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T Uchiyama

Publications and source records attributed to T Uchiyama.

At least 73 records · Page 4Linked to original sources
PubMed2001

Src tyrosine kinase is the trigger but not the mediator of ischemic preconditioning.

The signal cascade that triggers and mediates ischemic preconditioning (IPC) remains unclear. The present study investigated the role of the Src family of tyrosine kinases in IPC. Isolated and buffer-perfused rat hearts underwent IPC with three cycles of 5-min ischemia and 5-min reperfusion, followed by 30-min ischemia and 120-min reperfusion. The Src tyrosine kinase family-selective inhibitor PP1 was administered between 45 and 30 min before ischemia (early PP1 treatment) or for 15 min before IPC [early PP1-preconditioning (PC) treatment]. PP1 was also administered for 5 min before the sustained ischemia (late PP1 treatment) or after IPC (late PP1-PC treatment). Src kinase was activated after 30 min of ischemia in both the membrane and cytosolic fractions. Src kinase was also activated by IPC but was attenuated after the sustained ischemia. Early and late PP1 treatment inhibited Src activation after the sustained ischemia and reduced infarct size. Early PP1-PC inhibited Src activation after IPC but not after the sustained ischemia and blocked cardioprotection afforded by IPC. Late PP1-PC treatment abrogated IPC-induced activation of Src and protein kinase C (PKC)-epsilon in the membrane but not in the cytosolic fraction. This treatment modality abrogated Src activation after the sustained ischemia and failed to block cardioprotection afforded by IPC. These results suggest that Src kinase activation mediates ischemic injury but triggers IPC in the position either upstream of or parallel to membrane-associated PKC-epsilon.

Animals↗
PubMed2001

LysR-type transcriptional regulator ChiR is essential for production of all chitinases and a chitin-binding protein, CBP21, in Serratia marcescens 2170.

To identify the genes required for chitinase production by Serratia marcescens 2170, various Tn5 mutants somehow defective in chitinase production were isolated in a previous study. In order to identify the mutated gene in one of the chitinase-deficient mutants, N1, DNA regions flanking the Tn5 insertion were cloned and sequenced. Sequence comparison showed that the mutation occurred in the ORF located between chiB and cbp, which encode chitinase B and chitin-binding protein CBP21, respectively. The ORF encodes a 313-amino acid polypeptide which has significant similarity with various LysR-type transcriptional regulators, and thus the gene was designated chiR. Targeted mutagenesis confirmed that disruption of the chiR gene results in the phenotype of N1. Gel mobility shift assays using partially purified ChiR protein demonstrated that this protein specifically binds to the intergenic region between chiR and cbp. These results strongly suggest that ChiR is a LysR-type transcriptional regulator which is essential for production of all chitinases and CBP21.

Amino Acid Sequence↗
PubMed2001

Identification of 2,3-dihydro-gamma-ionylideneethanol in Cercospora cruenta.

During our scrutiny of GC-EI-MS date for C15 alcohols as putative intermediates on the ABA biosynthetic pathway in Cercospora cruenta, a trace amount of 5-[2',2'-dimethyl-6'-methylene-1'-cyclohexyl]-3-methyl-4-penten-1-ol (2,3-dihydro-gamma-ionylideneethanol) was identified. Feeding experiments indicated that this compound was not an intermediate to ABA, but a catabolite that originated from gamma-ionylideneacetaldehyde. The stereochemistry of 2,3-dihydro-gamma-ionylideneethanol was deduced to be (3R,1'S) from a comparison with an authentic specimen prepared via baker's yeast asymmetric reduction.

Alcohols↗
PubMed2001

Human parathyroid hormone 1-34 reverses bone loss in ovariectomized mice.

