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Biomedical subjects

T Akino

Publications and source records attributed to T Akino.

At least 145 records · Page 8Linked to original sources

A case of bronchioloalveolar carcinoma. Ultrastructural and lipid-biochemical studies.

A case of bronchioloalveolar carcinoma was studied electron microscopically and lipid biochemically. Electron microscopic examination revealed that the tumor was composed of three different types of cells, undifferentiated cells, cells possessing lamellar inclusion bodies within the cytoplasm, and cells containing mucus droplets. The characteristic findings in the phospholipid profiles of this case of bronchioloalveolar carcinoma were a high content of saturated classes of phosphatidylcholine, especially of the dipalmitoyl type, and the occurrence of appreciable amounts of phosphatidylglycerol. These observations indicate that some of the tumor cells examined in this study had the characteristic feature of alveolar type II cell differentiation which is responsible for production of pulmonary surface-active materials. The value of phospholipid analysis in assessing such tumors is emphasized.

Adenocarcinoma↗

Biochemical characterization of pulmonary washings of patients with alveolar proteinosis, interstitial pneumonitis and alveolar cell carcinoma.

We have studied the biochemical compositions of fifteen pulmonary washings from seven patients with alveolar proteinosis, and two washings from two patients with interstitial pneumonitis and two from two patients with alveolar cell carcinoma. The pulmonary washing was separated into the supernatant and precipitate fractions by a brief centrifugation. Analytical results revealed that the pulmonary washings from patients with alveolar proteinosis contained much more protein and lipids as well as a higher percentage of phospholipid than did the pulmonary washings from other patients. With regards to alveolar proteinosis, the precipitate fraction, i.e., water-insoluble material, contained lipids as the major component, the majority of which was dipalmitoyl phosphatidylcholine. Protein in the sedimental material was small in amount, but was composed of proteins mainly of molecular weights of 62,000, 36,000, 28,000 and 15,000 as measured by SDS-gel electrophoresis. On the other hand, the supernatant fraction, i.e., water-soluble material, was composed predominantly of serum proteins, with the lipid content being lower than those in the precipitate fraction. These analytical findings support the idea that materials normally existing in the alveoli are excessively accumulated as alveolar-filling materials in alveolar proteinosis. It was also noted that there were marked differences in the lipid profiles between pulmonary washings from patients with alveolar proteinosis, and those from patients with other diseases, indicating that the biochemical composition of pulmonary washings tends to reflect the nature of an underlying disease. From these findings, the cause of the alveolar-filling materials found in alveolar proteinosis was discussed.

Adenocarcinoma, Bronchiolo-Alveolar↗

Characteristics of phospholipids associated with fibrins in partial thromboplastin test.

With the aim to obtain information on the role of individual phospholipids in the coagulation process, lipids associated with fibrins formed with partial thromboplastin reagents were examined. In the absence of the partial thromboplastin reagents, phosphatidylethanolamine and phosphatidylserine plus phosphatidylinositol in citrated plasma were incorporated preferentially into fibrin, although the main phospholipid associated with the fibrin was phosphatidylcholine. In the presence of the partial thromboplastin reagents, most phospholipids unseparable from the corresponding fibrins appeared to be derived from the reagents with little selectivity for individual phospholipids, except for lysophosphatidylcholine. These results suggest that phospholipids other than thromboplastic phospholipids may play some role in the coagulation process. The incorporation of lysophosphatidylcholine in the reagent into fibrins was significantly enhanced by the addition of activating agents (celite and ellagic acid), suggesting one role of the activating agents in fibrin formation.

Blood Coagulation↗

Source of lung surfactant phospholipids: comparison of palmitate and acetate as precursors.

The phospholipids and the fatty acid compositions of major phospholipids in rat lung parenchyma, microsomes, lamellar bodies and alveolar wash were quantified. Adult rats were injected simultaneously with [3H]palmitate and [14C]acetate into the femoral vein. The appearance of labeled phosphatidylcholine (PC), desaturated phosphatidylcholine (DSPC) and phosphatidylglycerol (PG) in each lung fraction was measured during short periods of time (5 min to 2 hr) after isotope administration. Relatively more PC, DSPC and PG labeled with acetate radioactivity in lung microsomes entered lamellar body and alveolar wash fractions than those labeled with palmitate radioactivity. However, there was no difference between palmitate and acetate labeled phospholipids in the transport from microsomes to lamellar bodies by phospholipid exchange proteins. On the other hand, prior injection of colchicine resulted in decrease in the transport of PC from microsomes to alveolar space to a relatively greater extent in the acetate radioactivity than in the palmitate radioactivity.

Acetates↗

Metabolic changes in scaly lesions of rat skin produced by essential fatty acid deficiency.

