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Biomedical subjects

S Isoyama

Publications and source records attributed to S Isoyama.

At least 37 records · Page 2Linked to original sources
PubMed1994

Acute ischaemic preconditioning and chronic hypoxia independently increase myocardial tolerance to ischaemia.

OBJECTIVE: Myocardial adaptation has been reported to result from mild but chronic ischaemia in the hearts of patients with coronary artery disease. The aim of this study was to test the hypothesis that the responses of the chronically hypoxic myocardium to an episode of severe ischaemia, or the effects of acute ischaemic preconditioning on myocardial function after subsequent fatal ischaemia, may differ between the normoxic and the chronically hypoxic myocardium. METHODS: A rat model of three week hypoxia (10% O2) was used to simulate tissue hypoxia caused by chronic ischaemia. In isolated isovolumetrically contracting hearts perfused with oxygenated erythrocyte-containing Tyrode solution, systolic and diastolic functions during a 15 or 20 min period of ischaemia and reperfusion were measured in the normoxic control and chronically hypoxic groups. RESULTS: Increases in diastolic pressure during ischaemia were smaller and the recovery of developed pressure during reperfusion was greater in the chronically hypoxic group than in the normoxic group. The hearts of the normoxic group never recovered from ischaemic damage after 20 min ischaemia. The beneficial effects of acute preconditioning with 5 min ischaemia on myocardial function were observed after 15 min ischaemia in the normoxic group, and during and after 20 min ischaemia in the chronically hypoxic group. Changes in lactate production and high energy phosphates could not explain the increased tolerance to ischaemia in the chronically hypoxic group. CONCLUSIONS: Chronic hypoxia increased myocardial tolerance to ischaemia, and acute ischaemic preconditioning increased the tolerance further. Thus chronic hypoxia and acute ischaemic preconditioning independently activate protective mechanisms against ischaemia; the mechanisms may differ between the two types of insult.

Acute Disease↗
PubMed1994

Crossreactivity of IgE antibody against Dermatophagoides farinae with Limulus polyphemus agglutinin.

Crossreactivity of IgE antibody against Dermatophagoides farinae (Der f) with Limulus polyphemus agglutinin (LPA) was examined using RAST and immunoblot analysis. Of 40 Der f-sensitive asthmatic patients, 28 revealed a positive RAST reaction to LPA, while none of 20 Der f-insensitive hay fever patients showed this reaction. LPA-specific RAST levels of the 40 asthmatic patients correlated with their Der f-specific levels. The RAST reactivity to LPA was competitively inhibited by the addition of either soluble Der f or LPA, but not by the specific inhibitory sugar of sialic acid. LPA could also induce histamine release from leucocytes of Der f-sensitive asthmatic patients. IgE immunoblot analyses showed that the positive RAST sera for LPA had a strong IgE binding activity to the 30 kDa and 80 kDa components of Der f body extract, whereas gel filtration studies showed that the high molecular weight fractions above 150 kDa retained antigenic constituents associated with IgE reactivity to LPA. These results suggest that the antigenic materials of Dermatophagoides mites share some determinants with the haemagglutinin of horseshoe crabs.

Adolescent↗
PubMed1994

Effects of aging on induction of cardiocyte growth by extracardiac factors.

To examine the effect of aging on the induction of cardiac myocyte growth by extracardiac factors, we cultured myocytes obtained from neonates of the same litter and implanted them into the peritoneal cavity of developmental phase (2-mo-old), young adult (7-mo-old), and aged (18-mo-old) host Wistar rats. Hearts obtained from 2- to 4-day-old neonates were dissociated with gentle trypsinization, and cells were seeded in culture wells and inserts. The culture insert (9 mm in diam) has a thin membrane the pore size of which is 0.45 microns. After 24 h of usual extracorporeal incubation in the serum-supplemented medium, the inserts were implanted into the peritoneal cavity of the host rats of the three age groups. Zero, 24, 72, and 96 h after implantation into the peritoneal cavity, the inserts were removed from the peritoneal cavity. Surface area of plated myocytes, diameter, number, protein, and DNA content of the suspended cells were measured. Size, protein content per cell, and protein per DNA of cells implanted into the peritoneal cavity were significantly greater than those cultured in the usual extracorporeal method. Growth of the myocytes cultured in the peritoneal cavity of aged host rats was significantly less compared with that of myocytes implanted in the peritoneal cavity of younger rats. Thus aging attenuates the induction of cardiac myocyte growth by extracardiac factors.

