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Biomedical subjects

T Miyauchi

Publications and source records attributed to T Miyauchi.

At least 127 records · Page 7Linked to original sources
PubMed1995

An antigenic peptide inducing cross-reacting antibodies inhibiting the interaction of Streptococcus mutans PAc with human salivary components.

A 190-kDa surface protein antigen (PAc) of Streptococcus mutans, in particular the A region of this molecule, may be implicated in the induction of dental caries via an interaction with salivary components. For this reason, it was probably used successfully as an antigenic component for experimental vaccination to prevent dental caries in animals. While developing a synthetic peptide vaccine for dental caries, as reported herein, we have identified a unique peptide, TYEAALKQYEADL, as a candidate vaccinal immunogen. The amino acid sequence of this peptide completely corresponds to the sequence of a B-cell epitope in the A region of PAc and additionally contains its own T-cell epitope for B10.D2 mice within the molecule. This peptide strongly induces the production of only cross-reacting antibodies against PAc. In addition, as demonstrated by surface plasmon resonance analysis using the BIAcore system, these cross-reacting antibodies inhibit approximately 50% of the binding of fluid-phase salivary components to immobilized recombinant PAc.

Adult↗
PubMed1995

CBP-140, a novel endoplasmic reticulum resident Ca(2+)-binding protein with a carboxy-terminal NDEL sequence showed partial homology with 70-kDa heat shock protein (hsp70).

Antibodies against pokeweed agglutinin binding proteins isolated from F9 embryonal carcinoma cells were used to screen a lambda gt11 expression library constructed from the cells. A cDNA clone thus obtained encoded a novel calcium binding protein of 140 kDa (CBP-140). Antibodies raised against the CBP-140 fusion protein stained a 140 kDa band in extracts not only from F9 cells but also from various mouse organs. A calcium blot experiment using CBP-140 fusion protein verified the calcium binding property of the protein. In the partial amino acid sequence so far clarified (652 amino acid residues) we could not detect EF-hand, but could detect contiguous acidic amino acids, which may serve as a calcium-binding site. CBP-140 showed homology with 70-kDa heat shock protein, though it was not induced by heat shock treatment. Localization of CBP-140 in endoplasmic reticulum was shown by indirect immunofluorescence staining and also by subcellular fractionation. Amino acid sequence of CBP-140 contains a carboxyl-terminal Asn-Asp-Glu-Leu (NDEL) sequence, which resembles Lys-Asp-Glu-Leu (KDEL) sequence, a signal to retain the resident proteins in endoplasmic reticulum; NDEL sequence may indeed play a similar role.

3T3 Cells↗
PubMed1995

cDNA cloning and sequence analysis of a novel calcium binding protein with oligoproline motif.

Using antibodies against pokeweed agglutinin-binding proteins from F9 embryonal carcinoma cells, we isolated a cDNA clone PW29 reacting with the antibody. mRNA hybridizing with the cDNA was 4.7 kb, and was strongly expressed in the testis, brain, kidney and heart as well as in F9 cells. The size of mRNA in the testis was heterogeneous. Sequencing the cDNA clone revealed a putative polypeptide of 70 kDa, which is rich in hydrophilic amino acids and has a characteristic sequence of (Glu(Lys))5. The protein also has an oligoproline motif, which conforms to the rule of binding capability to Src homology region III. The cDNA was translated as a fusion protein with glutathione-S-transferase, and was verified to have calcium binding activity, upon a calcium blot experiment.

Amino Acid Sequence↗
PubMed1995

[Continuous subcutaneous injection therapy with interferon-alpha for renal cell carcinoma patients with bone metastasis].

