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T Koga

Publications and source records attributed to T Koga.

At least 19 recordsLinked to original sources
PubMed1992

Tissue selectivity of pravastatin sodium, lovastatin and simvastatin. The relationship between inhibition of de novo sterol synthesis and active drug concentrations in the liver, spleen and testis in rat.

Tissue selectivity of pravastatin sodium (pravastatin), lovastatin and simvastatin, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors was examined by measuring inhibition of de novo sterol synthesis and active drug concentrations in the liver, spleen and testis in rats after a single oral administration (25 mg/kg) of these drugs. Regarding tissue drug concentrations, all three drugs were liver selective: concentrations of drugs in the liver were about ten-times higher than those in the spleen and testis. On the other hand, pravastatin was far more liver selective in inhibiting sterol synthesis than two other inhibitors: pravastatin inhibited de novo sterol synthesis in the liver but minimally in the spleen and testis, whereas lovastatin and simvastatin inhibited in all three tissues. Microautoradiographic and in vitro cellular-uptake studies demonstrated that pravastatin remained in the extracellular space in the spleen, whereas the other drugs entered the cell. We conclude that pravastatin exhibits a liver-selective inhibition of sterol synthesis because the agent permeates the cell membrane in the liver, but not in non-hepatic tissues.

Animals↗
PubMed1992

Stimulation of three areas of the primary motor cortex interrupts micturition in dogs.

To clarify the area of the motor cortex (M1) in dogs, which corresponds to the cortical area participating in voluntary interruption of micturition in humans, the cortical portions related to the external urethral sphincter were first clarified by recording of somato-sensory evoked potentials, and then systematic cortical stimulation was performed in anesthetized and paralyzed dogs. The hypogastric, pelvic and pudendal nerves innervating the lower urinary tract and rectum were severed to eliminate the secondary reflexes. Five foci were recognized in the cortical potentials evoked after stimulation of the pudendal nerve. These foci existed in the sacral (Sacral-S) and hind leg (Leg-S) areas of the somato-sensory cortex (S1), and in the sacral (Sacral-M), hind leg (Leg-M) and trunk (Abd-M) areas of the M1. Stimulation of the three M1 foci, but not the two S1 foci, provoked centrifugal firings of the pudendal urethral branch. The firings disappeared after cutting of the ipsilateral bulbar pyramis. When the M1 foci were stimulated during the micturition reflex, the reflex discharge of a pelvic vesical branch was interrupted concomitantly with firings of the urethral branch. The interruption was still induced after the pyramidotomy. Pulse train stimulation of these M1 foci reset the cycles (about 2 Hz) in the alternative rhythmic firings of the urethral and vesical branches, which are known to be formed in the pontine micturition center [31,32]. These results suggest that the pyramidal cells in the three M1 foci inhibit the pontine micturition center and concomitantly contract the external urethral sphincter through the pyramidal tract. The possible roles of these M1 foci were discussed.

Animals↗
PubMed1992

Putative inositol 1,4,5-trisphosphate binding proteins in rat brain cytosol.

In previous works, we synthesized a series of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) analogs, with a substituent on the second carbon of the inositol ring. Using these analogs, the Ins(1,4,5)P3 affinity media were also synthesized (Hirata, M., Watanabe, Y., Ishimatsu, T., Yanaga, F., Koga, T., and Ozaki, S. (1990) Biochem. Biophys. Res. Commun. 168, 379-386). When the cytosol fraction from the rat brain was applied to an Ins(1,4,5)P3 affinity column, an eluate with a 2 M NaCl solution was found to have remarkable Ins(1,4,5)P3-binding activity. The active fraction was further fractionated with gel filtration chromatography, and two proteins with an apparent molecular mass of 130 or 85 kDa were found to be Ins(1,4,5)P3-binding proteins but with no Ins(1,4,5)P3 metabolizing activities. Partial amino acid sequences determined after proteolysis and reversed-phase chromatography revealed that the protein with an apparent molecular mass of 85 kDa is the delta-isozyme of phospholipase C and that of 130 kDa has no sequence the same as the Ins(1,4,5)P3-recognizing proteins hitherto examined. Ins(1,4,5)P3 at concentrations greater than 1 microM strongly inhibited 85-kDa phospholipase C delta activity, without changing its dependence on the concentrations of free Ca2+ and H+. Among inositol phosphates examined, Ins(3,4,5,6)P4 inhibited the binding of [3H]Ins(1,4,5)P3 to the 130-kDa protein at much the same concentrations as seen with Ins(1,4,5)P3. This report seems to be the first evidence for the presence of soluble Ins(1,4,5)P3-binding proteins in the rat brain, one of which is the delta isozyme of phospholipase C.

