Biomedical subjects

K Shigematsu

Publications and source records attributed to K Shigematsu.

At least 19 recordsLinked to original sources

PubMed1998

Endothelin-1 binding to endothelin receptors in the rat anterior pituitary gland: interaction in the recognition of endothelin-1 between ETA and ETB receptors.

1. 125I-Endothelin (ET)-1 binding to the rat anterior pituitary gland was saturable and single, with a Kd of 71 pM and a Bmax of 120 fmol/mg. 2. When 1.0 microM BQ-123 (ETA antagonist) was added to the incubation buffer, the binding parameters were 8.3 pM and 8.0 fmol/mg, whereas 10 nM sarafotoxin S6c (ETB agonist) exerted little change in these binding parameters (Kd, 72 pM; Bmax, 110 fmol/mg). 3. ETB receptor-related compounds such as sarafotoxin S6c, ET-3, IRL1620, and BQ-788 competitively inhibited 125I-ET-1 binding, only when 1.0 microM BQ-123 was present in the incubation buffer. 4. Thus, the ETB receptor is capable of binding ET-1 when the ETA receptor is being occupied by BQ-123. A collaboration mechanism between the ETA and the ETB receptor may function in the recognition of ET-1, a typical "bivalent" ligand.

Animals↗

PubMed1998

Participation of nitric oxide in the mucosal injury of rat intestine induced by ischemia-reperfusion.

The dual role of nitric oxide as a cytoprotective or a cytotoxic free radical gas has been noted in various types of pathophysiological conditions, including the digestive system. The aim of this study was to examine the role of nitric oxide in the mucosal injury induced by ischemia-reperfusion in the rat small intestine. A transient intestinal ischemia was produced in the catheterized ileal segments of rats by occluding the anterior mesenteric artery for 60 min. Nitric oxide metabolites (NO2- and NO3-) and lactate dehydrogenase activity in perfusates of the intestinal lumen were measured over 5 hr periods. The time-course of histological changes in small intestine was also observed. After ischemia-reperfusion, nitric oxide release in the intestinal lumen increased significantly and the dynamics of nitric oxide release correlated with that of lactate dehydrogenase leakage. The administration of NG-nitro-L-arginine methyl ester (1.0-2.5 mg/kg) inhibited this increased nitric oxide release and the lactate dehydrogenase leakage and afforded protection against the mucosal injury induced by ischemia-reperfusion. In conclusion, the nitric oxide production that was accelerated by ischemia-reperfusion of small intestine may possibly participate in the breakdown of intestinal mucosa after ischemia-reperfusion insult.

Animals↗

PubMed1997

Rat peritoneal macrophages express endothelin ET(B) but not endothelin ET(A) receptors.

The properties of endothelin receptors on rat peritoneal macrophages were examined in in vitro receptor autoradiographic binding experiments and in a reverse transcription-polymerase chain reaction (RT-PCR) study. Dense and specific [(125)I]endothelin-1 binding sites were detected on the macrophages. [(125)I]Tyr13-Suc-[Glu9,Ala(11,15)]-endothelin-1(8-21) , IRL1620, a selective endothelin ET(B) receptor ligand, but not [(125)I](N-[(hexahydro-1-azepinyl)carbonyl])L-Leu(1-Me)D-Trp-D-Tyr , PD151242, a selective endothelin ET(A) receptor ligand, specifically bound to rat macrophages (Kd = 0.75 +/- 0.19 nM, Bmax = 7.77 +/- 2.50 fmol/mg). RT-PCR experiments also showed the expression of endothelin ET(B) receptor mRNA, but not endothelin ET(A) receptor mRNA, in these macrophages. These results indicate that rat peritoneal macrophages apparently express the endothelin ET(B) receptor but not the endothelin ET(A) receptor.

Animals↗

PubMed1997

Endothelin receptors in kainic acid-induced neural lesions of rat brain.

