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Biomedical subjects

T Nakano

Publications and source records attributed to T Nakano.

At least 253 records · Page 14Linked to original sources

Association of remnant-like particle cholesterol with coronary artery disease in patients with normal total cholesterol levels.

BACKGROUND: Limited information is available as to whether there is a difference in the association of lipid and fibrinolytic variables with coronary artery disease according to the presence or absence of elevated serum total cholesterol. We examined the levels of various lipid and fibrinolytic variables including remnant-like particle cholesterol (RLP-C). RLP-C is a recently established simple assay method for the estimation of triglyceride-rich lipoprotein remnants. METHODS AND RESULTS: Levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglyceride, lipoprotein(a), RLP-C, uric acid, blood glucose, tissue plasminogen activator, tissue plasminogen activator inhibitor type 1, antithrombin III, and protein C were measured in 208 patients who underwent diagnostic coronary angiograms. Of these 208 patients, 57 were hypercholesterolemic (> or =220 mg/dL) and 151 were normocholesterolemic. HDL-C showed significant differences between patients with and those without angiographically determined coronary artery stenosis in both hypercholesterolemic and normocholesterolemic patients (P =.0025 and P =.0003, respectively). Both RLP-C and uric acid showed significant differences only in the normocholesterolemic subgroup (P =.0006 and P =.0060, respectively). This difference in uric acid was not significant by multivariable analysis. The ratio of RLP-C/HDL-C was demonstrated to be highly significantly (P <.0001) associated with coronary artery stenosis in patients with normal total cholesterol, whereas there was no statistically significant association in the hypercholesterolemic patient subgroup. CONCLUSIONS: Our current study disclosed that RLP-C levels are strongly associated with coronary artery disease, especially in patients with normal total cholesterol levels. Moreover, RLP-C/HDL-C ratio may be even more significantly associated with the presence of coronary artery stenosis in normocholesterolemic patients.

Adult↗

Lack of association between TTV viral load and aminotransferase levels in patients with hepatitis C or non-B-C.

TT virus (TTV) is a newly identified un-enveloped single-stranded DNA virus. Although TTV was initially thought to be a new hepatitis virus, it is still unclear whether it causes hepatitis. To clarify the natural history and pathogenesis of TTV infection, serial serum samples from patients with chronic hepatitis were analysed. TTV DNA was quantified by real-time detection polymerase chain reaction assay (RTD-PCR), which was adapted for TTV. Five patients with chronic hepatitis, 4 with hepatitis C and 1 with non-B-C, were studied. The study period ranged from 9 to 50 months. In 3 patients there were frequent increases in TTV DNA titres, but no concomitant elevation of the aminotransferase (ALT) levels. In 2 patients who were treated with interferon, the changes in TTV titres were not synchronized with those of the ALT levels. Thus, in cases of chronic hepatitis, no correlation was observed between the serum TTV DNA titres and the ALT levels.

Adult↗

The effects of microgravity on ligase activity in the repair of DNA double-strand breaks.

PURPOSE: In recent years, contradictory data have been reported about the effects of microgravity on radiation-induced biological responses in space experiments. The aim of the present study was to clarify whether enzymatic repair of DNA double-strand breaks is affected by microgravity using an in vitro enzymatic reaction system. MATERIALS AND METHODS: The DNA repair activity of T4 DNA ligase (EC 6.5.1.1) was measured in vitro for a DNA substrate damaged by restriction enzyme digestion during a US Space Shuttle mission (Discovery; STS-91). After the flight, the amount of ligated DNA molecules was measured using an electrophoresis method. RESULTS: Ligated products (closed circular DNA, open circular DNA and multimeric ligated products) were produced by T4 DNA ligase treatment of linear DNA containing double-strand breaks, and they increased with increasing T4 DNA ligase concentration (0-3 units per microg of plasmid DNA). Almost no difference in T4 DNA ligase activity was detected between the space experiments and the control ground experiments. CONCLUSIONS: No significant effect of microgravity on ligation of damaged DNA was found during space flight. Therefore, other mechanisms must account for the synergism between radiation and microgravity, if it exists.

DNA Damage↗

Preparation and characterization of milk calcium salts by using casein phosphopeptide.

