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Biomedical subjects

M Satoh

Publications and source records attributed to M Satoh.

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

Analysis of alpha1-adrenoceptor subtypes in rabbit aorta and arteries: regional difference and co-existence.

This study was done to determine the alpha1-adrenoceptor subtypes and to characterize the functional role of alpha1D-adrenoceptors in the following rabbit arteries: thoracic and abdominal aorta, mesenteric, renal and iliac arteries. In all arteries, selective alpha1D-adrenoceptor antagonist BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspirol(4,5) decane-7,9-dione dihydrochloride) dose dependently shifted the concentration-response curves for norepinephrine to the right. Schild plots of the results obtained from the inhibition by BMY 7378 for norepinephrine yielded a straight line with a slope of unity in thoracic (pA2 6.54+/-0.02) and abdominal (pA2 6.73+/-0.03) aorta. Slopes of Schild plots obtained from the inhibition by BMY 7378 for norepinephrine were significantly different from unity in mesenteric, renal and iliac arteries. Slopes of Schild plots for BMY 7378 were not different from unity in chloroethylclonidine-treated thoracic (pA2 6.49+/-0.14) and abdominal (pA2 6.61+/-0.11) aorta. Slopes of Schild plots for BMY 7378 were significantly different from unity in chloroethylclonidine-treated mesenteric, renal and iliac arteries. On the other hand, in Ca2+-free physiological saline solution (Ca2+-free PSS) slopes obtained from Schild plots for BMY 7378 were not different from unity in thoracic (pA2 6.41+/-0.09) and abdominal (pA2 6.28+/-0.07) aorta and mesenteric (pA2 6.55+/-0.06), renal (pA2 6.24+/-0.10) and iliac (pA2 6.64+/-0.13) arteries. BMY 7378 inhibited [3H]prazosin binding to thoracic (pKi 6.44+/-0.08) and abdominal (pKi 6.59+/-0.02) aorta with low potency, and mesenteric (pKi High 8.66+/-0.28, pKi Low 6.34+/-0.14), renal (pKi High 8.71+/-0.33, pKi Low 6.45+/-0.03) and iliac artery (pKi High 8.60+/-0.24, pKi Low 6.56+/-0.13). These results suggest that alpha1D-adrenoceptors play a significant role for contractile responses in renal and iliac artery, but play virtually no role in thoracic and abdominal aorta and that an alpha1-adrenoceptor subtype, which is pharmacologically distinguishable from the alpha1A-, alpha1B- and alpha1D-adrenoceptor subtype, may co-exist in mesenteric artery.

Adrenergic alpha-Antagonists↗
PubMed1999

Supersensitization of the adenylyl cyclase system in Chinese hamster ovary cells co-expressing cloned opioid receptors and Gz, a PTX-insensitive G protein.

Chronic and/or sustained stimulation of opioid receptors has been shown to lead to an increase in activity of the adenylyl cyclase (AC) system via pertussis toxin (PTX)-sensitive Gi/o, family G protein. In the present study, we examined whether supersensitization of the AC system is induced via a PTX-insensitive G protein, Gz, activation of which leads to the inhibition of AC activity. In Chinese hamster ovary (CHO) cells expressing either mu- or kappa-opioid receptors, acute treatment with morphine or U69,593, but not naloxone or norbinaltorphimine, respectively, suppressed forskolin-induced cyclic AMP (cAMP) accumulation, while sustained (4 h) treatment with the opioid agonists induced cAMP overshoot above the naive level (supersensitization of the AC system). Both effects were completely blocked by pretreatment with PTX. In CHO cells co-expressing mu- or kappa-opioid receptors and alpha(z), inhibitory effects of cAMP accumulation by acute treatment with the opioid agonists and supersensitization of the AC system by sustained treatment with them were induced despite pretreatment with PTX. These data suggest that supersensitization of the AC system is induced by sustained opioid agonist treatment not only via Gi/o but also via Gz.

Adenylate Cyclase Toxin↗
PubMed1999

Inhibition of inspiratory motor output by high-frequency low-pressure oscillations in the upper airway of sleeping dogs.

