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Biomedical subjects

J Takeda

Publications and source records attributed to J Takeda.

At least 109 records · Page 6Linked to original sources
PubMed1999

The relationship between modified pulse wave transit time and cardiovascular changes in isoflurane anesthetized dogs.

OBJECTIVE: To clarify the relationship between blood pressure and pulse wave transit time at the peripheral artery from the R wave of the electrocardiogram (m-PWTT), the effects of cardiovascular interventions on this relationship was evaluated. METHODS: Ten mongrel dogs were anesthetized by isoflurane inhalation, and catheter tip pressure transducers were inserted into the ascending aorta and at the bifurcation of abdominal aorta to measure central and peripheral pulse wave arrival. Pulse wave arrival at the ascending aorta from the R wave represents pre-ejection period (PEP) and pulse wave arrival between the ascending aorta and bifurcation of aorta represents pulse wave transit time (PWTT), thus m-PWTT = PEP + PWTT. Hypertension was induced by the continuous infusion of dobutamine and phenylephrine, and hypotension was induced by deepening isoflurane anesthesia, acute blood loss and nitroglycerine infusion. The relationship between timing components (PWTT, PEP, and m-PWTT) and blood pressure was recorded and analyzed by using the least squares method. RESULTS: The relationship between timing components (PWTT, PEP and, m-PWTT) and blood pressure was significant and highly correlated. When the change in blood pressure was due to the myocardial contractility, such as after dobutamine infusion, the relationship between all timing components and blood pressure was consistent and negative. However, when the change in blood pressure was due to the vasoactive agents, such as phenylephrine, the relationship between timing components and blood pressure was dependent on the reflex change in PEP. CONCLUSIONS: Change in m-PWTT is a good parameter to predict blood pressure changes, although the absolute blood pressure value cannot be obtained.

Anesthetics, Inhalation↗
PubMed1999

Permissive hypercapnia during thoracic anaesthesia.

BACKGROUND: While permissive hypercapnia is commonly practised in critical care, it remains unclear if the comparable manoeuvres are clinically acceptable during anaesthesia. This retrospective study aimed at describing the anaesthetic implications of hypercapnia associated with deliberate hypoventilation during thoracic surgery in patients with severe emphysema. METHODS: Thirteen patients with emphysema who required thoracic surgery under similar anaesthesia were reviewed: 3 patients were managed to maintain normocapnia (normocapnia group) whereas 10 patients developed hypercapnia (PaCO2 >70 mmHg) as a result of restricting peak airway pressures (hypercapnia group). RESULTS: In the normocapnia group (PaCO2: 45+/-1 mmHg, mean+/-SD), no event which required therapeutic intervention during the surgery was seen, whereas 2 of 3 patients showed postoperative air leakage which persisted over 5 days. In the hypercapnia group, the maximum PaCO2 during anaesthesia ranged between 70 mmHg and 135 mmHg (98-21 mmHg). During anaesthesia, all 10 patients required inotropic support to prevent hypotension, 4 patients required tracheal gas insufflation of oxygen to the operated lung to avoid hypoxaemia and 3 patients required lidocaine to treat ventricular arrhythmia. However, the trachea was extubated in the operation theatre in 9 of 10 patients and no organ dysfunction was observed postoperatively. Four patients showed postoperative air leak on the first postoperative day, one of which persisted over 5 days. CONCLUSION: Although there are some limitations, this preliminary study indicates that hypercapnia around 100 mmHg during anaesthesia for thoracic surgery may not be associated with serious consequences.

Aged↗
PubMed1999

Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response.

Missense mutations in the human presenilin-1 (PS1) gene, which is found on chromosome 14, cause early-onset familial Alzheimer's disease (FAD). FAD-linked PS1 variants alter proteolytic processing of the amyloid precursor protein and cause an increase in vulnerability to apoptosis induced by various cell stresses. However, the mechanisms responsible for these phenomena are not clear. Here we report that mutations in PS1 affect the unfolded-protein response (UPR), which responds to the increased amount of unfolded proteins that accumulate in the endoplasmic reticulum (ER) under conditions that cause ER stress. PS1 mutations also lead to decreased expression of GRP78/Bip, a molecular chaperone, present in the ER, that can enable protein folding. Interestingly, GRP78 levels are reduced in the brains of Alzheimer's disease patients. The downregulation of UPR signalling by PS1 mutations is caused by disturbed function of IRE1, which is the proximal sensor of conditions in the ER lumen. Overexpression of GRP78 in neuroblastoma cells bearing PS1 mutants almost completely restores resistance to ER stress to the level of cells expressing wild-type PS1. These results show that mutations in PS1 may increase vulnerability to ER stress by altering the UPR signalling pathway.