Milk calcium salt solution was prepared by the following procedures using casein phosphopeptides (CPP). To CPP solution, 1 M citric acid, 1 M CaCl2 and 1 M K2HPO4 were added with stirring, while adjusting the pH to 6.7. The prepared solution was left for 12 hr at 25 degrees C and then used for subsequent experiments, or lyophilized. The concentrations of organic phosphate of CPP, calcium, inorganic phosphate, and citrate in the typical milk salt solution were 7, 30, 22, and 10 mM, respectively, which were close to those in bovine milk. The lyophilized sample was easily dissolved in water. No crystal structure of hydroxyapatite was shown in the lyophilized milk calcium salts by X-ray diffraction analysis, although the pattern of KCl crystal was observed. The X-ray diffraction pattern of commercial whey mineral, which was prepared by precipitation at alkaline pH from rennet whey, was similar to that of hydroxyapatite. It was confirmed by high-performance gel chromatographic analysis that the form of calcium phosphate in the milk calcium salts was similar to that of casein micelles.

Animals↗

Presence of the 55 kDa glycosylation inhibiting factor in human serum.

An ELISA system for the human glycosylation inhibiting factor (GIF) was established using polyclonal antibodies against highly purified 13 kDa recombinant human GIF, and the concentration of GIF in the sera of healthy donors and patients with various diseases was determined. GIF was detected in the sera of most healthy individuals and its concentration tended to increase with age. It was also found that the serum GIF levels markedly increased in some patients with rheumatoid arthritis or malignant tumors. Analysis of serum samples by SDS-PAGE and immunoblotting revealed a 55 kDa protein that has both the GIF antigenic determinant and the TCR alpha chain determinant. A 13 kDa GIF was not detected in the sera. In view of our previous findings on antigen-specific GIF from murine suppressor T cell hybridomas indicating that the 55 kDa GIF is a post-translationally formed conjugate of a TCR alpha chain with 13 kDa GIF, we suspect that the 55 kDa GIF detected in human sera is a human homologue of the murine 55 kDa GIF.

Adult↗

Suicidal ideation in cancer patients with major depression.

BACKGROUND: Major depression is a well-documented risk factor for suicide in cancer patients as well as in the general population. However, there are no data explaining why some cancer patients suffering from major depression have suicidal ideation whereas others with the same disorder do not. METHODS: We investigated the background differences between cancer patients suffering from major depression with and without suicidal ideation by analyzing consultation data on patients referred to the Psychiatry Division, National Cancer Center Hospital, Japan. RESULTS: Univariate analysis showed that poor performance status, advanced stage and severe depression were the risk factors for suicidal ideation in these depressive cancer patients. Multivariate logistic regression analysis indicated that older age and severe depression are the final significant risk factors. CONCLUSION: These preliminary findings suggest that severe major depression may be an important indicator of suicidal ideation among cancer patients, that patients' age should be given greater attention and that closer monitoring and more intensive intervention against major depression may be needed.

Age Factors↗

Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6.

Gas6, a ligand of receptor tyrosine kinases Axl, Sky, and Mer, potentiates cell proliferation and prevents cell death. It also contains g-carboxylglutamic acid residues that mediate the interaction of some blood coagulation factors with negatively charged phospholipids. In our previous study, we demonstrated that Gas6 specifically binds to phosphatidylserine (PS) and links Axl-expressing cells to the PS-coated surface. In this study, to further understand the biological role of the interaction of Gas6 with PS, we examined the effect of Gas6 on the uptake of PS liposomes by macrophages. In vitro phagocytosis studies showed that Gas6 enhanced the uptake of PS liposomes approximately threefold and that the interaction of Gas6 with the surface of macrophages was essential for this enhancement. Analyses of the mechanism of the uptake of PS liposome suggested that Gas6 interacts with PS liposome via its N-terminal Gla domain and with macrophages via its C-terminal domain. Like that of PS liposomes, the uptake of apoptotic cells by macrophages was also enhanced, approximately twofold, in the presence of Gas6. These findings suggest that Gas6 may help phagocytic cells recognize cells with PS exposed on their surfaces, which is considered to be one of the mechanisms for clearing away dying cells. Thus, Gas6 may play a critical role in homeostasis by facilitating the clearance of PS-expressing cells.

Animals↗

Acclimation of leaf characteristics of Fagus species to previous-year and current-year solar irradiances.