Aging↗
PubMed1994

Diminished heat shock protein 70 mRNA induction in aged rat hearts after ischemia.

Vulnerability of aged hearts to ischemia may be due to defects in protective mechanisms provided by heat shock proteins (HSPs). To determine whether there is a defect in the induction of HSPs by ischemia in old hearts, HSP72 and HSP73 (inducible and constitutive HSP70, respectively) mRNA induction was examined in young (2-mo-old; n = 36) and old (18-mo-old; n = 32) rat hearts. Transient (10- or 20-min) ischemia was applied by tightening a snare placed around left coronary arterial branches 3 days before examination to avoid the effect of operation on induction. HSP72 mRNA was induced markedly in young hearts after 10-min ischemia, peaked at 2 h, but was induced only slightly in old hearts. HSP73 mRNA was also induced in young hearts, peaked at 4 h, but was not induced in old hearts. The mRNAs were markedly induced in old hearts as well after 20-min ischemia, which was accompanied by the induction of HSP72 protein. Thus the age-related modulation of HSP72 and HSP73 mRNAs suggests a defective sensing mechanism for ischemia in old hearts.

Aging↗
PubMed1994

Influence of age on IgE responsiveness to Dermatophagoides farinae: an immunoblot study.

IgE responsiveness to Dermatophagoides farinae body extract was compared by immunoblotting among four groups of mite-sensitive asthmatic children: group I aged 0-3, group II aged 4-7, group III aged 8-11 and group IV aged 12-15. In the group I subjects, the 15-kD component was bound by 88% of sera and strongly by 56% of sera. The 25-kD component was bound by 40% of sera, but most of the binding reactions were faint. IgE binding to other components was generally low. In the group II subjects, 15- and 25-kD components were bound by 96% and 56% of sera, 30-kD and 110-kD components by 76% and 60% of sera, respectively. In addition, 18-, 40-, 59- and 80-kD components were bound by more than 30% of sera. In group III and IV subjects, the frequencies of IgE binding to these components were not significantly changed as compared with those of group II subjects. The rabbit antisera against Der f I and Der f II specifically reacted with 25- and 15-kD components, respectively. These results suggest that the 15-kD Der f II allergen is the most important antigenic constituent associated with the early IgE response to house dust-mites in mite-reactive asthmatic children.

Adolescent↗
PubMed1994

Responses to hemodynamic stress in the aged heart.

In aged individuals the incidence of heart failure is higher than in younger subjects. Ischemic events are also common in the aged heart because of changes in the coronary vasculature and myocytes caused by aging. Adaptational responses to increased hemodynamic overload and to ischemia in the aged heart are discussed at the molecular, cellular and organ levels. One characteristic of the aged heart is a limited capacity for adaptation with hypertrophy to increased mechanical load. This age-related attenuation of the hypertrophic response may be attributed to the diminished induction of proto-oncogenes such as c-fos, c-myc and c-jun by hemodynamic stress. This diminution results from the aging of the heart per se and may be modulated by extracardiac factors. An age-related diminution was also observed in the mRNA induction of heat shock proteins by transient ischemia. However, this diminished induction of immediate early genes in the aged heart was not observed after more severe stress. With regard to the coronary vasculature, the age at which pressure-overload begins seems to be one of the important factors which determine the vascularity of hypertrophied hearts. Late-onset pressure-overload decreased dilator reserve in spite of the absence of myocardial hypertrophy. Thus, the responses to stress in the aged heart are quite different from those in the young heart. The limited capacity for adaptation to hemodynamic overload and poor protective mechanisms against stress may be causes of the higher incidence of heart failure in the aged.

Aged↗
PubMed1994

Hypertension and age-related changes in the heart. Implications for drug therapy.

