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Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 469 records · Page 26Linked to original sources
PubMed1995

Formation of 2-amino-3-methylimidazo[4,5-f]quinoline- and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline-sulfamates by cDNA-expressed mammalian phenol sulfotransferases.

In rat liver cytosol systems, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) were converted into their sulfamates in the presence of 3'-phosphoadenosine 5'-phosphosulfate at rates of 51.2 and 50.7 pmol/min/mg cytosol in the male, and 23.7 and 22.5 pmol/min/mg cytosol in the female, respectively. IQ-sulfamate formation was low (0.24 pmol/min/mg cytosol) in human liver cytosols, and MeIQx-sulfamate was not detected (< 0.1 pmol/min/mg cytosol). These results suggest only a minor contribution of IQ- and MeIQx-sulfamate formation to the detoxification of both heterocyclic amines in humans. Using sulfotransferase cDNA-expression systems, a rat ST1A1 arylsulfotransferase has been shown to catalyze the formation of the sulfamates, suggesting a role of the ST1A type of sulfotransferase in the N-sulfation of heterocyclic amines.

Animals↗
PubMed1995

A low M(r) GTP-binding protein, Rap1, in human platelets: localization, translocation and phosphorylation by cyclic AMP-dependent protein kinase.

Subcellular fractions were prepared from human platelet membranes by sucrose density gradient centrifugation and the localization of a low M(r) GTP-binding protein, rap1 protein (Rap1) was analysed by immunoblotting using a specific antibody. Rap1, which has been purified from human platelets, was found to be located in plasma membrane and alpha-granule fractions in resting platelets. Treatment of isolated alpha-granules with pronase led to proteolysis of Rap1, indicating that this protein is exposed to the cytoplasmic face of the granules. Degranulation of alpha-granules consists of translocation and subsequent fusion of the granules with the open canalicular system. Activation of this process by thrombin induced the redistribution of Rap1 on the alpha-granules to plasma membranes. On the other hand, Rap1 is known to be phosphorylated by cyclic AMP-dependent protein kinase (A-kinase) in vitro and in vivo. In intact human platelets, phosphorylation of Rap1 by A-kinase in response to prostaglandin E1 (PGE1) was observed only in Rap1 localized in plasma membranes and not on alpha-granules, although Rap1 was phosphorylated in a cell-free system when plasma membranes and alpha-granule membranes were exposed to A-kinase as substrates. These results strongly suggest that Rap1 in plasma membranes and the protein on alpha-granules are regulated by different mechanisms, and have different functions.

Blood Platelets↗
PubMed1995

Superoxide anions in the pathogenesis of talc-induced cerebral vasocontraction.

We have recently reported that sustained contraction of the canine basilar artery induced by the intrathecal injection of talc (crystallized hydrous magnesium silicate) mimicked delayed vasospasm following subarachnoid haemorrhage. The present study aims to examine the pathomechanism underlying talc-induced vasocontraction, from the viewpoint of free radical theory, which has been established as a cause of delayed vasospasm. We estimated the effects of a prolonged intrathecal infusion of human recombinant Cu/Zn superoxide dismutase (hr SOD) on the contraction of the basilar artery caused by the intrathecal injection of talc in beagle dogs, which were assigned to the three groups: G1, sham operation with saline treatment; G2, talc injection with saline treatment; and G3, talc injection with 2 ml of hr SOD (7 x 10(4) U/ml) treatment. Talc administration resulted in the reduction in the angiographic calibre of the basilar artery by 63 and 61% on days 3 and 7 (G2). The treatment with hr SOD (G3) led to a significant attenuation of talc-induced contraction of the basilar artery on days 3 (P < 0.05 vs. G2) and 7 (P < 0.05 vs. G2). In the basilar artery wall of days 3 and 7 in G2, pathological changes such as myonecrosis, cytoplasmic vacuolation and detached intercellular junctions were observed. However, these pathological changes almost disappeared in G3. The present findings suggest that superoxide anions may initiate and/or mediate talc-induced vasocontraction and subsequent structural damage of the basilar artery.

Animals↗
PubMed1995

Growth inhibition of Ureaplasma urealyticum by the proton pump inhibitor lansoprazole: direct attribution to inhibition by lansoprazole of urease activity and urea-induced ATP synthesis in U. urealyticum.

