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Biomedical subjects

K Takayanagi

Publications and source records attributed to K Takayanagi.

At least 73 records · Page 4Linked to original sources

Arrhythmia curve interpretation using a dynamic system model of the myocardial pacemaker.

A problem of identifying the phase response curve of the myocardial pacemaker was investigated using a simple dynamic system model of cardiac arrhythmia. A hybrid optimization method of a genetic algorithm and a local optimization technique was employed to obtain a solution of the model fitting. The method was applied to two categories of arrhythmias, ventricular parasystole and high-degree AV block. The present study offered a new insight into the mechanism of cardiac arrhythmias.

Animals↗

A novel activity of HMG domains: promotion of the triple-stranded complex formation between DNA containing (GGA/TCC)11 and d(GGA)11 oligonucleotides.

The high mobility group protein (HMG)-box is a DNA-binding domain found in many proteins that bind preferentially to DNA of irregular structures in a sequence-independent manner and can bend the DNA. We show here that GST-fusion proteins of HMG domains from HMG1 and HMG2 promote a triple-stranded complex formation between DNA containing the (GGA/TCC)11 repeat and oligonucleotides of d(GGA)11 probably due to G:G base pairing. The activity is to reduce association time and requirements of Mg2+ and oligonucleotide concentrations. The HMG box of SRY, the protein determining male-sex differentiation, also has the activity, suggesting that it is not restricted to the HMG-box domains derived from HMG1/2 but is common to those from other members of the HMG-box family of proteins. Interestingly, the box-AB and box-B of HMG1 bend DNA containing the repeat, but SRY fails to bend in a circularization assay. The difference suggests that the two activities of association-promotion and DNA bending are distinct. These results suggest that the HMG-box domain has a novel activity of promoting the association between GGA repeats which might be involved in higher-order architecture of chromatin.

Base Composition↗

Specific developmental changes in the regulatory subunits of the 26 S proteasome in intersegmental muscles preceding eclosion in Manduca sexta.

Previously, we have shown extensive reprogramming of the ATPase regulator of the 26S proteasome preceding the programmed destruction of intersegmental muscles (ISM) in the tabacco horn moth Manduca sexta (Dawson et al., J. Biol. Chem, 270, 1850-1858, 1995). We now show that the extensive reprogramming of the regulatory components of the 26S proteasome occurs only in ISM and not in flight muscles (FM), which undergo terminal differentiation at ecdysis. Unlike in ISM, the ATPase regulators, MS73, MSS1, TBP1 and mts2, remain at low levels in 26S proteasomes in FM from developmental Stage-0 to Stage-7. The non-ATPase regulator subunit 5a, which binds to multiubiquitin chains, increased in ISM similarly to the ATPases but not in FM. The ecdysteroid agonist RH-5849 prevented these subunit increases in ISM. These findings show that reprogramming of 26 S proteasomes is involved in the specific elimination of ISM during eclosion and does not occur in FM which are needed for adult moth flight.

Animals↗

Expression of polymorphonuclear leukocyte adhesion molecules and its clinical significance in patients treated with percutaneous transluminal coronary angioplasty.

OBJECTIVES: This study evaluated the role of neutrophil adhesion molecules LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18) and p150,95 (CD11c/CD18) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Several recent studies have suggested that cell adhesion molecules on both neutrophils and vascular endothelial cells play an important role in the process of tissue inflammation. METHODS: Thirty-eight patients (30 men, 8 women; mean [+/-SE] age 56 +/- 5 years, range 38 to 76) with single-vessel coronary artery disease of the left anterior descending artery underwent coronary angioplasty. Peripheral blood was sampled at baseline before, immediately after and 12, 24, 48 and 144 h after PTCA. The expression of CD18, CD11a, CD11b and CD11c on the surface of polymorphonuclear leukocytes was examined by flow cytometry with monoclonal antibodies. RESULTS: In patients without subsequent restenosis, there was no change in mean channel fluorescence intensity (MFI) of CD18 at each sampling time. However, in the patients with restenosis, the MFI of CD18 significantly increased at 48 h after PTCA (from 57 +/- 6 to 73 +/- 8, p = 0.0008). The MFI of CD11b increased slightly at 48 h after PTCA in patients without restenosis (from 584 +/- 121 to 735 +/- 114, p = 0.037). In patients with restenosis, the MFI of CD11b was slightly increased at 24 h after PTCA (from 586 +/- 122 to 768 +/- 214, p = 0.018) and significantly increased at 48 h after PTCA (to 1,534 +/- 268, p = 0.0006). The expression of CD11a and CD11c did not change at any sampling points after PTCA in either of the two patient groups. Percent change in the expression of CD18 at 48 h after PTCA (from baseline) and that of CD11b were correlated (r = 0.73, p = 0.0008) in patients with restenosis. CONCLUSIONS: Inflammatory stimuli within the coronary vessels associated with coronary angioplasty may upregulate Mac-1 expression on the surface of polymorphonuclear leukocytes. This process may be more marked in patients who experience later restenosis. Thus, activation of neutrophil adhesion molecule Mac-1 at 48 h after PTCA may have value as a predictor of subsequent restenosis.