Marked changes in the structure and metabolism of lipids were observed at scaly lesions induced in the skin of rats by the feeding for four months of a diet deficient in essential fatty acids. The concentration of neutral lipids increased in the experimental skin specimens with the exception of free cholesterol. Analysis of fatty acids in the skin lipids of these essential fatty acid deficient rats showed a marked increase in monoenoic and eicosatrienoic acids, with a concomitant decrease in linoleic and arachidonic acids. Incubation of skin specimens from the essential fatty acid deficient rats with [2-3H]glycerol and [1-14C]acetate showed a marked increase in the incorporation of both precursors into all lipid classes. Particularly, their incorporations into phosphatidylcholine were predominant compared to other lipid classes. With regard to the molecular species of phosphatidylcholine, saturated-monoenoic and monoenoic-monoenoic species were highly synthesized in the skin from essential fatty acid deficient animals, and the synthesis of saturated-dienoic and tetraenoic species was very low with either precursor. Significant decreases in these labelings were also noted in saturated-saturated species. Addition of prostaglandin E2 to the incubation medium did not significantly affect the metabolism of any of the lipid classes in the skin from the essential fatty acid deficient rats. The present results, therefore, suggest that phosphatidylcholine containing linoleic acid may be a key lipid in the epidermal barrier function.

Acetates↗

Lipid-protein interaction in the photolysis of octopus rhodopsin.

Microvillar membranes of octopus photoreceptor cells were treated with phospholipase A2, phospholipase C, hexane, or their combinations. By these means, various membrane preparations containing qualitatively and quantitatively different lipids were obtained. The lipid composition and phospholipid content of the membrane preparations obtained by the above methods were determined. Photochemical processes in the digitonin extract of the native and treated membranes have been studied by flash photometry. The results suggest that several different variations in the lipids can affect the rates of the photochemical transformations; these are: the content of phospholipid, the amount of unsaturated hydrocarbon chains and free fatty acids.

Animals↗

Comparison of phospholipid profiles of primary adenocarcinoma in the lung and other organs.

Phospholipid profiles, particularly molecular structure of phosphatidylcholine, of human primary lung adenocarcinoma were compared with those of the histologically same type of carcinoma from other organs in order to search for a possibility that differentiates between primary and metastatic tumors in the lung. The saturated class, mainly containing palmitic acid at both positions, accounted for 20.8% of phosphatidylcholine in lung adenocarcinoma, whereas it accounted for only 6-10.7% in the adenocarcinoma of other organs. Adenocarcinoma of organs other than the lung had specific characteristics of unsaturated molecular classes of phosphatidylcholine for each organ. Stomach tumor had high contents of dienes and tetraenes with particularly high proportion of arachidonic acid at the 2-position. Breast tumor had a high content of monoenes, containing palmitoleic acid at the 2-position. Adenocarcinomas of rectum, colon and thyroid contained more dienes compared to lung adenocarcinoma.

Adenocarcinoma↗

Biosynthetic routes of molecular species of lung phosphatidylglycerol.

Rat lung phosphatidylglycerol contained about 21% of saturated species, a predominant of which was dipalmitoyl. The biosynthetic features of molecular species of the phospholipid were investigated by incubating rat lung slices with radioactive precursors. The labeling profiles of molecular species of phosphatidylglycerol by [2-3H]glycerol and [1-14C]palmitate were significantly different from that of diacylglycerol and phosphatidylcholine. Mono- and dienoic species of phosphatidylglycerol were shown to have extremely high reactivity with [3H]glycerol, but the labeling of saturated species were almost half of the saturated diacylglycerol. The rate of [14C]palmitate incorporation was significantly lower in the saturated species of phosphatidylglycerol as compared to that in diacylglycerol and phosphatidylcholine. It was also noted that the lung tissue can utilize 1-[1-14C] palmitoyl lysophosphatidylglycerol to form tetraenoic and polyenoic phosphatidylglycerol by the direct acylation and saturated phosphatidylglycerol probably by the transacylation. The data indicate that the saturated species of phosphatidylglycerol may be synthesized de novo via phosphatidic acid CDP-diacylglycerol route and also via transacylation pathway, but it may not be synthesized by the direct acylation pathway.

Animals↗

Phospholipids of the lung in normal, toxic, and diseased states.

