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Biomedical subjects

S Morimoto

Publications and source records attributed to S Morimoto.

At least 145 records · Page 8Linked to original sources
PubMed1998

Unique association of pheochromocytoma with contralateral nonfunctioning adrenal cortical adenoma.

A 57-year-old woman complaining of hypertensive attacks associated with headache and palpitation was admitted to our hospital for examination of bilateral adrenal tumors in 1985. After right pheochromocytoma was diagnosed, right adrenalectomy was performed. The left adrenal tumor was small; thus, the left adrenal tumor was preserved to avoid adrenal insufficiency, although left adrenal pheochromocytoma could not be denied. In 1995, she was referred to our clinic again because of recurrent headache and palpitation, and enlargement of the left adrenal tumor. Although pheochromocytoma was suspected again, the enlarged left adrenal turned out to be a nonfunctioning cortical adenoma. This case was interesting, not only because of difficulty in identifying the left adrenal tumor, but also because of the rare coexistence of a pheochromocytoma and a nonfunctioning adrenal cortical tumor.

Adrenal Cortex Neoplasms↗
PubMed1998

Ay-4166 increases the sensitivity of insulin secretion to glucose in isolated perfused rat pancreas.

To study the effect of a therapeutic dose (3 microM) of AY-4166 on the glucose-stimulated insulin secretion, the rat pancreas was perfused with 5 to 15 mM glucose. AY-4166 did not affect the basal insulin secretion at 5 mM glucose, and increased the first and second phases of insulin secretion stimulated by 7.5 to 15 mM glucose. The dose-response curve of the insulin secretion to glucose was shifted to the left side by AY-4166. These results suggest that AY-4166 ist not a stimulator releasing insulin independently of glucose concentrations, but a potentiator of insulin secretion.

Animals↗
PubMed1998

Augmented response of endothelin-A and endothelin-B receptor stimulation in coronary arteries of hypertensive hearts.

To determine whether the vasoconstrictor response to endothelin-1 (ET-1) is altered in coronary vessels of hypertensive hearts and the role of ETA and ETB receptors in these responses to ET-1, the vasoconstrictor response to ET-1 in coronary vessels was measured with or without ETA and ETB receptor antagonists. In isolated hearts of spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat, the coronary perfusion pressure was measured on a Langendorff apparatus with constant pressure (75 mm Hg). Coronary perfusion resistance (CPR) (mm Hg/ml/min/g) was calculated. ET-1 elicited dose-dependent increases of CPR in both normotensive and SHR rat hearts. However, the responses were significantly greater in SHR than those of WKY. Pretreatment with the ETA antagonist FR139317 and the ETB antagonist BQ788 inhibited CPR increases with ET-1 infusion. However, vasoconstrictor responses to ET-1 were still greater in SHR than in WKY after FR139317 or BQ788 infusion. These findings suggest that the augmented vasoconstrictor response of coronary artery to ET-1 is mediated by both ETA and ETB receptors. These changes may contribute to the impaired coronary circulation in hypertension.

Animals↗
PubMed1998

Expression of parathyroid hormone/parathyroid hormone-related protein receptor in vascular endothelial cells.

The parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor has been reported to be expressed in many tissues, including vascular smooth-muscle cells (VSMCs), but it has not been identified in vascular endothelial cells. To determine whether vascular endothelial cells can express the PTH/PTHrP receptor, its gene expression was examined in simian virus 40-transformed rat lung vascular endothelial cells (TRLECs) by the reverse-transcription polymerase chain reaction (RT-PCR). Results in TRLEC, with rat VSMCs and kidney as controls, showed identical 741-bp products. Furthermore, incubation with PTHrP[1-34] reduced the thrombin-stimulated endothelin-1 (ET-1) expression in TRLECs. Our results demonstrate that vascular endothelial cells can express the PTH/PTHrP receptor and therefore are also a target tissue for PTHrP.

Animals↗
PubMed1998

Endothelin-1 enhances nitric oxide-induced cell death in cultured vascular smooth-muscle cells.

