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Biomedical subjects

K Saeki

Publications and source records attributed to K Saeki.

At least 235 records · Page 13Linked to original sources
PubMed1991

9-Amino-1,2,3,4-tetrahydroacridine is a potent inhibitor of histamine N-methyltransferase.

The effect of 9-amino-1,2,3,4-tetrahydroacridine (THA) on histamine N-methyltransferase (HMT), an enzyme catalyzing the methylation of histamine to form tele-methylhistamine in the brain, was studied in vitro using a partially purified enzyme preparation from bovine brain and in vivo in the mouse brain. THA inhibited the HMT activity in competitive and non-competitive mixed type manners with respect to histamine. The Ki and Ki' values were 75 nM and 1.2 microM, respectively. The IC50 values for THA, 9-aminoacridine and physostigmine in the inhibition of HMT determined at fixed concentrations of histamine (20 microM) and S-adenosylmethionine (50 microM) were 0.2, 0.37 and 20 microM, respectively. Neostigmine exhibited only 15% inhibition even at a concentration of 100 microM. THA (2-10 mg/kg, s.c.) dose-dependently inhibited HMT in the mouse brain. The inhibition of HMT by THA (10 mg/kg) was marked at 30 and 60 min after treatment, but disappeared by 120 min after. THA (10 mg/kg) significantly increased the histamine level and decreased the tele-methylhistamine level in the mouse brain. These results indicate that THA is a potent inhibitor of HMT.

Animals↗
PubMed1991

Adenocarcinoma in the ascending colon of ACI strain rat foster bred by WF-Osaka female rat.

We now keep HFRSV free WF-Osaka rats and ACI rats together in the separate three animal rooms (animal room 1, 2 and 3) and the incidence of colon carcinoma is still high on the WF-Osaka rats in animal room 1 with the high humidity. Two female ACI rats developed colon carcinomas in the ascending colon. The gross and the histological appearance of the colon carcinoma were completely the same as those of WF-Osaka rats. ACI and WF-Osaka rat strain together have been kept bred in neighborhood of each other in different racks in the identical animal room 1. To obtain HFRSV free ACI rat strain, Antecedents born by cesarean section of ACI female pregnant rat were foster-bred by WF-Osaka female nursing rat incidentally, and at the fourth mating generation after the start of foster-breeding, they developed colon carcinomas at the age of four months. Before five out of eight F1 hybrids by WF-Osaka cancer carrying female rat x male ACI rat had developed the same colon carcinoma, but none of F1 hybrids by the contrary mating had developed colon carcinomas in this same animal room 1. Animal room 1 and 2 where there was a high incidence of colon carcinomas, had happened to be kept moistened. However, after disinfection of these animal rooms, the animal room 2 and 3 occurred to be kept dried, and rats of WF-Osaka strain ceased to develop colon carcinomas in the animal room 2. Thereafter, animal room 2 and 3 were adjusted to be kept moistened again. Subsequently WF-Osaka rats in the animal room 2 began to have colon carcinomas in the ascending colon as before, but none of rats developed colon carcinomas in the animal room 3. Based on these findings, we consider that milk factor at the time of foster-breeding played an important role first and high moistened condition of the animal room resulted in promoting effect on colon carcinogenesis on ACI rats and WF-Osaka rats as well.

Adenocarcinoma↗
PubMed1991

Induced adenocarcinoma of the ascending colon on LE and Wistar/Shhi rats and virus like particles in the serum of colon cancer carrying WF rats.

Intraperitoneal injection of the serum of colon cancer carrying WF rats induced, within two months, colon carcinomas in the ascending colon of LE and Wistar/Shi rats when they were given it during their suckling. We had also induced colon carcinomas in the ascending colon of ACI rats by the same methods. Therefore, it is supported that this serum derived from colon cancer carrying WF rats must have some transmissible agent in itself. In addition, we ultracentrifuged the serum of cancer carrying WF rats and we found, in the sediment, numerous round or oval virus like corpuscles by electron microscopy studies. Negatively stained corpuscles by phosphotungstic acid staining clearly revealed fine spike appearance on their surface. We believe that these virus like corpuscles are the etiological agent for the transmissible colon carcinoma of WF rat strain.

Adenocarcinoma↗
PubMed1991

[A case of metastatic Enterococcus faecalis endophthalmitis].

