Yoshihiko Tsubura

Tissue and organ distribution of mammary tumor virus antigens in low and high mammary cancer strain mice.

Expression of mammary tumor virus (MTV) antigen was measured in a wide variety of organs and tissues of a series of high (GR, SHN, SHNf, DD, SLN, SLNf) and low (DDf, DDD, DDDf, KF, KFf, ddY, C57BL, BALB/c) mammary cancer strain mice. Tests were carried out by microimmunodiffusion (micro-ID) and immunoperoxidase tests on formalin-fixed tissues and radioimmunoassays in extracts for 2 viral proteins, MTVp27 from the viral core and MTVgp52 from the viral envelope. Organs with exocrine function, i.e. the mammary gland, salivary gland, coagulating gland and prostate, were mostly positive. The secretory epithelial cells of these organs showed viral antigen expression. Less positivity was encountered in brain, pancreas, stomach, urinary bladder, epididymis, uterus, thymus, spleen, lymph nodes and kidney, plasma and blood cell pools. Unexpectedly the uterus extracts showed MTV antigen expression, occasionally even by immunodiffusion, especially in mice of various DD stocks, but also in the GR strain. Another striking observation was the detection of MTV antigen expression in salivary glands in C57BL strain mice; most other organs of this strain (including the mammary glands) were negative. The implications of results of this extensive survey for MTV antigen expression are discussed for tumorigenesis by MTV of mammary gland and perhaps other tissues in the mouse.

Endogenous type-C viral expression during lymphoma development in irradiated NFS mice.

The expression of the type-C retrovirus and the virus-related components in NFS mice were examined during preleukemic and leukemic phases after fractionated whole-body X irradiation. The NFS mice were highly susceptible to induction of thymoma by fractionated X irradiation. The leukemic tissues were negative for infectious type-C virus, as detected by both the XC-plaque test and mink S+ L- focus-inducing assays, but contained a substantially higher level of viral-specific RNA-dependent DNA polymerase activity and a major core protein p30 than the corresponding tissues from unirradiated age-control mice. In the preleukemic phase, the amount of p30-related antigen increased transiently in spleen. The leukemic cell lines established from radiation-induced lymphomas produced particulate entities with a buoyant density of about 1.15 g/ml. These virus-like particles lacked in vitro infectivity to mouse cells and mink lung cells and leukemogenicity in syngeneic mice. The p30-related antigens of these particles were immunologically similar to that of xenotropic virus derived from NZB mouse.

Giant cell carcinoma of the pancreas.

A case of giant cell carcinom of the pancreas is reported herein. The patient is a 67‐year‐old Japanese woman complaining of ascites, general fatigue, loss of weight, abdominal distention, nausea, and vomiting. Cytological diagnosis of ascites revealed adenocarcinoma. At autopsy, a whitish tumor measuring around 5 cm in diameter was found at the head of the pancreas. Metastasis was seen only in the liver. Histological examination displayed bizarre multinucleated giant cells occasionally phagocytosing the tumor cells and neutrophils.

ESTABLISHMENT OF MONOCLONAL ANTIBODIES REACTIVE WITH EPITHELIAL and MYOEPITHELIAL CELLS IN THE BREAST

Monoclonal antibodies which are considered to be able to differentiate epithelial and myoepithelial cells in the breast have been developed. Human mammary carcinoma cell line (HBC‐4W) was used for immunization. Monoclonal antibodies‐B4B2F10 (epi‐1), E9E8B7 (myo‐l)‐with IgM was examined using tissues from diseased breast by avidin‐biotin‐peroxidase assay. Epi‐1 antibody reacted with epithelial cells while myo‐1 antibody reacted with myoepithelial cells in the mammary glands, respectively. The reaction was markedly visible, in particular, in fibroadenoma, mastopathy, and papilloma, which showed clear two‐cell‐type structures. In the infiltrating ductal carcinoma, epi‐1 antibody reacted with carcinoma cells, while myo‐1 antibody reacted with stromal cells rather than carcinoma cells suggesting that infiltrating ductal carcinoma was mainly of epithelial origin. In the infiltrating lobular carcinoma, however, myo‐1 as well as epi‐1 antibodies reacted with carcinoma cells. It is suggested that infiltrating lobular carcinoma was of a mixture of epithelial and myoepithelial cell origin. ACTA PATHOL. JPN. 36: 1319–1326, 1986.