Alzheimer Disease↗
PubMed1999

Accumulation of murine amyloidbeta42 in a gene-dosage-dependent manner in PS1 'knock-in' mice.

The establishment of an animal model with a missense mutation of presenilin-1 (PS1) is an initial step toward understanding the molecular pathogenesis of familial Alzheimer's disease (FAD) and developing therapeutic strategies for the disease. We previously described a Japanese family with FAD caused by the I213T mutation of PS1, in which typical signs and symptoms of Alzheimer's disease were observed at the age of 45 +/- 4.2 years [Hardy, J. (1997) Trends. Neurosci., 20, 154-159; Kamino, K et al. (1996) Neurosci. Lett., 208, 195-198]. Here, we report the establishment of 'knock-in' mice with the I213T PS1 missense mutation. Northern blot and reverse transcription polymerase chain reaction (RT-PCR) analyses showed that the mutated PS1 allele was expressed at the same level as the endogenous PS1 allele, demonstrating that the PS1 missense mutation was successfully introduced into the mouse PS1 locus, and therefore that the situation mimics that in FAD patients bearing PS1 missense mutations. Amyloid beta (Abeta) 42(43) peptide, but not Abeta40 peptide, accumulated in 'knock-in' mice at the age of 16-20 weeks. A clear gene-dosage effect on the increase of Abeta42(43) was observed in 'knock-in' mice: the percentage increase of Abeta42(43) in mice with mutations in both alleles was twice as high as that in mice with a single allele. These results indicate that the level of the mutated PS1 gene expression is likely to be critically involved in the production of highly amyloidogenic Abeta42(43), and confirm that PS1 mutation has an important effect on amyloid precursor protein (APP) processing, in proportion to the level of the expression of the mutant gene.

Alleles↗
PubMed1999

Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage.

To understand the molecular processes of continuous vasospasm of cerebral arteries after subarachnoid hemorrhage, mRNA differential display and screening of cDNA expression array were performed to identify genes that are differentially expressed in vasospastic arteries of canine two-hemorrhage models. The expression levels of 18 genes were found to be upregulated, and those of two genes to be downregulated. Of these, 12 represent known genes or homologues of genes characterized previously, and the other eight genes are not related to any sequences in the databases. The known genes include five upregulated inflammation-related genes encoding monocyte chemotactic protein-1, cystatin B, inter-alpha-trypsin inhibitor family heavy chain-related protein, serum amyloid A protein, and glycoprotein 130, suggesting that inflammatory reaction may be involved in the development of cerebral vasospasm. The upregulation of three known genes encoding stress-related proteins of vascular endothelial growth factor, BiP protein, and growth-arrest and DNA-damage-inducible protein may be involved in possible cell survival in the damaged arteries. A full-length cDNA for the unknown clone DVS 27, whose expression was most highly upregulated, was isolated from the cerebral artery cDNA library by hybridization. Characterization of these genes should help to clarify the molecular mechanism of continuous cerebral vasospasm after subarachnoid hemorrhage.

Amino Acid Sequence↗
PubMed1999

Human and mouse GPAA1 (Glycosylphosphatidylinositol anchor attachment 1) genes: genomic structures, chromosome loci and the presence of a minor class intron.

Many eukaryotic cell surface proteins are anchored to the membrane with glycosylphosphatidylinositol (GPI) that is covalently linked to the carboxyl-terminus. A Saccharomyces cerevisiae gaa1 mutant is defective in posttranslational attachment of GPI to proteins. A recent report demonstrated that the GPAA1 gene encodes a component of a transamidase that mediates GPI-anchor attachment. Here, we report structures and chromosome loci of human and mouse GPAA1 genes. Both genes consist of twelve exons that span about 4 kb. Human and mouse GPAA1s are located at 8q24.3 and 15E, respectively. There is a human pseudo GPAA1 gene (GPAA1P1) that is located at 2q12-->q14. Introns 8 of human and mouse GPAA1s were minor class introns bearing AT at the 5' splice sites and AC and AT at the 3' splice sites, respectively. The 3' splice sites of corresponding introns of African green monkey, Chinese hamster, dog and rat were AC, AT, AT and AA, respectively. The mouse GPAA1 gene (Gpaa1) bearing AG at the 3' splice site prepared by site-directed mutagenesis was functional, indicating that any nucleotide is allowed at the 3' end of a minor class intron.

Animals↗
PubMed1999

Effect of positive end-expiratory pressure on left and right ventricular diastolic filling assessed by transoesophageal Doppler echocardiography.

