Tokuzo Kasai

Detection of human papillomavirus type 16 DNA and evidence for integration into the cell DNA in cervical dysplasia

The presence of human papillomavirus (HPV) type 16 DNA in biopsies from precancerous lesions and from early lesions of human cervical cancer, and the integration of virus DNA into host cell DNA were analysed by dot blot and Southern blot hybridizations. HPV 16 DNA was detected in 23% of mild dysplasias, 32% of moderate dysplasias, 55% of severe dysplasias and 62% of carcinomas in situ by dot blot hybridization. Digestion of the DNA with restriction enzymes PstI and BamHI followed by Southern blot analysis revealed the presence of some typical restriction fragments of HPV 16 DNA in most virus-positive samples. In addition, we detected submolar fragments which might represent virus-cell junction sequences in 86% of dysplasias, suggesting that the integration of HPV 16 DNA could occur in the precancerous stage.

Detection of human papillomavirus DNA in genital warts, cervical dysplasias and neoplasias

Biopsies from human genital lesions in Japan (108 samples), including condyloma acuminata, squamous metaplasia, dysplasia, and cervical cancer, were screened for the presence of human papillomavirus (HPV) 6-, 11-, 16-, and 18-related DNAs by spot hybridization and Southern blot hybridization under stringent conditions. By spot hybridization, HPV 6/11-related DNA was found in 92.9% (13/14) of condyloma acuminata and in 6.7% (1/15) of cervical cancer biopsies. HPV 16/18-related DNA was found in 37.7% (5/14) of cervical cancer biopsies and was exclusively associated with invasive squamous cell cancer, 66.7% (8/12), and with cervical carcinoma in situ, 50% (9/18). Some sample DNAs were further characterized by restriction enzyme digestion followed by Southern blot analysis, and we confirmed the presence of HPV-specific DNA fragments and mixed infection with both HPV 6/11- and HPV 16/18-related HPVs in one lesion.

Cytocidal effects of hematoporphyrin derivative and argon dye laser on human gynecologic tumor cells in vitro

Antitumor effects of hematoporphyrin derivative (HpD) plus argon dye laser were examined using various human gynecologic tumor cells in vitro. Irradiation alone with argon dye laser showed no effect on the DNA synthesis of cells. Treatment of the cells with HpD inhibited the DNA synthesis depending on the concentration and the exposure time. Photoradiation by argon dye laser following treatment of the cells with HpD 40 μg/ml for 2 h killed more than 80% of cells when the cells were irradiated for more than 3 min. Prominent degenerative changes of the cytoplasm and the nucleus appeared within 1 h after photoradiation. These changes were confirmed by morphology and DNA histogram. There were no differences of sensitivity to photoradiation among the three histologically different kinds of cells lines used.

A case report of malignant ovarian carcinoid with ectopic ACTH- syndrome.

卵巣原発の悪性純粋型カルチノイドで, 異所性ACTH症候群を伴った1例を経験した. 症例は51歳, 1妊1産. 下腹部痛を主訴とし, 超音波検査にて卵巣腫瘍を認め, 腫瘍マーカーCA125300U/ml, CA19/9104U/mlにて悪性卵巣腫瘍が疑われた. さらに血中のACTH増加を伴ったクッシング症候群を呈した. 術後5ヵ月に腹壁直下に転移を認め, 放射線治療および化学療法の効なくその後3ヵ月で死亡した. 腫瘍は左卵巣に発生し, 長径16cmの嚢胞性で一部の充実性部の割面は黄色調を呈していた. その捺印細胞像では, 孤立散在性または充実性集団として腫瘍細胞を認め, 核は類円形で高度なクロマチンの増加を示し, 狭少不明瞭な細胞質を有していた. 腫瘍性多核巨細胞も少数散見され, 一部に相互封入像や腺管様あるいはロゼット様配列を認めた. 組織学的には未分化癌に類似した像が腫瘍の多くを占め, 一部に管状, 索状, 島状構造を示していた. Grimelius染色で強陽性を示し, 免疫染色ではChromograninA, ACTH, Serotoninに陽性であった. 電顕的には腫瘍細胞の細胞質内に長径200～300nmの神経分泌顆粒を多数認めた. 本例は世界で2例目と思われる.卵巣原発の悪性純粋型カルチノイドで, 異所性ACTH症候群を伴った1例を経験した. 症例は51歳, 1妊1産. 下腹部痛を主訴とし, 超音波検査にて卵巣腫瘍を認め, 腫瘍マーカーCA125300U/ml, CA19/9104U/mlにて悪性卵巣腫瘍が疑われた. さらに血中のACTH増加を伴ったクッシング症候群を呈した. 術後5ヵ月に腹壁直下に転移を認め, 放射線治療および化学療法の効なくその後3ヵ月で死亡した. 腫瘍は左卵巣に発生し, 長径16cmの嚢胞性で一部の充実性部の割面は黄色調を呈していた. その捺印細胞像では, 孤立散在性または充実性集団として腫瘍細胞を認め, 核は類円形で高度なクロマチンの増加を示し, 狭少不明瞭な細胞質を有していた. 腫瘍性多核巨細胞も少数散見され, 一部に相互封入像や腺管様あるいはロゼット様配列を認めた. 組織学的には未分化癌に類似した像が腫瘍の多くを占め, 一部に管状, 索状, 島状構造を示していた. Grimelius染色で強陽性を示し, 免疫染色ではChromograninA, ACTH, Serotoninに陽性であった. 電顕的には腫瘍細胞の細胞質内に長径200～300nmの神経分泌顆粒を多数認めた. 本例は世界で2例目と思われる.