Design and fabrication of a coupled high-Q photonic nanocavity system with large coupling coefficients.

In a previous work, we demonstrated a coupled cavity system where photons in one storage cavity can be transferred to another storage cavity at an arbitrary time by applying a voltage pulse to a third cavity placed in a p-i-n junction. In this work, we demonstrate methods to improve the transfer efficiency and photon lifetimes of such a coupled system. Firstly, we designed a photonic-crystal structure that achieves a large coupling coefficient without reducing the radiation quality factor compared to the previously proposed structure: The photonic-crystal design was changed to a more symmetric configuration to suppress radiation losses and then optimized using an automatic structure tuning method based on the Covariance Matrix Adaptive Evolutional Strategy (CMAES). Here we added two improvements to achieve an evolution toward the desired direction in the two-dimensional target parameter space (spanned by the coupling coefficient and the inverse radiation loss). Secondly, to improve the experimental cavity quality factors, we developed a fabrication process that reduces the surface contamination associated with the fabrication of the p-i-n junction: We covered the photonic structure with a SiO2 mask to avoid the contamination and the electrode material was changed from Al to Au/Cr to enable cleaning by a weak acid. Owing to these improvements of the cavity design and the fabrication process, the obtained system provides coupling strengths that are about three times stronger and photon lifetimes that are about two times longer, compared to the previously reported system.

Epicatechin downregulates adipose tissue CCL19 expression and thereby ameliorates diet-induced obesity and insulin resistance.

BACKGROUND AND AIMS: Epicatechin (EC) intake has been suggested to be beneficial for the prevention of cardiovascular disorders, and it is well known that adipose tissue inflammation is one of the major risk factors for coronary heart diseases. The purpose of the present study was to determine the in vitro and in vivo effects of EC on adipose tissue inflammation and obesity. METHODS AND RESULTS: DNA microarray analysis was performed to evaluate the effects of EC on gene expression in adipocytes co-cultured with bacterial endotoxin-stimulated macrophages. To determine the in vivo effects of the catechin, C57BL/6 mice were fed either a high-fat diet (HFD) or HFD combined with EC, and metabolic changes were observed EC suppressed the expression of many inflammatory genes in the adipocytes co-cultured with endotoxin-stimulated macrophages. Specifically, EC markedly suppressed chemokine (CC motif) ligand 19 (CCL19) expression. The target cell of EC appeared to macrophages. The in vivo study indicated that mice fed the EC-supplemented HFD were protected from diet-induced obesity and insulin resistance. Accordingly, the expression levels of genes associated with inflammation in adipose tissue and in the liver were downregulated in this group of mice. CONCLUSIONS: EC exerts beneficial effects for the prevention of adipose tissue inflammation and insulin resistance. Since we previously reported that mice deficient in the CCL19 receptor were protected from diet-induced obesity and insulin resistance, it can be concluded that the beneficial effects of EC could be mediated, at least in part, by marked suppression of CCL19 expression.

Comparison of direct and indirect occlusal contact examinations with different clenching intensities.

The aims of this study were to examine the change of occlusal contact area following the increment of clenching intensity using silicone materials and electromyography (EMG) in normal subjects and to compare direct intra-oral examination with indirect examination using dental casts mounted by means of two impression methods. Participants were 7 men and 5 women with no more than one missing tooth per quadrant and no pain in the head and neck region. During the task, intercuspal position was maintained with minimal force, 20% maximum voluntary contraction (MVC) and 40% MVC using electromyography visual feedback. Three types of occlusal contact examinations were performed with the aid of blue silicone material in randomised order: (i) intra-oral direct occlusal contact examination (DE), (ii) indirect occlusal contact examination with dental casts using conventional impression method (IEC) and (iii) using occlusal impression method (IEO). Total occlusal contact area during DE and IEO significantly increased from baseline to 20% MVC and from baseline to 40% MVC, but not during IEC. Total occlusal contact area during DE in all tooth clenching conditions was significantly larger compared to IEO and IEC (P < 0·05). At 40% MVC, total occlusal contact area during IEO was significantly larger than during IEC (P < 0·05). These findings suggest that indirect occlusal contact examinations may not accurately reflect the intra-oral occlusal condition. If the intra-oral condition is reproduced using dental casts, these findings also suggest the occlusal impression method was more accurate compared to the conventional method (240 words).

