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Biomedical subjects

H Matsuo

Publications and source records attributed to H Matsuo.

At least 199 records · Page 11Linked to original sources
PubMed1999

[Development and evaluation of a new target heart rate formula for the adequate exercise training level in healthy subjects].

Little data is available recommending the adequate exercise level for physical fitness, so we hypothesized that the anaerobic threshold (AT) point is an ideal exercise level. We aimed to determine a new target heart rate formula for the adequate exercise training level in healthy subjects. This study first developed a new formula in 405 subjects (221 males, 184 females, mean age 48.9 +/- 12.3 years). The AT was determined during cycle ergometer exercise with continuous respiratory gas measurements. The correlation of heart rate at the AT to resting heart rate, age and gender was analyzed by the multiple regression method. Based on this correlation, a new formula calculating target heart rate was established as 74.8 + 0.76 x (resting heart rate) - 0.27 x (age) + 7.3 x S (male: 0 or female: 1). This formula was then compared to Blackburn's method in 210 subjects (139 males, 71 females, mean age 44.5 +/- 14.4 years). The difference between the new target heart rate and the heart rate at the AT was significantly lower than that between the target heart rate by Blackburn's method [(220 - age) x 0.7] and the heart rate at the AT (8.8 +/- 6.3 vs 12.7 +/- 8.2 beat/min, p < 0.001). The resting heart rate and gender are important factors in determining the target heart rate for exercise. This new formula indicates the adequate exercise training level more accurately in healthy subjects.

Adult↗
PubMed1999

[A trial of new protocol of rush immunotherapy with standardized mite antigen].

The objective of the present study was (1) to establish a new protocol of rush immunotherapy (IT) using a purified mite antigen for the treatment of house-dust-mite-sensitive bronchial asthma. Ten adult asthmatics were enrolled in the initial trial which was based on a 7-day protocol using a house-dust antigen, to determine the optimal maintenance dose of mite antigen. No systemic side effects were observed when the antigen dose was lower than 50 AU. Consequently, the duration of rush IT was shortened to 5 days, and the maintenance dose was determined as 50 AU in the new protocol. To confirm its safety, another ten asthmatics were enrolled in a second trial. Rush IT using the new protocol was able to be performed without any systemic side effects in all patients except one who showed urticaria at 40 AU. These results suggest that the 5-day protocol of rush IT using the mite antigen is safe in patients with house-dust-mite-sensitive asthma.

Adolescent↗
PubMed1999

Simple, rapid, quantitative, and sensitive detection of telomere repeats in cell lysate by a hybridization protection assay.

BACKGROUND: Detection of telomere repeats by Southern hybridization of genomic DNA is time consuming, and the reading of a mean terminal restriction fragment (TRF) length from a smear pattern of an autoradiogram can be inaccurate. We developed a hybridization protection assay (HPA) for telomere repeats. METHODS: We heated 5 microL of DNA solution or 10 microL of cell or tissue lysate at 95 degrees C for 5 min, mixed it with 100 microL of hybridization solution containing 3 x 10(6) relative light units of acridinium ester-labeled probe, and incubated the mixture for 20 min at 60 degrees C. We then added 300 microL of selection buffer and incubated the mixture for 10 min at 60 degrees C to differentially hydrolyze unhybridized probe. Chemiluminescence was measured for 2 s per tube. RESULTS: The amount of telomere repeats was assayed by HPA within linearity from 10 to 3000 ng of purified genomic DNA or from 1000 to 100 000 cell equivalents of lysate. To normalize the amount of DNA in lysate, the amount of Alu sequence was measured by HPA. A ratio of telomere to Alu (TA ratio) = 0.01 corresponded to approximately 2 kbp of mean TRF length determined by Southern blotting in cultured fibroblast and colorectal tissue samples. The TA ratio decreased from 0.06 to 0.02 with increasing division age from 30 to 90 population doubling levels of cultured human fetal fibroblasts. The assay required approximately 45 min from collection of cell or tissue samples. CONCLUSIONS: The amount of telomere repeats was quantitatively measured by HPA in 10 ng of sheared genomic DNA or in the lysate of 1000 cells. This method is simple, rapid, quantitative, sensitive, and applicable to the measurement of telomere repeats in clinical samples such as needle biopsy specimen or as few as 1000 cells in body fluid or washings.

