Search PubMed⌕ Search

Biomedical subjects

Hiroshi Takeda

Publications and source records attributed to Hiroshi Takeda.

At least 19 recordsLinked to original sources
PubMed2007

Tuberculous gumma associated with idiopathic thrombocytopenic purpura: report of a Japanese female patient.

Our patient was a 77-year-old Japanese woman, who was under treatment for idiopathic thrombocytopenic purpura (ITP) and chronic renal failure. She had warm nodules and cord-like induration on her left knee that appeared similar to Bazin's erythema induratum. A chest X-ray examination revealed miliary tuberculosis; after anti-mycobacterial therapy, the warm nodules and cord-like induration were transformed into a cold, non-tender abscess that drained. Histopathological findings showed caseation necrosis in the subcutaneous tissue, however, mycobacteria were directly detected by Ziehl-Neelsen staining from cutaneous lesions, and cultures from the same lesion also grew Mycobacterium tuberculosis. Tuberculous gumma demonstrated multiple, cold, painless abscesses and thrombosis were also seen. This is a rare and unusual clinical form of cutaneous tuberculosis, and the result of hematogenous dissemination from a primary focus during periods of lowered resistance.

Abscess↗
PubMed2006

Polaprezinc protects human colon cells from oxidative injury induced by hydrogen peroxide: relevant to cytoprotective heat shock proteins.

AIM: To investigate the effect of polaprezinc on cellular damage induced by hydrogen peroxide (H(2)O(2)) in human colon CaCo2 cells. METHODS: CaCo2 cells were treated with polaprezinc (10-100 micromol/L) for 6 h. After polaprezinc treatment, the cells were incubated with H(2)O(2) (20 micromol/L) for 1 h. Cell viability was measured by MTT assay. Western blot analysis for heat shock protein (HSP) 27 and HSP72 in the cells was performed. Moreover, cells were pretreated with quercetin (200 micromol/L), an inhibitor of HSP synthesis, 2 h before polaprezinc treatment, and cell viability and the expression of HSP27 and 72 were assessed in these cells. RESULTS: Polaprezinc significantly protected CaCo2 cells from cell damage induced by H(2)O(2), and up-regulated the expressions of HSP27 and HSP72 in the cells (10, 30 and 100 micromol/L of polaprezinc; 35.0% +/- 7.7%, 58.3% +/- 14.6% and 64.2% +/- 8.2%, respectively. P < 0.01 versus polaprezinc-nontreated cells; 6.0% +/- 4.4%). Quercetin inhibited the up-regulation of HSP27 and HSP72 by polaprezinc and diminished the protective effect of polaprezinc against H(2)O(2)-caused injury in the cells. CONCLUSION: Polaprezinc is a useful therapeutic agent for treatment of colitis and its effects depend on the function of cytoprotective HSP in colon.

Anti-Ulcer Agents↗
PubMed2006

Resistance to experimental colitis depends on cytoprotective heat shock proteins in macrophage migration inhibitory factor null mice.

Macrophage migration inhibitory factor plays an important role in inflammatory diseases. We investigated the role of macrophage migration inhibitory factor (MIF) in the development of dextran sulfate sodium (DSS)-induced colitis using MIF null ((-/-)) mice. MIF(-/-) mice given 3% DSS showed no clinical and histological feature of colitis in contrast to wild-type (WT) mice. Lack of MIF suppressed the up-regulation of TNF-alpha and IFN-gamma as Th1-derived cytokines, and increased the level of IL-4 as Th2-derived cytokine in the colon tissues. Moreover, we found that the expressions of heat shock protein (HSP)40 and HSP70 were markedly up-regulated in the colon of MIF(-/-) mice in response to DSS compared with WT mice. Additionally, quercetin, an inhibitor of HSP synthesis, inhibited the up-regulation of HSP40 and 70 expressions and developed DSS-induced colitis in MIF(-/-) mice. Our findings in this study provide more information in the role of MIF in colitis.

Animals↗
PubMed2006

Antidepressants enhance the antinociceptive effects of carbamazepine in the acetic acid-induced writhing test in mice.

