Studies on Ectopic ACTH-Producing Tumors: III. An Ectopic Melanocyte-Stimulating Hormone: Gel Chromatographic Finding and Time-Lapse Color Change of Frog Skin

On isolation of the main melanocyte-stimulating factor fromthe metastatic liver tumor of islet cell carcinoma of the pancreas,it was found to be a peptide resembling human ß-MSHin the time-lapse skin darkening response of Xenopus frogs,but different in the volume of elution on Sephadex gel chromatography.     

Effect of FK506 on the activation state of hepatic macrophages in Propionibacterium acnes-treated rats

Activated hepatic macrophages can provoke massive liver necrosis following endotoxin stimulation through microcirculatory disturbances due to sinusoidal fibrin deposition in rats pretreated with heat-killed Propionibacterium acnes. In these rats, FK506 (tachlorinus) administered 24 h before and at the time of endotoxin injection, significantly attenuated liver injury compared with the rats given no FK506. The effect of FK506 on hepatic macrophage activation and its action sites were studied in Propionibacterium acnes-treated rats. When rats received Propionibacterium acnes intravenously, hepatic-mRNA expression of interferon-γ-inducing factor and interleukin-2 and splenic-mRNA expression of interferon-γ were significantly increased compared with normal rats. Hepatic-mRNA expression of CD14, a receptor for lipopolysaccharide and its binding protein complex, was also increased preceding the expressions of the three cytokines in the liver and spleen. FK506 administration attenuated hepatic-mRNA expression of interleukin-2 and both superoxide anions as well as tumour necrosis factor-α production by hepatic macrophages, but did not change CD14-mRNA expression in Propionibacterium acnes-treated rats. It is suggested that a cytokine network through interferon-γ-inducing factor, interferon-γ and interleukin-2 may operate during activation of hepatic macrophages in rats treated with heat-killed Propionibacterium acnes, while CD14 expression on the cells may increase independently of this network. FK506 seems to attenuate such activation by suppressing hepatic interleukin-2 expression, without affecting CD14 expression on the cells.     

Prostate-specific antigen doubling time among Japanese men in an annual health screening program

BACKGROUND: Prostate-specific antigen doubling time (PSA-DT) has been studied as a parameter reflecting the biological doubling rate of clinically localized prostate cancer treated expectantly. With the use of PSA-DT, we studied the natural history of PSA changes among Japanese men in a health screening program. METHODS: Between July 1994 and December 2002, a cohort of 1995 men aged 40-79 years underwent a total of 5700 PSA measurements in an annual multiphasic health screening program. Prostate-specific antigen doubling time was calculated using a log-linear regression model for 994 (49.8%) men who had three or more serial PSA measurements with a mean follow-up of 46.2 months. RESULTS: Of the 994 men, 192 (19.3%) had a PSA-DT of less than 10 years and 12 (1.2%) had a PSA-DT of less than 2 years. Median PSA-DT in 14 men with a subsequent diagnosis of prostate cancer was 41.6 months (range, 12.2 to stable). A log-linear model statistically fitted 65 of 180 non-cancer patients with a PSA-DT of less than 10 years. The percentages of statistically fit cases increased with higher baseline PSA (5.3%, 7.7% and 8.7% among men with <1.0, 1.0-1.99 and 2.0-3.99 ng/mL, respectively) and older baseline age (3.7%, 8.5% and 6.9% among ages 40-49, 50-59 and 60 or older, respectively). CONCLUSION: In a small but significant portion of men, PSA increases exponentially when it is still less than 4.0 ng/mL, with a PSA-DT of less than 10 years. The clinical significance of this finding should be evaluated by a prospective screening including biopsy.     

