Biomedical subjects

A Taguchi

Publications and source records attributed to A Taguchi.

At least 37 records · Page 2Linked to original sources

PubMed2000

Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases.

The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development and inflammation, and certain diseases such as diabetes and Alzheimer's disease. Engagement of RAGE by a ligand triggers activation of key cell signalling pathways, such as p21ras, MAP kinases, NF-kappaB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin, a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumours and tumours developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44/p42, p38 and SAP/JNK MAP kinases; molecular effector mechanisms importantly linked to tumour proliferation, invasion and expression of matrix metalloproteinases.

Animals↗

PubMed2000

Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome.

INTRODUCTION: Brugada syndrome is characterized by an ST segment elevation in leads V1-V3 and a high incidence of ventricular fibrillation (VF). A mutation in a cardiac Na+ channel gene, SCN5A, has been linked to Brugada syndrome, and sodium channel blockers have been shown to be effective in unmasking the syndrome when concealed. The aim of this study was to examine the effects of Na+ channel blockers on ST segment elevation, QRS, corrected QT (QTc) interval, and ventricular arrhythmias in patients with Brugada syndrome. METHODS AND RESULTS: We examined the effects of three different Na+ channel blockers (flecainide, disopyramide, and mexiletine) on the amplitude of the ST segment 20 msec after the end of QRS (ST20), QRS duration, QTc interval measured from 12-lead ECG, and ventricular arrhythmias in 12 Brugada and 10 control patients. Maximum ST20 observed in the V2 or V3 leads under baseline conditions was greater in the Brugada patients than in control patients, whereas QRS duration and maximum QTc interval were no different between the two groups. Flecainide and disopyramide, but not mexiletine, significantly increased maximum ST20 and QRS duration in both groups, although these effects were much more pronounced in the Brugada patients. The increases in ST20 and QRS duration with flecainide were significantly larger than those with disopyramide. An increase of 0.15 mV in ST20 with flecainide separated the two groups without overlap. Ventricular premature complexes developed only with flecainide in Brugada patients (3/12) displaying a marked ST elevation but not widening of QRS. CONCLUSION: Our findings suggest that Na+ channel blockers amplify existing I(Na) and possibly other ion channel defects, with a potency inversely proportional to the rate of dissociation of the drug from the Na+ channel, thus causing a prominent elevation of the ST segment and, in some cases, prolongation of QRS duration in patients with Brugada syndrome.

Adult↗

PubMed2000

RAGE: a multiligand receptor contributing to the cellular response in diabetic vasculopathy and inflammation.

RAGE is a multiligand member of the immunoglobulin superfamily of cell surface molecules whose properties extend the paradigm of ligand-receptor interactions. The receptor recognizes families of ligands with diverse structural features, such as advanced glycation endproducts (AGEs), amyloidogenic peptides/polypeptides, amphoterins, and S100/calgranulins rather than individual species. Engagement of RAGE by its ligands upregulates the receptor and initiates a cycle of sustained cellular perturbation; increased levels of RAGE on the cell surface make it an ideal target for subsequent ligand interactions and for propagating cellular dysfunction. At this time, the only means known to break this apparently vicious cycle appears to be blocking access to RAGE or removing the ligands. Taken together, these data suggest that RAGE has the potential to function as a progression factor in a range of disorders (AGEs are relevant to diabetes and other settings of oxidant stress, amyloidogenic peptides are relevant to amyloidoses, S100/calgranulins are relevant to inflammatory disorders, etc.) in which its ligands accumulate. The chronic juxtaposition of ligand and receptor triggers sustained cellular perturbation favoring mechanisms eventuating in tissue injury rather than those that would restore homeostasis.

Animals↗

PubMed2000

Case-control study on self-reported osteoporotic fractures and mandibular cortical bone.

