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Biomedical subjects

F Sato

Publications and source records attributed to F Sato.

At least 163 records · Page 9Linked to original sources
PubMed1997

New ulcerative colitis model induced by sulfhydryl blockers in rats and the effects of antiinflammatory drugs on the colitis.

We tried to produce a new ulcerative colitis model in rats by topical administration of sulfhydryl blockers. After male SD rats were fasted for 24 hr, 100 microliters of 3% N-ethylmaleimide (NEM) or iodoacetamide (IA) was introduced into the colon via a Nelaton's catheter. Both NEM and IA caused severe diarrhea with rectal bleeding and decreased body weight for about 7 days. At autopsy, adhesions and dilatation of the colon and severe mucosal lesions were observed. Both the weight and myeloperoxidase activity of the colon increased markedly. Maximum changes were observed within 1-3 days followed by gradual recovery, but even on day 21, some abnormalities were still observed. The ulceration and inflammation of the colon were confirmed by histological studies. Antiinflammatory drugs such as indomethacin inhibited the inflammation of the colon by NEM, but aggravated the ulceration. These results revealed that sulfhydryl blockers instilled into the colon caused ulcerative colitis in the rat. This model may be useful in studies on the pathogenesis of ulcerative colitis and the evaluation of drugs for therapy. Furthermore, it was suggested that antiinflammatory drugs may delay the healing of colonic ulcers.

Animals↗
PubMed1997

Role of endogenous basic fibroblast growth factor in the healing of gastric ulcers in rats.

Recently, it has been pointed out that growth factors play an important role in the healing of gastrointestinal ulcers. In the present study, we examined the role of endogenous basic fibroblast growth factor (bFGF) in the healing of gastric ulcers in the rat. In male SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Time-dependent changes in the area and bFGF content in the ulcerated area and distribution of bFGF in the ulcerated mucosa were examined. Effects of bFGF mutein CS23 (TGP-580) and a monoclonal antibody for bFGF (MAb 3H3) on the healing of the gastric ulcers and angiogenesis in the ulcer bed were also examined. The content of bFGF in the ulcerated area increased with time as the ulcer healed and reached a maximum 7 days after ulcer formation. In the gastric ulcer bed, many cells such as fibroblasts and macrophages were positively stained immunohistochemically by anti-bFGF antiserum. MAb 3H3 (0.1 mg/rat/day, i.v.) inhibited angiogenesis in the ulcer bed and significantly delayed ulcer healing, while TGP-580 (0.001-0.1 mg/kg x 2/day, p.o.) increased the number of microvessels in the ulcer bed and accelerated the healing. These results suggest that endogenous bFGF may play an important role in the healing of gastric ulcers in the rat and that the angiogenic properties of bFGF (TGP-580) may be involved in its effect on ulcer healing.

Animals↗
PubMed1997

[Cystic lymphangioma of the tunica vaginalis testis. A case report].

A 42-year-old man who complained progressive enlargement of an intrascrotal mass visited to our hospital. Preoperative sonography revealed multiple cystic masses adjacent to the left testis. Total surgical excision was performed. The cystic masses were arising from tunica vaginalis testis. Histopathologically, a cystic lymphangioma was diagnosed because of the morphological features and the immunohistochemical stainings of CD34 and Factor VIII related antigen which were observed positive reactions in endothelial cells of the cysts.

Adult↗
PubMed1997

[Aortic valve regurgitation due to quadricuspid valve: a report of complicated case].

A 66-year-old male with the congestive heart failure was diagnosed grade 4 aortic valve regurgitation due to quadricuspid valve associated with bacterial endocarditis, widely patent left coronary artery ostium, chronic renal failure, and secondary hyperparathyroidism. Coronary arteriography showed that the size of left coronary ostium was widely patent 10 mm in diameter, and trans-esophageal echo cardiogram revealed perforation and vegetations on the coronary cusps of the aortic valve.