We reported a case of successful treatment of early-stage metastatic endophthalmitis caused by Enterococcus faecalis with vitrectomy and lensectomy. The case was a 50-year-old male with poorly controlled diabetes. Following T-tube drainage for a necrotic cholecystitis operation, he developed iridocyclitis in both eyes as well as fever. At the time of his first visit to our clinic, his right eye had already lost light perception. His left eye had visual acuity recognizing of hand movement, marked uveitis, complicated cataract, and dense vitreous opacity. As gram positive cocci were isolated from the aspirated vitreous, we conducted lensectomy and vitrectomy under irrigation of antibiotics. With systemic postoperative antibiotics and human immunoglobulin, the patient showed remarkable improvement in his ocular fundus. By 60 days after the operation, the visual acuity of his left eye recovered to 4/20. Metastatic Enterococcus faecalis endophthalmitis has almost nerve been reported in Japan. The diagnosis and treatment of this disease with a reference to the above findings were discussed.

Endophthalmitis↗
PubMed1991

Effect of reserpine on histamine metabolism in the mouse brain.

The effect of reserpine on brain histamine (HA) metabolism in vivo was examined in mice. The level of tele-methylhistamine, a major metabolite of HA, was decreased dose-dependently by reserpine (1-5 mg/kg s.c.), whereas the HA level was unaffected. This effect was observed in all brain regions examined. The accumulation of tele-methylhistamine induced by pargyline (65 mg/kg i.p.), an inhibitor of monoamine oxidase, was inhibited to 19% of the control value 24 hr after the treatment with reserpine (5 mg/kg s.c.). However, the HA decrease induced by (S)-alpha-fluoromethylhistidine (50 mg/kg i.p.) a specific inhibitor of histidine decarboxylase, was not significantly affected by pretreatment with reserpine (5 mg/kg s.c.) 1 or 24 hr before. The HA increase induced by metoprine (10 mg/kg i.p.), an inhibitor of histamine-N-methyltransferase, or by L-histidine (0.5-1.5 g/kg i.p.) was inhibited markedly by pretreatment with reserpine. This effect was more marked when reserpine was administered 1 hr than 24 hr before. In addition, the L-histidine-induced increase in HA level was enhanced markedly by the simultaneous administration of metoprine in the control mice but not in the mice treated with reserpine 1 hr before L-histidine injection. From these results the following are suggested. 1) There may be both of reserpine-resistant and reserpine-sensitive HA pools in histaminergic nerve endings. 2) Most of the neuronal HA in the brain may be located in the former pool. 3) However, the capacity of the former pool may be limited and thus most of the increased HA by L-histidine and metoprine may be transferred into the latter pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Is monoamine turnover in the brain regulated by histamine H3 receptors?

To clarify whether monoamine neuron activity in the brain is regulated by histamine H3 receptors, the effects of a potent and selective H3 agonist, (R) alpha-methylhistamine and an antagonist, thioperamide, on monoamine metabolism were examined in the telencephalon, hypothalamus and brainstem of the rat and the whole mouse brain. Histamine turnover estimated from the pargyline-induced tele-methylhistamine accumulation decreased markedly with (R) alpha-methylhistamine administration (6.3 mg/kg i.p.) and increased with thioperamide administration (5 mg/kg i.p.) in all the brain regions examined. (R) alpha-Methylhistamine and thioperamide, at the doses tested, neither induced any significant changes in the levels of noradrenaline or 3,4-dihydroxyphenylacetic acid nor had any significant influence on the alpha-methyl-p-tyrosine-induced declines of the noradrenaline and dopamine levels in all the brain regions examined. However, thioperamide significantly decreased the dopamine level only in the rat telencephalon. In general, thioperamide increased 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratios and pargyline-induced 5-HT accumulation. However, (R) alpha-methylhistamine affected neither the 5-HT nor the 5-HIAA level. The pargyline-induced 5-HT accumulation was slightly enhanced by (R) alpha-methylhistamine in the whole mouse brain. The enhancement by thioperamide of pargyline-induced 5-HT accumulation was not inhibited by (R) alpha-methylhistamine. These results suggest that H3 receptors have no important roles in the regulation of monoaminergic activity in contrast with their regulatory function in histaminergic activity. In addition, thioperamide at high doses may enhance 5-HT turnover independently of H3 receptors.

Animals↗
PubMed1990

Inhibition by antimanic drugs of hyperactivity induced by methamphetamine-chlordiazepoxide mixture in mice.

