Case Report: The leopard sign as a potential characteristic of chronic granulomatous disease-associated colitis, unrelated to colitis severity.

Background: Chronic granulomatous disease (CGD) is an inborn immune disorder in which the phagocytic system cannot eradicate pathogens, and autoinflammation occurs. Approximately half of the patients have associated gastrointestinal symptoms. Although most cases with CGD-associated colitis present nonspecific histology, colonoscopy in some cases shows brownish dots over a yellowish oedematous mucosa, which is termed a "leopard sign". However, the significance of these signs remains unclear. Methods: We collected data from patients with CGD whose colonoscopic findings showed the leopard sign. Results: Three patients with CGD and leopard signs were enrolled in this study. One patient underwent colonoscopy for frequent diarrhoea and weight gain failure, and another for anal fistula. The third patient was without gastrointestinal symptoms and underwent colonoscopy as a screening test before allogeneic haematopoietic cell transplantation (HCT). Endoscopic findings showed a mild leopard sign in the first case; however, non-contiguous and diffuse aphthae were observed throughout the colon. The other two cases were unremarkable except for the leopard sign. All the patients achieved remission with oral prednisolone or HCT. One patient underwent colonoscopy after HCT; results revealed improvements in endoscopy (including the leopard sign) and histological findings. However, another patient underwent colonoscopy after prednisolone treatment; this revealed no change in the leopard sign. Conclusion: The leopard sign in the colon may be a characteristic endoscopic finding of CGD, even in patients who do not develop severe gastrointestinal symptoms; however, it does not reflect the severity of CGD-associated colitis.

Rheumatoid factor value for determining the first biologic agent to use for non-systemic juvenile idiopathic arthritis.

OBJECTIVES: Currently, no indicators on which biologic disease-modifying anti-rheumatic drugs (bDMARDs) should be used first for juvenile idiopathic arthritis (JIA) have been established. Thus, this study aimed to determine the useful biomarkers in JIA to enable the best selection of the first bDMARDs without primary failure. METHODS: This retrospective study used data of patients examined for JIA between 2015 and 2021 at Kagoshima University Hospital in Japan. RESULTS: Altogether, 67 cases of non-systemic JIA were analyzed, excluding cases that had been treated for <6 months. Of the 67 cases, 52 were treated with bDMARDs and all rheumatoid factor (RF)+ types (32 cases) were treated with bDMARDs. Eleven cases (31.4&) (all were RF+ types and used anti-tumor necrosis factor (TNF)α agents) switched to other bDMARDs because of primary failure, and nine cases had secondary failure (6;anti-TNF, 3;anti-Interleukin-6). A significant difference in pre-treatment RF values (177.9 vs 25.7 IU/ml, p = 0.002) and presence (Odds Ratio 1.952,p = 0.004) were observed between the primary failure group and effective group. CONCLUSIONS: RF+ JIA required bDMARDs with high probability. JIA with high titre of RF tends to be refractory to anti-TNFα agents. Tocilizumab or abatacept could be a first-choice bDMARD in such cases.

A Method Enabling Comprehensive Isolation of Arabidopsis Mutants Exhibiting Unusual Root Mechanical Behavior.

Root penetration into soils is fundamental for land plants to support their own aboveground parts and forage water and nutrients. To elucidate the molecular mechanisms underlying root mechanical penetration, mutants defective in this behavior need to be comprehensively isolated; however, established methods are currently scarce. We herein report a method to screen for these mutants of Arabidopsis thaliana and present their phenotypes. We isolated five mutants using this method, tentatively named creep1 to creep5, the primary roots of which crept over the surface of horizontal hard medium that hampered penetration by the primary root of the wild type, thereby forcing it to spring up on the surface and die. By examining root skewing, which is induced by a touch stimulation that is generated as the primary roots grow along a vertical impenetrable surface, the five creep mutants were subdivided into three groups, namely mutants with the primary root skewing leftward, those skewing rightward, and that growing dispersedly. While the majority of wild type primary roots skewed slightly leftward, nearly half of the primary roots of creep1 and creep5 skewed rightward as viewed from above. The primary roots of creep4 displayed scattered growth, while those of creep2 and creep3 showed a similar phenotype to the wild type primary roots. These results demonstrate the potential of the method developed herein to isolate various mutants that will be useful for investigating root mechanical behavior regulation not only in Arabidopsis, but also in major crops with economical value.

Anti-inflammatory effects of ozenoxacin, a topical quinolone antimicrobial agent.