1. We utilized a chronically tracheostomized, unanaesthetized dog model to study the reflex effects on inspiratory motor output of low-amplitude, high-frequency pressure oscillations (HFPOs) applied to the isolated upper airway (UA) during stable non-rapid eye movement (NREM) sleep. 2. HFPOs (30 Hz and +/-2 to +/-4 cmH2O) were applied via a piston pump during eupnoea, inspiratory resistive loading and tracheal occlusion. 3. When applied to the patent UA during expiration, and especially during late expiration, HFPOs prolonged expiratory time (TE) and tonically activated the genioglossus muscle EMG. When applied to the patent UA during inspiration, HFPOs caused tonic activation of the genioglossus muscle EMG and inhibition of inspiratory motor output by either: (a) a shortening of inspiratory time (TI), as inspiration was terminated coincident with the onset of HFPOs; or (b) a prolonged TI accompanied by a decreased rate of rise of diaphragm EMG and rate of fall of tracheal pressure. These effects of HFPOs were observed during eupnoea and inspiratory resistive loading, but were maximal during tracheal occlusion where the additional inhibitory effects of lung inflation reflexes were minimized. 4. During eupnoea, topical anaesthesia of the UA abolished the HFPO-induced prolongation of TE, suggesting that the response was mediated primarily by mechanoreceptors close to the mucosal surface; whereas the TE-prolonging effects of a sustained square wave of negative pressure (range, -4.0 to -14.9 cmH2O) sufficient to close the airway were preserved following anaesthesia. 5. These results demonstrate that high-frequency, low-amplitude oscillatory pressure waves in the UA, similar to those found in snoring, produce reflex inhibition of inspiratory motor output. This reflex may help maintain UA patency by decreasing the collapsing pressure generated by the inspiratory pump muscles and transmitted to the UA.

Afferent Pathways↗
PubMed1999

Intracerebroventricular administration of nocistatin reduces inflammatory hyperalgesia in rats.

Nocistatin is a biologically active peptide derived from prepronociceptin, and its intrathecal administration has been reported to reduce nociceptin- or prostaglandin E2-induced hyperalgesia and allodynia in mice. In this study, we investigated the effects of intracerebroventricular (i.c.v.) administration of nocistatin on the inflammatory hyperalgesia induced by hindlimb intraplantar injection of carrageenan/kaolin in the rat paw-pressure test. Intracerebroventricular administration of nocistatin (0.5-50 pmol/rat) dose-dependently reduced carrageenan/kaolin-induced hyperalgesia, which peaked at 15-30 m. However, i.c.v. administration of nocistatin (50 pmol/rat) had no effect on the nociceptive threshold of non-inflamed rats. These results indicate that nocistatin has anti-hyperalgesic effects on the inflammatory hyperalgesia induced by carrageenan/kaolin at the supraspinal level.

Animals↗
PubMed1999

Real-time monitoring of glutamate transmitter release with anoxic depolarization during anoxic insult in rat striatum.

In vivo continuous real-time measurement of glutamate concentration was performed during anoxia using a dialysis electrode. By this method, the temporal resolution of the measurement of glutamate concentration was improved due to shortening of the time delay compared with the microdialysis method, and changes in the glutamate concentration were more clearly represented with greater reproducibility. After exposure to anoxia, the glutamate concentration showed biphasic changes. A relationship between the DC potential and release of glutamate was confirmed by the synchronization of anoxic depolarization (AD) with the 1st phase of glutamate release. Since the 1st phase disappeared and AD was delayed and suppressed by blocking Ca2+ influx, exocytosis is considered to play an important role in the construction of the 1st phase, which had a close relation with the occurrence of AD. Moreover, since blocking Ca2+ influx also had an effect on the glutamate release from the metabolic pool (2nd phase), reversed uptake may be involved with energy failure in the 1st phase, Ca2+ influx into the cell and rapid changes of the ionic environment associated with AD.

Animals↗
PubMed1999

The alkaline single cell gel electrophoresis assay with mouse multiple organs: results with 30 aromatic amines evaluated by the IARC and U.S. NTP.