Increased expression of endothelin-1 (ET-1) immunoreactivity is demonstrated in the active atherosclerotic plaque. Here we show that both ETA and ETB receptors are expressed in rat vascular smooth-muscle cells (VSMCs). ET-1 binding to ETB receptors enhances nitric oxide-induced cell death in VSMCs. These findings suggest that ET-1 may participate in the mechanism of cell death (apoptosis) in the plaque through activation of ETB-mediated pathways and that a selective ETB receptor antagonist could be useful in preventing acute plaque alterations, such as plaque rupture.

Amino Acid Sequence↗
PubMed1998

Blockade of angiotensin II receptors inhibits the increase in blood pressure induced by insulin.

To elucidate whether hyperinsulinemia increases blood pressure by increasing sympathetic outflow via the activation of the central angiotensin system, insulin was infused into urethane-anesthetized rats intravenously (i.v.) or intracerebroventricularly (i.c.v.) under euglycemic conditions. Infusion (i.v.) of insulin elicited pressor effects in a dose-dependent manner (13, 20, and 40 mU/min). Although depressor responses to i.v. injections of hexamethonium were significantly greater in insulin-infused than in saline-infused rats, i.v. captopril and d(CH2)5Tyr(Me)-arginine vasopressin did not show any differences between the groups. Infusions (i.c.v.) of insulin (8 mU/10 microl) also induced cardiovascular acceleration and augmented the depressor response to i.v. hexamethonium in insulin-infused rats. The i.c.v. pretreatment with the angiotensin II antagonist losartan inhibited the pressor responses to both the i.c.v. and i.v. infusion of insulin. These results suggest that the increase in blood pressure induced by euglycemic hyperinsulinemia is elicited by sympathetic activation and that hyperinsulinemia stimulates the angiotensin system in the brain to increase sympathetic nerve activity.

Angiotensin II↗
PubMed1998

Myasthenia gravis with alopecia totalis.

Myasthenia gravis was diagnosed on the basis of a positive Tensilon test in a 4-year-old male child with alopecia totalis. His scalp hair and eyebrows had began to disappear at the age of 10 months. No other physical abnormalities such as motor paralysis, were seen except for left ptosis and alopecia totalis. His serum titer of anti-acetylcholine receptor antibody was elevated. No immune system abnormalities (C3, C4, CH50, C-reactive protein, antinuclear antibody or lymphocyte function disorders) were detected. Although alopecia areata and alopecia totalis are sometimes present in adults with autoimmune diseases and myasthenia gravis, this association is rare in children. The present case represents the youngest patient with myasthenia gravis associated with alopecia totalis.

Alopecia↗
PubMed1998

Ca2+-sensitizing effects of the mutations at Ile-79 and Arg-92 of troponin T in hypertrophic cardiomyopathy.

Several mutations in human cardiac troponin T (TnT) gene have been reported to cause hypertrophic cardiomyopathy (HCM). To explore the effects of the mutations on cardiac muscle contractile function under physiological conditions, human cardiac TnT mutants, Ile79Asn and Arg92Gln, as well as wild type, were expressed in Escherichia coli and exchanged into permeabilized rabbit cardiac muscle fibers, and Ca2+-activated force was determined. The free Ca2+ concentrations required for tension generation were found to be significantly lower in the mutant TnT-exchanged fibers than in the wild-type TnT-exchanged fibers, whereas no significant differences were found in tension-generating capability under maximal activating conditions and in cooperativity. These results suggest that a heightened Ca2+ sensitivity of cardiac muscle contraction is one of the factors to cause HCM associated with these TnT mutations.

Animals↗
PubMed1998

Antihypertensive effect of sesamin. III. Protection against development and maintenance of hypertension in stroke-prone spontaneously hypertensive rats.

