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Biomedical subjects

Tadashi Nakamura

Publications and source records attributed to Tadashi Nakamura.

At least 19 recordsLinked to original sources
PubMed2003

Measurement of fasting serum apoB-48 levels in normolipidemic and hyperlipidemic subjects by ELISA.

The present study was designed to evaluate the metabolism of chylomicron and chylomicron remnants by measuring serum apolipoprotein B-48 (apoB-48) levels in 335 normolipidemic and 253 hyperlipidemic subjects using a novel ELISA system. The distribution of fasting serum apoB-48 levels in normolipidemic subjects varied widely, ranging from <1 to >24 microgram/ml (mean, 5.2 +/- 3.8 microgram/ml; median, 3.9 microgram/ml). Serum apoB-48 levels correlated with serum triglyceride (TG) concentrations (r = 0.45, P < 0.001), but not with total cholesterol levels. Serum apoB-48 levels were 7 to 18 times higher in patients with Type I, Type V, and Type III hyperlipidemia, and only slightly higher in patients with Type IIa, Type IIb, and Type IV hyperlipidemia, compared with normolipidemic subjects. The calculated apoB-48/TG ratio was elevated only in patients with dysbetalipoproteinemia (apoE2/2 phenotype). In normolipidemic subjects, oral fat loading resulted in about 2-fold increase in serum apoB-48 levels, with a peak level recorded at 3-4 h postloading, and then returned to the baseline level within 6 h. On the other hand, in patients with dysbetalipoproteinemia, serum apoB-48 levels did not change considerably. Our results indicate that serum apoB-48 is a very useful parameter for evaluating lipoprotein metabolism in exogenous pathways.

Adult↗
PubMed2003

Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue.

BACKGROUND: High-sensitive C-reactive protein (hs-CRP) is a well-known risk factor for coronary artery disease (CAD). Recently, we have demonstrated that adiponectin served as an antiatherogenic plasma protein which was secreted specifically from adipocytes. The present study investigated the association between adiponectin and CRP in the blood stream and adipose tissue. METHODS AND RESULTS: We studied a total of 101 male patients, 71 of whom had angiographically documented coronary atherosclerosis. As a control group, 30 patients with normal coronary angiogram were included. The plasma hs-CRP levels were negatively correlated with the plasma adiponectin levels (r=-0.29, P<0.01). The plasma adiponectin concentrations were significantly lower and the hs-CRP levels were significantly higher in the CAD patients compared with control subjects. The mRNA levels of CRP and adiponectin were analyzed by quantitative real-time polymerase chain reaction method. We found that the CRP mRNA was expressed in human adipose tissue. A significant inverse correlation was observed between the CRP and adiponectin mRNA levels in human adipose tissue (r=-0.89, P<0.01). In addition, the CRP mRNA level of white adipose tissue in adiponectin deficient mice was higher than that of wild-type mice. CONCLUSIONS: The reciprocal association of adiponectin and CRP levels in both human plasma and adipose tissue might participate in the development of atherosclerosis.

Adiponectin↗
PubMed2003

Association of hypoadiponectinemia with coronary artery disease in men.

BACKGROUND: Adiponectin is an adipocyte-derived plasma protein that accumulates in the injured artery and has potential antiatherogenic properties. This study was designed to determine whether a decreased plasma adiponectin level (hypoadiponectinemia) can be independently associated with the prevalence of coronary artery disease (CAD). METHODS AND RESULTS: The consecutive 225 male patients were enrolled from inpatients who underwent coronary angiography. Voluntary blood donors (n=225) matched for age served as controls. Plasma adiponectin levels in the CAD patients were significantly lower than those in the control subjects. Multiple logistic regression analysis including plasma adiponectin level, diabetes mellitus, dyslipidemia, hypertension, smoking habits, and body mass index revealed that hypoadiponectinemia was significantly and independently correlated with CAD (P<0.0088). The entire study population was categorized in quartiles based on the distribution of plasma adiponectin levels. The interquartile cutoff points were 4.0, 5.5, and 7.0 microg/mL. The multivariate-adjusted odds ratios for CAD in the first, second, and third quartiles were 2.051 (95% confidence interval [CI], 1.288 to 4.951), 1.221 (95% CI, 0.684 to 2.186), and 0.749 (95%CI, 0.392 to 1.418), respectively. CONCLUSIONS: Male patients with hypoadiponectinemia (<4.0 microg/mL) had a significant 2-fold increase in CAD prevalence, independent of well-known CAD risk factors.

