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S Isoyama

Publications and source records attributed to S Isoyama.

At least 19 recordsLinked to original sources
PubMed1997

Eosinophils as a source of matrix metalloproteinase-9 in asthmatic airway inflammation.

Bronchial asthma is characterized by eosinophil infiltration and tissue remodeling. Matrix metalloproteinases (MMPs) are thought to play critical roles by degradating interstitial matrices in a wide range of lung diseases associated with reorganization of the airway architecture. To investigate whether MMPs are involved in the pathologic processes of bronchial asthma, we examined MMP expression in asthmatic subjects. In situ hybridization revealed abundant expression of MMP-9 (gelatinase B) mRNA in biopsy specimens from asthmatic subjects (n = 5), with an average positive cell distribution of 117.8 +/- 41.1 (mean +/- SEM)/mm2. In contrast, sparse expression of the mRNA (10.8 +/- 4.8 /mm2) was observed in specimens from normal subjects (n = 4). The vast majority of cells expressing the mRNA were eosinophils in asthmatic tissues (92.2 +/- 1.2%). MMP-9 protein, which was confined to the submucosal cells in the normal subjects, was not abundantly expressed in inflammatory cells, but there was positive reactivity for MMP-9 protein in the extracellular matrix. Immunoelectron microscopic analysis showed sparse immunolocalization of MMP-9 in the perinuclear spaces of eosinophils, but not in the granules. These findings suggest the overexpression of MMP-9 by eosinophils in bronchial tissues of asthmatic individuals, and the participation of MMPs in the pathologic changes in asthmatic airways.

Adult↗
PubMed1996

Age-related changes before and after imposition of hemodynamic stress in the mammalian heart.

This review focusses on the following issues: how the mammalian heart grows and ages; age-related changes in the mammalian heart before and after imposition of hemodynamic stress; and antiaging modulation in the mammalian heart. The heart and other organs grow and age together in the whole body, and interactions occur between these organs. Therefore, the age-related changes at the molecular and cellular level in the in vivo heart are the summation of the changes of the heart per se and the effects of other organs or tissues on the heart. Furthermore, myocytes grow and age under the influence of age-related changes in other myocytes and other types of cells in the myocardial tissue through autocrine or paracrine mechanisms, because myocytes are exposed to many biologically active substances which are released from those cells. Since hypertension and ischemia are very common hemodynamic events in aged hearts, the characteristics in aged hearts are discussed in terms of responses to hypertension or ischemia. The induction of proto-oncogenes and heat shock protein genes in response to milder hemodynamic stress such as pressure-overload and ischemia is diminished in aged hearts. However, the aged heart can respond to more severe stress to a level similar to that of young-adult hearts. Therefore, the senescent heart is characterized by its attenuated adaptation to hemodynamic stress and by its ability to adapt to limited environmental changes. Several interventions have antiaging effects on the heart at the molecular and cellular level.

Aging↗
PubMed1996

Coronary angioplasty ameliorates hypoperfusion-induced endothelial dysfunction in patients with stable angina pectoris.

OBJECTIVES: This study sought to investigate the effect of coronary angioplasty on chronic hypoperfusion-induced endothelial dysfunction in patients with coronary heart disease. BACKGROUND: The endothelium is an important component for organ flow regulation. Ischemia with or without reperfusion is known to cause endothelial dysfunction. We tested the hypothesis that chronic hypoperfusion impairs endothelial function in the angiographically normal coronary artery segment distal to stenosis and that the impairment by chronic hypoperfusion is reduced by coronary angioplasty. METHODS: In 13 patients with stable angina pectoris, substance P (10, 30 and 100 pmol) and nitroglycerin (200 micrograms) were sequentially infused into the coronary artery in a cumulative manner on the day after coronary angioplasty. In 10 of these patients, vascular responses to these agents were again investigated 3 months after angioplasty. Changes in vascular diameter were evaluated in vessels located proximal and distal to the target lesion, both of which were angiographically normal, by performing computer-assisted quantitative coronary angiography. In five patients, the transstenotic pressure gradient was also measured with a pressure sensor-mounted guide wire before angioplasty. RESULTS: On the day after angioplasty, the magnitude of dilation by substance P in distal segments was significantly less than that in proximal segments and inversely correlated with the transstenotic pressure gradient (p < 0.05) and lesion stenosis (p < 0.05). There was no difference in nitroglycerin-induced vasodilation between the two vessel segment groups. Three months later, the impaired response to substance P in the distal segment was restored to normal. CONCLUSIONS: We conclude that chronic hypoperfusion impairs endothelium-dependent dilation of coronary artery distal to critical stenosis in patients with ischemic heart disease and that coronary angioplasty ameliorates the endothelial dysfunction within 3 months.