Ozenoxacin is a topical quinolone showing potent antimicrobial activities against Gram-negative and Gram-positive bacteria and is widely used for the treatment of inflammatory acne. However, the anti-inflammatory activities of ozenoxacin have not been examined so far. In the present study, we investigated the in vitro and in vivo anti-inflammatory effects of ozenoxacin. The production of interleukin (IL)-6 and IL-8 by human epidermal keratinocytes stimulated by heat-killed Cutibacterium acnes was significantly inhibited by ozenoxacin at concentrations from 1 to 30 µg ml-1. Likewise, the production of IL-6, IL-8, and tumor necrosis factor alpha by stimulated THP-1 cells, a human monocyte cell line, was inhibited by ozenoxacin at concentrations from 1 to 30 µg ml-1. The production of IL-1ß by THP-1 was also inhibited by ozenoxacin at the concentration of 30 µg ml-1. Phosphorylation of the mitogen-activated protein kinases and degradation of IκB-α, an inhibitory factor of NF-κB in keratinocytes and THP-1 cells, was increased by stimulation with heat-killed C. acnes. Of these activated intracellular pathways, the p38 phosphorylation pathway was remarkably reduced by ozenoxacin in both keratinocytes and THP-1 cells. In addition, the application of 2% ozenoxacin suppressed the increase in the ear thickness of rats induced by an intracutaneous injection of heat-killed C. acnes. These findings suggest that ozenoxacin possesses an anti-inflammatory activity, which may contribute to its therapeutic effects on inflammatory acne.

Anti-inflammatory effect of lanoconazole on 12-O-tetradecanoylphorbol-13-acetate- and 2,4,6-trinitrophenyl chloride-induced skin inflammation in mice.

BACKGROUND: Lanoconazole (LCZ) is a topical antifungal agent clinically used to treat fungal infections such as tinea pedis. LCZ has not only antifungal effects but also anti-inflammatory effects, which have the potential to provide additional clinical benefits. However, the characteristic features of the inhibitory effects of LCZ on skin inflammation remain unclear. OBJECTIVE: We evaluated the inhibitory effects of topical application of LCZ, and compared the effects of LCZ with those of other antifungal agents including liranaftate, terbinafine and amorolfine. METHODS: Each antifungal agent was topically applied on 12-O-tetradecanoylphorbol-13-acetate-induced irritant dermatitis and 2,4,6-trinitrophenyl chloride-induced contact dermatitis in mice (BALB/c). The ear thickness, myeloperoxidase activity and inflammatory mediator contents were evaluated. RESULTS: LCZ dose-dependently suppressed 12-O-tetradecanoylphorbol-13-acetate-induced irritant dermatitis, suppressed the production of neutrophil chemotactic factors such as keratinocyte-derived chemokine and macrophage inflammatory protein-2, and inhibited neutrophil infiltration to the inflammation site. Moreover, 1% LCZ reduced the ear swelling in mice with 2,4,6-trinitrophenyl chloride-induced contact dermatitis in accordance with the inhibition of interferon-γ production. The inhibitory potency of LCZ on these types of dermatitis in mice was stronger than that of other types of antifungal agents. CONCLUSION: The anti-inflammatory effects of LCZ were exerted through the inhibition of inflammatory mediator production. These effects may contribute to the relief of dermatitis symptoms in patients with tinea pedis.

Chaperonin TRiC/CCT supports mitotic exit and entry into endocycle in Drosophila.

Endocycle is a commonly observed cell cycle variant through which cells undergo repeated rounds of genome DNA replication without mitosis. Endocycling cells arise from mitotic cells through a switch of the cell cycle mode, called the mitotic-to-endocycle switch (MES), to initiate cell growth and terminal differentiation. However, the underlying regulatory mechanisms of MES remain unclear. Here we used the Drosophila steroidogenic organ, called the prothoracic gland (PG), to study regulatory mechanisms of MES, which is critical for the PG to upregulate biosynthesis of the steroid hormone ecdysone. We demonstrate that PG cells undergo MES through downregulation of mitotic cyclins, which is mediated by Fizzy-related (Fzr). Moreover, we performed a RNAi screen to further elucidate the regulatory mechanisms of MES, and identified the evolutionarily conserved chaperonin TCP-1 ring complex (TRiC) as a novel regulator of MES. Knockdown of TRiC subunits in the PG caused a prolonged mitotic period, probably due to impaired nuclear translocation of Fzr, which also caused loss of ecdysteroidogenic activity. These results indicate that TRiC supports proper MES and endocycle progression by regulating Fzr folding. We propose that TRiC-mediated protein quality control is a conserved mechanism supporting MES and endocycling, as well as subsequent terminal differentiation.