Some antidepressants, as well as antiepileptics, are effective for treating pain of varying etiology. The present study was designed to characterize the antinociceptive effects of imipramine, a tricyclic antidepressant, fluvoxamine, a selective serotonin reuptake inhibitor, milnacipran, a serotonin noradrenaline reuptake inhibitor, and carbamazepine, an antiepileptic drug, using the acetic acid-induced writhing test in mice. Imipramine (1.25-10 mg/kg, i.p.), fluvoxamine (5-40 mg/kg, i.p.) and milnacipran (2.5-20 mg/kg, i.p.) all dose-dependently and significantly reduced the number of writhes induced by the injection of acetic acid (0.8% (v/v)), although the maximal effect of milnacipran was weaker than those of imipramine and fluvoxamine. Similarly, carbamazepine (5-20 mg/kg, i.p.) also showed a dose-dependent and significant antinociceptive effect. In combination studies, the co-administration of a sub-effective dose of carbamazepine (5 mg/kg, i.p.) with imipramine (1.25 and 2.5 mg/kg, i.p.), fluvoxamine (10 mg/kg, i.p.) or milnacipran (1.25 and 2.5 mg/kg, i.p.) significantly reduced the number of writhes. Additionally, the hole-board test revealed that the medications with significant antinociceptive effects barely produced changes in motor activity that could possibly affect writhing behavior. Thus, the present study demonstrated that the antinociceptive effect of carbamazepine is enhanced by combination with imipramine, fluvoxamine and milnacipran. Therefore, the combined therapy using antidepressants and carbamazepine may be useful clinically for the control of pain.

Acetic Acid↗
PubMed2006

Functional expression of the organic cation/carnitine transporter 2 in rat astrocytes.

In this study, we sought to identify the transporters that mediate the uptake of L-carnitine and acetyl-L-carnitine in cultured rat cortical astrocytes. L-[(3)H]carnitine and acetyl-L-[(3)H]carnitine uptake were both saturable, and mediated by a single Na(+)-dependent transport system. Uptake of both was inhibited by L-carnitine, D-carnitine, acetyl-L-carnitine and various organic cations. Acylcarnitines (acetyl-, butyryl-, hexanoyl-, octanoyl- and palmitoyl-L-carnitine) also interacted with L-[(3)H]carnitine and acetyl-L-[(3)H]carnitine transport. 2-Amino-2-norbornane carboxylic acid, a known inhibitor of amino acid transporter B(0,+) (ATB(0,+)), did not cause any significant inhibition. A highly significant correlation was found between the potencies of acylcarnitines in the inhibition of L-[(3)H]carnitine and acetyl-L-[(3)H]carnitine uptake and the acyl chain length of acylcarnitines. The expression of mRNA for organic cation/carnitine transporters (OCTNs), carnitine transporter 2 (CT2) and ATB(0,+) in astrocytes was investigated by reverse transcription (RT)-PCR. OCTN2 mRNA was expressed in astrocytes, whereas the expression of OCTN1, OCTN3 and CT2 mRNA could not be detected. ATB(0,+) mRNA was expressed at very low levels in astrocytes. Western blotting analysis indicated that anti-OCTN2 polyclonal antibody recognized a band of 70 kDa in both kidney and astrocyte preparations. OCTN2 immunoreactivity was detected in rat astrocytes by immunocytochemical staining. Inhibition of OCTN2 expression by RNA interference significantly inhibited L-[(3)H]carnitine and acetyl-L-[(3)H]carnitine uptake into astrocytes. These results suggest that OCTN2 is functionally expressed in rat astrocytes, and is responsible for L-carnitine and acetyl-L-carnitine uptake in these cells.

Animals↗
PubMed2006

Caffeic acid attenuates the decrease in cortical BDNF mRNA expression induced by exposure to forced swimming stress in mice.

