Primary aldosteronism and hypercortisolism due to bilateral functioning adrenocortical adenomas

A 50-year-old male patient with a 15-year history of hypertension was referred to our hospital for evaluation of bilateral adrenal tumors. No Cushingoid features were observed. Computed tomographic scan showed 10-mm masses in each adrenal gland. Preoperative endocrinological examinations revealed autonomous cortisol and aldosterone secretion in this patient. The results of a subsequent adrenal venous catheterization study were consistent with the presence of a left cortisol-producing tumor and a right aldosterone-producing tumor. A left partial adrenalectomy was performed initially, but cortisol and aldosterone over-secretion persisted. Accordingly, the patient underwent a right adrenalectomy. Pathological examination of the resected specimens, including immunohistochemical analysis, demonstrated that both adenomas possibly produced cortisol and aldosterone. This is an extremely rare case of bilateral adrenal tumors, in which the left adrenocortical tumor produced and secreted cortisol or both cortisol and aldosterone and the right one produced and secreted both aldosterone and cortisol, as confirmed by clinical findings and pathological studies using immunohistochemical analysis.     

The role of homocysteine as a significant risk factor for white matter lesions in Japanese women with rheumatoid arthritis

The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. Plasma total homocysteine (tHcy), which increases with diabetes, has been flagged as a novel predictor for cerebrovascular events. We tested the hypothesis that the presence of WML correlates with tHcy in rheumatoid arthritis patients. Based on brain magnetic resonance imaging findings, 65 rheumatoid arthritis patients were divided into 2 groups: WML-positive group (61 ± 6 years, mean ± SD; n = 25) and WML-negative group (60 ± 7 years, n = 40). The level of metabolic parameters was assessed by total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and homocysteine (tHcy). The duration of rheumatoid arthritis was longer in the WML-positive group than in the WML-negative group (P < .05). Plasma levels of triglyceride was higher whereas high-density lipoprotein cholesterol was lower in the WML-positive group than in the WML-negative group (P < .05 and P < .01, respectively). Fasting plasma glucose (P < .05) and tHcy (<.0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the tHcy (odds ratio, 1.35; 95% confidence interval, 1.12-1.63; P < .0001). Our findings indicate that the presence of WML was associated with the tHcy in Japanese patients with rheumatoid arthritis.     

A case of Addison's disease confirmed with low dose cosyntropin stimulation test

An eighty-year-old man who had complained of skin pigmentation and weight loss was referred to our hospital. Upon physical examination, marked hyperpigmentation was found on the whole body including oral mucosa, tongue and fingernails. Endocrinological findings showed increased ACTH (126 pg/ml) and normal serum cortisol (15.4 microg/dl). First, we used a 250 microg cosyntropin stimulation test which is valid to diagnose Addison's disease, resulting in an adequate cortisol response. Second, we performed 1 microg cosyntropin stimulation test, and the cortisol response was blunted. Since the diagnosis of Addison's disease was fairly certain, he was treated with hydrocortisone 15 mg/day, and improvement of his skin pigmentation and an increase in body weight were observed. To our knowledge, this is the first report that 1 mug cosyntropin stimulation test was helpful to make diagnosis as having Addison's disease rather than the 250 microg cosyntropin stimulation test, although it is established that the 1 mug cosyntropin stimulation test is useful in secondary or relative adrenal insufficiency.     

Anti-tumor effect of the anti-KL-6/MUC1 monoclonal antibody through exposure of surface molecules by MUC1 capping

Human polymorphic epithelial mucin (MUC1) is a heavily glycosylated large protein that is frequently overexpressed on the surface of many human adenocarcinomas. Studies using monoclonal antibodies (mAb) identified MUC1 as a tumor-associated antigen that has been intensely studied as a target for cancer immunotherapy. We previously identified a mouse IgG(1) mAb that recognizes a sialylated sugar chain, designated as KL-6, classified in 'Cluster 9 (MUC1)'. Using the anti-KL-6 mAb, we investigated antitumor effects of anti-MUC1 mAb on breast cancer cell lines expressing MUC1 abundantly. We showed that anti-KL-6 mAb induced capping of MUC1 and facilitated E-cadherin-mediated cell-cell interaction in the breast cancer cell lines YMB-S and ZR-75-1S, which proliferate in suspension culture without aggregation. Moreover, anti-KL-6 mAb enhanced the cytotoxic activity of lymphokine-activated killer cells. These results indicate that the capping of MUC1 restores cell surface proteins, such as adhesion molecules and tumor antigens, to work in cell-cell interactions, leading to inhibition of tumor proliferation due to cell-cell adhesion and increased accessibility to effector cells that are needed to kill tumor cells.     

Aminopeptidase N is involved in cell motility and angiogenesis: its clinical significance in human colon cancer

BACKGROUND & AIMS: The molecular basis of cell motility is highly complex and is controlled by a number of molecular systems, whereas angiogenesis is an important biological component of tumor progression. The aims of this study were to investigate the possible involvement of proteins at the cell surface in controlling cell motility and angiogenesis, and to identify the cell surface molecules involved in gastrointestinal tumors. METHODS: We addressed these issues using functional monoclonal antibodies, which inhibit cell motility, endothelial cell migration, and tube formation. Furthermore, we investigated the relationship between this antigen and colon cancer, and showed the prognostic significance in human colon cancer. RESULTS: We established a murine monoclonal antibody MH8-11, which inhibits cell motility and in vitro angiogenesis. This epitope was a 165-kilodalton protein, and the sequencing analysis revealed that it was almost identical to aminopeptidase N (APN)/cluster of differentiation (CD) 13. APN/CD13 expression was associated with tumor status (P = 0.025). The disease-free and overall survival rate for patients with positive APN/CD13 expression tumors was significantly lower than that for patients with negative APN/CD13 expression tumors (P = 0.014, 0.033, respectively). Among 47 node-positive patients, the survival rate of patients with negative APN/CD13 expression was better than that of those with positive APN/CD13 expression. CONCLUSIONS: Our data suggest that APN/CD13 is involved in cell motility and angiogenesis, and APN/CD13 expression may be a useful indicator of a poor prognosis for node-positive patients with colon cancer.