The experimental work characterizing the anabolic effect of parathyroid hormone (PTH) in bone has been performed in nonmurine ovariectomized (OVX) animals, mainly rats. A major drawback of these animal models is their inaccessibility to genetic manipulations such as gene knockout and overexpression. Therefore, this study on PTH anabolic activity was carried out in OVX mice that can be manipulated genetically in future studies. Adult Swiss-Webster mice were OVX, and after the fifth postoperative week were treated intermittently with human PTH(1-34) [hPTH(1-34)] or vehicle for 4 weeks. Femoral bones were evaluated by microcomputed tomography (microCT) followed by histomorphometry. A tight correlation was observed between trabecular density (BV/TV) determinations made by both methods. The BV/TV showed >60% loss in the distal metaphysis in 5-week and 9-week post-OVX, non-PTH-treated animals. PTH induced a approximately 35% recovery of this loss and a approximately 40% reversal of the associated decreases in trabecular number (Tb.N) and connectivity. PTH also caused a shift from single to double calcein-labeled trabecular surfaces, a significant enhancement in the mineralizing perimeter and a respective 2- and 3-fold stimulation of the mineral appositional rate (MAR) and bone formation rate (BFR). Diaphyseal endosteal cortical MAR and thickness also were increased with a high correlation between these parameters. These data show that OVX osteoporotic mice respond to PTH by increased osteoblast activity and the consequent restoration of trabecular network. The Swiss-Webster mouse model will be useful in future studies investigating molecular mechanisms involved in the pathogenesis and treatment of osteoporosis, including the mechanisms of action of known and future bone antiresorptive and anabolic agents.

Animals↗
PubMed2001

FR167653, a p38 mitogen-activated protein kinase inhibitor, prevents Helicobacter pylori-induced gastritis in Mongolian gerbils.

FR167653 was discovered as a cytokine production inhibitor, but its target molecule has remained unclear. We examined the effect of FR167653 on activities of purified protein kinases. FR167653 dose dependently inhibited p38alpha mitogen-activated protein kinase activity without affecting the activities of other kinases. FR167653 had no effect on cyclooxygenase (COX)-1 or COX-2 activities, whereas SB203580 inhibited them. FR167653 suppressed endogenous p38 kinase activity in interleukin-1-stimulated NRK-F cells. These results indicate that FR167653 is a p38 kinase-selective inhibitor without affecting COX activity. To evaluate the role of p38 kinase in Helicobacter pylori gastritis, we therefore examined the effect of FR167653 on H. pylori-induced gastritis in Mongolian gerbils. H. pylori infection activated p38 kinase in the gastric mucosa and caused neutrophil infiltration from 2 and 3 weeks of infection, respectively. At 4 weeks, severe mucosal inflammation with erosive injury was observed. When FR167653 was administered to H. pylori-infected gerbils from 2 weeks, both neutrophil infiltration and mucosal injury at 4 weeks were significantly prevented. FR167653 markedly reduced the H. pylori-induced increase in endogenous p38 kinase activity in the gastric mucosa, and also significantly inhibited neutrophil chemokine production. In contrast, the drug did not affect H. pylori colonization or acid secretion. FR167653 did not cause any pathological change in the gastric mucosa of normal animals. These results indicate that p38 kinase plays a crucial role in H. pylori-induced gastritis in Mongolian gerbils.

Animals↗
PubMed2001

Modulation of intestinal permeability by nitric oxide donors: implications in intestinal delivery of poorly absorbable drugs.

The effects of nitric oxide (NO) donors NOC5 [3-(2-hydroxy-1-(methylethyl)-2-nitrosohydrazino)-1-propanamine ] and NOC12 [N-ethyl-2-(1-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine] on the permeability of 5(6)-carboxyfluorescein (CF) across the intestinal membrane were examined by an in vitro Ussing chamber method. The NO donors significantly increased the intestinal permeability of CF and their absorption-enhancing effects were concentration-dependent over the range of 0.01 to 0.1 mM. Regional differences in the absorption-enhancing effects of the NO donors were observed (colon > jejunum). The absorption-enhancing effect of NOC12 reduced as the molecular weights of compounds increased. Therefore, the degree of absorption-enhancing effect of NOC12 was dependent on the molecular weights of compounds. In the pretreatment studies with NOC12 and lactate dehydrogenase release studies, the absorption-enhancing effect of 0.1 mM NOC12 was reversible and less toxic to the colonic membrane. On the other hand, the absorption-enhancing effect of NOC12 was inhibited by the coadministration of 2-(4-carboxyphenyl) 4,4,5, 5-tetramethylimidazole-1-oxyl 3-oxide sodium salt, an NO scavenger, suggesting that NO can regulate the permeability of water-soluble drugs in the gut. Furthermore, NOC12 (0.1 and 1 mM) significantly decreased the transepithelial electrical resistance value of the colonic membrane, suggesting that the absorption-enhancing mechanism of NOC12 may be partly related to the dilation of the tight junction in the epithelium via a paracellular route. These findings suggest that NO donors may be useful to enhance the intestinal absorption of poorly absorbable drugs.