The genotoxicity of 30 aromatic amines selected from IARC (International Agency for Research on Cancer) groups 1, 2A, 2B and 3 and from the U.S. NTP (National Toxicology Program) carcinogenicity database were evaluated using the alkaline single cell gel electrophoresis (SCG) (Comet) assay in mouse organs. We treated groups of four mice once orally at the maximum tolerated dose (MTD) and sampled stomach, colon, liver, kidney, bladder, lung, brain, and bone marrow 3, 8 and 24 h after treatment. For the 20 aromatic amines that are rodent carcinogens, the assay was positive in at least one organ, suggesting a high predictive ability for the assay. For most of the SCG-positive aromatic amines, the organs exhibiting increased levels of DNA damage were not necessarily the target organs for carcinogenicity. It was rare, in contrast, for the target organs not to show DNA damage. Organ-specific genotoxicity, therefore, is necessary but not sufficient for the prediction of organ-specific carcinogenicity. For the 10 non-carcinogenic aromatic amines (eight were Ames test-positive and two were Ames test-negative), the assay was negative in all organs studied. In the safety evaluation of chemicals, it is important to demonstrate that Ames test-positive agents are not genotoxic in vivo. Chemical carcinogens can be classified as genotoxic (Ames test-positive) and putative non-genotoxic (Ames test-negative) carcinogens. The alkaline SCG assay, which detects DNA lesions, is not suitable for identifying non-genotoxic carcinogens. The present SCG study revealed a high positive response ratio for rodent genotoxic carcinogens and a high negative response ratio for rodent genotoxic non-carcinogens. These results suggest that the alkaline SCG assay can be usefully used to evaluate the in vivo genotoxicity of chemicals in multiple organs, providing for a good assessment of potential carcinogenicity.

Amines↗
PubMed1999

Effects of opioids on neuronal survival in culture of embryonic chick dorsal root ganglion neurons.

We studied the effects of endogenous and synthetic opioids on survival of primary-cultured dorsal root ganglion neurons of 8-day chick embryos. In the basal growth medium containing nerve growth factor (NGF), [Leu5]enkephalin, [Met5]enkephalin or selective mu-agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin (DAMGO) produced significant increase of neuronal survival in a naloxone-reversible manner. On the other hand, dynorphin A (1-13), [D-Pen2, L-Pen5] enkephalin (DPLPE) (a delta-agonist) and U-50,488 (a kappa-agonist) showed no such effect. No viable neurons were observed in the absence of NGF in spite of the presence of any opioid peptides. These results suggest that [Leu5]enkephalin and [Met5]enkephalin might increase neuronal survival by stimulating mu-opioid receptors, and that these opioid peptides are working with other growth factors but, in and by themselves, do not promote survival.

Animals↗
PubMed1999

Metallothionein in radiation exposure: its induction and protective role.

Since its discovery about 40 years ago, there has been a wide interdisciplinary research interest in metallothionein (MT) on its physiological and toxicological aspects. Functionally, MT is involved not only in metal detoxification and homeostasis, but also in scavenging free radicals during oxidative damage. Among over 4500 publications which can be retrieved by Medline search, only about 50 reports have been published on the relationship of MT with ionizing and UV radiation. In this review, we have evaluated critically the published data on the induced synthesis of MT by radiation, and the potential functions of MT in radiation induced cell damage. MT mRNA expression or MT synthesis was found to be induced by exposure of cells in vitro or tissues in vivo to ionizing or UV radiation. In most of the studies in animals and tissue cultures, high doses of ionizing radiation were used to induce MT, and, therefore, it is difficult to extrapolate these results to low level of repeated exposures to radiation in humans. Induced synthesis of MT is considered as one of the mechanisms involved in the adaptive response to low dose radiation exposure. The presence of MT in normal cells may provide protective effects from radiation-induced genotoxicity and cytotoxicity. However, in tumor cells, the presence of MT can result in drug and radiation resistance as well. These effects are modulated by other cellular factors, besides MT, such as antioxidants, and by the cell cycle stages in cell proliferation and differentiation.

Adaptation, Physiological↗
PubMed1999

Apoptotic DNA fragmentation and upregulation of Bax induced by transient ischemia of the rat retina.