Heart disease in older individuals can be characterised as the result of 2 processes, hypertension and atherosclerosis, which are the major causes of heart failure in the elderly population. The aging heart undergoes changes at the molecular, cellular and organ levels. These age-related changes may then be modulated by pathological conditions, such as hypertension, and by the reduction of blood pressure. One characteristic of the aged heart is a limited capacity for adaptation, by hypertrophy, to increased mechanical load. This age-related attenuation of the hypertrophic response may be attributed to the diminished induction of proto-oncogenes such as c-fos, c-myc and c-jun. This diminution results from aging of the heart per se and may be modulated by extracardiac factors. With regard to the coronary vasculature, the age at which hypertension develops seems to be an important factor for determining the vascularity of hypertrophied hearts. Late-onset hypertension is not accompanied by coronary angiogenesis, and it decreases dilator reserve in spite of the absence of myocardial hypertrophy. In contrast, mechanical overload in infant hearts is accompanied by angiogenesis and normal dilator reserve. In principle, the normalisation of hypertension results in the regression of myocardial hypertrophy and decreased coronary dilator reserve. In aged hearts, it is not clear how hypertension-induced myocardial hypertrophy or coronary vascular changes regress. Although antihypertensive treatment is clearly associated with an improvement of cardiovascular mortality and morbidity in hypertensive elderly individuals, it remains unclear how treatments ameliorate the hypertension-induced alterations.

Aging↗
PubMed1993

Separate regulation of heme oxygenase and heat shock protein 70 mRNA expression in the rat heart by hemodynamic stress.

To elucidate the role of heat shock proteins in hearts, we examined the expression of heme oxygenase (HO) and heat shock protein 70 (HSP70) mRNAs in hearts of rats subjected to hypoxia or pulmonary artery banding, both of which produce pressure overload to the right ventricle. At 3 d of hypoxia, HO mRNA levels were elevated about fourfold compared to the basal levels in both right and left ventricles, while HSP70 mRNA was not induced at all. Pulmonary artery banding markedly and immediately (within 6 h) increased HO mRNA levels in both ventricles, but induced HSP70 mRNA only in the right ventricle. This is the first in vivo evidence showing the separate regulation of HO and HSP70 gene expression in hearts by hemodynamic stress.

Animals↗
PubMed1993

Coronary dilator reserve and morphological changes after relief of pressure-overload in rats.

Using a rat model of short- (4 weeks) and long-term (10 weeks) ascending aortic banding and debanding, we examined the relationship between coronary dilator reserve and morphological vascular changes. After 4 or 10-week banding, in vivo systolic left ventricular pressure and ventricular wt/body wt ratio increased to a similar level, compared with controls. The coronary dilator reserve measured in an isolated heart preparation decreased similarly in the two banded groups, compared with controls. The ratios of medial to luminal area and perivascular collagen to luminal area in coronary microvessels increased in the banded groups. At 4 weeks after debanding, cardiac hypertrophy regressed to the control level, and the duration of banding did not alter the extent of the regression. The coronary dilator reserve normalized in the group debanded after 4-week banding, but did not regress in the group debanded after 10-week banding. In both of the debanded groups, the hypertrophied media regressed completely. The increased perivascular collagen regressed almost completely in the group debanded after 4-week banding, but remained greater in the group debanded after 10-week banding than in the controls. From these results, we conclude that (i) the regression of medial hypertrophy does not always improve the decreased coronary dilator reserve, and (ii) the vascular fibrosis may be the major cause of the irreversibility of decreased coronary dilator reserve in long-term cardiac hypertrophy.

Animals↗
PubMed1993

Effects of age on c-fos and c-myc gene expression in response to hemodynamic stress in isolated, perfused rat hearts.

Using an ex vivo model we examined whether the age-associated modulation of proto-oncogene expression was due to the aging of the heart per se. In the two age groups of Wistar rats (2 and 18 months), expression of c-fos and c-myc genes was determined in isolated, isovolumically contracting hearts (balloon in the left ventricle) perfused with Tyrode's solution containing bovine serum and red blood cells. In both age groups, a c-fos signal was detected at 30 min, increased further at 60 min, and declined at 120 min, while the c-myc signal was detected at 60 min and increased for a further 120 min after initiation of perfusion at 25 mmHg of end-diastolic pressure (EDP). The expression of these genes by 60 min of relatively mild hemodynamic stress was depressed in old hearts compared to that in young hearts (c-fos at 0 (P < 0.05), 5 (P < 0.05) and 15 mmHg of EDP (P < 0.01); c-myc at 5 (P < 0.05) and 15 mmHg (P < 0.05)). The age-associated differences in the expression of these genes were smaller under severe hemodynamic stress (25 mmHg of EDP). Peak systolic and diastolic wall stress calculated from left ventricular pressure, cavity volume and muscle weight were similar in the two age groups. Thus, aging diminishes the expression of proto-oncogenes and seems to elevate the threshold at which hemodynamic stress to the heart results in a response at the gene level. The age-associated modulation is caused by aging of the heart per se.

Aging↗
PubMed1993

Preferential expression of HSC70 heat shock mRNA in gerbil heart after transient brain ischemia.

