Biomedical subjects

A Wada

Publications and source records attributed to A Wada.

At least 55 records · Page 3Linked to original sources

PubMed2001

Adrenomedullin and proadrenomedullin N-terminal 20 peptide (PAMP) in adrenal chromaffin cells.

Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are peptides having multiple physiological functions and are most abundantly expressed in the adrenal medulla. In addition to PAMP, PAMP12, a 12 amino acid peptide with sequence identity to PAMP between amino acids 9-20, has also been shown to be expressed in the adrenal medulla. AM, PAMP and PAMP12 are released along with catecholamines by regulated exocytosis upon stimulation of adrenal chromaffin cells. PAMP and PAMP12 regulate catecholamine release and synthesis by interfering with nicotinic cholinergic receptors in these chromaffin cells. AM may also cause gradual release of catecholamine from these cells. AM, PAMP and PAMP12 are endogenous peptides that modulate chromaffin cell function via different mechanisms.

Adrenal Medulla↗

PubMed2001

Adrenomedullin in the cerebral circulation.

The central nervous system requires an effective autoregulation of cerebral circulation in order to meet the critical and unusual demands of the brain. In addition, cerebral microvessels has a unique feature, the formation of the blood-brain barrier, which contributes to the stability of the brain parenchymal microenvironment. Many factors are known to be involved in the regulation of cerebral circulation and blood-brain barrier functions. In the last few years a new potential candidate, adrenomedullin, a hypotensive peptide was added to this list. Adrenomedullin has a potent vasodilator effect on the cerebral vasculature, and it may be implicated in the pathologic mechanism of cerebrovascular diseases. In this review, we describe current knowledge about the origin and possible role of adrenomedullin in the regulation of cerebral circulation and blood-brain barrier functions.

Adrenomedullin↗

PubMed2001

Selective expression of aquaporin 1, 4 and 5 in the rat middle ear.

The middle ear cavity is an air-filled space that must be maintained for effective sound transmission to the inner ear. To examine the mechanisms of water homeostasis in the middle ear, we investigated whether aquaporins (AQPs), a family of water-permeable channels, were expressed in the middle ear. Reverse transcription-polymerase chain reaction and immunoblot analyses revealed that mRNAs encoding AQP1, 4 and 5 (but not 2 or 3) subtypes were expressed in rat middle ear epithelium; AQP1, 4 and 5 were detected as 28-, 30- and 30-kDa proteins, respectively. Immunohistochemical analysis showed that AQP1 was localized at capillary endothelial cells and fibroblasts in lamina propria mucosae; AQP4 was present solely at the basolateral membrane of ciliated cells, whereas AQP5 was on the apical surface of ciliated cells as well as of flat and columnar epithelial cells. The characteristic different localizations of AQP1, 4 and 5 subtypes in the middle ear suggest that middle ear water homeostasis requires the coordinated operation of these AQPs.

Animals↗

PubMed2001

A case of schwannoma on the nasal septum.

We present a case of nasal septal schwannoma. The patient was a 62-year-old female complaining of bilateral nasal obstruction. Anterior rhinoscopy revealed a smooth-surfaced mass arising from the nasal septum in both nasal cavities. Computed tomography scan showed a mass with enhancement in the two nasal cavities and the ethmoid sinuses, and this mass extended to the skull base. Lateral rhinotomy was performed under general anesthesia. The tumor arose from the nasal septum, occupied both nasal cavities, and extended to the anterior ethmoid sinuses. It was encapsulated and could be totally removed en bloc. Pathological examination of the excised specimen showed that it was an Antoni type A schwannoma. The tumor cells were immunoreactive for S-100 protein. The patient is doing well with no evidence of recurrence.

Adult↗

PubMed2001

Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure.