The proton pump inhibitors (PPIs) omeprazole and lansoprazole and the acid-activated analog of lansoprazole AG-2000, which potently inhibit the urease of Helicobacter pylori (K. Nagata, H. Satoh, T. Iwahi, T. Shimoyama, and T. Tamura, Antimicrob. Agents Chemother. 37:769-774, 1993), also inhibited the urease activities of cell-free extracts as well as intact cells of Ureaplasma urealyticum. The 50% inhibitory concentrations were between 1 and 25 microM. These compounds also inhibited the ATP synthesis induced by urea in ureaplasma cells. The 50% inhibitory concentrations for ATP synthesis were close to those for urease activity, but they were lower than those of urease inhibitors, such as acetohydroxamic acid, hydroxyurea, and thiourea. In addition, one of the metabolites of lansoprazole found in human urine, M-VI, also inhibited ureaplasmal urease activity and the ATP synthesis induced by urea at almost the same concentrations as those of lansoprazole. The inhibition of PPIs against ureaplasma urease was very similar to those against H. pylori urease, suggesting that the inhibitory mechanism against these ureases was due to the blockage of the SH residues on the cysteine of the enzyme. Omeprazole, lansoprazole, AG-2000, and M-VI inhibited the growth of U. urealyticum. Since ureaplasma urease is thought to be involved in the pathogenicity of this organism in the urogenital tract, PPIs and their analogs may be useful as chemotherapeutic agents against diseases caused by U. urealyticum.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Inhibitory action of lansoprazole and its analogs against Helicobacter pylori: inhibition of growth is not related to inhibition of urease.

The proton pump inhibitors omeprazole and lansoprazole and its acid-activated derivative AG-2000, which are potent and specific inhibitors of urease of Helicobacter pylori (K. Nagata, H. Satoh, T. Iwahi, T. Shimoyama, and T. Tamura, Antimicrob. Agents Chemother. 37:769-774, 1993), inhibited the growth of H. pylori. The growth was inhibited not only in urease-positive clinical isolates but also in their urease-negative derivatives which had no urease polypeptides. AG-1789, a derivative of lansoprazole with no inhibitory activity against H. pylori urease, also inhibited the growth of both strains even more strongly than the urease inhibitors lansoprazole and AG-2000. Furthermore, the antibacterial activity of omeprazole and lansoprazole was not affected by glutathione or dithiothreitol, which completely abolished the inhibitory activity of lansoprazole against H. pylori urease. These results indicated that the inhibitory action of these compounds against the growth of H. pylori was independent from the inhibitory action against urease.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock.

Administration of monoclonal anti-CD3 antibody to mice treated with Propionibacterium acnes induced secretion of a high level of gamma interferon (IFN-gamma) into the circulation system, while it induced no significant release in untreated mice. In order to analyze this high-level induction of IFN-gamma in these bacterium-treated mice, we investigated the factors that might be involved. An activity that induces IFN-gamma in T cells was observed in the liver extracts of mice treated with P. acnes and subsequently challenged with lipopolysaccharide. Here, we purified an IFN-gamma-inducing factor from the liver extract to homogeneity and characterized it. Its molecular mass was 18 to 19 kDa, and its pI was 4.9. The amino acid sequence of the NH2-terminal portion was determined and shown to have no similarities to any protein in the EMBL, GenBank, and PIR data bases. The same molecule was also demonstrated in the serum factor that was previously reported to have an IFN-gamma-inducing activity and to have an apparent molecular mass of 75 kDa. Moreover, the activity of this serum factor was recovered in the fraction containing the 18- to 19-kDa protein under reducing conditions and was shown to have the same NH2-terminal amino acid sequence as that of the factor from the liver extract. In addition to the ability to induce IFN-gamma, this protein augmented T-cell proliferation and NK activity in the spleen cells. Thus, several of its biological activities were apparently similar to those of interleukin-12. These results indicated that this novel protein, which exhibited marked costimulatory activity on IFN-gamma production in vitro, was elevated vivo in response to P. acnes treatment. This factor, probably released from the producing cells by lipopolysaccharide stimuli, may be involved in the high-level induction of IFN-gamma in the P. acnes-treated mice.

Amino Acid Sequence↗
PubMed1995

Actinobacillus actinomycetemcomitans Y4 capsular-polysaccharide-like polysaccharide promotes osteoclast-like cell formation by interleukin-1 alpha production in mouse marrow cultures.

