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Biomedical subjects

Y Kikkawa

Publications and source records attributed to Y Kikkawa.

At least 91 records · Page 5Linked to original sources
PubMed1989

Oxygen tolerance in neonatal rats: role of subcellular superoxide generation.

We compared the superoxide anion generating capacity of subcellular fractions from the lungs of neonatal and adult rats. Microsomal and mitochondrial fractions from adult rats produced approximately three times more superoxide (nanomoles per minute per milligram protein) than fractions from neonatal rats in the presence of 100% O2. Subcellular superoxide anion generating capacity was also examined in adult and neonatal rats exposed to greater than 95% fractional concentration of O2 in inspired gas. The O2- produced by mitochondrial and microsomal fractions of adult and neonatal rats increased above control levels for the first 24 h and declined below control values after 48 h of exposure in adults, whereas the elevated O2- production was sustained in microsomal fractions of neonates through 60 h. During the course of hyperoxic exposure, the largest difference in the superoxide generating capacity between adult and neonate was observed after 8-24 h of hyperoxia. The microsomal and mitochondrial fractions from adult rats produced three to seven times more O2- compared with neonatal rats. Cu,Zn superoxide dismutase (SOD) increased during the course of hyperoxia only in neonates at 8, 24, and 48 h of exposure. No change was observed in the activity of Mn SOD. The ratio of SOD activity (units per lung) to subcellular superoxide generating capacity (nanomoles per minute per lung) was calculated for the normal adults and neonates. The ratio for adult rats averaged 23 and 17 for mitochondrial and microsomal fractions, respectively, and 51 for neonatal rats for both subcellular fractions under normoxic conditions. These results suggest that O2- tolerance of neonates may be explained by the favorable balance between antioxidant defenses and subcellular superoxide generating capacity. The role of increased activity of Cu,Zn SOD as an accompanying or a causative phenomenon in O2 tolerance of neonates could not be determined from these experiments.

Aging↗
PubMed1989

Effect of alveolar hypoxia on pulmonary mast cells in vivo.

This study was undertaken to explore the effects of alveolar hypoxia on perivascular and periairway mast cell populations. Pulmonary mast cells were exposed to unilateral alveolar hypoxia by ventilating one lung of a cat with nitrogen. Mast cells from the contralateral lung, which was simultaneously ventilated with air, were used as a control. The granule content of perivascular and airway mast cells was determined from electron micrographs using morphometric methods. In response to alveolar hypoxia there was a 12% (p less than 0.005) decrease in the granule content of perivascular mast cells but no statistically significant change in periairway mast cell content. Perivascular mast cells from the hypoxic lungs did not show any of the morphological changes seen in IgE-mediated mast cell degranulation, such as granule swelling, fusion, or exocytosis. In the hypoxic lung, morphometric analysis revealed a significant decrease in the proportion of heterogeneous-appearing granules in the perivascular mast cells. The different reactivity of perivascular and periairway mast cells may explain why alveolar hypoxia does not induce significant bronchospasm.

Animals↗
PubMed1987

Effects of poly I: poly C on rat pulmonary and hepatic cytochromes P-450 and b5.

