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Biomedical subjects

N Nakajima

Publications and source records attributed to N Nakajima.

At least 73 records · Page 4Linked to original sources
PubMed2000

Surface modification of poly(ethylene-co-vinyl alcohol) (EVA). Part I. Introduction of carboxyl groups and immobilization of collagen.

To enhance the surface biocompatibility of poly(ethylene-co-vinyl alcohol) (EVA) and high-density polyethylene (HDPE), carboxyl groups were introduced by ozone exposure. Type I collagen was immobilized onto the surface through polyion complexing. The carboxyl groups on the EVA were characterized by electron spectroscopy for chemical analysis and neutralization. The amounts of the carboxylic group and collagen increased with increases in time and temperature of exposure. Water-soluble fragments were produced by ozone exposure to EVA, and they acted as collagen crosslinkers. The differences in charge distribution of carboxyl groups affected the amount of collagen immobilization. Graft polymerization of acrylic acid was also carried out onto EVA and HDPE surfaces. The amount of collagen immobilized by graft polymerization was much higher than that by ozone exposure despite the introduction of almost the same amounts of carboxylic groups. It was suggested that the negative charge distribution influences the amount of collagen immobilized onto films.

Biocompatible Materials↗
PubMed2000

MTABC3, a novel mitochondrial ATP-binding cassette protein involved in iron homeostasis.

Atm1p, a mitochondrial half-type ATP-binding cassette (ABC) protein in Saccharomyces cerevisiae, transports a precursor of the iron-sulfur (Fe/S) cluster from mitochondria to the cytosol. We have identified a novel half-type human ABC protein, designating it MTABC3 (mammalian mitochondrial ABC protein 3). MTABC3 mRNA is ubiquitously expressed in all of the rat and human tissues examined. MTABC3 protein is shown to be present in the mitochondria, as assessed by immunoblot analysis and confocal microscopic analysis of subcellular fractions of Chinese hamster ovary cells stably expressing MTABC3. Accumulation of iron in the mitochondria, mitochondrial DNA damage, and respiratory dysfunction in the yeast ATM1 mutant strain (atm1-1 mutant cells) were almost fully reversed by expressing MTABC3 in these mutant cells. These results indicate that MTABC3 is a novel ortholog of the yeast and suggest an important role in mitochondrial function. Interestingly, the human MTABC3 gene has been mapped to chromosome 2q36, a region within the candidate locus for lethal neonatal metabolic syndrome, a disorder of the mitochondrial function associated with iron metabolism, indicating that MTABC3 is a candidate gene for this disorder.

ATP-Binding Cassette Transporters↗
PubMed2000

Low levels of NPM gene expression in UV-sensitive human cell lines.

Nucleophosmin (NPM) is a major nuclear matrix protein associated with neoplastic growth in various cell types. We recently suggested that expression of the NPM gene is involved in an increased resistance to UV irradiation in human cells against the cell-killing effects of UV (mainly 254nm wavelength far-ultraviolet ray) [Y. Higuchi, K. Kita, H. Nakanishi, X-L. Wang, S. Sugaya, H. Tanzawa, H. Yamamori, K. Sugita, A. Yamaura, N. Suzuki, Biochem. Biophys. Res. Commun. 248 (1998) 597-602]. In the present study, expression levels of the NPM gene were examined in human cell lines with a high sensitivity to UV cell-killing. Cockayne syndrome patient-derived cell lines, CSAI and CSBI, and the Xeroderma pigmentosum patient-derived cell line, XP2OS(SV), XP13KY, XP3KA, XP6BE(SV), XP101OS and XP3BR(SV), have been investigated for their NPM mRNA expression with Northern blotting analysis. All of these UV-sensitive cells demonstrated lower expression levels compared with those of normal fibroblast cells, FF, or an UV-resistant cell line, UH(r)-10; quite a lower level of expression in XP205(SV) cells after UV irradiation in contrast to a distinguishable increase in the expression in UV(r)- cells. These results confirmed an intimate correlation between degree of UV sensitivity and expression levels of the NPM gene in human cells.