Aged↗
PubMed1996

Treatment of whole houses with liquid nitrogen for control of dust mites.

A large volume of liquid nitrogen, (120-150 L) was applied to the houses of 4 asthmatic patients, and the mite densities of the floor dust from these houses were monitored every 2 wk for 4 mo from July to November 1989. The 1st liquid nitrogen treatment was applied in early August and decreased the mite densities to 20-44% of the pretreatment level in all cases, but they returned to the pretreatment level 3-4 wk later (on 3 occasions). The 2nd liquid nitrogen treatment was applied in early September and decreased the mite densities to 6-27% of the pretreatment level within 3 wk in all cases. However, mite numbers again increased to the pretreatment level 4 wk after treatment. The 3rd treatment was applied in mid-October and reduced the mite densities to < 6% of the pretreatment level within 2 wk, and mite numbers remained low thereafter. The results suggested that using liquid nitrogen to freeze houses reduces mite numbers, but that mite recolonization of the houses is an important problem.

Animals↗
PubMed1996

Comparisons of IgE, IgG, and IgG4 responsiveness to Dermatophagoides farinae in children by immunoblotting.

Although asthmatic children are often sensitized to the house-dust mite (HDM) during early childhood, it is not clear what antigenic components are associated with the early immune response of these children. To investigate this problem, we evaluated IgE, IgG, and IgG4 antibody responses to Dermatophagoides farinae (Df) by immunoblotting among three groups of children: group I aged 0-4 years, group II aged 5-9 years, and group III aged 10-14 years. In the group I subjects, positive IgE-binding reactions to 15- and 25-kDa components were found in 76% and 44% of sera, respectively. Those to other components were generally low in frequency. In contrast, positive IgG-binding reactions to 15- and 25-kDa components were found in 44% and 24% of sera, and those to 30- and 110-kDa components in 48% and 88% of sera, respectively. Positive IgG4 reactions to 15- and 25-kDa components were found in 48% and 24%, respectively, and those to other components were very low. Positive IgE-binding reactions to these components gradually became more frequent with increasing age in groups II and III, while IgG and IgG4 reactivities were not markedly different in these age groups. These results suggest that the 15- and 25-kDa proteins of Df are important antigens associated with the initial IgE response to HDM in early childhood, while the 30- and 110-kDa proteins are associated with IgG and 15-kDa components with IgG4.

Adolescent↗
PubMed1994

Remodelling of microvessels by coronary hypertension or cardiac hypertrophy in rats.

We attempted to clarify the individual effects of coronary hypertension and ventricular pressure-overload on the remodelling of coronary arterial microvessels. We examined structural vascular changes in the right ventricular free walls using two experimental rat models: 12-week ascending aortic banding, i.e. a model of coronary hypertension without ventricular pressure-overload and 12-week pulmonary artery banding, i.e. a model of ventricular pressure-overload without coronary hypertension. In vivo peak systolic left ventricular pressure and left ventricular weight to body weight ratio in the aortic banding model increased to 198 +/- 10 mmHg and by 39% above the controls, respectively. In vivo peak right ventricular pressure and right ventricular weight to body weight ratio in the pulmonary artery banding model increased to 87 +/- 7 mmHg and by 69% above the controls, respectively. The right coronary reserve measured by the Doppler method decreased in both experimental models. Aortic banding increased the medial area and perivascular collagen to lumen area ratios in the microvessels > 30 microns in lumen diameter but not in those < 30 microns. Pulmonary artery banding increased the perivascular collagen to lumen area ratio in the microvessels < 60 microns, but not in those > 60 microns. Medial thickening was not observed over the whole range of lumen diameter. These results suggest that the mechanisms responsible for the remodelling of coronary microvessels differ between non-hypertrophied hearts with coronary hypertension and hypertrophied hearts without coronary hypertension.

Animals↗
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↗