Adiponectin↗
PubMed2003

Wallenberg's syndrome: neurotological classification.

OBJECTIVES: Visually induced eye movements were investigated in 26 patients with Wallenberg's syndrome. METHODS: Slow-phase optokinetic nystagmus (OKN) velocities, pursuit gains, and percentage fixation suppression (%FS) of caloric nystagmus were recorded by DC electrooculography (EOG), and stored directly onto FM magnetic tape. RESULTS: OKN velocities, pursuit gains, and %FS decreased toward the lesion side (group A), whereas OKN velocities and pursuit gains decreased toward the side contralateral to the lesion side. %FS decreased toward the lesion side (group B). MR images in group A showed that lesions were only in and near to the vestibular nuclei, and images in group B showed that lesions extended to the cerebellum. CONCLUSION: Visually guided eye movements allow classification of Wallenberg's syndrome into two types, one with brainstem lesions and one with both brainstem and cerebellar lesions. This demonstrates that assessing eye movements is helpful in supplementing MRI data.

Adult↗
PubMed2003

Saccadic adaptation in the horizontal and vertical directions in normal subjects.

We studied the properties of adaptive gain control in the saccadic system and examined whether the adaptations in the horizontal direction transferred to those in the vertical direction, and vice versa, in 16 normal subjects. Eye movements were measured using search coil system. In the adaptive session, a target moved randomly in amplitude steps of 20 degrees or 30 degrees, with half of the subjects performing in the horizontal direction and the others in the vertical direction. The target eccentricity was changed by a constant percentage (70%) during each saccade aimed at the target. Gains were gradually decreased during the course of 120 repetitions, and then approached approximately 70%. Comparison was made of the accuracy (saccadic amplitude/first target step amplitude) of horizontal and vertical vectors of oblique saccades before and after the adaptation. After the horizontal adaptation, the accuracy of horizontal vectors decreased in the horizontal direction (P<0.05) but not in the vertical direction. After the vertical adaptation, however, the accuracy of horizontal and vertical vectors did not decrease. Our data show that adaptive gain control in the horizontal direction might not transfer to that in the vertical direction, nor vice versa.

Adult↗
PubMed2003

End-to-end anastomosis in chronic tracheal stenosis.

OBJECTIVE: This study assessed the efficacy and safety of end-to-end anastomosis of the trachea following segmental resection in chronic tracheal stenosis. METHODS: End-to-end anastomoses of the trachea were performed in 35 patients with chronic tracheal stenosis; 18 patients with tracheal invasion of thyroid cancer and 17 patients with long-term intubation and blunt injuries of the trachea. RESULTS: All operations were successful, except one whose unilateral recurrent nerve had not been identified in the recurrent thyroid cancer invasion with trachea. CONCLUSION: This operation provides a one-step cure for the stenosed trachea and can be applied to the resection of less than six tracheal segments.

Adenocarcinoma↗
PubMed2003

Determination of each neutral oligosaccharide in the milk of Japanese women during the course of lactation.

Using reverse-phase HPLC after pyridylamination, we quantified the concentrations of major neutral oligosaccharides in the milk of sixteen Japanese women collected at 4, 10, 30 and 100 d postpartum. In colostrum and mature milk (30 d lactation), lacto-N-fucopentaose (LNFP) I was the most abundant oligosaccharide, followed by 2'-fucosyllactose (2'-FL) + lacto-N-difucotetraose (LNDFT), LNFP II + lacto-N-difucohexaose II (LNDFH II), and 3-fucosyllactose (3-FL). Together these accounted for 73 % of the total weight of neutral oligosaccharides in colostrum and mature milk. Changes in concentration occurred during the course of lactation. LNFP I and 2'-FL + LNDFT increased from 4 to 10 d postpartum, and then declined by 100 d. LNFP II + LNDFH II steadily increased during the first 30 d and then declined. In contrast, 3-FL increased steadily throughout the entire 100 d of study. Large differences were observed between our data and previously published data in Italian women, in terms of both the concentration and temporal changes of each oligosaccharide. These differences may be caused by different assay methodology, although racial differences cannot be ruled out.