Cell Survival↗
PubMed2000

Identification of a novel retinoic acid-responsive element within the lamin A/C promoter.

A-type lamins are not present in either early embryos or the embryonal carcinoma (EC) cell line. P19 cells, which are EC cell line, are able to express A-type lamins upon retinoic acid (RA) treatment. Here we report that a novel RA-responsive element, termed lamin A/C-RA-responsive element (L-RARE), is located within the lamin A/C promoter. RA activated the luciferase activity of the reporter which had four tandem repeats of the wild-type L-RARE, while a loss of function mutant, which altered CACCCCC to CACtatC within L-RARE, did not respond. Four specific binding complexes of L-RARE, Complexes-A, -B, -C, and -D, were detected in protein extracts obtained from P19 cells treated with and without RA. Specific antibodies revealed that Sp1 and Sp3 were included in Complex-A and Complexes-B and -C, respectively. Thus, L-RARE was important in the RA-mediated activation of the lamin A/C promoter and was recognized by DNA binding proteins.

Animals↗
PubMed2000

Free energy landscapes of peptides by enhanced conformational sampling.

The free energy landscapes of peptide conformations in water have been observed by the enhanced conformational sampling method, applying the selectively enhanced multicanonical molecular dynamics simulations. The conformations of the peptide dimers, -Gly-Gly-, -Gly-Ala-, -Gly-Ser-, -Ala-Gly-, -Asn-Gly-, -Pro-Gly-, -Pro-Ala-, and -Ala-Ala-, which were all blocked with N-terminal acetyl and C-terminal N-methyl groups, were individually sampled with the explicit TIP3P water molecules. From each simulation trajectory, we obtained the canonical ensemble at 300 K, from which the individual three-dimensional landscape was drawn by the potential of mean force using the three reaction coordinates: the backbone dihedral angle, psi, of the first amino acid, the backbone dihedral angle, phi, of the second amino acid, and the distance between the carbonyl oxygen of the N-terminal acetyl group and the C-terminal amide proton. The most stable state and several meta-stable states correspond to extended conformations and typical beta-turn conformations, and their free energy values were accounted for from the potentials of mean force at the states. In addition, the contributions from the intra-molecular energies of peptides and those from the hydration effects were analyzed. Consequently, the stable beta-turn conformations in the free energy landscape were consistent with the empirically preferred beta-turn types for each amino acid sequence. The thermodynamic values for the hydration effect were decomposed and they correlated well with the empirical values estimated from the solvent accessible surface area of each molecular conformation during the trajectories. The origin of the architecture of protein local fragments was analyzed from the viewpoint of the free energy and its decomposed factors.

Algorithms↗
PubMed2000

Two classes of enzymes of opposite stereochemistry in an organism: one for fluorinated and another for nonfluorinated substrates.

Reduction of methyl ketones by dried cells of Geotrichum candidum (APG4) afforded (S)-alcohols in excellent enantiomeric excess (ee), whereas the reduction of trifluoromethyl ketones gave the corresponding alcohols of the opposite configuration also in excellent ee. The replacement of the methyl moiety with a trifluoromethyl group alters both the bulkiness and the electronic properties, the effect of which on the stereoselectivity was examined. No inversion in stereochemistry was observed in the reduction of hindered ketones such as isopropyl ketone, while the stereoselectivity was inverted in the reduction of ketones with electron-withdrawing atoms such as chlorine. The mechanism for the inversion in stereochemistry was investigated by enzymatic studies. Several enzymes with different stereoselectivities were isolated; one of them catalyzed the reduction of methyl ketones, and another with the opposite stereoselectivity catalyzed the reduction of trifluoromethyl ketones. Furthermore, both APG4 and the isolated enzyme were applied to the reduction of fluorinated ketones on a preparative scale, which resulted in the synthesis of chiral fluorinated alcohols with excellent ee.

Fluorine↗
PubMed2000

TNF-alpha induced p21(WAF1) but not Bax in colon cancer cells WiDr with mutated p53: important role of protein stabilization.