OBJECTIVES: We sought to evaluate the effects of spironolactone on neurohumoral factors and left ventricular remodeling in patients with congestive heart failure (CHF). BACKGROUND: Aldosterone (ALD) promotes collagen synthesis and structural remodeling of the heart. Spironolactone, an ALD receptor antagonist, is reported to reduce mortality in patients with CHF, but its influence on left ventricular remodeling has not been clarified. METHODS: Thirty-seven patients with mild-to-moderate nonischemic CHF were randomly divided into two groups that received treatment with spironolactone (n = 20) or placebo (n = 17). We measured left ventricular volume and mass before treatment and after four months of treatment. We also measured the plasma levels of neurohumoral factors, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), as well as plasma procollagen type III aminoterminal peptide (PIIINP), a marker of myocardial fibrosis. RESULTS: Left ventricular volume and mass were significantly decreased and ejection fraction was significantly increased in the spironolactone group, while there were no changes in the placebo group. Plasma levels of ANP, BNP and PIIINP were significantly decreased after spironolactone treatment, but were unchanged in the placebo group. There was a significant positive correlation between the changes of PIIINP and changes of the left ventricular volume index (r = 0.45, p = 0.045) as well as the left ventricular mass index (r = 0.65, p = 0.0019) with spironolactone treatment. CONCLUSIONS: These findings indicate that four months of treatment with spironolactone improved the left ventricular volume and mass, as well as decreased plasma level of BNP, a biochemical marker of prognosis and/or ventricular hypertrophy, suggesting that endogenous aldosterone has an important role in the process of left ventricular remodeling in nonischemic patients with CHF.

Aged↗

PubMed2001

Heterogeneous increases of cytoplasmic calcium: distinct effects on down-regulation of cell surface sodium channels and sodium channel subunit mRNA levels.

1. Long-term (> or = 12 h) treatment of cultured bovine adrenal chromaffin cells with A23187 (a Ca(2+) ionophore) or thapsigargin (TG) [an inhibitor of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)] caused a time- and concentration-dependent reduction of cell surface [(3)H]-saxitoxin (STX) binding capacity, but did not change the K:(D:) value. In A23187- or TG-treated cells, veratridine-induced (22)Na(+) influx was reduced (with no change in veratridine EC(50) value) while it was enhanced by alpha-scorpion venom, beta-scorpion venom, or Ptychodiscus brevis toxin-3, like in nontreated cells. 2. The A23187- or TG-induced decrease of [(3)H]-STX binding was diminished by BAPTA-AM. EGTA also inhibited the decreasing effect of A23187. A23187 caused a rapid, monophasic and persistent increase in intracellular concentration of Ca(2+) ([Ca(2+)](i)) to a greater extent than that observed with TG. 2,5-Di-(t-butyl)-1,4-benzohydroquinone (DBHQ) (an inhibitor of SERCA) produced only a rapid monophasic increase in [Ca(2+)](i), without any effect on [(3)H]-STX binding. 3. Reduction in [(3)H]-STX binding capacity induced by A23187 or TG was attenuated by Gö6976 (an inhibitor of conventional protein kinase C) or calpastatin peptide (an inhibitor of calpain). When the internalization rate of cell surface Na(+) channels was measured in the presence of brefeldin A (an inhibitor of vesicular exit from the trans-Golgi network), A23187 or TG accelerated the reduction of [(3)H]-STX binding capacity. 4. Six hours treatment with A23187 lowered Na(+) channel alpha- and beta(1)-subunit mRNA levels, whereas TG had no effect. 5. These results suggest that elevation of [Ca(2+)](i) caused by A23187, TG or DBHQ exerted differential effects on down-regulation of cell surface functional Na(+) channels and Na(+) channel subunit mRNA levels.

Animals↗

PubMed2001

Expression of ribosome modulation factor (RMF) in Escherichia coli requires ppGpp.

