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Biomedical subjects

A Wada

Publications and source records attributed to A Wada.

At least 109 records · Page 6Linked to original sources
PubMed2000

Significant roles of endothelin-A- and -B-receptors in renal function in congestive heart failure.

Endothelin-1 (ET-1) not only causes potent vasoconstriction but also leads to fluid retention, both actions mediated by ET(A)- and/or ET(B)-receptors. Selective ET(A)- and combined ET(A)/ET(B)-receptor antagonists improve hemodynamics in heart failure; however, it is also important to evaluate the effects of these antagonists on urine output in heart failure. We administered an acute dose of either the selective ET(A)-receptor antagonist FR139317 (FR, n=5, 1 and 3 mg/kg) or the mixed ET(A)/ET(B)-receptor antagonist TAK-044 (TAK, n = 5, 1 and 3 mg/kg) to dogs with heart failure induced by rapid ventricular pacing. Renal hemodynamic and tubular functions were subsequently investigated. FR increased urinary excretion in association with increased renal plasma flow (RPF) and glomerular filtration rate (GFR) with no significant changes in the fractional reabsorption of water distally (FRWD). In contrast, despite increased GFR, TAK did not alter urine volume or RPF with significantly increased FRWD. The increase of GFR and RPF induced by FR was significantly larger than that of TAK. These findings indicate that ET(B)-receptor activation may result in diuresis by renal vasodilatation and reduction of water reabsorption in the distal tubules and collecting ducts. Acute ET(A)-receptor antagonism may therefore be more beneficial to diuresis than dual ET(A)/ET(B)-receptor inhibition in heart failure.

Animals↗
PubMed2000

Chronic effects of an orally active selective endothelin-B-receptor antagonist in experimental congestive heart failure.

Endothelin-B- (ETB) receptors located in vascular beds mainly mediate vasorelaxation, however, long-term treatment with a mixed ETA/ETB receptor antagonist has been shown to improve the survival rate of rats with heart failure in a similar way to ETA-receptor inhibitors. The inhibition of ETB-receptor-mediated action should therefore be beneficial in preventing the deterioration seen in heart failure, despite various adverse hemodynamic effects. We administered K-8794 (Kowa Co. Ltd, Japan, 2mg/kg/day, n = 6), an orally active selective ETB-receptor antagonist, to dogs with heart failure induced by rapid right ventricular pacing for 14 days, commencing 8 days after pacing. Control dogs were given a placebo (n = 6). Mean arterial pressure decreased and systemic vascular resistance increased in both groups at the end of the protocol. In the K-8794 group, however, those values were higher than in the control group. Cardiac output decreased in both groups, but there were no significant differences observed between the two groups. Plasma renin activity and aldosterone increased in both groups at the end of the protocol, however levels in the K-8794 group were significantly lower than those in the control group. In the K-8794 group, it was quite interesting to note that Na excretion and urine flow rate were higher than in the control group. Our findings thus suggest that, although ETB-receptor antagonism produces some hemodynamic disadvantages, it can successfully prevent body fluid retention through the suppression the activation the renin-angiotensin-aldosterone system in dogs with heart failure.

Administration, Oral↗
PubMed2000

Molecular epidemiological investigation of enterohaemorrhagic Escherichia coli isolates in Japan.

We have established several measures for control and prevention of EHEC infection including designation of the disease as notifiable since there was the sudden increase in the incidence of infection with EHEC O157:H7 in Japan in 1996, involving multiple outbreaks. Improvements in methodologies for isolation of these organisms and enhanced laboratory screening have revealed a variety of sources in food and animals. Although there seems to be a bovine reservoir for O157 EHEC in Japan as well as North America and UK, different foods have been linked to EHEC infection including salads, radish sprouts and salmon roe. There is clear evidence that divergent clones of EHEC O157:H7 are prevalent throughout Japan based on laboratory surveillance, however, we still need to better define the role of EHEC serogroups other than Escherichia coli O157 as important causes of human infection.

