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The tissue distribution of Cu/Zn- and Mn-superoxide dismutases (SOD) in adrenal tumors was studied by an immunohistochemical technique, and the concentrations of both SODs were measured by a sensitive sandwich enzyme immunoassay technique. In the normal adrenal gland, both Cu/Zn- and Mn-SODs were localized predominantly in the reticular zone of the cortex. Cu/Zn-SOD was stained clearly in the inner fascicular zone of the cortex, but not in the medulla, whereas Mn-SOD was stained weakly in the medulla. In different adrenal tumors, the localization of both stained SODs reflected the origin of the tumor cell. Thus, in one section of a pheochromocytoma only Mn-SOD was stained clearly. The concentrations of both SODs in the tissues of medullary tumors were lower than those in the normal adrenal gland and adrenocortical adenomas. The concentration of Cu/Zn-SOD in the tumor tissue of Cushing's syndrome adenoma was higher, and that of Mn-SOD was lower than the concentrations in the normal adrenal gland. The ratio of the tissue concentrations of Mn-SOD to Cu/Zn-SOD was lower in adrenal medullary tumors and Cushing's syndrome adenomas than in the normal adrenal gland and primary aldosteronism adenomas, indicating the predominance of Cu/Zn-SOD in the former, and Mn-SOD in the latter. These data suggest that the localization of Cu/Zn- and Mn-SODs in adrenal tissues reflects the specificity of the adrenal cells that produce the tissue-specific hormones. An investigation of changes in these enzymes in adrenal tumors may also provide useful information on adrenal tumor cell differentiation.

症例は48歳の女性.主訴は左前頸部の腫瘤.既往歴として20歳時より,進行性筋ジストロフィーに罹患し,車椅子生活を送っていた. 2000年4月,前頸部腫脹を初発症状として来院.甲状腺左葉の単発性腫瘤で, USおよび穿刺吸引細胞診で良性濾胞腫瘍と診断され,経過観察されていた. 2002年11月,突然の下血を初発として多発性肺転移を伴う直腸癌が診断され,ハルトマン手術(人工肛門造設)が施行された. 2003年4月,頸部腫瘤の増大と嚥下時の違和感が出現し, US,穿刺吸引細胞診上悪性所見は認めなかったが,患者の強い希望で, 5月手術目的で入院となった.入院時の患者の身体所見は,筋ジストロフィーのため下半身麻痺があるが,全身状態は良好.前頸部から左側頸部にかけて大きさ6×5cmの弾性硬の腫瘤を触れ,一部に硬い結節(1.0×1.0cm)を触れた.甲状腺機能は正常で,血中サイログロブリンは軽度上昇し, CEAとCA19-9は著しい上昇を示し,直腸癌の再燃・増殖が推定された. 2003年5月,全麻下に甲状腺左葉切除術を施行.腫瘍は左葉から峡部に及ぶが,周囲組織への浸潤,リンパ節転移などを疑う所見はなかった.病理所見では,全周性に明瞭な被膜を有する濾胞腺腫の中に壊死傾向の著しい腫瘍細胞の増殖を認め,既往の直腸癌の転移と診断された.良性腫瘍である甲状腺濾胞腫瘍の内部に他の癌の転移が起きることは極めて稀である.

症例は54歳,男性. 1994年6月,腹痛を主訴にCT検査を受け,左副腎腫瘤を指摘された.高血圧症は認めないが,尿中カテコラミン(CA)は高値を示した. CT, MRIでは,左腎門部と大動脈に接し,腎動静脈の間に発育する境界明瞭で嚢胞性変化を伴う最大径約10cmの腫瘤を認めた. 131I-MIBGシンチで腫瘤部と骨盤部に集積を認め, CTで仙骨部に腫瘤を確認し,仙骨転移を伴う左副腎悪性褐色細胞腫(無症候性)と診断した. 10月,左腎合併左副腎摘出術を施行.腫瘍は径10×6×4.5cm,重量145gで腎実質への浸潤はなかった.組織学的には,分泌顆粒を持つ大小不同の好塩基性細胞の充実性増殖を認め,褐色細胞腫と診断された,術後,尿中CAおよび代謝物は高値を持続し, 4カ月後に仙骨部分切除術施行後には,全ての尿中CAは正常化した. 4カ月後歩行可能となり退院.術後8年経過した現在,再発を認めない.悪性褐色細胞腫の治療には手術,化学療法,動脈塞栓, 131I-MIBG内照射などが挙げられるが,いまだ確立されてはいない.われわれは仙骨部に単発性転移を伴った悪性副腎褐色細胞腫に対して,原発および転移病変の二期的切除を施行し良好な結果を得た.