Adult↗
PubMed2002

Endomorphins suppress nociception-induced c-Fos and Zif/268 expression in the rat spinal dorsal horn.

We evaluated the potency of endomorphin-1 and -2 as endogenous ligands on c-Fos and Zif/268 expression in the spinal dorsal horn by formalin injection to the rat hind paw. Endomorphin-1, -2, or morphine was administered intrathecally or intracerebroventricularly 5 min before formalin injection (5%, 100 microl). All drugs produced marked reductions of formalin-induced c-Fos and Zif/268 immunoreactivity in laminae I and II, and laminae V and VI in the rat lumbar spinal cord. The reductions of Zif/268 expression by endomorphins were greater than those by morphine, while the reductions of c-Fos expression by endomorphins were smaller than those by morphine. These effects of endomorphins were attenuated by pretreatment with naloxone. These results indicate that endomorphin-1 and -2 act as endogenous ligands of mu-opioid receptor in neurons of the spinal dorsal horn and suppress the processing of nociceptive information in the central nervous system.

Analgesics, Opioid↗
PubMed2002

Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell.

BACKGROUND: Vascular smooth muscle cell proliferation plays an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipocyte-specific plasma protein, accumulated in the human injured artery and suppressed endothelial inflammatory response as well as macrophage-to-foam cell transformation. The present study investigated the effects of adiponectin on proliferation and migration of human aortic smooth muscle cells (HASMCs). Methods and Results- HASMC proliferation was estimated by [(3)H] thymidine uptake and cell number. Cell migration assay was performed using a Boyden chamber. Physiological concentrations of adiponectin significantly suppressed both proliferation and migration of HASMCs stimulated with platelet-derived growth factor (PDGF)-BB. Adiponectin specifically bound to (125)I-PDGF-BB and significantly inhibited the association of (125)I-PDGF-BB with HASMCs, but no effects were observed on the binding of (125)I-PDGF-AA or (125)I-heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) to HASMCs. Adiponectin strongly and dose-dependently suppressed PDGF-BB-induced p42/44 extracellular signal-related kinase (ERK) phosphorylation and PDGF beta-receptor autophosphorylation analyzed by immunoblot. Adiponectin also reduced PDGF-AA-stimulated or HB-EGF-stimulated ERK phosphorylation in a dose-dependent manner without affecting autophosphorylation of PDGF alpha-receptor or EGF receptor. CONCLUSIONS: The adipocyte-derived plasma protein adiponectin strongly suppressed HASMC proliferation and migration through direct binding with PDGF-BB and generally inhibited growth factor-stimulated ERK signal in HASMCs, suggesting that adiponectin acts as a modulator for vascular remodeling.

Adipocytes↗
PubMed2002

Effect of ionotropic glutamate receptor antagonists on Fos-like immunoreactivity in the dorsal horn following transection of the rat sciatic nerve.

Fos-like immunoreactivity (FLI) was investigated in the lumbar dorsal horn 2 h after transection of the rat sciatic nerve and sham operation. FLI following nerve transection was distributed through the medio-lateral extension of the superficial layer of the dorsal horn, while FLI after sham operation, tissue injury, was restricted to the lateral one-third of this layer. The number of FLI neurons in the lateral one-third was similar in the two operations, indicating that neurons expressing FLI in the medial two-thirds and in the lateral one-third of the superficial layer after nerve transection are derived from nerve injury and tissue injury, respectively. FLI in the lateral one-third, but not the medial two-thirds, after nerve transection was significantly reduced by pretreatment with NMDA and AMPA/KA receptor antagonists, indicating that there is a considerable difference in the contributions of ionotropic glutamate receptors to FLI in this layer induced by nerve injury and tissue injury.