The p21(WAF1)induces cell cycle arrest at G(1)and its expression is regulated by the functional p53. TNF-alpha induced expression of p21(WAF1)at protein and mRNA levels in a dose-dependent fashion with an association with G(1)-arrest in human colon cancer cells WiDr that carry mutated p53 at codon 273 (His(273)). However, TNF-alpha did not affect the levels of the Bax protein, which also has p53-binding sites on its promoter and causes apoptosis. Further experiments suggested that cycloheximide (CHX), a protein synthesis inhibitor, increased the levels of p21(WAF1)mRNA and the induction of p21(WAF1)mRNA by TNF-alpha did not require new protein synthesis. Co-transfection of the p53 His(273)expression construct with a luciferase gene controlled by the p21(WAF1)promoter showed that the p53 His(273)was inactive, although TNF-alpha increased the transcriptional rate of p21(WAF1)in these cells. Further study found that TNF-alpha markedly stabilized the p21(WAF1)protein. These findings suggest that TNF-alpha induces expression of p21(WAF1)through a distinct pathway from Bax and that protein stabilization is an important mechanism in the expression of p21(WAF1)independent of p53.

Apoptosis↗
PubMed2000

Cytomorphometric differentiation of intraductal proliferative breast lesions.

BACKGROUND: Although cytologic examination has been an indispensable procedure for the diagnosis of various breast diseases, it is often difficult to make a precise diagnosis of intraductal proliferative breast lesions preoperatively. The present study attempts to clarify the differentiation of the lesions by the cytologic morphometric approach. METHODS: Cytologic specimens from 21 intraductal lesions, including nine ductal carcinomas in situ (DCIS), seven ductal hyperplasias (DH), and five papillomas were evaluated. Using a microscope connected to a computerized video system, the mean nuclear area, the perimeter, the form factor, the largest to smallest diameter ratio of the nuclei (LS ratio), and the coefficient of variation of the nuclear area (NACV) were measured and analyzed. RESULTS: The mean nuclear area and perimeter were significantly higher in the cases of DCIS than in DH (p < 0.01) and papilloma (p < 0.005). Similarly, DCIS had higher NACV values than the other groups (p < 0.05 and p < 0.005, respectively). There were no significant differences in form factor or LS ratio. CONCLUSIONS: The quantitative estimation of cytologic nuclear features is useful for preoperative differential diagnosis of intraductal proliferative lesions of the breast.

Adult↗
PubMed2000

Quantitative ultrasound as a predictor of node metastases and prognosis in patients with breast cancer.

BACKGROUND: A retrospective study was performed to determine whether preoperative quantitative ultrasound assessment could predict axillary lymph node metastases and prognosis in patients with breast cancer. We focused on the presence of a halo, which is one of the features of breast cancer on ultrasound and represents reflections from the invading margin around infiltrating malignancies. METHODS: We evaluated ultrasonography from 187 infiltrating breast carcinoma patients with tumors 5 cm or less in greatest dimension (T1, T2). Using computer image analysis, the halo area (H) and the sum of the area of halo and internal echo (total tumor area (T)) were measured, and the ratio of halo to entire tumor (H/T, halo ratio) was calculated and compared with lymph node status and prognosis. RESULTS: The mean of the halo ratio was 0.38+/-0.13. Using the value of 0.42 as a cut-off, the high halo ratio group had significantly worse prognoses for both overall and disease-free survival at 49 months in median follow-up (p <0.001 and p <0.0005, respectively). The specificity of a high halo ratio in the T1 classification for predicting axillary node metastasis was 83.1%, with a negative predictive value of 86.8%. In patients with tumors 1.0 cm or smaller, the negative predictive value was 100%. In a multivariate analysis, halo ratio was an independent predictor of disease-free survival of breast carcinoma patients (p =0.0232). CONCLUSIONS: Preoperative quantitative ultrasound may be a useful non-invasive method for predicting the presence of axillary lymph node metastases and prognosis in patients with primary breast cancer.

