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HDL has been proposed to possess anti-inflammatory properties; however, the detail mechanisms have not been fully elucidated.We investigated the roles of Apolipoprotein D (ApoD) in the pathogenesis of inflammation in the mouse model of diet-induced obesity and that of lipopolysaccharide-induced sepsis and the in vitro experiments. Furthermore, we analyzed serum ApoD levels in human subjects.The overexpression of human ApoD decreased the plasma IL-6 and TNF-a levels in both mice models. Lipidomics analyses demonstrated association of ApoD with increase of arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, as well as of their metabolites, and of the anti-inflammatory molecule sphingosine 1-phosphate, and decrease of proinflammatory lysophosphatidic acids and lysophosphatidylinositol. ApoD-containing lipoproteins might directly bind eicosapentaenoic acid and docosahexaenoic acid. The modulations of the lysophosphatidic acid and sphingosine 1-phosphate levels resulted from the suppression of autotaxin expression and elevation of apolipoprotein M (ApoM), respectively. Moreover, ApoD negatively regulated osteopontin, a proinflammatory adipokine. The activation of PPARg by ApoD might suppress autotaxin and osteopontin. Serum ApoD levels were negatively correlated with the serum osteopontin and autotaxin levels and, positively with serum ApoM levels.ApoD is an anti-inflammatory apolipoprotein, which modulates lipid mediators and osteopontin in an anti-inflammatory direction.

We investigate thermal convection in two horizontal layers of miscible fluids with an initial state in which the fluids are at rest and the temperature has a linear continuous vertical distribution, but the concentration takes different constant values in each layer. Because the initial layered state is not a stationary state, most theoretical methods available for immiscible fluids are not applicable to the miscible case. Here we propose a new model of the thermal convection of miscible fluids, which is devised in such a way that the horizontal average of the width of the transitional layer is kept constant. Both the stability of the stationary state in the linear stage and the asymptotic attractors in the nonlinear stage of the model closely describe the transition of the convection pattern in the original system, which is associated with the change of the width of the transitional layer.

Background and Study Aims We previously reported that normalization of motor evoked potential (MEP) monitoring amplitude by compound muscle action potential (CMAP) after peripheral nerve stimulation prevented the expression of anesthetic fadeanesthetic fade (AF), suggesting that AF might be due to reduced synaptic transfer in the neuromuscular junction. Methods We calculated the time at which anesthetic fadeAF began for each of craniotomy and spinal cord surgery, and examined whether anesthetic fadeAF was avoided by CMAP after peripheral nerve stimulation normalization in each. Similar studies were also made with respect to the upper and lower limb muscles. Results AF was observed in surgery lasting 160 minutes for craniotomy and 260 minutes or more for spinal surgery, and 195 minutes in upper-limb muscles and 135 minutes in lower-limb muscles. In all series, AF could be avoided by CMAP after peripheral nerve stimulation normalization. Conclusion In craniotomy, AF of MEP occurred as well as spinal cord surgery, and it was also corrected by CMAP after peripheral nerve stimulation. AF is considered to be mainly due to a decrease in the synaptic transfer of the neuromuscular junction due to the accumulation of propofol because of the avoidance by CMAP normalization. However, it may be partially due to a decrease in the excitability of pyramidal tracts and α-motor neurons, because AF occurred earlier in lower-limb muscles than in upper-limb muscles.

Purpose A few previous basic and clinical reports implied that roxadustat, a drug recently approved for treating renal anemia, might activate thyroid hormone receptors (TRα and TRβ). We thus investigated the direct effects of roxadustat on intact TRα and TRβ in vitro. Methods U2OS, MCF-7, COS-7 and Caco-2 cells were transiently transfected with a firefly luciferase reporter plasmid highly responsive to activation of TRα and TRβ, along with a plasmid overexpressing either TRα or TRβ. Transfected cells were incubated for 3 h in 100% thyroid hormone-stripped fetal bovine serum (FBS) with or without either roxadustat or triiodothyronine (T3). Also, transfected U2OS cells were placed for 3 h in 100% unprocessed normal adult human serum with or without the addition of either roxadustat or T3. Cell lysates were measured for firefly luciferase activities. Results Roxadustat induced firefly luciferase activities when added at clinically achievable serum concentrations in TRα- or TRβ-transfected U2OS, MCF-7, COS-7 and Caco-2 cells placed in thyroid hormone-deprived FBS. The induction was comparable to or greater than that observed with T3 added at normal or even supranormal serum concentrations. Roxadustat also increased firefly luciferase activities in TRα- or TRβ-transfected U2OS cells in adult human serum. Conclusions Roxadustat does activate TRα and TRβ at clinically relevant concentrations. Physicians prescribing roxadustat should be aware of its thyromimetic activity.

