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Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 757 records · Page 42Linked to original sources
PubMed1992

Noninvasive assessment of cardiomyopathy development with simultaneous measurement of topical 1H- and 31P-magnetic resonance spectroscopy.

Background. It might be possible to estimate the metabolic derangement of cardiac muscle by topical nuclear magnetic resonance spectroscopy (MRS) in vivo without killing the animal. Methods and Results. By use of topical 1H- and 31P-MRS focused on the heart of Syrian hamsters with or without cardiomyopathy (CM; BIO 14.6 strain), the chemical constituents were measured in vivo nondestructively and repetitively at several stages of development of CM. A phantom experiment and two-dimensional plot of chain methylenes (CH2) of lipid/water ratio by 1H-MRS versus creatine phosphate (CP)/[beta-P]ATP ratio by 31P-MRS indicated that signal cross talk from the adjacent organs was negligible. Even before the onset of clinical or pathological manifestation of CM (7 weeks after birth), CH2/water ratio by 1H-MRS was lower in the CM group (7.3 +/- 0.7%) than in control (11.8 +/- 2.0%, p less than 0.05), and it decreased further at the hypertrophic stage (17 weeks, 4.1 +/- 0.7%, p less than 0.05) and the congestive stage (27 weeks, 4.3 +/- 0.9%, p less than 0.05). In contrast, the CP/[beta-P]ATP ratio by 31P-MRS started to decrease at the hypertrophic stage (1.90 +/- 0.18 versus 2.52 +/- 0.24, p less than 0.05) and decreased further at the congestive stage to 1.53 +/- 0.18 (p less than 0.01). These in vivo MRS data were confirmed by both biochemical assay and in vitro MRS analysis in heavy water after the animals were killed. Conclusions. A combination of topical 1H-MRS and 31P-MRS in vivo is promising for the noninvasive and sensitive assessment of cardiac muscle metabolism. Comparison of these MRS studies and biochemical analysis suggested not only the modification of water, lipid, CP, or ATP contents but also the reduction of flexibility or fluidity of lipids in cardiomyopathic heart.

Adenosine Triphosphate↗
PubMed1992

Interferon gamma attenuates hypertensive renal injury in salt-sensitive Dahl rats.

Evidence has been provided that the immunological mechanism is involved in the genesis or maintenance of hypertension. In the present study, we investigated the effects of interferon gamma, a potent immunomodulator derived from lymphocytes, on hypertension and organ damage in Dahl salt-sensitive rats and in spontaneously hypertensive rats. Subcutaneous injection of interferon gamma (5 x 10(4) units/kg body wt once a week for 10 weeks) reduced blood pressure in Dahl salt-sensitive rats fed a 4% high salt diet (174 versus 194 mm Hg, p less than 0.025). This blood pressure reduction was associated with an improvement of renal functions, an increase in glomerular filtration rate (690 versus 569 ml/day/100 g body wt, p less than 0.05), and decreases in urinary protein excretion (48 versus 78 mg/day/100 g body wt, p less than 0.025) and urinary N-acetyl-beta-D-glucosaminidase excretion (143 versus 183 milliunits/day/100 g body wt, p less than 0.05). Morphological investigation showed a marked resolution of the vascular injuries seen in untreated Dahl salt-sensitive rats, e.g., intimal and medial hyperplasia, with infiltration of inflammatory cells, and significant amelioration of the glomerular sclerotic changes. In contrast, interferon gamma affected neither blood pressure nor renal functions in spontaneously hypertensive rats. These data indicate that interferon gamma ameliorates the development of hypertension and vascular and renal injuries in Dahl salt-sensitive rats. The resolution of vascular and renal injuries contributes, in part, to the antihypertensive action of interferon gamma.

Acetylglucosaminidase↗
PubMed1992

Cellular mechanisms for synthesis and secretion of atrial natriuretic peptide and brain natriuretic peptide in cultured rat atrial cells.