Adult↗

Population pharmacokinetics of phenytoin in Japanese patients with epilepsy: analysis with a dose-dependent clearance model.

The population pharmacokinetic parameters of phenytoin were estimated using routine therapeutic drug monitoring data from 116 epileptic patients. The 531 serum concentration values at steady-state after repetitive oral administration were analyzed using a nonlinear mixed effects model (NONMEM) program designed for estimation of population pharmacokinetic parameters. A one-compartment model with dose-dependent clearance was used for the pharmacokinetic analysis of phenytoin. The volume of distribution (V) was estimated to be 1.231/kg in a typical 42-kg patient, assuming that the bioavailability of orally administered phenytoin is 100%. The maximal elimination rate (V(max)) and the Michaelis-Menten constant (K(m)) were 9.80 mg/d/kg and 9.19 micrograms/ml, respectively. The parameter of power function of weight to adjust V and V(max) was estimated to be 0.463. In addition, K(m) for phenytoin appeared to be 16% increased in patients receiving zonisamide concurrently. The population pharmacokinetic parameters of phenytoin will be useful for designing dosage regimens in epileptic patients.

Adolescent↗

Relationship of thallium-201 clearance on exercise stress myocardial scintigraphy to coronary flow reserve in patients with coronary artery disease.

OBJECTIVE: We evaluated thallium-201 (201Th) clearance measurement during exercise myocardial scintigraphy in patients with coronary artery disease, for the assessment of coronary circulatory function and diagnosis. DESIGN: The clearance rate of 201Th was compared with the coronary flow reserve measured by Doppler coronary flow velocimetry. METHODS: We selected 20 patients who had chronic stable angina with single-vessel coronary artery disease of the left anterior descending artery (LAD) and underwent percutaneous transluminal coronary angioplasty (PTCA). Ten control patients had atypical chest pain but no detectable heart disease. Regional net clearance of 201Th was measured from the early and delayed bull's-eye images of 201Th exercise stress single photon emission tomography (SPECT). Using a Doppler catheter, we also measured coronary flow reserve of the LAD, which was obtained by the intracoronary administration of papaverine. RESULTS: The net 201Th clearance in the anterior wall myocardium in the patients with coronary artery disease before PTCA was significantly less than that in the controls. At follow-up angiography after successful PTCA, it increased. The coronary flow reserve before PTCA was also lower than that in the controls. It was increased immediately after PTCA, and was more markedly increased at the follow-up angiography. Before PTCA, regional net clearance in the anterior myocardium was correlated with the coronary flow reserve of the LAD. The ratio for the net clearance of the anterior myocardium at follow-up angiography to that before PTCA was also correlated with the ratio for coronary flow reserve. CONCLUSIONS: In patients with coronary artery disease, the regional 201Th clearance in the ischaemic area measured by exercise 201Th SPECT is correlated with the coronary flow reserve of the affected artery. Moreover, the increase in the clearance rate after PTCA is also correlated with that in the coronary flow reserve. Thus the measurement of regional 201Th clearance might be a useful non-invasive method of estimating of the coronary flow reserve.

Analysis of Variance↗

Spinal cord injures in children observed over many years.

The known salient features of spinal cord injuries in children are that 1) plane X-rays may not show dislocations or fractures, 2) many of these injuries are complete transections, 3) many injuries are located at the level of upper thoracic spine, and 4) the duration of spinal shock is short. Complications such as pressure sores occur just as easily in children as in adults and the injuries tend to be just as intractable. Complications characteristic in children with spinal cord injuries are spinal deformity and hip dislocation. In this paper, we describe a case involving a C7 spinal cord injury caused by a fall when the patient was 3 years old. We have observed the physical complications for 15 years following that injury. We also report on other observed cases of spinal cord injury.

Age Factors↗

Differential display identifies developmentally regulated genes during somatic embryogenesis in eggplant (Solanum melongena L.).

Changes in gene expression patterns during early somatic embryogenesis of eggplant (Solanum melongena L.) were characterized by means of differential display. Eight products of polymerase chain reaction (PCR) derived from newly expressed mRNAs after four days of culture were identified and cloned. One clone, pTM002, was found to contain a 416 bp insert and identical to the proximal arbitrary primer at both ends. Based on the terminal sequences, reverse-transcription PCR (RT-PCR) was carried out to monitor the expression level of pTM002. The results indicated that the message of pTM002 was increased to correlate with the intensities obtained in the differential display. The significance of this method in investigation of differentially expressed genes is also discussed.