We previously reported that caffeic acid produces antidepressive-like effects in the forced swimming test in mice, an animal model of depression. Increased evidence suggests that brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family that has high affinity for the tyrosine kinase receptor B (TrkB), plays an important role in the pathophysiology and treatment of depression. The present study examined whether caffeic acid affects the expression levels of BDNF and TrkB mRNA in brain regions of mice subjected to a forced swimming test. Caffeic acid (4 mg/kg, i.p.) reduced the duration of immobility of mice in the forced swimming test. The levels of BDNF mRNA in the frontal cortex as well as TrkB mRNA in the amygdala were significantly decreased after the forced swimming test, and the former reduction was significantly inhibited by caffeic acid (4 mg/kg, i.p.). Caffeic acid (4 mg/kg, i.p.) did not modify the levels of BDNF and TrkB mRNA in brain regions of naive mice. These results suggest that caffeic acid can attenuate the down-regulation of BDNF transcription that results from stressful conditions.

Animals↗
PubMed2006

Protective effects of heat shock protein 70 induced by geranylgeranylacetone on oxidative injury in rat intestinal epithelial cells.

OBJECTIVE: Geranylgeranylacetone (GGA), an anti-ulcer agent, has recently been demonstrated to protect a variety of cells and tissues via induction of heat shock protein (HSP)70 against numerous stresses. We investigated whether GGA induces HSP70 and protects against an oxidative stressor, monocrolamine (NH(2)Cl), in a rat intestinal epithelial cell line (IEC-18). MATERIAL AND METHODS: IEC-18 cells pretreated with GGA (0.1-10 microM) were subjected to injury induced by NH(2)Cl. Cell viability was assessed, and endogenous HSP70 levels were determined by enzyme-linked immunosorbent assay in IEC-18 cells. RESULTS: Treatment with GGA (0.1-10 microM) was found rapidly to elevate HSP70 levels and to protect against NH(2)Cl-induced injury in IEC-18 cells. Furthermore, quercetin, an inhibitor of HSP70 synthesis, diminished the protective effects of GGA in IEC-18 cells upon NH(2)Cl-caused injury. CONCLUSIONS: The results of this study suggest that GGA plays an important role in defense mechanisms against oxidative injury in the intestine, primarily via induction of HSP70.

Animals↗
PubMed2006

Helicobacter pylori seropositivity predicts outcomes of acid suppression therapy for laryngopharyngeal reflux symptoms.

OBJECTIVES: Although an inverse relationship has been reported between the rates of reflux esophagitis and Helicobacter pylori infection in Japan, infection rates among patients complaining of laryngopharyngeal reflux symptoms, such as abnormal laryngopharyngeal sensation, chronic coughing, and hoarseness, have not previously been investigated. The effects of H. pylori infection on outcomes of acid suppression therapy have not been studied. STUDY DESIGN: Retrospective cohort study. METHODS: We investigated the relationships between H. pylori antibody positivity, laryngopharyngeal reflux symptoms, objective laryngopharyngeal findings, and rate of response to acid-suppression therapy in 42 subjects who were diagnosed with gastroesophageal reflux disease, using upper gastrointestinal endoscopy, and were assayed for the serum H. pylori antibody. RESULTS: The incidence of H. pylori antibody positivity in the targeted patient group was 59.5%. Kaplan-Meier analysis showed that the laryngopharyngeal symptom-improvement rate, measured using the symptom score, was significantly lower for H. pylori antibody-negative cases than for H. pylori antibody-positive cases (30.0 vs. 84.6%; P = .002) 60 days after the start of acid-suppression therapy. No significant differences in the esophageal symptom-improvement rate were noted between the two groups (76.2 vs. 89.5%; P = .576) CONCLUSIONS: By focusing on the involvement of H. pylori infection in laryngopharyngeal reflux, we determined the relationships between H. pylori antibody positivity and response to acid-suppression therapy among patients. The laryngopharyngeal, not esophageal, symptom relief by acid-suppression therapy was significantly lower among H. pylori antibody-negative cases than among antibody-positive cases.

Adult↗
PubMed2006

The substrate specificity of tRNA (m1G37) methyltransferase (TrmD) from Aquifex aeolicus.