To investigate the cellular mechanism for the synthesis and secretion of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), we examined the effects of vasoactive agents on the secretion rates and gene expression of ANP and BNP in cultured rat atrial cells. Endothelin (10(-7) M, +61%), 12-O-tetradecanoylphorbol 13-acetate (TPA, 10(-6) M, +62%), the calcium ionophore A23187 (10(-6) M, +95%), and Bay K 8644 (10(-6) M, +34%) (p < 0.05 each) all increased the secretion of ANP into the culture media in a dose-dependent fashion. On the other hand, endothelin (10(-7) M, +57%) and TPA (10(-6) M, +55%) (p < 0.01 each) increased the secretion of BNP in a dose-dependent manner, whereas A23187 (10(-6) M, -45%, p < 0.001) suppressed the secretion of BNP in a dose-dependent manner, and Bay K 8644 caused no significant effects on BNP secretion. The molecular forms of intracellular ANP were exclusively gamma-ANP, whereas those of BNP were gamma-BNP and its carboxy terminal 45-amino-acid peptide, BNP-45. The ratio of media to cell contents was much higher in BNP than in ANP. Northern blot analysis revealed that both ANP mRNA and BNP mRNA levels were significantly increased by 10(-7) M endothelin (ANP mRNA, +52%; BNP mRNA, +36%; p < 0.05 each) and 5 x 10(-5) M 1-oleoyl-2-acetylglycerol (ANP mRNA, +296%; BNP mRNA, +133%; p < 0.01 each) but not by 10(-6) M A23187. Thus, the secretion of ANP is stimulated by both the elevation of [Ca2+]i and the activation of protein kinase C, whereas its synthesis is increased mainly by the activation of protein kinase C. The synthesis and secretion of BNP are augmented by the activation of protein kinase C rather than the elevation of [Ca2+]i. Furthermore, the processing and secretion of ANP and BNP may be regulated in different manners.

Animals↗
PubMed1992

Alterations of urinary acetylcarnitine in valproate-treated rats: the effect of L-carnitine supplementation.

Urinary excretion of acetylcarnitine was measured by high-performance liquid chromatography in two experimental groups of valproate-treated rats. In the urine of mature rats weighing 180 to 200 g treated with valproate (500 mg/kg/day), acetylcarnitine levels were higher than those in controls on days 4 and 7, while L-carnitine-supplemented rats showed lower levels than the valproate group. The valproate-treated rats showed an increased acetylcarnitine/acylcarnitine ratio on and after day 4, while the L-carnitine-supplemented rats showed no significant change compared to the controls on any days. In the urine of immature rats weighing 80 to 90 g treated with valproate (50 mg/kg/day), acetylcarnitine levels were increased after the 14th day of treatment. These results suggest that an increase in urinary acetylcarnitine occurs when small doses of valproate are administered for a longer time. We speculate that increased acetylcarnitine is not a product of beta-oxidation in mitochondria, because L-carnitine supplementation decreases the acetylcarnitine levels. Although the mechanism of acetylcarnitine excretion during valproate administration is not clear, L-carnitine supplementation is effective in decreasing the level of urinary acetylcarnitine and keeping the acetylcarnitine/acylcarnitine ratio normal.

Acetylcarnitine↗
PubMed1992

Effects of concentration reduction and partial replacement of paraquat by diquat on human toxicity: a clinical survey.

Paraquat poisoning was studied in 174 patients over a 12-month period when a new, low concentration paraquat product (4.5% w/v paraquat ion mixed with 4.5% w/v diquat ion; 63 cases) replaced the original high concentration paraquat product (20% w/v paraquat ion only; 111 cases). In both groups approximately 60% of the patients died from circulatory failure accompanied by multiple organ failure within a week of ingesting the products. However, a remarkable reduction in late deaths from respiratory failure was noted in the new product group (17.1% vs 6.3%). This was reflected in this group's improved survival (23.4% vs 34.9%). The improvement in survival seems to be attributable to the dilution of paraquat with diquat which seems to have a different toxicological profile to paraquat.

Blood Urea Nitrogen↗
PubMed1992

New method of detecting nitric oxide production.

Nitric oxide (NO) reacts with H2O2 to produce a rise in potent luminol-dependent chemiluminescence under neutral pH conditions. We applied this reaction to the continuous detection of NO released from the rat isolated perfused kidney with simultaneous pressure changes. Acetylcholine increased NO release dose-dependently with the pressure reduction. An NO synthesis inhibitor, NG-monomethyl-L-arginine, abolished the release. This inhibition was reversed by the addition of L-arginine.

Animals↗
PubMed1992

Genetic analysis of dilated cardiomyopathy--HLA and immunoglobulin genes may confer susceptibility.