Animals↗
PubMed2001

[Disseminated atypical mycobacteriosis in a patient with chronic myelogenous leukemia].

A 61-year-old woman with a 6-year history of chronic myelogenous leukemia (CML) presented with recurrent fever in July 1996. Bone marrow aspiration, biopsy and chromosome analysis showed that CML was in the chronic phase. Bone marrow biopsy revealed nonspecific inflammatory lesions. Chest X-ray and computed tomography examinations demonstrated interstitial pneumonia. Cultures of gastric juice and bone marrow yielded colonies of Mycobacterium avium complex (MAC), and a diagnosis of disseminated atypical mycobacteriosis was made. Multidrug treatment including rifampicin, ethambutol, clarithromycin and ciprofloxacin was begun. The cultures subsequently became negative and the fever was resolved. However, fever eventually recurred and the patient died of multiple organ failure in October 1997. since disseminated atypical mycobacteriosis complicating hematological disorders worsens the prognosis, its early diagnosis and prompt treatment are important. Although it is often difficult to identify atypical mycobacterium as a causal agent, frequent culturing of atypical mycobacterium from various sources including bone marrow fluid can be helpful for early diagnosis whenever fever of undetermined origin occurs in patients with hematological disorders.

Female↗
PubMed2001

[A focal usual interstitial pneumonia lesion: an important risk factor in diffuse alveolar damage--acute exacerbation of a focal usual interstitial pneumonia patient].

The aim of this study was to clarify whether the presence of a focal usual interstitial pneumonia lesion (F-UIP) is a risk factor for diffuse alveolar damage (DAD). Our subjects were 977 patients (681 males, 296 females, mean age, 64 years). The incidence of F-UIP increased significantly with age (between 50 and 60 years, 3% and 8%, p < 0.05; between 60 and 70 years, 8% and 14.1%, p < 0.05; and between 70 and 80 years, 14.1% and 27.9%, p < 0.01). The mean age of the non-UIP group was 64 years, and of the F-UIP group was 75 years, showing significance (p < 0.001). The incidence of DAD was higher in the F-UIP group (100 patients, 30%, p < 0.01) and the diffuse UIP group (60 patients, 30%, p < 0.01) than in the non-UIP group (817 patients, 5.3%). Although the causes of DAD were various, the presence of F-UIP was a important risk factor of DAD.

Acute-Phase Reaction↗
PubMed2001

[Dissecting aneurysm of the anterior cerebral artery with later development of collateral circulation: a case report].

Intracranial dissecting aneurysm (DA) is much less frequent than berry aneurysm. Such dissection involves mostly the vertebral and basilar arteries, followed by the internal carotid and middle cerebral arteries. DA of the anterior cerebral artery (ACA) is relatively rare and little is known about its natural Development. Only 23 cases have been reported previously. Our present patient, a 44-year-old man, suddenly developed paresis of the left leg while bathing. Diffusion magnetic resonance imaging indicated an area of high signal intensity in the territory of the ACA. Angiography on day 3 following onset showed a DA involving the left A2 segment. Antiplatelet therapy was administered. Further luminal narrowing in the lesion was demonstrated by repeat angiography on day 17. Occlusion of the distal A2 segment was demonstrated together with sufficient collateral supply on day 41. Symptoms resolved completely. DA of the ACA usually presents with ischemic attacks. Its etiology remains uncertain, and its natural course is unclear. Surgical intervention is recommended for patients with intracranial hemorrhage, while non surgical therapies have achieved good outcomes in ischemic cases.

Adult↗
PubMed2000

Comparative study of the effects of magnetic versus electrical stimulation on inhibition of detrusor overactivity.