Amino Acid Sequence↗
PubMed1992

Signal transduction by tumor necrosis factor alpha is mediated through a guanine nucleotide-binding protein in osteoblast-like cell line, MC3T3-E1.

Transmembrane signalling mechanisms of tumor necrosis factor alpha (TNF alpha) were examined with special reference to the involvement of G-protein, in intact and permeabilized murine osteoblast-like cells. TNF alpha stimulated the release of 3H radioactivity from intact cells labeled with [3H]arachidonic acid within 10 min in a dose dependent manner and the production of lyso forms of phospholipids, an event presumably mediated through the activation of phospholipase A2. Production of cAMP and inositol 1,4,5-trisphosphate was not affected by TNF alpha. Pretreatment of the cells with pertussis toxin inhibited the liberation of [3H]arachidonate. GTP gamma S (guanosine 5'-3-O-(thio)triphosphate) reduced the binding affinity of [125I]TNF alpha to beta-escin-permeabilized cells. The addition of TNF alpha together with an unhydrolyzable analog of GTP, GTP gamma S, to the beta-escin-permeabilized cells prelabeled with [3H]arachidonic acid led to a release of the 3H radioactivity. The production of prostaglandin E2 (PGE2) was markedly stimulated by TNF alpha in a dose over 100 ng/ml, with a latent time of about 3 h, and the stimulation was abolished by pretreatment with pertussis toxin. The time and dose requirements for this process differed from those for the possible activation of phospholipase A2, thereby indicating that other process(es) in addition to the activation of phospholipase A2 may be responsible for the enhanced production of PGE2. The activity of cyclooxygenase (i.e. the combined activities of prostaglandin endoperoxide syntase and PGH2-PGE2 isomerase) was stimulated by TNF alpha with much the same time and dose requirements as for the production of PGE2, and the activation was found to be due to the increased amount of the enzyme, as assessed by a Western blot analysis with anti-cyclooxygenase antibody. This process was also sensitive to pertussis toxin. Therefore, receptors for TNF alpha in MC3T3-E1 cells apparently couple to G-protein sensitive to pertussis toxin and the coupling regulates the activations of phospholipase A2 and the de novo synthesis of cyclooxygenase.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Carrier-mediated uptake of pravastatin by rat hepatocytes in primary culture.

The transport mechanism of pravastatin, a new cholesterol-lowering drug, was compared in vitro with rat hepatocyte primary culture and mouse skin fibroblasts (L-cells). The uptake of 14C-labeled pravastatin by cultured hepatocytes was temperature- and dose-dependent. The temperature-dependent uptake as a function of [14C]pravastatin concentration showed saturation kinetics with Km = 32.2 microM and a maximal uptake rate of 68 pmol/mg protein/min. The uptake of pravastatin was inhibited significantly by metabolic inhibitors such as rotenone, oligomycin A, antimycin A, 2,4-dinitrophenol and KCN. Unlabeled pravastatin as well as R-416 and R-195, structural analogues of pravastatin, effectively competed for the hepatic uptake of [14C]pravastatin at 37 degrees. These results indicate that pravastatin is taken up by the liver by an active transport. In contrast, the transport of pravastatin by L-cells was temperature-independent and non-saturable, suggesting that the uptake of pravastatin by L-cells is mediated by passive diffusion. The marked difference in the uptake mechanism of pravastatin between hepatocytes and L-cells may account for a unique feature of this drug in that the uptake and inhibition of cholesterol biosynthesis occur selectively in the liver.