Transfer RNA (m(1)G37) methyltransferase (TrmD) catalyzes methyl-transfer from S-adenosyl-L-methionine to the N(1) atom of G37 in tRNA. In Escherichia coli cells, TrmD methylates tRNA species possessing a G36G37 sequence. It was previously believed that G36 was the positive determinant of TrmD recognition. In the current study, we demonstrate that TrmD from Aquifex aeolicus methylates tRNA transcripts possessing an A36G37 sequence as well as tRNA transcripts possessing a G36G37 sequence. In contrast, tRNA transcripts possessing pyrimidine36G37 were not methylated at all. These substrate specificities were confirmed by an in vitro kinetic assay using 16 tRNA transcripts. The modified nucleoside and the position in yeast tRNA(Phe) transcript were confirmed by LC/MS. Furthermore, nine truncated tRNA molecules were tested to clarify the additional recognition site. Unexpectedly, A. aeolicus TrmD protein efficiently methylated the micro helix corresponding to the anti-codon arm. Because the disruption of the anti-codon stem caused the complete loss of the methyl group acceptance activity, the anti-codon stem is essential for the recognition. Moreover, the existence of the D-arm structure inhibited the activity. Recently, it was reported that E. coli TrmD methylates yeast tRNA(Phe) harboring a sequence A36G37. Thus, recognition of the purine36G37 sequence is probably common to eubacteria TrmD proteins.

Amino Acid Sequence↗
PubMed2006

Cost and probability of flowering at the shoot level in relation to variability in shoot size within the crown of Vaccinium hirtum (Ericaceae).

Size-related variation in the cost and probability of flowering among shoots within a crown of Vaccinium hirtum was investigated to clarify patterns and regulation of flowering at the shoot-module level, below the level of the individual. The apices of previous-year shoots differentiated into current-year shoots vegetatively (vegetative branches) or became reproductive by developing inflorescences (reproductive branches). Length growth and fate of current-year shoots were determined, and the future potential for reproduction was estimated using a matrix model of shoot dynamics. Reproductive branches had fewer current-year shoots and shorter total shoot lengths and thus had a reduced potential for reproduction compared with vegetative branches, indicating the cost of flowering at the shoot level. This cost of flowering was higher in longer shoots. The probability of the initiation of flowering in a shoot increased with increasing shoot length in shorter shoots, reached a maximum in medium-sized shoots, and decreased in longer shoots. The size-related changes in the probability of flowering at the shoot level can be largely explained by the size-dependent changes in shoot-level resource availability and cost of flowering.

Flowers↗
PubMed2006

Protective effect of geranylgeranylacetone on trinitrobenzene sulfonic acid-induced colitis in mice.

Geranylgeranylacetone (GGA) has recently been reported to have a protective effect against ischemic, injurious and apoptotic stress in several tissues. The aim of this study was to determine the effect of GGA on colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. Colitis was induced by intrarectal instillation of TNBS in 50% ethanol in BALB/c mice. Survival, change in body weight and change in wet colon weight were assessed. Histological score in the colon was evaluated 5 days after TNBS treatment. The level of myeloperoxidase (MPO) activity in the colon was also determined. Immunohistochemistry for CD4 in the colon was performed. In addition, the level of heat shock protein (HSP) 70 in the colon was determined by Western blot analysis. Mice were orally treated with GGA (300 mg/kg) 2 h before and every other day after starting TNBS administration. Treatment with GGA markedly improved the survival rate, and reduced the loss of body weight and loss of wet colon weight in mice with TNBS-induced colitis. GGA also suppressed the increase in MPO activity and the number of CD4-positive cells infiltrating the colons of mice with TNBS-induced colitis. Furthermore, treatment with GGA remarkably up-regulated the expression of HSP70 in the colons of mice with TNBS-induced colitis. Our results provide further evidence that GGA has therapeutic potential for intestinal inflammation.

Animals↗
PubMed2006

[A case of pulmonary aspergillosis presenting the pulmonary arterial supply suggested with dynamic MRI].