The effects of lithium chloride and other antimanic drugs on locomotor hyperactivity induced by a mixture of methamphetamine (MAMP) and chlordiazepoxide (CDZP) were examined in mice, using an Animex activity meter. CDZP (12.5 mg/kg) given SC in combination with MAMP (1 mg/kg) caused a marked increase in locomotor activity, as compared with that in mice treated with MAMP alone. However, when CDZP (12.5 mg/kg) was administered together with 0.5 or 2.0 mg/kg of MAMP, no significant enhancement was observed. Lithium (2 and 3 mEq/kg, IP) and carbamazepine (4 and 8 mg/kg, IP) inhibited the hyperactivity induced by the MAMP (1 mg/kg)-CDZP (12.5 mg/kg) mixture to the level of activity in animals treated with MAMP (1 mg/kg) alone. Lithium and carbamazepine alone at these doses caused no significant inhibition of locomotor activity in saline- or MAMP-treated mice. Haloperidol (0.1 mg/kg, IP) and chlorpromazine (0.5 mg/kg, IP) decreased the MAMP-CDZP mixture-induced hyperactivity without significantly inhibiting locomotor activity in the saline- or MAMP-treated group. However, haloperidol (0.2 mg/kg) and chlorpromazine (1 mg/kg) alone significantly inhibited locomotor activity in all of the saline-, MAMP- and MAMP-CDZP mixture-treated groups. These results indicate that antimanic drugs selectively inhibit the hyperactivity induced by the MAMP-CDZP mixture, but that neuroleptics are less selective in inhibiting the hyperactivity.

Animals↗
PubMed1990

Two distinct ferredoxins from Rhodobacter capsulatus: complete amino acid sequences and molecular evolution.

Two distinct ferredoxins were purified from Rhodobacter capsulatus SB1003. Their complete amino acid sequences were determined by a combination of protease digestion, BrCN cleavage and Edman degradation. Ferredoxins I and II were composed of 64 and 111 amino acids, respectively, with molecular weights of 6,728 and 12,549 excluding iron and sulfur atoms. Both contained two Cys clusters in their amino acid sequences. The first cluster of ferredoxin I and the second cluster of ferredoxin II had a sequence, CxxCxxCxxxCP, in common with the ferredoxins found in Clostridia. The second cluster of ferredoxin I had a sequence, CxxCxxxxxxxxCxxxCM, with extra amino acids between the second and third Cys, which has been reported for other photosynthetic bacterial ferredoxins and putative ferredoxins (nif-gene products) from nitrogen-fixing bacteria, and with a unique occurrence of Met. The first cluster of ferredoxin II had a CxxCxxxxCxxxCP sequence, with two additional amino acids between the second and third Cys, a characteristics feature of Azotobacter-[3Fe-4S] [4Fe-4S]-ferredoxin. Ferredoxin II was also similar to Azotobacter-type ferredoxins with an extended carboxyl (C-) terminal sequence compared to the common Clostridium-type. The evolutionary relationship of the two together with a putative one recently found to be encoded in nifENXQ region in this bacterium [Moreno-Vivian et al. (1989) J. Bacteriol. 171, 2591-2598] is discussed.

Amino Acid Sequence↗
PubMed1990

Expression of histocompatibility antigen HLA-DR on the epithelial cells of the pancreatic duct and thyroid follicle. An autopsy case.

An autopsy case of chronic pancreatitis associated with unusual chronic thyroiditis in a 54-year-old woman is presented. Microscopically, the pancreas was densely infiltrated by lymphocytes and its exocrine parenchyma was completely replaced by sclerotic tissue. The thyroid gland was also infiltrated by lymphocytes, but no lymphoid follicles were observed. These morphological changes are rare findings with respect to the severity of inflammation and the association of the affected organs. Further findings suggested involvement of an autoimmune mechanism in the pathogenesis of these lesions. Using the avidin-biotin-conjugate technique and antibodies (Abs) against T lymphocyte and HLA-DR antigens (Ags), immunological aspects of the lesions were studied. Most of these infiltrating lymphocytes were revealed to be T lymphocytes, and HLA-DR Ags were observed on the epithelial cells of the pancreatic ducts and thyroid follicles. As a control, 45 surgical specimens of pancreas and thyroid gland were studied for detection of HLA-DR expression on the epithelial cells. One case of chronic pancreatitis was revealed to express HLA-DR Ag on the epithelium. The patient was a 44-year-old woman who had silently developed pancreatic cyst due to chronic inflammation. This finding also suggests a role of autoimmunity in the pathogenesis of chronic idiopathic pancreatitis.