This study was performed to examine the involvement of apoptosis and the expression of bcl-2 family genes in ischemia-induced retinal injury. Retinal ischemia was induced in adult rats by raising the intraocular pressure to 130 mmHg for 45 min. Selective damage to the inner retina was observed 7 days after ischemia. No terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) positive cells were observed in the normal retina, but there was a significant number of TUNEL positive cells 6-48 h after transient ischemia followed by a decrease at 96 and 168 h. The number of TUNEL positive cells reached a maximum at 24 h after ischemia. DNA laddering was observed on agarose gel electrophoresis with the retinas 24 and 48 h after ischemia but not in the normal retina. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed that bax gene expression did not change immediately after cessation of ischemia, but gradually increased as early as 6 h, reached a peak at 24 h, then decreased to near baseline levels at 168 h. On the other hand, bcl-2 gene expression showed no obvious changes at any time after transient ischemia. Moreover, intense Bax protein immunoreactivity was detected in the retinal sections at 24 h after ischemia although little immunoreactivity was present in the normal sections. These results suggest that apoptosis associated with the expression of Bax is involved in retinal cell loss after ischemic insult.

Animals↗
PubMed1999

Expression of MUC2 gene in gastric regenerative, metaplastic, and neoplastic epithelia.

It has been reported that MUC2 mucin is expressed in goblet cells of gastric intestinal metaplasia, but not in its normal epithelium. To confirm this finding, we have examined the expression of the MUC2 gene by reverse transcriptase-polymerase chain reaction and immunohistochemical methods in gastric tissues obtained by routine upper gastrointestinal tract endoscopy and compared the results with pathological findings based on hematoxylin and eosin (H&E) staining. In 16.7% of the tissue specimens tested, MUC2 mRNA was detected in spite of the absence of intestinal metaplasia in HE specimens. A possible explanation for this was the identification by immunohistochemistry of MUC2 protein in regenerative gastric mucosal cells in biopsies that did not contain intestinal metaplasia. Sialyl-Le(x) epitope, which is suggested to be located on MUC2 mucin core protein (MUC2 protein), was also immunohistochemically detected in both goblet cells of intestinal metaplasia and regenerative epithelium. With regard to carcinoma, MUC2 protein was predominantly expressed in intestinal-type adenocarcinoma. These data indicate that MUC2 mucin is expressed in gastric regenerative epithelium in addition to intestinal metaplasia and intestinal type adenocarcinoma.

Adult↗
PubMed1999

Intraoperative enzyme-amperometric monitoring of extracellular glutamate concentration with a dialysis electrode in ischemic human brain.

Changes in the extracellular concentration of glutamate in the brain ([Glu]e) were monitored continuously by an enzyme-amperometric technique employing a dialysis electrode during ischemia caused by isolation of the brain tissue in rats and human patients. In the rat (n = 10), the dialysis electrode was placed in the frontal cortex and the frontal lobe was transected. A transient sharp increase in [Glu]e was frequently observed during the transection. A biphasic elevation (a rapid increase followed by a slowly continuing increase) subsequently occurred with a latent period of 1-3 min after the transection of the rat frontal lobe. In patients (n = 7), the dialysis electrode was placed in tumor-free cortical areas which were planned to be resected together with gliomas. Progressive increases in [Glu]e were observed in all of the patients as the isolation of the brain tissue progressed. A biphasic increase, similar to that seen in the rat, was identified in 2 patients in whom the cortical area surrounding the dialysis electrode was rapidly isolated. The present enzyme-amperometric technique employing a dialysis electrode appears to be useful for detecting the occurrence of potentially harmful ischemia and for securing minimal metabolic stress caused during various surgical manipulations.

Animals↗
PubMed1999

Propofol does not affect the canine cardiac conduction system under autonomic blockade.

PURPOSE: To determine the effects of propofol on the cardiac conduction system in dogs with pharmacological autonomic blockade. METHODS: In eight mongrel dogs receiving 6 mg.kg-1.hr-1 propofol and vecuronium under pharmacological autonomic blockade with atropine and propranolol the infusion rates of propofol were increased from 6, (baseline), to 12, 18 and 24 mg.kg-1.hr-1 at 60-min intervals. An electrophysiological study assessed sinus rate, sinus node recovery time, corrected sinus node recovery time, intraatrial conduction time, AV nodal effective refractory period, Wenckebach cycle length and AV conduction times. Electrocardiographical variables and arterial pressures were also measured. All measurements were repeated at 30 min after the beginning of each infusion of propofol. RESULTS: Propofol did not produce direct effects on the electrophysiological or electrocardiographical variables at any infusion rates. Heart rates did not change at higher infusion rates in the presence of decreases in arterial pressures. CONCLUSION: Propofol did not affect the cardiac conduction system in the presence of autonomic blockade. Thus, the direct cardiac effects of propofol do not play a causative role in the genesis of propofol-associated bradyarrhythmias.