DNA↗
PubMed1999

Effects of thiopental, ketamine, etomidate, propofol and midazolam on the production of adrenomedullin and endothelin-1 in vascular smooth muscle cells.

Endothelin-1 (ET-1) and adrenomedullin (AM) are potent vasoconstrictive and vasodilative peptides. Vascular smooth muscle cells are one of the major producing tissues of these peptides. We investigated effect of thiopental, ketamine, etomidate, midazolam and propofol on the production of ET-1 and AM in cultured rat aorta vascular smooth muscle cells. Rat cultured vascular smooth muscle cells are used and the dose-dependent effect (10(-8)-10(-4) M) of thiopental, ketamine, etomidate, midazolam, and propofol on the production of ET-1 and AM was examined. The concentration of these peptides in the culture medium were measured by radioimmunoassay. Ketamine, etomidate, propofol and midazolam, but not thiopental, decreased the production of ET-1 at a concentration of 10(-4) M and the effect of midazolam is the most potent. Thiopental and etomidate produced small but significant increases in the production of AM at a concentration of 10(-4) M. Ketamine did not affect the production, but propofol and midazolam decreased the production at 10(-4) M and 10(-5) M, respectively. These results suggest that thiopental, ketamine, etomidate, propofol and midazolam differentially affect the production of ET-1 and AM in rat vascular smooth muscle cells.

Adrenomedullin↗
PubMed1999

Correlation between in vivo and in vitro hepatic uptake of metabolic inhibitors of cytochrome P-450 in rats.

To predict the degree of accumulation of hepatic metabolic inhibitors in the liver from the in vitro data, we investigated the relationship between cell/medium concentration ratios (C/M ratios) in isolated rat hepatocytes and liver/blood unbound concentration (K(Bf)) after i.v. administration of various metabolic inhibitors such as itraconazole, ketoconazole, verapamil, diltiazem, enoxacin, ciprofloxacin, clarithromycin, cimetidine, and nizatidine. The C/M ratios of itraconazole were approximately 6,000 and 200 at the concentrations of 0.1 and 10 microg/ml, respectively, and the uptake of ketoconazole and verapamil into the hepatocytes also showed a concentration dependence, although the degree was smaller than that of itraconazole. The uptake of diltiazem, enoxacin, ciprofloxacin, and clarithromycin into the hepatocytes showed linear profiles on concentration dependence. There was an excellent correlation between C/M ratios and K(Bf) values of all nine drugs with a slope of 1. This finding suggested the possibility of predicting drug concentrations in the liver (C(H)) from C/M ratios, the blood concentrations of drugs (C(B)) and unbound fraction in blood (f(B)), which was expressed by C(H) = (C/M). C(B). f(B). It may be possible to predict the drug concentrations in human liver from K(Bf) values estimated with isolated human hepatocytes and concentrations in the blood in a similar manner as in rats.

Animals↗
PubMed1999

Application of low-intensity ultraviolet irradiation to the treatment for pharmacological vasoconstriction via a percutaneous transluminal approach.

We applied low-power ultraviolet (UV) laser irradiation via a thin flexible optical fiber to an in vivo model of vasospasm using an intravascular transluminal approach. The surgically exposed left femoral arteries of a rabbit were constricted by norepinephrine. A quartz fiber of 400 microm in diameter was introduced into the artery via the right common carotid artery through a 2.5F catheter. The femoral artery lumen was then irradiated with a helium-cadmium laser (wavelength 325 nm, output power 8 mW) through the fiber for 30 s. The UV irradiation increased the mean luminal diameter by 85% in comparison to the precontracted state, while the increase was only 45% in a sham operation. A histopathologic examination revealed no thermal damage and an intact internal elastic lamina. These results suggest that intravascular transluminal irradiation with a low-power UV laser may thus have potentially clinical applications to reverse acute arterial vasospasm.

