[An autopsy case of Parkinson's disease manifesting hyperphagia and dysphagia followed by severe achalasia (disorder of motility) of the esophagus].
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Biomedical subjects
Publications and source records attributed to M Shoji.
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At least two substrate proteins for phospholipid-sensitive Ca2+-dependent protein kinase and at least six substrates for calmodulin-sensitive Ca2+-dependent protein kinase were identified in the cytosol of the guinea pig heart. In the particulate subfractions enriched in nuclei, mitochondria, microsome, or plasma membrane, no substrates for the phospholipid-sensitive enzyme were demonstrated but at least four substrates for the calmodulin-sensitive enzyme were identified. The present studies suggest that phospholipid, acting independently of calmodulin, is likely to be involved in the regulation of Ca2+-dependent protein phosphorylation in the heart. Phosphorylation of endogenous substrates for the two enzyme systems was effectively inhibited by palmitoylcarnitine. When histone was used as exogenous substrate, the carnitine ester inhibited the cardiac phospholipid-sensitive Ca2+-dependent protein kinase but not the cardiac cyclic AMP-dependent and cyclic GMP-dependent protein kinases. It is suggested that inhibition of the Ca2+-dependent phosphorylation of cardiac proteins, regulated by either phospholipid or calmodulin, is probably related in part to the great increase in this fatty acid metabolic intermediate in the ischemic heart.
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A widespread occurrence of Ca2+-dependent protein kinase was shown in various tissues and phyla of the animal kingdom. Phosphatidylserine appeared to be more effective than calmodulin in supporting the Ca2+-dependent phosphotransferase activity. The phospholipid-sensitive Ca2+-dependent protein kinase activity, distributed in both the cytosolic and particulate fractions, was not inhibited by trifluoperazine, a specific inhibitor of calmodulin-sensitive, Ca2+-dependent reactions or processes. The enzyme activity levels, compared to those of cyclic AMP-dependent and cyclic GMP-dependent protein kinases, were exceedingly high in certain tissues (such as brain and spleen) and exhibited a much greater disparity among tissues. The Ka for Ca2+ was about 100 microM in the presence of phosphatidylserine; the value was as low as 2 microM in the presence of phosphatidylserine and diolein. It is suggested that phospholipid-sensitive Ca2+-dependent protein kinase may mediate certain actions of Ca2+ in tissues, acting independently or in a complementary manner with other protein phosphorylation systems stimulated by calmodulin-Ca2+, cyclic AMP, or cyclic GMP.
The plasma and 24-hr urinary levels of cyclic adenosine 3':5'-monophosphate and of cyclic guanosine 3':5'-monophosphate (cGMP) were determined for 19 healthy normal patients, 54 patients with six types of nonneoplastic diseases (cholelithiasis, peptic ulcer, coronary heart disease, hypertension, regional ileitis, and cirrhosis), and 54 patients with five types of neoplastic disease (cancers of the lung, colon, and breast, acute myelocyte leukemia, and Hodgkin's disease). The cyclic adenosine 3':5'-monophosphate levels of urine and plasma in normal subjects, in noncancer subjects, and in cancer subjects did not differ significantly. The cGMP levels in the noncancer group were similarly unchanged from those in the normal group. However, mean cGMP levels in the urine and plasma of patients with neoplastic diseases were, respectively, 2- and 3-fold greater than the normal values (p less than 0.005 for urine and p less than 0.05 for plasma). Pharmacokinetic studies with [3H]cGMP in nine healthy controls and 15 patients with neoplasia showed that the mean production rate of this nucleotide in patients with metastatic cancer was elevated when compared to normal patients, but many values fell within the normal range. In acute leukemia, the production rate was seven times normal, with four of five patients having values clearly outside the normal range. The plasma clearance rate in patients with neoplasia was not decreased when compared to that in normal patients. It is proposed that an increased production rate, rather than any change in plasma clearance, accounts for the increased levels of cGMP in the plasma and urine of some patients with neoplastic disease.
The cellular origin and the mechanism of steroidogenesis were investigated on one case of recurrent type of granulosa cell tumor. Light and electron microscopic findings indicated the cell component was non-luteinized granulosal element and neither fibroblastic nor thecal ones. These tumor cells were cultured as monolayers and steroids (estradiol-17 beta, dehydroepiandrosterone, progesterone and 17-hydroxyprogesterone) secreted in the medium were measured by radioimmunoassay. Despite low level of estrogen, progesterone or testosterone in the serum or urine preoperatively, the estradiol-17B level in the culture medium after three days of cultivation reached over 900 pg/ml. In both light and electron microscopic observations of the cultured cells, morphological characteristics of activation of steroidogenesis were noted. It is concluded that this type of granulosa cell tumor consisting exclusively of the granulosa element without thecal one has the activity of estrogen production.
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35 deaths of 299 operated early stomach cancers have been studied retrospectively. These cases can be grouped in the following categories: 2 deaths directly due to operation, 7 due to recurrence of carcinoma, 19 due to other diseases including cancer in other sites and 7 cases in which the real causes of death could not be elucidated. Special attention was paid on the 7 recurrent cases: In 4 of 7 patients the histological study revealed lymph and blood vessels invasion in their resected stomachs, lymphnodes metastases in 5 patients and positive cut-end in 2 patients. 5 of 7 patients died within 3 years after operation.
Plasma and 24-h urinary adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclic GMP) were measured by radioimmunoassay in 12 normal subjects, 33 patients with six types of non-neoplastic disease (cholelithiasis, peptic ulcer, coronary heart disease, hypertension, regional ileitis, and cirrhosis), and 34 patients with five types of disseminated neoplastic disease (acute myelocytic leukemia; Hodgkin's disease; and metastatic cancer of the lung, colon, and breast). In patients with non-neoplastic disease, cyclic nucleotide values in plasma and urine did not differ significantly (P greater than 0.05) from those in normal subjects. In patients with disseminated cancer, cyclic AMP values in plasma and urine likewise did not differ significantly from those in normal subjects. Plasma cyclic GMP, in contrast, was significantly elevated in all five types of cancer patients, and urinary cyclic GMP was significantly elevated (five times the normal mean) in patients with acute myelogenous leukemia and Hodgkin's disease.
12-O-Tetradecanoylphorbol-13-acetate, a potent promoter of carcinogenesis in mouse skin, enhanced differentiation of cultured mouse myeloid leukemia cells (M1) induced by human urinary protein or by lipopolysaccharide from Salmonella typhosa. 12-O-Tetradecanoylphorbol-13-acetate enhanced differentiation of all the markers tested, such as phagocytosis, Fc rosette formation, lysozyme activity, and morphological change. Other potent tumor-promoting macrocyclic plant diterpenes also enhanced the induction of differentiation, but no-tumor-promoting diterpenes did not. These findings were in marked contrast with generally accepted findings on the inhibitory effect of 12-O-tetradecanoylphorbol-13-acetate on terminal differentiation observed in other cell culture systems but consistent with the observations with some kinds of leukemia cells.