The highly pulmonary concentration of 1,2-dipalmitoyl-sn-glycerol-3-phosphorylcholine (dipalmitoyllecithin) and its implication as an important component of lung surfactant have promoted investigation of phospholipid metabolism in the lung. This review will set the contents including recent informations for better understanding of phospholipid metabolism of the lung in normal state (physiological significances of lung phospholipids, characteristics of phospholipids in lung tissue and alveolar washing, biosynthetic pathways of dipalmitoyllecithin, etc.) as well as in toxic states (pulmonary oxygen toxicity, etc.) and in diseased states (idiopathic respiratory distress syndrome, pulmonary alveolar proteinosis, etc.) Since our main concern has been to clarify the most important route for supplying dipalmitoyllecithin, this review will be focused upon the various biosynthetic pathways leading to the formation of different molecular species of lecithin and their potential significance in the normal, toxic, and diseased lungs.

Fetus↗

Dietary regulation of dipalmitoyl phosphatidylcholine in the lung. Effects of essential fatty acid deficiency.

An essential fatty acid deficiency resulted in a significant decrease of saturated phosphatidylcholine in rat lung tissue, with the reduction being mainly due to that of dipalmitoyl species. This decrease was almost completely reversed by administration of a diet containing linoleate from seven days. The features of saturated phosphatidylcholine synthesis in the deficient rat lung slices were studied with labeled precursors in the presence of different concentrations of linoleate and oleate in the medium. Labeling patterns of saturated phosphatidylcholine using [2-3H]glycerol and [Me-14C]choline were unaffected in all ratios of linoleate to oleate examined. The incorporation rates of both [3H]acetate and [1-14C]palmitate into saturated phosphatidylcholine decreased in the deficient state, but that of the palmitate label increased markedly with increase in the concentration of linoleate in the medium. This stimulatory effect due to the increased linoleate concentration, however, was not found with the acetate label. While the utilization of 1-[1-14C]palmitoyl glycerophosphocholine by lung tissue was enhanced in the deficient state, in the presence of linoleate it showed almost the same level as that of the controls. The essential fatty acid deficiency resulted in an increase in the activity of liver choline kinase by 46%. However, other enzyme activities involved in phosphatidylcholine synthesis in the lung and liver were unaffected by the deficient state.

Acetates↗

Biosynthesis and turnover of individual molecular species of phosphatidylcholine in liver and bile.

The individual molecular species of rat liver diacylglycerol and phosphatidylcholine, and bile phosphatidylcholine were analyzed and the metabolism of the individual molecular species of liver and bile phosphatidylcholines was studied using bile fistual rats. 1. Bile phosphatidylcholine contained more palmitoyl-linoleoyl, and less stearoyl-linoeoyl and stearoyl-arachidonyl species than liver phosphatidylcholine. 2. More rapid incorporation of [2-(3H)]glycerol into palmitoyl-oleoyl and palmitoyl-linoleoyl species of phosphatidylcholine in bile as compared with that in the liver was found. This result seems to support the concept that a specific subpool, termed a dynamic pool, of phosphatidylcholine in the liver appears to serve for bile phosphatidylcholine. 3. When 1-[9,10-(3H)]palmitoyl- and 1-[1-(14C)]stearoyl-glycero-3-phosphocholines were injected intraportally, the specific activity of palmitoyl species of bile phosphatidylcholine exceeded that of liver phosphatidylcholine at 60 min after the injection, while that of stearoyl species in bile was still significantly lower than that in the liver. This result supports the idea that there is a specific mechanism concerning the preferential secretion of palmitoyl species into bile. 4. It was noted that liver phosphatidylcholine species in the dynamic pool have the same specific activity as that of bile phosphatidylcholine, and the size of the dynamic pool is about 5% of the total liver phosphatidylcholine. The turnover rate of palmitoyl-linoleoyl phosphatidylcholine in the dynamic pool was very rapid, and was almost the same as the formation rate of the phosphatidylcholine species from the corresponding species of diacylglycerol.

Animals↗

Metabolism of individual molecular species of phosphatidylcholine in the liver subcellular membranes and bile. Origin of bile phosphatidylcholine.

Membrane fractions, particularly microsomes and bile canalicular membranes, isolated from rat liver were examined, in order to elucidate the site of a subpool of phosphatidylcholine destined for bile in the liver cell which was demonstrated in a previous paper (Kawamoto, T., Okano, G. and Akino, T. (1980) Biochim. Biophys. Acta 619, 20--34). 1. The bile canalicular membranes isolated from rat liver were not contaminated by other membranes when examined by membrane marker enzymes, and showed typical membrane structure, when examined by electron microscopy. The activity of DCPcholine : diacylglycerol cholinephosphotransferase was almost absent from the bile canalicular membranes and acyl CoA : 1-acyl-sn-glycero-3-phosphocholine acyltransferase activity was 17% of that found in the microsomes. 2. The molecular class composition of phosphatidylcholine was similar in the bile canalicular membranes and microsomes. The proportion of palmitoyl and stearoyl species in the major molecular classes was also similar in both membrane types. 3. In the in vivo experiments with [2-(3H)]glycerol, the specific radioactivity of phosphatidylcholine and its species such as palmitoyl-linoleoyl species in the bile canalicular membranes were significantly higher than that in other membranes. When compared with the specific radioactivity of phosphatidylcholine species in bile that in the bile canalicular membranes was also distinctly higher.