Animals↗
PubMed1992

Neurons in the nucleus of the solitary tract mediating inputs from emetic vagal afferents and the area postrema to the pattern generator for the emetic act in dogs.

Roles of neurons in the nucleus of the solitary tract corresponding to the area subpostrema (mNST) for the retching reflex were investigated in decerebrate, paralyzed dogs. Retching was defined as rhythmic coactivation of the phrenic and abdominal muscle nerves. Retching which had been induced by stimulation of the left and right abdominal vagus nerves was impaired by cooling the left and right mNSTs, respectively. This result indicates that the mNST neurons mediate activities of emetic vagal afferents. All 40 non-respiratory neurons in the mNST, which had excitatory response to pulse train stimulation of the vagus nerve, were also activated by continuous stimulation of the vagus nerve to provoke retching. During provoked retching, however, these neurons did not exhibit any activities modulated in association with retching. The average latency of responses of these neurons to the pulse train stimulation (306.5 ms) was significantly shorter than that of the inspiratory neurons in the lateral NST and the adjacent reticular formation. Discharge frequencies of these neurons in the mNST gradually increased after administration of apomorphine (6/10) and glutamate (14/14) to the 4th ventricle. Antidromic responses to stimulation of the Bötzinger complex were observed in some (20/289) of the mNST neurons. These findings suggest that neurons in the mNST mediate the information from both the abdominal vagal afferents and the area postrema and drive the pattern generator for retching and vomiting, which is assumed to be located in the Bötzinger complex.

Animals↗
PubMed1992

Non-respiratory neurons in the Bötzinger complex exhibiting appropriate firing patterns to generate the emetic act in dogs.

This work was performed to prove the hypothesis that the pattern generator for the emetic act exists in the Bötzinger complex (BOT) and is driven by vagal afferents via the subpostrema portion of the nucleus of the solitary tract (mNST). Non-respiratory neurons (78) intermingling with BOT respiratory neurons in decerebrate dogs responded to pulse train stimulation of vagal afferents with a mean latency of 387 ms. During retching induced by vagal stimulation, one-half of the non-respiratory neurons exhibited high frequency burst firings synchronous with each retch (SH-firing, SH-neurons) and one-third of these neurons showed similar firings synchronous with the periods between retches (BH-firing, BH-neurons). Two-thirds of the SH-neurons and one-half of the BH-neurons fired with gradually augmenting frequencies (augmenting firing) during the period prior to retching, which may correspond to the period of prodromal signs of vomiting. Three SH-neurons were observed at fictive expulsion: all 3 exhibited burst firings concomitant with expulsion. During cooling block of transmission in the mNST, stimulation of the vagus nerve ipsilateral to the cooling failed to induce not only retching but also augmenting firing and SH-firing in all 11 BOT SH-neurons observed. In contrast, contralateral vagal stimulation induced retching and neuronal firings which had been observed before the cooling. These results support the hypothesis mentioned above. Respiratory firings were changed during retching in all BOT respiratory neurons observed. Respiratory firings were depressed during retching in the majority (15/25) of inspiratory (I) neurons and in a few expiratory (E) neurons (6/45). SH-firing was exhibited by 3 I- and 13 E-neurons. A few (2) I- and half (23) E-neurons showed BH-firing. These results indicate that all BOT respiratory neurons participate in central patterning of the emetic act.

Animals↗
PubMed1992

Combination of patch test and IgE for dust mite antigens differentiates 130 patients with atopic dermatitis into four groups.