Afferent Pathways↗
PubMed2002

Differential effects of NMDA and AMPA/KA receptor antagonists on c-Fos or Zif/268 expression in the rat spinal dorsal horn induced by noxious thermal or mechanical stimulation, or formalin injection.

The involvement of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate (KA) receptors in the induction of c-Fos and Zif/268 expression in spinal dorsal horn neurons following noxious thermal or mechanical stimulation, or formalin injection into the rat hind paw was examined by intrathecal administration of a competitive NMDA receptor antagonist, 2-amino-5-phosphonopentanoic acid (APV) or an AMPA/KA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), or both, 30 min prior to noxious stimulation. APV caused a significant reduction in the level of c-Fos expression in the superficial layer induced by each of these three noxious stimuli. The effects of APV on Zif/268 expression or of CNQX on c-Fos or Zif/268 expression in the superficial layer induced by these three noxious stimuli were dependent on the type of stimulus applied to the rat hind paw. The noxious thermal stimulus-evoked c-Fos expression level was reduced by APV and/or CNQX, while Zif/268 expression was hardly changed. Both c-Fos and Zif/268 expressions following formalin injection were reduced by APV alone and APV+CNQX, but not by CNQX alone. Zif/268 expression following noxious mechanical stimulation was significantly reduced only by APV+CNQX although APV or CNQX alone did not affect the expression, while c-Fos expression was reduced by APV and APV+CNQX but not by CNQX alone. These findings suggest that NMDA and AMPA/KA receptors are differentially involved in c-Fos and Zif/268 expression in the spinal dorsal horn following noxious thermal, formalin and mechanical stimulation.

2-Amino-5-phosphonovalerate↗
PubMed2002

Chemical characterization of the oligosaccharides in beluga (Delphinapterus leucas) and Minke whale (Balaenoptera acutorostrata) milk.

Carbohydrates were extracted from the milk of a beluga, Delphinopterus leucas (family Odontoceti), and two Minke whales, Balaenoptera acutorostrata (Family Mysticeti), sampled late in their respective lactation periods. Free oligosaccharides were separated by gel filtration and then neutral oligosaccharides were purified by preparative thin layer chromatography and gel filtration, while acidic oligosaccharides were purified by ion-exchange chromatography, gel filtration and high performance liquid chromatography (HPLC). Their structures were determined by 1H-NMR. In one of the Minke whale milk samples, lactose was a dominant saccharide, with Fuc(alpha1-2)Gal(beta1-4)Glc(2'-fucosyllactose), Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc(lacto-N-neotetraose), GalNAc(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)Glc(A-tetrasaccharide), Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc (para lacto-N-neohexaose), Neu5Ac(alpha2-3)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc (sialyl lacto-N-neotetraose), Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc (LST c) and Neu5Ac(alpha2-3)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc (sialyl para lacto-N-neohexaose) also being found in the milk. The second Minke whale sample contained similar amounts of lactose, 2'-fucosyllactose and A-tetrasaccharide, but no free sialyl oligosaccharides. Sialyl lacto-N-neotetraose and sialyl para lacto-N-neohexaose are novel oligosaccharides which have not been previously reported from any mammalian milk or colostrum. These and other oligosaccharides of Minke whale milk may have biological significance as anti-infection factors, protecting the suckling young against bacteria and viruses. The lactose of Minke whale milk could be a source of energy for them. The beluga whale milk contained trace amounts of Neu5Ac(alpha2-3)Gal(beta1-4)Glc(3'-N-acetylneuraminyllactose), but the question of whether it contained free lactose could not be clarified. Therefore, lactose may not be a source of energy for suckling beluga whales.

Animals↗
PubMed2002

Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation.

