCH (40 mg/kg bw/day) and TXIB (30 mg/kg bw/day) compared with DEHT, DINA and ATBC. DEHT, TXIB and ATBC have been reported to have reproductive/developmental effects at relatively high doses in rats. For DINA and TBC, available data are insufficient for assessing the hazards, and therefore, adequate toxicity studies should be conducted. In the present review, the toxicity information on 6 alternatives to phthalate plasticizers is summarized, focusing on the effects after oral exposure, which is the route of most concern.

Crl:CD(SD)rats were given 3-cyanopyridine by gavage at 0, 5, 30 or 180 mg/kg/day. Males were dosed for 42 days beginning 14 days before mating, and females for 40–53 days beginning 14 days before mating to day 3 of lactation, including throughout the mating and gestation periods. General toxicity, mainly liver damage, was observed in males at ≥30 mg/kg/day and in females at ≥5 mg/kg/day. Sertoli cell vacuolation was observed at 180 mg/kg/day, and spermatocyte damages were observed at ≥30 mg/kg/day. Effects on estrous cycles, corpora lutea and implantations, and unsuccessfully mated females, despite additional mating, were observed at 180 mg/kg/day. Delayed initiation of delivery, dystocia, and deaths or moribundities of pregnant females were observed at 180 mg/kg/day, and only two pregnant rats delivered live pups at that dose. The NOAEL for reproductive/developmental toxicity was concluded to be 30 mg/kg/day.

This study reports on brain activity induced by picture-based personality tests. Near-infrared spectroscopy is a newly developed, noninvasive technology in neuroimaging that can measure brain activity through blood volume changes. We measure the prefrontal cortex (Brodmann Area 10 [BA10]) activities of adolescents during the Rorschach (1921), the Rosenzweig Picture-Frustration Study (PFS; Hayashi, 1964), and Thematic Apperception Test (TAT; Murray, 1943). BA10 showed that the PFS was left-hemisphere dominant and significantly different from the Rorschach and TAT, which showed a tendency to be right-hemisphere dominant. We believe that this tendency reflects emotion and sociality.

A chemical category is a group of chemicals whose toxicological properties are expected to be similar or follow a regular pattern as a result of structural similarity. The category approach is beneficial for decreasing in the resource of risk assessment for huge amount of unevaluated existing chemicals, and also in the use of all kinds of animal tests including even in vivo genotoxicity tests from a point of view of the animal welfare. The present paper reports the results of in vivo micronucleus tests of o-sec-butylphenol (CAS:89-72-5) and 2-isopropyl-5-methylphenol (CAS:89-83-8) and discusses genotoxic potential of seven alkylphenols, o-sec-butylphenol, 2-isopropyl-5-methylphenol, p-sec-butylphenol (CAS:99-71-8), 2-tert-butylphenol (CAS:88-18-6), 2, 4-di-tert-butylphenol (CAS:96-76-4), 4-tert-butylphenol (CAS:98-54-4) and 6-tert-butyl-m-cresole (CAS:88-60-8) by the category approach. Based on the negative results of in vivo micronucleus tests, it can be concluded that these category chemicals are not likely clastogenic in vivo. Further in vivo micronucleus assays on untested substances may not be required by using the category approach, but further supporting information such as physicochemical profiles and (Q) SAR predictions may be necessary to strengthen the rationale for the category approach.

Although the relative risk of lung cancer due to smoking is reported to be lower in Japan than in other countries, few studies have examined the characteristics of Japanese cigarettes or potential differences in smoking patterns among Japanese smokers.To examine tar, nicotine and carbon monoxide (TNCO) emissions from ten leading cigarettes in Japan, machine smoking tests were conducted using the International Organization for Standardization (ISO) protocol and the Health Canada Intense (HCI) protocol. Smoking topography and tobacco-related biomarkers were collected from 101 Japanese smokers to examine measures of exposure.The findings indicate considerable variability in the smoking behavior of Japanese smokers. On average, puffing behaviors observed among smokers were more similar to the parameters of the HCI protocol, and brands with greater ventilation that yielded lower machine values using the ISO protocol were smoked more intensely than brands with lower levels of ventilation. The smokers of "ultra-low/low" nicotine-yield cigarettes smoked 2.7-fold more intensively than those of "medium/high" nicotine-yield cigarette smokers to achieve the same level of salivary cotinine (p = 0.024). CO levels in expiratory breath samples were associated with puff volume and self-reported smoking intensity, but not with nominal values of nicotine-yield reported on cigarette packages.Japanese smokers engaged in "compensatory smoking" to achieve their desired nicotine intake, and levels of exposure were greater than those suggested by the nominal value of nicotine and tar yields reported on cigarette packages.