BACKGROUND: Patients with atopic dermatitis sometimes have positive responses to patch testing (PT) with dust mite antigens, which is believed to correlate with the elevated levels of specific IgE for those antigens. OBJECTIVE: The purpose of this study is to identify the correlation between the PT and serum IgE concerning the mite antigens. METHODS: We studied 130 patients with atopic dermatitis by the PT reaction and the serum level of specific IgE for Dermatophagoides pteronyssinus antigens. RESULTS: Fifty-one of the 130 patients assessed as PT-positive had either high (32 of 130 patients; 24.6%) or low or no (19 of 130 patients; 14.6%) levels of mite-specific IgE; there was a significant difference between the groups with elevated and low IgE. Similarly, a total of 79 PT-negative patients also showed an elevated or low mite-specific IgE (42 of 130 patients [32.3%] or 37 of 130 patients [28.5%], respectively). It was noted that clinical morphologic findings were peculiar to three of the four groups; however, the patients who were PT-negative with a low IgE (37 of 130 patients) showed no particular clinical lesions. CONCLUSION: Comparing the results from our 130 patients, there was no correlation between the serum IgE level and the PT reaction for dust mite antigens. Conversely, the results of PT and mite-specific IgE could be used to divide these patients into four distinct groups, each with its own particular clinical morphology, suggesting the heterogeneity of this disease.

Adolescent↗
PubMed1992

Construction of mutants of Actinobacillus actinomycetemcomitans defective in serotype b-specific polysaccharide antigen by insertion of transposon Tn916.

Mutants of Actinobacillus actinomycetemcomitans strain Y4 defective in the capsular-like serotype b-specific polysaccharide antigen (SPA) were constructed by inserting the transposon Tn916. Southern blot analysis suggested that the transposon was inserted into a variety of different sites on the chromosome. Whole cells from two mutants (strains ST1 and ST2) lacked reactivity with a monoclonal antibody to SPA of A. actinomycetemcomitans Y4 (mAb S5) in enzyme-linked immunosorbent assay, but those from another nine mutants (e.g. strains ST3 and ST5) reacted very weakly with mAb S5. Immunodiffusion tests showed that mAb S5 or rabbit antiserum against whole cells of strain Y4 produced a fused precipitin band with purified SPA and autoclaved extract from strain Y4, but no precipitin band with autoclaved extracts from these four mutants. The hydrolysate of autoclaved extract from strain Y4 contained equal amounts of rhamnose and fucose, component sugars of SPA. The hydrolysates of autoclaved extracts from strains ST1 and ST2 contained a trace amount of rhamnose, but not fucose. Those of autoclaved extracts from strains ST3 and ST5 contained a trace amount of fucose, but not rhamnose. All of these SPA-defective mutants reacted with a mAb to lipopolysaccharide of strain Y4. The cell hydrophobicity of SPA-defective mutants was higher than that of the parent strain. These mutant clones will be useful for analysing the gene complex responsible for the synthesis of SPA of A. actinomycetemcomitans and the regulation of expression of the polysaccharide.

Aggregatibacter actinomycetemcomitans↗
PubMed1992

A broad-host-range vibriophage, KVP40, isolated from sea water.

A broad-host-range vibriophage, KVP40, was isolated from sea water by using Vibrio parahaemolyticus 1010 (EB101) as the indicator host. The host range of KVP40 extended over at least 8 Vibrio and 1 Photobacterium species. KVP40 was a large tailed phage containing double-stranded DNA and belonged to Ackermann's morphotype A2. KVP40 DNA was cleaved by 11 different type II restriction endonucleases including EcoRI and HindIII, but not by 17 other enzymes including BamHI, KpnI and SalI.

Bacteriophages↗
PubMed1992

Characterization of an amorphous and soluble hemagglutinin from Yersinia pseudotuberculosis.

Yersinia pseudotuberculosis which were screened out depending on auto-agglutination and Ca2+ dependency, were examined for their production of hemagglutinin (HA), and its purification and characterization were performed. The HA with a broad reactivity with various mammalian erythrocytes was recovered from the culture supernatant of these strains grown at 37 C but not 25 C. HAs from two strains, R148R and T1040, were purified by salt precipitation, gel filtration and anion-exchange chromatography by HPLC. Both purified HAs were cysteine-deficient acidic protein with an apparent molecular weight in the range of 15,000 to 16,000. N-terminal amino acid sequences of the first 25 residues were found to share 12% identity with that of afimbrial adhesin from enterotoxigenic Escherichia coli 2230. Immunoelectron microscopy and immunodiffusion test with polyclonal antiserum raised against the purified R148RHA demonstrated that the HA was associated with the amorphous aggregates which were detached from bacteria. These results suggest that the HA of Y. pseudotuberculosis belongs to a third type of HA produced by the yersinial species.