Angiography↗
PubMed1999

[Clinical significance of allergen specific immunotherapy in adult house-dust-mite-sensitive bronchial asthma: impact on disease severity and medical cost].

The objective of this study was to evaluate the clinical significance of allergen-specific immunotherapy in house-dust-mite-sensitive adult bronchial asthma. Fifty patients treated with rush immunotherapy using house dust antigen were examined. The disease severity was compared between before and a year after the maintenance immunotherapy: reduction in the severity was observed in 27 patients (54.0%) following the treatment. The response rate was greater in the patients with step 3 (moderate, persistent) or step 4 (severe, persistent), disease period less than 10 years, or reversible airway obstruction. Patients who showed favorable clinical response also demonstrated the reduction in medical costs. These results suggest that allergen immunotherapy reduces the disease severity and medical cost in a certain population of adult atopic asthma.

Adolescent↗
PubMed1999

Increased plasma levels of adrenomedullin in patients with pulmonary hypertension.

Adrenomedullin, a potent hypotensive peptide, reduces blood pressure and pulmonary vascular resistance, and increases pulmonary blood flow. The mRNA for adrenomedullin and its receptor is highly expressed in the lung, suggesting a regulatory role for adrenomedullin in the pulmonary circulation. To investigate the clinical significance of adrenomedullin in patients with pulmonary hypertension, we studied the relationship between plasma levels of adrenomedullin and pulmonary haemodynamics. Venous, arterial and pulmonary arterial blood samples were obtained during cardiac catheterization and plasma levels of adrenomedullin were measured by specific radioimmunoassay in 33 consecutive patients with severe pulmonary hypertension (12 cases of primary pulmonary hypertension, 21 with chronic thromboembolic pulmonary hypertension; age 49+/-16 years, mean pulmonary arterial pressure 50+/-15mmHg). In addition, plasma levels of adrenomedullin were measured before and after acute nitric oxide inhalation. The changes in plasma adrenomedullin during the follow-up period of 10.3+/-4.3 months were also evaluated (n=5). Sixty-two healthy subjects served as the control group. Adrenomedullin was measured in an antecubital vein in the controls. Plasma levels of adrenomedullin were significantly higher in the patients with pulmonary hypertension than in the control subjects (10.1+/-8.7 versus 4.9+/-1.1pmol/l, P<0.01). Plasma levels of adrenomedullin, expressed as their natural logarithm, were significantly correlated with mean right atrial pressure (r=0.71, P<0.01), stroke volume (r=-0.63, P<0.01), total pulmonary resistance (r=0.60, P<0.01), mean pulmonary arterial pressure (r=0.37, P<0.05), and the natural logarithm of plasma atrial natriuretic peptide (r=0. 63, P<0.01). Plasma levels of adrenomedullin did not change significantly after nitric oxide inhalation, but significantly increased in association with the elevation of the total pulmonary resistance during the long-term follow-up period. These results suggest that plasma levels of adrenomedullin increase in proportion to the extent of pulmonary hypertension.

Administration, Inhalation↗
PubMed1999

Sustained elevation of plasma brain natriuretic peptide levels associated with progressive ventricular remodelling after acute myocardial infarction.

Previous studies have shown that levels of plasma brain natriuretic peptide (BNP) increase in an early phase of acute myocardial infarction. However, the relations between plasma BNP levels and left ventricular remodelling, which occurs long after acute myocardial infarction, are not fully understood. Venous plasma BNP levels were measured 2, 7, 14, 30, 90 and 180 days after the onset of acute myocardial infarction in 21 patients. Left ventricular end-diastolic volume index (EDVI, ml/m2) in acute (5 days) and chronic (6 months) phases were assessed by electron-beam computed tomography using Simpson's method. The remodelling group (n=9) was defined by an increase in EDVI >/=5 ml/m2 relative to the baseline value. Plasma BNP levels on days 2, 7, 14, 30 and 90 were significantly higher in the remodelling group than in the non-remodelling group (n=12, P<0.05). Sustained elevation of plasma BNP levels was noted from day 2 (61+/-12 pmol/l) to day 90 (55+/-12 pmol/l) and significantly decreased on day 180 (24+/-3 pmol/l) in the remodelling group. In contrast, plasma BNP levels significantly decreased from day 2 (25+/-4 pmol/l) to day 90 (9+/-1 pmol/l) and reached a steady level thereafter in the non-remodelling group. Plasma BNP levels on day 7 correlated positively with an increase in EDVI (r=0.70, P<0.001) from the acute to chronic phase. More importantly, the sustained elevation of plasma BNP (percentage decrease smaller than 25%) from day 30 to day 90 identified patients in the remodelling group with a sensitivity of 100% and a specificity of 83%. In conclusion, not only the high levels of plasma BNP in an acute phase, but also the sustained elevation of plasma BNP in a chronic phase, may be associated with progressive ventricular remodelling occurring long after acute myocardial infarction.