Ca2+-permeable mechanosensitive channels MCA1 and MCA2 mediate cold-induced cytosolic Ca2+ increase and cold tolerance in Arabidopsis.

Cold shock triggers an immediate rise in the cytosolic free calcium concentration ([Ca2+]cyt) in Arabidopsis thaliana and this cold-induced elevation of [Ca2+]cyt is inhibited by lanthanum or EGTA. It is suggested that intracellular calcium mainly contributes to the cold-induced [Ca2+]cyt response by entering into the cytosol. Two calcium-permeable mechanosensitive channels, MCA1 and MCA2 (mid1-complementing activity), have been identified in Arabidopsis. Here, we demonstrate that MCA1 and MCA2 are involved in a cold-induced increase in [Ca2+]cyt. The cold-induced [Ca2+]cyt increase in mca1 and mca2 mutants was markedly lower than that in wild types. The mca1 mca2 double mutant exhibited chilling and freezing sensitivity, compared to wild-type plants. Expression of At5g61820, At3g51660, and At4g15490, which are not regulated by the CBF/DREB1s transcription factor, was down-regulated in mca1 mca2. These results suggest that MCA1 and MCA2 are involved in the cold-induced elevation of [Ca2+]cyt, cold tolerance, and CBF/DREB1-independent cold signaling.

Immediate-type allergic and protease-mediated reactions are involved in scratching behaviour induced by topical application of Dermatophagoides farinae extract in NC/Nga mice.

Atopic dermatitis (AD)-like dermatitis can be induced by repeated topical application of an ointment containing Dermatophagoides farinae body (Dfb) extract in NC/Nga mice. This AD-like murine model also exhibits a biphasic increase in the number of scratching behaviour after topical application of Dfb ointment. In this study, we investigated the possible mechanisms underlying the scratching behaviour in each phase. An increase in the content of mast cell-derived mediators such as histamine and 5-hydroxytryptamine in the lesional skin and increased vascular permeability were observed in the early phase after the Dfb ointment application. Chlorpheniramine (H1 receptor antagonist) and cromoglycate (mast cell stabilizer) reduced the scratching behaviour in the early phase but not that in the later phase. Furthermore, the content of various endogenous pruritogens such as interleukin-31 and thymic stromal lymphopoietin in the lesional skin was increased 1 or 24 hours after the Dfb ointment application. Elevated expression of proteinase-activated receptor-2 (PAR-2) was also observed in the epidermis. Finally, gabexate (serine protease inhibitor) reduced the scratching behaviour in both phases, and anti-PAR2 antibody also showed a tendency to reduce both scratching behaviours. These findings suggest that immediate-type allergic reactions caused by mast cell degranulation and PAR-2 activation by proteases are involved in the scratching behaviour in this AD-like model.

Biphasic increase in scratching behaviour induced by topical application of Dermatophagoides farinae extract in NC/Nga mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied by severe itching and eczematous lesion. In this study, we applied an ointment containing Dermatophagoides farinae body (Dfb) extract repeatedly on the dorsal skin of NC/Nga mice with barrier disruption to investigate the characteristics of this murine model of human AD. Following repeated topical application of Dfb ointment twice weekly for 2 weeks, the dermatitis score increased gradually, accompanied by an elevation of total immunoglobulin E level in plasma. Topical application of Dfb ointment also caused epidermal hyperplasia and accumulation of inflammatory cells in the lesional skin and increased expression of T-helper (Th) 1/Th2/Th17 cytokines in axillary lymph node cells. Furthermore, increased sprouting of intraepidermal nerve fibres was observed with an increase in the content of nerve growth factor and decrease in that of semaphorin 3A in the lesional skin. These findings suggest that the characteristics in this model were similar to those observed in patients with AD. Interestingly, it was observed for the first time that scratching behaviour increased in a biphasic fashion by topical application of Dfb ointment in addition to an increase in spontaneous scratching behaviour in this model. It is also suggested that further clarifying the underlying mechanisms of scratching behaviour in this model leads not only to elucidating the pathogenesis of AD but also to discovering novel therapeutic drugs for AD.

Anti-inflammatory activity of lanoconazole, a topical antifungal agent.