Aged↗
PubMed1997

Pharmacological profile of a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

Pharmacological properties of NK-104 ((+)-monocalcium bis¿(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl++ +]-3,5-dihydroxy-6- heptenoate¿, CAS 147526-32-7), a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, were investigated. The kinetic study, using rat liver microsomal HMG-CoA reductase, revealed that NK-104 is a competitive inhibitor of HMG-CoA reductase with a Ki of 1.7 nmol/l. To examine the inhibitory effect on sterol synthesis in vivo, de novo synthesis of sterols from [14C]acetate 3 h after oral administration of NK-104 was measured in rats. NK-104 showed marked inhibition in liver (ED50 0.13 mg/kg) and in ileum (ED50 0.20 mg/kg), but much weaker in the other tissues. The inhibitory effect of NK-104 on liver sterol synthesis lasted over 6 h, while that of pravastatin and simvastatin disappeared 6 h after administration of the drugs twice the ED50s. Due to induction of HMG-CoA reductase, initial suppression of hepatic sterol synthesis by pravastatin and simvastatin was compensated, and the cumulative change in hepatic sterol synthesis during 12 h after drug administration was remarkably negative only with long-acting NK-104. Hypolipidemic effects of NK-104 (0.03, 0.1, 0.3 and 1 mg/kg p.o. for 2 weeks) were examined in beagle dogs. NK-104 reduced plasma total cholesterol dose-dependently (13.1, 18.5 and 20.2% at doses of 0.1, 0.3 and 1 mg/kg, respectively), and also plasma triglycerides by 0.1 mg/kg or more. Pravastatin (1 and 3 mg/kg) and simvastatin (3 mg/kg) lowered plasma total cholesterol (14.0, 15.4 and 17.4%, respectively), but did not significantly affect plasma triglyceride levels. These results indicate that NK-104 is a potent, liver-selective, long-acting HMG-CoA reductase inhibitor with a high cholesterol- and triglyceride-lowering potency.

Animals↗
PubMed1997

Concentration of levofloxacin in cervical mucus and its clinical effects on cervicitis.

An investigation was made on the concentration of levofloxacin (LVFX) in cervical mucus and its clinical effects on cervicitis. The results were as follows: 1) The concentrations of orally administered LVFX in the cervical mucus of 110 subjects were determined by HPLC. During 1-4 hour after the administration the mean concentration of LVFX in the cervical mucus reached a level of 2 micrograms/g, which was higher than the serum level. The transfer of LVFX to the cervical mucus was almost the same as that to other genital organs. 2) When LVFX was given to 102 patients at a dose of 100-200 mg, t.i.d for 4-5 days and the efficacy was evaluated with clinical improvement, the clinical efficacy rate of LVFX was 72/102 (70.6%). Significant bacteriological effects were observed in 70/73 (95.9%), especially, the disappearance rate of C. trachomatis was 18/18 (100%). 3) The administration LVFX did not cause any subjective or objective side effects and any abnormalities were not detected in the laboratory test done in this study. These results demonstrate that LVFX can be sufficiently transferred to the cervical mucus for the treatment of cervicitis due to the infection of C. trachomatis etc.

Adult↗
PubMed1996

Inhibition of adenylyl cyclases by 12(S)-hydroxyeicosatetraenoic acid.

The inhibition of adenylyl cyclase (AC) by a 12-lipoxygenase metabolite of arachidonic acid, 12(S)-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE), was investigated using three different kinds of cells: NRK-49F (normal rat kidney fibroblasts), AtT-20 (mouse pituitary tumor cell line) and HL-60 (human leukemia cells) cells. The inhibition was very obvious in NRK-49F and AtT-20 cells, but it was almost negligible in HL-60 cells. There was no difference in terms of the binding of 12-HETE to NRK-49F and HL-60 cells. Pretreatment of NRK-49F cells with pertussis toxin almost completely ADP-ribosylated Gi proteins, but it did not affect the inhibition of 12-HETE on AC in this cell. This result excludes the involvement of Gi proteins in 12-HETE-mediated inhibition of AC. It was revealed that the characteristics of ACs in these cells were quite different in response to agonists and forskolin, suggesting that these cells do have different isoform of AC. We conclude that 12-HETE inhibits the activity of AC depending upon the isoform.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1996

Three-dimensional analysis of cerebellar terminals and their postsynaptic components in the ventral lateral nucleus of the cat thalamus.