OBJECTIVES: The purpose of this case-control study was to determine whether the radiographic appearance of the mandibular cortical bone in patients who were elderly and noninstitutionalized was related to a self-reported history of osteoporotic fractures. STUDY DESIGN: Patients who had a billing statement at the School of Dentistry dated between 1993 and 1996, who were older than 60, and who had a panoramic radiograph were invited to be interviewed regarding fracture history (circumstances and year of fracture) and risk factors for osteoporosis. Cases (n = 93) were individuals reporting osteoporotic fractures (fractures occurring after minor impact). Controls (n = 394) were individuals reporting traumatic fractures (n = 105) or no fractures (n = 289). Blinded to case-control status, we evaluated the mandibular cortex on a panoramic radiograph and classified them as normal (even and sharp endosteal margin), moderately eroded (evidence of lacunar resorption or endosteal cortical residues), or severely eroded (unequivocal porosity). In addition, cortical thickness was measured below the mental foramen. RESULTS: After adjustment for potentially confounding factors, the odds ratio for an osteoporotic fracture associated with moderately eroded and severely eroded mandibular cortices was 2.0 (95% CI, 1.2 to 3.3) and 8.0 (95% CI, 2.0 to 28.9), respectively. After adjusting for all potentially confounding factors, we found that the cortex was 0.54 mm (or 12%) thinner in subjects with an osteoporotic fracture compared with controls (95% CI, 0.25 to 0.84 mm). CONCLUSIONS: Subjects with a self-reported history of osteoporotic fractures tend to have increased resorption and thinning of the mandibular lower cortex.

Aged↗

PubMed2000

Mutations modulating the Argos-regulated signaling pathway in Drosophila eye development.

Argos is a secreted protein that contains an EGF-like domain and acts as an inhibitor of Drosophila EGF receptor activation. To identify genes that function in the Argos-regulated signaling pathway, we performed a genetic screen for enhancers and suppressors of the eye phenotype caused by the overexpression of argos. As a result, new alleles of known genes encoding components of the EGF receptor pathway, such as Star, sprouty, bulge, and clown, were isolated. To study the role of clown in development, we examined the eye and wing phenotypes of the clown mutants in detail. In the eye discs of clown mutants, the pattern of neuronal differentiation was impaired, showing a phenotype similar to those caused by a gain-of-function EGF receptor mutation and overexpression of secreted Spitz, an activating ligand for the EGF receptor. There was also an increased number of pigment cells in the clown eyes. Epistatic analysis placed clown between argos and Ras1. In addition, we found that clown negatively regulated the development of wing veins. These results suggest that the clown gene product is important for the Argos-mediated inhibition of EGF receptor activation during the development of various tissues. In addition to the known genes, we identified six mutations of novel genes. Genetic characterization of these mutants suggested that they have distinct roles in cell differentiation and/or survival regulated by the EGF receptor pathway.

Animals↗

PubMed2000

Temperature monitoring and management during neuraxial anesthesia: an observational study.

UNLABELLED: Temperature monitoring and thermal management are rare during spinal or epidural anesthesia because clinicians apparently restrict monitoring to patients with an expected risk of hypothermia. This implies that anesthesiologists can predict patient thermal status without monitoring core temperature. We therefore, tested the hypotheses that during neuraxial anesthesia: 1) amount of core hypothermia depends on the magnitude and duration of surgery; 2) temperature monitoring and thermal management are used selectively in patients at high risk of hypothermia; and 3) anesthesiologists can estimate patient thermal status. We evaluated thermal status on arrival in the recovery room along with intraoperative thermal management and monitoring in 120 patients. Anesthesiologists were asked if their patients were hypothermic (<36 degrees C). There was no correlation between the magnitude or duration of surgery and initial postoperative core temperature in unwarmed patients. Temperature monitoring and thermal management were not used selectively in high-risk patients. Initial postoperative tympanic membrane temperatures were <36 degrees C in 77% of patients and <35 degrees C in 22%. Body temperature was monitored intraoperatively in 27% of the patients and forced-air warming was used in 31%. Anesthesiologists failed to accurately estimate whether their patients were hypothermic. Our results suggest that temperature monitoring and management during neuraxial anesthesia is currently inadequate. IMPLICATIONS: In this observational study, we evaluated core temperatures and intraoperative thermal management in patients undergoing spinal or epidural anesthesia. Hypothermia was common, however, rarely detected either by temperature monitoring or estimates by anesthesiologists. In addition, it was not treated with active warming. Consequently, temperature monitoring and management have to be done during neuraxial anesthesia.