Animals↗

Characteristics of phospholipids in human lung carcinoma.

Human lung carcinoma tissues with histological types of adenocarcinoma, squamous cell and small cell carcinoma were investigated for phospholipids. There were marked differences in the phospholipids between these lung carcinoma and normal lung tissue. A marked decrease in saturated phosphatidylcholine (PC), predominantly the dipalmitoyl species, was noted in the carcinoma, although they still contained 17-20% of the saturated classes. The lung carcinoma contained less phosphatidylglycerol (PG) and lyso-bis-phosphatidic acid and more cardiolipin and phosphatidylinositol (PI) than the normal lung tissue. These alterations observed in the lung carcinoma appeared to show that they lose the characteristic feature of phospholipids in the lung tissue. The differences in the lipid composition among different cell types of lung carcinoma were also noted. The squamous cell and small cell carcinoma contained more triacylglycerol and relatively higher dienes I (monoenoic-monoenoic) and lower dienes II (saturated-dienoic) of PG, respectively, as compared to adenocarcinoma.

Adenocarcinoma↗

Structural and metabolic alterations of lung phosphatidylcholines by essential fatty acid deficiency.

The influences of early changes in essential fatty acid deficiency on the structure and metabolism of lung phosphatidylcholine were studied. In addition to general characteristics observed due to essential fatty acid deficiency such as significant decreases in linoleate and arachidonate, and concomitant increases in oleate and eicosatrienoate, a pronounced decrease in palmitate was noted in lung phosphatidylcholine, particularly in the 2-position. The decrease of palmitate in lung phosphatidylcholine was due to a similar decrease in disaturated classes, particularly in the dipalmitoyl species. These structural changes in phosphatidylcholine were found to be more significant in alveolar wash than in lung parenchyma and lamellar body fractions. The specific activities of phosphatidylcholine and its disaturated classes in lung parenchyma and alveolar wash were significantly lower in the deficient state than in the controls at 2, 6, and 12 hr after the injection of [9,10(-3)H]palmitate. However, relatively more of the phosphatidylcholine in the deficient state appeared in the alveolar space, disappearing more rapidly from the alveolar space than did the phosphatidylcholine in the controls. These results suggest that dietary linoleate may be a factor in regulating the amount of disaturated phosphatidylcholine in the lung, a principal component of lung surfactant, and also a factor in controlling the metabolism of alveolar phosphatidylcholine.

Animals↗

Characteristics of phospholipids in microvillar membranes of octopus photoreceptor cells.

Characteristics of lipids in the microvillar membranes of octopus photoreceptor cells were studied in order to obtain some information on the membrane environment with rhodopsin in the invertebrate. (1) The membranes contain lipid and protein in almost equal proportion. The majority of lipids are phospholipids. Neutral lipids make up 16% of the total lipids, the major constituent of which is cholesterol. (2) Phosphatidylethanolamine and phosphatidylcholine are the major phospholipids. Phosphatidylserine, ceramide 2-aminoethylphosphonate and sphingomyelin occur as minor components. An unidentified alkaline and acid stable phospholipid was found. (3) The predominant fatty acids of phosphatidylethanolamine and phosphatidylcholine are highly unsaturated such as 22 : 6, 20 : 5 and 20 : 4. The 22 : 6 and 20 : 5 are exclusively linked at the 2-position, but the 20 : 4 is linked significantly at the 1-position of the phospholipids. (4) Major molecular species are 16 : 0/22 : 6 (48.4%) and 16 : 0/20 : 4 (19.6%) in phosphatidylcholine, and 20 : 4/22 : 6 (50.7%) and 16 : 0/22 : 6 (25.6%) in phosphatidylethanolamine.

Animals↗

Variations in the molecular species of lung phosphatidylglycerol.

Approximately 20% of the phosphatidylglycerol of the lung tissue of several animals was found to have both fatty acids saturated. Pulmonary washings from the lung of the rabbit and guinea pig had more saturated phosphatidylglycerol than the washed lung tissue. Lung-saturated phosphatidylglycerol was relatively low in the perinatal period, a time during which saturated phosphatidylcholine accumulated predominantly. This suggests that the metabolism of the saturated species of lung phosphatidylcholine and phosphatidylglycerol, which are considered to be the major pulmonary surfactants, may not be regulated in the same manner, at least in the perinatal lung.

Aging↗