Relationships among cerebellar terminals (CTs), dendrites of thalamocortical projection neurons (TCNs), and dendrites of local circuit neurons in the ventral lateral nucleus of the cat thalamus were analyzed quantitatively by observing several series of serial ultrathin sections and by using a computer-assisted program for the three-dimensional reconstruction from serial ultrathin sections. In pentobarbital-anesthetized cats, CTs were labeled either by injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the cerebellar nuclei or by intra-axonal injection of HRP after electrophysiological identification. By using two series of 133 and 73 serial sections, mutual relationships between 43 WGA-HRP-labeled CTs and their postsynaptic structures were analyzed based on their synaptic specializations and shapes of synaptic vesicles. Thirty-nine of these CTs formed a synapse with one TCN dendrite, whereas only four CTs formed synapses with two TCN dendrites. These CTs also synapsed on dendrites containing pleomorphic synaptic vesicles (presynaptic dendrites). Single CTs synapsed on 0-6 presynaptic dendrites (2.2 +/- 1.5, N = 43) through their whole extents, and about 40% of these presynaptic dendrites that were contacted by CTs established synaptic contacts with the same TCN dendrites on which the CTs synapsed. Thus, a CT, a presynaptic dendrite, and a TCN dendrite formed a triadic arrangement. Triadic arrangements were identified in approximately 60% of these 43 CTs. However, they rarely had a glomerulus-like appearance, as described previously in the ventral lateral nucleus and other main thalamic relay nuclei. In another series of 83 and 43 serial sections along dendrites of TCNs, observations were focused on the triadic arrangement. Triadic arrangements were located evenly on the primary and secondary dendrites of TCNs. Computer-assisted three-dimensional reconstructions were made on one WGA-HRP-labeled CT and two intra-axonally labeled CTs (a bouton en passant and a bouton terminal) with their surrounding neuronal elements, and complex spatial arrangement of neuronal processes became obvious. These results provide the quantitative assessment of synaptic arrangements among CTs, presynaptic dendrites, and TCN dendrites and reveal their spatial interrelations in the cat ventral lateral nucleus.

Animals↗
PubMed1996

Distribution of Ca2+/calmodulin-dependent protein kinase kinase alpha in the rat central nervous system: an immunohistochemical study.

Ca2+/calmodulin-dependent protein kinase IV (CaM-kinase IV) is activated by CaM-kinase IV kinase. We provided a rabbit antiserum against 20 amino acid residues at the carboxyl-terminal end of CaM-kinase IV kinase, and examined regional and intracellular distribution of CaM-kinase IV kinase immunohistochemically in the central nervous system of the rat by light and electron microscopy. The immunoreactivity was found in cellular nuclei of virtually all neurons. However, the immunoreactivity was weak in the nuclei of the granule cells in the cerebellar cortex, although the nuclei of the granule cells were reported to contain high CaM-kinase IV activity. Thus, it was suggested that other types of CaM-kinase IV kinase might exist in the cerebellum, and the present CaM-kinase IV kinase was named as CaM-kinase kinase alpha.

Amino Acid Sequence↗
PubMed1996

The effects of alpha-phenyl-tert-butyl nitrone (PBN) on copper-induced rat fulminant hepatitis with jaundice.

In the present study we demonstrated the protective effects of the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN) against fulminant hepatitis with jaundice in LEC rats. In LEC rats an excess amount of copper is accumulated in the liver and causes hepatitis with severe jaundice. PBN was subcutaneously administered every 2 d at the concentration of 128 mg/kg, beginning with 13-week-old rats and continuing for 17 weeks. PBN prevented the loss of body weight, reduced death rate, and suppressed the increase in GTP and GOT values reflecting hepatic cell destruction. Ocular inspection also confirmed the suppressive effects of PBN on jaundice. In parallel with these phenomena, the amounts of thiobarbituric acid-reactive substances (TBARS) in livers of PBN-administered rats were found to be lower than those of non-PBN-administered rats. Little histological changes were observed in PBN-administered rats in comparison with non-PBN-administered rats. The protective effect of PBN on the formation of oxidative damage in liver DNA was observed but not so remarkable as that on lipid peroxidation. From these results, it was concluded that PBN had the liver-protective effects against fulminant hepatitis with jaundice. This suggested that free radicals play an important role in abnormally accumulated copper-induced liver injury and that PBN potentially has therapeutic value for the treatment of hepatitis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

Studies on the site of ethanol action in inducing prolactin release in male rats.

Hypersecretion of prolactin (PRL) has been implicated as one of the factors that mediate ethanol-induced hypogonadism, but the site(s) in the central nervous system where ethanol acts to lead to the stimulation of PRL secretion is unknown. To clarify the site(s) of ethanol action, medial basal hypothalamic deafferentation (MBHD) or medial basal hypothalamic ablation (MBHA) were performed stereotaxically in male rats, and their PRL secretory capacity in response to acute ethanol administration was compared with that of intact or sham-operated controls. In intact control rats, plasma immunoreactive PRL concentration increased markedly (P < .001 v saline injection) following ethanol 400 to 500 mg/100 g body weight (BW) intraperitoneally (IP). The PRL response was dose-related and reached a maximum plateau level at 15 minutes. Plasma PRL returned to a near-basal level by 60 minutes. The response was blocked completely (P < .001) by pretreatment with dopamine (1 mg per rat), a specific inhibitor of adenohypophyseal PRL secretion. In sham-operated rats and in MBHD and MBHA rats, ethanol (500 mg/100 g BW IP) induced a significant (P < .001 to .05) elevation of PRL relative to the respective saline treatment. The basal level was significantly (P < .005) lower in the MBHD group (5.3 +/- 0.9 ng/mL) and significantly (P < .001) higher in the MBHA group (101.1 +/- 15.7 ng/mL) than in the sham group (17.2 +/- 5.9 ng/mL). These results suggest the following: (1) acute ethanol administration stimulates PRL secretion from the pituitary in a dose-related manner, (2) ethanol appears to have direct stimulatory effects on adenohypophyseal PRL secretion, and (3) extrahypothalamic brain areas exert a stimulatory influence and the hypothalamus an inhibitory influence on basal PRL secretion.