The mechanism of osteoclast-like cell formation induced by periodontopathic bacterium Actinobacillus actinomycetemcomitans Y4 (serotype b) capsular-polysaccharide-like polysaccharide (capsular-like polysaccharide) was examined in a mouse bone marrow culture system. When mouse bone marrow cells were cultured with A. actinomycetemcomitans Y4 capsular-like polysaccharide for 9 days, many multinucleated cells were formed. The multinucleated cells showed several characteristics of osteoclasts, including tartrate-resistant acid phosphatase (TRACP) and the ability to resorb the calcified dentine. In this study, we examined the effects of antisera to interleukins on the formation of osteoclast-like cells induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide. Monospecific anti-mouse recombinant interleukin-1 alpha (rIL-1 alpha) serum completely inhibited the formation of osteoclast-like cells in the presence of A. actinomycetemcomitans Y4 capsular-like polysaccharide. However, anti-mouse rIL-1 beta and anti-mouse rIL-6 sera showed no effect on osteoclast-like cell formation. IL-1 receptor antagonist significantly inhibited the osteoclast-like cell formation mediated by A. actinomycetemcomitans Y4 capsular-like polysaccharide in mouse marrow cultures. The bioactive IL-1 was detected in the culture media of mouse bone marrow cells stimulated with A. actinomycetemcomitans Y4 capsular-like polysaccharide. These results indicate that IL-1 alpha is involved in the mechanism of the formation of osteoclast-like cells induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide. We sought to determine whether osteoclast-like cell formation induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide could be modulated by the protein kinase inhibitors H8 and HA1004. The formation of osteoclast-like cells was suppressed by H8 and HA1004. These findings suggest that the signals by protein kinases may regulate osteoclast-like cell formation induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide. Furthermore, a correlation between IL-1 alpha and prostaglandin E2 in the osteoclast recruitment induced by A. actinomycetemcomitans Y4 capsular-like polysaccharide is discussed.

Acid Phosphatase↗
PubMed1995

The DNA-binding properties of two heat shock factors, HSF1 and HSF3, are induced in the avian erythroblast cell line HD6.

Avian cells express three heat shock transcription factor (HSF) genes corresponding to a novel factor, HSF3, and homologs of mouse and human HSF1 and HSF2. Analysis of the biochemical and cell biological properties of these HSFs reveals that HSF3 has properties in common with both HSF1 and HSF2 and yet has features which are distinct from both. HSF3 is constitutively expressed in the erythroblast cell line HD6, the lymphoblast cell line MSB, and embryo fibroblasts, and yet its DNA-binding activity is induced only upon exposure of HD6 cells to heat shock. Acquisition of HSF3 DNA-binding activity in HD6 cells is accompanied by oligomerization from a non-DNA-binding dimer to a DNA-binding trimer, whereas the effect of heat shock on HSF1 is oligomerization of an inert monomer to a DNA-binding trimer. Induction of HSF3 DNA-binding activity is delayed compared with that of HSF1. As occurs for HSF1, heat shock leads to the translocation of HSF3 to the nucleus. HSF exhibits the properties of a transcriptional activator, as judged from the stimulatory activity of transiently overexpressed HSF3 measured by using a heat shock element-containing reporter construct and as independently assayed by the activity of a chimeric GAL4-HSF3 protein on a GAL4 reporter construct. These results reveal that HSF3 is negatively regulated in avian cells and acquires DNA-binding activity in certain cells upon heat shock.

Animals↗
PubMed1995

Localization of types I and III collagen and fibronectin in the developing mouse palatal shelves.

The detailed distribution of types I and III collagen and fibronectin was studied in the developing mouse palatal shelf using a double immunofluorescence technique. Just prior to palatal shelf elevation, type I collagen showed denser localization on the nasal side than on the oral side of the middle hard palate region. Such a distribution extended as far as the posterior hard palate region but not to the soft palate region. In type III collagen and fibronectin, this uneven distribution was not so distinct even in the middle hard palate region during the same period. The correspondence of the most conspicuous region of this distribution of extracellular matrix components with the region of first shelf elevation suggests that the extracellular matrix, especially type I collagen, participates in palate development.

Animals↗
PubMed1995

Expression and phosphorylation of BiP/GRP78, a molecular chaperone in the endoplasmic reticulum, during the differentiation of a mouse myeloblastic cell line.

To determine the functional significance of endoplasmic reticulum chaperones in hematopoietic cells, we analyzed the expression and post-translational modification of BiP/GRP78 and GRP94 as well as the cytoplasmic chaperones HSP70 and HSC70 during the differentiation of a mouse myeloid leukemia cell line, M1. The amounts of BiP/GRP78 and GRP94 increased several-fold when M1 cells were induced to differentiate into macrophage-like cells by treatment with interleukin-6 (IL-6). Synthesis began to increase at 4 hr after IL-6 treatment. The phosphorylated form of BiP/GRP78 increased during the later stages of differentiation. These data suggested that the chaperone activity of BiP/GRP78 and GRP94 may be needed for differentiated macrophage-like cells or for the differentiation event itself, and that functionally different BiP/GRP78 accumulate during the differentiation of M1 cells.