Inductions of mRNAs for heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 were examined in the cerebral cortex, cerebellum, heart, lung, kidney, and liver of gerbils after a 10-min transient forebrain ischemia. HSP70 mRNA was normally expressed in a small amount in the cerebellum, lung, and kidney, but was not expressed in the heart or liver in a detectable amount. A very small amount of HSP70 mRNA was also present in the cerebral cortex. HSC70 mRNA was normally present in all the organs examined with a variety in the amount. Eight hours after the cerebral ischemia, the level of HSP70 mRNA increased in the cerebral cortex, lung, and kidney. HSC70 mRNA levels also increased in all the organs. However, the increase of HSC70 mRNA was remarkable in the heart. Transient cerebral ischemia caused subsequent hyperthermia. Treatment of gerbils with an artificial hyperthermia without cerebral ischemia increased the HSP70 and HSC70 mRNA levels as well. However, the HSC70 mRNA level in the heart after cerebral ischemia was much higher than that in the case with hyperthermic treatment. These results suggest that HSC70 mRNA was preferentially induced in the heart after transient forebrain ischemia that was not only due to the subsequent hyperthermia.

Animals↗
PubMed1992

Effects of duration of pressure overload on the reversibility of impaired coronary autoregulation in rats.

The aim of this study was to determine the effects of duration of pressure overload on the reversibility of impaired coronary autoregulation in hypertropied hearts. The experiments were performed on 38 anesthetized male Wistar rats aged 6 to 8 weeks. The ascending aorta was banded for 4 or 10 weeks, then in some rats the bands were removed for 4 weeks. We estimated coronary hemodynamics in a model consisting of isolated non-working hearts perfused with Tyrode's solution containing bovine red blood cells and serum albumin. Myocardial mass increased significantly in 4 and 10-week banded groups compared to controls. Four weeks after debanding in 4- and 10-week banded groups, the value returned to that of controls. Autoregulation gain was significantly lower in banded groups than in controls in the range between 50 and 100 mmHg of coronary perfusion pressure. Although the gain normalized in the debanded group after 4 weeks of banding, the value in the debanded groups after 10 weeks of banding remained less than zero between 25 and 150 mmHg of perfusion pressure. In transient flow response to a stepwise increase of perfusion pressure within the autoregulatory range, promptly increased flow was followed by more rapid and greater decrease in controls than in banded groups. The flow response regressed in the debanded group after 4 weeks of banding, while it remained unchanged in the debanded group after 10 weeks of banding. Thus, duration of pressure overload alters the regression of impaired coronary autoregulation in cardiac hypertrophy.

Animals↗
PubMed1992

Interaction of lectins with human IgE: IgE-binding property and histamine-releasing activity of twelve plant lectins.

We examined the IgE-binding reaction and the histamine-releasing response of basophils to a panel of 12 lectins: concanavalin A (Con A), Lens culinaris hemagglutinin (LcH), Pisum sativum agglutinin (PSA), wheat germ agglutinin (WGA), soybean agglutinin (SBA), Bauhinia purpurea agglutinin (BPA), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA-I), Lotus tetragonolobus agglutinin (Lotus A), Ulex europeus agglutinin I (UEA-I), phytohemagglutinin E (PHA-E) and phytohemagglutinin L (PHA-L), IgE from allergic patients bound with high affinity to Con A, LcH, PSA, RCA-I and PHA-E, and with lower affinity to WGA, BPA, Lotus A and UEA-I, but they did not bind to SBA, PNA or PHA-L. There was no apparent individual difference in the reactivity of IgE to these lectins between 10 IgE preparations from allergic patients. The binding to these lectins, except Lotus A and UEA-I, were competitively inhibited by the lectin-specific sugars or glycopeptide. Upon stimulation by Con A, LcH, PSA, WGA, RCA-1 and PHA-E, leukocytes from allergic patients showed a significant release of histamine, but cells from IgE-deficient subjects did not respond to these lectins. The histamine-releasing responses by these lectins were also inhibited by specific sugars or glycopeptides.

Basophils↗
PubMed1992

Collagen deposition and the reversal of coronary reserve in cardiac hypertrophy.