Adolescent↗
PubMed2000

Sphingosine-1-phosphate inhibits haptotactic motility by overproduction of focal adhesion sites in B16 melanoma cells through EDG-induced activation of Rho.

We investigated the molecular mechanism by which Sph-1-P affects the FN-dependent haptotactic motility of serum-starved mouse melanoma B16/F10 cells. We found that EDG-5-induced Rho activation followed by enhanced tyrosine phosphorylation of FAK and paxillin, and beta 1-integrin activation leading to overexpression of focal adhesion sites, as well as increment of stress fiber formation, must be the molecular basis of inhibition of haptotactic cell motility by Sph-1-P.

3T3 Cells↗
PubMed2000

Contribution of natural amino acid substitutions in SHV extended-spectrum beta-lactamases to resistance against various beta-lactams.

SHV extended-spectrum beta-lactamases (ESBLs) arise through single amino acid substitutions in the parental enzyme, SHV-1. In order to evaluate the effect of genetic dissimilarities around the structural gene on MICs, we had previously devised an isogenic system of strains. Here, we present an extended version of the system that now allows assessment of all major types of SHV beta-lactamases as well as of two types of promoters of various strengths. Moreover, we devised a novel vector, pCCR9, to eliminate interference of the selection marker. A substitution within the signal sequence, I8F found in SHV-7, slightly increased MICs, suggesting more efficient transfer of enzyme precursor into the periplasmic space. We also noted that combination of G238S and E240K yielded higher resistance than G238S alone. However, the influence of the additional E240K change was more pronounced with ceftazidime and aztreonam than with cefotaxime and ceftriaxone. The SHV enzymes characterized by the single change, D179N, such as SHV-8, turned out to be the weakest SHV ESBLs. Only resistance to ceftazidime was moderately increased compared to SHV-1.

Amino Acid Substitution↗
PubMed2000

Cloning and sequencing of the gene encoding an aldehyde dehydrogenase that is induced by growing Alteromonas sp. Strain KE10 in a low concentration of organic nutrients.

The protein composition of Alteromonas sp. strain KE10 cultured at two different organic-nutrient concentrations was determined by using two-dimensional polyacrylamide gel electrophoresis. The cellular levels of three proteins, OlgA, -B, and -C, were considerably higher in cells grown in a low concentration of organic nutrient medium (LON medium; 0.2 mg of carbon per liter) than cells grown in a high concentration of organic nutrient medium (HON; 200 mg of C liter(-1)) or cells starved for organic nutrients. In the LON medium, the cellular levels of the Olg proteins were higher at the exponential growth phase than at the stationary growth phase. A sequence of the gene for OlgA revealed that the amino acid sequence had a high degree of similarity to the NAD(+)-dependent aldehyde dehydrogenases of several bacteria. OlgA, expressed in Escherichia coli, catalyzed the dehydrogenation of acetaldehyde, propionaldehyde, and butyraldehyde. The aldehyde dehydrogenase activity of KE10 was higher in cells growing exponentially in LON medium than in HON. OlgA may be involved in the growth under low-nutrient conditions. The physiological role of OlgA is discussed here.

Aldehyde Dehydrogenase↗
PubMed2000

Activation of intercellular adhesion molecule 1 expression by Helicobacter pylori is regulated by NF-kappaB in gastric epithelial cancer cells.