BACKGROUND: During the transition from the logarithmic to the stationary phase, 70S ribosomes are dimerized into the 100S form, which has no translational activity. Ribosome Modulation Factor (RMF) is induced during the stationary phase and binds to the 50S ribosomal subunit, which directs the dimerization of 70S ribosomes. Unlike many other genes induced in the stationary phase, rmf transcription is independent of the sigma S. To identify the factors that regulate the growth phase-dependent induction of rmf, mutant strains deficient in global regulators were examined for lacZ expression directed by the rmf promoter. RESULTS: Among mutants of defective global regulators, only ppGpp deficiency (relA-spoT double mutant) drastically reduced the level of rmf transcription to less than 10% of that seen in the wild-type. Neither RMF nor 100S ribosomes were detected in this mutant in the stationary phase. rmf transcription correlated well with cellular ppGpp levels during amino acid starvation, IPTG induction of Ptrc-relA455 and in other mutants with artificially increased ppGpp levels. Although the growth rate also correlated inversely with both ppGpp levels and rmf transcription, the observation that the growth rates of the ppGpp-deficient and wild-type strains varied equivalently when grown on different media indicates that the link between rmf transcription and ppGpp levels is not a function of the growth rate. CONCLUSIONS: ppGpp appears to positively regulate rmf transcription, at least in vivo. Thus, RMF provides a novel negative translational control by facilitating the formation of inactive ribosome dimers (100S) under the stringent circumstances of the stationary phase.

Cell Division↗

PubMed2001

Helicobacter pylori-mediated transcriptional regulation of the human beta-defensin 2 gene requires NF-kappaB.

Human beta-defensin 2 (hBD-2) is an antimicrobial peptide involved in host defence against bacterial infection in epithelial tissues. Its levels are dramatically increased after bacterial infection. The involvement of NF-kappaB in Helicobacter pylori-mediated induction of hBD-2 promoter activity was examined. A luciferase reporter plasmid containing the hBD-2 promoter extending from -2110 base pairs to -1 was transiently expressed in MKN45 cells, and promoter activity was determined after incubation with H. pylori for 6 h. Deletion or mutation of the NF-kappaB site at -208 abolished activation of the hBD-2 promoter. Only H. pylori strains carrying a cag pathogenicity island (PAI) induced activation of the NF-kappaB site of the hBD-2 promoter gene. By gel retardation analyses, H. pylori increased NF-kappaB binding to hBD-2 promoter gene sequences. Supershift analysis demonstrated that whereas H. pylori activated NF-kappaB p65-p65 and p50-p50 homodimers, and the p65-p50 heterodimer of NF-kappaB, only the p65-p65 homodimer bound to the NF-kappaB site of the hBD-2 promoter. Thus, specific NF-kappaB proteins are important cis-elements for induction of hBD-2 gene transcription by H. pylori.

Cell Line↗

PubMed2001

Effect of absorbable polydioxanone flexor tendon repair and restricted active mobilization in a canine model.

We performed an experimental study to evaluate the mechanical and histologic healing process of flexor tendon repair using absorbable polydioxanone monofilament followed by active mobilization. Sixty-four canine flexor digitorum profundus tendons were repaired using polydioxanone monofilament or control braided polyester. Animals were evaluated 7, 14, 28, and 42 days after surgery with 12 day 0 control tendons. All repaired tendons healed without rupture or gap formation. Mechanically, all specimens had adequate tensile strength enabling active mobilization. The tendons that were repaired using braided polyester healed without initial tensile depression; however, the ultimate tensile strength values of polydioxanone specimens showed a significant decrease at day 14. Histologically, an inflammatory response was observed around the polydioxanone monofilament; this reaction increased from day 14 to day 42. However, the inflammatory response did not cause large adhesions or large tendon callus formation. This method of using absorbable suture material for tendon repair has the potential for use in the clinical setting.

Animals↗

PubMed2001

Relationship between plasma levels of cardiac natriuretic peptides and soluble Fas: plasma soluble Fas as a prognostic predictor in patients with congestive heart failure.