The aim of this study was to clarify how collagen deposition or medial hypertrophy of the vascular wall affects the coronary dilator reserve in pressure-overloaded hearts and whether inhibition of collagen deposition reverses the abnormalities after relief of pressure overload. We used ascending aortic banding and debanding methods and superimposed beta-aminopropionitrile in some of the banded rats (50 mg/kg i.p., twice a day). Ten weeks of banding increased in vivo peak systolic left ventricular pressure and produced medial hypertrophy, an increase in collagen deposition in the myocardial and perivascular tissues, and myocardial hypertrophy in the banded group without beta-aminopropionitrile treatment. Superimposition of beta-aminopropionitrile treatment on banding inhibited the increase in collagen deposition. In the groups debanded after the 10-week banding period, both with and without beta-amino-propionitrile treatment, medial and myocardial hypertrophy regressed 4 weeks after debanding. We estimated coronary dilator reserve in Langendorff preparations perfused with modified Tyrode's solution containing oxygenated bovine red blood cells and serum albumin. The ratio of reactive peak flow after brief ischemia-to-resting flow decreased in both of the banded groups. After debanding, the ratio remained lower in the banded group without beta-aminopropionitrile treatment than in the control group. However, debanding in the group with beta-aminopropionitrile treatment increased the ratio to a level similar to that of the control group. Thus, in pressure-overloaded cardiac hypertrophy with coronary hypertension, coronary reserve seems to be determined by medial hypertrophy independently of collagen deposition, but collagen deposition plays an important role in the reversal of vasodilator reserve after relief of the overload.

Aminopropionitrile↗
PubMed1992

Age-related differences in the expression of proto-oncogene and contractile protein genes in response to pressure overload in the rat myocardium.

Cardiac adaptation to hemodynamic stress involves both quantitative (hypertrophy) and qualitative (pattern of gene expression) changes. Our previous studies have shown that advancing age in the rat is associated with diminished capacity to develop left ventricular hypertrophy in response to either ascending aortic constriction (AoC). In this study, we examined whether the expression of protooncogenes and contractile protein genes in response to AoC differs between adult (9-mo-old) and old (18-mo-old) rats. RNA was isolated from the left ventricles of AoC animals of both age groups subjected to a similar hemodynamic stress. Immediately after AoC, the levels of the ventricular expression of c-fos and c-jun protooncogenes were markedly lower in the old rats than in the adult animals. 5 d after the operation, the ratio of beta- to alpha-myosin heavy chain mRNAs increased significantly after AoC in both age groups. In contrast, AoC was associated with a marked reduction in the levels of mRNAs encoding sarcoplasmic reticulum Ca(2+)-ATPase (by 69%) and cardiac calsequestrin (by 49%) in the old rats but not in the adults. The mRNAs encoding atrial natriuretic factor and skeletal alpha-actin increased in response to AoC only in the adult rats. There were no significant differences in expression of the cardiac alpha-actin mRNA among the experimental groups. These data suggest that (a) the expression of protooncogenes in response to acute pressure overload is significantly reduced in the aged rats and (b) the pattern of expression of the contractile protein gene in response to AoC in the old rats differs qualitatively as well as quantitatively from that in younger animals. These age-related differences may play a role in the higher frequency of heart failure in the aged during hemodynamic stress.

Actins↗
PubMed1992

Aging effects on myocardial hypertrophic response and coronary circulation in pressure-overload.

We examined the effect of age on capacity for myocardial hypertrophy, pressure-generating ability and coronary circulation after imposition of pressure-overload. Marked right ventricular and cellular hypertrophy was observed 1 week after pulmonary artery constriction in the developmental phase of rats (2 months of age) and after 3 weeks in the young-adult rats (7 months). In old rats (18 months) similar increases in peak right ventricular pressure did not produce significant hypertrophy even after 3 weeks. The right ventricular hypertrophy at the organ and cell levels in response to pressure-overload decreased with age. In vivo pressure-generating ability, which was determined by maximum isovolumic pressure during pulmonary artery occlusion, correlated with the degree of myocardial hypertrophy in each age group. During the ascending aortic constriction experiment the age-associated diminution in hypertrophic response was also observed in the left ventricle. Coronary dilator capacity, which was determined after brief ischemia in an isolated, blood-perfused, beating but nonworking heart model, was decreased in the presence of myocardial hypertrophy in young-adult rats (7 months) and in the absence of significant myocardial hypertrophy in old rats (18 months). The age-associated diminution in capacity for myocardial hypertrophy, pressure-generating ability and maladaptation in the coronary circulation may explain the higher incidence of heart failure or increased vulnerability of the myocardium to ischemic episodes during hemodynamic stress in aged patients.

Aging↗