Dinoseb (2-sec-butyl-4,6-dinitrophenol; CAS No. 88-85-7), a dark reddish-brown solid or dark orange viscous liquid, depending on the temperature (melting point: 32-42 °C) (Kidd & James, 1991), was approved for sale in the US in 1948 as a nitrophenolic herbicide in soybeans, vegetables, fruits, nuts, citrus and other field crops for the selective control of grass and broadleaf weeds (EXTOXNET, 1996; Schneider, 1986). Dinoseb is also used as an insecticide for grapes and as a seed crop drying agent (EXTOXNET, 1996). Dinoseb is one of the chemicals available on the market on the basis of safety tests conducted by Industrial Bio-Test Laboratory, a concern later found to have submitted many flawed and even fraudulent reports on its procedures and results (Shabecoff, 1986). Subsequently, several studies showed that dinoseb has the potential to produce developmental toxicity including teratogenicity in rats, mice and rabbits (Giavini et al., 1986; Johnson, 1988; Preache & Gibson, 1975a; Preache & Gibson, 1975b). Dinoseb as a pesticide was banned in the US in 1986 and the EU in 1991 owing to the potential risk of adverse health effects in humans (EXTOXNET, 1996; Rotterdam Convention, 2006), but dinoseb and its salts are still widely used as other agricultural products (PAN, 2006). Dinoseb as a pesticide is also banned in Japan, but its import is permitted (PAN, 2006). The volumes of dinoseb imported into Japan were estimated to be 615 tons in fiscal year 2008 and 726 tons in fiscal year 2009 (NITE, 2009). Dinoseb is a highvolume chemical with production or importation exceeding 1,000 tons per year in Organisation for Economic Co-operation and Development (OECD) member countries (OECD, 2004). Dinoseb is well absorbed from the gastrointestinal tract by the oral route and can pass through the placenta into the fetus in mice (Gibson & Rao, 1973). A dermal study showed that in six hours young and adult female rats absorbed about 44% of the dose, while at 120 hours 75.9% was absorbed in young and 92.5% in adults (Hall et al., 1992). Dinoseb shows relatively strong acute toxicity with an oral LD50 of 5-50 mg/kg in female rats (MHLW, 2005), an intraperitoneal LD50 of 14.1-22.5 mg/kg in mice (US EPA, 2003b) and a dermal LD50 of 40 mg/kg in rabbits (US EPA, 2003b). Inhalation LC50 is 33-290 mg/m3 for 4-hour exposure in rats (US EPA, 2003b). The basic mechanism of toxicity is thought to be

A bovine colostral antibody against verotoxin (VT) 2 of Escherichia coli O157:H7 was administered orally to beagle dogs. The antibody remained in the dogs’ small intestine for at least 2 h, whereas little serum antibody remained 1.5 h after administration. Furthermore, the antibody activity of secretory IgA did not change until 2 h after administration; however, the activity of IgG and IgM antibodies decreased by approximately 60% and 40% at 2 h after administration, respectively. Seven beagle dogs inoculated with Escherichia coli O157:H7 producing VT2 were administered bovine colostral antibody or bovine colostral whey without antibody. With administration of bovine colostral whey without antibody, the amount of VT2 in feces decreased gradually after administration and increased again at 5 d after inoculation, whereas bovine colostral antibody significantly reduced the amount of VT2 in feces on the day after administration. In addition, 9 beagle dogs were given bovine colostral antibody, bovine plasma antibody, or saline. The amount of VT2 in feces again decreased significantly more rapidly after administration of bovine colostral antibody than after administration of bovine plasma antibody or saline.

