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.     

Inhibitory Effect of Laser Irradiation on Dermal Syngeneic Tumor Growth in Mice

Mice (C57BL/6) with established intradermal tumors (melanomaB-16 or glioma 203G1) and inbred Swiss mice (SWM/Ms) with establishedintradermal tumors (3-methylcholanthrene-induced sarcoma) weretreated by either surgical excision or laser irradiation. Laserirradiation is effective in preventing the growth of dermalmelanoma, and laser therapy may be more efficacious than surgicaltherapy for induction of a reaction against melanoma in mice. The results also suggest that determination of a suitable laserwavelength may be required to obtain a good therapeutic effecton each tumor.     

High prevalence of antibody to hepatitis C virus in heavy drinkers with chronic liver diseases in Japan

To investigate the prevalence of antibody to hepatitis C virus (anti-HCV) in heavy drinkers with liver disease in Japan, we tested serum samples from 113 heavy drinkers with liver disease and 121 without liver disease. All were negative for HBsAg with no history of blood transfusion. These subjects had consumed more than 80 g of ethanol daily for 5 years or more. Findings for anti-HCV determined by recombinant immunoblot assay testing were positive in 14 (35.9%) of the 39 patients with liver cirrhosis, 14 (58.3%) of the 24 patients with hepatocellular carcinoma and in 8 (53.3%) of the 15 patients with chronic hepatitis. The anti-HCV positive rate in the drinkers with these liver diseases was significantly higher than in those with such disorders as fatty liver (0/10), hepatic fibrosis (0/22), and alcoholic hepatitis (0/3), as well as in the alcoholics without liver disease (5/121, 4.2%). Considering histologic findings in the anti-HCV positive cirrhotics, the occurrence of lymph follicle formation (71.4%), piecemeal necrosis (78.6%) and loose fibrosis (64.3%) were observed to a significantly higher extent than in cirrhotics who were negative for anti-HCV. These findings suggest that advanced chronic liver disease among heavy drinkers in Japan, especially of hepatocellular carcinoma, is closely associated with HCV infection. In the livers of heavy drinkers who were positive for anti-HCV, histologic findings indicated the possibility of viral infection.     

Changes in the enzymatic activities of beagle liver during maturation as assessed both in vitro and in vivo

1. The metabolism of 50 μM [3-¹⁴C] coumarin has been studied in a panel of 12 human liver microsomal samples of known P450 isoenzyme profile.

2. [3-¹⁴C] coumarin was metabolized by human liver microsomes to various polar products including 3-, 4- and 7-hydroxycoumarins (3-HC, 4-HC and 7-HC) 6,7-dihydroxycoumarin (6,7-DiHC), o-coumaric acid (o-CA), o-hydroxyphenyl-acetaldehyde (o-HPA), o-hydroxyphenylethanol (o-HPE), o-hydroxyphenylacetic acid (o-HPAA) and o-hydroxyphenylpropionic acid (o-HPPA) and to product(s) that bind covalently to microsomal proteins.

3. For all 12 subjects, mean rates of [3-¹⁴C] coumarin metabolism to total polar products (metabolism to all products except product(s) covalently bound to microsomal proteins), 7-HC, the 3-hydroxylation pathway (sum of 3-HC, o-HPA, o-HPE and o-HPAA), o-HPPA, 6,7-DiHC and covalent binding were 1420, 1230, 73.8, 52.5, 9.5 and 4.8 pmol/min/mg protein respectively.

4. Marked interindividual differences in [3-¹⁴C] coumarin metabolism to total polar products (30-fold variation) and 7-HC (2250-fold variation) were observed.

5. Good correlations were observed between [3-¹⁴C] coumarin metabolism and total polar products, 7-HC, o-HPPA and 6,7-DiHC, but not to 3-hydroxylation pathway products and levels of 2A6 and 2B6 in human liver microsomes.

6. [3-¹⁴C] coumarin metabolism to any polar products did not correlate with levels of 1A2, 2C8, 2C9, 2E1, 3A3/4 and 4A1 in human liver microsomes.