[A case of polymyositis associated with hypertriglyceridemia due to decline of lipoprotein lipase activity].
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Biomedical subjects
Publications and source records attributed to T Kodama.
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Abnormalities in plasma lipoproteins from patients with familial partial lecithin:cholesterol acyltransferase deficiency were studied. In these patients the plasma cholesterol ester ratio was about 40% and plasma apolipoprotein B level remained within the normal range. The content of large-sized low-density-lipoproteins (LDL) was low. Apolipoprotein B-100 and B-48 were detected in very-low-density lipoproteins (VLDL) and LDL in patients' plasma. In patients' LDL, apolipoprotein B-48 was primarily present in large-sized particles. Apolipoprotein E and A-I were mainly detected in intermediate-sized LDL. High-density lipoproteins (HDL) were separated into three fractions by gel permeation chromatography. Large-sized HDL particles (150-200 A) including discoidal particles contained apolipoproteins, E, A-IV and A-I. The content of discoidal HDL was low and, on electron micrograph, rouleau-formed particles were rarely seen. Normal-sized HDL (80-100 A) contained apolipoproteins A-I and A-II and small-sized HDL (about 60 A) contained only apolipoprotein A-I. Although several lipoprotein abnormalities were similar to those in classical familial lecithin:cholesterol acyltransferase deficiency, remaining lecithin:cholesterol acyltransferase activity may, however, cause a lack of reduction of apolipoprotein B level, a low level of large-sized LDL and also a low level of discoidal HDL.
Light and electron microscopic changes in human liver cells which were considered to be precancerous lesions, were studied. In our micrometrical examination, dysplastic liver cells were classified into two types: large and small dysplastic cell. Each type had nuclear pleomorphism and multinucleation; however, the nucleocytoplasmic ratio of the large dysplastic cell remained normal. Electron microscopically, the large dysplastic cell had some features of regenerative cells. The nucleocytoplasmic ratio of the small dysplastic cell was between that of normal hepatocytes and liver cancer cells. The difference in the incidence of the small and large dysplastic cells in normal livers and cirrhotic livers having hepatocellular carcinoma was statistically significant. In addition, the small dysplastic cell had more of a tendency to produce a small round focus. It was morphologically suggested that the more important candidate for the precancerous cell in the liver was the small dysplastic cell.
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Cell suspensions of human solid tumors could be separated into 5 or 6 subfractions for flow cytometry by centrifugation on a continuous silica gel (Percoll, Pharmacia Fine Chemicals, Upsalla, Sweden) density gradient. In all cases, there were one or more subfractions with enrichment of the aneuploid tumor cells. The greatest enrichment occurred in cases with fewer than 20% aneuploid cells in the original specimen; for these cases the enrichment factor ranged from 2.8- to 11.7-fold increase. In six cases with fewer than 7% aneuploid G0/1 cells initially, the aneuploid G0/1 DNA peak was difficult to demonstrate on the original specimen but became quite obvious in the subfraction. In no case were the tumor cells confined to a single subfraction. The distribution of tumor cells within two or more subfractions appeared related to differentiation in the case of squamous cells and to RNA content for other tumor cells. DNA/RNA flow cytometry proved useful in defining subpopulations of tumor cells with different DNA stemlines and varying positions in the cell cycle according to the RNA content of the respective subpopulation.
The cell source of peptide hormone production and the morphological differentiation were investigated in 18 adenocarcinomas of the lung by immunohistochemistry and/or by electron microscopy. These tumors were found by radioimmunoassay of tumor extracts to contain either one or more of 7 peptide hormones, i.e. adrenocorticotropin (ACTH), beta- and gamma-melanocyte stimulating hormones (MSH), somatostatin (SS), vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP) and calcitonin (CT). In a combined adeno- and small cell carcinoma, a considerable number of small tumor cells were positively stained for ACTH, beta- and gamma-MSHs and GRP. In a poorly differentiated adenocarcinoma with mucin and CT production, these products were localized in some single cells. Electron microscopy revealed secretory granules indistinguishable from exocrine or endocrine types. In another mucin-positive adenocarcinoma with high SS and CT contents, some tumor cells were stained for SS and/or CT. Two distinct exocrine and endocrine type secretory granules were found in the same cells. In tumors with 100 ng or less of the peptides/g tissue, most tumor cells were not stained for the peptides but a small number showed morphological endocrine differentiation. In conclusion, a considerable proportion of the adenocarcinomas of the lung may show heterogeneous differentiation in both endocrine and exocrine directions.