Total laryngopharyngectomy is common in the treatment for most of hypopharyngeal cancer. Reconstructive surgery was performed byusing of a pedicled pectoralis major myocutaneous flap to the two male patients in our hospital. Additional operation of making a tracheoesophageal shunt was performed at the same time for the purpose of voice restora tion. Both of the two patients speak well in comparatively short period after the operation. It is well known that acquirement of esophageal voice after total laryngopharyngectomy is very difficult. Therefore, it is very significant to perform laryngopharyngectomy and reconstructive surgery for voice restoration at the same time.

Meningioma is a common tumor of the central nervous system, accounting for 13-18% of all intracranial tumors. Extracranial meningiomas, especially with extension into the temporal bone, are very rare.A 56-year-old female complained of left hearing loss for 15 years. Her physical examination revealed a cholesteatoma-like mass which was seen through the tympanic membrane, and a pure tone audiogram showed left combined hearing loss. At the time of operation, a white mass was seen in the mastoid cavity and the tympanic cavity. Postoperative pathological study revealed it to be a meningioma. After the operation, CT and MRI scans showed a large mass in the middle and posterior fossas. We conclude that CT and MRI examinations are valuable when there is a possibility of tumor.

2-(3',5'-Di-tert-butyl-2'-hydroxyphenyl)-5-chlorobenzotriazole (DBHCB) is widely used as an ultraviolet (UV) absorber. In this study, the repeated dose and reproductive toxicity of DBHCB was evaluated in rats. Crj:CD(SD)IGS rats were given DBHCB by gavage at 0, 2.5, 25, or 250 mg/kg/d. Male and female rats were dosed beginning 28 d before mating, and each female rat was mated with a male rat of the same dosage group. Males were dosed for a total of 56-57 d, and females were dosed for a total of 55-69 d up to Day 3 of lactation throughout the mating and pregnancy periods. Ten males from each group were killed on the next day of the last administration, and 10 females were killed on Days 4-6 after parturition. Five rats/sex treated at 0 and 250 mg/kg/d for 56 d were then kept without treatment for 14 d (recovery period). No deaths were found in any group. No effects of DBHCB on general condition, body weight, food consumption, or reproductive/developmental parameters were observed. Significant increases in serum albumin and an albumin/globulin ratio at 25 mg/kg/d and higher and alkaline phosphatase levels at 250 mg/kg/d were noted in males. The absolute and relative weights of the liver were significantly increased in males at 25 mg/kg/d and higher. Significantly increased serum albumin and absolute and relative liver weight were also found in males at 250 mg/kg/d after the recovery period. No changes in these parameters were observed in females of any DBHCB-treated groups. No significant changes in organ histopathology were found in males or females. These findings indicated a sex difference in the toxicity of DBHCB in rats.

The present review paper summarizes the data available in the literature concerning dinitrophenolic compounds and evaluates male reproductive toxicity in experimental animals. Gavage and feeding doses of 2-sec-butyl-4,6-dinitrophenol (dinoseb; CAS No. 88-85-7) manifested testicular toxicity, and 4,6-dinitro-o-cresol (DNOC; CAS No. 534-52-1) showed similar but weaker testicular toxicity in laboratory animals. Consecutive doses of dinoseb and DNOC by gavage seemed to induce spermatotoxicity by disturbing spermiogenesis or the maturation process of sperm in the epididymis, and the most probable target cells of spermatotoxicity were thought to be testicular spermatids in rats. Prolonged exposure to dinoseb and DNOC in the diet also induced testicular toxicity in rats. However, the feeding dose of dinoseb irreversibly affected the early stage of spermatogenesis and produced infertility in rats. On the other hand, 2,4-dinitrophenol (DNP; CAS No. 51-28-5) did not show testicular toxicity in laboratory animals according to available literature. Further studies in laboratory animals with nitrophenolic compounds are required for clarification of their testicular toxicity and for risk assessment in humans.

The 22nd Screening Information Data Set (SIDS) Initial Assessment Meeting (SIAM 22) was held at the Organisation for Economic Co-operation and Development (OECD) headquarters in Paris, France. The initial assessment documents of five substances (CAS numbers: 75-59-2, 80-51-3, 101-83-7, 103-24-2, 27813-02-1) sponsored by Japan were all agreed at the meeting. In this report, the documents of these substances are introduced.