Interactions between leukocytes and epithelial cells may play a key role in Helicobacter pylori-associated gastric mucosal inflammation. This process is mediated by various cell adhesion molecules. The present study examined the molecular mechanisms leading to H. pylori-induced epithelial cell intercellular adhesion molecule-1 (ICAM-1; also called CD54) expression. Coculture of epithelial cells with cytotoxin-associated gene pathogenicity island-positive (cag PAI(+)) H. pylori strains, but not with a cag PAI(-) strain or H. pylori culture supernatants, resulted in upregulation of steady-state mRNA levels and cell surface expression of ICAM-1. Coculture with H. pylori induced an increase in luciferase activity in cells which were transfected with a luciferase reporter gene linked to the 5'-flanking region of the ICAM-1 gene. H. pylori activated the ICAM-1 promoter via the NF-kappaB binding site. An inducible nuclear protein complex bound to the ICAM-1 NF-kappaB site and was identified as the NF-kappaB p50-p65 heterodimer. H. pylori induced the degradation of IkappaB-alpha, a major cytoplasmic inhibitor of NF-kappaB, and stimulated the expression of IkappaB-alpha mRNA. Pretreatment of epithelial cells with pyrrolidine dithiocarbamate, which blocks NF-kappaB activation, inhibited H. pylori-induced ICAM-1 expression. THP-1 macrophagic cells, peripheral blood mononuclear cells, and purified neutrophils adhered to H. pylori-infected epithelial cells to a greater extent than to uninfected cells. These results show that H. pylori directly induces expression of ICAM-1 on gastric epithelial cells in an NF-kappaB-dependent manner that may support leukocyte attachment during inflammation.

Antineoplastic Agents↗
PubMed2000

Growth phase-coupled changes of the ribosome profile in natural isolates and laboratory strains of Escherichia coli.

The growth phase-dependent change in sucrose density gradient centrifugation patterns of ribosomes was analyzed for both laboratory strains of Escherichia coli and natural isolates from the ECOR collection. All of the natural isolates examined formed 100S ribosome dimers in the stationary phase, and ribosome modulation factor (RMF) was associated with the ribosome dimers in the ECOR strains as in the laboratory strain W3110. The ribosome profile (70S monomers versus 100S dimers) follows a defined pattern over time during lengthy culture in both the laboratory strains and natural isolates. There are four discrete stages: (i) formation of 100S dimers in the early stationary phase; (ii) transient decrease in the dimer level; (iii) return of dimers to the maximum level; and (iv) dissociation of 100S dimers into 70S ribosomes, which are quickly degraded into subassemblies. The total time for this cycle of ribosome profile change, however, varied from strain to strain, resulting in apparent differences in the ribosome profiles when observed at a fixed time point. A correlation was noted in all strains between the decay of 100S ribosomes and the subsequent loss of cell viability. Two types of E. coli mutants defective in ribosome dimerization were identified, both of which were unable to survive for a prolonged period in stationary phase. The W3110 mutant, with a disrupted rmf gene, has a defect in ribosome dimerization because of lack of RMF, while strain Q13 is unable to form ribosome dimers due to a ribosomal defect in binding RMF.

Escherichia coli↗
PubMed2000

Insufficient secretion of atrial natriuretic peptide at acute phase of myocardial infarction.

To investigate the secretion of the plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction (AMI), we evaluated the relationship between plasma levels of ANP and pulmonary capillary wedge pressure (PCWP) in 45 consecutive patients during the acute phase of AMI ( approximately 12 h after the attack) (group 1) and compared data with those obtained after 1 mo (group 2). In both groups 1 and 2, plasma ANP levels significantly correlated with PCWP. The slope of the linear regression line between the PCWP and ANP in group 1 was significantly lower, by about one-third, than that in group 2. In addition, we examined changes in ANP levels and left ventricular end-diastolic pressure (LVEDP) over 180 min after AMI induced by injection of microspheres into the left coronary arteries of three dogs. The LVEDP and ANP levels 30 min after AMI were significantly higher than those before; however, despite the persistent high LVEDP during the 180 min after AMI, ANP levels decreased gradually and significantly to 63% of the peak level at 150 min. These findings suggest that the secretion of ANP during the acute phase of myocardial infarction may be insufficient relative to the chronic phase.

Acute Disease↗
PubMed2000

Arrhythmogenic right ventricular cardiomyopathy with an initial manifestation of severe left ventricular impairment and normal contraction of the right ventricle.

