Screening of biomarker genes activated by irradiation of ultraviolet B rays in mouse lymph node M10 cells

When M10 cells derived from mouse lymph nodes were irradiated with the UVB lamp at a peak emission of 312 nm, the cell growth was suppressed in proportion to irradiation time (10-30 s) and cell apoptosis was also induced by the irradiation. Dynamic changes in 597 genes after exposing these cells to UVB irradiation were investigated by DNA array analysis using array membranes and a (33)P-labeling probe. After 2 h of irradiation, the gene expression in the cells was examined and compared with that in untreated cells. Radioactivity was analyzed using Array Gauge software. The data were further processed using software, EX-ARRAY, which was developed for extracting significant data from the results of 2 background-subtraction methods, i.e., global and local background subtraction. The number of genes suppressed under UV irradiation increased with irradiation time, while that of activated genes decreased. Finally, we confirmed 4 genes (HMG-14, CDX-2, MCP-3, and GRP-78) to be up-regulated and confirmed their activation by northern blot. We propose these genes as the new biomarkers of lymphocyte sensitive to UVB irradiation.     

Human Parainfluenza Virus Type 3 in Wild Nonhuman Primates,Zambia

Human parainfluenza virus type 3 (HPIV3) genome was detected in 4 baboons in Zambia. Antibody for HPIV3 was detected in 13 baboons and 6 vervet monkeys in 2 distinct areas in Zambia. Our findings suggest that wild nonhuman primates are susceptible to HPIV3 infection.     

Identification of three distinct papillomavirus genomes in a single patient with epidermodysplasia verruciformis

Benign papillomas from a patient with a family history of epidermodysplasia verruciformis were examined for the presence of human papillomavirus (HPV) DNA. Employing stringent hybridization conditions that allow identification of a single type of HPV and radioactively labeled HPV-5 DNA as a probe, we have detected HPV DNA exhibiting sequence homology to HPV-5 in these tumors. Restriction endonuclease analysis of this HPV DNA confirmed its identity as HPV type 5. However, when hybridization was performed under less stringent conditions that allow all of the known types of HPV to react with the radioactively labeled HPV-5 DNA probe, two additional species of HPV DNA unrelated to HPV-5 were identified. As these two HPV types do not hybridize with HPV 1, 2, 3, or 4 under stringent conditions, they appear unique and have, as yet, not been reported to be associated with patients exhibiting epidermodysplasia verruciformis. Thus we have observed three distinct HPV species in benign papillomas from a single patient. These observations have important implications when attempting to correlate the type of HPV present in the various wart disease syndromes that have been described to date and further suggest that extreme care must be taken when analyzing carcinomas, occupying similar anatomic sites and suspected to have arisen from papillomas, for HPV species.     

Sevelamer hydrochloride reverses parathyroid gland enlargement via regression of cell hypertrophy but not apoptosis in rats with chronic renal insufficiency.

BACKGROUND: Dietary phosphate restriction suppresses parathyroid hormone (PTH) secretion, synthesis, and parathyroid cell proliferation in experimental animals with chronic renal insufficiency (CRI), independently of serum calcium and 1,25(OH)2D3 levels. This study was conducted to examine whether sevelamer hydrochloride (sevelamer), a metal-free phosphate binder, could regress an advanced parathyroid gland (PTG) hyperplasia and enlargement in rats with CRI. METHODS: Male Sprague-Dawley rats were fed a diet containing adenine for 6 weeks to establish CRI. Normal rats and adenine-treated rats were sacrificed to obtain the PTG (baseline group). The adenine diet was changed to a normal diet or diet containing 1 or 3% sevelamer for another 4 weeks. Time course changes of serum levels of calcium, phosphorus, and PTH were measured. At the end of the study, the PTG was weighed and examined histologically. RESULTS: Adenine-treated rats developed severe CRI with marked elevation of serum phosphorus and PTH. The PTG weight markedly increased with enlarged cell volume (i.e. cell hypertrophy) at baseline. Sevelamer treatment rapidly lowered serum phosphorus and PTH levels within 6 days, and after 4 weeks, reduced the PTG weight by 38% compared to adenine-treated rats at baseline. The reduction in PTG weight was due to regression of cell hypertrophy, but not to decreased cell number by apoptosis. Decreased expression of calcium receptor in the PTG at baseline was partially recovered by the sevelamer treatment. CONCLUSIONS: The sevelamer treatment can reduce the PTG weight with a reduction in serum PTH levels via regression of cell hypertrophy but not apoptosis in rats with CRI. Reduced PTG function might contribute to the regression of cell hypertrophy.     

Study for tumor-initiating effect of acetaminophen in two-stage liver carcinogenesis of male F344 rats

The potential liver-tumor-initiating activity of acetaminophen(paracetamol, APAP) was investigated in male F344 rats. APAPwas administered by intragastric intubation either as 10 dosesof 1 g/kg body weight over 5 weeks or as a single dose of 0.5g/kg body weight 24 h after two-thirds partial hepatectomy.These initiating treatments were followed by administrationof 0.1% phenobarbital in the drinking water for 12 weeks asthe promoting regimen. Quantitative examination of placentalglutathione S-transferase-positive foci revealed no enhancingeffect of APAP on the induction of the foci consisting of morethan two positive cells with either initiating treatment. Ifsolitary positive hepatocytes were included in the effectivenumber of foci, 10 repeated doses of 1 g/kg APAP increased thenumber of foci while the validity of the single positive cellsis uncertain. This dose of APAP caused centrilobular necrosis.By ³²P-postlabeling, although the active metabolite of APAPformed DNA adducts when incubated with isolated DNA, no DNAadduct formation was detected in the liver of rats either fed0.1–1.5% APAP for 1 week or given 1 g/kg by gastric intubation.These results indicate that APAP possesses no tumor-initiatingactivity in the rat liver.     

Characterization of tumor-induced inflammation and the effect of some anti-inflammatory drugs on the increased vascular permeability

The vascular bed in a murine dermal tissue responded to inoculated tumor cells by two-phased changes in the vascular permeability. The initial increase in the vascular permeability was seen in an early stage (1 to 3 day post tumor cells inoculation), and the inflammation was sensitive to glutathione (GSH). Glucocorticoids reduced the increased vascular permeability, but neither acetylsalicylic acid nor indomethacin did. The later vascular response was produced by a growing solid tumor in a continuous mode beginning at 5th to 10th day post inoculation. The degree of the increased vascular permeability in this chronic phase was in direct proportion to the wet weight of the solid tumor, and the inflammation was insensitive to glutathione. Glucocorticoids reduced the increased vascular permeability, but neither acetylsalicylic acid nor indomethacin did. The action of glucocorticoids on the tumor-induced vascular hyper-permeability was discussed in connection with a tumor factor possibly responsible for the vasoexudation.     

Activated T lymphocytes in cerebrospinal fluid of patients with HTLV-I-associated myelopathy (HAM/TSP)

In order to detect activated T lymphocytes in the cerebrospinal fluid (CSF) of patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we studied CSF lymphocytes in untreated patients with HAM/TSP and other neurological diseases (OND). Dual-immunofluorescence staining technique was performed using fluorescence microscopy. No significant difference in the CD4+/CD8+ ratio of CSF lymphocytes was observed between HAM/TSP patients and patients with OND. However, both CD4+ and CD8+ CSF lymphocytes of HAM/TSP patients contained higher percentages of HLA-DR-positive cells than those of patients with OND (P less than 0.05), suggesting that the activated CSF T lymphocytes were composed of both CD4+ and CD8+ subsets in patients with HAM/TSP.