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Apolipoproteins B100 and B48 in human and rat plasma were studied by using sodium dodecyl sulfate (SDS) polyacrylamide gradient gel electrophoresis. On SDS gradient gel electrophoresis, human and rat apoprotein B100 co-migrated and had an apparent Mr equal 258,000 +/- 12,000. Human and rat apoprotein B48 had an apparent Mr equal 189,000 +/- 6,000. The molecular weight of human apoprotein B100 determined by sedimentation equilibrium analysis was 270,000 +/- 20,000, which was similar to the value determined by SDS gradient gel electrophoresis. However, on SDS polyacrylamide gel electrophoresis at constant concentration, the relative migration value of human apoprotein B100 was not constant when the concentration of polyacrylamide was changed. These results indicate that SDS gradient gel electrophoresis is more suitable for the analysis of apolipoprotein B's than ordinary SDS polyacrylamide gel electrophoresis.
To investigate morphological features of the human pancreatic ductal system, light and electron microscopic studies were performed, on the comparative basis with those of several species of mammals. The human pancreas possessed relatively well-developed ductal system, as compared with those of other mammals. Furthermore, it had unique centroacinr cells containing numerous mitochondria. The mode of innervation to the ducts, and cytological features such as cilia formation and mucin production were also revealed. Several kinds of endocrine cells including A, B, D1, ECn, presumptive EC1, and presumptive EC2 or K could be identified, but a few remained unclassifiable. The above findings are considered to be prerequisite for understanding the physiology, especially of bicarbonate production, and pathology, especially of oncogenesis of the exocrine and endocrine pancreas.
The earliest morphological evidence of altered growth potential of pancreatic acinar cells of the rats treated with carcinogen, such as azaserine, is the development of nodules of atypical acinar cells, some of which are considered to appear, eventually, as acinar cell carcinomas. On the other hand, there exist nodular lesions in the human pancreas, which are similar to atypical acinar cell nodules of the rats, in the sense of nodularity, multiplicity, size, and cytological features, such as pale cytoplasm. To clarify the plausibility of the human nodular lesions as a precursor of acinar cell carcinoma of the pancreas, light and electron microscopical studies were performed, using pancreases of 115 semi-consecutive series of autopsy cases and 20 surgical cases. Multiple nodular lesions were found in 3 autopsy cases and one surgical cases. Ultrastructurally, markedly dilated cysterna of rough-surfaced endoplasmic reticulum and intracisternal granules were the most prominent characteristics of the atypical cells of the nodules. These features are neither reported in chemically induced atypical acinar cell nodules and carcinomas nor in human acinar cell carcinomas. The human lesions were considered to be of degenerative nature rather than neoplastic.
Clinical and radiological findings in a 2-year-old boy with a large multilocular infratentorial arachnoid cyst are presented. The cyst was extended in the bilateral paracollicular and retrocerebellar region and was communicating with each other but not with the ventricular system. Associated with those cysts was a significant degree of hydrocephalus due to compression of the fourth ventricle. Delayed metrizamide CT scan showed totally isolated cysts from CSF circulation although the cystic content was determined as the CSF.
The rate of turnover of aqueous humor (Kout), as measured by the decay of radioactive inulin from the anterior chamber of the enucleated eye, was similar to the rate of loss of 125I-RISA (radioiodinated serum albumin) from the eye of a living rabbit. Arterial perfusion with 125I-RISA or rabbit serum showed that the permeability characteristics of the blood-aqueous barrier to protein molecules are unaffected in the enucleated eye. The viability of the enucleated eye for secretion of ascorbic acid was also examined, but the results were inconclusive.
