Focal infiltration of lymphocytes with parenchymal destruction was noted in both salivary and lacrimal glands of IQI/Jic mice. The sialadenitis was found in more than 80% of female mice at all ages examined. The lesion progressed after 6 months and became more prominent with age. In contrast, male mice had slight and stable salivary lesions independent of age, though the incidence increased with age. Infiltrating lymphocytes consisted of both T and B cells. The dominant lymphocytes in small foci were CD4+ cells, but the majority of infiltrating cells were B cells (B220+), followed by CD4+ T cells in larger lesions. The ductual epithelium in the foci aberrantly expressed MHC class II antigen. Eight of 24 15-month-old female mice with sialadenitis produced speckled-type IgG antinuclear autoantibody. These findings are similar to those in patients with Sjögren's syndrome. IQI/Jic mice could be a novel animal model of Sjören's syndrome.

No abstract

High basal protein levels of GRP94 were correlated with a modest decrease in sensitivity to X-ray cell death in some cervical cancer cell lines. These results suggest that higher GRP94 protein expression is one of the molecular mechanisms causing resistance to radiation, and therefore GRP94 siRNA might be useful in tumor-specific gene therapy by reversing radio-resistance prior to radiation in cervical cancer.

The potential for health effects on humans with exposure to bisphenol A (BPA) has raised concerns, and the adverse effects of low-dose exposure to BPA on reproduction have been controversial. The purpose of the present study was to investigate the effects of low-dose exposure to BPA on reproductive development in F(1) rat offspring. Pregnant female Sprague-Dawley rats (F(0)) were fed a diet containing low doses of BPA (0, 0.33, 3.3, or 33 ppm) from gestational day (GD) 6 through postnatal day (PND) 21. The weanlings (F(1)) from all dose groups were fed a normal diet ad libitum after weaning and then were subjected to necropsy at 5 weeks or 3 months of age. No BPA-related changes were observed in body weight or weight of any of the major reproductive organs in F(1) males and females. Epididymis weight was significantly lower only in 3-month-old F(1) males exposed to 33 ppm BPA. Anogenital distance (AGD), the ratio of AGD to the cube root of body weight, and relative ovary weight were significantly lower in 5-week-old F(1) females exposed to 3.3 and 33 ppm BPA, but significant differences were not observed in 3-month-old females. There were no BPA-related effects on cauda epididymal sperm motility in 3-month-old F(1) males. Plasma reproductive steroid hormone concentrations were not altered among groups in either sex. These outcomes indicate that low-dose exposure to BPA in the diet does not adversely affect reproductive development in F(1) rat offspring.

Intratracheal instillation is widely used for respiratory toxicity tests in experimental animals. However, there are wide variations in the techniques used for instillation, and it is thus difficult to compare the results obtained using different techniques. To examine the effect of instillation methods, we compared the distribution of a test substance in the lungs of rats after intratracheal instillations under various conditions. Rats received an intratracheal instillation of 0.3 mL of india ink suspension under different conditions as follows: 3 different angles of body restraint, 0° (supine horizontal), 45° (supine head up) and 90° (vertical head up); 2 instillation speeds, high (40 mL/min) and low (4 mL/min); and 2 different devices, a standard bulb-tipped gavage needle and an aerosolizing microsprayer designed for intratracheal instillation. One hour after treatment under these various conditions, rats were sacrificed, and the local distribution of the suspension in the lungs was observed. No animal restrained in the supine head-up or vertical head-up position died from the treatment; however, fatalities were observed when rats were restrained in the supine horizontal position except under high-speed dosing conditions with a microsprayer. Better distribution of the suspension in the lungs was observed in the rats restrained in the supine head-up position after instillation at high speed when compared with other conditions. These results indicated that high-speed instillation to the subject restrained in the supine head-up position is an appropriate condition for performing intratracheal instillation.

Much concern has been raised over the health consequences of workers exposed to carbon nanotubes. In order to characterize multi-wall carbon nanotubes (MWCNT) suspended in a phosphate-buffered saline containing 0.1% Tween 80 for an intratracheal instillation study.

The present study was conducted to examine the effects of low-dose exposure to bisphenol A on reproduction and development in two generations of mice. Pregnant female C57BL/6J mice (F0) were fed a diet containing low doses of bisphenol A (0, 0.33, 3.3, or 33 ppm) from gestational day 6 through postnatal day 22, and the weanlings (F1 and F2) from each F0 and F1 dam group, respectively, were also fed these same concentrations of bisphenol A ad libitum until sacrifice. There were no treatment-related changes in body weight, body weight gain, food consumption, gestation length, or the number of live births on postnatal day 1 in F0 dams between the control group and bisphenol A groups. Sex ratio and viability were similar in all F1 pups. No treatment-related changes were observed in body weight, food consumption, developmental parameters, anogenital distance, or weight of any of the organs (liver, kidney, heart, spleen, thymus, testis, ovary, or uterus) in F1 and F2 adults in either sex. The epididymis weight was slightly higher with 0.33 and 3.3 ppm in F1 males, but this slight increase was neither dose dependent nor seen across generations. There were no treatment-related effects of bisphenol A on cauda epididymal sperm count or sperm motility in F1 or F2 males. These findings indicate that dietary exposure to bisphenol A between 0.33 and 33 ppm does not adversely affect reproduction or development as assessed in two generations of mice.

In order to assess the extrapulmonary effects of multiwall carbon nanotubes (MWCNT), deposition of MWCNT and histopathologic changes in lung-associated lymph nodes (LALN) were examined in MWCNT-administered rats. At the age of 13 wk, male F344 rats were intratracheally instilled with MWCNT at a dose of 0 (vehicle), 40 or 160 μg/rat. The rats were sacrificed on Day 1, 7, 28 or 91 after instillation and light microscopic examinations were performed on LALN tissues. MWCNT was translocated to right and left posterior mediastinal lymph nodes and parathymic lymph nodes. Deposition of MWCNT was greater in the posterior mediastinal lymph node than in the parathymic lymph node, and the amount of MWCNT deposited in these two lymph nodes increased gradually and dose-dependently with time. MWCNT was phagocytosed by nodal macrophages, and some of the MWCNT-laden macrophages were aggregated. Transmission electron microscopic (TEM) observation confirmed the presence of MWCNT fibers with a characteristic multi-walled cylindrical structure.