Adult↗
PubMed2000

Evaluation of leukocyte-reducing arterial line filter (LG6) for postoperative lung function, using cardiopulmonary bypass.

OBJECTIVE: To prevent postoperative pulmonary dysfunction, we have investigated the effect of the Leuko-Guard 6 leukocyte-reducing arterial line filter (LG6) on postoperative lung function. METHODS: Twenty-six cases of adult valvular heart disease were included in this study. Thirteen cases were operated upon using the LG6 (Group LG), and 13 cases were operated upon using a conventional arterial line filter (Group C). Neutrophil, polymorphonuclear leukocyte elastase and lipoperoxide were measured for this study, and the lung function was evaluated using the Oxygenation Index (PaO2/FiO2). RESULTS: Statistically significant differences were observed in neutrophil counts between Group LG and Group C (LG = 2225 +/- 572/mm3, C = 3157 +/- 1413/mm3, p = 0.04) at 5 minutes after the onset of cardiopulmonary bypass. In simultaneous blood sampling from the pulmonary artery and the pulmonary vein, the sequestration of neutrophil in the lung decreased in Group LG after the discontinuation of cardiopulmonary bypass. Release of polymorphonuclear leukocyte elastase from the lungs was significantly decreased (p = 0.04) in the Group LG at 1 hour post-bypass. Significant differences were observed in the Oxygenation Index between Group LG and Group C (LG = 398 +/- 72, C = 326 +/- 71, p = 0.019) at 3 hours post-bypass. CONCLUSION: We concluded that LG6 improved the postoperative lung function, and its mechanism might be derived from the prevention of leukosequestration in the lungs that occurs during the rewarming phase due to selective absorption of activated leukocyte by the LG6.

Adsorption↗
PubMed2000

Aortic dissection complicated with aorto-right atrium fistula.

Aorto-right atrium fistula associated with aortic dissection is a very rare complication. Here report a case of successful surgical repair of ascending aortic dissection complicated with aorto-right atrium fistula. A 65-year-old man was presented with sudden chest pain and dyspnea. Fifteen years ago, he had aortic valve replacement. An aortic dissection with fistula to the right atrium was diagnosed by echocardiography and cardiac catheterization. At operation, dense adhesion of the aortic root due to the previous cardiac operation was confirmed, and this was suggested as the cause for this rare complication.

Aged↗
PubMed2000

Strategy for reduction of stroke incidence in coronary bypass patients with cerebral lesions. Early results and mid-term morbidity using pulsatile perfusion.

OBJECTIVES: Cerebral complication is an important factor affecting the outcome after coronary artery bypass surgery under cardiopulmonary bypass. One of the causes for cerebral complication is preoperative cerebrovascular stenotic lesion. Here, we have studied the effect of pulsatile perfusion on the rate of cerebral complication due to a cerebrovascular lesion in patients undergoing coronary arterial bypass graft under cardiopulmonary bypass. METHODS: 261 consecutive elective patients underwent operation using cardiopulmonary bypass for management of the atherosclerotic ascending aorta. Group 1 consisted of 62 patients with a cerebrovascular stenotic lesion (> or = 75%) identified on a magnetic resonance angiogram or multiple cerebral infarction diagnosed using a computer tomogram. Group 2 consisted of 199 patients diagnosed with no significant cerebral lesion. In Group 1, the systolic blood pressure during cardiopulmonary bypass was maintained at a level of 80 mmHg by means of pulsatile flow. In Group 2, non-pulsatile perfusion was used as usual. RESULTS: The overall hospital mortality was 1.5%, and no mortality was caused by a cerebral event. Only one patient in Group 1 suffered from temporary hemiparalysis. A cerebral complication occurred in only 1.6% in Group 1, and 0.4% overall. The actuarial freedom from cerebrovascular accident after 54 months was 84.4% in Group 1, and 96.2% in Group 2 (p = 0.0011). CONCLUSIONS: Management of the atherosclerotic ascending aorta and the use of pulsatile perfusion were helpful in preventing cerebral injury during CABG.