Topical antifungal agents which have anti-inflammatory effects have the potential to provide additional clinical benefits. Therefore, an anti-inflammatory activity of lanoconazole (LCZ), a topical antifungal agent, was investigated against in vitro and in vivo models of inflammation. The release of interleukin-8 (IL-8) from human epidermal keratinocytes stimulated by the addition of 100 µg ml(-1) ß-glucan of Saccharomyces cerevisiae was significantly inhibited by LCZ at the concentration of 10(-5) mol l(-1). The release of interferon-γ and IL-2 from human peripheral blood mononuclear cells stimulated by the addition of 30 and 100 µg ml(-1) phytohemagglutinin was significantly inhibited by LCZ at the concentrations of 10(-7) and 10(-6) mol l(-1), respectively. The increase in the ear thickness induced by topical application of 0.01% 12-O-tetradecanoyl phorbol-13-acetate and 1% 2,4,6-trinitrochlorobenzene (TNCB) after sensitisation with 3% TNCB were established as the mouse models of irritant and contact dermatitis, respectively. Application of 1% and 3% LCZ showed a significant anti-inflammatory activity against both the irritant and contact dermatitis models. These findings suggest that LCZ possesses an anti-inflammatory activity, which may be partially helpful in the treatment of dermatomycoses.

Relationship between health-related quality of life and clustering of metabolic syndrome diagnostic components.

PURPOSE: To examine the association of the number of metabolic syndrome diagnostic components (MetS-DC) with health-related quality of life (HR-QOL). METHODS: We examined the baseline data from 4,480 healthy workers in Japan (3,668 men and 812 women) aged 19-69 years. We assessed HR-QOL based on scores for five scales of the SF-36. We defined four components for MetS in this study as follows: (1) high blood pressure (BP); (2) dyslipidemia; (3) impaired glucose tolerance; and (4) overweight: a body mass index ≥25 kg/m(2). Logistic regression analysis adjusted for lifestyle factors was used to examine the association of the number of MetS-DC with the HR-QOL sub-scales. RESULTS: Those who had 0-4 MetS-DC accounted for 2,287, 1,135, 722, 282, and 54 participants. The number of MetS-DC inversely contributed significantly to General Health (norm-based scoring >50) (odd ratios [OR] 0.59-0.82, P < 0.05) and positively associated with Mental Health (OR 1.37, P < 0.05). CONCLUSION: When adjusted for lifestyle factors, the number of MetS-DC was inversely associated with General Health and positively with Mental Health in men and women.

Pioglitazone-induced body weight gain is prevented by combined administration with the lipoprotein lipase activator NO-1886.

Pioglitazone improves insulin resistance in diabetics but often causes body weight gain. The lipoprotein lipase activator NO-1886 has been shown to exert both anti-obesity and anti-insulin-resistance effects. In this study, we investigated the effect of the combined administration of pioglitazone with NO-1886 (pioglitazone+NO-1886) in preventing body weight gain in insulin-resistant, high-fat fed rats. The rats were fed a standard or high-fat diet for 16 weeks. The high-fat fed rats were randomized at week 9 into 4 groups (i.e., control, pioglitazone (30 mg/kg/day), NO-1886 (100mg/kg/day), and pioglitazone+NO-1886 (30 and 100mg/kg/day, respectively)). The high-fat fed control rats developed obesity and insulin resistance. After 7 weeks of drug treatment, pioglitazone+NO-1886 was found to prevent the body weight gain caused by pioglitazone alone (pioglitazone+NO-1886: Δ76.0 ± 16.8 g vs. pioglitazone: Δ127.8 ± 39.5 g, P<0.05) and to increase glucose infusion rate during insulin clamp, compared with the results in the high-fat fed control group. No differences in plasma nonesterified fatty acid, leptin, adiponectin, glucose, or insulin levels were observed between the pioglitazone+NO-1886 and the pioglitazone-alone groups. However, plasma total cholesterol and HDL-cholesterol levels were significantly increased and plasma triglyceride levels were slightly decreased in the pioglitazone+NO-1886 group, compared with the values in the pioglitazone-alone group. In summary, the combined administration of pioglitazone and NO-1886 prevented the pioglitazone-induced body weight gains and ameliorated insulin resistance observed in high-fat fed rats. These results indicate that combined therapy with pioglitazone and NO-1886 may be beneficial for the treatment of type 2 diabetes.

Activation of lipoprotein lipase increases serum high density lipoprotein 2 cholesterol and enlarges high density lipoprotein 2 particles in rats.