A case of arrhythmogenic right ventricular cardiomyopathy (ARVC) with an initial manifestation of severe impairment of the left ventricle (LV) and normal contraction of the right ventricle (RV) is presented. A 43-year-old man was admitted to hospital because of congestive heart failure following a common cold. The LV function was diffusely and severely hypokinetic. Coronary arteriogram revealed normal vessels. An endomyocardial biopsy specimen obtained from the RV septum revealed mild infiltration of lymphocytes with focal myocytes necrosis and so healing myocarditis was suspected. The specimen did not include any fatty replacement of myocytes. Since then, the patient suffered from recurrent congestive heart failure as well as nonsustained ventricular tachycardia and required frequent hospitalization. Progressive impairment, dilation, and thinning of both ventricles were observed on serial echocardiographic examinations. Although the RV gradually enlarged and became impaired, severe dilatation and impairment of the LV has always been predominant in the patient's clinical course. After medical follow-up for 10 years, he died suddenly of ventricular fibrillation and pump failure. The autopsy revealed extensive fibrofatty replacement of myocytes in both the ventricles, extending from the outer layer to the inner layer of myocardium in the RV and to the middle layer in the LV. These features were compatible with arrhythmogenic right ventricular cardiomyopathy or perimyocarditis, although only the rightsided bundle of the interventricular septum was completely replaced by fatty tissue, which can not be explained as a sequel of perimyocarditis. Moreover, apoptosis was present in the myocyte nuclei of the myocardial layers bordering the area of fatty replacement. Therefore, myocarditis may have triggered or accelerated the process of apoptosis leading to ARVC.

Adult↗
PubMed2000

Establishment and characterization of the MSKR inbred strain originated from Japanese wild mice (Mus musculus molossinus).

A new inbred strain, MSKR, originated from Japanese wild mice was established in April, 1998. The MSKR mice were 60% of the C57BL/6N inbred mice in the 60-day body weight. Tail length/head-body length and hind-foot length/head-body length of the MSKR mice were significantly smaller than those of the C57BL/6N mice (0.896 vs 1.061, 0.189 vs 0.204), but ear length/head-body length of the MSKR mice was significantly larger than that of the C57BL/6N mice (0.143 vs 0.137). The age of the first parturition and size of the first litter were 63.20 +/- 2.71 days and 6.20 +/- 0.37, respectively, at the 20th and 22nd inbreeding generations. Genetic characterization of the MSKR strain was performed using 34 microsatellite markers, 29 biochemical markers, 9 immunogenetic markers, 3 coat color markers, and mitochondrial DNA RFLP-haplotypes. The result indicated that this newly established inbred strain has some different gene constitution from already known molossinus and common laboratory strains.

Animals↗
PubMed2000

Unmyelinated nerve fiber analysis of the human oculomotor nerve.

Unmyelinated nerve fibers of the oculomotor nerve have occasionally been observed in experimental animals with the use of electron microscopes, but no details concerning normal oculomotor nerves in humans have been published. We measured and analyzed unmyelinated nerve fibers in the human oculomotor nerve with an image analyzer and a computer, using a new staining method, the Luxol fast blue-periodic acid-Schiff-hematoxylin (LPH) discriminative staining method which is the only one suitable for morphometric research on nervous tissues. We studied the numbers and transverse areas of unmyelinated fibers of the oculomotor nerve in 20 cadavers. The number of unmyelinated axons did not change with age, but the mean transverse area decreased with age. These fibers were distributed diffusely in the transverse area of the oculomotor nerve, not localized in any part of the nerve. These findings may be important for the analysis of clinical and neurological signs in relation to aging and ophthalmologic functions.

Adult↗
PubMed2000

[Calcification in culprit lesions of coronary artery disease].