Autopsy↗
PubMed1990

Regulation of histamine turnover via muscarinic and nicotinic receptors in the brain.

To clarify the regulation of central histaminergic (HAergic) activity by cholinergic receptors, the effects of drugs that stimulate the cholinergic system on brain histamine (HA) turnover were examined, in vivo, in mice and rats. The HA turnover was estimated from the accumulation of tele-methylhistamine (t-MH) during the 90-min period after administration of pargyline (65 mg/kg, i.p.). In the whole brain of mice, oxotremorine, at doses higher than 0.05 mg/kg, s.c., significantly inhibited the HA turnover, this effect being completely antagonized by atropine but not by methylatropine. A large dose of nicotine (10 mg/kg, s.c.) also significantly inhibited the HA turnover. This inhibitory effect was antagonized by mecamylamine but not by atropine or hexamethonium. A cholinesterase inhibitor, physostigmine, at doses higher than 0.1 mg/kg, s.c., significantly inhibited the HA turnover. This effect was antagonized by atropine but not at all by mecamylamine. None of these cholinergic antagonists used affected the steady-state t-MH level or HA turnover by themselves. In the rat brain, physostigmine (0.1 and 0.3 mg/kg, s.c.) also decreased the HA turnover. This inhibitory effect of physostigmine was especially marked in the striatum and cerebral cortex where muscarinic receptors are present in high density. Oxotremorine (0.2 mg/kg, s.c.) and nicotine (1 mg/kg, s.c.) also decreased the HA turnover in the rat brain. However, these effects showed no marked regional differences. These results suggest that the stimulation of central muscarinic receptors potently inhibits the HAergic activity in the brain and that strong stimulation of central nicotinic receptors can also induce a similar effect.

Animals↗
PubMed1990

Electrophysiological and anatomical substrates for late potential recorded by signal averaging in seven-day-old myocardial infarction in dogs.

A filtered QRS (fQRS) was recorded by signal averaging in 7-day-old myocardial infarction (MI) in dogs to detect late potential (LP). The criteria for the LP included a duration of fQRS (D) greater than or equal to 60 msec and a voltage in the last 15 msec (V15) less than or equal to 10 microV. These parameters were determined from the control data from 15 dogs without infarction (D: 45 to 60 msec and V15: 12.0 to 83.6 microV). On the seventh day of infarction, the D had increased from 53.5 +/- 4.7 to 62.2 +/- 9.6 msec (P less than 0.05) and the V15 decreased from 38.6 +/- 19.5 to 18.4 +/- 16.0 microV (P less than 0.01). Of 23 dogs, 14 met the LP criteria (group A) and 9 did not (group B). Sustained ventricular tachycardia (SVT) was induced in 12 group A dogs and in none of the group B dogs. The delayed epicardial activation (DEA) was recorded after the end of QRS at 5.1 +/- 4.7 sites in group A dogs and 1.3 +/- 1.8 sites in group B dogs (P less than 0.05). The maximum value of epicardial activation time was more prolonged in group A than in group B (70.0 +/- 28.3 vs 44.4 +/- 9.8 msec, P less than 0.01). The area of MI was more extensive in dogs with DEA than those without (24.9 +/- 5.8% vs 10.3 +/- 9.0% of the total left ventricular weight, P less than 0.01). In 72 of 90 sites with DEA, the thickness of the surviving epicardial muscle was less than or equal to 1 mm. The sensitivity and specificity of the criteria for LP in detecting DEA were 71.4% and 55.6%, and 100% and 81.8% for predicting inducibility of SVT. It was thus concluded that LP, reflected the DEA, was identified from infarct areas of slow conduction within a reentry circuit of SVT.

Action Potentials↗
PubMed1990

Effect of microinjection of histamine into the brain on plasma levels of epinephrine and glucose in freely moving rats.

The effect of histamine administered to the brain on the plasma levels of epinephrine, norepinephrine and glucose was investigated in freely moving rats. Histamine (10 micrograms) administered intracerebroventricularly (into the lateral ventricle) induced a hyperglycemic response with preceding increases in plasma catecholamines, especially epinephrine. When histamine (5 micrograms) was injected into three different levels of the ventricular system, the magnitude and duration of the resulting increases in plasma epinephrine and glucose were in the following rank order: the third ventricle greater than aqueduct much greater than fourth ventricle. These results suggest that the sites of action of histamine are located rostrally from the midbrain. Microinjections of histamine (1 microgram) into the hypothalamic nuclei including the medial preoptic area, paraventricular nucleus, ventromedial hypothalamic nucleus, posterior hypothalamic nucleus and mammillary body had no elevating effect on the plasma levels of epinephrine and glucose. Other brain regions, such as the lateral septum, medial amygdaloid nucleus and periaqueductal grey of the midbrain, were also excluded as possible sites of histamine action. From the present results, it seems that histamine stimulates plural sites close to the ventricular system to induce hyperglycemic responses.