Animals↗
PubMed1996

Oestrogen producing adrenocortical adenoma: clinical, biochemical and immunohistochemical studies.

Oestrogen producing adrenocortical tumours are extremely rare. We report a 65-year-old woman who presented with abnormal vaginal bleeding, with no significant abnormalities in her uterus or ovaries, who was found to have a right adrenal mass by radiological examination. Excessive secretion of oestrogens from the tumour was demonstrated by adrenal venous sampling. Basal levels of corticosteroids were within normal limits. Adrenalectomy was performed and pathological examination revealed an adrenocortical adenoma measuring 5.5 cm in its greatest dimension, in which both clear and compact tumour cells were observed. Oestrogen levels normalized following the removal of the adrenal mass. Tissue concentrations of oestrone and oestradiol in the tumour were 6.9 (69.5 pmol/g wet tissue weight) and 34.6 (93.6 pmol/g wet tissue weight)-fold greater respectively than those of adjacent non-neoplastic adrenal cortex. Aromatase activity in the tumour tissue determined by the 3H-water method was 118.6 pmol/h/mg protein, equivalent to that of a full-term human placenta. Immunohistochemical analysis of aromatase demonstrated immunoreactivity in the tumour cells, especially in compact cells, but not in adjacent non-neoplastic adrenal cells. This is the first reported case of an oestrogen producing adrenocortical adenoma in which aromatase in the tumour cells was documented.

Adenoma↗
PubMed1996

Life span and tumours in the first-generation offspring of the gamma-irradiated male mouse.

C57BL/6 male mice were exposed to 3 Gy 60Co gamma-rays and mated with unirradiated females after 15 days to produce F1 progeny produced following irradiation of the spermatids. After weaning the offsprings were allowed to live their normal life span. The mean litter size of the irradiated group significantly decreased from 7.1 to 4.9 (p < 0.01), but the sex ratio was not altered by the irradiation. No significant differences in the survival curve and mean life-span between the irradiated and control groups were noted. The only radiation effect in tumour incidence was a decrease of histiocytic sarcoma in female offspring of irradiated males. Except for this, there were no significant differences between the irradiated group and the control group in the incidence or age distribution of tumours.

Animals↗
PubMed1996

Ethylene-induced gene expression of osmotin-like protein, a neutral isoform of tobacco PR-5, is mediated by the AGCCGCC cis-sequence.

Osmotin-like protein (OLP) is a neutral isoform in the group 5 pathogenesis-related (PR) tobacco proteins. The OLP gene, like the basic PR protein genes, is constitutively expressed in tobacco roots and cultured cells. OLP is not naturally present in intact healthy leaves, but ethylene treatment induces a high accumulation there. To study the mechanism of OLP gene expression as induced by ethylene, we cloned the gene from Nicotiana sylvestris, an ancestor of N. tabacum. Sequence analysis showed that it has no intron and that its promoter region contains two AGCCGCC sequences that are conserved in most basic PR-protein genes. The function of the AGCCGCC sequences in transgenic tobacco plants that harbor the wild and mutated OLP promoter::GUS fusion genes was analyzed. Mutation in the AGCCGCC sequences clearly inhibited the GUS expression induced by ethylene, indicative that the AGCCGCC sequence(s) is a DNA element(s) responsive to ethylene. An EREBP2 protein, isolated as one of the proteins binding to the AGCCGCC sequence of the tobacco beta-1,3-glucanase gene, also was found to bind to the AGCCGCC sequence(s) of OLP gene. These results suggest that the ethylene-induced expression of OLP is regulated by a trans-acting factor(s) common to basic PR-proteins.

Amino Acid Sequence↗
PubMed1996

In vitro contraction of the canine corpus cavernosum penis by direct perfusion with prolactin or growth hormone.