Adult↗
PubMed1998

Rat aortic smooth-muscle cell proliferation is bidirectionally regulated in a cell cycle-dependent manner via PACAP/VIP type 2 receptor.

In the cardiovascular system, vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) have been well characterized as potent vasodepressors or vasodilators. However, their pathophysiological implication in proliferation of vascular smooth muscle cells has not yet been elucidated. In the present study, we have first identified PACAP/VIP type 2 receptor as a dominant type in rat vascular smooth muscle cell (VSMC) by RT-PCR. PACAP and VIP increased cyclic AMP accumulation with similar potency. In 24-h [3H]thymidine incorporation assay, PACAP or VIP exhibited a suppressive effect on the DNA synthesis of rat VSMC stimulated by serum when added at the late G1 phase. In contrast, when added at G0/G1 phase of the cell cycle, PACAP or VIP enhanced the serum-induced DNA synthesis. In 24-h incubation, PACAP alone has little mitogenic activity. However, when incubated up to 48 h, PACAP stimulated significantly the DNA synthesis and the cell proliferation of rat VSMC. These results suggest that PACAP and VIP regulate the proliferation of rat VSMC by enhancing or suppressing in a cell cycle-dependent manner and induce delayed mitogenesis and cell proliferation.

Animals↗
PubMed1998

Regulation of peroxisomal proteins and organelle proliferation by multiple carbon sources in the methylotrophic yeast, Candida boidinii.

A methylotrophic yeast, Candida boidinii, was grown on various combinations of peroxisome-inducing carbon source(s) (PIC(s)), i.e. methanol, oleate and D-alanine, and the regulation of peroxisomal proteins (both matrix and membrane ones) and organelle proliferation were studied. This regulation was followed (1) at the protein or enzyme level by means of the peroxisomal enzyme activity and Western analysis; (2) at the mRNA level by Northern analysis; and (3) at the organelle level by direct observation of peroxisomes under a fluorescent microscope. Peroxisomal proliferation was followed in vivo by using a C. boidinii strain producing a green fluorescent protein having peroxisomal targeting signal 1. When multiple PICs were used for cell growth, C. boidinii induced specific peroxisomal proteins characteristic of all PIC(s) present in the medium, responding to all PIC(s) simultaneously. Thus, these PICs were considered to induce peroxisomal proliferation independently and not to repress peroxisomes induced by other PICs. Next, the sensitivity of the peroxisomal induction to glucose repression was studied. While the peroxisomal induction by methanol or oleate was completely repressed by glucose, the D-alanine-induced activities of D-amino acid oxidase and catalase, Pmp47, and the organelle proliferation were not. These results indicate that peroxisomal proliferation in yeasts is not necessarily sensitive to glucose repression. Lastly, this regulation was shown to occur at the mRNA level.

Acyl-CoA Oxidase↗
PubMed1998

Chronic infusion of adrenomedullin reduces pulmonary hypertension and lessens right ventricular hypertrophy in rats administered monocrotaline.