Seven days after an intracerebroventricular injection of 0.8 microgram kainic acid, a time of neural tissue-repair after damage, we applied our receptor autoradiographic method to examine changes in the endothelin receptors in kainic acid-induced neural lesions of the rat brain. There were belt-shaped areas with the de novo expressed [125I]endothelin-1 binding sites in the damaged hippocampus CA1, CA3, and CA4 subfields. We also noted a homogeneous zone with a low binding-density, the area sandwiched by the belt-shaped areas. In a "remote" area corresponding anatomically to the deep soma layer of the piriform cortex plus lateral parts of amygdaloid complex we noted a well-defined area with "punched hole-figure" of low density [125I]endothelin-1 binding sites. The lesion was surrounded by areas rich in binding sites. The de novo expressed [125I]endothelin-1 binding sites were characterized endothelin B receptor. Microglia were present in the area with "punched hole-figure" and in the hippocampus pyramidal cell layer with neuronal death. In contrast to microglia, astrocytes were rich with hypertrophia in kainic acid-induced neural lesions anatomically corresponding to areas with the de novo endothelin B receptor. Taken together with the present observations of microscopic evidence of cellular distribution, we suggest that the de novo expressed endothelin B receptor was carried by astrocytes aggregating in neural lesions. In light of our findings, the possibility that astrocytes can be activated by the endothelin B receptor in response to neural tissue repair after damage to neurons would have to be considered.

Animals↗

PubMed1997

Anti-angiogenic drug AGM1470 suppresses smooth muscle cell migration induced by endothelial PDGF.

OBJECTIVES: To examine the effects of the anti-angiogenic drug AGM1470 on smooth muscle cell (SMC) migration activity stimulated by endothelial cell (EC)-derived mitogen. MATERIALS AND METHODS: Study 1; EC's were cultured under pulsatile flow using MCDB151 medium. From the supernatant of these EC dishes we devised two types of conditioned medium; anti-PDGF(+) containing 10 micrograms/ml anti-PDGF antibody, and anti-PDGF(-) containing no antibody. SMC's were cultured using both media. Study 2; EC's were cultured under the same conditions using both types of medium; MCDB151 medium containing 10 ng/ml AGM1470, and MCDB151 medium alone. After the AGM1470 concentration had been adjusted to 10 ng/ml, SMC's were cultured using each medium; AGM-exposed EC and AGM-non-exposed EC. SMC colony spreading distances were measured as an index of mitogenic activity for 4 days. RESULTS: Study 1; the anti-PDGF(-) group showed an apparently greater spreading distance than the anti-PDGF(+) group. Study 2; the AGM-non-exposed EC group showed a significantly greater spreading distance than the AGM-exposed EC group. However, MTT assay revealed no differences in proliferation between the two groups. CONCLUSION: AGM1470 suppresses the EC production of this PDGF-like mitogen as well as SMC migration activity.

Analysis of Variance↗

PubMed1997

Prion protein is necessary for latent learning and long-term memory retention.

1. The cellular prion protein, designated PrPc, is a key molecule in the prion diseases but its physiological function remains unknown. To elucidate whether PrPc plays some role in the central nervous system, we established a line of mice in which the PrP gene had been disrupted and subsequently conducted long-term observations. 2. Performance in latent learning and passive avoidance was evaluated using water-finding and step-through tests, respectively. 3. PrP-/- mice showed impaired performance in the water-finding test, indicating a disturbance in latent learning, at 23 weeks of age. In the step-through test, although the PrP-/- mice showed normal learning ability and short-term memory retention, they evidenced a significant disturbance in long-term memory retention. 4. These results indicate that PrPc is needed for certain types of learning and memory and that the loss of function of this protein may contribute to the pathogenesis of prion diseases.

Animals↗

PubMed1997

The endothelin ETA receptor exists in the caudal solitary tract nucleus of the rat brain.

1. The receptor autoradiographic method done on the rat lower brain stem and cerebellum plus 125I-endothelin-1, BQ-123, an antagonist for the endothelin ETA receptor, and sarafotoxin S6c, an agonist for the ETB receptor, revealed minute amounts of the ETA receptor coexisting with the ETB receptor in the caudal solitary tract nucleus of the rat lower brain stem. 2. The ETB receptor is present predominantly in other parts of the lower brain stem. 3. Knowledge of the heterogeneous distribution of the central endothelin receptor subtypes aids in understanding the neurophysiology of endothelins.

Amino Acid Sequence↗

PubMed1997

Endothelin receptors in rat pituitary gland.