Male and female Crl:CD(SD) rats were fed a diet containing the rubber accelerator N,N-dicyclohexyl-2-benzothiazolesulfenamide (DCBS) at 0, 1500, 3000, 6000 or 10 000 p.p.m. (0, 83, 172, 343 or 551 mg/kg bw/day in males and 0, 126, 264, 476 or 707 mg/kg bw/day in females) for a total of 57 days beginning 16 days before mating in males, and a total of 61–65 days from 16 days before mating to day 21 of lactation in females. Body weight gains and food consumption were reduced in males at 6000 p.p.m. and higher and in females at 3000 p.p.m. and higher. The weights of the spleen at 6000 and 10 000 p.p.m. and of the thymus at 10 000 p.p.m. were decreased in females. No changes in estrous cyclicity, copulation index, fertility index, gestation index, delivery index, precoital interval or gestation length were observed at any dose of DCBS. Numbers of implantations at 6000 and 10 000 p.p.m. and pups delivered at 10 000 p.p.m. were reduced. There were no changes in the sex ratio or viability of pups. The body weights of male and female pups were lowered at 6000 p.p.m. and higher. Decreased weight of the spleen in weanlings was also observed in males at 1500 p.p.m. and higher and in females at 3000 p.p.m. and higher. The data indicate that DCBS possesses adverse effects on reproduction and development in rats.

Male and female rats were fed a diet containing flame retardant hexabromocyclododecane (HBCD) at 0, 150, 1500 or 15,000 ppm throughout the study beginning at the onset of a 10-week pre-mating period and continuing through the mating, gestation and lactation periods for two generations. The mean daily intakes of HBCD during the whole period of administration were 10.2, 101 and 1008 mg/kg bw in F0 males, 14.0, 141 and 1363 mg/kg bw in F0 females, 11.4, 115 and 1142 mg/kg bw in F1 males, and 14.3, 138 and 1363 mg/kg bw in F1 females for 150, 1500 and 15,000 ppm, respectively. The incidence of rats with decreased thyroid follicles size was increased in F0 and F1 males and females at 1500 ppm and higher. Serum TSH levels were increased in F0 and F1 females at 1500 ppm and higher, and serum T4 levels were decreased in F0 males and females at 15,000 ppm. The number of the primordial follicles in the ovary of F1 females was reduced at 1500 ppm and higher. There were increases in the absolute and relative weights of the liver in male adults and male and female weanlings at 1500 ppm and higher, and in female adults at 15,000 ppm, and of the thyroid in male and female adults at 15,000 ppm. Decreased body weight and body weight gain associated with reduced food consumption were found in F1 males and females at 15,000 ppm. Decreases were found in the viability index of F2 pups and the body weight of male F1 and F2 pups and female F2 pups at 15,000 ppm. In F2 pups, there were low incidences of the completion of eye opening in males at 15,000 ppm and in females at 1500 ppm and higher, and of completed mid-air righting in females at 15,000 ppm. The data indicate that the NOAEL of HBCD in this study was 150 ppm (10.2mg/kg bw/day). The estimated human intake of HBCD is well below the NOAEL in the present study.

Various phthalic acid esters (PAEs) have been used for a wide range of products. PAEs and their metabolites produce reproductive and developmental toxicities in laboratory animals. These findings have raised concern about the possibility of PAEs as contributors to reproductive and developmental adverse effects in humans. This paper focuses on PAE exposure and health effects in human populations and summarizes recent studies. The exposure data in human populations indicate that the current methodology of estimation of PAE exposure is inconsistent. It is therefore important to obtain improved data on human PAE exposure and better understanding of the toxicokinetics of PAEs in each subpopulation. Studies on health effects of PAEs in humans have remained controversial due to limitations of the study designs. Some of findings in human populations are consistent with animal data suggesting that PAEs and their metabolites produce toxic effects in the reproductive system. However, it is not yet possible to conclude whether phthalate exposure is harmful for human reproduction. Studies in human populations reviewed in this paper are useful for showing the strength of the association. It is sometimes claimed that the use of animal data for estimating human risk does not provide strong scientific support. However, because it is difficult to find alternative methods to examine the direct toxic effects of chemicals, animal studies remain necessary for risk assessment of chemicals including PAEs.