The antihypertensive effect of sesamin, a lignan from sesame oil, was examined using salt-loaded and unloaded stroke-prone spontaneously hypertensive rats (SHRSP). The animals at 6 weeks of age were separated into a salt-loaded group and an unloaded group. Salt-loaded animals were maintained on 1% NaCl drinking water. Each group was further divided into two groups: normal-diet group and sesamin-diet group. Systolic blood pressure of all animals was monitored once weekly. At the end of the feeding periods, cardiovascular hypertrophy and renal damage were evaluated. In the salt-loaded group, sesamin feeding significantly suppressed the development of hypertension, and efficient suppression was maintained from 9 to 26 weeks (e.g., 215+/-4 vs. 180+/-4 mmHg, at 17 weeks old). The left ventricle plus septum weight-to-body weight ratio was slightly but significantly lowered by sesamin feeding. When the degree of vascular hypertrophy of the aorta and superior mesenteric artery was histochemically evaluated, wall thickness and wall area of these vessels were significantly decreased by the sesamin feeding. Histological renal damage such as thickening of the tunica intima and fibrinoid degeneration of the arterial wall were often observed in the normal-diet group, but this damage was efficiently reduced in the sesamin-fed animals. On the other hand, in the salt-unloaded group, only a slight and nonsignificant suppressive effect of sesamin on the development of hypertension was observed. Although the wall area of the aorta was significantly decreased by the sesamin feeding, other vascular parameters were not ameliorated. The incidence of histological renal damage tended to decrease in sesamin-fed animals, but these alterations were not statistically significant. Thus, sesamin feeding was much more effective as an antihypertensive regimen in salt-loaded SHRSP than in unloaded SHRSP, thereby suggesting that sesamin is more useful as a prophylactic treatment in the malignant status of hypertension and/or hypertension followed by water and salt retention.

Animals↗
PubMed1998

National survey of the use of endomyocardial biopsy in Japan.

A national survey of endomyocardial biopsy procedures was conducted in Japan. Questionnaires were mailed to 852 institutions and statistical analysis of the 213 completed questionnaires (25.0% of the total) was performed. Cardiac biopsies were being performed at 134 of these institutions (62.9%), representing a 5.5-fold increase over 1980. A total of 19,964 cardiac biopsies have been performed in Japan. Specimens were obtained from the right ventricle at 113 institutions, and from the left ventricle at 76 centers. The Konno-Sakakibara bioptome was used at 32 institutions, whereas the long sheath method was used at 98 institutions. Sixty of the institutions (44.8%) had encountered ventricular wall perforation. The perforation rate of the two ventricles combined was 0.7% (147 of 19,964 cases), with a mortality rate of 0.05% (10 of 19,964 cases). Endomyocardial biopsy has become widespread in Japan, and its safety was ascertained by this national survey.

Adult↗
PubMed1998

Exogenous ouabain is accumulated in the adrenals and mimics the kinetics of endogenous digitalis-like factor in rats.

Ouabain has been isolated as an endogenous pathogenetic factor in salt-induced hypertension and has been shown to be rich in the adrenals. In this study, organ accumulation of orally administered [3H]ouabain was examined in rats. Exogenous [3H]ouabain was accumulated in high levels in the adrenals, especially in the zona intermedia, and was not metabolized in the rat. Accumulated [3H]ouabain mimicked the movement of "endogenous" digitalis-like factor, since 1) the plasma [3H]ouabain level decreased in bilaterally adrenalectomized rats, 2) the plasma [3H]ouabain level increased accompanied by a decrease in [3H]ouabain content in the adrenals in reduced renal mass hypertensive rats, and 3) [3H]ouabain levels in plasma and in the adrenals increased in spontaneously hypertensive rats, as compared with those in respective control animals. Moreover, the rat diet contained a relatively high amount of ouabain-like immunoreactivity (OLI), and the ratio of the [3H]ouabain content to OLI in each organ was comparable to that of the daily intake of dietary [3H]ouabain to OLI. Furthermore, high 3H-radioactivities were also observed in the adrenals of rats that ingested [3H]digoxin and [3H]digitoxin. These data suggest that exogenous ouabain, related cardiotonic glycosides of plant origin, or both accumulate in the adrenals and, at least in part, act as "endogenous" digitalis-like factor(s).

Adrenal Cortex↗
PubMed1998

Long-term outcome of rotational acetabular osteotomy: 145 hips followed for 10-23 years.