PURPOSE: It is well established that hyperprolactinemia, most typically seen in prolactinoma patients, causes hypogonadism and impotence. There seems to be a good possibility that hyperprolactinemia causes impotence, at least partially via some intrinsic property of prolactin (PRL), rather than through its suppressive effects on the hypothalamic-pituitary-gonadal testosterone dynamics. In the present investigation, we used an in vitro canine model to attempt to clarify whether direct action of PRL on the corpus cavernosum penis may lead to erectile insufficiency. Growth hormone (GH) and placental lactogen (PL), both having close structural and functional homologies to PRL, were also studied. MATERIALS AND METHODS: Isometric tension measurement with cavernous strips was performed in the presence or absence of 10(-5) to 10(-9) M. PRL, GH, or PL in the perfusion medium. The tension change induced by the test substances was normalized relative to that induced by 120 mEq KCl. RESULTS: Both PRL and GH produced dose-related elevations (p < 0.01) of the cavernous tension, whereas PL and thiol-cleaved PRL in comparable doses were without effect (p > 0.05). When the tension rise produced by 120 mEq KCl was taken as 100%, the maximum contractions produced by PRL and GH were 80% and 110%. The minimum effective concentration was 10(-8) to 10(-7) M. for both PRL and GH. Pretreatment with indomethacin (10(-5) M.), but not tetrodotoxin (10(-5) M., partially suppressed (p < 0.05) the effects of PRL. CONCLUSION: These results suggest that PRL and GH directly and specifically produced contraction of the corpus cavernosum penis, resulting in erectile insufficiency, and that the effect of PRL is partially mediated by prostaglandin.

Animals↗
PubMed1996

Effects of exercise and CO2 inhalation on intersubject variability in ventilatory and heart rate responses to progressive hypoxia.

Although the ventilatory and heart rate responses to hypoxia are known to vary widely among subjects, it is not known how exercise or hypercapnia influence the intersubject variability of these responses. If the intersubject variability increases under such conditions, the inherent response of individuals will have more impact on ventilation and heart rate under a variety of hypoxic conditions during exercise or with hypercapnia than at rest or with normocapnia. Seventeen healthy male volunteers underwent tests to measure ventilatory response to isocapnic progressive hypoxia three times respectively: at rest; during CO2 inhalation (end-tidal carbon dioxide tension (PET,CO2) raised by 5 torr from the baseline level); and during mild exercise with a cycle ergometer (12.5 W) in a supine position. The mean (SEM) value of hypoxic ventilatory response (HVR) (delta minute ventilation (V'E)/delta arterial oxygen saturation (Sa,O2) was significantly increased both in the exercise and hypercapnic runs compared with that in the control run (0.45 +/- 0.12, 0.34 +/- 0.08, respectively, vs 0.12 +/- 0.02 L.min-1/% fall), although the respiratory pattern was different under the two loaded conditions. The intersubject variation in HVR was also significantly increased during the two loaded conditions compared with the control, although a significant correlation remained between the control value and that obtained during either loaded condition (r = 0.66 and r = 0.60, respectively). The heart rate (HR) response evaluated by the slope factor (delta HR/delta Sa,O2) was not significantly different either in the mean value or in the intersubject variability among the three experimental conditions. In conclusion, exercise or CO2 inhalation not only increase the slope value of HVR but also amplify the intersubject variability of the response. In contrast, the HR response to hypoxia evaluated as a slope factor does not change with exercise or CO2 inhalation.

Adult↗
PubMed1996

Vagus-dependent and vagus-independent mechanisms of action of the erythromycin derivative EM574 and motilin in dogs.

The motor-stimulating action of de(N-methyl)-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (EM574) on the upper gastrointestinal tract was studied in fasted conscious dogs using chronically implanted force transducers and compared with those of porcine motilin and cisapride. EM574 induced gastric phase III-like migrating contractions and increased the plasma motilin levels slightly. The gastric motility induced by low doses of EM574 and motilin was abolished by a 5HT3-receptor antagonist ondansetron and acute vagal blockade, whereas under these conditions, high doses of both agents induced contractions, which were abolished by atropine. Cisapride-induced gastric motility was inhibited by atropine and acute vagal blockade, but not by ondansetron. EM574 did not stimulate gastric secretion in the basal state. These results indicate that EM574- and motilin-induced gastrointestinal motility is attributable mainly to motor-stimulating vagal cholinergic neurons, and 5HT3-receptors are probably involved in the process. At high doses, EM574 and motilin also appear to stimulate cholinergic neurons in a non-vagal pathway, probably the enteric nervous system.

Animals↗