Aged↗
PubMed2000

Differences in left ventricular response between rheumatic and myxomatous mitral valve disease following mitral valve replacement.

OBJECTIVE: We studied whether differences exist between hearts having rheumatic mitral valves and those having myxomatous mitral valves, in functional, geometrical, and mass changes in the left ventricle after mitral valve replacement. METHODS: Patients who underwent mitral valve replacement without preservation of annular-papillary continuity for pure mitral incompetence were classified into rheumatic and myxomatous based on valvular histopathology. Echographic data measured before surgery was compared to that about 3 weeks after surgery. RESULTS: In the rheumatic group, ejection fraction decreased from 57.5 +/- 10.8 to 47.7 +/- 12.0, indexed left ventricular internal dimension in systole (mm/m2) from 24.7 +/- 6.8 to 20.7 +/- 6.2 (P = 0.0001), and left ventricular mass index (g/m2) from 205 +/- 55 to 138 +/- 54 (P = 0.0002). In the myxomatous group, ejection fraction decreased from 60.4 +/- 11.6 to 39.7 +/- 14.5 (P = 0.0001), indexed left ventricular internal dimension in systole from 24.2 +/- 5.6 to 23.1 +/- 5.5, and left ventricular mass index from 195 +/- 83 to 111 +/- 72 (P = 0.0004). Mean wall thickness index and relative wall thickness showed significant differences between the two groups postoperatively but no significant difference preoperatively. CONCLUSION: Hearts dilated due to chronic mitral incompetence respond differently after valvular replacement with total chordal excision depending on whether a rheumatic or myxomatous mitral valve is involved.

Chordae Tendineae↗
PubMed2000

Phenotypic modulation of smooth muscle cells in human cerebral aneurysmal walls.

We used immunohistochemical methods to analyze the phenotypes of smooth muscle cells (SMCs) in human cerebral arteries and aneurysmal walls. Thirty-two aneurysmal walls were studied; 31 aneurysmal walls were resected at operation and 1 aneurysm was obtained at autopsy. Seven control arteries were obtained at autopsy. Semiserial sections were subjected to immunohistochemical staining with antibodies to alpha-smooth muscle actin (alpha-SMA), desmin and smooth muscle myosin heavy chain isoforms: SM1, SM2 and SMemb. In control cerebral arteries, SMCs in the media were strongly immunostained for alpha-SMA, desmin, SM1 and SM2; immunoreactivity for SMemb was faint or weakly positive. SMCs in both non-ruptured and ruptured aneurysmal walls showed no staining for desmin; the expression of alpha-SMA was well preserved. Compared with control cerebral arteries, in 4 of 11 non-ruptured aneurysmal walls, the staining intensity of SMCs for SMemb was clearly increased. In ruptured aneurysmal walls, the expression of SM2 was lower than in control cerebral arteries and non-ruptured aneurysmal walls. Our study suggests that the phenotype of SMCs in aneurysmal walls is different from the contractile type in the media of normal cerebral arteries, at least partially changing to the synthetic type in some non-ruptured aneurysms. SMCs in ruptured aneurysmal walls may have lost both phenotypes before rupture. Phenotypic modulation of SMCs in the aneurysmal walls appears to be related to a remodeling of the aneurysmal wall and to a rupture mechanism.

Actins↗
PubMed2000

Recurrent incompetence of repaired floppy mitral valves and the severity of myxomatous degeneration.

The purpose of this study was to clarify whether or not severe myxomatous degeneration impairs the stability of a repaired mitral valve after valve-conservative surgery. A total of 21 patients who underwent successful valve-conservative surgery for pure isolated mitral incompetence were classified into two groups, one comprising those with stable mitral valve function and the other comprising those who developed recurrent incompetence within 1 year after surgery. The histological severity of myxomatous degeneration of the mitral leaflet was compared between the two groups, based upon microscopic observation and quantification of the myxomatous area in the fragment that had been surgically excised from the floppy mitral leaflet during valve-conservative surgery. The degree of myxomatous degeneration of the surgically excised fragment was significantly higher in the "recurrent" group than in the "stable" group (P = 0.02). As a microscopically confirmed severely degenerative myxomatous mitral valve may develop recurrent incompetence after valve-conservative surgery within a relatively short period, careful and regular follow-up is required.