We report the long-term outcome of rotational acetabular osteotomy in 145 dysplastic hips of 131 patients after an average follow-up of 13 (10-23) years. The mean age at operation was 28 (11-52) years. The radiographic severity of osteoarthrosis before operation, according to the criteria of the Japanese Orthopaedic Association, was stage I (no degenerative change) in 63 hips, stage II (early degenerative stage) in 49, stage III (progressive stage) in 21 and stage IV (end stage) in 12. The clinical outcome based on the Merle d'Aubigné and Postel score was excellent or good for 90 (80%) of the 112 hips which had stage I or II osteoarthrosis preoperatively, and was excellent or good for only 9 of the 33 hips which had stage III or IV osteoarthrosis (p < 0.001, chi-square test). The radiographic severity of osteoarthrosis at the most recent review was stage I or II for 79 (70%) of the 112 hips which had stage I or II osteoarthrosis preoperatively. The long-term outcome of rotational acetabular osteotomy was satisfactory for a dysplastic hip with little, if any, osteoarthrosis, but was unsatisfactory for a hip with more advanced osteoarthrosis.

Adolescent↗
PubMed1997

Platelets enhance contractility in perfused rat mesenteric arteries: involvement of endothelin-1.

We investigated the effects of platelet supernatant on pressor responses to norepinephrine in isolated perfused rat mesenteric arteries. Perfusion of the arteries with platelet supernatant for 2 h markedly enhanced the pressor responses to norepinephrine (10(-6) and 3 x 10(-6) M). This enhancement was significantly inhibited by phosphoramidon (10(-4) M), an endothelin converting enzyme inhibitor. Both BQ788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D -1-methoxycarbonyltryptophanyl-D-norleucine] (10(-6) M), an endothelin ET(B) receptor antagonist, and bosentan (Ro47-0203, 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2-bipyri midin-4-yl]-benzenesulfonamide) (10(-5) M), a nonselective endothelin receptor antagonist, also prevented the potentiation of responses to norepinephrine evoked by platelet supernatant, but FR 139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-+ ++methylpentanoyl] amino-3-[3-(1-methyl-1H-indoyl)]propionyl]amino-3-(2-pyridyl) propionic acid) (10-6 M), an endothelin ET(A) receptor antagonist, had little effect. Suppressor doses of endothelin-1 (3 x 10(-10) M) or sarafotoxin S6c (S6c) (3 x 10(-10) M) potentiated significantly the norepinephrine-induced vasoconstriction, in the same preparation. Moreover, supernatant-induced enhancement of pressor responses to norepinephrine was markedly suppressed by TGF-beta1 neutralizing antibody. Transforming growth factor-beta1 (TGF-beta1) (40 pM) also significantly enhanced the pressor responses to norepinephrine (10(-6) M) and this enhancement was significantly inhibited by phosphoramidon. These results suggest that platelet-derived TGF-beta1 stimulates the vascular production of endothelin-1 and thereby enhances vasoconstrictor responses to norepinephrine. Platelet-induced enhancement of vasoconstrictor responses to norepinephrine seems to be mainly mediated by endothelin ET(B) receptor, in rat mesenteric arteries.

Animals↗
PubMed1997

Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4.

Epiregulin is a member of the epidermal growth factor (EGF) family, and has certain characteristics that are different from that of EGF, including mitogenic responses and binding to EGF receptor (EGFR). Epiregulin may also have another cell surface receptor and/or induces different receptor heterodimerizations for intracellular signaling. We investigated the binding ability of epiregulin to four ErbB family receptors using four human breast carcinoma cell lines that expressed different subsets of receptors. Chemical cross-linking experiments showed that [125I]epiregulin directly bound to each of EGFR and ErbB-4 but not to ErbB-2 and ErbB-3. Furthermore, although epiregulin stimulated tyrosine phosphorylation of all four ErbB receptors, the main intracellular signal was mediated by ErbB-4 and/or EGFR. The pattern of activation of ErbB family receptors was different from that of other EGF-related ligands. Our findings indicate that ErbB-4 and EGFR are receptors for epiregulin, and suggest that EGF-related ligands transduce signals for different biological responses by the hierarchical mechanism.