Thirteen patients with renal cell carcinoma who had proven bony metastases were treated with multimodal treatment including surgery, radiotherapy and immunotherapy in the form of subcutaneous continuous injection of by natural type interferon-alpha (INF). The mode of administration of IFN was as follows: IFN, 2,5000 x 10(4) unit dissolved in 60 ml saline, was continuously injected (0.5 ml/hr) via a subcutaneous route as one course of the treatment and was given two courses in two weeks preoperatively. Postoperatively, IFN was given every week and the number of courses totally amounted to 15. In some cases IFN was given thereafter either every week or every other week. In four patients whose serum concentration of IFN was measured during and after administration of continuous IFN, the concentration of IFN rose after injection and showed 40.5 IU/ml in average 24 hours later. The concentration was kept measurable in six to eight days long and the maximum concentration was 167 IU/ml. In IFN-treated patients nine survived including two CRs, two NCs, five PDs and four deaths. The five year survival rate was 53%. Continuous subcutaneous injection of IFN in combination with surgery and/or radiotherapy is effective in the treatment of bony metastasis from renal cell carcinoma.

Aged↗
PubMed1995

[The effect of subconjunctival injection of endothelin-1 on intraocular pressure in the rabbit].

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced in part by vascular endothelial cells. In order to investigate its effects on the episcleral vascular system and intraocular pressure (IOP), we injected ET-1 (3, 10, 30, 100, 300, 1,000 pmol) into the subconjunctival space of rabbits and measured IOP with a manometer. Injection of a dose higher than 10 pmol caused a transient increase of IOP. Mean maximum elevation rate of IOP for each dose of ET-1 was 14.9 +/- 0.9%, (mean +/- standard error) 43.5% +/- 9.5%, 40.8 +/- 7.5%, 46.9 +/- 9.8%, and 84.1 +/- 22.6. Next, we injected 1,000 pmol into the subconjunctival space, and continuously measured IOP and ocular pulse pressure with a manometer. IOP increased rapidly after ET-1 injection. Maximal increase of IOP was observed at 22.7 +/- 9.2 min after ET-1 injection, and IOP decreased after the peak. The ocular pulse pressure increased with IOP elevation and decreased with the IOP reduction. We speculated that the transient elevation of IOP was caused by increase of aqueous outflow resistance, and the decrease of IOP was caused by decrease of aqueous outflow resistance and decrease of blood flow in the ciliary body and the choroid. This strongly suggests that subconjunctival injection of ET-1 could have a large effect on the episcleral vascular system, aqueous outflow, and blood flow in the ciliary body and the choroid.

Animals↗
PubMed1995

Influence of pulmonary blood pressure and flow on endothelin-1 production in humans.

To investigate the regulation of endothelin-1 (ET-1) production, cardiac catheterization was performed in young patients with congenital heart disease (27 +/- 5 months old, mean +/- SEM), and plasma levels of ET-1 in the inferior vena cava were measured by a sandwich-enzyme immunoassay. Plasma ET-1 levels of age-matched healthy controls were 1.55 +/- 0.07 pg/ml (n = 6). In patients with atrial septal defect [without pulmonary hypertension (PH)] who had volume but not pressure overload to the pulmonary circulation (PC), plasma ET-1 levels were significantly lower than in controls. In patients with PH due to ventricular septal defect (VSD) who had both volume and pressure overload to PC, the levels were significantly higher than in controls. In patients with PH and severe pulmonary congestion due to pulmonary venous stenosis (PVS), plasma ET-1 levels were significantly higher than in those with VSD, suggesting that ET-1 production is also augmented by pulmonary congestion. The present findings suggest that ET-1 production is increased by pressure overload to PC but decreased by volume overload to PC.

Endothelins↗
PubMed1995

Increased endothelin-1 binding sites in the cardiac membranes in rats with chronic heart failure.

The effects of experimental chronic heart failure (CHF) on the density and affinity for endothelin-1 (ET-1) binding was studied in the rat heart. Because it has been reported that ET-1 binding sites on cultured cardiocytes are downregulated by pretreatment with ET-1, we also studied the plasma concentrations of ET-1 in rats with CHF. Three weeks after ligation of the left coronary artery, rats developed chronic heart failure (CHF rats). The plasma concentrations of ET-1, as measured by a sandwich-enzyme immunoassay, were significantly higher in CHF rats than in sham-operated rats [4.80 +/- 0.33 vs. 0.91 +/- 0.11 (mean +/- SEM) pg/ml; p < 0.01]. [125I]ET-1 binding experiments on rat cardiac membranes revealed that the binding site density (Bmax) was significantly higher in the CHF rats than in the sham-operated rats (243.0 +/- 20.0 vs. 154.8 +/- 17.4 fmol/mg protein; p < 0.05), whereas the values for the dissociation constant (Kd) were not different between the two groups (28.7 +/- 7.0 vs. 29.8 +/- 1.9 pM). Therefore, in the CHF rats, although plasma concentrations of ET-1 were elevated, the density of myocardial ET receptors was increased. Because ET-1 has potent inotropic and hypertrophic effects on cardiac myocytes, it is suggested that the effects of endogenous ET-1 in the heart are different between the CHF rats and the sham-operated rats.