Serum dehydroepiandrosterone sulfate (DHEA-S) levels reflect the state of adrenocorticotropic hormone (ACTH) secretion. However, it is difficult to use serum DHEA-S to diagnose hypothalamic-pituitary-adrenal (HPA) axis insufficiency due to its non-normal and highly skewed distribution. In this study, we focused on HPA insufficiency caused by hypothalamic and/or pituitary dysfunction and evaluated the usefulness of the standard deviation score of log-transformed DHEA-S (ln DHEA-S SD score), which was calculated from the established age- and sex-specific reference values. We retrospectively reviewed the medical records of 94 patients suspected of having HPA insufficiency, in whom serum DHEA-S measurement and the rapid ACTH stimulation test were performed, and included 65 patients who met our criteria in this study. The ln DHEA-S SD scores were distributed more normally than measured DHEA-S levels and were significantly higher in patients with a peak cortisol level ≥18 μg/dL than in those below this value, suggesting that this score is a legitimate and strong indicator of adrenocortical function. The optimal cut-off value for impaired HPA function was -0.853, with a sensitivity of 70.3% and a specificity of 100%. Among the 37 patients whose peak cortisol levels were below 18 μg/dL, 11 patients with ln DHEA-S scores ≥-0.853 exhibited significantly higher basal ACTH and basal and peak cortisol levels than the 26 patients with scores

Aims: The proper management of atherosclerotic risk factors (ARFs) and attainment of target levels (TLs) for ARFs are crucial in preventing atherosclerotic cardiovascular disease (ASCVD). In this study, utilizing data from the “Specific Health Check and Guidance in Japan,” which was conducted from 2008 to 2011, we examined TL attainment status of low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) and prescription status of dyslipidemia and hypertension in patients with diabetes undergoing medical treatment, and analyzed the factors that affected prescription status. Methods: Subjects receiving medical treatment for diabetes were selected from the database. Subjects were classified by prescription status for dyslipidemia and hypertension, and TL attainment status was assessed for each ARF. Results: The percentage of subjects who did not attain TLs and were not under medication was higher for LDL-C than for BP. The un-prescribed rates among non-TL-attained subjects were 60%–75% for LDL-C, and around 30%–40% for BP. The un-prescribed rates to those who were qualified for prescription therapy were also higher for LDL-C than for BP. Logistic regression analyses revealed that the subjects who were prescribed for dyslipidemia had the following characteristics compared with the un-prescribed non-TL-attained subjects: older age, higher body mass index, lower estimated glomerular filtration rate, previous heart or cerebrovascular disease, and higher medication rate for other ARFs. Conclusions: The present study revealed that, in Japan, the adequate prescription rate for dyslipidemia was lower than that for hypertension in patients with diabetes, suggesting the proper prescription therapy for dyslipidemia should be pursued to further prevent ASCVD.