Influence of different narrative instructions to record the occlusal contact with silicone registration materials.

This study examined the influence of narrative instructions on the occlusal contact area, occlusal contact point and masticatory muscle activities in normal subjects. Twelve healthy men and 12 healthy women with no more than one missing tooth per quadrant participated. Surface EMG was recorded from the masseter and temporal muscle. As a control measurement, intercuspal position was maintained to produce a habitual clenching record (NCR) while the occlusal contact area and occlusal contact point was recorded by means of silicone material. Subsequently, the occlusal contact area was recorded with the narrative instruction for minimum clenching record (MCR), light clenching record (LCR) and strong clenching record (HCR). While the EMG activity (%MVC) increased modestly from MCR to LCR (from 9·3 ± 2·0% to 11·5 ± 1·5%), the occlusal contact area increased rapidly (from 17·2 ± 11·3 mm(2) to 26·8 ± 15·6 mm(2) ) (P < 0·05). Both EMG activity and occlusal contact area increased gradually from LCR to NCR (to 17·7 ± 2·0% and to 31·4 ± 14·2 mm(2) , respectively). Finally, EMG activity still increased from NCR to HCR (to 44·5 ± 3·7%) (P < 0·05), but the occlusal contact area remained stable (to 36·8 ± 16·6 mm(2) ). Occlusal contact points at left posterior, right posterior, anterior and total area were not significantly different between each task. This study showed that narrative instructions while recording the bite can result in largely stable occlusal contact area. An adequate narrative instruction may therefore contribute to taking a stable occlusal recording in natural dentition.

Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase.

The hallmark of type 2 diabetes, the most common metabolic disorder, is a defect in insulin-stimulated glucose transport in peripheral tissues. Although a role for phosphoinositide-3-kinase (PI3K) activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggested in vitro, its role in vivo and the molecular link between activation of PI3K and translocation has not yet been elucidated. To determine the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5). Pik3r1-/- mice showed increased insulin sensitivity and hypoglycaemia due to increased glucose transport in skeletal muscle and adipocytes. Insulin-stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full-length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene in Pik3r1-/- mice. This isoform switch was associated with an increase in insulin-induced generation of phosphatidylinositol(3,4,5)triphosphate (PtdIns(3,4,5)P3) in Pik3r1-/- adipocytes and facilitation of Glut4 translocation from the low-density microsome (LDM) fraction to the plasma membrane (PM). This mechanism seems to be responsible for the phenotype of Pik3r1-/- mice, namely increased glucose transport and hypoglycaemia. Our work provides the first direct evidence that PI3K and its regulatory subunit have a role in glucose homeostasis in vivo.

Radiation doses of workers engaged in decontamination of the environment.

After the accident at Fukushima Daiichi nuclear power plant on 11 March 2011, radioactive materials were released into the atmosphere resulting in environmental contamination. Following the implementation of environmental decontamination efforts, the Radiation Dose Registration Centre of the Radiation Effects Association established the radiation dose registration system for decontamination and related workers to consolidate and prevent the loss of radiation records. This article presents statistics on the radiation doses of decontamination and related workers using official records. Since approximately 10 years have passed since the accident in Fukushima, the types of work conducted in the affected restricted areas have changed over time. Therefore, changes in radiation dose for each type of work and comparisons with nuclear workers are presented.

Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus.

Transplantation of bone marrow cells of lpr/lpr mice into irradiated normal mice fails to develop massive lymphadenopathy or autoimmunity but causes severe graft-vs.-host-like syndrome. To elucidate an abnormality of lpr/lpr bone marrow-derived T cells, we transplanted bone marrow cells of Mlsb lpr/lpr mice into H-2-compatible Mlsa non-lpr mice. Although lpr/lpr T cell precursors repopulated the host thymus as well as +/+ cells, a proportion of CD4+CD8+ cells decreased, and that of both CD4- and CD8- single-positive cells increased compared with those of +/+ recipients. Notably, in MRL/lpr----AKR and C3H/lpr----AKR chimeras, CD4 single-positive thymocytes contained an increased number of V beta 6+ cells in spite of potentially deleting alleles of Mlsa, whereas V beta 6+ mature T cells were deleted in the MRL/+ ----AKR and C3H/+ ----AKR chimeras. There was no difference between MRL/+ ----AKR and MRL/lpr----AKR chimeras in their proportion of V beta 3+ cells because both host and donor strain lack the deleting alleles. Interleukin 2 receptor expression of mature T cells, in the thymus and lymph node, was obviously higher in the MRL/lpr----AKR chimeras, in particular in the "forbidden" V beta 6+ subset. Moreover, lpr donor-derived peripheral T cells showed vigorous anti-CD3 response. These results indicate that lpr-derived T cells escape not only tolerance-related clonal deletion but also some induction of unresponsiveness in the non-lpr thymus.