A novel vasorelaxant peptide, adrenomedullin, its messenger ribonucleic acid (mRNA), and the mRNA for its receptor are highly expressed in the lung, suggesting that adrenomedullin may play a role in the regulation of the pulmonary circulation. We investigated whether the chronic infusion of rat adrenomedullin would affect pulmonary hypertension and right ventricular hypertrophy produced by the administration of monocrotaline. Four-week-old male Wistar rats received a single subcutaneous injection of 60 mg/kg monocrotaline and were then chronically and subcutaneously infused with rat adrenomedullin (PH + AM group, n = 8) or saline (PH group, n = 10) by an osmotic minipump for a period of 21 days. Plasma levels of adrenomedullin were significantly higher in the PH vs. the control group. The chronic infusion of adrenomedullin in rats with pulmonary hypertension increased the plasma levels of adrenomedullin to a value 94% greater than that of the control group and 55% greater than that of the untreated PH group. Chronic infusion of adrenomedullin significantly lessened the increase in right ventricular systolic pressure and the ratio of right ventricular weight to body weight seen after monocrotaline treatment. Histological examination revealed that adrenomedullin also attenuated the medial thickening of the pulmonary artery. These results suggest that chronic infusion of adrenomedullin attenuates the pulmonary hypertension and right ventricular hypertrophy seen in rats treated with monocrotaline.

Adrenomedullin↗
PubMed1998

Detection of nivalenol genotoxicity in cultured cells and multiple mouse organs by the alkaline single-cell gel electrophoresis assay.

We tested the genotoxicity of nivalenol (NIV), a potent toxic trichothecene from Fusarium nivale, in cultured CHO cells and in several mouse organs and tissues (liver, kidney, thymus, bone marrow and mucosa of stomach, jejunum, and colon) using the alkaline single-cell gel electrophoresis (SCG, or Comet) assay. NIV at 50 and 100 micrograms/ml damaged the nuclear DNA of CHO cells in the absence of S9 mix, showing that NIV was a direct mutagen. In an in vivo study, mice were sacrificed 2, 4, and 8 h after either oral (20 mg/kg) or intraperitoneal (3.7 mg/kg) administration of NIV. DNA damage was measured by the SCG assay as modified by us. After oral dosing, DNA damage appeared in the kidney and bone marrow at 2 h (returning to almost control level within the following 2 h), and in the stomach, jejunum, and colon at 2, 4, and 8 h, respectively. Liver and thymus DNA were not damaged. After intraperitoneal injection, no DNA damage appeared in any of the organs or tissues tested except for the colon, where extensive DNA damage was observed, as in the oral study, at 8 h. For histopathological examination, mice were sacrificed 2, 4, and 8 h after oral (20 mg/kg) administration of NIV. No necrotic changes were detected in any of the organs where NIV yielded statistically significant DNA damage. To measure the effect of NIV on transport activity in mice, 10 ml/kg (same volume as NIV treatments) of 1% brilliant blue FCF (BB) was administered orally. Thirty minutes later, the BB reached the colon, and simultaneous oral administration of NIV (20 mg/kg, dissolved in 10 ml BB solution) did not affect the dye transport rate. Thus, the strong yet delayed damage to colon DNA may follow from a systemic absorption rather than a topical effect. As a direct mutagen, NIV showed organ specific genotoxicity in mice in time and intensity.

Alkalies↗
PubMed1998

Effect of adrenomedullin on cAMP and cGMP levels in rat cardiac myocytes and nonmyocytes.

The purpose of the present study was to determine if cardiac myocytes and nonmyocytes secrete adrenomedullin, to investigate the effects of adrenomedullin on cAMP and cGMP levels in cardiac myocytes and nonmyocytes, to study the effect of calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) and adrenomedullin-specific receptor antagonist, adrenomedullin-(22-52) on response to adrenomedullin and CGRP. Neonatal (days 1-2) cardiac myocytes and nonmyocytes were prepared from the ventricle of Wistar rats. Not only cardiac myocytes, but also nonmyocytes secrete almost equal amounts of adrenomedullin into the media. Both adrenomedullin and CGRP increased the cAMP levels, not the cGMP levels, both in the myocytes and nonmyocytes. In myocytes, CGRP-(8-37), almost completely inhibited the adrenomedullin- and CGRP-induced cAMP formation. In nonmyocytes, CGRP-(8-37) completely inhibited the cAMP levels induced by adrenomedullin and CGRP. More profound antagonistic effect of CGRP-(8-37) on cAMP levels induced by adrenomedullin was observed in nonmyocytes than in myocytes. In contrast, antagonistic effect of adrenomedullin-(22-52) for adrenomedullin-stimulated cAMP formation was considerably less potent than CGRP-(8-37) both in myocytes and nonmyocytes. Adrenomedullin-(22-52) did not affect the cAMP formation induced by CGRP either in myocytes or nonmyocytes. These results suggest that myocytes and nonmyocytes secrete adrenomedullin and that adrenomedullin increases cAMP levels possibly via different receptors in myocytes and nonmyocytes.