The possible multiple effect of galactose diet and X-irradiation on cataract development in mice was investigated by scanning electron microscopy. X-ray cataracts were induced by maintaining animals either on a normal or 50% galactose diet. No detectable changes in lens morphology were seen in animals fed galactose alone compared with normal controls. 2 months after X-ray, less damage had occurred to the lenses of the galactose-fed animals compared to those on a normal diet. At 4 months after X-ray, animals on a normal diet developed mature cataracts, while in the galactose-fed animals they were delayed by 0.5-1.5 months. Suppression of the development of X-ray cataract by galactose feeding may be related to the ability of this sugar, which accumulates in mouse lens due to the low levels of aldose reductase, to act as a free radical scavenger.
Serum ferritin levels were studied in 264 patients who were consisted of 153 patients with various malignant neoplasms and 111 patients with various benign diseases. Positive rate of serum ferritin in all patients with malignant neoplasms was 35%. Hepatomas and pulmonary cancer showed relatively high positive rate, respectively 65% and 42%. In patients with benign diseases, hepatic diseases showed the high positive rate (52%) and the other benign diseases was low positive rate (11%). The relationship between serum ferritin and alpha-feto-protein in patients with hepatomas and other liver diseases was low. And the relationship between serum ferritin and CEA (carcinoembryonic antigen) in patients with malignant neoplasms of gastrointestinal tract was also low. It seemed that the measurement of serum ferritin levels will be of low value in the differentiation of the patients with malignant neoplasms.
The incidence and the behavior of endocrine cells in carcinomatous tissues were studied in 84 autopsy cases and 10 surgical or autopsy cases of pancreatic carcinoma, by light and electron microscope, respectively. It was found that the islets persistently survived in the carcinomatous tissues. In large duct type carcinomas, the islets showed unique familiarity with the carcinomatous ducts, which may be interpreted as suggesting interactions between ductal cells and islet cells in pancreatic carcinogenesis. Aside from these survivor islet cells, carcinomas exhibited different degree and kind of differentiation to endocrine cells, depending upon their histological types. Namely, neoplastic argyrophil cells were found at the incidence of 82% (large duct type carcinoma), 39% (small duct), 43% (adenosquamous), and 18% (undifferentiated one). Moreover, argyrophil cells with their apexes stretching far to the neoplastic lumen were found only in large duct type carcinoma and cystadenocarcinoma. In three cases of carcinoid or oat cell type carcinoma, argyrophil cells were diffusely scattered and irregular in shape. These findings further justify the classification, reported in the previous article. The differentiation to endocrine cells was confirmed also by electron microscope.
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Activities of beta-hexosaminidase A and beta-hexosaminidase B (Hex B) were measured both in human lung carcinoma and the adjacent normal tissues of 47 patients. The specific activity of total beta-hexosaminidase in the tumors was considerably higher than in the adjacent normal tissues, irrespective of histological types. In isoelectric focusing experiments, Hex B purified from normal lung exhibited a single peak with an isoelectric point (pI) of 7.9, while Hex B purified from adenocarcinoma contained two forms with pI 7.6 and 7.9. With respect to heat stability, Hex B from the normal lung was very stable at 52 degrees, while the tumor Hex B (mixture of pI 7.6 and 7.9 forms) was unstable. After treatment of the tumor enzyme with dithiothreitol, heat stability was restored. When the tumor pI 7.6 form was treated with dithiothreitol and subjected to polyacrylamide gel electrophoresis, the enzyme converted to a pI 7.9 form similar to that of the normal lung. Determination of the sulfhydryl group of the tumor pI 7.6 form under nondenaturing conditions showed that the enzyme had some easily reducible disulfide bonds on its surface. These findings indicate that the formation of mixed disulfide bonds in the tumor Hex B increases the net negative charge and results in the appearance of a heat-labile form.