Aged↗

PubMed2000

Clinical characteristics of patients with spontaneous or inducible ventricular fibrillation without apparent heart disease presenting with J wave and ST segment elevation in inferior leads.

INTRODUCTION: The clinical characteristics of three patients with spontaneous or inducible ventricular fibrillation (VF) without apparent heart disease, who presented with J wave and ST segment elevation in inferior leads, are described. METHODS AND RESULTS: All patients were male and experienced syncope. Their symptoms occurred at night or early in the morning. Holter ECG revealed infrequent premature ventricular complexes. Injection with disopyramide 2 mg/kg augmented ST segment elevation. CONCLUSION: These characteristics were very similar to those of patients with Brugada syndrome. These three patients with these specific features might have a variant of Brugada syndrome.

Adult↗

PubMed2000

Recovery time dispersion measured from 87-lead body surface potential mapping as a predictor of sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy.

INTRODUCTION: The clinical usefulness of QT dispersion in 12-lead ECG has been controversial in identifying subjects at risk for sustained ventricular tachycardia (VT) in patients with idiopathic dilated cardiomyopathy (DCM). We hypothesized that increasing the spatial resolution of the ECG improves the accuracy of risk stratification. The purpose of this study was to test the ability of recovery time dispersion measured from 87-lead body surface potential mapping (BSPM) to identify patients at risk for sustained VT in idiopathic DCM. METHODS AND RESULTS: We obtained 87-lead BSPM and 12-lead ECG in 33 patients with idiopathic DCM (15 patients with a history of sustained VT [VT(+) group] and 18 patients without a history of sustained VT [VT(-) group]) and in 20 normal control subjects. We measured the corrected QT dispersion and corrected recovery time dispersion from 12-lead ECG (QTc-12 dispersion and RTc-12 dispersion, respectively) and 87-lead BSPM (QTc-87 dispersion and RTc-87 dispersion, respectively). Signal-averaged ECG also was recorded in 25 patients. Neither the QTc-12 nor QTc-87 dispersion discriminated between the VT(+) and VT(-) groups patients. The VT(+) group patients had a larger but insignificant RTc-12 dispersion than the VT(-) group patients. In contrast, the RTc-87 dispersion was significantly larger in the VT(+) group patients than in the VT(-) group patients (236 +/- 39 msec vs 184 +/- 28 msec, P < 0.001). Receiver operating curve analysis indicated that the RTc-87 dispersion was as good as late potentials in predicting susceptibility to sustained VT; its sensitivity, specificity, and negative predictive value were 73%, 76%, and 76%, respectively (cutoff value 200 msec). RTc-87 dispersion >200 msec combined with positive late potentials provide high sensitivity (92%) and high negative predictive value (88%) for sustained VT. CONCLUSION: The RTc-87 dispersion is a useful tool to identify subjects at risk for sustained VT in patients with idiopathic DCM.

Body Surface Potential Mapping↗

PubMed2000

Body surface distribution and response to drugs of ST segment elevation in Brugada syndrome: clinical implication of eighty-seven-lead body surface potential mapping and its application to twelve-lead electrocardiograms.