Amino Acid Sequence↗
PubMed1992

Genetic control of immune responses in mice to synthetic peptides of a Streptococcus mutans surface protein antigen.

The immune responses to a cell surface protein antigen (PAc) of Streptococcus mutans and a peptide corresponding to residues 301 to 319 of the protein antigen [PAc(301-319)] in various strains of mice were studied, with attention being given to the haplotype of major histocompatibility complex (MHC) class II genes. Subcutaneous immunization of mice carrying the MHC class II I-Ad gene [BALB/c, B10.D2, B10.GD, and (B10.D2 x B10.G)F1 mice] with the peptide induced strong serum immunoglobulin G (IgG) responses to recombinant PAc (rPAc) and the peptide. Subcutaneous immunization of mice carrying the haplotype k or b of the H-2 I-A gene (C3H/HeN, C57BL/6, B10.BR, B10.A, or B10 mice) with the peptide induced intermediate serum IgG responses to rPAc and the peptide, and subcutaneous immunization of mice carrying the haplotype s or q of the H-2 I-A gene (DBA/1, B10.S, or B10.G mice) induced weak serum IgG responses to rPAc and the peptide compared with the responses of mice carrying the I-Ad gene. PAc(301-319) strongly induced PAc(301-319)-specific T-cell proliferation in B10.D2 mice but not in B10.G mice. The T-cell proliferation in B10.D2 mice was inhibited by treatment of antigen-presenting cells with anti-I-Ad monoclonal antibody but not with anti-I-Ab monoclonal antibody. These results indicate that the immune responses to the peptide in mice are genetically restricted or dominated by the MHC class II gene (I-Ad). To map antigenic epitopes in PAc(301-319) and PAc in mice bearing different H-2 haplotypes, 10 overlapping decapeptides covering PAc(301-319) and 153 decapeptides covering the entire mature PAc were synthesized. Of 10 decapeptides covering PAc(301-319), 6, 7, 1, and 1 decapeptides showed strong reactions with anti-PAc(301-319) sera from B10.D2 (H-2d), B10.GD (H-2g2), B10.BR (H-2k), and B10.A (H-2a) mice, respectively. None of these overlapping decapeptides reacted with anti-PAc(301-319) sera from B10.S (H-2s) and B10.G (H-2q) mice. Epitope-scanning analyses of the mature PAc molecule showed that antigenic epitopes scattered throughout the molecule and that antigenic epitope patterns differed in mice with different H-2 haplotypes. In addition, there was little overlap of immunogenic peptides among the mice with different haplotypes.

Amino Acid Sequence↗
PubMed1992

Intestinal anisakiasis: US in diagnosis.

Eighteen consecutive patients with intestinal anisakiasis were studied with high-resolution ultrasound (US) and barium studies. US showed markedly thickened bowel loops associated with luminal narrowing, swelling of Kerckring folds, and decreased peristalsis. A small amount of ascitic fluid around the bowel loops was found, and cytologic examinations of the ascites revealed a dense infiltration of eosinophils. Barium studies demonstrated segmental mucosal edema of the small intestine: The most common site was the distal ileum, and the mean length of the edematous lesion was 19 cm. All patients underwent treatment of symptoms without laparotomy, and their symptoms disappeared by the eighth day after onset. Patients with acute abdominal symptoms should be asked about the intake of raw or undercooked fish. If the above US features are found, the diagnosis of intestinal anisakiasis must be seriously considered to avoid unnecessary surgical treatment.

Adult↗
PubMed1992

Age-related changes in P2-purinergic receptors on vascular smooth muscle and endothelium.