Case-Control Studies↗
PubMed2000

Molecular mechanisms, lipoprotein abnormalities and atherogenicity of hyperalphalipoproteinemia.

Hyperalphalipoproteinemia (HALP) is caused by a variety of genetic and environmental factors. Among these, plasma cholesteryl ester transfer protein (CETP) deficiency is the most important and frequent cause of HALP in the Asian populations. CETP facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein (apo) B-containing lipoproteins, and is a key protein in the reverse cholesterol transport system. The deficiency of CETP causes various abnormalities in the concentration, composition, and function of both HDL and low density lipoprotein (LDL). The significance of CETP in terms of atherosclerosis had been controversial. However, the in vitro evidence showed large CE-rich HDL particles in CETP deficiency are defective in cholesterol efflux. Similarly, scavenger receptor BI (SR-BI) knockout mice show a marked increase in HDL-cholesterol but accelerated atherosclerosis in atherosclerosis-susceptible mice. Recent epidemiological studies in Japanese-Americans and in Omagari area where HALP subjects with the intron 14 splicing defect of CETP gene are markedly frequent, have demonstrated an increased incidence of coronary atherosclerosis in CETP-deficient patients. Thus, CETP deficiency is a state of impaired reverse cholesterol transport which may possibly lead to the development of atherosclerosis. The current review will focus on the molecular mechanisms and atherogenicity of HALP, especially CETP deficiency.

Animals↗
PubMed2000

Obstructive jaundice impairs hepatic sinusoidal endothelial cell function and renders liver susceptible to hepatic ischemia/reperfusion.

BACKGROUND/AIMS: Obstructive jaundice is associated with increased surgical morbidity and mortality. While parenchymal injury has been defined in obstructive jaundice, the pathogenesis of hepatic sinusoidal endothelial cell injury in obstructive jaundice is unclear. The aims of this study were to investigate hepatic sinusoidal endothelial cell injury in obstructive jaundice by determining serum hyaluronic acid levels, purine nucleoside phosphorylase/alanine aminotransferase ratios, and hyaluronic acid elimination rate, and also to determine whether hepatic parenchymal cell injury in obstructive jaundice is induced more than in normal liver after hepatic ischemia/reperfusion. METHODS: Male Wistar rats underwent ligation and division of the common bile duct (obstructive jaundice group) or sham operation (Sham group). Serum hyaluronic acid levels and purine nucleoside phosphorylase/alanine aminotransferase ratios in both groups were examined at intervals up to 21 days after surgery. Hepatic blood flow, permeability, neutrophil accumulation, and hyaluronic acid elimination rates in both groups were measured 14 days after surgery. Changes in serum hyaluronic acid and alanine aminotransferase concentrations were determined after 15 min of hepatic ischemia followed by reperfusion. RESULTS: Serum hyaluronic acid levels remained elevated after bile duct ligation. Hepatic sinusoidal endothelial cell swelling was observed by electron microscopy, and hepatic permeability was increased 14 days after bile duct ligation in association with neutrophil accumulation. Hepatic blood flow in obstructive jaundice remained unchanged, but hyaluronic acid elimination capacity was less than that in the Sham group. After hepatic reperfusion, the disappearance rate of serum hyaluronic acid in obstructive jaundice was lower, and serum alanine aminotransferase levels were higher than those in the Sham group. CONCLUSIONS: Our findings suggest that obstructive jaundice impairs sinusoidal endothelial cells and that sinusoidal endothelial cell damage in association with sinusoidal deterioration during obstructive jaundice renders liver susceptible to ischemia/reperfusion relative to normal liver.

Animals↗