BACKGROUND: Cardiac natriuretic peptides may induce apoptosis in myocytes; however, the relationship between plasma levels of cardiac natriuretic peptides and those of soluble Fas (sFas) and tumor necrosis factor (TNF)-alpha remains unknown in patients with congestive heart failure (CHF). METHODS AND RESULTS: We measured plasma levels of sFas and TNF-alpha and those of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, and endothelin 1 in 96 patients with CHF (ejection fraction < 45%). The patients were monitored for 3 years. Plasma levels of sFas and TNF-alpha increased with the severity of CHF. There was no significant correlation between sFas plasma levels and those of ANP and BNP. Cox proportional hazard analysis showed that high levels of sFas (P = .009) and BNP (P < .0001) and a low ejection fraction (P = .019) were independent significant prognostic predictors. CONCLUSIONS: There is no significant correlation between cardiac natriuretic peptide and sFas levels in plasma. Plasma sFas is a useful prognostic marker independent of neurohumoral factors, suggesting that immune activation and/or apoptosis play a significant role in the pathogenesis of CHF.

Age Factors↗

PubMed2001

Comparison of mechanical properties of polyvinylidene fluoride and polypropylene monofilament sutures used for flexor tendon repair.

We performed an experimental study to evaluate the mechanical properties of polyvinylidene fluoride sutures and to compare their use with that of standard polypropylene sutures for the circumferential, epitendinous suture of a flexor tendon repair. Polyvinylidene fluoride sutures had a smaller suture diameter, a greater knot pull strength and less delayed extension when under creep testing, than polypropylene sutures. Tendons repaired using polyvinylidene fluoride sutures had significantly greater gap and breaking strengths than those repaired using polypropylene sutures.

Animals↗

PubMed2001

Comparison of postoperative early active mobilization and immobilization in vivo utilising a four-strand flexor tendon repair.

We evaluated a technique of four-strand double-modified locking Kessler flexor tendon repair in healing tendons. Seventy-two canine flexor digitorum profundus tendons in Zone 2 were repaired and evaluated following either active mobilization or immobilization at 0, 7, 14, 28 and 42 days after surgery. Fifty-six tendons were examined for gap and ultimate strength using a tensile testing machine and 16 were evaluated with standard hematoxylin and eosin, and Masson's trichrome staining. All tendons healed without rupture or gap formation of more than 1 mm, thus demonstrating that this repair technique has enough tensile strength to withstand early active mobilization. The gap and ultimate strength of actively mobilized tendons did not decrease significantly during the first 7 days, and were significantly greater than those of immobilized tendons throughout the 42-day study period. Actively mobilized tendons healed without the extrinsic adhesions and large tendon calluses that were found in immobilized tendons.

Animals↗

PubMed2001

Taste-enhancing effects of glycine on the sweetness of glucose: a gustatory aspect of symbiosis between the ant, Camponotus japonicus, and the larvae of the lycaenid butterfly, Niphanda fusca.

The lycaenid butterfly, Niphanda fusca, has a parasitic relationship with its host ant, Camponotus japonicus: the caterpillars may use chemical mimicry to enter the ant nest where they are fed mouth-to-mouth by the adult ants until pupation. Nevertheless, larvae offer their host ants a nutritious secretion that contains 160 mM glucose and 43 mM glycine. Using glucose and glycine mixture as artificial secretions, we investigated the gustatory effect of glucose and/or glycine on the ants. Glycine induced neither feeding behavior nor gustatory response in the ants if its concentration was <500 mM. In the presence of glycine at the concentration in the secretion, however, the ants improved their preference to glucose, and the sugar receptor cell exhibited electrophysiological enhancement of response to glucose in a glycine-concentration-dependent manner. By adding glycine to glucose in their secretions, therefore, the butterfly larvae can manipulate the gustatory sense of the ants. The alluring taste of 'glycine-flavored glucose' could motivate the host ants to feed the larvae and thereby receive the secretions as a reward. The taste enhancement created by the combination of sugar and amino acid may play a role in the evolution of the parasitic relationships of these insects. The taste-enhancing effect appears to be analogous to taste enhancement by 'umami' substances in humans.

Amino Acids↗

PubMed2001

Angiotensin(1-7) potentiates bradykinin-induced vasodilatation in man.