OBJECTIVES: To perform a randomized comparative study investigating the urodynamic effects of functional magnetic stimulation (FMS) and functional electrical stimulation (FES) on the inhibition of detrusor overactivity. METHODS: Thirty-two patients with urinary incontinence due to detrusor overactivity (15 men, 17 women; age 62. 3 +/- 16.6 years) were randomly assigned to two treatment groups (15 patients in the FMS group and 17 in the FES group). Stimulation was applied continuously at 10 Hz in both groups. For FMS, the magnetic stimulator unit was set on an armchair type seat and had a concave-shaped coil, so that the patients could sit during stimulation. For FES, a vaginal electrode was used in the women and a surface electrode on the dorsal part of the penis was used in the men. Cystometry was performed before and during the stimulation. RESULTS: The bladder capacity at the first desire to void and the maximum cystometric capacity increased significantly during stimulation compared with prestimulation levels in both groups (P = 0.0054 and 0.0026, respectively, in the FMS group and P = 0.0015 and 0.0229, respectively, in the FES group). However, the increase in the maximum cystometric capacity was significantly (P = 0.0135) greater in the FMS group (114.2 +/- 124.1 mL or an increase of 105. 5% +/- 130.4% compared with the pretreatment level) than that in the FES group (32.3 +/- 56.6 mL or an increase of 16.3% +/- 33.9%). Detrusor overactivity was abolished in 3 patients in the FMS group but not in any patient in the FES group. CONCLUSIONS: Although both treatments were effective, the inhibition of detrusor overactivity appeared greater in the FMS group than in the FES group.

Adult↗
PubMed2000

Nonimmunoglobulin (non-Ig)/BCL6 gene fusion in diffuse large B-cell lymphoma results in worse prognosis than Ig/BCL6.

Chromosomal translocation involving the BCL6 gene affects not only immunoglobulin (Ig) genes but also a number of non-Ig genes as partners. The molecular anatomy of the BCL6 gene rearrangements in 39 cases with diffuse large B-cell lymphoma (DLBCL) by long-distance polymerase chain reaction-based assays was determined. The results showed that Ig genes were affected in 21 cases; non-Ig genes, 15 cases; a deletion of more than a 1-kb segment, 2 cases; and a point mutation, 1 case. Comparative studies between the 21 cases with Ig gene partners and the 17 cases with non-Ig gene partners, including 2 cases with the deletion, showed that the overall survival of the latter group of patients was significantly inferior to that of the former (P = .0440), and the estimated 2-year overall survival rates were 58.3% vs 17.6% (P = .005). Non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL, and DLBCL with BCL6 translocation could be subclassified according to the individual partner locus and/or gene. (Blood. 2000;96:2907-2909)

Adult↗
PubMed2000

Molecular cloning, genomic structure, chromosomal localization, and alternative splice forms of the platelet collagen receptor glycoprotein VI.

Glycoprotein VI (GPVI) is the major collagen receptor underlying platelet activation. We cloned the full-length cDNA for GPVI (GPVI-1) and its two isoforms (GPVI-2 and -3) from phorbol-ester-stimulated CMK cells. The GPVI-1 cDNA was identical in the coding region with the cDNA that has recently been reported to belong to the immunoglobulin superfamily. The GPVI gene consisted of 8 exons spanning over 23 kbp and was mapped on the chromosome 19q13. 4. The promoter of GPVI gene lacked TATA and CAAT boxes and had multiple transcription start sites like other megakaryocytic genes. When COS-7 cells were cotransfected with the GPVI isoforms and Fc receptor gamma chain, Fc receptor gamma chain was associated with GPVI-1 and -2 but did not affect the GPVI expression levels. GPVI-1 and -2 could bind the collagen-related peptide, which exhibits triple-helical and polymeric structure of collagen to activate platelets via GPVI.

Alternative Splicing↗
PubMed2000

IL-10, but not IL-4, suppresses infection-stimulated bone resorption in vivo.

