Urinary organic acid profiles of a 12 year-old asymptomatic boy and his 14-year-old symptomatic male sibling were studied by means of gas chromatography-mass spectrometry, and both were chemically diagnosed as having propionic acidemia. The elder brother had developed frequent hyperammonemic attacks during infancy, while the younger had always been asymptomatic. The asymptomatic boy excreted diagnostic metabolites in quantities similar to those of his elder brother. Our observations indicate that propionyl CoA carboxylase deficiency is reflected in urinary organic acid profiles even in an asymptomatic case, and emphasize the importance of investigating the urinary organic acids of asymptomatic siblings of a propionic acidemia patient, especially when their urinary glycine levels are significantly elevated.
Serum adenylate kinase (AK) activity was measured in cerebral vascular diseases and the AK isoenzyme pattern was studied in the patients suffering from cerebral infarction, cerebral hemorrhage, myocardial infarction, and polymyositis. There was a significant difference in AK activity between the control subjects and patients with acute cerebral infarction. Serum AK activity showed a peak on the 2nd day to the 4th day after the stroke attack, maintained at high level for about one week, and decreased gradually thereafter. There were three isoenzymes (AK-1, AK-2, AK-3) of AK, and we found that the AK isoenzyme patterns were different in different disease. The AK isoenzyme patterns in patients with cerebral infarction and cerebral hemorrhage were different from those of control subjects. The AK-3 isoenzyme was dominant in the control subjects. The proportion of AK-1 isoenzyme was increased in cerebral infarction and cerebral hemorrhage compared with that for the control subjects, and the proportion of AK-2 isoenzyme was elevated in acute myocardial infarction and polymyositis. These results suggest that serum AK is a sensitive indicator of cerebral infarction and a useful marker to follow the course of patient recovery. Moreover, the analysis of AK isoenzymes is useful in the diagnosis of cerebral vascular diseases.
This study assessed the biochemical status of serum α-tocopherol (Toc) and lipid in university students (60 males and 51 females) and searched for risk factors of coronary heart disease (CHD). No significant differences were observed between the sexes in total cholesterol (T-C) (170 and 181mg/100ml for males and females, respectively), low density lipoprotein-cholesterol (LDL-C) (116 and 118mg/100ml), and phospholipids (PL) (193 and 199mg/100ml). The levels of high density lipoprotein-cholesterol (HDL-C) were lower in males (54mg/100ml) than in females (62mg/100ml, p<0.001) and those of triglyceride (TG) were higher (74 and 59mg/100ml for males and females, respectively, p<0.01). There were also no significant differences in HDL-C as a percentage of T-C (32 and 35%) and the LDL-C/HDL-C ratio (2.3 and 2.0). Toc level and the Toc/T-C ratio were significantly lower in males (5.16μg/ml and 3.11μg/mg, respectively) compared with females (6.15μg/ml and 3.46μg/mg, respectively) (p<0.001 for Toc and p<0.05) for Toc/T-C. A direct relationship was found between the T-C level and LDL-C (r=0.92, p<0.001) and HDL-C (r=0.40, p<0.001). The atherogenic index, the LDL-C/HDL-C ratio, showed a positive correlation with the T-C level (r=0.43, p<0.001) and a negative correlation with the HDL-C level (r=-0.63, p<0.001). The T-C levels also could be correlated with the levels of Toc (r=0.37, p<0.001) and inversely correlated with the Toc/T-C ratio (r=-0.41, p<0.001). The Toc/T-C ratio showed an inverse correlation with the LDL-C/HDL-C (r=-0.31, p<0.001). These results reveal that the T-C level affects the vitamin E status and that the Toc/T-C ratio can be used to assess trends in CHD risk factors.
To investigate the lipoprotein abnormalities in cachexic cancer hosts, we examined the apoprotein composition of high density lipoprotein (HDL) in patients with advanced gastric cancer. The patients had less apo A-I and apo A-II in the plasma and in HDL (specifically HDL3), less apo C-III0 and apo C-III1 in HDL2, and less apo C-III0 in HDL3 than the healthy controls. The major difference in apo HDL of the patients was the appearance of two abnormal apo-lipoproteins of pI 6.34 and pI 5.98 which were considered to be apo serum amyloid A antigen (SAA). Apo SAA showed an affinity for control HDL in the recombination study in vitro. But apo SAA-rich HDL was indistinguishable from control HDL by Sephacryl S300 column chromatography and an Agarose-Sephadex IEF.
