岩瀬 克己

The possible role of abnormal T cell-dependent B-cell activation in Graves' disease was investigated by comparing lymphocyte subset distribution and the production of soluble CD8 (sCD8), sCD23, IL-10 and IL-12 by peripheral blood cells (PBMC) and thyroid-infiltrating lymphocytes (TL) in vitro. In TL, the percentage of CD8(+) cells was slightly higher and the sCD8 concentration was significantly higher than in PBMC. The ratio CD23(+) cells to CD20(+) cells (activated B/pan B cells) was increased in TL compared to PBMC from Graves' or normal controls, although the percentage of CD20(+) cells was decreased. Compared to PBMC in Graves' disease, the relative ratio of IL-10 to IL-12 release (IL-10/IL-12) by unstimulated TL was increased, despite a lack of significant difference between PBMC and TL in mean values for either IL-10 or IL-12 secretion. Incubating PBMC with a combination of anti-CD40 monoclonal antibodies and interleukin-4 (IL-4) resulted in B cell activation, reflected in an increase in the sCD23 level in both controls and Graves' patients, but especially prominent in the latter. Stimulation with anti-CD40 antibody and IL-4 also decreased the percentage of CD8+ cells in PBMC but not TL from both Graves' disease and normal controls, and the percentage of CD8(+) cells in TL was higher than PBMC after the stimulation. The sCD23 concentration in TL was decreased compared to PBMC both in patients with Graves' disease and normal controls. However, in contrast to the increased responses observed in Graves' PBMC or normal controls after stimulation, sCD23 levels remained the same in stimulated TL from Graves' patients. This combination of B cell stimulants increased production of IL-10 in PBMC but not in TL obtained from patients with Graves' disease, and the increased IL-10/IL-12 ratio declined to a value no different from that in PBMC group after stimulation. Thus, T cell-dependent B-cell activation via a CD40 pathway may cause a shift in the Th-1/Th-2 balance to Th-2 dominance in Graves' disease, while increased CD8(+) cells in TL may suppress sCD23 production and IL-10-producing Th2 cells. (C) 2002 Elsevier Science Ltd. All rights reserved.

In general, many cases of malignancy-associated hypercalcemia are due to HHM. In patients with humoral hypercalcemia of malignancy (HHM), it has been reported that plasma parathyroid hormone-related protein (PTHrP) and cyclic adenosine monophosphate (cAMP) levels were elevated, while plasma PTH and active vitamin D-3 levels were suppressed. Our patient showed hypercalcemia with a concurrent increase in plasma and tumor tissue PTHrP and PTH concentrations and also high cAMP and low 1-25(OH)(2)VD3 levels in the plasma. These data suggest that the hypercalcemia exhibited by our patient was consistent with HHM due to lung cancer and its liver metastasis. Moreover, diagnostic imaging and autopsy findings showed no appreciable lesions of the parathyroid gland. In addition, histopathologic examination of the primary and metastatic tumors revealed the existence of PTH immunohistochemically stained with anti-PTH antibodies, suggesting an ectopic-PTH-producing lung tumor. From these data, our patient was diagnosed with a rare case of lung cancer, which produced both ectopic PTH and PTHrP. Copyright 2002, Elsevier Science (USA). All rights reserved.

乳癌検診では画像診断の併用が勧められており, とくにマンモグラフィの併用について検討されているが問題点も多い。春日井市健康管理センターでマンモグラフィを併用した乳癌検診を導入して3年を経過し, その結果を検討した。当施設では30歳以上の女性を対象に視触診とマンモグラフィを併用し, 有所見者やマンモグラフィが読影困難なものには超音波検査を行っている。乳癌は16例 (0.51%) 発見され, そのうち11例が触知可能で, マンモグラフィでは14例に異常所見が, 超音波検査では15例に腫瘤所見が認められた。検診時に癌を疑ったものは12例, 病期は0～I期が11例でそのうち5例に乳房温存手術が行われた。良性腫瘤性病変の代表である線維腺腫は要精検121例中16例で, マンモグラフィで捉えられた13例中7例は非触知であった。検診時には8例が悪性疑いまたは診断困難とされ, 8例は線維腺腫と診断された。一方, 検診時に良性病変の診断であったが要精検とした41例中癌は1例 (2.4%) のみで, 後期は要精検の判定基準から良性病変を除外し, 癌発見率を低下させることなく, 要精検例中の非癌例の割合を減少させ得た。視触診とマンモグラフィを併用した検診は乳癌の早期発見に有用で, 見逃し例の減少と有所見者の性状診断のためには超音波検査が有用と考えられた。画像診断の併用は, 要精検率を増大させ, 受診者や医療側の負担を増加させる可能性があるが, 検診の精度を高くすることにより改善可能と考えられた。

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.

S-100 protein is detectable in various human tissues, though it was first recognized as a protein specific to nervous tissues. It consists of dimers composed of α(α) and β-subunit (β). We elucidated the localization and the concentration of α and β in thyroid tissues from various thyroid disorders, using highly purified anti-human a and anti-human β antibodies.<BR>The concentration of α in thyroid tissues from Basedow's disease, papillary carcinoma and follicular carcinoma was higher, and that from medullary carcinoma was lower than that from the normal thyroid tissues. The concentration of β in malignant thyroid tumors was higher than that in either benign thyroid tumor or Basedow's thyroid. These findings were also confirmed by the immunostainings. The ratio of α to β(α/β) in Basedow's disease was higher, but the ratio in medullary carcinoma was lower than that present in the normal thyroid.<BR>In conclusion, since the concentration and localization of α and β in thyroid tissues differed in various thyroid disorders, each subunit may have different functions in the thyroid. Namely, α may be related to the cell differentiation, proliferation, and hormonal secretion from follicular cells, and β may have a close relationship to the function of parafollicular cells. These data imply that the analysis of the concentration and localization of α and β particularly in various thyroid tumors is useful in diagnosing the characteristic features of various thyroid tumors.

To clarify the effect of glucocorticoid on glucose transporters (GLUT) in adipocytes and muscle, we examined the changes of GLUT4 in rat heart muscle, skeletal muscle and adipocytes during long-term administration of dexamethasone and the translocation of GLUT4. The levels of GLUT4 in the plasma membrane and the low-density microsome fraction were measured by Western blotting using anti-GLUT4 peptide antibody. The levels of GLUT4 in the heart and skeletal muscles of rat were unchanged by treatment of dexamethasone. In the adipocytes the level of GLUT4 in plasma membrane was changed, but it was decreased in the low-density microsome fraction. Although adipocytes are less involved in blood sugar regulation than skeletal muscle, this finding suggests that glucose metabolism in Cushing's syndrome is affected partly by a decrease of GLUT4 in the adipocytes.