Adrenomedullin↗
PubMed1998

Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment.

Apoptosis requires recruitment of caspases by receptor-associated adaptors through homophilic interactions between the CARDs (caspase recruitment domains) of adaptor proteins and prodomains of caspases. We have solved the CARD structure of the RAIDD adaptor protein that recruits ICH-1/caspase-2. It consists of six tightly packed helices arranged in a topology homologous to the Fas death domain. The surface contains a basic and an acidic patch on opposite sides. This polarity is conserved in the ICH-1 CARD as indicated by homology modeling. Mutagenesis data suggest that these patches mediate CARD/CARD interaction between RAIDD and ICH-1. Subsequent modeling of the CARDs of Apaf-1 and caspase-9, as well as Ced-4 and Ced-3, showed that the basic/acidic surface polarity is highly conserved, suggesting a general mode for CARD/CARD interaction.

Amino Acid Sequence↗
PubMed1998

Production of adrenomedullin in macrophage cell line and peritoneal macrophage.

We demonstrate that adrenomedullin (AM) is produced and secreted from cultured murine monocyte/macrophage cell line (RAW 264.7) as well as mouse peritoneal macrophage. Immunoreactive (IR) AM secreted from RAW 264.7 cells was chromatographically identified to be native AM. To elucidate the regulation mechanism of AM production in macrophage, we examined the effects of various substances inducing differentiation or activation of monocyte/macrophage. Phorbol ester (TPA), retinoic acid (RA), lipopolysaccharide (LPS), and interferon-gamma (IFN-gamma) increased AM production 1.5-7-fold in RAW 264.7 cells in a dose- as well as time-dependent manner. By LPS stimulation, the AM mRNA level in RAW 264.7 cells was augmented up to 7-fold after 14 h incubation. RA exerted a synergistic effect when administered with TPA, LPS, or IFN-gamma, whereas IFN-gamma completely suppressed AM production in RAW 264.7 cells stimulated with LPS. Dexamethasone, hydrocortisone, estradiol, and transforming growth factor-beta dose-dependently suppressed AM production in RAW 264.7 cells. AM production was also investigated in mouse peritoneal macrophage. Primary mouse macrophage secreted IR-AM at a rate similar to that of RAW 264.7 cells, and its production was enhanced 9-fold by LPS stimulation. AM was found to increase basal secretion of tumor necrosis factor alpha (TNF-alpha) from RAW 264.7 cells, whereas AM suppressed the secretion of TNF-alpha and interleukin-6 from that stimulated with LPS. Thus, macrophage should be recognized as one of the major sources of AM circulating in the blood. Especially in cases of sepsis and inflammation, AM production in macrophage is augmented, and the secreted AM is deduced to function as a modulator of cytokine production.

Adrenomedullin↗
PubMed1998

Identification of proteins mediating clearance of liposomes using a liver perfusion system.

The objective of this paper is to identify the principal blood components governing the fate of liposomes in blood circulation. Information based on an isolated perfused liver system in rats has revealed the central role of the complement system in enhancing the uptake of liposomes by the liver. A species difference was an important factor in determining the uptake mechanisms of liposomes by the liver. Limited evidence revealed the tendency that opsonin-dependent hepatic uptake is principal in rats, while opsonin-independent or dysopsonin-dependent uptake governs in mice, although there are some exceptions. These studies provide us with important information for understanding the uptake mechanisms of liposomes by the liver, and useful insights in predicting the in vivo disposition of liposomes in humans.

Journal Article↗