Male and female Crl:CD(SD) rats were fed a diet containing rubber accelerator N,N-dicyclohexyl-2-benzothiazolesulfenamide (DCBS) at 0, 80, 600 or 4500ppm throughout the study beginning at the onset of a 10-week pre-mating period and continuing through the mating, gestation, and lactation periods for two generations. At 4500ppm, decreases in the body weight, body weight gain, and food consumption were found in F0 males and females. No changes in the estrous cyclicity, copulation index, fertility index, gestation index, delivery index, number of implantations, precoital interval, or gestation length were observed in any generation at any dose of DCBS. Delayed preputial separation at 4500ppm as well as delayed vaginal opening and higher body weight at the age of vaginal opening at 600 and 4500ppm were found in the F1 generation. A transient change in performance in a water-filled multiple T-maze was found at 600 and 4500ppm in F1 females. There were no compound-related changes in number of pups delivered, sex ratio of pups, viability of pups, anogenital distance, surface righting reflex, negative geotaxis reflex, mid-air righting reflex, pinna unfolding, incisor eruption, or eye opening in the F1 and F2 generations. The body weight of F1 and F2 male and female pups was lowered at 4500ppm. Reduced uterine weight of the weanlings was noted in the F1 generation at 4500ppm and in the F2 generation at 600 and 4500ppm. The data indicate that the NOAEL of DCBS for two-generation reproductive toxicity is 80ppm (5.2mg/kgbw per day) in rats.

The 19th Screening Information Data Set (SIDS) Initial Assessment Meeting (SIAM 19) was held in Berlin, Germany, hosted by the Germen Federal Agency for the Environment. The initial assessment documents of four substances (CAS numbers: 92-70-6, 126-33-0,131-17-9, 7580-85-0) and one category (High Molecular Weight Phthalate Esters) at SIAM 19 were submitted by the Japanese Government with or without the International Council of Chemical Associations (ICCA) and all of them were agreed at the meeting. In this report, the documents of these substances are introduced.

This study was undertaken to investigate whether the concentration of carbonic anhydorase isoenzyme I (CA-I) in canine feces and urine is useful as a temporary marker of occult blood. Concentrations of CA-I were measured by enzyme-linked immunosorbent assay (ELISA). Fecal CA-I concentrations in 113 healthy beagle dogs (50 male and 63 female) of various ages ranged from 4.3 to 16.7 ng/g feces (mean; 7.0 +/- 2.9 ng/g feces). One milliliter of blood from 3 healthy beagle dogs was found to contain 1,047, 1,062 and 1,150 microg CA-I. The fecal CA-I concentrations of dogs receiving intragastric infusions of autologous blood (10 ml) were very low. However, the fecal CA-I concentrations of dogs receiving infusion of autologous blood (5 ml) into the ascending colon were very high. Detection of fecal CA-I would be useful for identifying dogs with hemorrhaging of the large intestine. Of 55 urinary samples collected from healthy beagle dogs by catheter, chemical tests for occult blood were negative in 44, but CA-I concentrations ranged from 1.8 to 12.6 ng/ml (mean; 6.9 +/- 5.4 ng/ml) by ELISA. The CA-I concentrations of the other 11 samples, which tested positive for occult blood on chemical testing, ranged from 41.2 to 525.0 ng/ml by ELISA. Although CA-I is not a specific marker of erythrocytes, CA-I may be used to detect occult blood in canine feces and urine until a specific immunological test kit using antibody for Hb is developed.

There are few reports regarding auricular seroma, and the definition for it is unclear. Herein, we report 16 cases of auricular seroma. We found several common characteristics: (1) no obvious history of trauma, insect bite, or bruising, (2) accumulation of a small amount of rose-wine– or straw-colored serum in the hypodermis but above the perichondrium, determined by puncture aspiration, (3) most often located between the antihelix and concha, (4) no sign of marked inflammation or severe pain, and (5) disappearance without marked disfigurement. We advocate treating auricular seroma as an independent disease entity apart from other auricular swellings such as hematoma and pseudocyst.