To examine the effects of different solar irradiances on leaf characteristics at the leaf primordium and expansion stages, we shaded parts of branches in the upper canopies of two adult beech trees, Fagus crenata Blume and Fagus japonica Maxim., for 4 years. The treatments during the leaf primordium and leaf expansion stages, respectively, were: (1) high light and high light (H, control), (2) high light and low light (HL), (3) low light and low light (LL), and (4) low light and high light (LH). Both number of cell layers in palisade tissue and individual leaf area were affected by the previous-year irradiance, whereas cell length of palisade tissue was larger in LH leaves than in LL leaves, suggesting determination by current-year irradiance. Lamina chlorophyll/nitrogen ratio was higher in HL and LL leaves than in LH leaves, suggesting determination by current-year irradiance. Diurnal minimum values of leaf water potential measured under sunlit conditions were lower in H and LH leaves than in HL and LL leaves. Effective osmotic adjustment was found in H and LH leaves, suggesting that leaf water relations were affected by current-year irradiance. Net photosynthetic rate and stomatal conductance measured under sunlight conditions were higher in H and LH leaves than in HL and LL leaves. Thus, effects of current-year irradiance had a greater effect on leaf-area-based daily carbon gain than previous-year irradiance.

Acclimatization↗

Treatment of micrognathia with edentulous maxilla by sagittal split mandibular osteotomy and a subperiosteal implant immobilized with transmaxillary screws.

Micrognathia complicated by edentulous maxilla was treated by performing sagittal-split mandibular osteotomy and immobilizing a subperiosteal implant using transmaxillary screws. The patient was a 42-year-old man who had a birdlike facial deformity caused by significant hypoplasia of the mandible. He also demonstrated significant malocclusion attributable to micrognathia and edentulous maxilla caused by resorption of the alveolar bone. These conditions impaired his mastication and articulation, making it impossible for him to eat regular food or carry out normal conversation. A subperiosteal implant was placed on the edentulous maxilla, and was rigidly immobilized to the maxilla using five transmaxillary screws. A prosthesis was then attached to the implant, and by using the implant as the point of reference and the anchor, the mandible was moved forward by sagittal-split mandibular osteotomy. Intermaxillary fixation was subsequently performed. The postoperative course has been favorable, and his facial complexion has improved significantly. One and a half years after his surgery, there has been no sign of complications or malocclusion caused by mandibular retraction. He is now able to eat regular food and speak normally.

Adult↗

The negative inotropic effect of beta3-adrenoceptor stimulation in the beating guinea pig heart.

Although beta3-adrenoceptors (ARs) have been extensively characterized in brown and white adipocytes, their actions in the beating heart are unclear. We examined the effects of a beta3-AR agonist, BRL37344, on cardiac function and calcium transients in Langendorff-perfused guinea pig hearts by simultaneously measuring left ventricular (LV) pressure and Ca2+-dependent indo-1 fluorescence. BRL37344 induced a dose-dependent negative inotropic effect at concentrations from 10(-11) to 10(-8) M. Maximally, LV developed pressure decreased to 80+/-2%, +dP/dt to 81+/-2%. and -dP/dt to 81+/-3% of their respective control values (p < 0.01). The amplitude of the Ca2+ transient also decreased (to 92+/-3% of the control level; p < 0.01). The BRL37344 dose-response curve was not altered by nadolol (10(-5) M), a potent beta1- and beta2-AR antagonist, but completely suppressed by bupranolol (10(-6) M), a potent beta1-, beta2- and beta3-AR antagonist. To assess the potential role of a nitric oxide synthase (NOS) pathway, we determined whether the NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), modified the contractile response to BRL37344. L-NAME (10(-7) and 10(-4) M) attenuated the negative inotropic effects on LV developed pressure by 35 and 50%, suggesting that beta3-AR stimulation induces a negative inotropic effect on guinea pig hearts partly through a decrease in the Ca2+ transient and partly by the NOS pathway.

Adrenergic beta-Agonists↗

Electrophysiological determinants of persistent dual atrioventricular nodal pathway physiology after slow pathway ablation in atrioventricular nodal reentrant tachycardia.