INTRODUCTION: Body surface distribution and magnitude of ST segment elevation and their reflection in 12-lead ECGs have not been clarified in Brugada syndrome. METHODS AND RESULTS: Eighty-seven-lead body surface potential mapping and 12-lead ECGs were recorded simultaneously in 25 patients with Brugada syndrome and 40 control patients. The amplitude of the ST segment 20 msec after the end of QRS (ST20) was measured from all 87 leads, and an ST isopotential map was constructed. The maximum ST elevation (maxST20) was distributed in an area of the right ventricular outflow tract in all Brugada patients, and it was larger than that in control patients (0.37 +/- 0.13 vs 0.12 +/- 0.04 mV; P < 0.0005). The maximum was observed on the level of the parasternal fourth intercostal space, on which the V1 and V2 leads of the standard 12-lead ECG were located, in 18 of the 25 Brugada patients in whom typical coved- or saddleback-type ST elevation was seen in leads V1 and V2. The maximum was located on the second intercostal space in the remaining seven Brugada patients in whom only a mild saddleback-type ST elevation was seen in leads V1 and V2 of the 12-lead ECG. Typical ST segment elevation was recognized in leads V1 and V2, which were recorded on the second or third intercostal space. ST elevation in Brugada patients was dramatically normalized by isoproterenol, a beta-adrenergic agonist (maxST20 = 0.17 +/- 0.08 mV; P < 0.0005 vs control conditions), and accentuated by disopyramide, an Na+ channel blocker (maxST20 = 0.50 +/- 0.15 mV; P < 0.0005 vs control conditions), without any change in the location of the maxST20. CONCLUSION: Our data indicate that recordings of leads V1-V3 of the 12-lead ECG on the parasternal second or third intercostal space would be helpful in diagnosing suspected patients with Brugada syndrome. The data suggest that Na+ channel blockers are capable of accentuating ST elevation in leads V1-V3.

Action Potentials↗

PubMed2000

Intracoronary positive and negative contrast jets at a 'napkin ring' coronary stenosis: a case report.

A very short coronary stenosis is somewhat difficult to correctly evaluate by conventional coronary angiography. The demonstration of positive and negative contrast jets observed just distal to the lesion is helpful in identifying the severity of the disease causing this disorder. In the present case, intravascular ultrasound confirmed the presence of a very short stenosis and membranous disease at the site of the lesion. The presence of intracoronary contrast jets reflects the morphology and severity of disease of the membranous type, although the reason for the appearance of contrast jets with this type of lesion should be sought.

Contrast Media↗

PubMed1999

N(epsilon)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression.

Recent studies suggested that interruption of the interaction of advanced glycation end products (AGEs), with the signal-transducing receptor receptor for AGE (RAGE), by administration of the soluble, extracellular ligand-binding domain of RAGE, reversed vascular hyperpermeability and suppressed accelerated atherosclerosis in diabetic rodents. Since the precise molecular target of soluble RAGE in those settings was not elucidated, we tested the hypothesis that predominant specific AGEs within the tissues in disorders such as diabetes and renal failure, N(epsilon)-(carboxymethyl)lysine (CML) adducts, are ligands of RAGE. We demonstrate here that physiologically relevant CML modifications of proteins engage cellular RAGE, thereby activating key cell signaling pathways such as NF-kappaB and modulating gene expression. Thus, CML-RAGE interaction triggers processes intimately linked to accelerated vascular and inflammatory complications that typify disorders in which inflammation is an established component.

Animals↗

PubMed1999

Cloning, sequencing, and characterization of ribosomal protein and RNA polymerase genes from the region analogous to the alpha-operon of escherichia coli in halophilic archaea, halobacterium halobium.

A determination was made of the nucleotide sequence of the 3215-bp region of a ribosomal protein gene cluster (HS13, HS4, HS11, and HeL18), RNA polymerase (RNA poly D), and tRNA genes (tRNAser and tRNAarg) of halophilic Archaea Halobacterium halobium, which is analogous to the alpha-operon of Escherichia coli (tRNAser-HS13-HS4-HS11-RNA poly D-tRNAarg-HeL18). The seven-gene string was preceded by a pseudoknot-like structure similar to the proposed S4 ribosomal protein binding site of the alpha-operon mRNA leader in E. coli. Using an inducible expression system H. halobium HS4 was produced in large amounts in E. coli, and immunoblot analysis showed the S4 to constitute a 21-kDa polypeptide component of the ribosome. Analysis of the deduced amino acids sequence revealed that the HS13, HS4, and HS11 sequences including the RNA polymerase subunit are more similar to their eukaryotic than to their bacterial counterparts. HeL18, located downstream of the gene cluster analogous to the E. coli alpha-operon (S13-S11-S4-RNA poly D-L17), was similar to both the eukaryotic (eL18) and eubacterial ribosomal protein L15 located in the spc-operon, but not to L17 positioned as the terminal gene of the bacterial alpha-operon.