Interferon inducing agents such as poly I:poly C have been shown to reduce the hepatic hemoproteins cytochromes P-450 and b5 along with the associated monooxygenase activities [el Azhary and Mannering, Molec. Pharmac. 15, 698 (1979)]. In a previous study [Kikkawa et al., Lab. Invest. 50, 62 (1984)], we demonstrated that the interferon inducing agent poly I:poly C reduces pulmonary microsomal hemoprotein by 50% when administered to rats. The current investigation was conducted to characterize these changes in more detail and compare them to analogous changes in the liver. Compared to controls, cytochrome P-450 in both the lungs and livers of poly I:poly C treated rats declined by 40% at 24 hr and 55% at 48 hr (P less than 0.01). By 72 hr the decline was only 25%. In contrast, cytochrome b5 levels declined by less than 30% of control values during the first 48 hr following poly I:poly C injection (P less than 0.01) and returned to control levels by 72 hr. These changes in both cytochrome P-450 and b5 were reflected in decreases in pulmonary microsomal hemoprotein. Benzphetamine-N-demethylase activity declined by 45% in lung microsomes at 48 hr (P less than 0.01) after injection of poly I:poly C, while 7-ethoxycoumarin-O-deethylase (P less than 0.05) and 7-ethoxyresorufin-O-deethylase activities declined by approximately 41%. In the liver from these same poly I:poly C treated groups, benzphetamine-N-demethylase declined by 66% (P less than 0.05), while 7-ethoxycoumarin-O-deethylase and 7-ethoxyresorufin-O-deethylase activities declined by 60% (P less than 0.02 and P less than 0.05 respectively).

Animals↗
PubMed1987

Antioxidant enzymes and survival of normal and simian virus 40-transformed mouse embryo cells after hyperthermia.

Relative cell survival and activity of the free radical scavenging enzymes superoxide dismutase, catalase, and glutathione peroxidase were measured in cloned normal (MEA) and SV40-transformed (SVMEA) mouse embryo cells exposed at 44 degrees C for 0-3 h. At 37 degrees C, all three enzymes were 2-5 times higher in MEA than in SVMEA. Hyperthermia did not significantly alter enzyme levels in either cell line but selectively reduced transformed cell survival to less than 5% while relative survival of normal cells remained above 75%. The latter, however, could be reduced to 25% when normal cells were pretreated with 3 mM diethyldithiocarbamate, an inhibitor of copper- and zinc-containing superoxide dismutase. Similar treatment rendered SVMEA extremely thermosensitive. On the other hand, sublethal heat treatment (15 min at 45 degrees C) of cultured cells resulted in a relative thermal resistance upon subsequent exposure to 45 degrees C for 1-4 h. This induced thermotolerance was associated with a rise in antioxidant enzyme levels and both became significant only 4-6 h after the initial heat treatment. Induced enzyme and thermotolerance levels in transformed cells remained, nonetheless, far below those of normal cells. The data show that inherent (in MEA) as well as induced (in SVMEA) thermotolerance is associated with high antioxidant enzyme levels while the reverse is true in the case of inherent (in SVMEA) and induced (in MEA) thermosensitivity. These findings suggest that increased production of oxygen free radicals may be involved in hyperthermic cell injury, which then becomes a function of basal or inducible levels of antioxidant enzymes. Induction of the latter by hyperthermia is apparently inefficient in transformed cells making them more vulnerable. Enzyme induction seems also to require a lag period of 4-6 h suggesting the possible involvement of an intermediate inducer(s) at molecular level. The so-called heat shock proteins may be candidates for such a role.

Animals↗
PubMed1987

Thyroid antigen-antibody nephritis: possible involvement of fucosyl-GM1 as the antigen.

Hyperthyroidism, microscopic hematuria, and proteinuria developed in an 11-year-old girl. Proteinuria decreased during treatment of hyperthyroidism with an antithyroid drug. On admission, serum anti-thyroglobulin antibody, antimicrosomal antibody, and immune complex were present. The thyrotropin binding inhibitory immunoglobulin (TBII) level was low. On the other hand, an antibody to the ganglioside component (fucosyl-GM1) was detected by an enzyme linked immunosolvent assay (ELISA). A thyroid biopsy specimen showed massive lymphocytic infiltration and interstitial fibrosis. A renal biopsy specimen showed marked proliferation of mesangial cells and increased mesangial matrix with focal segmental capillary wall abnormality. Electron microscopec studies demonstrated mild paramesangial dense deposits. By indirect immunofluorescence, granular glomerular basement membrane and mesangial staining were not detected with rabbit antibody to thyroglobulin, but were detected with rabbit antibody to fucosyl GM1. Fucosyl GM1 was also seen along the basilar aspect of the thyroid follicular epithelial cells. These observation suggests the development of glomerulonephritis mediated by thyroid antigen, particularly ganglioside component.