UNLABELLED: The purpose of this study was to examine the electrophysiological determinants of the elimination of recurrent atrioventricular nodal reentrant tachycardia (AVNRT) despite the persistence of dual AV nodal pathway physiology or single echo beats after ablation procedures. The study included 26 patients with common AVNRT who had undergone successful ablation treatment and no long-term recurrence of AVNRT. The slow pathway potential was targeted, and the endpoint of ablation was one echo during atrial extrastimulus testing (ET) with isoproterenol. Persistent dual pathways physiology or single echoes were present in 12 patients (group I) and absent in 16 (group II) after ablation. The number of anterograde AV nodal pathways and maximum AH interval (Max AH) during ET were measured before and after ablation, and ventriculoatrial conduction during ventricular pacing was examined. RESULTS: (1) multiple AV nodal pathways were more frequently observed in group I than in group II (50.0% vs 7%, P < 0.05); (2) Max AH decreased significantly after ablation in both groups (309 +/- 157 vs 171 +/- 53 ms in group II; P < 0.01, and 409 +/- 65 vs 274 +/- 86 ms in group I; P < 0.001); and (3) retrograde dual pathway conduction was more common in group I than in group II. These data suggest the presence of nonuniform conductive properties of the AV node in group I and that ablation targeting the slow pathway potential prevents recurrences of AVNRT by eliminating the pathway with the longest conduction time.

Adult↗

Mechanism of the incidental production of a melanin-like pigment during 6-demethylchlortetracycline production in Streptomyces aureofaciens.

The secondary metabolite 6-demethylchlortetracycline (6-DCT), which is produced by Streptomyces aureofaciens, is used as a precursor of semisynthetic tetracyclines. Strains that produce 6-DCT also produce a melanin-like pigment (MP). The correlation between MP production and 6-DCT production was investigated by using S. aureofaciens NRRL 3203. Production of both MP and 6-DCT was repressed by phosphate or ammonium ions, suggesting that syntheses of these compounds are controlled by the same regulators. Ten chlortetracycline-producing recombinants were derived from 6-DCT-producing mutant NRRL 3203 by gene replacement. All of the recombinants produced chlortetracycline but not MP, indicating that MP production is the results of a defect in the 6-methylation step and suggesting that the polyketide nonaketideamide is a common intermediate leading to MP as well as 6-DCT. To further examine the possibility that MP might be synthesized via the 6-DCT-biosynthetic pathway, mutants defective in 6-DCT biosynthesis were derived from a 6-DCT producer. Some of these mutants were able to produce MP, while others, including mutants with mutations in the gene encoding anhydrotetracycline oxygenase, an enzyme catalyzing the penultimate step in the pathway, produced neither 6-DCT nor MP. Production of 6-DCT and production of MP were restored simultaneously by integrative transformation with the corresponding 6-DCT-biosynthetic genes, indicating that some of 6-DCT-biosynthetic enzymes are indispensable for MP production. These findings suggest that a defect in the 6-methylation step results in redirection of carbon flux from a certain intermediate in the 6-DCT-biosynthetic pathway to a shunt pathway and results in MP production.

Anti-Bacterial Agents↗

Development of a TT virus DNA quantification system using real-time detection PCR.

Although TT virus (TTV) was isolated from a cryptogenic posttransfusion hepatitis patient, its pathogenic role remains unclear. It has been reported that the majority of the healthy population is infected with TTV. To elucidate the differences between TTV infection in patients with liver diseases and TTV infection in the healthy population, a quantification system was developed. TTV DNA was quantified by a real-time detection PCR (RTD-PCR) assay on an ABI Prism 7700 sequence detector. With this system, TTV DNA was quantified in 78 hepatitis C virus (HCV)-infected patients (63 with elevated serum alanine aminotransferase [ALT] levels and 15 with normal ALT levels) and in 70 voluntary blood donors (BDs). The quantification range was 2.08 to 7.35 log copies/ml. The intra-assay and interassay coefficients of variation were 0.37 to 6.33% and 0.60 to 7.07%, respectively. The mean serum TTV DNA levels in the HCV-infected patients with both elevated and normal ALT levels and BDs were 3.69 +/- 0.89, 3.45 +/- 0.76, and 3.45 +/- 0.67 log copies/ml, respectively. Comparison of the serum TTV DNA levels among the HCV-infected patients revealed that they were not related to the serum ALT and HCV core protein levels or to the histopathological score on liver biopsy. This study showed that (i) the RTD-PCR assay for the detection of TTV was accurate and had a high degree of sensitivity, (ii) the mean serum TTV DNA level was similar among HCV-infected patients, irrespective of their ALT level, and also among BDs, and (iii) a high serum TTV DNA level does not affect the serum ALT and HCV levels or liver damage in HCV-infected patients.