Aquaporin adipose (AQPap), which we identified from human adipose tissue, is a glycerol channel in adipocyte [Kishida et al. (2000) J. Biol. Chem. 275, 20896-20902]. In the current study, we determined the genomic structure of the human AQPap gene, and identified three AQPap-like genes that resembled (approximately 95%) AQPap, with little expression in human tissues. The AQPap promoter contained a putative peroxisome proliferator response element (PPRE) at -46 to -62, and a putative insulin response element (IRE) at -542/-536. Deletion of the PPRE abolished the pioglitazone-mediated induction of AQPap promoter activity in 3T3-L1 adipocytes. Deletion and single base pair substitution analysis of the IRE abolished the insulin-mediated suppression of the human AQPap gene. Analysis of AQPap sequence in human subjects revealed three missense mutations (R12C, V59L and G264V), and two silent mutations (A103A and G250G). The cRNA injection of the missense mutants into Xenopus oocytes revealed the absence of the activity to transport glycerol and water in the AQPap-G264V protein. In the subject homozygous for AQPap-G264V, exercise-induced increase in plasma glycerol was not observed in spite of the increased plasma noradrenaline. We suggest that AQPap is responsible for the increase of plasma glycerol during exercise in humans.

Aquaporins↗
PubMed2002

Coordinated regulation of fat-specific and liver-specific glycerol channels, aquaporin adipose and aquaporin 9.

Plasma glycerol is a major substrate for hepatic gluconeogenesis. Aquaporin adipose (AQPap/7), an adipose-specific glycerol channel, provides fat-derived glycerol into plasma. In the present study, we cloned the coding and promoter regions of mouse aquaporin 9 (AQP9), a liver-specific glycerol channel. Fasting and refeeding of mice increased and decreased hepatic AQP9 mRNA levels, respectively. Insulin deficiency induced by streptozotocin resulted in increased hepatic AQP9 mRNA. These changes in hepatic AQP9 mRNA were accompanied by those of hepatic gluconeogenic mRNAs and plasma glycerol levels. In cultured hepatocytes, insulin downregulated AQP9 mRNA. The AQP9 promoter contained the negative insulin response element TGTTTTC at -496/-502, similar to the promoter of the AQPap/7 gene. In contrast, in insulin-resistant db+/db+ mice, AQPap/7 mRNA in fat and AQP9 mRNA in liver were increased, despite hyperinsulinemia, with high plasma glycerol and glucose levels. Glycerol infusion in the db+/db+ mice augmented hepatic glucose output. Our results indicate that coordinated regulations of fat-specific AQPap/7 and liver-specific AQP9 should be crucial to determine glucose metabolism in physiology and insulin resistance.

Amino Acid Sequence↗
PubMed2002

Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein.

Adiponectin, an adipose-specific secretory protein, exhibits antidiabetic and antiatherogenic properties. In the present study, we examined the effects of sex hormones on the regulation of adiponectin production. Plasma adiponectin concentrations were significantly lower in 442 men (age, 52.6 +/- 11.9 years [mean +/- SD]) than in 137 women (53.2 +/- 12.0 years) but not different between pre- and postmenopausal women. In mice, ovariectomy did not alter plasma adiponectin levels. In contrast, high levels of plasma adiponectin were found in castrated mice. Testosterone treatment reduced plasma adiponectin concentration in both sham-operated and castrated mice. In 3T3-L1 adipocytes, testosterone reduced adiponectin secretion into the culture media, using pulse-chase study. Castration-induced increase in plasma adiponectin was associated with a significant improvement of insulin sensitivity. Our results indicate that androgens decrease plasma adiponectin and that androgen-induced hypoadiponectinemia may be related to the high risks of insulin resistance and atherosclerosis in men.

3T3 Cells↗
PubMed2002

[Disorder of lipid metabolism in visceral fat syndrome--relation to familial combined hyperlipidemia].

'Visceral fat syndrome' is a clinical entity compatible with Syndrome X, Deadly quartet, and insulin resistance syndrome. All of these entities express the pathophysiology of multiple risk factor syndrome in which multiple risks of arteriosclerosis, i.e., hypertension, hyperlipidemia, and glucose intolerance, cluster in an individual. The accumulation of visceral fat plays a crucial role in the pathogenesis of visceral fat syndrome. On the other hand, familial combined hyperlipidemia (FCHL) is a common hyperlipidemia associated with premature arteriosclerosis. The pathogenesis of FCHL is not fully elucidated but the visceral fat accumulation may play an important role in the pathophysiology of FCHL. In this review, we will discuss the relationship between visceral fat syndrome and FCHL.

Female↗