Antigen-Antibody Complex↗
PubMed1986

Myocardial infarction in rats. Infarct size, myocyte hypertrophy, and capillary growth.

To determine the compensatory reserve capacity of the ventricular myocardium following infarction, the left coronary artery in rats was ligated, and the animals were killed 40 days later. Infarcts affecting an average 23% of the left ventricle were characterized by a 27% hypertrophic growth of the remaining myocardium that produced a complete replacement of the necrotic tissue. In contrast, infarcts with an average 50% loss of mass resulted in 83% expansion of the spared myocardium that was inadequate for a complete restoration of ventricular tissue. Myocyte hypertrophy was 26% and 78% in small and large infarcts, respectively. Cellular hypertrophy in both cases involved significant increases in myocyte transverse area and myocyte length. After large infarcts, there was an 18% reduction in capillary surface and a 16% increase in the diffusion distance. Corresponding values for small infarcts were -10% and 9%. These alterations combined with the deficient reconstitution of myocardial mass following large infarcts resulted in 25%, 29%, and 30% deficits in the absolute amounts of capillary lumen, surface, and length per ventricle respectively. Even with small infarcts, a deficit was seen in capillary luminal surface (-16%), and length (-19%). In conclusion, we have demonstrated that cardiac hypertrophy following myocardial infarction is consistent with cellular shape changes characteristic of a combination of concentric and eccentric hypertrophic growth. However, cardiac muscle cells appear to be unable to compensate for the loss of mass induced by a 50% infarct. The inadequate adaptation of the capillary vasculature in the infarcted hearts suggests that the injured ventricle is more vulnerable to additional ischemic episodes.

Animals↗
PubMed1985

Effects of strenuous exercise on the quantitative morphology of left ventricular myocardium in the rat.

The adaptation of the structural components in the myocardium of the left ventricle to strenuous exercise was studied morphometrically in rats following a treadmill running program. The response of the left ventricle was evaluated separately in the interventricular septum and in the left ventricular free wall. Exercise produced a 24% growth of the septum without altering free wall volume. The hypertrophic expansion of the septum was characterized by a decrease in the volume fraction of capillary lumen in the myocardium (-20%), a reduction in the capillary luminal surface per unit volume of myocytes (-17%) and by an increase in the maximum distance from the capillary wall to the mitochondria of myocytes (9%). Although none of these changes were demonstrable on a statistical basis in the left ventricular free wall, similar results were obtained in the whole left ventricle by combining the data from the septum and free wall. Since the septum constitutes a functional unit with the free wall, it was concluded that the effect of excessive physical activity on the capillary parameters responsible for oxygen availability and diffusion could lead to a local reduction in the oxygenation potential of ventricular myocardium.

Animals↗
PubMed1985

Alteration in phospholipid content of lung of adult rats treated with methylprednisolone of high doses.

The effect of methylprednisolone (MP) of high dosage on not only surfactant lipids but also other phospholipid components of adult rat lungs was studied. In spite of the decrease in body weight after one and two intraperitoneal injections of MP of 50 and 100 mg/kg, the increase in content of phospholipids of post-lavaged lung tissue, alveolar white layer, and alveolar macrophages occurred. Although the phospholipid content in the lung tissue and white layer started to decrease by following MP treatment of higher doses, its amount in the white layer and macrophages continued to increase by 25 mg/kg of MP. These changes in the phospholipid content with MP treatment was mainly a consequence of the changes in the content of phosphatidylcholine, especially disaturated phosphatidylcholine, as a main component of lung surfactant. The changes in percentages of other phospholipid components, except for phosphatidylglycerol among total phospholipid in the white layer were not significant. Changes in the content and composition of phospholipid of the isolated epithelial type II cells from adult rat lung after one and two injections of MP (50 mg/kg) were similar to those shown in the lung tissue. Our results indicate that, in the adult rat lung, not only the biosynthesis of phospholipid including surfactant lipids but also its secretion into alveolar space are greatly stimulated by administration of MP of high doses.