Ras mediates effector pathways responsible for pre-B cell survival, which is essential for the developmental progression to the late pre-B cell stage.

Ras is essential for the transition from early B cell precursors to the pro-B stage, and is considered to be involved in the signal cascade mediated by pre-B cell antigen receptors. To examine the role of p21(ras) in the late stage of B cell differentiation, we established transgenic mice (TG) expressing a dominant-inhibitory mutant of Ha-ras (Asn-17 Ha-ras) in B lineage cells at high levels after the early B cell precursor stage. Expression of p21(Asn-17) (Ha-ras) was associated with a prominent reduction in the number of late pre-B cells, but had little effect on proliferation of early pre-B cells. Inhibition of p21(ras) activity markedly reduced the life span of pre-B cells, due, at least in part, to downregulation of the expression of an antiapoptotic protein, Bcl-xL. Thus, the apparent role for p21(ras) activity in pre-B cell survival may explain the decreased numbers of late pre-B cells in Asn-17 Ha-ras TG. Consistent with this possibility, overexpression of Bcl-2 in Asn-17 Ha-ras TG reversed the reduction in the number of late pre-B cells undergoing immunoglobulin light chain gene (IgL) rearrangement and progressing to immature B cells. These results suggest that p21(ras) mediates effector pathways responsible for pre-B cell survival, which is essential for progression to the late pre-B and immature B stages.

STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma.

BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes that mediate cell survival, proliferation, and angiogenesis and is aberrantly activated in various types of malignancies, including renal cell carcinoma (RCC). We examined whether it could be a novel therapeutic target for RCC by using the STAT3 inhibitor WP1066. METHODS: The antitumour activities and related mechanisms of WP1066 were investigated in vitro on renal cancer cell lines and in vivo on murine xenografts. RESULTS: In Caki-1 and 786-O renal cancer cells, 5 muM WP1066 prevented the phosphorylation of STAT3, and 2.5 muM WP1066 significantly (P<0.01) inhibited cell survival and proliferation. WP1066 suppressed the expression of Bcl-2, induced apoptosis, and inhibited the basal and hypoxia-induced expression of HIF1alpha and HIF2alpha, as well as vascular endothelial growth factor secretion into cell culture medium. Human umbilical vascular endothelial cells cocultured with media from WP1066-treated cells showed significantly reduced tubulogenesis (P<0.05). Systemic oral administration of WP1066 to mice for 19 days significantly inhibited the growth of Caki-1 xenograft tumours (P<0.05), and pathological analysis of xenografts of WP1066-treated mice showed decreased immunostaining of phosphorylated STAT3 and reduced length of CD34-positive vessels (P<0.05). CONCLUSION: Our results suggest that using WP1066 to inhibit the STAT3 signalling pathway could be a novel therapeutic strategy against RCC.

Partial paternal uniparental disomy of chromosome 6 in monozygotic twins with transient neonatal diabetes mellitus and macroglossia.

Transient neonatal diabetes mellitus (TNDM) usually develops within the first few weeks of life and resolves at a median age of 3 months. In most of the cases, TNDM is caused by the over-expression of a paternally expressed imprinted PLAGL1 locus on chromosome 6q24. The most frequent manifestation other than TNDM is intrauterine growth retardation (IUGR), and in some cases macroglossia. We investigated monozygotic twins who had macroglossia without IUGR. Both of the twins developed insulin-dependent hyperglycemia within the first week of life, which subsequently resolved. DNA profiling with polymerase chain reaction amplification was performed for polymorphic microsatellite markers of chromosome 6. The six informative markers, located between 6p24 and 6q15, showed normal biparental inheritance. However, the six distal informative markers, located between 6q23.2 and the 6q telomeric region, showed the absence of a maternal allele and the presence of a single paternal allele. The monosomy of the 6q telomeric region was not confirmed by chromosome banding showing 46, XX. These findings provide further evidence that partial paternal uniparental disomy of chromosome 6 (pUPD6) causes TNDM. The phenotypes other than diabetes observed in patients with partial pUPD6 may differ from those observed in patients with complete pUPD6.