The present study examined age-related changes in the vascular relaxation response to adenine nucleotides in hypertensive and normotensive rats. Aortic ring segments from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), age 4-6, 9-10, and 13-14 weeks, were examined for relaxation to adenosine 5'-triphosphate (ATP). The extent of ATP-induced relaxation in aortic ring segments with intact endothelium was unchanged with advancing age. Rubbed (endothelium-denuded) ring preparations at the age of 4-6 weeks showed a dose-dependent relaxation similar to that of the unrubbed rings. With advancing age, the ATP-induced relaxation in the rubbed rings decreased and was abolished. The relaxation response did not differ between the SHR and WKY animals at any age, whether the preparations were rubbed or unrubbed. The stable ATP analogue beta,r-methylene ATP induced a relaxation response similar to ATP in rubbed rings at 4-6 weeks of age. In addition, treatment with 8-phenyltheophylline did not diminish the relaxation induced by ATP. ATP-induced relaxation may be manifested via the direct action on the vascular smooth muscle in young rats and may be altered through the response mediated by endothelium with advancing age. This suggests that the vascular smooth muscle of young rats has a P2-purinergic receptor leading to relaxation and that this receptor activity declines with advancing age. In contrast, a P2-purinergic receptor leading to the generation of endothelium-derived relaxing factor may be activated in endothelial cells with advancing age. The alterations with age of P2-purinergic receptor in the vascular smooth muscle and endothelial cell are not affected by genetic hypertension.

Adenosine Triphosphate↗
PubMed1992

Decreased endothelium-dependent hyperpolarization to acetylcholine in smooth muscle of the mesenteric artery of spontaneously hypertensive rats.

The endothelium-dependent vascular relaxation to acetylcholine (ACh) in spontaneously hypertensive rats (SHR) may be impaired because of an imbalance of endothelium-derived relaxing factor and contracting factor. However, the role of the endothelium-dependent hyperpolarization remains undetermined. We examined the ACh-induced hyperpolarization and its contribution to relaxation in arteries of SHR. Membrane potentials were recorded from the mesenteric artery trunk of 6-8-month-old male SHR and also Wistar-Kyoto (WKY) rats. Endothelium-dependent hyperpolarization to ACh was unaffected by NG-nitro-L-arginine, indomethacin, or glibenclamide; was reduced by tetraethylammonium or high K+ solution; and was enhanced by low K+ solution or methylene blue, thereby indicating that hyperpolarization is not mediated by nitric oxide (endothelium-derived relaxing factor) but is presumably mediated by a hyperpolarizing factor and is due to an opening of K+ channels that probably differ from the ATP-sensitive ones. Hyperpolarizations to ACh were markedly reduced in SHR compared with findings in WKY rats (maximum, 8 +/- 1 versus 17 +/- 1 mV). In addition, under conditions of depolarization with norepinephrine (10(-5) M), the ACh-induced hyperpolarization was even less and transient in SHR, while it was large and sustained in WKY rats (6 +/- 1 versus 29 +/- 2 mV). Endothelium-dependent relaxations to ACh in arterial rings precontracted with 10(-5) M norepinephrine were far less in SHR than in WKY rats, even in the presence of indomethacin. Furthermore, high K+ solution showed smaller inhibitory effects on the relaxations in SHR than in WKY rats. Endothelium-independent hyperpolarizations and relaxations to cromakalim, a K+ channel opener, were similar between SHR and WKY rats. It would thus appear that the endothelium-dependent hyperpolarization to ACh is reduced in SHR and this would, in part, account for the impaired relaxation to ACh in SHR mesenteric arteries.

Acetylcholine↗
PubMed1992

A 72-year-old female with adult Still's disease.

We treated a 72-year-old woman with adult Still's disease. The diagnosis was made on the basis of a prolonged, high grade, quotidian fever, polyarthritis, maculopapular skin rashes and exclusion of other possible diseases. A high serum ferritin value was a key factor both in making the diagnosis and in the follow-up. The patient responded to the administration of oral prednisolone at 30 mg/day, which was tapered to 10 mg/day, with no recurrence of symptoms. This disorder can be an important cause of prolonged fever in the elderly as well as in the younger population.

Aged↗