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If activation of the p53 gene is involved in the progression or metastasis of colon cancer, it may affect the angiogenic phenotype in vivo. To verify this hypothesis, we studied the correlation between p53 accumulation and expression of thrombospondin-1 (TSP1) in colon cancer specimens. Levels of TSP1 gene expression were estimated by Northern blotting in 65 colon cancers. Accumulation of p53 and the distribution of TSP1 protein were evaluated immunohistochemically. Various levels of TSP1 gene expression were seen in colon cancers, while p53 accumulation was confirmed in 42 of the 65 colon cancers. The level of TSP1 gene expression demonstrated a significant inverse correlation with p53 accumulation in colon cancer. Colon cancer cells expressed TSP1 protein and p53 accumulation reciprocally in the same nests. These results suggest that alterations in the tumour suppressor gene p53 may inhibit TSP1 expression in colon cancer.

Allergic conjunctivitis is one of the typical atopic diseases. Recently, a number of patients in Japan have been suffering from Japanese cedar pollinosis with symptoms that include allergic rhinitis and conjunctivitis. The prevalence of allergic conjunctivitis is estimated to occur in approximately 20% of the general Japanese population. The ocular allergy is characterized by severe itching, hyperemia and edema. Medical therapy consists of topical applications of antihistamines with or without vasoconstrictors, mast cell stabilizers, nonsteroidal anti-inflammatory drugs and glucocorticoids. 1)Among these treatments, antihistamine is one of the most common medications for allergic conjunctivitis. 1) However, Howarth 2) has suggested that antihistamines do not fully modify the disease since histamine is not the only contributor to symptom generation in allergic conjunctivitis. Despite the existence of a histamine-independent mechanism, in the majority of experimental allergic conjunctivitis models, antihistamines are significantly effective in the reduction of symptoms. [3][4][5] Most experimental ocular allergy animal models have been developed by actively sensitizing guinea pigs with an intraperitoneal injection of a non-airborne antigen such as ovalbumin 6) and dinitrophenylated lysine 7) mixed with an adjuvant or by passively sensitizing animals with antisera, 8,9) which is followed by the subsequent single conjunctival challenge with a solution of the specific antigen. These models are considerably different from the clinical situation because the antigen challenges are not performed chronically. To address this situation, we have developed a guinea pig model of allergic conjunctivitis in which sensitized animals are repeatedly challenged by the dropping of a Japanese cedar pollen suspension in the eye.10) We previously reported that the multiple challenge approach aggravates the disease in proportion to the number of challenges.10) In the present study, we evaluated whether involvement of histamine in the induction of symptoms of allergic conjunctivitis is altered by the multiple pollen challenges in the model. In addition, in order to know a part of mechanisms underlying the histamine-independent allergic conjunctivitis, we determined whether the symptoms mediated by nitric oxide (NO) synthesis. MATERIALS AND METHODSAnimals Male, 3-week-old, Hartley guinea pigs weighing 250-300 g were purchased from Japan SLC, Hamamatsu, Japan. The animals were housed in an air-conditioned room at a temperature of 23Ϯ1°C and 60Ϯ10% humidity with a controlled 12 h light/dark cycle, and fed a standard laboratory diet with water given ad libitum. The first sensitization was started 1-2 weeks after the purchase. The Experimental Animal Research Committee at Kyoto Pharmaceutical University approved this animal study.Materials The following reagents were obtained from the indicated commercial sources: mepyramine maleate and L-arginine hydrochloride (Sigma Chem., St. Louis, MO, U.S.A.); N w -nitro-L-arginine methyl ester (L-NAME) ...

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