IL-8 in cerebrospinal fluid from children with acute encephalopathy is higher than in that from children with febrile seizure.

We identify possible differences in the cytokine/chemokine profiles in cerebrospinal fluid (CSF) from children with encephalopathy and febrile seizure. Interleukin (IL)-1beta, 2, 4, 5, 6, 7, 8, 10, 12, 13, 17, interferon-gamma, tumour necrosis factor-alpha, granulocyte colony-stimulating factor, granulocyte monocyte colony-stimulating factor, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1beta were measured simultaneously in CSF supernatants from children with encephalopathy (n = 8), febrile seizure (n = 16) and fever without neurological complications (n = 8). IL-8 in CSF from children with encephalopathy was significantly elevated compared to that in CSF from children with febrile seizure and fever without neurological complications. IL-8 in CSF was also higher than serum IL-8, suggesting that increased IL-8 was generated from glia cells or astrocytes, not by leakage from serum. Increased IL-8 in CSF in encephalopathy may protect against severe brain damage.

Comparison of cerebral activity during teeth clenching and fist clenching: a functional magnetic resonance imaging study.

Using functional magnetic resonance imaging (fMRI), we compared the cerebral activity during bilateral light fist-clenching and light-teeth clenching to provide more information on the central processing mechanisms underlying awake bruxism. Fourteen subjects participated in our study. Statistical comparisons were used to identify brain regions with significant activation in the subtraction of light fist clenching and light teeth clenching activity minus baseline. Participants also evaluated the perceived effort of clenching for each task, using a visual analogue scale of 0-100, after fMRI was performed. Bilateral light fist-clenching significantly activated the bilateral sensorimotor cortex, while light teeth-clenching was significantly associated with activation of the bilateral sensorimotor cortex, supplementary motor area, dorsolateral prefrontal cortex, and posterior parietal cortex. The VAS scores for fist clenching and teeth clenching were not significantly different. As light teeth-clenching activates a more extensive cortical network compared with light fist-clenching, we suggest that the teeth clenching may induce a more complex cerebral activity compared with the performance of a hand motor task. The clinical significance of these findings remains unknown but could perhaps be related to the propensity to trigger awake bruxism.

Withdrawal of pioglitazone in patients with type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVE: The remodelling of the adipose tissue by pioglitazone may be associated with the sustained therapeutic effects. We studied the effects of withdrawal of pioglitazone after 3-month treatment on glucose, lipid and high-molecular weight (HMW) adiponectin levels as well as liver function in patients with type 2 diabetes mellitus. METHODS: Forty-nine Japanese patients with type 2 diabetes mellitus were randomly assigned into the withdrawal group after 3-month treatment with pioglitazone (15 or 30 mg daily) and the non-withdrawal group. RESULTS AND DISCUSSION: Three-month treatment with pioglitazone improved glycaemic control, homeostasis model assessment for insulin resistance (HOMA), dyslipidaemia and liver function tests in association with a marked increase in serum HMW adiponectin level. Three months later after the withdrawal of pioglitazone, however, fasting plasma glucose and HOMA increased, whereas serum HMW adiponectin decreased to the pretreatment levels. Dyslipidaemia also returned to the pretreatment level. On the other hand, liver enzymes at 3 months after the withdrawal remained lower after a mild rebound. In addition, the bone formation marker, serum bone-specific alkaline phosphatase, was significantly reduced by pioglitazone treatment in post-menopausal women. CONCLUSIONS: The present study suggests that 3-month treatment with pioglitazone has no sustained beneficial effects except in liver function tests in patients with type 2 diabetes mellitus.

Spectrally selective thermal radiation based on intersubband transitions and photonic crystals.