To identify genetic factors in the immune system which control the susceptibility to dilated cardiomyopathy (DCM), HLA class II DNA typing was performed in 61 Japanese patients, using PCR/SSO probe analyses. The frequencies of HLA-DQB1*0503 (15% vs 5%; RR = 3.06, chi 2 = 7.19) and DQB1*0604 (21% vs 10%; RR = 2.41, chi 2 = 6.20) were significantly increased and that of HLA-DQB1*0502 (RR = 1.74) was slightly increased in the DCM patients. The frequency of DQB1*0303 (16% vs 31%; RR = 0.44, chi 2 = 5.16) was significantly decreased in the patients. The increased HLA-DQB1 alleles have a histidine residue in common at the 30th codon for the HLA-DQ beta chain. Among the genetic markers studied by Southern blot analyses, IGLV (immunoglobulin lambda light chain, pV3.3) showed a strong association with DCM, i.e. A2/A2 genotype was found in 37.7% of patients whereas it was observed in only 18.9% of the control subjects (RR = 2.6, chi 2 = 7.77). The frequency of this genotype was higher in patients under age 45 years at the time of diagnosis (45.5%, RR = 3.6, chi 2 = 10.02). These results suggest that HLA and immunoglobulin genes are closely linked to susceptibility to DCM.

Adolescent↗
PubMed1992

Cardiac adaptation and its limitation in an experimental model of congestive heart failure.

To elucidate mechanisms of adaptation and maladaptation in heart failure, abnormalities of left ventricular function and their relationships to myocardial contractile protein were studied in the Syrian hamster Bio 14.6. Left ventricular and heart weights were both increased in 20-week-old cardiomyopathic hamsters, indicating cardiac hypertrophy as a compensatory mechanism to the disease process of cardiomyopathy. However further increase in the left ventricular weight was not observed in older (40-week-old) cardiomyopathic hamsters. On the other hand left ventricular volume and volume/mass ratio were increased progressively. Correspondingly, V3 type myosin was increased and myosin sliding velocity was decreased. Left ventricular function of cardiomyopathic hamsters evaluated using an isovolumically beating perfused heart preparation was depressed, and this functional impairment was also progressive. Chronic administration of metoprolol, a beta-blocking agent, induced further increase in left ventricular volume and mass without changing left ventricular function and myosin isozyme pattern. Thus in cardiomyopathic hamsters, left ventricular function progressively deteriorates in spite of a variety of adaptive mechanisms, and remodeling occurs.

Adaptation, Physiological↗
PubMed1992

[The vasospasmolytic effects of nicorandil, cromakalim and pinacidil on 3,4-diaminopyridine-induced phasic contractions in canine coronary arteries as an experimental vasospasm model].

The spasmolytic mechanisms of nicorandil, a novel antianginal drug, were investigated using 3,4-diaminopyridine (3,4-DAP)-induced phasic contractions of isolated canine coronary arteries in comparison with those of cromakalim and pinacidil. Nicorandil (10(-4) M), cromakalim (10(-6) M) and pinacidil (10(-5) M) suppressed the phasic contractions. Pretreatment with glibenclamide (10(-6) M), a specific blocking agent of ATP-sensitive K+ channel, eliminated the suppression of phasic contractions by these drugs; glibenclamide completely eliminated the suppression by cromakalim, while the eliminations against nicorandil and pinacidil were incomplete. The recoveries of peak tensions were only 56.8% and 76.1% for nicorandil and pinacidil, respectively. Nicorandil and pinacidil may suppress the phasic contractions via K+ channel opening and additional mechanisms. Methylene blue (10(-7)-10(-5) M) alone, a guanylate cyclase inhibitor, had no effect on the suppression of phasic contractions by nicorandil. In the presence of glibenclamide (10(-6) M), however, the pretreatment with methylene blue significantly augmented the recovery of peak tension for nicorandil. These results indicate that K+ channel openers may suppress the phasic contractions induced by 3,4-DAP via ATP-sensitive K+ channels, and that additionally, nicorandil may suppress the phasic contractility through guanylate cyclase stimulation, as a nitrate.

4-Aminopyridine↗
PubMed1992

Severe hypoxia due to ventilation-perfusion mismatch caused by aortic arch aneurysm.

We report a very rare case of hugh aortic arch aneurysm associated with aortic restenosis, which caused severe hypoxia due to ventilation-perfusion mismatch by compression of the left main bronchus and the right pulmonary artery. Aortic arch replacement was performed under circulatory arrest and deep hypothermia in addition to aortic valve replacement as a redo operation, and consequently such hypoxia was relieved.

Adult↗
PubMed1992

Diastereomers of neopterin and biopterin in human urine.