Toxicologic studies of the hormonal form of vitamin D3: Acute and subacute toxicity of 1α-hydroxycholecalciferol

Abstract Toxicologic examination of 1α-hydroxycholecalciferol (1α-HCC) revealed its acute toxicity to be high, and the sex variation in sensitivity of the rat to be slightly different. In subacute toxicity studies in rats, body weight gain was extremely inhibited in the animals which received 12.5, 25 and 50 μg/kg. Urinalysis revealed higher calcium concentration in the urine of experimental groups while excretion of urinary phosphate was reduced in the rats receiving 12.5, 25 and 50 μg/kg. Proteinuria was seen in rats of 12.5 μg/kg and higher dose groups. Blood cell counts showed moderate leukocytosis in the higher dose groups than in the 12.5 μg/kg group. Laboratory tests in blood indicated that plasma calcium concentration, total protein, total cholesterol, and blood urea nitrogen in the 12.5-μg/kg and higher dose groups were elevated significantly. Though scattered histological changes were seen in the kidney, heart, aorta, testes, thymus, lung, liver, thyroid, and intestinal mucosa. The main action of 1α-HCC was recognized in the necrosis of the intima of the arteriole in the heart, in digestive tracts and in voluntary muscles, resulting from the degeneration and fibrosis of muscles. However, all those lesions which were caused by the administration of 1α-HCC were fully reversible after 50 days in the recovery group. In rats, oral administration of 2.5 μg/kg of 1α-HCC for 30 days was considered to be a nontoxic dose under the conditions of this experiment.

Comparison of mammary tumorigenesis between litters in relation to mammary tumor virus antigenic expression in the milk of C3H/He mice

As a possible step to estimate the relationship between mammary tumor virus (MTV) and mammary tumorigenesis in mice, MTV antigenic expression in mothers milk and spontaneous mammary tumorigenesis in their daughters were compared between the 1st, the 2nd and the 3rd litters of the highly inbred strains of C3H/H3 mice with low mammary tumor incidence. While MTV antigenic expression was detected in all undiluted samples at each litter by immunodiffusion test, the amount of antigen as measured by the single radial immunodiffusion method was increased with increasing litter numbers. On the other hand, the development of preneoplastic mammary hyperplastic alveolar nodules was different little between litters and mammary tumor incidence by 13 months of age was very low with no difference in all litters. The pattern of estrous cycles and plasma prolactin level were also similar in each litter. The results suggest that spontaneous mammary tumorigenesis in mice is not always affected quantitatively by the amount of MTV when endocrine and genetical conditions are similar.

Cytological findings of cranial chordoma.

頭蓋底部のBlumenbach斜台に原発した脊索腫の1例を報告した.患者は20歳の女性で主訴は複視であった.腫瘍は灰白色で軟らかく, 小脳橋角部に浸潤しており, 組織学的には大部分が線維性結合組織で境された小葉構造を呈していた.細胞学的には, 腫瘍細胞は担空胞細胞と空胞を有しない上皮性細胞を認めた.前者は脊索腫に出現する独特の腫瘍細胞で, 大きな細胞質内空胞と偏在した濃染核を有し, PAS染色で細胞質は陽性でmucinを有すると考えられるが細胞質内空胞は陰性であった. 脊索腫はその発育段階によって3つの細胞学的特徴が認められるといわれているが, 本症例は担空胞細胞が大部分を占め比較的悪性度の低い成熟傾向を示す脊索腫であったと考えられる.

A case report of mixed types of keratinizing squamous cell carcinoma and transitional cell carcinoma of urinary-bladder.

膀胱癌の大部分は移行上皮癌であるが, 扁平上皮癌と移行上皮癌との混合癌の報告は比較的少ない. われわれは, 入院時より連続して尿細胞診にてfollow upし得た膀胱混合癌の1症例を経験したので報告する.症例は60歳の男性で, 肉眼的血尿を主訴とした. 入院後10回にわたり自然尿および膀胱洗浄液の尿細胞診検査を行い, すべて移行上皮癌と扁平上皮癌との混合癌と細胞診断がなされた. 入院2ヵ月後の膀胱全摘手術材料での組織診断では, 強い扁平上皮化生を伴う移行上皮癌と診断されている.死亡後, 病理解剖が行われ, 膀胱原発の角化型扁平上皮癌と確定診断された. 剖検時, すべての転移腫瘍部 (腎, 副腎, 肺, 甲状腺, 肝, 脳, 胃, 小腸, 大腸) での捺印細胞診を行ったが, いずれも癌細胞は角化型扁平上皮癌で, 次のような細胞形態を示した.1) 細胞の形は円形より特殊型さらには多辺形まで種々の形態を有し, 2) また, 細胞の大きさも傍基底型より表層型まで多種であった. 3) さらに, 細胞質は核周明量や層状構造を有する多彩な染色性を示す細胞で占められ, 4) 核所見も濃染顆粒状および塊状のクロモセンターからなる核が大部分であった.

A case report of malignant hemangioendothelioma.

89歳の男性に発生した左側頭部頭皮原発の内皮細胞型血管肉腫の1症例につき, その細胞学的特徴について検討を行った.この症例の細胞学的特徴としては,1) 壊死物質や赤血球を背景として, 悪性腫瘍細胞が集団的にも, また散在的にも認められた.2) 腫瘍細胞は, 細長い線維状の異型細胞が一部分認められたが, 大部分幅広い扁平な細胞質を有する不整形の細胞質で占められていた.以上, 本症例に出現した上記異型細胞は, 山田らの報告している内皮細胞由来の異型細胞とほぼ一致していた.また, 電顕所見においても内皮細胞の特徴であるWeibe1-palade bodyが認められ, この血管肉腫の症例が内皮細胞型であることが確認できた.