We propose to use a combination of intersubband transitions in semiconductor quantum wells with a two dimensional photonic crystal cavity to obtain narrow, strong thermal radiation spectra. Single peak thermal radiation is obtained due to the Lorentzian shape absorption spectrum of the intersubband transition and the single mode cavity embedded within the photonic band gap. We present an analysis based on the quantum Langevin theory. It is shown that local radiance of the narrow emission peak can be maximized to approximately 80% of the radiation from the blackbody devices when the photon dissipation rates of the cavity mode due to the intersubband absorption and that due to the radiation to the free space modes are equal. Guidelines for concrete device design are introduced, and an example device structure is shown.

Identification of the gene encoding pro-phenoloxidase A(3) in the fruitfly, Drosophila melanogaster.

The fruitfly, Drosophila melanogaster, has three proPO genes (DoxA1, CG8193 and CG2952). DoxA1 has been shown to encode proPO A(1), one of the two proPO isoforms (A(1) and A(3)). However, which of CG8193 or CG2952 encodes proPO A(3) has so far remained elusive. In Northern analysis, CG8193 expression was strong during the larval stage, yet expression of CG2952 was not detected at any stage. Immunoblot analyses with specific antibodies detected CG8193 in the larval hemolymph at the mobility of the endogenous proPOA(3), though no signal for CG2952. These results indicate that the expression of CG2952 is very low and that CG8193 is the gene that encodes proPO A3. Processing of A(1)and A(3) isoforms in adult homogenate and activity of recombinant proPOs were also investigated.

Serum high-molecular weight adiponectin is related to early postprandial glycemic increases and gastric emptying in patients with type 2 diabetes mellitus.

BACKGROUND: Postprandial hyperglycemia and hyperlipidemia are frequently associated with type 2 diabetes mellitus. The aim of the present study is to investigate the clinical determinants of postprandial glycemia and lipemia, especially serum high-molecular weight adiponectin. METHODS: Twenty-seven diabetic patients treated with diet alone and 13 healthy volunteers took liquid test meal containing 53 g carbohydrate and 47 g lipid, dosed with nonradioactive isotope (13)C-acetate. Venous blood and breath samples were obtained for 180 min after the meal. Gastric emptying was evaluated by peak excretion time of (13)CO(2) in the breath samples. Delayed gastric emptying was defined as peak excretion time > 2.5 h (mean + 2 SD in the healthy volunteers). RESULTS: Diabetic patients showed delayed insulin secretion, postprandial hyperglycemia and hyperlipidemia compared with control. Postprandial glycemic increases significantly correlated with enhanced gastric emptying. Serum high-molecular weight adiponectin correlated with postprandial glycemic increases at 30 and 60 min after meal (r = 0.42, p < 0.05; r = 0.37, p < 0.05, respectively). Serum high-molecular weight adiponectin also correlated with gastric emptying (versus peak excretion time r = - 0.58, p < 0.05). In addition, diabetic patients with delayed gastric emptying showed the suppressed postprandial glycemia with lower serum high-molecular weight adiponectin than those with normal gastric emptying. On the other hand, postprandial increases in serum triglyceride were not related to serum high-molecular weight adiponectin or gastric emptying, but significantly related to liver function test (serum transaminases) and body mass index. CONCLUSIONS: Early postprandial glycemic increases were related to elevated serum high-molecular weight adiponectin, which might be associated with enhanced gastric emptying.

Reciprocal role of ERK and NF-kappaB pathways in survival and activation of osteoclasts.

To examine the role of mitogen-activated protein kinase and nuclear factor kappa B (NF-kappaB) pathways on osteoclast survival and activation, we constructed adenovirus vectors carrying various mutants of signaling molecules: dominant negative Ras (Ras(DN)), constitutively active MEK1 (MEK(CA)), dominant negative IkappaB kinase 2 (IKK(DN)), and constitutively active IKK2 (IKK(CA)). Inhibiting ERK activity by Ras(DN) overexpression rapidly induced the apoptosis of osteoclast-like cells (OCLs) formed in vitro, whereas ERK activation after the introduction of MEK(CA) remarkably lengthened their survival by preventing spontaneous apoptosis. Neither inhibition nor activation of ERK affected the bone-resorbing activity of OCLs. Inhibition of NF-kappaB pathway with IKK(DN) virus suppressed the pit-forming activity of OCLs and NF-kappaB activation by IKK(CA) expression upregulated it without affecting their survival. Interleukin 1alpha (IL-1alpha) strongly induced ERK activation as well as NF-kappaB activation. Ras(DN) virus partially inhibited ERK activation, and OCL survival promoted by IL-1alpha. Inhibiting NF-kappaB activation by IKK(DN) virus significantly suppressed the pit-forming activity enhanced by IL-1alpha. These results indicate that ERK and NF-kappaB regulate different aspects of osteoclast activation: ERK is responsible for osteoclast survival, whereas NF-kappaB regulates osteoclast activation for bone resorption.