3T3 Cells↗
PubMed1997

Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family.

We have recently identified epiregulin as a new growth regulator and a member of the epidermal growth factor (EGF) family. Epiregulin has certain characteristics that are different from those of the classical members of the EGF family, EGF and transforming growth factor alpha, including mitogenic responses on several normal cells and binding to EGF receptors on epidermoid carcinoma A431 cells. In the present study we cloned and identified the expression of human epiregulin transcript. The human epiregulin gene encoded a 163-residue putative transmembrane precursor containing an EGF-like domain in the internal segment, and the structural organization was similar to that of other members of the EGF family that bind to EGF receptors. Northern blot analysis showed the expression of human epiregulin to be mainly on peripheral blood macrophages and the placenta in normal tissues, and was highest on epithelial tumour cell lines in various types of tumour cell lines. The expression profile was quite different from that of other members of the EGF family in normal and tumour cells. Recombinant expression in mammalian cells also showed that human epiregulin was secreted as a soluble form of approx. 5 kDa that is biologically active on the basis of the stimulation of DNA synthesis. Our findings suggest that epiregulin is involved in certain physiological processes such as maintenance or development of normal cell growth, and the progression of carcinomas.

3T3 Cells↗
PubMed1997

Movements of truncated kinesin fragments with a short or an artificial flexible neck.

To investigate the role of the neck domain of kinesin, we used optical trapping nanometry to perform high-resolution measurements of the movements and forces produced by recombinant kinesin fragments in which the neck domains were shortened or replaced by an artificial random coil. Truncated kinesin fragments (K351) that contain a motor domain consisting of approximately 340 aa and a short neck domain consisting of approximately 11 aa showed fast movement (800 nm/s) and 8-nm steps. Such behavior was similar to that of recombinant fragments containing the full-length neck domain (K411) and to that of native kinesin. Kinesin fragments lacking the short neck domain (K340), however, showed very slow movement (<50 nm/s), as previously reported. Joining an artificial 11-aa sequence that was expected to form a flexible random chain to the motor domain (K340-chain) produced normal fast ( approximately 700 nm/s) and stepwise movement. The results suggest that the neck domain does not act as a rigid lever arm to magnify the structural change at the catalytic domain as has been believed for myosin, but it does act as a flexible joint to guarantee the mobility of the motor domain.

Animals↗
PubMed1997

A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion.

Cytokines and various cellular stresses are known to activate c-Jun NH2-terminal kinase (JNK), which plays a role in conveying signals from the cytosol to the nucleus. Here we investigate the translocation and activation of JNK1 during ischemia and reperfusion in perfused rat heart. Ischemia induces the translocation of JNK1 from the cytosol fraction to the nuclear fraction in a time-dependent manner. Immunohistochemical observation also shows that JNK1 staining in the nucleus is enhanced after ischemia. During reperfusion after ischemia, further nuclear translocation of JNK1 is apparently inhibited. In contrast, JNK1 activity in the nuclear fraction does not increased during ischemia but increases significantly during reperfusion with a peak at 10 min of reperfusion. The activation of JNK1 is confirmed by the phosphorylation of endogenous c-Jun (Ser-73) with similar kinetics. The level of c-jun mRNA also increases during reperfusion but not during ischemia. Based on fractionation and immunohistochemical analyses, an upstream kinase for JNK1, SAPK/ERK kinase 1 (SEK1), is constantly present in both the nucleus and cytoplasm throughout ischemia and reperfusion, whereas an upstream kinase for mitogen-activated protein kinase, MAPK/ERK kinase 1, remains in the cytosol. Furthermore, phosphorylation at Thr-223 of SEK1, necessary for its activation, rapidly increases in the nuclear fraction during postischemic reperfusion. These findings demonstrate that JNK1 translocates to the nucleus during ischemia without activation and is then activated during reperfusion, probably by SEK1 in the nucleus.

Animals↗