Blood Donors↗

Coexistence of giant aneurysm of sinus of Valsalva and coronary artery aneurysm associated with idiopathic hypereosinophilic syndrome.

Aneurysms of the coronary sinuses of Valsalva and coronary artery aneurysms are uncommon cardiac anomalies, and cases in which these two uncommon lesions occur at the same time are extremely rare. A case of a woman with unstable angina who had a giant aneurysm of the left coronary sinus and multiple coronary artery aneurysms associated with an idiopathic hypereosinophilic syndrome is presented. Her sustained eosinophilia, elevated eosinophilic cationic protein concentration, and pathological findings of eosinophil infiltration of the aortic wall suggested the association of eosinophilia induced vascular injury as the cause of these aneurysms. This is the first such case to survive following surgical treatment.

Aortic Aneurysm↗

Cross talk of shear-induced production of prostacyclin and nitric oxide in endothelial cells.

We tested the hypothesis that vessel homeostasis is maintained through the cross talk of shear-induced production of prostacyclin and nitric oxide (NO). Confluent human umbilical vein endothelial cells (HUVEC) were exposed to fluid shear stress at 15 dyn/cm(2) using a cone-plate device, and the concentrations of 6-keto-PGF(1alpha) and NO metabolites (nitrate and nitrite) in the medium were measured with radioimmunoassay and the Greiss method, respectively. Compared with static control, shear stress increased cumulative prostacyclin production by twofold after 90 min of exposure. Inhibition of NO synthase enhanced flow-induced prostacyclin production by twofold without affecting the baseline production. Guanylyl cyclase inhibitor enhanced flow-induced prostacyclin production to the same degree. In contrast, a stable agonist of cGMP attenuated the rapid early phase of flow-dependent prostacyclin production. Shear-induced NO metabolite production was unaffected even after indomethacin inhibited prostacyclin production. We conclude that NO shows an inhibitory effect on prostacyclin production under shear stress and that vessel homeostasis may be maintained through an increase in prostacyclin production when NO synthesis is impaired in endothelial cells.

Cell Survival↗

Pulsatile flow enhances endothelium-derived nitric oxide release in the peripheral vasculature.

The effects of pulsatility in blood flow on endothelium-derived nitric oxide (EDNO) release in the peripheral vasculature were investigated. The basal and flow-stimulated EDNO release were compared between pulsatile and nonpulsatile systemic flows before and after the administration of NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Peripheral vascular resistance (PVR) was significantly lower in pulsatile flow than in nonpulsatile flow, but this difference disappeared after L-NMMA. The percent increase in PVR by L-NMMA was significantly larger in pulsatile flow. In reactive hyperemia in the hindlimb, the peak flow did not differ; however, both the repayment flow and the duration were significantly larger in pulsatile flow. Percent changes of these parameters by L-NMMA were significantly larger in pulsatile flow. These data indicated that pulsatility significantly enhances the basal and flow-stimulated EDNO release in the peripheral vasculature under in vivo conditions. We also studied the involvement of the Ca(2+)-dependent and Ca(2+)-independent pathways in flow-induced vasodilation using calmodulin inhibitor calmidazolium and tyrosine kinase inhibitor erbstatin A. PVR was significantly elevated by erbstatin A but not by calmidazolium, suggesting that flow-induced vasodilation was largely caused by tyrosine kinase inhibitor-sensitive activation of NO synthase.

Angiotensin II↗

Effects of nonpulsatile left heart bypass on renal sympathetic nerve activity in rabbits.

To determine the effects of nonpulsatile left heart bypass (LHB) on sympathetic nerve activity the renal sympathetic nerve activity (RSNA) was directly measured in rabbits. In anaesthetized rabbits (n=6), LHB was instituted with a centrifugal pump. Before and during LHB, heart rate (HR), arterial pressure (AP), central venous pressure (CVP), left atrial pressure (LAP) and spike counts of RSNA were measured. After bilateral vagotomy (section of the afferent inputs of the cardiac reflex arc) the same parameters were measured before and during LHB. Data were obtained at the same level of mean AP before and during LHB. Mean AP and CVP were not changed by LHB before and after vagotomy. LAP was significantly decreased by LHB before and after vagotomy. RSNA and HR were not significantly changed by LHB before and after vagotomy. Our results clarify the complex baroreflex control during nonpulsatile LHB and indicate that RSNA is not altered by LHB.

Action Potentials↗