A 49-year-old woman with membranous nephropathy was referred to our hospital during the tapering of oral prednisolone, because of suspicion of primary adrenal insufficiency based on a plasma ACTH level of 399.1 pg/mL in the Elecsys assay and a serum cortisol level of 3.1 μg/dL. A rapid ACTH stimulation test revealed a suboptimal response, whereas a prolonged ACTH simulation test showed a sufficient increase in her urinary free cortisol. Also, big ACTH was not detected by gel exclusion chromatography. Therefore, we speculated that ACTH levels were falsely elevated due to some interference substances. Pretreatment of her plasma with either polyethylene glycol precipitation or a heterophilic blocking tube substantially reduced her ACTH values. When either the Immulite ACTH II or the TOSOH II ACTH was tried instead of the Elecsys ACTH, her plasma ACTH values turned out to be lower and appropriate for her clinical status. These results indicated that heterophilic antibodies interfered only with the Elecsys ACTH assay presumably by bridging the capture and tracer antibodies. To our knowledge, this is the first case in which the Elecsys ACTH assay yielded falsely elevated results. Regardless of the measurement system used, if there is a discordance between assay results and clinical findings, it should be considered to adopt additional procedures and/or another assay.

We present the first astrometry catalog from the Japanese VLBI (very long baseline interferometer) project VERA (VLBI Exploration of Radio Astrometry). We have compiled all the astrometry results from VERA, providing accurate trigonometric annual parallax and proper motion measurements. In total, 99 maser sources are listed in the VERA catalog. Among them, 21 maser sources are newly reported while the rest of 78 sources are referred to previously published results or those in preparation for forthcoming papers. The accuracy in the VERA astrometry are revisited and compared with those from the other VLBI astrometry projects such as BeSSeL (The Bar and Spiral Structure Legacy) Survey and GOBELINS (the Gould's Belt Distances Survey) with the VLBA (Very Long Baseline Array). We have confirmed that most of the astrometry results are consistent with each other, and the largest error sources are due to source structure of the maser features and their rapid variation, along with the systematic calibration errors and different analysis methods. Combined with the BeSSeL results, we estimate the up-to-date fundamental Galactic parameter of $R_{0}=7.92\pm0.16_{\rm{stat.}}\pm0.3_{\rm{sys.}}$~kpc and $\Omega_{\odot}=30.17\pm0.27_{\rm{stat.}}\pm0.3_{\rm{sys.}}$~km~s$^{-1}$~kpc$^{-1}$, where $R_{0}$ and $\Omega_{\odot}$ are the distance from the Sun to the Galactic center and the Sun's angular velocity of the Galactic circular rotation, respectively., Comment: 35 pages, 7 figures, accepted for publication in the Publications of the Astronomical Society of Japan

Background On 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET), diffuse uptake in the thyroid gland is often observed in patients with Hashimoto’s thyroiditis. In this study, we evaluated the factors associated with diffuse uptake by comparing Hashimoto’s thyroiditis patients with or without diffuse uptake in the thyroid. Methods A retrospective study was conducted of 18 patients with Hashimoto’s thyroiditis who underwent blood tests, thyroid ultrasonography, and FDG-PET during the period from 2014 to 2015. The patients were divided into two groups: one with diffuse thyroid uptake (group 1, n = 13) and one without diffuse thyroid uptake (group 2, n = 5). Clinical and laboratory parameters, including maximum standardized uptake in the thyroid (SUVmax), which was defined as the higher value obtained in either the right or left thyroid lobe, were compared in the two groups. Results The frequency of abnormal findings, such as a rough or heterogeneous pattern, was significantly higher in group 1 (p

Pheochromocytoma rupture is rare, and emergent adrenalectomy is associated with a high mortality. We herein report a patient with pheochromocytoma rupture who was stabilized by transcatheter arterial embolization (TAE) and subsequently underwent elective surgery. A 45-year-old man presented with the sudden onset of left lateral abdominal pain, headache, chest discomfort, high blood pressure, and adrenal hemorrhaging on enhanced abdominal computed tomography. TAE was performed under a provisional diagnosis of pheochromocytoma rupture. Following oral doxazosin, he underwent elective left adrenalectomy four and a half months after TAE. Stabilizing the hemodynamic status by TAE before adrenalectomy is a viable option for treating pheochromocytoma rupture.

Background: Exosomes or small extracellular vesicles secreted from cells are nanovesicles with a diameter of 40–150 nm, which play a number of roles in both physiologic and pathologic processes. In...