Low levels of apoptosis and proliferative activity in colorectal villous tumors: Comparison with tubular tumors

In order to clarlfy the cell kinetics of colorectal villous tumors (VT), 21 villous adenomatous areas and 12 carcinomatous areas within villous adenomas were investigated for proliferative activity and apoptosis and compared with a series of 41 tubular tumors (TT), demonstrating elements of intramucosal carcinomas as well as tubular adenomas (so-called carcinoma in tubular adenoma). Proliferation was estimated in terms of KI-67 labeling indices and mitotic indices, and apoptosis was assessed by DNA nick-end labeling to give apoptotic Indices. Apoptotic indices of villous adenomatous and carcinomatous regions were significantly lower than the values for their tubular counterparts. Kl-67 labeling indices were also significantly lower for adenoma components. Apoptotic indices, Ki-67 labeling indices and mitotic Indices increased with atypia raised in tubular adenoma components. Correlations of mitotic indices with apoptotic indices, Ki-67 labeling Indices with apoptotic indices and mitotic Indices with Ki-67 labeling indices were found for each villous tumor group and tubular tumor group, and the apoptosis and proliferation ratios for villous tumors were relatively low, suggesting a tendency for greater growth due to less cell deletion. Although this is only one of the biological features of villous tumor groups, it might play a major role in generation of malignancy.     

Pregnancy outcome after treatment with etoposide (VP-16) for low-risk gestational trophoblastic tumor

The aim of this study was to evaluate subsequent fertility and pregnancy in patients treated for persistent trophoblastic tumors with single-agent VP-16. Records of all patients treated for persistent trophoblastic tumors at the Chiba University Hospital between January 1, 1986 and December 31, 1997 were reviewed. Of these, 85 patients were initially treated with single-agent VP-16. Subsequent pregnancy outcome of these patients was investigated. After remission with VP-16, 36 patients (92.3%) of those who wished for a pregnancy (45.9% of all patients studied) conceived, and 91.7% had at least one live birth. A total of 56 conceptions resulted in 42 (75.0%) term live births, seven (12.5%) first-trimester spontaneous abortions, one (1.8%) second-trimester spontaneous abortion, four (7.1%) therapeutic abortions, and two (3.6%) repeated moles. There were no congenital anomalies, no stillbirths, and the neonates' physical growth was comparable to that of the standard population in Japan. Single VP-16 regimen for patients with low-risk gestational trophoblastic tumor appears to have no adverse effects on fertility potential and pregnancy outcome.     

Renal cell carcinoma in dialysis patients: A single center experience

AIM: Renal cell carcinoma (RCC) is a life-threatening complication of end-stage renal disease with an unclear pathogenesis. We evaluated RCC developing in patients undergoing dialysis. METHODS: In 2624 patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis at our hospital between July 1993 and March 2004, we performed annual screening for RCC using abdominal computed tomography and ultrasonography. Patients diagnosed with RCC underwent radical nephrectomy as well as clinical and pathologic evaluation. RESULTS: RCC was detected in 44 patients (1.68%; 31 males and 13 females). The age of RCC patients was 55.5 +/- 11.1 years. Dialysis duration before RCC diagnosis was 11.2 +/- 7.2 years. Most RCC were early stage and low stage by TNM classification, 43 patients had N0M0 RCC, whereas one had N1M0. Tumor size was 2.9 +/- 1.9 cm. The predominant histological type of RCC was common or conventional cell-type carcinoma (clear cell carcinoma and granular cell carcinoma). Of patients, 5(11.4%) had bilateral RCC, and satellite tumor lesions in RCC were detected in 13 (29.5%). In 36 patients (81.8%) RCC was accompanied by acquired cystic disease of the kidney. These patients had longer dialysis durations (P = 0.01) and smaller tumors (P = 0.048). RCC metastasized postoperatively in 4 patients (9.1%), while one (2.3%) died of cancer. CONCLUSIONS: Our dialysis patients showed a higher incidence of RCC than the general population. Prognosis was favorable because tumors were detected by screening when they were small. Therefore, periodical screening for RCC seems very important in dialysis patients.     

Beneficial Effects of Cervical Spinal Cord Stimulation (cSCS) on Patients with Impaired Consciousness: A Preliminary Report

Electrical stimulation of the spinal cord can be used for treatment of intractabie pain and spasticity. Based on our experimental findings cervical spinal cord stimulation (cSCS) was performed on eight patients with severe brain dysfunction due to traffic accidents, pronounced vasospasm caused by subarachnoid hemorrhage or surgery of huge cerebral tumors (chordoma). After a 1 to 2 month period of stimulation, two patients became conscious and began to speak. It remains unclear whether cSCS induced the restoration of consciousness and improved neurological deficits. Although the successful results might be due to chance, cSCS might have stimulated brain function. This preliminary report shows such excellent results that further studies are warranted.