A new pteridine compound, named umanopterin, was isolated from human urine both of cancer patients and non-cancer controls. The structure was confirmed to be 2-amino-4(3H)-oxo-6-[(1'R,2'R)-1',2',3'-trihydroxypropyl]pteridine , a diastereomer of neopterin. The amount of umanopterin relative to neopterin was about 10%, which was practically the same among the non-cancer controls and the patients of various cancers. A small amount of a threo diastereomer of biopterin, named orinapterin, was isolated from human urine for the first time. Its structure was shown to be 2-amino-4(3H)-oxo-6-[(1'S,2'S)-1',2'-dihydroxypropyl]pteridine. A non-enzymatic transformation of 7,8-dihydroneopterin and 7,8-dihydrobiopterin by a mechanism analogous to keto-enol tautomerism is postulated for the formation of umanopterin and orinapterin in human body.

Acetylation↗
PubMed1992

Alterations of calcium channels in vascular smooth muscle cells from spontaneously hypertensive rats.

We examined the possible alterations in calcium handling through the calcium channels of spontaneously hypertensive rats (SHR) using 45Ca2+ uptake measurements in cultured aortic cells. Primary cultures of vascular smooth muscle cells (VSMC) were obtained by enzymatic dissociation of the thoracic aortas from 8-week-old SHR and age-matched Wistar-Kyoto rats (WKY). The functions of voltage sensitive calcium channels (VSCC) and receptor operated calcium channels (ROCC) were estimated from the activated 45Ca2+ uptake in VSMC with high K+ depolarization and arginine vasopressin (AVP), respectively. Compared to basal conditions, depolarization with 55 mM KCl increased 45Ca2+ uptake at 20 min by 94 +/- 17 (SE) % in SHR and 38 +/- 6% in WKY. The activated 45Ca2+ uptake was significantly greater in SHR than in WKY (p < 0.01). There was no significant difference in 45Ca2+ uptake at 20 min in the presence of 5 x 10(-8)M AVP between SHR and WKY. These results suggest that calcium uptake, at least through VSCC, is increased in VSMC of SHR. This enhanced activity may be implicated in the hypertensive mechanisms in this model of hypertension.

Animals↗
PubMed1992

A biphasic effect of noradrenaline on renin release from rat juxtaglomerular cells in vitro is mediated by alpha 1- and beta-adrenoceptors.

The direct effect of noradrenaline on renin release from juxtaglomerular (JG) cells in vitro were investigated in a dynamic superfusion system of dispersed rat renal cortical cells. At low concentrations (1-100 nmol/l), noradrenaline stimulated renin release in a dose-dependent manner, while at higher concentrations (0.1-1 mmol/l) it inhibited renin release. The stimulatory effect of 0.1 mumol noradrenaline/l was completely blocked by a beta-adrenoceptor antagonist, propranolol (0.1 mumol/l). When applied at concentrations of 1 mumol/l or 10 mumol/l, noradrenaline had no consistent effect on renin release, although 10 mumol noradrenaline/l had an inhibitory effect in the presence of propranolol (0.1 mumol/l). The inhibitory effect of noradrenaline (0.1 mmol/l) was converted to a stimulatory effect by the addition of an alpha 1-adrenoceptor antagonist (bunazosin, 1 mumol/l), but was not altered by the addition of an alpha 2-adrenoceptor antagonist (yohimbine, 1 mumol/l). These results indicate that low concentrations of noradrenaline directly stimulate renin release from JG cells by the activation of beta-adrenoceptors, while high concentrations of noradrenaline inhibit renin release by the activation of alpha 1-adrenoceptors. Accordingly, a dynamic balance may exist between beta-adrenergic stimulation and alpha 1-adrenergic depression of renin release.

Adrenergic alpha-Antagonists↗
PubMed1992

Absence of response to hypothalamic stimulation test in brain death.

Immunoreactive corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone (GHRH) are present in the plasma of the brain dead patients. These hypothalamic hormones may reflect some residual brain function after brain death. To examine the hypothalamic function, insulin-induced hypoglycemia and arginine infusion were performed in brain dead patients. Plasma CRH and GHRH were present initially, but levels did not increase significantly for 120 minutes after insulin injection. GH, adrenocorticotropic hormone, and cortisol levels did not increase either. Arginine load did not induce GH. These results suggest that hypothalamic hormones in the plasma after whole brain death do not reflect hypothalamic functions. The hormones may originate from extrahypothalamic sources such as the pancreas or adrenal gland.

Adolescent↗