[Introduction] Immune checkpoint inhibitors (ICIs) are widely used for the treatment of several malignancies. Despite their effectiveness, they may cause immune-related adverse effects on endocrine organs. Here we describe three cases of isolated ACTH deficiency (IAD) that has occurred after ICI therapy. [Case presentation] Case 1: An 80-year-old female patient with advanced melanoma received nivolumab (NIVO) (3 mg/kg intravenously (IV) every two weeks) for 16 weeks, followed by ipilimumab (3 mg/kg IV every three weeks). After the third injection of ipilimumab, she was alert but complained of general fatigue and anorexia. Her laboratory tests revealed hyponatremia (Na 126 mEq/l), hypoglycemia (Glu 65 mg/dl), low ACTH (ACTH

It has been shown that metastases to the thyroid from extrathyroidal malignancies occur as solitary or multiple nodules, or may involve the whole thyroid gland diffusely. However, diffuse metastasis of gastric cancer to the thyroid is extremely rare. Here, we report a case of a 74-year-old woman with diffuse infiltration of gastric adenocarcinoma (signet-ring-cell carcinoma/poorly differentiated adenocarcinoma) cells in the thyroid. The pathological diagnosis was made based on upper gastrointestinal endoscopy with biopsy and fine-needle aspiration cytology of the thyroid. An 18F-FDG PET/CT revealed multiple lesions with increased uptake, including the bilateral thyroid gland. On thyroid ultrasound examination, diffuse enlargement with internal heterogeneity and hypoechoic reticular lines was observed. On color Doppler imaging, a blood-flow signal was not detected in these hypoechoic lines. These findings were similar to those of diffuse metastases caused by other primary cancers, such as lung cancer, as reported earlier. Therefore, the presence of hypoechoic reticular lines without blood-flow signals is probably common to diffuse thyroid metastasis from any origin and an important diagnostic finding. This is the first report to show detailed ultrasound findings of diffuse gastric cancer metastasis to the thyroid gland using color Doppler.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in 2013, and its official Japanese version was published in 2014. The Japanese Government uses classifications from the 10th revision of the I nternational C lassification of D iseases (ICD-10) to categorize disorders and determine treatment fees. However, since the publication of the DSM-III, the use of the DSM system has become prevalent in research and educational settings in Japan. In addition to traditional psychiatry, both the ICD and the DSM are taught by many Japanese medical schools, and virtually all clinical research and trials refer to the DSM to define targeted disorders. Amid the current backdrop in which the reputation of the DSM-5 is being established, the editorial board of P sychiatry and C linical N eurosciences has asked Japanese experts across 12 specialties to examine the structure of the DSM-5, including the following categories: Neurodevelopmental Disorders, Schizophrenia Spectrum Disorders, Major Depression, Bipolar Disorders, Obsessive-Compulsive Disorders, Somatic Symptom Disorder, Eating Disorders, Substance-Related and Addictive Disorders, Gender Dysphoria, and Neurocognitive Disorders. Although opinions were only obtained from these selected experts, we believe that we have succeeded, to a certain extent, in presenting views that are representative of each specialty.

The functional c.385C>A single-nucleotide polymorphism (SNP) in the fatty acid amide hydrolase (FAAH) gene, one of the major degrading enzymes of endocannabinoids, is reportedly associated with anorexia nervosa (AN). We genotyped the c.385C>A SNP (rs324420) in 762 lifetime AN and 605 control participants in Japan. There were significant differences in the genotype and allele frequencies of c.385C>A between the AN and control groups. The minor 385A allele was less frequent in the AN participants than in the controls (allele-wise, odds ratio = 0.799, 95% confidence interval [CI] 0.653–0.976, P = 0.028). When the cases were subdivided into lifetime restricting subtype AN and AN with a history of binge eating or purging, only the restricting AN group exhibited a significant association (allele-wise, odds ratio = 0.717, 95% CI 0.557–0.922, P = 0.0094). Our results suggest that having the minor 385A allele of the FAAH gene may be protective against AN, especially restricting AN. This finding supports the possible role of the endocannabinoid system in susceptibility to AN.