The 15th Screening Information Data Set (SIDS) Initial Assessment Meeting (SIAM 15) was held in Boston, USA. The initial assessment documents of twelve substances at SIAM 15 (CAS numbers: 79-39-0, 88-60-8, 92-70-6, 102-76-1, 110-83-8, 135-19-3, 7647-01-0, 8007-18-9, 10043-52-4, 11070-44-3, 25321-09-9, 68186-90-3) were submitted by the Japanese Government with or without the International Council of Chemical Associations (ICCA) and all of them on the human health effect parts were agreed at the meeting. In this report, the human health effect parts in their 12 substance documents are introduced.

Reports on clear identification of fungi in subdermal tissue in chronic fungal external otitis are rare in recent years. Our patient was an immunocompetent adult male with an 8 year history of chronic otitis externa who presented with pustules on the external auditory canal (EAC) and necrosis and perforation of the tympanic membrane. Type I tympanoplasty was performed, but wound healing was delayed and swelling of the EAC occurred. Incision biopsy and staining (Gomori-Grocott and PAS) revealed fungal hyphae within small, calcified, subepidermal masses. A 3 month course of oral itraconazole was effective in healing the lesion. Calcification, a rarely reported finding in otomycosis, may represent a protective reaction against topical use of antifungal drugs.

Twelve male and female rats per group were exposed to the rubber accelerator 1,3-di-o-tolylguanidine (DTG) by gavage at 0, 8, 20 or 50 mg/kg bw/day. Males were dosed for a total of 49 days beginning 14 days before mating. Females were dosed for a total of 40–49 days beginning 14 days before mating to day 3 of lactation throughout the mating and gestation period. At 50 mg/kg bw/day, deaths were observed in two males and three females. Lowered body weight gain and food consumption were noted in males at 50 mg/kg bw/day and females at 20 and 50 mg/kg bw/day. Mydriasis, decreased locomotor activity, bradypnea, prone position, tremor and/or salivation were observed in males and females at 20 and 50 mg/kg bw/day. No effects of DTG were found on the estrous cyclicity, precoital interval, copulation, fertility and gestational indices, numbers of corpora lutea and implantations, or gestation length. A significant decrease in the number, body weight and viability of offspring and increase in the incidence of fetuses with external malformations were found at 50 mg/kg bw/day. Oligodactyly, anal atresia and tail anomalies were observed. These data suggest that DTG may be teratogenic. The NOAELs of DTG for general and developmental toxicity in rats are 8 and 20 mg/kg bw/day, respectively.

Serum C-reactive protein (CRP) concentrations in healthy beagle dogs of various ages and in pregnant beagles were measured by enzyme-linked immunosorbent assay (ELISA). Serum CRP concentrations were 1.5-16.0 microg/ml (mean 7.9 +/- 3.4 microg/ml) in male, and 1.8-18.9 microg/ml (mean 8.3 +/- 4.0 microg/ml) in female dogs. No significant sex-related differences were observed in the values. Further, there were no significant age-related differences either. Serum CRP concentrations increased during pregnancy. The concentration of serum CRP in pregnant dogs peaked at 70.2-90.4 microg/ml (mean 77.5 +/- 7.1 microg/ml) 30 or 45 days after ovulation, demonstrating two characteristic features of CRP concentration change in pregnant dogs.

Coronal tooth lesions, such as caries, enamel cracking, and composite resin restoration cavities, have been observed by optical coherence tomography (OCT). This pilot study was performed to verify whether OCT could reveal details of root canals filled with resin core build-up. A dual-cure, one-step, self-etch adhesive system-bonding agent (Clearfil Bond SE ONE, Kuraray Noritake Dental) and dual-cure resin composite core material (Clearfil DC Core Automix ONE, Kuraray Noritake Dental) were used according to the manufacturer's instructions in root canals. OCT was performed at three stages of the core build-up: after the post space preparation, after bonding application, and after resin core fabrication. The cementum was removed in the cementum absent group and the root was left untreated in the cementum present group. Bubbles were observed in the resin cores and gaps formed between the resin core and dentin. In the cementum absent group, the internal structure of the root could be visualized clearly compared with the cementum present group. The root internal structure could be observed by OCT and the image became clearer when cementum was removed.