1. We used the quantitative receptor autoradiographic method plus 125I-endothelin-1 (125I-ET-1), BQ-123, a specific antagonist for the endothelin ETA receptor, and sarafotoxin S6c, a selective agonist for the ETB receptor to investigate the ET receptor in the rat pituitary gland. 2. The method revealed that the BQ-123-sensitive ETA receptor was present predominantly in the anterior lobe and Rathke's pouch. 3. The posterior lobe contained BQ-123-sensitive ETA and sarafotoxin S6c-sensitive ETB receptors, in almost the same proportion. There was no significant 125I-ET-1 binding to the intermediate lobe. 4. Knowledge of the heterogeneous distribution of ET receptor subtypes in the pituitary gland supplies information that will be pertinent to physiological investigations of the gland.

Animals↗

PubMed1996

Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene.

Prion protein (PrP) is a glycoprotein constitutively expressed on the neuronal cell surface. A protease-resistant isoform of prion protein is implicated in the pathogenesis of a series of transmissible spongiform encephalopathies. We have developed a line of mice homozygous for a disrupted PrP gene in which the whole PrP-coding sequence is replaced by a drug-resistant gene. In keeping with previous results, we find that homozygous loss of the PrP gene has no deleterious effect on the development of these mice and renders them resistant to prion. The PrP-null mice grew normally after birth, but at about 70 weeks of age all began to show progressive symptoms of ataxia. Impaired motor coordination in these ataxic mice was evident in a rotorod test. Pathological examination revealed an extensive loss of Purkinje cells in the vast majority of cerebellar folia, suggesting that PrP plays a role in the long-term survival of Purkinje neurons.

Animals↗

PubMed1996

Two subtypes of endothelin receptors and endothelin peptides are expressed in differential cell types of the rat placenta: in vitro receptor autoradiographic and in situ hybridization studies.

We studied the localization of endothelin (ET) receptors and ET peptides in the rat placenta. In vitro receptor autoradiographic and in situ hybridization studies revealed the differential and cell-specific distribution of ET receptor subtypes, suggesting that each ET receptor plays a different role in the function of the placenta. The expression of the ETB receptor was concentrated to cytotrophoblasts and trophoblastic giant cells of the basal zone, in which fetal cells directly face maternal cells. The ETA receptor was confined to the decidual tissue and vascular wall. Both ET receptors coexisted in the labyrinth in an approximately 50:50 ratio. Prepro-ET-1 messenger RNA (mRNA) was detected in cytotrophoblasts and trophoblastic giant cells of the basal zone and endothelial cells of vessels, whereas ET-1-like immunoreactivity was present not only in trophoblasts and endothelial cells, but also in the decidual tissue and vascular wall. ET-3 mRNA was localized in migrating cells. We also found changes in the expression levels of ET receptors by means of a cold ligand saturation study. The number of specific [125I]ET-1-binding sites was increased in the basal zone and labyrinth with gestation, but not in the decidual tissue. The enhancement of ETA receptor, ETB receptor, and prepro-ET-1 mRNA levels was also supposed, based on data obtained by RT-PCR Southern hybridization. On the other hand, ET-3 mRNA levels were reduced with gestation. These findings support the idea that ETs, through interaction with ETA and ETB receptors, play an important role in the regulation of placental growth and fetoplacental circulation through autocrine and paracrine mechanisms.

Animals↗

PubMed1995

NMDA receptor involvement in endothelin neurotoxicity in rat striatal slices.

The high K(+)-evoked dopamine release from rat striatal slices remained impaired by 50% up to 2 h after pulse exposure of the tissues to endothelin-3, under conditions of hypoglycemia/hypoxia. This striatal dysfunction was significantly improved by D-2-amino-5-phosphonopentanoic acid, a NMDA receptor antagonist, at a much lower concentration than that providing protection against NMDA-evoked dysfunction. In light of these findings, the important role of glutamatergic mechanisms, especially NMDA receptors, in mediating endothelin neurotoxicity warrants further attention.

2-Amino-5-phosphonovalerate↗

PubMed1995

Splenic metastasis from lung cancer.