Periapical bone resorption occurs following infection of the dental pulp and is mediated mainly by IL-1alpha in the murine model. The production and activity of IL-1alpha is modulated by a network of regulatory cytokines, including those produced by Th1 (pro-inflammatory) and Th2 (anti-inflammatory) subset T cells. This study was designed to assess the functional role of the Th2-type cytokines IL-4 and IL-10 in infection-stimulated bone resorption in vivo. The dental pulps of the first molars were exposed and infected with a mixture of four common endodontic pathogens, and bone destruction was determined by micro-computed tomography at sacrifice on day 21. The results demonstrate that IL-10(-/-) mice had significantly greater infection-stimulated bone resorption in vivo compared with wild-type mice (p < 0.001), whereas IL-4(-/-) exhibited no increased resorption. IL-10(-/-) had markedly elevated IL-1alpha production within periapical inflammatory tissues (>10-fold) compared with wild type (p < 0.01), whereas IL-4(-/-) exhibited decreased IL-1alpha production (p < 0.05). IL-10 also suppressed IL-1alpha production by macrophages in a dose-dependent fashion in vitro, whereas IL-4 had weak and variable effects. We conclude that IL-10, but not IL-4, is an important endogenous suppressor of infection-stimulated bone resorption in vivo, likely acting via inhibition of IL-1alpha expression.

Animals↗
PubMed2000

Micturitional disturbance in neuro-Behçet's syndrome.

BACKGROUND: Micturitional disturbance is known to occur in neuro-Behçet's syndrome (NBS). However, its pathophysiology is uncertain and few data are available concerning urodynamic findings. We describe our findings on micturitional histories and urodynamic studies in patients with NBS. METHODS: A history of urinary symptoms was obtained from nine patients with NBS [seven male, two female, aged 26 to 54 years; mean, 41 years]. Neurological and CT/MRI findings indicated that their lesions were located mainly in the cerebral cortex, basal ganglia, cerebellum, brainstem and the spinal cord. Symptomatic patients underwent urodynamic studies, including measurement of post-micturition residuals, urethral pressure profilometry and EMG cystometry. RESULTS: Six of the nine patients (67%) had urinary symptoms that included diurnal urinary frequency in five, sensation of urgency in five, urge urinary incontinence in five, voiding difficulty in five and nocturnal urinary frequency in four. None had urinary retention. Urodynamic studies performed in six patients showed post-micturition residuals in five (50-180 ml), increased maximum urethral closure pressure in two, decrease in four and increase in one of bladder capacities, detrusor hyperreflexia in five, decreased bladder sensation in one, brisk bulbocavernosus reflex in four, detrusor-sphincter dyssynergia in two and neurogenic sphincter EMG in one. CONCLUSION: Our results indicate that micturitional disturbance is not rare in patients with NBS. Supranuclear pelvic nerve dysfunction seems to be mainly responsible for the disturbance.

Adult↗
PubMed2000

Pyk2 and Syk participate in functional activation of granulocytic HL-60 cells in a different manner.

The roles of the protein tyrosine kinases Pyk2 (also called RAFTK or CAK beta) and Syk in the process of functional activation of human myeloid cells were examined. During granulocytic differentiation of HL-60 cells with dimethyl sulfoxide (DMSO), the amounts of Pyk2 and beta2 integrin increased, whereas the amount of Syk was abundant before differentiation and did not change during differentiation. When the granulocytic cells were stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), tyrosine phosphorylation of Pyk2 occurred promptly and subsequent association of Pyk2 with beta2 integrin was detected. In contrast, Syk was not tyrosine phosphorylated by fMLP stimulation but constitutively associated with beta2 integrin. Stimulation with fMLP also caused the alteration of beta2 integrin to an activated form, a finding that was confirmed by the observation of fMLP-induced cell attachment on fibrinogen-coated dishes and inhibition of this attachment by pretreatment with anti-beta2 integrin antibody. Cell attachment to fibrinogen caused the enhanced tyrosine phosphorylation of Pyk2 and the initial tyrosine phosphorylation of Syk, which was also inhibited by pretreatment with anti-beta2 integrin antibody. In vitro kinase assays revealed that Pyk2 and Syk represented kinase activities to induce tyrosine phosphorylation of several molecules in the anti-beta2 integrin immunoprecipitates of the attached cells. These results showed that Pyk2 is involved in the functional activation of granulocytic cells in 2 signaling pathways: an fMLP receptor-mediated "inside-out" signaling pathway that might cause beta2 integrin activation and a subsequent beta2 integrin-mediated "outside-in" signaling pathway. Syk was activated in relation to cell attachment to fibrinogen as a result of "outside-in" signaling, although it was already associated with beta2 integrin before fMLP stimulation. (Blood. 2000;96:1733-1739)

CD18 Antigens↗