Coronary calcification, a type of coronary atherosclerosis, has recently been closely examined in clinical cardiology because its presence may influence the selection of interventional therapy. In addition, plaque instability is one of the most important factors in the mechanism of acute coronary syndrome, and calcium deposit is frequently detected in advanced lesions. However, little is known about the clinical significance of coronary calcification. The incidence of calcium deposits was investigated in the culprit lesions (culprit coronary calcification) of patients with serious coronary artery disease to discover any cardioprotective effect. Initial coronary angiography was performed in 179 consecutive patients with acute myocardial infarction with Q wave on electrocardiography (AMI group; male 139, female 40, mean age 60.2 +/- 10 yr) and in 119 consecutive patients with stable effort angina pectoris (SAP group; male 78, female 41, mean age 63.8 +/- 8 yr) for which balloon plasty or bypass surgery was necessary from 1990 to 1997. Culprit coronary calcification was defined positive if the calcification deposit was present cinefluoroscopically within 5 mm from the culprit point. The culprit point was defined as the narrowest point after successful intracoronary thrombolytic therapy or the latest point to be dilated during a balloon inflation in direct or rescue percutaneous transluminal coronary angioplasty in the AMI group, and the narrowest point of the culprit lesion in the SAP group. There was no statistical difference in clinical background between the 2 groups other than male dominance in the AMI group and high incidence of family history of ischemic heart disease in the SAP group (p < 0.05). Culprit coronary calcification in patients over 50 years old was less frequently positive in the AMI group than the SAP group (26% vs 66%, p < 0.005, respectively). In younger patients under 50 years old, the incidence of culprit coronary calcification was low (14-15%) in both groups. Culprit coronary calcification was frequently positive in the right or the left anterior descending coronary artery in the SAP group (p < 0.005). There was no incidental sex difference of culprit coronary calcification. This comparison suggests that if a plaque contains cinefluoroscopically visible calcification, it may be regarded as less vulnerable or having a history of chronic process of atherosclerosis which results in protecting plaque rupture.

Adult↗
PubMed2000

[No significant influence of serum amyloid A1 genotypes on serum lipids or HDL clearance].

Serum amyloid A1(SAA1), the major acute phase isotype of SAA protein family, consists of three common allelic variants(SAA1.1, SAA1.3 and SAA1.5) in the Japanese population. We have recently reported that subjects with the SAA1.5 allele have higher plasma SAA concentrations than those without it, a phenomenon probably due to the delayed catabolism of the isotype SAA1.5. Since SAA is present in high density lipoprotein(HDL), this study assessed whether SAA genotype influenced the serum lipid study by altering HDL metabolism. In a total of 279 healthy adults, no difference was noted in their total cholesterol, HDL-cholesterol or triglyceride concentrations among six genotype groups. Plasma clearance of human apolipoprotein AI(apoAI) was studied in mice by giving HDL reconstituted with each recombinant human SAA1 isotype. The apoAI clearance did not differ among each of the SAA1 isotype-conjugated HDLs. Moreover, the changes in content of SAA in HDL also did not alter the apoAI clearance. These results suggest that SAA1 may not play an active role in plasma HDL metabolism.

Adult↗
PubMed2000

[Right middle cerebral artery occlusion during endovascular embolisation of cerebral aneurysm by Guglielmi detachable coil: a case report].

Right middle cerebral artery embolism by thrombus occurred in 63-year-old female during endovascular embolisation of cerebral aneurysm by Guglielmi detachable coil. Middle cerebral artery occlusion lasted for 60 minute, and haemodynamics was stable during this period. Middle cerebral artery occlusion was detected only by digital subtraction angiography and information from neurosurgeons. Middle cerebral artery blood flow was restored with thrombolytic agents. After tracheal extubation, transient confusion and seizure occurred, but cerebral infarction was not seen in postoperative CT and there was no complication. In case of endovascular embolisation of cerebral aneurysm by Guglielmi detachable coil, systemic heparinization is necessity to decrease the risk of embolism by thrombus, and anesthetist is required to pay attention to cerebral angiography to maintain, close relationship with neurosurgeons and to take measures for cerebral protection.

Anesthesia↗
PubMed2000

[Skin diseases].

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Antihypertensive Agents↗