BACKGROUND: It has been clearly demonstrated that angiotensin(1-7) potentiates the vasodilating effect of bradykinin in isolated vessels of animals. OBJECTIVE: To investigate the interaction between angiotensin(1-7) Ang(1-7) and bradykinin in human forearm resistant vessels of normotensive healthy men in vivo, by the measurement of forearm blood flow using venous occlusion, strain-gauge plethysmography with intra-arterial infusions of peptides in a placebo-controlled, double-blind, cross-over design. METHODS: In eight men, bradykinin was infused intra-arterially twice; placebo, Ang(1-7), or angiotensin II was co-infused with the second infusion. The effect of inhibition of nitric oxide synthase on the interaction between Ang(1-7) and bradykinin was also tested in eight other individuals. The effects of Ang(1-7) were analyzed by analysis of variance (ANOVA) and by the ratios of individually derived areas under the dose-response curves (AUC) of bradykinin, adjusted for changes in the AUCs by repeated infusions of bradykinin with placebo. RESULTS: Ang(1-7) (1000 pmol/min) significantly potentiated the vasodilating effect of bradykinin compared with the effect of saline (P = 0.0471, ANOVA) and in a dose-dependent manner (adjusted AUC ratio [95% confidence interval (CI)] 2.75 (1.72 to 3.78) with 1000 pmol/min, 1.62 (1.31 to 1.93) with 100 pmol/min, and 0.98 (0.80, to 1.09) with 10 pmol/min). This effect was completely abolished by co-infusion of NG-monomethyl-l-arginine [AUC ratio 0.98 (0.90 to 1.04)]. Ang(1-7) did not affect the vasodilating effects of either acetylcholine or sodium nitroprusside. CONCLUSIONS: Ang(1-7) potentiates the vasodilating effect of bradykinin, possibly through a mechanism(s) involving nitric oxide release, in human forearm resistance vessels.

Adult↗

PubMed2001

Induction of monocyte chemoattractant protein 1 by Helicobacter pylori involves NF-kappaB.

Helicobacter pylori stimulates secretion of monocyte chemoattractant protein 1 (MCP-1) from gastric epithelial cells. Secretion of this chemokine may be instrumental in monocyte infiltration of the gastric epithelium that characterizes H. pylori gastritis. The aim of this study was to identify the mechanism by which H. pylori induces MCP-1 production. Induction of MCP-1 mRNA was assessed by reverse transcription-PCR. We used luciferase reporter assays to monitor activation of the MCP-1 gene promoter and electrophoretic mobility shift assays to explore binding of transcription factors to this promoter. H. pylori infection increased MCP-1 mRNA expression from gastric epithelial cells. Induction of MCP-1 mRNA relies on an intact cag pathogenicity island. We identified two closely spaced NF-kappaB-binding sites within the MCP-1 distal enhancer as required for H. pylori-induced MCP-1 gene transcription. H. pylori infection led to the specific activation of NF-kappaB complexes containing p50 and p65. Kinase-deficient mutants of NF-kappaB-inducing kinase (NIK) and IkappaB kinases (IKK) caused suppression of MCP-1 distal enhancer-dependent reporter activity following H. pylori infection. H. pylori infection induces the activation of NF-kappaB via the NIK-IKK signaling complex, leading to MCP-1 gene transcription in gastric epithelial cells.

Chemokine CCL2↗

PubMed2001

Escherichia coli ribosome-associated protein SRA, whose copy number increases during stationary phase.