Splenic metastasis from lung cancer is a rare clinical event, most often diagnosed at the time of autopsy. We report 2 cases of splenic metastasis with a primary lung cancer. The first case was a 76-year-old man presenting with a recurrent solitary splenic metastasis 14 months after surgical removal of a squamous cell carcinoma of the lung. The second patient was a 72-year-old woman who had a poorly differentiated carcinoma of the lung and multiple abdominal metastasis. We also investigated 267 autopsy cases of lung cancer from 1975 to 1992. Histologically, there were 73 cases of squamous cell carcinoma, 123 adenocarcinoma, 29 large cell carcinoma, 36 small cell carcinoma, and 7 other miscellaneous tumours. The number of splenic metastasis from lung cancer in these cases was 15 (5.6%). Splenic metastasis from a primary cancer of the left lung was more frequent than that from the right lung. Nine of 15 splenic metastases were smaller than 1 cm in size. Splenic metastasis was associated with liver and pancreas metastasis. All 15 autopsy cases with splenic metastasis from lung cancer had other abdominal organ metastasis. Our analysis indicates that a solitary splenic metastasis is rare. Selection of a suitable therapeutic approach is important.

Aged↗

PubMed1995

Adrenocorticotropic hormone-independent bilateral macronodular adrenocortical hyperplasia associated with Cushing's syndrome.

A case of adrenocorticotropic hormone independent bilateral adrenocortical macronodular hyperplasia (AIMAH) is reported. A 59 year old male was admitted to hospital because of hypertension. Subsequently, hypercortisolism, low plasma adrenocorticotropic hormone (ACTH), loss of diurnal rhythm of ACTH, lack of suppression with high dose dexamethasone were found and bilateral adrenal enlargement was detected by abdominal computerized tomography and adrenal scintigraphy. Bilateral total adrenalectomy was performed under a diagnosis of bilateral adrenal hyperplasia associated with Cushing's syndrome. Both adrenal glands were enlarged in size and weight. Bulging nodules were found at the cut section. Microscopically, a variegated histologic pattern including trabecular, adenoid and zona glomerulosa-like (ZG-like) structures was revealed in the nodules. Immunohistochemical examination disclosed positive staining of cytochrome P-450 17 alpha, negative of 3 beta-HSD in the ZG-like structure. Ultrastructurally, the cells composing the ZG-like structure were similar to those of the ZG in normal adrenal cortex. The authors agree that AIMAH is one of the entities causing Cushing's syndrome, and advise pathologists to keep this disorder in mind when they examine the adrenals in Cushing's syndrome.

17-Ketosteroids↗

PubMed1995

Accumulation of proteinase K-resistant prion protein (PrP) is restricted by the expression level of normal PrP in mice inoculated with a mouse-adapted strain of the Creutzfeldt-Jakob disease agent.

Creutzfeldt-Jakob disease (CJD) is a transmissible neurodegenerative disease of humans caused by an unidentified infectious agent, the prion. To determine whether there was an involvement of the host-encoded prion protein (PrPc) in CJD development and prion propagation, mice heterozygous (PrP+/-) or homozygous (PrP-/-) for a disrupted PrP gene were established and inoculated with the mouse-adapted CJD agent. In keeping with findings of previous studies using other lines of PrP-less mice inoculated with scrapie agents, no PrP-/- mice showed any sign of the disease for 460 days after inoculation, while all of the PrP+/- and control PrP+/+ mice developed CJD-like symptoms and died. The incubation period for PrP+/- mice, 259 +/- 27 days, was much longer than that for PrP+/+ mice, 138 +/- 12 days. Propagation of the prion was barely detectable in the brains of PrP-/- mice and was estimated to be at a level at least 4 orders of magnitude lower than that in PrP+/+ mice. These findings indicate that PrPc is necessary for both the development of the disease and propagation of the prion in the inoculated mice. The proteinase-resistant PrP (PrPres) was undetectable in the brain tissues of the inoculated PrP-/- mice, while it accumulated in the affected brains of PrP+/+ and PrP+/- mice. Interestingly, the maximum level of PrPres in the brains of PrP+/- mice was about half of the level in the similarly affected brains of PrP+/+ mice, indicating that PrPres accumulation is restricted by the level of PrPc.