It is known that postheparin plasma lipoprotein lipase (LPL) activity correlates with serum high density lipoprotein cholesterol (HDL-C) levels in humans and animals. Furthermore, LPL has been reported to cause enlargement of HDL particle size in vitro. However, these effects have not yet been experimentally proven. The aim of this study was to determine whether LPL has a role in increase in HDL-C and enlargement of HDL particle by activating the LPL function with NO-1886, the LPL promoting agent. NO-1886 administration increased postheparin plasma LPL activity without influencing hepatic triglyceride lipase activity. NO-1886 increased serum HDL(2)-cholesterol (HDL(2)-C) concentration and enlarged HDL(2) particle size, but did not increase serum HDL(3)-cholesterol concentration or enlarge HDL(3) particle size. Also, serum HDL(2)-C concentrations were positively correlated with HDL(2) particle size (r=0.910). Our study demonstrates that the LPL activation induced with NO-1886 may cause production of HDL(2)-C by catabolism of triglyceride-rich lipoproteins and enlarges HDL(2) particle size in rats.

Relationship between sleep duration and clustering of metabolic syndrome diagnostic components.

OBJECTIVE: To examine the relation between sleep duration and metabolic syndrome (MetS). METHODS: We examined the baseline data from 4356 healthy workers (3556 men and 800 women) aged 19-69 years. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). We defined four components of MetS diagnostic components in this study as follows: 1) high blood pressure (BP) systolic BP [SBP] ≥ 130 mmHg, or diastolic BP [DBP] ≥ 85 mmHg, or on medication; 2) dyslipidemia (high-density lipoprotein-cholesterol concentration <40 mg/dL, or triglycerides concentration ≥150 mg/dL, or on medication; 3) impaired glucose tolerance (fasting blood sugar concentration ≥ 110 mg/dL, or if less than 8 hours after meals ≥ 140 mg/dL), or on medication; and 4) overweight (body mass index [BMI] ≥ 25 kg/m(2)), or obesity (BMI ≥ 30 kg/m(2)). There were 680 participants in the group, with sleep duration <6 hours (15.6%). RESULTS: Those who had 0-4 MetS diagnostic components, including overweight, accounted for 2159, 1222, 674, 255, and 46 participants, respectively, in the Poisson distribution. Poisson regression analysis revealed that independent factors that contributed to the number of MetS diagnostic components were being male (regression coefficient b = 0.752, P < 0.001), age (b = 0.026, P < 0.001), IPAQ classification (b = -0.238, P = 0.034), and alcohol intake (mL/day) (b = 0.018, P < 0.001). Short sleep duration (<6 hours) was also related to the number of MetS (b = 0.162, P < 0.001). The results of analyses with obesity component showed a similar association. CONCLUSION: Short sleep duration was positively associated with the number of MetS diagnostic components independent of other lifestyle habits.

Association of short sleep duration with impaired glucose tolerance or diabetes mellitus.

UNLABELLED: Aims/Introduction: To examine the cross-sectional relationship between sleep duration and impaired glucose tolerance (IGT), including diabetes mellitus (DM), we analyzed a large-scale healthy workers database in Japan. MATERIALS AND METHODS: We examined the baseline database of 4143 participants (3415 men and 728 women) aged 19-69 years. Sleep duration of participants was categorized into four groups: <6, 6 to <7, 7 to <8 and ≥8 h. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). We defined IGT including DM (IGT/DM) in the present study according to previous studies as follows: fasting blood sugar level ≥110 mg/dL, or if <8 h after meals ≥140 mg/dL, or on medication for diabetes mellitus, or those diagnosed as having DM. Logistic regression was applied to estimate the odds ratio (OR) to examine the relationship between IGT/DM, sleep duration and other related factors. RESULTS: The number of participants with IGT/DM was 402 (9.7%). The factors that significantly associated with IGT/DM were age (OR 1.08, 95% confidence interval [CI] 1.07-1.10, P < 0.001), high blood pressure (OR 1.94, CI 1.52-2.47, P < 0.001), and <6 h of sleep duration in comparison with 6 to <7 h sleep (OR 2.32, CI 1.18-4.55, P = 0.015). The associations of difficulty in sleep initiation, IPAQ classification, current smoking and alcohol intake with IGT/DM were not statistically significant. CONCLUSIONS: Our results showed that shorter sleep duration (<6 h of sleep duration per night) was associated with a risk of IGT/DM independent of other lifestyle habits and metabolic risk factors. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00114.x, 2011).

Relationship among physical activity, smoking, drinking and clustering of the metabolic syndrome diagnostic components.