The effect of positive end-expiratory pressure (PEEP) on left and right ventricular diastolic filling dynamics was assessed by transmitral and transtricuspid flow patterns. Using transoesophageal Doppler echocardiography in fourteen ASA physical status 1 female patients, the following measurements were performed at baseline (0 cm H2O PEEP) and at 5, 10, 15, and 20 cm H2O PEEP: 1. peak velocity of early filling (peak E velocity), 2. peak velocity of atrial contraction (peak A velocity), 3. the ratio of the peak E to A velocity (peak E/A velocity ratio), 4. isovolumic relaxation time (IRT), 5. acceleration half-time (AHT), 6. deceleration half-time (DHT) of early filling, and 7. end-diastolic and end-systolic areas of both ventricles. Increasing PEEP progressively deceased peak E velocity of both ventricles. In contrast, peak A velocity did not change and the peak E/A velocity ratio decreased significantly with PEEP. IRT and AHTs remained unchanged, but DHTs of both ventricles increased following PEEP. End-diastolic and end-systolic areas of both ventricles decreased gradually and significantly with PEEP. It is concluded that PEEP was associated with decreased preload as well as reduced compliance of both ventricles, which was considered to contribute to the changes in diastolic ventricular filling.

Adult↗
PubMed1999

pH-dependent inhibitory effects of angiotensin-converting enzyme inhibitors on cefroxadine uptake by rabbit small intestinal brush-border membrane vesicles and their relationship with hydrophobicity and the ratio of zwitterionic species.

The inhibitory effects of five angiotensin-converting enzyme (ACE) inhibitors on the uptake of an aminocephalosporin antibiotic, cefroxadine, by rabbit small intestinal brush-border membrane vesicles were examined in the presence of an inward H+ gradient. Dixon plot analysis showed that all these ACE inhibitors inhibited the uptake of cefroxadine, which is transported by a H+/oligopeptide transporter in the membrane, in the order of enalapril<quinapril, benazepril<temocapril, trandolapril at extravesicular pH 6.0. These drugs, except for enalapril, which are relatively hydrophobic, exhibited a mix of competitive and noncompetitive inhibition. We also examined the inhibitory effects of quinapril and temocapril at extravesicular pH 5.5, at which the ratio of the zwitterionic species of the drugs increased. The inhibition occurred in a nearly competitive manner at this pH and the inhibitory effects were stronger than at pH 6.0. Regression analysis of the inhibitory effects suggested that the affinity of these ACE inhibitors for the transporter was regulated by the hydrophobicity of these ACE inhibitors and the ratio of the zwitterionic species of the drugs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Uptake of enalapril by rabbit small intestinal brush-border membrane vesicles.

Uptake of the angiotensin-converting enzyme (ACE) inhibitor enalapril by rabbit small intestinal brush border membrane vesicles was examined. In the presence of an inward H+ gradient the uptake of this peptide mimetic drug was accelerated and an overshoot phenomenon was observed. The uptake was more stimulated by higher H+ gradient. Initial uptake rate was saturable in the presence of an inward H+ gradient, with apparent Km value of 4.2 mM. These findings suggest the involvement of the H+-coupled carrier-mediated transport in the uptake of enalapril. The uptake was inhibited by ACE inhibitor trandolapril but hardly or only slightly inhibited by aminocephalosporins.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Genes expressed during the differentiation of pancreatic AR42J cells into insulin-secreting cells.

Pancreatic AR42J cells have the feature of pluripotency of the common precursor cells of the pancreas. Dexamethasone (Dx) converts them to exocrine cells, whereas activin A (Act) converts them into endocrine cells expressing pancreatic polypeptide. A combination of Act and betacellulin (BTC) converts them further into insulin-secreting cells. The present study identifies some of the genes involved in the process of differentiation that is induced by these factors, using the mRNA differential display and screening of the cDNA expression array. The expression levels of 7 genes were increased by Act alone, and a combination of Act and BTC increased the expression of 25 more genes. Of these, 16 represented known genes or homologues of genes characterized previously. Nine of the identified genes were unrelated to any other sequences in the database. An inhibitor of the mitogen-activated protein kinase pathway, PD098059, which blocks the differentiation into insulin-secreting cells, inhibited the expression of 18 of the 25 genes, suggesting that the proteins encoded by these genes are associated with the differentiation into insulin-producing cells. These include known genes encoding extracellular signaling molecules, such as parathyroid hormone-related peptide, cytoskeletal proteins, and intracellular signaling molecules. Identification and characterization of these differentially expressed genes should help to clarify the molecular mechanism of differentiation of pancreatic cells and the gene products that enable the beta-cells to produce insulin.

Activins↗
PubMed1999

Histopathological findings of the lower esophagus after total gastrectomy in rat.