Summary Aims Dipeptidyl-peptidase 4 inhibitors have become one of the most popular antidiabetic drugs. However, what kind of combinations with other drugs were advantageous was not known. Here, we tried to elucidate it in a real-life clinical setting. Methods We retrospectively studied efficacies of sitagliptin in 87 Japanese patients with type 2 diabetes mellitus for 52 weeks. We divided subjects into excellent, effective and unresponsive subgroups according to glycemic responses to sitagliptin. Results In the excellent and effective groups the minimum HbA1c values were attained at 16 weeks while HbA1c levels in the unresponsive group kept increasing during the study period. There was a significant difference in the baseline HbA1c values between the excellent and unresponsive groups ( p = 0.02). Interestingly, the mean doses of pioglitazone were highest in the excellent group and lowest in the unresponsive group ( p = 0.02). When we compared the effective and unresponsive groups, the mean doses of sulfonylureas were constantly higher in the effective group than in the unresponsive group ( p = 0.05). Conclusions These data suggest that the baseline HbA1c value can be a factor that predicts the extent of HbA1c reduction and reveal a possibility that the concomitant use of pioglitazone augments glycemic responsiveness to sitagliptin.

Aim Statins have many anti-atherogenic effects apart from reducing the serum level of low density lipoprotein cholesterol (LDL-C). For instance, statins can enhance the expression of endothelial nitric oxide synthase (eNOS), at least partly by upregulating its transcription. Although it has been reported that -786 T/C polymorphism of the promoter region has an important influence on statininduced transcription of the human eNOS gene, much remains unclear about statin-induced eNOS transcription. We tried to identify other statin-responsive promoter regions. Methods A human endothelial cell line (EA.hy926 cells) was treated with pitavastatin, atorvastatin, or fluvastatin, after which eNOS mRNA levels were assessed by quantitative real-time RT-PCR. EA.hy926 cells were also transiently transfected with luciferase reporter genes driven by various lengths of the human eNOS promoter and were treated with statins before luciferase activity was measured. Results Statin treatment increased eNOS mRNA levels in EA.hy926 cells. In addition, cells transfected with the reporter gene driven by the eNOS promoter fragment starting from position -740 exhibited a pitavastatin-induced increase of luciferase activity, which was not observed in cells transfected with the reporter gene driven by the fragment starting from -727. Similar results were also obtained with atorvastatin and fluvastatin. Conclusions Statins enhanced eNOS expression in EA.hy926 cells, at least partly by inducing its transcription. Although a statin-responsive sequence that could function even in a heterologous promoter was not precisely identified, the region of the human eNOS promoter around position -730 seems to be critical for statin-induced transcriptional activation.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in 2013, and its official Japanese version was published in 2014. The Japanese Government uses classifications from the 10th revision of the I nternational C lassification of D iseases (ICD-10) to categorize disorders and determine treatment fees. However, since the publication of the DSM-III, the use of the DSM system has become prevalent in research and educational settings in Japan. In addition to traditional psychiatry, both the ICD and the DSM are taught by many Japanese medical schools, and virtually all clinical research and trials refer to the DSM to define targeted disorders. Amid the current backdrop in which the reputation of the DSM-5 is being established, the editorial board of P sychiatry and C linical N eurosciences has asked Japanese experts across 12 specialties to examine the structure of the DSM-5, including the following categories: Neurodevelopmental Disorders, Schizophrenia Spectrum Disorders, Major Depression, Bipolar Disorders, Obsessive-Compulsive Disorders, Somatic Symptom Disorder, Eating Disorders, Substance-Related and Addictive Disorders, Gender Dysphoria, and Neurocognitive Disorders. Although opinions were only obtained from these selected experts, we believe that we have succeeded, to a certain extent, in presenting views that are representative of each specialty.