Animals↗
PubMed1985

Myocardial response to infarction in the rat. Morphometric measurement of infarct size and myocyte cellular hypertrophy.

For determination of the effects of myocardial infarction on the recovery potential of muscle mass in the surviving tissue, ligation of the left coronary artery was performed in 3-month-old rats, and the infarcted ventricles were analyzed morphometrically a month after surgery. Comparisons were made with 4-month-old control rats that underwent sham operations and with 3-month-old control rats that were not operated upon for evaluation of the magnitude of infarct size and discrimination of the relative contribution of tissue growth that occurred in the surviving myocardium solely as a result of the change in age, from 3 to 4 months (postoperative tissue growth, or POTG), from the additional growth induced by infarction (hypertrophic growth, or HG). Coronary occlusion induced a 276-cu mm loss of ventricular tissue volume that corresponded to 43% of the total left ventricular mass, 648 cu mm. Over a 30-day period the remaining 372 cu mm of viable tissue expanded by 90% with an overall volume gain of 334 cu mm. This tissue augmentation consisted of 20% POTG, 67 cu mm, and 80% HG, 267 cu mm. Total myocyte volume increased 89%, from 302 cu mm to 571 cu mm, and average myocyte cell volume per nucleus increased 92%, from 16,500 cu mu to 31,600 cu mu. The expansion of the myocyte mass was the result of a 21% POTG and a 79% HG. Corresponding values for the myocyte population were 19% and 81%.

Age Factors↗
PubMed1984

Essential fatty acid deficiency: a suggestion concerning experimental design.

In experiments on essential fatty acid deficiency, various strategems have been used to balance the deficient and control groups for all nutrients except essential fatty acids. We suggest the use of a single fat-free diet for both groups, with essential fatty acids administered parenterally to the control (nondeficient) group once each week.

Animals↗
PubMed1984

Morphometry of right ventricular hypertrophy induced by myocardial infarction in the rat.

The growth response of the right ventricle was studied in rats following ligation of the left coronary artery, which produced infarcts comprising approximately 40% of the left ventricle. A month after surgery the weight of the right ventricle was increased 30%, and this hypertrophic change was characterized by a 17% wall thickening, consistent with the 13% greater diameter of myocytes. Myocardial hypertrophy was accompanied by an inadequate growth of the microvasculature that supports tissue oxygenation. This was seen by relative decreases in capillary luminal volume density (-27%) and capillary luminal surface density (-21%) and by an increase in the average maximum distance from the capillary wall to the mitochondria of myocytes (19%). In contrast, measurements of the mean myocyte volume per nucleus showed a proportional enlargement of these cells (32%), from 16,300 cu mu in control animals to 21,500 cu mu in experimental rats. Quantitative analysis of the right coronary artery revealed a 33% increase in its luminal area, commensurate with the magnitude of ventricular hypertrophy.

Animals↗
PubMed1984

Type II epithelial cells of the lung. VII. The effect of ascorbic acid and glutathione.

Ascorbic acid and glutathione deficiencies during the isolation of tissue cells could compromise metabolic functions involving their participation. This possibility was assessed by supplementing the medium used in the isolation of rabbit pulmonary type II cells with varying concentrations and combinations of ascorbic acid, glutathione, and glutathione's constituent amino acids, glutamine, cysteine, and glycine. Isolated type II cells were monitored for changes in their biosynthetic capabilities by examination of 3H-choline and 3H-leucine incorporation into phospholipids and proteins. In the presence of glutathione's constituent amino acids and low concentrations of ascorbic acid (0.056 and 0.56 mM) incorporation of radiolabeled choline and leucine by isolated type II cells was decreased by 50% compared with unsupplemented controls. Morphologic examination revealed that type II cells isolated in the presence of glutathione's constituent amino acids had reduced surface membrane blebbing and dilation of endoplasmic reticulum cisternae compared with unsupplemented controls. Intracellular glutathione levels in these cells was also increased by 100% compared with those isolated without the constituent amino acids. Type II cells isolated in the presence of ascorbic acid and the constituent amino acids attached to culture dishes with a 5-fold greater efficiency compared with unsupplemented controls. The supplementation of type II cell's isolation media with ascorbic acid and glutathione's constituent amino acids produces several beneficial affects possibly through reducing intracellular oxidant damage, although other mechanisms of action cannot be ruled out.