Base Sequence↗

A new strategy of gene trapping in ES cells using 3'RACE.

"Gene trapping" in embryonic stem (ES) cells is a novel approach to identify a series of genes in mammals concomitant with the production of the corresponding mutant mice. However, this approach is currently unable to identify genes that are not expressed in ES cells. Here we describe a strategy to identify gene trapping clones which is not based on expression of a reporter gene. It uses the neor gene which lacks a polyadenylation signal and has a splice donor signal. Expression of the neor gene as fusion transcripts with the 3' end containing the polyadenylation signal of tagged genes allows the identification of these clones by 3' rapid amplification of the cDNA end in undifferentiated ES cells, even if the genes are not expressed in ES cells. Amplification was observed in about 25% of G418-resistant clones. Sequence analyses suggested the amplifications represent gene trapping events. The feasibility of this approach was further assessed by analysing one clone, PAT-12, in detail.

Amino Acid Sequence↗

Spinal cord injury in a child: a long term follow-up study. Case report.

The main features of spinal cord injuries in children are known to be that (1) plain radiographs do not show the bony injury; (2) many of the injuries are complete spinal cord injuries; (3) many involve the upper thoracic spine; and (4) the duration of spinal shock is short. Complications such as pressure sores occur just as easily in children as in adults and the injuries are intractable. Typical complications in children with spinal cord injuries are spinal deformity and hip dislocation. We discuss a patient with a C7 spinal cord injury caused by a fall when the patient was 3 years old, and the physical complications occurring during the 15 years following the injury.

Adolescent↗

Heart failure progression due to secondary organ dysfunction in acute heart failure.

Although the pathophysiology of heart failure progression is important to survival it is not fully understood. In 92 patients with acute heart failure due to myocardial infarction or dilated cardiomyopathy, secondary organ dysfunction was evaluated to determine whether this factor contributed to heart failure progression and death. Forty-one patients had renal dysfunction, hepatic disease or loss of consciousness after the onset of the acute heart failure, and 26 of them (63%) died of progressive heart failure during the follow-up period of 20 months on average. The one-year survival rate was 22%. Although 51 other patients showed the same initial clinical features and cardiac function, they did not develop concurrent organ dysfunction during the course and only 11 (22%, p < 0.001) died of progressive heart failure. The one-year survival rate was 67%. The survival rate decreased in the order of renal dysfunction, hepatic disease and loss of consciousness. Transient low cardiac output of less than 2.2 l/min/m2 was more frequent in patients with organ dysfunction. It is suggested that heart failure progresses, in part, due to organ dysfunction secondary to heart failure and careful treatment to prevent organ dysfunction is important to long term survival.

Acute Disease↗

Systemic amyloidosis following ankylosing spondylitis associated with congestive heart failure. A case report.

We report the case of a 38-year-old man who developed fatal, systemic amyloidosis following ankylosing spondylitis. He was admitted for symptoms of congestive heart failure. Based on parotid gland biopsy and echocardiography, he was diagnosed as having systemic amyloidosis following active ankylosing spondylitis. However, the clinical course was rapidly progressive and eventually the patient died of acute necrotizing pancreatitis. The association has been reported thus far in a limited number of cases worldwide. The literature has featured localized lesions and a benign clinical course of the amyloidosis. This case, the first report from Japan, indicates that the amyloidosis associated with ankylosing spondylitis might exhibit a rapidly progressive clinical course, thereby suggesting that in such a case, meticulous treatment is required.

Acute Disease↗

[Cell kinetics of rat lens epithelium by cytofluorometric nuclear DNA determination].

The cell kinetics of rat lens epithelium was assessed by measuring the changes in the nuclear DNA contents during sugar cataract formation. Six-and-12-week-old Sprague-Dawley male rats were used and divided into the following groups: fed on normal chow, fed on 25% galactose diet, and fed on normal chow after 5 days on the 25% galactose diet. Every second day following the beginning of each chow feeding, lenses were extracted, and lens capsules with epithelial cells were obtained. After a few day's fixation in 4% paraformaldehyde dissolved in 0.1M phosphate buffer (pH 7.4), DAPI (4'6-diamidino-2-phenylindole)-stained lens epithelial cells were measured by fluorescence cytophotometry. The epithelia in the normal chow-fed rats contained many 2C and a few 4C nuclei. In the 25% galactose-fed rats, 4C nuclei increased gradually in number until the fifth day, and then decreases slowly day by day. Abnormal polyploid nuclei (8C) were observed in the 25% galactose-fed rats. 4C nuclei decreased rapidly after the diet reversal. These results indicate that galactose feeding caused higher DNA synthesis of rat lens epithelial cells and a higher possibility of abnormal cell division.

Animals↗