Animals↗
PubMed1995

Altered production of endothelin-1 in the hypertrophied rat heart.

Although endothelin-1 (ET-1) has been shown to have potent hypertrophic effects in cultured cardiac myocytes, there is no evidence that the production of ET-1 is altered in the hypertrophied heart in vivo. We investigated mRNA and peptide levels of ET-1 in the rat heart hypertrophied due to pressure or volume overload. One week after surgery of abdominal aortic banding (AB) or aortic valve regurgitation (AR; the aortic valve was destroyed by a polyethylene catheter), the rats were sacrificed. Control sham-operated rats were also studied (AB-sham and AR-sham). The left ventricular (LV) weight to body weight ratio was significantly higher in AB rats than in AB-sham rats. It was also significantly higher in AR rats than in AR-sham rats. Therefore, AB rats and AR rats developed LV hypertrophy due to pressure and volume overload, respectively. The expression of ET-1 mRNA in the LV was markedly higher in AB rats than in AB-sham rats. The peptide level of ET-1 was also significantly higher in the LV of AB rats than in that of AB-sham rats. However, the expression of ET-1 mRNA in the LV of AR rats was similar to that of AR-sham rats. The present findings suggest that the production of ET-1 in the heart differs between pressure and volume overload-induced hypertrophy in rats.

Animals↗
PubMed1995

Plasma endothelin-1 levels after exercise in patients with congenital heart disease.

We have previously reported that plasma endothelin-1 (ET-1) levels were significantly increased after exercise in healthy athletes. In the present study, venous plasma ET-1 levels were measured to investigate whether the role of ET-1 during exercise differs between healthy athletes and patients with congenital heart disease. Seven patients (mean age 13 years) performed symptom-limited treadmill exercise (Bruce protocol). All patients were in class I of the NYHA functional classification. The mean end-exercise O2 utilization was 32 ml/min/kg (166% of ventilatory threshold). Blood sampling was carried out in the seated position. The plasma ET-1 level was 1.21 pg/ml before exercise and did not alter immediately after or 30 min after exercise. The plasma level of norepinephrine was markedly elevated immediately after exercise and returned to the basal level 30 min after exercise. The present study demonstrated that exercise failed to alter plasma ET-1 levels in patients with congenital heart disease.

Adolescent↗
PubMed1994

Mechanisms of hypotension in iminoctadine poisoning: pharmacological analysis in rats.

Iminoctadine, a fungicide used widely in fruit culture, causes hypotension in human acute oral poisoning. In an attempt to elucidate this mechanism, we investigated the effects of iminoctadine on the cardiovascular system of rats. In anesthetized rats, intravenously administered iminoctadine produced hypotension and tachycardia. In isolated right atria beating spontaneously in Krebs-Ringer's solution, iminoctadine produced an increase in heart rate. It also produced a positive inotropic response in electrically driven left atria. These responses were partially diminished by atenolol, a beta 1-adrenoceptor antagonist, and also partially diminished to a similar degree in atria of reserpinized rats. Therefore, the positive inotropic and chronotropic effects of iminoctadine were partially mediated via the release of norepinephrine from sympathetic nerve terminals. In aortic ring segments, iminoctadine caused a rightward shift of the concentration-contractile response curve for phenylephrine but did not affect those for prostaglandin F2 alpha or KCl. Iminoctadine produced a potent vasodilation in aortic segments precontracted with phenylephrine. Removal of the aortic endothelium produced a rightward shift of the concentration-response curve for iminoctadine. When the aortic ring preparations were precontracted with prostaglandin F2 alpha or KCl, iminoctadine produced only slight vasodilation. Therefore, the vasodilation caused by iminoctadine is due mostly to its alpha 1-adrenoceptor antagonizing action, and partly to endothelium-dependent mechanisms our data suggest that the hypotension induced by iminoctadine is due to its vasodilator effects.