Protein D has previously been demonstrated to be associated with Escherichia coli ribosomes by the radical-free and highly reducing method of two-dimensional polyacrylamide gel electrophoresis. In this study, we show that protein D is exclusively present in the 30S ribosomal subunit and that its gene is located at 33.6 min on the E. coli genetic map, between ompC and sfcA. The gene consists of 45 codons, coding for a protein of 5,096 Da. The copy number of protein D per ribosomal particle varied during growth and increased from 0.1 in the exponential phase to 0.4 in the stationary phase. For these reasons, protein D was named SRA (stationary-phase-induced ribosome-associated) protein and its gene was named sra. The amount of SRA protein within the cell was found to be controlled mainly at the transcriptional level: its transcription increased rapidly upon entry into the stationary phase and was partly dependent on an alternative sigma factor (sigma S). In addition, global regulators, such as factor inversion stimulation (FIS), integration host factor (IHF), cyclic AMP, and ppGpp, were found to play a role either directly or indirectly in the transcription of sra in the stationary phase.

Amino Acid Sequence↗

PubMed2001

Expression of human beta-defensin 2 (hBD-2) in Helicobacter pylori induced gastritis: antibacterial effect of hBD-2 against Helicobacter pylori.

BACKGROUND: Human beta-defensin 2 (hBD-2) plays a role in the innate defence system at mucosal surfaces. Colonisation of Helicobacter pylori in the stomach is an important pathological factor in gastrointestinal illnesses, including gastritis, peptic ulcer, and gastric adenocarcinoma. AIMS: To evaluate the antibacterial role of hBD-2 against H pylori infection in the gastric mucosa. SUBJECTS: Biopsied gastric mucosa specimens from H pylori positive (n=6) and H pylori negative (n=6) individuals were used. H pylori was determined by the presence of urease activity and microscopic examination. METHODS: The specimens were examined for hBD-2 expression by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and in situ hybridisation. The antibacterial effect of hBD-2 against H pylori was evaluated by the number of colony forming units of H pylori after incubation with 0, 10(-9), 10(-8), 10(-7), 10(-6), or 10(-5) M of hBD-2 peptide. RESULTS: All six H pylori positive specimens expressed a high level of hBD-2 mRNA while hBD-2 mRNA was not detected in the H pylori negative specimens by RT-PCR. Immunohistochemistry using anti-hBD-2 antiserum revealed that hBD-2 was expressed in the surface epithelium of H pylori infected specimens. In gastric specimens obtained after H pylori eradication, hBD-2 immunoreactivity had dramatically decreased. In situ hybridisation confirmed that hBD-2 transcripts were localised in the epithelium of H pylori infected gastric specimens. Incubation with hBD-2 reduced the growth rate of cultured H pylori in a dose dependent manner, and incubation with 10(-5) M hBD-2 completely inhibited the proliferation of H pylori. CONCLUSIONS: H pylori infection induces hBD-2 expression in the human gastric epithelium. hBD-2 inhibited the growth of H pylori in vitro, suggesting that hBD-2 plays an antibacterial role in H pylori induced gastritis.

Aged↗

PubMed2001

Dynamin is involved in human epithelial cell vacuolation caused by the Helicobacter pylori-produced cytotoxin VacA.

The Helicobacter pylori-produced cytotoxin VacA induces intracellular vacuolation. To elucidate the molecular mechanism of vacuole formation by VacA, we examined the participation of dynamin, a GTPase functioning in intracellular vesicle formation, in human HeLa cells. Immunocytochemistry revealed that endogenous dynamin was localized to vacuoles induced by VacA. In cells transiently transfected with a GTPase-defective (dominant-negative) dynamin mutant, VacA failed to induce vacuolation. In contrast, VacA did induce vacuolation in cells transiently transfected with wild-type dynamin. Furthermore, under VacA treatment, neutral red dye uptake, a parameter of VacA-induced vacuolation, was inhibited in cells stably transfected with the dominant-negative dynamin mutant. In contrast, uptake was markedly enhanced in cells stably transfected with wild-type dynamin. Moreover, VacA cytopathic effects on the viability of HeLa cells were inhibited in cells stably transfected with dominant-negative dynamin-1. Sequential immunocytochemical observation confirmed that expression of dominant-negative dynamin did not affect VacA attachment to or internalization into HeLa cells. We suggest that dynamin is involved in the intracellular vacuolation induced by VacA.

Bacterial Proteins↗