The lipid peroxides in terms of malondialdehyde concentration, glutathione peroxidase activity and selenium level were determined in the blood of 22 elderly non-insulin-dependent diabetics of both sexes. The results were compared with the values obtained for 43 healthy persons of the same age. The lipid peroxide concentration in plasma and selenium level in whole blood and plasma were the same in both diabetics and controls. In the diabetes group a nonsignificantly lower (7%) selenium concentration in red blood cells was observed, whereas the glutathione peroxidase activity in erythrocytes of the patients tested was statistically lower (p<0.02) as compared with normals. In plasma, activity of this enzyme was increased by 14% as compared with healthy people, but without statistical significance. We found that selenium excretion in the urine found was significantly higher in the diabetics than in healthy people. We found a statistically significant, linear correlation (r=0.435, p<0.05) between enzyme activity and lipid peroxide concentration in plasma, and between plasma and urine selenium levels (r=0.937, p<0.001) in diabetes.
The content of cobalamin-binding protein (Cb1BP) was measured in stomach extracts and various cell lines. Cb1BP was increased in the cancer extract compared with non-cancerous control. The level of Cb1BP was also increased in serum-free culture medium of a gastric cancer cell line, but was almost undetectable in media of control cell lines. This output of Cb1BP in medium was suppressed by cycloheximide. These Cb1BPs were immunologically cross-reactive with anti saliva R binder antibody. The Mr, determined by immunoprecipitation, was 70kDa and the pI, 2.8-3.2. From these properties, this Cb1BP in cancer cells was considered to be an isoprotein of the cobalamin R binder. Histochemical studies showed that immunoreactive Cb1BP was confined to cytosol of cancer cells and cells in metaplasia. The present results suggest that Cb1BP of the R binder type is synthesized de novo in some type of gastric cancer cells and in metaplastic cells.
Adriamycin entrapped in small unilamellar vesicles (SUV-ADM) and that in multilamellar vesicles (MLV-ADM), composed of egg yolk phosphatidylcholine, cholesterol, and sulfatide in a molar ratio of 5:4:1, were examined for their effects on ovarian carcinoma AMOC-1 cells in comparison with free adriamycin. Cellular uptake and cytotoxicity were demonstrated for both SUV-ADM and MLV-ADM. The degrees of cellular uptake and cytotoxicity of SUV-ADM were comparable with those of free adriamycin, though those of MLV-ADM were somewhat lower than those of the free or SUV-entrapped drug. From these results and previous data obtained by pharmacokinetic study, the liposomes with the above composition are considered to be useful drug carriers for chemotherapy of ovarian tumors.
The mechanism of stimulation of glycogen synthesis by fructose was examined in perfused rat livers by application of a newly developed glycogen synthase assay method that measures UDP formation by high-performance liquid chromatography. In a liver perfused with 10mM glucose, glycogen accumulated at 0.10μmol glucosyl units/min/g, 13% of the rate in livers of refed rats. With 20mM glucose, the rate was 0.18μmol glucosyl units/min/g, and without glucose, glycogen decreased at a rate of 0.02μmol glucosyl units/min/g. With the addition of 2mM fructose to the perfusate, the rate was increased to 0.12, 0.34, and 0.54μmol glucosyl units/min/g at glucose concentrations of 0, 10, and 20mM, respectively. Thus, at the higher concentration of glucose, the larger increase of glycogen synthesis by fructose was observed. Similar phenomena were also observed in the changes of the activity of glycogen synthase and glucose 6-phosphate (glucose 6-P) level by fructose administration. Based on the good correlations observed between the rate of glycogen synthesis, % a form of glycogen synthase, and cellular glucose 6-P level, we conclude that stimulation of glycogen synthesis by fructose was due to activation of glycogen synthase, which in turn was brought about by the increase in glucose 6-P level. The increase in glucose 6-P level by fructose loading is thought to be due to not only increased supply of glucose 6-P but also inhibition of microsomal glucose 6-phosphatase by fructose 1-phosphate.
To detect the endogenous lipid peroxides in rat liver, the thiobarbituric acid (TBA) and hemoglobin-methylene blue (HMB) tests were used. The endogenous lipid peroxidation in rat liver was induced by peroxidative drugs, and then these tests were carried out. When CCl4, paraquat or phenobarbital was intraperitoneally injected, the HMB values were significantly increased only at the early period after the doses (1h), whereas two peaks of TBA value were observed at 1h and around 24h after the doses. When peroxidation was induced by thiopental or alcohol, the TBA value also gave two peaks. It was suggested that the agreement between detections by both HMB and TBA (the early peak) indicated the peroxide formation, and that the independent increase in TBA value (second peak) the accumulation of aldehydes in the liver. The life span of HMB-reactive substances was short in vivo compared with that of the TBA-reactive substances. It is considered that the TBA test was useful to detect the endogenous lipid peroxidation under the conditions that TBA test could detect aldehydes originating from lipid peroxidation because lipid peroxides were unstable in vivo.