Animals↗
PubMed1994

The effect of Nicorandil on chronic cerebral vasospasm.

The present study is aimed at examining the therapeutic effect of Nicorandil on chronic vasospasm using beagle dogs subjected to a "two-haemorrhage" insult, as well as its dilatory effect on the PDA [phorbol-12,13 diacetate]-induced contraction of the canine basilar artery. 1. A total of 12 animals of either sex, weighing 7 to 12 kg, were assigned into saline control and Nicorandil-treated groups. Immediately after the second induction of subarachnoid haemorrhage (SAH), animals started to receive the agent via the venous route at the constant rate of 10 micrograms/kg/minute for six hours (day 3). On days 4, 5, and 6, the drug was given twice at the same rate for three hours. After the final angiograms, animals were sacrificed by exsanguination. 2. Using ring specimen of the canine basilar artery at a resting tension of 3 g, isometric tension was monitored to examine the effect of Nicorandil on PDA induced contraction. Nicorandil significantly ameliorated chronic vasospasm and inhibited PDA-induced contraction in a dose-dependent fashion. The present data indicate that Nicorandil provides a useful way of treating chronic vasospasm after SAH.

Animals↗
PubMed1994

Endothelin receptor subtypes in human versus rabbit pulmonary arteries.

We studied which endothelin (ET) receptor subtypes mediate ET-1-induced vasocontraction in the human pulmonary artery (PA) compared with the rabbit PA. ET-1 produced potent contraction in both human and rabbit isolated PAs. In human PA, ET-1-induced contraction was competitively antagonized by BQ-123 (an ETA receptor antagonist) with a pA2 value of 7.68. In rabbit PA, however, even a high concentration of BQ-123 (1 microM) did not affect the contraction. BQ-3020 (an ETB receptor agonist) produced potent contraction in rabbit PA but not in human PA. Binding assays of the membrane preparations showed that human and rabbit PAs contained ETA and ETB receptors in ratios of 93:7 and 23:77, respectively. These results suggest interspecies differences in the ET receptor subtypes that mediate ET-1-induced vasocontraction; ETA receptors are dominant in the human PA, whereas ETB receptors are dominant in the rabbit PA. Furthermore, the predominance of ETA receptors in human PA was supported by autoradiographical studies. If ET-1 acts as a physiological and/or pathophysiological vasocontractor in the human pulmonary circulation, an ETA receptor antagonist would function as a pulmonary vasodilator in humans.

Aged↗
PubMed1994

Alteration of plasma endothelin-1 by exercise at intensities lower and higher than ventilatory threshold.

The purpose of this study was to investigate whether the release of endothelin-1 (ET-1), a potent vasoconstrictor peptide produced by vascular endothelial cells, is induced by exercise. Venous plasma concentrations of ET-1 were measured by sandwich-enzyme immunoassay before and after endurance exercise with a cycle ergometer at different intensities. Male intercollegiate athletes participated in the study and performed cycle ergometer exercise of 30 min duration at intensities of 90 or 130% of their individual ventilatory threshold (VT). The plasma concentration of ET-1 was slightly but significantly increased after exercise at 90% and markedly increased after exercise at 130% of individual VT. The increase in ET-1 was greatest 30 min after exercise at both intensities. It was first demonstrated that the plasma concentration of ET-1 was significantly increased after exercise: the greater the intensity, the greater the extent of the increase in plasma ET-1 concentration. However, the precise physiological roles of ET-1 during exercise remain to be elucidated.

Adolescent↗
PubMed1994

[Surgical neoadjuvant chemo-hormonal therapy for advanced prostatic carcinoma].