Cavity resonator for circularly polarized microwave irradiation mounted on a cryostat.

We have constructed a cylindrical cavity resonator with a hybrid coupler where circularly polarized microwaves can be irradiated to a sample. The polarity of the microwave can be switched by changing the input ports of the hybrid coupler. The cavity resonator is small enough to be mounted on a cryostat which enables us to change the sample temperature in a wide range. To demonstrate the performance of the cavity resonator mounted on a cryostat, Yttrium Iron Garnet (YIG) was used as a test sample. We succeeded in selectively exciting left and right circularly polarized modes with high polarization (>80%). We also evaluated the susceptibility tensor of YIG in the cryostat. The technique presented here would offer a new direction in the fields of spintronics and quantum information.

Essential roles of ERK-mediated phosphorylation of vinexin in cell spreading, migration and anchorage-independent growth.

Vinexin is an adaptor protein supposed to play pivotal roles in various cellular events such as cell adhesion, cytoskeletal organization, signaling and gene expression. Despite the possible importance, physiological functions and regulatory mechanisms of vinexin are largely unknown. In addition, although vinexin was reported to be phosphorylated by extracellular signal-regulated kinase (ERK), physiological significance of the phosphorylation remains to be elucidated. Here we carried out characterization of endogenous vinexin and found that it was enriched at the leading edge of migrating cells and focal adhesions of spread cells. In the analyses using ERK-phosphorylated vinexin-specific antibody, the phosphorylation signal was also detected at the leading edges of migrating cells and at cell periphery of spreading cells, whereas only faint signal was observed at focal adhesions of well-spread cells. We then established LNCaP cell lines stably expressing GFP-fused vinexinbeta or two mutants at Ser189 that mimic the ERK-phosphorylated or -unphosphorylated vinexin beta. Based on the analyses using the lines, the phosphorylation was likely to inhibit the cell spreading and migration. On the other hand, anchorage-independent cell growth was inhibited by unphosphorylated vinexinbeta. Taken together, ERK-mediated phosphorylation of vinexinbeta is strongly suggested to occur in a spatio-temporally regulated manner and play important roles in cell spreading, migration and anchorage-independent growth.

DNA microarray analyses of genes expressed differentially in 3T3-L1 adipocytes co-cultured with murine macrophage cell line RAW264.7 in the presence of the toll-like receptor 4 ligand bacterial endotoxin.

Recent studies have suggested that macrophages were integrated into adipose tissues to interact with adipocytes, thereby exacerbating inflammatory responses. Furthermore, both adipocytes and macrophages appear to express toll-like receptor-4 (TLR-4), and free fatty acids may stimulate cells through TLR-4. Herein, we analyzed genes differentially expressed in adipocytes when co-cultured with macrophages in the presence of a ligand for TLR-4, bacterial lipopolysaccharide (LPS). RAW264.7, a murine macrophage cell line and differentiated 3T3-L1 adipocytes were co-cultured using a transwell system. Genes differentially expressed in adipocytes were analyzed by the DNA microarray method following 4, 8, 12 and 24 h stimulation with 1 ng ml(-1) of Escherichia coli LPS. Randomly selected genes with high expressions were confirmed by quantitative methods at both the gene and the protein level. Co-culture of macrophages and adipocytes with a low LPS concentration (1 ng ml(-1)) markedly upregulated gene expressions associated with inflammation and/or angiogenesis, such as those of interleukin-6 (IL-6), MCP-1, RANTES and CXCL1/KC, in adipocytes. Furthermore, several genes associated with insulin resistance were differentially expressed. Upregulations of genes encoding MCP-1, RANTES and CXC/KC were confirmed by quantitative methods. These results suggest that ligands for TLR-4 stimulate both adipocytes and macrophages to upregulate the expressions of many genes associated with inflammation and/or angiogenesis.