Amino Acid Sequence↗

PubMed1999

RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides.

S100/calgranulin polypeptides are present at sites of inflammation, likely released by inflammatory cells targeted to such loci by a range of environmental cues. We report here that receptor for AGE (RAGE) is a central cell surface receptor for EN-RAGE (extracellular newly identified RAGE-binding protein) and related members of the S100/calgranulin superfamily. Interaction of EN-RAGEs with cellular RAGE on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Blockade of EN-RAGE/RAGE quenches delayed-type hypersensitivity and inflammatory colitis in murine models by arresting activation of central signaling pathways and expression of inflammatory gene mediators. These data highlight a novel paradigm in inflammation and identify roles for EN-RAGEs and RAGE in chronic cellular activation and tissue injury.

Amino Acid Sequence↗

PubMed1999

Ectopic expression of constitutively activated Ral GTPase inhibits cell shape changes during Drosophila eye development.

The small GTP-binding protein Ral is activated by RalGDS, one of the effector molecules for Ras. Active Ral binds to a GTPase activating protein for CDC42 and Rac. Although previous studies suggest a role for Ral in the regulation of CDC42 and Rac, which are involved in arranging the cytoskeleton, its in vivo function is largely unknown. To examine the effect of overexpressing Ral on development, transgenic Drosophila were generated that overexpress wild-type or mutated Ral during eye development. While wild-type Ral caused no developmental defects, expression of a constitutively activated protein resulted in a rough eye phenotype. Activated Ral did not affect cell fate determination in the larval eye discs but caused severe disruption of the ommatidial organization later in pupal development. Phalloidin staining showed that activated Ral perturbed the cytoskeletal structure and cell shape changes during pupal development. This phenotype is similar to that caused by RhoA overexpression. In addition, the phenotype was synergistically enhanced by the coexpression of RhoA. These results suggest that Ral functions to control the cytoskeletal structure required for cell shape changes during Drosophila development.

Animals↗

PubMed1999

Crystal structure of the E166A mutant of extended-spectrum beta-lactamase Toho-1 at 1.8 A resolution.

Bacterial resistance to beta-lactams is mainly due to the production of beta-lactamase. Especially through the production of extended-spectrum beta-lactamases (ESBLs), bacteria have acquired resistance not only to penicillins, but also to expanded-spectrum cephems. Here, we describe the crystal structure of the E166A mutant of class A beta-lactamase Toho-1 at 1.8 A resolution, the first reported tertiary structure of an ESBL. Instead of the wild-type enzyme, a mutant Toho-1, in which Glu166 was replaced with alanine, was used for this study, because of the strong tendency of the wild-type enzyme to form twinned crystals. The overall structure of Toho-1 is similar to the crystal structures of non-ESBLs, with no pronounced backbone rearrangement of the framework. However, there are some notable local changes. First, a difference in the disposition of an arginine residue, which is at position 244 in non-ESBLs but at position 276 in Toho-1 and other ESBLs, was revealed and the role of this arginine residue is discussed. Moreover, changes in the hydrogen-bonding pattern and in the formation of the hydrophobic core were also observed near the Omega loop. In particular, the lack of hydrogen bonds in the vicinity of the Omega loop could be a cause of the extended substrate specificity of Toho-1. Through the generation of a model for the enzyme-substrate complex, a conformational change of Toho-1 occurring on complex formation is discussed based on the active-site cleft structure and the substrate profile.