A 67-year-old man with a past history of pulmonary tuberculosis had been referred to our department complaining of bloody sputum. The chest radiograph on admission showed a cavity in the left upper lung field. Chest CT showed a mass-like fungus ball in the cavity. Pulmonary aspergillosis was diagnosed from the sputum mycology, serum Aspergillus antigen and antibody. Even though 150 mg per day Funguard (micafungin sodium) was given intravenously for 4 weeks, the pulmonary aspergillosis did not improve. Dynamic MRI obtained 20 seconds after intravenous injection of contrast material revealed penetrating vessels in the wall of the cavity, and dilated and proliferative vessels surrounding the cavitary lesion. On the basis of the MRI findings which suggested the risk of massive hemoptysis, we performed left upper lobectomy. The histological specimen revealed dilated pulmonary arteries in the wall of the cavity, corresponding to the penetrating vessels on MRI. This is the first report of radiologic-pathologic correlation using dynamic MRI for pulmonary aspergillosis, to the best of our knowledge.

Aged↗
PubMed2005

Regulation of Toll-like receptor 4 expression in mouse colon by macrophage migration inhibitory factor.

Recent studies have indicated that macrophage migration inhibitory factor (MIF) and Toll-like receptor (TLR) play an important role in the regulation of innate immune responses. In this study, we investigated the effect of MIF on the expression of TLR4, a receptor that recognizes lipopolysaccharide, in colon using MIF-deficient mice. TLR4 mRNA expression in the colon tissues was determined by northern blot analysis. Western blot analysis and immunohistochemistry in the colon tissues were performed to evaluate the expression of TLR4 protein. The expressions of TLR4 mRNA and protein were remarkably down-regulated in colon tissues of MIF-deficient mice compared with wild-type mice and up-regulated by treatment with recombinant MIF. Immunohistochemical study revealed the presence of TLR4-positive staining in mononuclear cells in the lamina propria and intraepithelial mononuclear cells as well as weak staining in epithelial cells and crypts in colon tissues of wild-type mice. In contrast, MIF-deficient mice did not show TLR4-positive staining in the colonic mucosa. In MIF-deficient mice injected with recombinant mouse MIF (rMIF), TLR4-positive staining cells were observed in colon tissues similar to the findings in wild-type mice. Administration of dextran sulfate sodium (DSS) up-regulated the expression of TLR4 in the colons of WT mice but not in those of MIF-deficient mice. Furthermore, pretreatment with rMIF up-regulated the expression of TLR4 in response to DSS in MIF-deficient mice. Our results suggest that MIF affects the expression of TLR4 in mouse colon under both normal and colitic conditions.

Animals↗
PubMed2005

Effects of a 5-HT7 receptor antagonist DR4004 on the exploratory behavior in a novel environment and on brain monoamine dynamics in mice.

The present study examined whether serotonin (5-hydroxytryptamine; 5-HT)7 receptors play a role in the modulation of emotionality in mice using the selective 5-HT7 receptor antagonist 2a-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)butyl]-2a,3,4,5-tetrahydrobenzo (c,d)indol-2-(1H)-one (DR4004). The emotionality of mice was evaluated in terms of exploratory activity in the hole-board test. The mice treated with DR4004 (2.5-10 mg/kg, i.p.) displayed a dose-dependent decrease in locomotor activity by moving less distance in the hole-board, and statistically significant decreases were observed at 5 and 10 mg/kg. On the other hand, DR4004 (10 mg/kg, i.p.) did not affect spontaneous motor activity. In a neurochemical study, decreases in amygdaloid dopamine and 5-HT turnover were observed in mice in which locomotor activity in the hole-board test was attenuated following the administration of DR4004 (10 mg/kg, i.p.). Also, a simple linear regression analysis revealed that locomotor activity on the hole-board was significantly correlated with dopamine and 5-HT turnover in amygdala. Furthermore, co-injection of the selective dopamine reuptake inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR12909; 1.25-5 mg/kg, i.p.) or the selective 5-HT reuptake inhibitor fluvoxamine (20 mg/kg, i.p.) significantly reversed the DR4004 (10 mg/kg, i.p.)-induced decrease in locomotor activity in the hole-board test. These findings constitute the behavioral evidence that 5-HT7 receptors may play a role in the modulation of emotionality. Furthermore, it is also suggested that amygdaloid dopamine and 5-HT neuronal systems may be involved in this modulation.

