Katsumi Iwase

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.

Recently, breast cancer screening with mammography has been recommended for detection of early cancer. We have carried out mammography screening for women aged over 30 years at Kasugai City Medical Care Center over the last 3 years. Every examinee underwent physical examination by a surgeon and mammography, and those who had abnormal findings and were unsuitable for mammography underwent ultrasonography. Sixteen breast cancer patients with a detection rate of 0.51% were found by the screening. Eleven tumors were palpable, 14 were detected by mammography, and 15 were detected by ultrasonography. Eleven of the 16 cancers were found at an early stage (stage 0 or I) and 5 were treated by partial mastectomy. Fibroadenoma was found in 16 of 121 women who received further examinations. Thirteen of the fibroadenomas were detected by mammography and 7 of them were not palpable. In 8 cases, malignancy could not be completely ruled out. Forty-one patients considered to have benign lesions at the screening were further examined during the first half of the study period, and only one case of cancer was found. Therefore, we omitted the examinees with obviously benign lesions from further examination in the second half of this period. Consequently, the number of examinees who required further examination was markedly decreased without any decrease in the cancer detection rate. <BR>In conclusion, breast cancer screening with physical examination and mammography is excellent for detecting early cancer. Furthermore, the ultrasonography is useful for further observation of lesions found by screening, and in patients who are unsuitable for mammography. The use of mammography or ultrasonography for screening increases the number of patients who require further examination, increases the psychological burden on examinees and raises medical expenditure. But the keeping better quality of the screening can improve these drawbacks.

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.