To improve the therapeutic results as well as the patient's quality of life (QOL) in advanced prostatic carcinoma, total cystprostatectomy or pelvic exenteration was performed in combination with chemo-hormonal therapy before and after operation on twelve patients with stage D2 prostatic carcinoma who had infiltration in the periprostatic organs including urinary bladder and large intestine and showed strong bladder irritation, gross hematuria and ileus symptoms. Eight patients with severe cystic infiltration underwent total cystprostatectomy, urinary division and lymph node dissection, and four with ileus symptoms had pelvic exenteration, urinary division, proctostomy and lymph node dissection. As a rule of dosing schedule for chemo-hormonal therapy, 30-60mg/sq m of etoposide was continuously administered for 5 days before operation in addition to 250-500 mg of diethylbestrol diphosphate given for 30 days after operation. Furthermore, 2-3 courses of 30-60 mg/sq m of etoposide was administered for successive days, at 3-week intervals and then 30-60 mg/sq m of etoposide at 6-to-8-week intervals for 2 years together with 75-100 mg of chrolmadinone acetate as maintenance treatment. Nine of the 12 patients survived, including 4 patients with complete response, 3 patients with partial response and 2 patients with no change. These findings, suggested that the combination of surgical treatment and chemo-hormonal therapy is of use not only for providing an effective therapeutic means but also for improving the QOL in patients with advanced prostatic carcinoma.

Aged↗
PubMed1994

Quantitative EEG in patients with presenile and senile dementia of the Alzheimer type.

EEG data obtained from 27 patients with presenile Alzheimer's disease (AD) and 28 patients with senile dementia of the Alzheimer type (SDAT) were compared with data from 30 age- and sex-matched controls. Both patient groups exhibited more pronounced delta and theta activity and less prominent alpha and beta activity than the controls. AD, however, was accompanied by more severe slowing than SDAT. The slowing was distributed in the left temporal and frontal regions in AD, and bilaterally in the frontal regions in SDAT. As the severity of the dementia increased, delta activity alone increased in AD, whereas, there were significantly greater increases in both delta and theta activity and decreases in alpha and beta activity in SDAT. These EEG differences appear to be related to the degree of brain damage and the speed of progression of the disease process.

Aged↗
PubMed1994

Possible involvement of endothelin-1 in cardiac hypertrophy.

In an attempt to ascertain a possible involvement of endothelin-1 (ET-1) in the development of cardiac hypertrophy induced by hemodynamic overloads in vivo, the expression of prepro ET-1 mRNA in the cardiac tissue and the plasma level of ET-1 were determined in rats undergoing various treatments for inducing cardiac hypertrophy. One week after aortic banding (AB), the rat exhibited left ventricular hypertrophy characterized by ventricular wall thickening, i.e. concentric hypertrophy. In contrast, the aortic regurgitation (AR) produced left ventricular enlargement without wall thickening 1 week after the operation, i.e. eccentric hypertrophy. Monocrotaline treatment (s.c.) also caused marked hypertrophy in the right ventricle (concentric hypertrophy) 3 weeks later, which was accompanied by a severe pulmonary hypertension (MCT-PH). A Northern blot analysis revealed that AB and MCT-PH markedly increased the expression of prepro ET-1 mRNA in the left and right ventricles, respectively. The rats with MCT-PH but not with AB displayed a significant higher level in their plasma ET-1 levels compared with control animals. In contrast, the rats undergoing AR surgery exhibited no significant elevation in either prepro ET-1 mRNA in the heart or the plasma ET-1 concentration. The results of the present study suggest that ET-1 is involved at least in part in the development of concentric but probably not eccentric cardiac hypertrophy induced by hemodynamic overloads.

Animals↗
PubMed1993

Increased production of endothelin-1 in the hypertrophied rat heart due to pressure overload.

Endothelin-1 (ET-1) has been demonstrated to induce hypertrophy in cultured cardiac myocytes. We investigated the production of ET-1 in the heart of aorta-banded rats in vivo. Seven days after the banding of the abdominal aorta, rats developed a significant left ventricular hypertrophy. The tissue content of mature ET-1 and the level of expression of prepro ET-1 mRNA were higher in the left ventricle of aorta-banded rats than in those of sham-operated rats. The expression of prepro ET-1 mRNA in the right ventricle was not different between the two groups. These findings indicate that the production of ET-1 increased in the hypertrophied left ventricle, thereby suggesting the possible involvement of endogenous ET-1 in the development of cardiac hypertrophy due to pressure overload.

Animals↗