Amygdala↗
PubMed2005

Molecular and functional characterization of an Na+-independent choline transporter in rat astrocytes.

In this study, we examined the molecular and functional characterization of choline uptake into cultured rat cortical astrocytes. Choline uptake into astrocytes showed little dependence on extracellular Na+. Na+-independent choline uptake was saturable and mediated by a single transport system, with an apparent Michaelis-Menten constant (Km) of 35.7 +/- 4.1 microm and a maximal velocity (Vmax) of 49.1 +/- 2.0 pmol/mg protein/min. Choline uptake was significantly decreased by acidification of the extracellular medium and by membrane depolarization. Na+-independent choline uptake was inhibited by unlabeled choline, acetylcholine and the choline analogue hemicholinium-3. The prototypical organic cation tetrahexylammonium (TEA), and other n-tetraalkylammonium compounds such as tetrabutylammonium (TBA) and tetrahexylammonium (THA), inhibited Na+-independent choline uptake, and their inhibitory potencies were in the order THA > TBA > TEA. Various organic cations, such as 1-methyl-4-tetrahydropyridinium (MPP+), clonidine, quinine, quinidine, guanidine, N-methylnicotinamide, cimetidine, desipramine, diphenhydramine and verapamil, also interacted with the Na+-independent choline transport system. Corticosterone and 17beta-estradiol, known inhibitors of organic cation transporter 3 (OCT3), did not cause any significant inhibition. However, decynium22, which inhibits OCTs, markedly inhibited Na+-independent choline uptake. RT-PCR demonstrated that astrocytes expressed low levels of OCT1, OCT2 and OCT3 mRNA, but the functional characteristics of choline uptake are very different from the known properties of these OCTs. The high-affinity Na+-dependent choline transporter, CHT1, is not expressed in astrocytes as evidenced by RT-PCR. Furthermore, mRNA for choline transporter-like protein 1 (CTL1), and its splice variants CTL1a and CTL1b, was expressed in rat astrocytes, and the inhibition of CTL1 expression by RNA interference completely inhibited Na+-independent choline uptake. We conclude that rat astrocytes express an intermediate-affinity Na+-independent choline transport system. This system seems to occur through a CTL1 and is responsible for the uptake of choline and organic cations in these cells.

Animals↗
PubMed2005

Pathophysiological roles of macrophage migration inhibitory factor in gastrointestinal, hepatic, and pancreatic disorders.

Macrophage migration inhibitory factor (MIF) is a unique protein, participating in inflammation, immune response, and cell growth. MIF was first discovered as a lymphokine involved in delayed hypersensitivity and various macrophage functions, including phagocytosis, spreading, and tumoricidal activity. It has been reported that MIF is associated with the pathogenesis of a variety of diseases. MIF expression was increased at inflammatory sites in diseases such as rheumatoid arthritis and glomerulonephritis. In experimental inflammatory disease, blockade of MIF bioactivity inhibited the severity of disease activity. On the other hand, MIF expression is also increased in tumor lesions, and MIF plays a role as a cell growth factor. MIF has been reported to be constitutively expressed in gut, liver, and pancreas. In patients with gastritis, inflammatory bowel disease, hepatitis, and pancreatitis, MIF expression was remarkably increased in both the serum and the local lesions. Blockade of MIF bioactivity inhibited and prevented inflammation in experimental gastritis, colitis, hepatitis, and pancreatitis. On the other hand, MIF expression was higher than that in normal tissues in colonic carcinomas and hepatocellular carcinoma both in vivo and in vitro. Blockade of MIF bioactivity successfully inhibited tumor cell growth in vivo and in vitro. MIF plays important roles in the pathogenesis of gastrointestinal, hepatic, and pancreatic disorders.

Colonic Neoplasms↗