Amino Acid Sequence↗

PubMed1999

Relationship between bone mineral density and tooth loss in elderly Japanese women.

OBJECTIVE: To evaluate the relationship between vertebral bone mass and tooth loss and jaw bone mass in elderly Japanese women. METHODS: Mandibular cortical bone mass, alveolar bone height and number of teeth present (total, anterior, and posterior) were compared with the 3rd lumbar vertebral bone mineral density (L3BMD), measured by dual energy computed tomography (DEQCT), in 90 Japanese women by means of multiple regression analysis, controlling for body mass index, menopausal status, years since menopause and self-reported periodontal condition. RESULTS: Mandibular cortical bone mass and number of posterior teeth were associated with both alveolar bone height and L3BMD, but there was no association between alveolar bone height, number of anterior teeth present and L3BMD. CONCLUSION: Our results suggest that the loss of posterior teeth may be associated with a decrease not only in alveolar bone height, but also alveolar bone mineral density (BMD). The latter may be related to a decrease of lumbar vertebral BMD.

Adult↗

PubMed1999

Molecular cloning of a novel member of the HSP110 family of genes, ischemia-responsive protein 94 kDa (irp94), expressed in rat brain after transient forebrain ischemia.

To identify genes induced by transient forebrain ischemia, we used the mRNA differential display technique in the four-vessel occlusion model in rats. Some genes were identified as candidates that encode ischemia-responsive protein, and one of them was cloned as ischemia-responsive protein 94 kDa (irp94) from the rat hippocampal cDNA library. Sequence analysis suggested that rat irp94 was a transcriptional variant or a homologue of mouse apg-2 and human heat shock protein (hsp) 70RY and a member of the HSP110 family, because IRP94 was >90% identical to APG-2 and HSP70RY and approximately 60% identical to the other members of the HSP110 family. Although irp94 mRNA was constitutively expressed in the normal hippocampus, it was clearly enhanced 4-24 h after ischemia for 10 (1.9-fold increase) and 15 min (3.4-fold increase). These changes mainly occurred in neuronal cells, as judged by the localization of irp94 mRNA using in situ hybridization histochemistry. On the other hand, hyperthermic stress did not enhance irp94 mRNA expression, suggesting that irp94 expression was enhanced under ischemic stress and not related to the heat shock signaling mechanism. Our study suggested that irp94, a novel member of the HSP110 family, might play an important role in the environment altering neuronal functions, especially after transient forebrain ischemia.

Animals↗

PubMed1999

The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome.

AIMS: Brugada syndrome is considered to be a distinctive subgroup of idiopathic ventricular fibrillation. Identification of the circadian pattern of ventricular fibrillation would contribute to the elucidation of its underlying pathophysiology, but this pattern remains unknown in patients with Brugada syndrome. METHODS: and Results A total of 12 consecutive Brugada syndrome patients (46+/-14 years, all male) who underwent implantation of an implantable cardioverter defibrillator were studied. The distribution of the time of ventricular fibrillation detection was examined and classified into four 6-hour time periods of the day. The mean follow-up period following implantation was 777+/-535 days. In six out of the 12 patients, ventricular fibrillation occurred during follow-up. The data logs revealed that ventricular fibrillation was detected 30 times (range, 3-9). Ventricular fibrillation was observed more frequently at night ( 1800 h to 0600 h) than in the day (0600 h to 1800 h) (93.3% [28/30] vs 6.7%[2/30], P<0.001), and during sleep than while awake (86.7% [26/30] vs 13.3%[4/30], P<0.001). Ventricular fibrillation occurred most frequently between midnight and 0600 h in patients with ventricular fibrillation episodes during sleep (76.9% [20/26] vs 23.1%[6/26], P<0.01). CONCLUSION: These results suggest that increased nocturnal vagal activity and withdrawal sympathetic activity may play an important role in the arrhythmogenesis of the Brugada syndrome.

Adult↗