Animals↗
PubMed1984

Protective effect of interferon inducers against hyperoxic pulmonary damage.

Interferon inducers, poly I:poly C, endotoxin, hepatic RNA, and Tilorone, were administered to rats at different time points in relation to the onset of hyperoxic exposure (O2 greater than 97%). All interferon inducers tested significantly reduced the mortality of rats when compared with the control groups. In hyperoxia alone, malondialdehyde, a product of lipid peroxidation, was significantly increased and the microsomal enzyme NADPH cytochrome c reductase decreased as measured in the whole lung. With the administration of either endotoxin or poly I:poly C these two parameters remained within the range of control values. These data suggest that the administration of interferon inducers protects against hyperoxic microsomal damage. After the administration of these interferon inducers with or without hyperoxia the increased activity of heme oxygenase and marked reduction of the heme content of microsomes were demonstrated. Since cytochrome P-450 and b5 are the major hemoproteins of microsomes and the known source of oxygen-free radical generation, the results obtained in this study appear to indicate that the depression of the hemoprotein of microsomes by the administration of interferon inducers may be largely responsible for the protective effects of these agents against hyperoxia.

Animals↗
PubMed1983

The effect of anti-oxidants and medium composition on isolation and culture of alveolar type II pneumocytes.

Alveolar type II pneumocytes were isolated from adult male rabbits and were placed in primary culture. The presence of anti-oxidants throughout the isolation procedure, particularly ascorbic acid and glutathione, was found to enhance in vitro attachment efficiency of cells. The use of a culture medium substituting D-valine for L-valine also significantly enhanced attachment efficiency. Although these cells do not ordinarily proliferate in culture, a low-serum medium containing insulin, transferrin, selenium and hydrocortisone allowed limited proliferation in addition to promoting dome formation in culture.

Animals↗
PubMed1983

Morphometry of exercise-induced right ventricular hypertrophy in the rat.

In our morphometric study of the effects of exercise on the heart, male Wistar-Kyoto rats at 5 weeks of age were subjected daily to a moderate treadmill running program that lasted for 7 weeks. The heart responded to physical conditioning by different magnitudes of tissue growth of the right (22%) and left (7%) ventricular myocardium, the latter change not statistically significant. The increase in right ventricular volume was associated with a 25% enlargement of ventricular area, a 26% average lengthening of the myocytes, and no change in sarcomere length and in ventricular midwall thickness. Exercise produced significant alterations in the quantitative parameters of the microvasculature of the right ventricle, but no appreciable changes in the left ventricle. Right ventricular hypertrophy was characterized by an absolute 44% growth of the endothelial luminal surface brought about through a 16% increase in capillary numerical density, and a 41% augmentation of the total length of the capillary network. Maximum diffusion distance from the capillary wall to the mitochondria of myocytes decreased 10% as a result of capillary proliferation and the lack of lateral expansion of myocyte cross-sectional area. Evaluation of the subcellular constituents of myocytes showed no change in the mitochondria:myofibrils volume ratio, indicating a growth of these components proportional to each other and to the growth of the myocyte population as a whole. It was concluded that, as a result of running exercise, right ventricular growth is analogous to eccentric hypertrophy in which the structural adaptations of the capillary bed can be expected to improve the diffusion and transport of oxygen within the tissue.

Animals↗