A case of invasive ductal carcinoma of the breast and localized in the right nipple is reported. The patient was a 65-year-old woman. Beginning in January 1997, she noticed gelosis surrounding the right nipple, but did nothing about it. During an examination in April of that year, she was persuaded to undergo additional tests, and was referred to this clinic. The right nipple measured 15×15mm, with a height of 10mm, and was slightly larger than the left nipple. Through palpation, a mass was found with indistinct, elastic boundaries directly under the nipple, but no bleeding or sores on the surface. Mammography confirmed the presence and shape of the mass, while ultrasonography showed a low-echo, uneven tumor area measuring 18×17×10mm with an irregular edge. Biopsy results suggested ductal carcinoma, with the possibility of an adenoid tumor; therefore, we elected to resect the nipple area. A pathological study showed the tumor to be an invasive type of ductal carcinoma, but there was no residual tumor at the resection site, and the remaining breast and axillary region were treated with radiotherapy. Discussion: Other diseases localized to the nipple include Paget's disease and adenoma of the nipple, so it is important to distinguish these from breast cancer. In particular, the latter type leads often to resection of the nipple. Most cases of cancer of the nipple are Paget's disease complicated by noninvasive ductal carcinoma, so it is unusual to find a case where the primary tumor in the nipple was an invasive tumor.

The localization of Cu/Zn- and Mn-superoxide dismutase (SOD) in breast cancer tissue (12 papillotubular carcinomas, 21 solid-tubular carcinomas, 16 scirrhous carcinomas, 1 medullary carcinoma, 1 secreting carcinoma, 1 lobular carcinoma, 1 Paget’s disease) was investigated via an immunohistochemical technique using antihuman Cu/Zn- and Mn-SOD antibodies in 10% formalin fixed-paraffin embedded thin sections. Both SODs stained strongly in the normal breast gland, but not clearly in many cancer tissues. Furthermore, Cu/Zn-SOD stained more strongly in well differentiated tubular carcinomas than in poorly differentiated tubular carcinomas. It tended to stain less in tumors which recurred or had a poor outcome, and in tumors with a diploid pattern on DNA flow cytometry. Mn-SOD staining was similar to that of Cu/Zn-SOD, but no significant differences among subgroups was found, since the incidence of positively staining tumors was too small in all groups. The intensity of SOD staining seems to change in relation to cell proliferation and differentiation in breast carcinoma, and may be a prognostic indicator, since SOD decreased in poorly differentiated carcinoma and in tumors which developed distant metastasis. Thus, the localization of SOD in breast cancer tissue can provide useful information for cancer treatment.