Animals↗
PubMed1990

Activation of protein kinase C by myristate and its requirements of Ca2+ and phospholipid.

Myristate (C14:0) was found to significantly activate partially purified rat brain Ca(2+)- and phospholipid-dependent protein kinase (PKC). The Ka value, the concentration needed for half maximum activation, for C14:0 in the presence of 1 microM Ca2+ and 20 microM phosphatidylserine (PS) was 20 microM. This activation required Ca2+ and acidic phospholipid and was associated with a decreased Ka for Ca2+ of the enzyme to 10 microM in an analogous fashion as dioleoylglycerol (DO) or phorbol myristate acetate (PMA). The phospholipid requirement for the activation was concentration dependent and was inhibited by 1-(5-isoquinolinesulfonyl)-methylpiperazine dihydrochloride (H-7), a inhibitor of this enzyme. The concentration of H-7 required for half inhibition of the enzyme was about 15 microM and maximum inhibition was about 75%. The concentration profile of cytoplasmic proteins phosphorylated by C14:0-activated PKC was similar to that by PMA-activated PKC. The 47 kDa protein of guinea pig neutrophil was also phosphorylated by the C14:0-activated PKC. It is further discussed whether PKC can function as signal transduction for stimulus-mediated generation of superoxide in neutrophils.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

In vivo measurement of noradrenaline and 3,4-dihydroxyphenylethyleneglycol in the rat hypothalamus by microdialysis: effects of various drugs affecting noradrenaline metabolism.

The extracellular concentrations of noradrenaline (NA) and 3,4-dihydroxyphenylethyleneglycol (DOPEG), one of the major metabolites of brain NA, in the hypothalamus of urethane-anesthetized rats were monitored by in vivo microdialysis followed by a sensitive and simultaneous determination of the two substances using high-performance liquid chromatography with electrochemical detection. The effects of various drugs that affect central NA metabolism were also examined. Resting levels of NA and DOPEG were constant during 1 and 6 hr after the start of perfusion, the mean values being 3.8 +/- 0.4 pg/30 min for NA and 107.5 +/- 9.1 pg/30 min for DOPEG (mean +/- S.E.M. of 7 animals). Tetrodotoxin (1 microM), when added to the perfusion medium, reduced the output of NA below the detection limit (0.5 pg) and also decreased the DOPEG output by 60%. Clonidine (0.2 mg/kg i.p.) caused a marked reduction in both the NA and DOPEG outputs, whereas yohimbine (5 mg/kg i.p.) significantly increased both the NA and DOPEG outputs. Desipramine (2 and 5 mg/kg i.p.) produced a dose-dependent increase in the NA output, although it caused a gradual decline of the DOPEG output. The atypical antidepressant mianserin (2 and 5 mg/kg i.p.), which possesses both alpha-2 antagonist and weak NA uptake inhibitory actions, produced a less marked increase in the NA output with no or only a small decrease in the DOPEG output. Therefore, it is suggested that monitoring the extracellular concentrations of both NA and DOPEG enables the discrimination between the action of drugs inhibiting the NA uptake and that of drugs enhancing the NA release, and that this method is useful to obtain detailed information about central NA metabolism in vivo.

Animals↗
PubMed1990

[An autopsy case of quadruple carcinoma].

Discussed is a case of male cancer patient whose initial lesion was a transitional cell carcinoma of the left renal pelves. A bladder tumor (TCC) was subsequently found 6 months after a left nephro-ureterectomy. After treatment of these tumors, the patient remained well for 8 years. An inoperable lung cancer (squamous cell carcinoma) then developed 6 months prior to death. The patient died of an aneurysmal rupture of the ascending aorta. At autopsy, 2 latent carcinomas were identified, one in the prostate and the their in the thyroid gland. If the renal pelvic and the bladder tumors and the lung carcinomas were all independent, this would seem to be a case of six-fold carcinoma.

Adenocarcinoma↗