Animals↗

PubMed1994

Endothelin-3 stimulates inositol 1,4,5-trisphosphate production and Ca2+ influx to produce biphasic dopamine release from rat striatal slices.

1. Real-time monitoring of dopamine (DA) release from rat striatal slices demonstrated that endothelin (ET)-3 (0.1-10 microM) produced a biphasic DA release consisting of transient and sustained components. When extracellular Ca2+ was removed, the sustained but not transient response remarkably decreased. 2. ET-3 (1-10 microM) stimulated an increase in the intracellular Ca2+ concentration ([Ca(2+)]i), which also consisted of two components. The external Ca2+ depletion inhibited primarily the sustained component of the Ca2+ response to ET-3. 3. ET-3 increased inositol 1,4,5-trisphosphate (IP3) concentrations in striatal slices. This response peaked at 10 to 20 sec and returned to the basal level 2 min after stimulation, an event which was in good accord with a prompt and transient phase of both cytosolic Ca2+ activity and DA release evoked by ET-3. 4. Thus, ET-3 produces a transient and a sustained release of DA from striatal slices by stimulating intracellular Ca2+ mobilization via IP3 formation and extracellular Ca2+ influx, respectively.

Animals↗

PubMed1994

Microglia with an endothelin ETB receptor aggregate in rat hippocampus CA1 subfields following transient forebrain ischemia.

We examined endothelin (ET) receptors in the hippocampus CA1 subfields of stroke-prone spontaneously hypertensive rats subjected to a 10-min bilateral carotid occlusion and reperfusion. When delayed neuronal death had occurred in the pyramidal cell layer at 7 days after transient forebrain ischemia, the quantitative receptor autoradiographic method we used revealed a dramatic increase in number of 125I-ET-1 binding sites in the hippocampus CA1 subfields. The highest number of de novo binding sites appeared in the area corresponding anatomically to the pyramidal cell layer with neuronal death. These binding sites were characteristically the ETB receptor. The de novo 125I-ET-1 binding was mainly present on microglia aggregating with a high density in the damaged pyramidal cell layer. As ET-1- and ET-3-like immunoreactivities were highly expressed within astrocytes in damaged neural tissue, the possibility that microglia with the ETB receptor are activated to participate in the pathophysiology of ischemia-related neural tissue damage by astrocytic ET-1 and ET-3 produced in response to transient forebrain ischemia would have to be considered.

Amino Acid Sequence↗

PubMed1994

Intrapulmonary lymph nodes.

We report two cases of intrapulmonary lymph nodes detected by a chest roentgenogram or CT scan. The first patient was a 61-year-old fisherman referred complaining of cough and hemosputum. Chest roentgenogram showed a subpleural small nodular shadow at the superior segment of the right lower lobe. Thoracotomy showed a small anthracotic lymph node. The other case was a 68-year-old female patient admitted for further examination of a subpleural small nodular shadow at the latero-basal segment of the left lower lobe detected on a chest CT scan. Thoracoscopic surgery revealed that the black nodule was an anthracotic lymph node. The appearance of an intrapulmonary lymph node on radiological examination is rare, however, it should be considered in the differential diagnosis of a solitary or multiple peripheral pulmonary nodules in adults. A small nodular shadow should be resected if malignancy is suspected though not proven. Subpleural intrapulmonary lymph node warrants thoracoscopic surgery.

Aged↗

PubMed1993

Periventricular nucleus lesioning modulates specific somatostatin binding in various brain regions and anterior pituitary.

The effects of periventricular nucleus (Pe) lesioning on the plasma growth hormone (GH) levels and the anterior pituitary (A.P.) and brain somatostatin (SRIF) receptors were studied. A transient significant increase in plasma GH level in lesioned rats was detected 1 day after the operation. This elevated level of plasma GH started to decrease 3 days after lesioning. These changes were paralleled by an increase in binding of 125I-Tyr11-SRIF-14 to the A.P. 1 day after lesioning. This result could further confirm that the SRIF inhibitory action on GH release takes place at the A.P. level. Also, a transient increase in binding of the radioligand was detected in some brain areas 1 and 4 days after the lesion. However, the mechanism by which this increase takes place remains to be elucidated.

Animals↗