Animals↗
PubMed1995

Changes in the level of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid in cerebrospinal fluid after subarachnoid hemorrhage.

A high concentration of a type of cholic acid, 7 alpha-hydroxy-3-oxo-4-cholestenoic acid, is observed in the content of chronic subdural hematoma. To investigate the possible causes, the level of this compound was measured in the cerebrospinal fluid of patients who underwent surgery for aneurysmal subarachnoid hemorrhage or non-hemorrhagic diseases. The maximum level was significantly higher in the aneurysmal subarachnoid hemorrhage patients, indicating that surgical intervention did not cause the postoperative increase in the level of this compound in the cerebrospinal fluid. Monitoring of plasma levels showed no postoperative increase. In vitro culture of a mixture of arterial blood and cerebrospinal fluid failed to show the de novo production of this compound. These results strongly suggest extrahepatic intracranial production of this cholic acid occurs in subarachnoid hemorrhage. The high concentration of this compound in both chronic subdural hematoma and subarachnoid hemorrhage suggests a possible role for 7 alpha-hydroxy-3-oxo-4-cholestenoic acid in intracranial hemorrhagic disorders.

Adult↗
PubMed1995

Trigeminal neuralgia associated with venous angioma--case report.

A 35-year-old male presented with trigeminal neuralgia associated with venous angioma at the root entry zone. Magnetic resonance imaging and angiography demonstrated a venous angioma with a dilated petrosal draining vein, and displacement of the anterior inferior cerebellar artery (AICA). The AICA and dilated petrosal vein were both decompressed, resulting in complete relief from symptoms of trigeminal neuralgia for 30 months. Microvascular decompression rather than resection of venous angioma is recommended for treatment of such cases. The possibility of a venous anomaly should be considered in younger patients with trigeminal neuralgia.

Adult↗
PubMed1995

The effect of basic and acidic fibroblast growth factors (bFGF and aFGF) on the growth of leukemic blast progenitors in acute myelogenous leukemia.

The effect of basic and acidic fibroblast growth factors on leukemic blast progenitors was studied in 14 patients with acute myelogenous leukemia and in one patient with chronic myelocytic leukemia in myeloid crisis. bFGF and aFGF stimulated blast-colony formation by leukemic blast progenitors cultured in methylcellulose in two patients. In the other 13 patients, no significant effect of either FGF on blast-colony formation was noted. The combination of bFGF or a FGF and G-CSF, GM-CSF, interleukin-3, or stem cell factor (SCF) had a synergistic effect on blast-colony formation in three patients. In the other patients, however, synergism between FGF and CSF was not detected. In fact, bFGF was found to suppress the stimulation of blast-colony formation due to GM-CSF in one of 10 patients and that due to SCF in four of eight patients. aFGF suppressed the stimulation of blast-colony formation due to GM-CSF in two of 11 patients and that due to SCF in four of eight patients. The results show that bFGF and aFGF do not directly play a major role in leukemic hematopoiesis but that they may modulate the cytokine network affecting leukemic cell growth.

Adult↗
PubMed1995

[Two cases of CA19-9 producing pulmonary papillary adenocarcinoma].

Two cases of CA 19-9 producing pulmonary papillary adenocarcinoma were reported. Pathological examination showed a well differentiated papillary adenocarcinoma with partially bronchiolo-alveolar cell type. Immunohistochemical study showed a positive straining for CA 19-9 on tumor cells. The level of CA 19-9 decreased after lobectomy and anti-cancer chemotherapy using CDDP and VDS. The series of CA 19-9 level is very useful to evaluate the effect of surgery and chemotherapy. Also it is useful to find out the recurrence of carcinoma.

Adenocarcinoma, Papillary↗
PubMed1995

Possible interaction of haemoglobin with a low Mr GTP-binding protein, ram p25.

Haemoblobin (Hb) was observed to inhibit the GDP/GTP exchange activity of a low M(r) GTP-binding protein, ram p25. Hb also inhibited the [32P]GTP-hydrolysis activity of ram p25. These inhibitory effects of Hb were lost after incubation of Hb at 80 degrees C for 3 min, indicating that the ternary tetrameric structure of Hb is essential for the inhibitory effects on ram p25 activities. Hb did not inhibit [35S]GTP gamma S-binding of nucleotide-free ram p25. Methaemoglobin (MetHb) also inhibited both [3H]GDP-dissociation and [32P]GTP-hydrolysis activities of ram p25 in a very similar manner to Hb. The results strongly suggest that Hb may suppress physiological function(s) of ram p25 in vivo by inhibiting both [32P]GTP-hydrolysis and [3H]GDP-dissociation of ram p25.

Animals↗