AIM: To examine the relation between lifestyle and the number of metabolic syndrome (MetS) diagnostic components in a general population, and to find a means of preventing the development of MetS components. METHODS: We examined baseline data from 3,365 participants (2,714 men and 651 women) aged 19 to 69 years who underwent a physical examination, lifestyle survey, and blood chemical examination. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). We defined four components for MetS in this study as follows: 1) high BP: systolic BP > or = 130 mmHg or diastolic BP > or = 85 mmHg, or the use of antihypertensive drugs; 2) dyslipidemia: high-density lipoprotein-cholesterol concentration < 40 mg/dL, triglycerides concentration > or = 150 mg/dL, or on medication for dyslipidemia; 3) Impaired glucose tolerance: fasting blood sugar level > or = 110 mg/d, or if less than 8 hours after meals > or = 140 mg/dL), or on medication for diabetes mellitus; 4) obesity: body mass index > or = 25 kg/m(2). RESULTS: Those who had 0 to 4 MetS diagnostic components accounted for 1,726, 949, 484, 190, and 16 participants, respectively, in the Poisson distribution. Poisson regression analysis revealed that independent factors contributing to the number of MetS diagnostic components were being male (regression coefficient b=0.600, p < 0.01), age (b=0.027, p < 0.01), IPAQ class (b=-0.272, p= 0.03), and alcohol consumption (b=0.020, p=0.01). The contribution of current smoking was not statistically significant (b=-0.067, p=0.76). CONCLUSION: Moderate physical activity was inversely associated with the number of MetS diagnostic components, whereas smoking was not associated.

Enhancement of reaction efficiency by functionalized alcohols on gold(I)-catalyzed intermolecular hydroalkoxylation of unactivated olefins.

Intermolecular hydroalkoxylation of unactivated olefins catalyzed by the combination of gold(I) and electron deficient phosphine ligands has been developed. Although pairings of unactivated olefins and common aliphatic alcohols gave unsatisfactory results in gold catalyzed hydroalkoxylations, the use of alcohol substrates bearing coordination functionalities such as halogen or alkoxy groups showed great improvement of reactivity.

Identification of cis-acting promoter sequences required for expression of the glycerol-3-phosphate acyltransferase 1 gene in mice.

Glycerol-3-phosphate acyltransferase 1 (GPAT1) is a rate limiting enzyme in de novo glycerophospholipid synthesis. The murine GPAT1 promoter sequence (the "classical" sequence) was reported previously. However, the organization of this DNA sequence does not fully match the mouse genome sequences on NCBI/GenBank. Here we have identified net cis-acting promoter sequences for the mouse GPAT1 gene: promoter 1a which includes part of the classical sequence and the downstream promoter 1b. Promoter 1a facilitates transcription of two alternative GPAT1 transcript variants, GPAT1-V1 and V2, while promoter 1b produces a third transcript variant, GPAT1-V3. Upstream stimulating factor-1 (USF-1) controlled both promoters whereas sterol regulatory element-binding protein-1 (SREBP-1) exclusively regulated promoter 1a activity in vitro. Feeding increased GPAT1-V1 and V2, but not V3 mRNA levels in mouse liver. The obese condition of db/db mice did not alter the hepatic expression levels of any of the three GPAT1 variants. Feeding enhanced hepatic mRNA levels, intranuclear protein levels and promoter 1a-binding levels of SREBP-1, but not of USF-1. Thus, promoter 1a was exclusively activated by routine feeding in vivo. Our results indicate differential roles of the two promoters in the regulation of hepatic GPAT1 gene expression in mice.

[A successful case of advanced nasal adenocarcinoma treated with tumor dormancy therapy with S -1 alone].

We report a 65-year-old female case of low-grade non-intestinal type adenocarcinoma of the nasal cavity with bilateral metastases to the cervical lymph nodes(T3N2cM0: Stage IV A). Chemoradiotherapy administered as first-line therapy yielded only a partial response in the primary tumor and metastatic lesions, and subsequent chemotherapy with S-1(at a dose of 80 mg per day)alone was applied as tumor dormancy therapy(TDT)on an outpatient basis. Adverse events during S-1 medication were limited to a decrease in leukocyte count and hemoglobin level, both of which were grade 1. The tumor has not enlarged, and the patient has survived 29 months since the beginning of chemotherapy with S-1 alone without any decrease in quality of life. Although the effectiveness of S-1 for adenocarcinoma of the head and neck has not been fully demonstrated, S-1 might be useful in patients with advanced head and neck adenocarcinoma for the purpose of TDT.