Anesthetics, Intravenous↗
PubMed1999

Pulmonary alveolar proteinosis in infants.

UNLABELLED: We investigated the histological and molecular characteristics of pulmonary alveolar proteinosis (PAP) in two siblings (a brother and sister) who did not exhibit respiratory distress at birth but who each developed symptoms during infancy. Histological analysis of lung specimens showed positive staining for surfactant proteins in both patients. The polymerase chain reaction revealed expression of messenger RNA for surfactant protein B (SP-B) in the lung specimens. No defect in SP-B which is characteristic of the congenital form of PAP was observed. The concentration of surfactant protein A (SP-A) in bronchial alveolar lavage (BAL) fluid was elevated in patient 1 suggesting the BAL concentration of SP-A may be a clue to the diagnosis of this form of PAP. CONCLUSION: The accumulation of surfactant protein A in two siblings with an infantile form of pulmonary alveolar proteinosis could be a clue to the diagnosis.

Biopsy↗
PubMed1999

Association of cyclin D1 expression with factors correlated with tumor progression in human hepatocellular carcinoma.

The amplification and/or rearrangement of the cyclin D1 gene, a positive regulatory element of the G1 to S phase of the cell cycle, has been reported in various human tumors, suggesting an oncogenic role of this gene. In this study, we investigated the expression of cyclin D1 in the formalin-fixed and paraffin-embedded human hepatocellular carcinoma (HCC) tissues of 25 patients, using monoclonal antibody 5D4 raised against cyclin D1. Two distinct patterns of staining were observed in HCC cells, nuclear and cytoplasmic. The nuclear staining pattern of cyclin D1 was detected in the tissues of only 2 of the 25 HCC patients (8%) examined and no particular clinicopathological characteristics were found in these patients. In contrast, the cytoplasmic staining pattern, without nuclear staining, was detected in 8 of the 25 patients with HCC (32%). A significant correlation was found between the expression of cytoplasmic cyclin D1 and patients with tumor thrombus in the portal vein (Vp), as well as those with intrahepatic metastasis (IM). These results indicate that the cytoplasmic cyclin D1 expression appears to be related to the prognosis of HCC. The Ag nucleolar organizer regions (NORs) counts in cyclin D1-positive and -negative patients were not significantly different, suggesting that immunostaining for cyclin D1 has the potential to be a unique prognostic marker in human HCC. Simultaneous immunohistochemical study with p53 antibody in the same series of HCC revealed that 88% of the patients positive for cyclin D1 also expressed p53 and that in 91% of the patients negative for p53, cyclin D1 was not expressed. These results suggest that cyclin D1 is expressed later than the alteration of p53 in the progression of human HCC.

Adult↗
PubMed1999

Pulmonary toxicity caused by acute exposure to mercury vapor is enhanced in metallothionein-null mice.

This study examined the protective role of metallothionein (MT) against pulmonary damage caused by acute exposure to metallic mercury (Hg0) vapor using MT-null and wild-type mice. Both strains of mice were exposed to Hg0 at 6.6 to 7.5 mg/m3 for 4 hr each day for 3 consecutive days. This dosing protocol was lethal to over 60% of MT-null mice but did not kill any wild-type mice. More severe pulmonary damage was found by histopathological observation in MT-null mice than in wild-type mice. MT levels in the lung were elevated in wild-type mice after Hg0 vapor exposure, and gel filtration of the lung cytosol revealed that most of the mercury was associated with MT. In MT-null mice, MT levels were below the limit of detection (0.2 microg/g tissue) for the MT assay even after exposure. After exposure to Hg0 vapor for 3 consecutive days, the pulmonary mercury levels in wild-type mice were significantly higher than in MT-null mice. These findings suggest that MT plays a protective role against the acute pulmonary toxicity of Hg0 vapor.

Administration, Inhalation↗