It is now accepted that the incidence of esophageal carcinoma is highest in the middle thoracic region. Esophageal carcinoma after gastrectomy, however, has a tendency to develop in the lower region. This study was designed to investigate the role of reflux of gastroduodenal juice in the genesis of carcinoma in the esophagus. We found a possible correlation between the development of esophageal carcinoma and gastrectomy, related to alkaline reflux into the esophagus. To elucidate this correlation, the role of alkaline reflux of duodenal contents in the development of esophageal squamous cell carcinoma was investigated in Wister rats. Gastrectomized rats with regurgitation of duodenal contents into the esophagus were not administered any carcinogen and were sacrificed some at the end of 8 weeks and others at 50 weeks for pathological examination. Hyperplasia was found in rats at 8 weeks, and the esophageal squamous cell carcinoma was found in rats at 50 weeks. The carcinomas were found exclusively in the area of the reflux esophagitis and were accompanied by severe dysplasia. These results suggested that alkaline reflux of duodenal contents was strongly correlated to the development of the esophageal squamous cell carcinoma.

Animals↗
PubMed1999

Submucosal gastric cancer with lymph node metastasis--a clinicopathological study.

We have reviewed the clinicopathological features of submucosal gastric cancer with lymph node metastasis. The degree of vertical submucosal infiltration was classified into three stages as sm1, sm2 or sm3. The number of cases with lymph node metastasis of sm3 was significantly more than that of sm1 or sm2. We found no correlation between the tumor size and the rate of lymph node metastasis from submucosal invasive cancer. Accordingly, we concluded that the vertical submucosal infiltration was a more important factor for lymph node metastasis than horizontal infiltration. Minimal invasive surgery was recommended for a tumor measuring 1 cm or less in size with vertical submucosal invasion of sm1 or sm2.

Gastric Mucosa↗
PubMed1999

Developmental abnormalities of glycosylphosphatidylinositol-anchor-deficient embryos revealed by Cre/loxP system.

One mode used to link membrane proteins to a cell membrane is by means of a special glycolipid anchor termed glycosylphosphatidylinositol (GPI). Pig-a, an X-linked gene, is involved in the first step of GPI-anchor biosynthesis. Disruption of this gene causes cessation of GPI biosynthesis on the endoplasmic reticulum, thereby leading to the absence of GPI-anchored proteins on the cell surface. We have previously reported that mice with high chimerism was never obtained from Pig-a disrupted ES cells, suggesting that GPI-anchored protein(s) may have important roles for mouse development such that the absence of GPI-anchored proteins causes a lethal effect to mice. In this study, this lethal effect has been investigated by using a conditional approach to "knockout" the Pig-a gene. For this, mice harboring a Pig-a gene flanked by two loxP sites (Pig-aflox) were mated with hCMV-Cre transgenic mice, which express Cre recombinase before implantation. The allele disruptions were identified by PCR analysis of embryo yolk sac DNA. Embryos harboring a complete disruption of Pig-a gene ceased to develop beyond the ninth day of gestation. Female embryos in which one Pig-a allele was disrupted by Cre such that only half of the cells in the embryo proper did not express GPI-anchored proteins due to random X inactivation developed until 19 days post coitum (dpc), but showed abnormal phenotypes such as insufficient closure of neural tube and cleft palate. These data further highlight the importance of GPI-anchored proteins during mouse embryonic development.

Animals↗
PubMed1999

Minimally invasive port-access coronary artery bypass grafting.

The Port-Access endovascular cardiopulmonary bypass system (Heartport, Inc., Redwood City, CA, USA), a recent technological innovation in minimally invasive cardiac surgery, was conducted successfully in coronary artery bypass grafting on a 69-year-old woman. The left internal thoracic artery was harvested through a limited left anterior thoracotomy and anastomosed to the left anterior descending coronary artery on a protected and arrested heart. Intraoperative coronary angiography confirmed good graft patency. The patient was discharged from the hospital in good condition 7 days after the operation. This was the first successful minimally invasive Port-Access coronary artery bypass grafting in Japan.

Aged↗
PubMed1999

[Influence of PEEP on left ventricular diastolic function].

We investigated the influence of PEEP on left ventricular diastolic function using the pressure-volume loops by employing a micromanometer catheter and a conductance catheter placed in the left ventricle of the eight mongrel dogs. Time constant of diastolic interval was shortened under the condition of 15 cmH2O of PEEP compared with the control value (PEEP 0 cmH2O) and the diastolic stiffness constant was prolonged under 15 cmH2O of PEEP. It was considered that the shortened time constant of diastolic interval was due to the decrease of preload. The prolongation of diastolic stiffness constant was possibly due to compression of the heart by increased intrapleural pressure. We conclude that decreased compliance of left ventricle caused by PEEP might impair the left ventricular function.

Animals↗