Expression of Glycolipids Bearing Lewis Phenotypes in Tissues and Cultured Cells of Human Gynecological Cancers

Transformation-associated expression of Le^b (Lewis antigen-b) or Le^Y in human colorectal carcinomas has been well described. To examine the expression of glycosphingolipids (GSLs) bearing Lewis-phenotypes in human gynecological carcinoma-derived cells, we determined the concentrations of all GSLs. Although neither Le^b nor Le^Y was present in HEC-108 cells established from the poorly differentiated type of endometrial adenocarcinoma, other cell lines from moderately or well-differentiated types expressed either Le^b or Le^Y, or both, at concentrations of 0.01 to 0.03 μg per mg of dry cells, which comprised 0.3 to 1.3% of the total GSLs. In the cervical and ovarian carcinoma-derived cell lines, Lewis phenotypes tended to be carried by nLc₄Cer, which was accumulated in the cells without sialylation or fucosylation. These results indicated that expression of Le^b- or Le^Y-phenotypes was strongly dependent on the metabolic ability to supply the precursor GSLs. Both Le^b and Le^Y were successfully detected by monoclonal antibody MSN-1, which was a useful probe for the simultaneous detection of Le^b and Le^Y. On application of MSN-1, either Le^b or Le^Y was detected in tissues from patients with well- and moderately differentiated types of endometrial adenocarcinoma at concentrations of 0.01 to 0.04 μg per mg of dry tissues, but not in the tissues of poorly differentiated type. Normal endometria at the follicular and luteal phases also contained the antigens, but the concentrations and the frequency of antigen expression were lower than those in the well- and moderately differentiated types of endometrial adenocarcinoma.     

Interesting RI accumulation in hepatic images with Tc-99m GSA SPECT scintigraphy in idiopathic portal hypertension

The authors report a case of idiopathic portal hypertension (IPH), which showed interesting RI accumulation on Single Photon Emission CT (SPECT) images, with Tc-99m galactosyl human serum albumin (GSA) scintigraphy. Accumulation of Tc-99m GSA was decreased in the periphery of the liver where strong enhancement was revealed only in the arterial phase on dynamic CT. These findings imply that portal flow is decreased in the periphery of the liver where arterial flow is dominant. It was thought that secondary reduced activity of GSA due to a decrease in portal flow results in reduced radioactivity in the periphery of the liver in IPH. This interesting accumulation of Tc-99m GSA may be one of the sign of IPH.     

Enhanced Incorporation of 1-β-D-Arabinofuranosylcytosine by Pretreatment with Etoposide

We examined the effects of timing of administration of etoposide on cytosine arab-inoside (ara-C) incorporation into DNA in L1210 ascites tumor. At 1 hr after injection of ara-C, 3-hr and 6-hr pretreatments with 15 mg/kg of etoposide increased ara-C incorporation to more than 200% as compared to that of ara-C given alone. Simultaneous administration of etoposide, however, decreased ara-C incorporation to 33% of that of ara-C alone. These results might explain the previously reported sequence dependency of the antitumor effect of etoposide and ara-C.     

Sequential Observation of Rat Prostate Lesion Development Induced by 3,2'-Dimethyl-4-aminobiphenyl and Testosterone

3,2'-Dimethyl-4-aminobiphenyl (DMAB), when combined with high doses of testosterone propionate (TP) induces invasive adenocarcinomas with metastatic potential in the rat prostate. The processes underlying this tumor development, including the involvement of atypical hyperplasias, were sequentially investigated in F344 rats. DMAB was given subcutaneously at a dose of 50 mg/kg body weight 10 times at 2-week intervals. TP was administered chronically (in Silastic tubes) from the beginning of the experiment or after the DMAB administration until termination (week 60). Invasive adenocarcinomas were induced in the lateral and anterior prostate as well as the seminal vesicles. Atypical hyperplasias appeared from an early stage, with the later appearance of cancers being closely associated with such foci of morphological alteration. The findings confirm that combined administration of DMAB and pharmacological doses of TP yields invasive adenocarcinomas in the rat prostate and provide further support for the conclusion that atypical hyperplasias are premalignant lesions.     

Correlation between Medium-term Multi-organ Carcinogenesis Bioassay Data and Long-term Observation Results in Rats

The effects of four test chemicals [2-acetylaminofluorene (2-AAF), D, L-ethionine (ethionine), butylated hydroxyanisole (BHA), and catechol] were compared in medium- and long-term in vivo systems. In the medium-term assay, animals were sequentially treated with N-diethylnitrosamine (100 mg/kg body weight, i.p., single injection), N-methylnitrosourea (20 mg/kg body weight, i.p., 4 times during weeks 1 and 2), N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05% in the drinking water during weeks 1 and 2), 1,2-dimethylhydrazine (40 mg/kg body weight, s.c., 4 times during weeks 3 and 4) and dihydroxy-di-N-propylnitrosamine (0.1% in the drinking water during weeks 3 and 4) for multi-organ initiation, and then treated with one of the four test chemicals for 24 weeks, and killed at week 28 (group 1). In the long-term assay, animals were treated in the same manner and then given hasal diet and tap water (group 3) or test chemical continuously (group 4) for the remainder of the lifespan. Animals receiving multi-organ initiation and then maintained on hasal diet for 24 weeks (group 2) or their lifespan (group 5) served as controls. Detailed histopathological examinations were performed on all rats. Hepatocellular carcinoma incidences in the long-term assay were found to reflect closely the respective medium-term results. Induction of proliferative forestomach or glandular stomach lesions by BHA and/or catechol, and bladder lesions by 2-AAF and BHA in the mediumterm assay also correlated with tumor development in the long-term. Furthermore, inhibition of thyroid proliferative lesions by all test chemicals corresponded with low thyroid tumor incidences in the long-term assay. The observed strong correlation between medium- and long-term results confirms the applicability of our medium-term multi-organ carcinogenesis bioassay system for detection of modifying effects of test chemicals in different organs.     

The prevalence of vestibular schwannoma among patients treated as sudden sensorineural hearing loss

Objective

To assess the prevalence of vestibular schwannoma (VS) in patients with sudden sensorineural hearing loss (SSNHL).

Prion diseases: disease diversity and therapeutics]

More than one hundred victims of iatrogenic CJD with cadaveric dura mater grafting have been recognized in Japan, and the people have been also exposed to a risk of outbreaks of variant CJD. These diseases are distinct from other forms of prion diseases as well as other neuropsychiatric disorders, but on an early clinical stage, their differential diagnoses from other atypical forms of prion diseases are not necessarily easy. Thus, atypical forms of prion diseases were overviewed and discussed here. In addition, data on recent clinical trials of enteral antimalarial drug (quinacrine or quinine) treatment or intracerebroventricular pentosan polysulfate treatment were presented and discussed, because research progress in the therapeutics for prion diseases has been remarkably made on the basis of the prevalence of those acquired forms of prion diseases.     

CONGENITAL NEPHROTIC SYNDROME (FINNISH TYPE)

The case was a one year and four months old boy, who had been diagnosed as congenital nephrotic syndrome on the 4th day of life. He died of septicemia from peritonitis. Large pale kidneys, dilated trunk of pulmonary artery, and thickened left atrial endocardium were observed at autopsy. Renal histology seemed to be compatible with congenital nephrotic syndrome of the Finnish type. Viral antigens of herpes simplex type 1 and varicella-zoster in paraffin-embedded sections were proven to be negative. Besides renal change, increased number of pancreatic islets without hypertrophy was noticed. ACTA PATHOL. JPN. 35: 517–525, 1985.