Vascular endothelial growth factor (VEGF) is involved in tumor angiogenesis and other pathophysiological processes. We studied the localization of VEGF in human thyroid tissues to clarify its involvement in proliferative processes in a variety of thyroid disorders. Immunohistochemical analysis using purified rabbit polyclonal anti-human VEGF or anti-human CD34 antibody and a streptavidin–biotin peroxidase complex detection system was performed on 58 tissue specimens from 53 patients with different thyroid disorders and 5 normal thyroid glands. Vascular endothelial growth factor was not detected in normal thyroid follicular cells. However, some thyroid tumor cells expressed VEGF in the cytoplasm (papillary carcinoma, 10/18; follicular carcinoma, 1/3; medullary carcinoma, 2/2; follicular adenoma, 3/11; adenomatous goiter, 2/4). In benign follicular adenoma and adenomatous goiter, weak expression of VEGF was found in small areas of the tumor, whereas in malignant thyroid tumors, it was strongly expressed in many cells. However, VEGF was not expressed in anaplastic carcinoma, malignant lymphoma, or Graves’ disease. Angiovascular cells stained with CD34 antibody in tissues from different thyroid disorders reflected statistically significant differences in papillary carcinoma, follicular adenoma, and Graves’ disease compared with normal thyroids, and such cells showed a trend toward increases in medullary carcinoma and adenomatous goiter. In contrast, low vascularity was observed in anaplastic carcinoma, malignant lymphoma, and follicular carcinoma. Because VEGF probably functions as a hypoxia-inducible angiogenic factor, overexpression of this mediator, concomitant with hypervascularity, may be induced more strongly in malignant thyroid tumors, which need more oxygen to proliferate, than in benign follicular tumors. However, neither VEGF nor CD34 was expressed in anaplastic thyroid carcinoma, which is an extremely poorly differentiated malignant tumor. CD34 but not VEGF was expressed in the hyperplastic thyroid tissues of Graves’ disease composed of nontransformed cells. Thus, the expression of VEGF concomitant with CD34 is suggested to reflect both the transformation and differentiation state of malignant tumors.

About 28% of patients with the Crow-Fukase syndrome exhibit glucose intolerance which may be induced by low serum levels of dehydroepiandrosterone (DHEA). We report a patient with the Crow-Fukase syndrome who exhibited non-insulin dependent diabetes mellitus (NIDDM) worsened prior to admission. He received the DHEA sulfate (DHEA-S) infusion test to evaluate aromatase activity. This patient exhibited an increase in aromatase activity measured by the conversion of the intravenously loaded DHEA-S to estrogen, and low serum levels of DHEA and DHEA-S. These abnormalities returned to nearly normal during the administration of prednisolone, 60 mg per day. No adverse effect on his diabetes was observed during the corticosteroid treatment. Five control patients with diabetes but without the Crow-Fukase syndrome showed no increase in the conversion of DHEA-S to estrogen, which suggests that aromatase activity is normal in diabetes. The increase in aromatase activity in our patient may have led to a low serum concentration of DHEA that in turn caused glucose intolerance and a deterioration of the diabetes prior to admission. Glucocorticoid therapy may be beneficial in Crow-Fukase syndrome to improve the distorted metabolism of DHEA with no adverse effect on the diabetes.

A new antibiotic SF2487 has been isolated from the culture broth of Actinomadura sp. SF2487. The structure of antibiotic SF2487 was determined by spectroscopic analyses of the sodium salt and X-ray diffraction analysis of the silver salt. The antibiotic represents a new member of polyether group antibiotics known as the acyltetronic acid type 4. The antibiotic is weakly active against Gram-positive bacteria and exhibits antiviral activity against influenza virus in vitro.

Derivatives of ascorbic acid were synthesized, and the studies were made on their effects in Ehrlich ascites carcinoma cells, in regard to the inhibition and the prolongation of survival time as well as on the morphological degeneration in HeLa cells. In a model infection study carried out by using tetraacetyl-bis-dehydroascorbic acid in dd mice infected with Ehrlich cells, it was proved that the prolongation of survival time was nearly double in comparison to the control group mice. Also, it was noted that hypertrophy due to abdominal dropsy and body weight were reduced much more than in the control group. From these results, the inhibiting effect of tetraacetyl-bis-dehydroascorbic acid was confirmed. While in the case of DHA and other derivatives, almost no inhibition and prolongation of survival time were observed. As for HeLa cells in a tissue culture, tetraacetyl-bis-DHA, in a dosage of 125-250 mug/ml, demonstrated definitely its morphological degeration. After 125 mug/ml of tetraacetyl-bis-DHA was added to a tissue culture solution of HeLa cells, the cells were washed and recultured. No growth of the cells was observed. Consequently, this substance was confirmed to be anti-HeLa substance with a low toxicity.