Objective:This study aimed to investigate the function of tissue plasminogen activator in the olfactory epithelium of mice following neural injury.Method:Transmission electron microscopy was used to study the changes in the morphology of the olfactory epithelium 1–7 days after surgical ablation of the olfactory bulb (bulbectomy).Results:Prior to bulbectomy, a uniformly fine material was observed within some regions of the olfactory epithelium of mice deficient in tissue plasminogen activator. At 2–3 days after bulbectomy, there were degenerative changes in the olfactory epithelium. At 5–7 days after bulbectomy, we noted drastic differences in olfactory epithelium morphology between mice deficient in tissue plasminogen activator and wild-type mice (comparisons were made using findings from a previous study). The microvilli seemed to be normal and olfactory vesicles and receptor neuron dendrites were largely intact in the olfactory epithelium of mice deficient in tissue plasminogen activator.Conclusion:The tissue plasminogen activator plasmin system may inhibit the regeneration of the olfactory epithelium in the early stages following neural injury.

The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by xenobiotic substances such as dioxin. After activation, it binds to dioxin response elements of DNA, thereby inducing transcription of a variety of xenobiotic metabolizing enzymes. To investigate whether AhR-activating substances accumulate in patients with endocrine disorders, we tested serum samples for AhR-stimulating activity.Serum AhR-stimulating activity was evaluated by exposing the HepG2 cells transiently transfected with an AhR-responsive reporter plasmid to serum samples. On the basis of preliminary findings that implicated methimazole (MMI), wild-type and AhR-null mice were treated with MMI, and their plasma AhR-stimulating activities and thyroxine levels were quantified.In 28 randomly chosen patients, 7 out of 10 Graves' disease patients exhibited increased serum AhR-stimulating activity. The increased activity did not correlate with thyroid hormone status. However, we hypothesized that it might be caused by MMI. Subsequent analyses revealed that in 25 of 26 MMI-treated Graves' patients, serum samples collected after the MMI treatment had significantly higher AhR-stimulating activity compared to samples obtained when the same patients were not on MMI. By contrast, serum AhR-stimulating activity was unchanged in samples from the seven patients on propylthiouracil (PTU) compared to serum taken before the PTU treatment. In vitro experiments demonstrated that an MMI metabolite 3-methyl-2-thiohydantoin, but not MMI, activated AhR. MMI increased plasma AhR-stimulating activities and reduced plasma thyroxine concentrations, in both wild-type and AhR-deficient mice.Graves' patients taking MMI have increased serum AhR-stimulating activity, which is unrelated to thyroid hormone status, but correlates with MMI treatment. The AhR activation is likely caused by 3-methyl-2-thiohydantoin. Further studies are required to determine the potency of 3-methyl-2-thiohydantoin as an AhR activator and the significance of the differences between MMI and PTU observed in this study.

Aryl hydrocarbon receptor (AhR) is a transcription factor activated by xenobiotics, including dioxins and polycyclic aromatic hydrocarbons (PAHs). Although AhR is also activated by some dietary constituents, it has not been completely clarified in what circumstances AhR ligands are ingested in our daily life. Because PAHs are formed by the incomplete combustion of organic materials, we hypothesized that scorched foods might contain and leach out AhR ligands sufficient to stimulate AhR in vitro. To test this hypothesis, scorched foods (bread, cheese, etc.) were mixed vigorously with water, and the supernatants were retrieved as samples. The samples were added to HepG2 cells stably expressing an AhR-responsive reporter gene. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was analyzed by RT-PCR in different cell lines treated with the samples. We further tested whether pretreatment of the samples with activated charcoal would alter their AhR-stimulating activity. All the supernatant samples tested induced AhR-dependent reporter gene activity and CYP1A1 mRNA expression. In some samples, these inductions were inhibited by pretreatment with activated charcoal. Our findings indicate that scorched food leachates stimulate AhR in cultured cells and that activated charcoal adsorbs the AhR-stimulating substances in some leachates. Thus, people who habitually eat scorched foods are exposed to AhR ligands on a regular basis. Further studies are needed to elucidate whether burnt foods actually exert biological effects on our health.

The Met66 allele of the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been reported to be associated with anorexia nervosa (AN), and also lower minimum body mass index (BMI) and higher harm avoidance in AN. We genotyped the Val66Met polymorphism (rs6265) in 689 AN cases and 573 control subjects. There were no significant differences in the genotype or allele frequencies of the Val66Met between AN and control subjects (allele wise, odds ratio = 0.920, 95% CI 0.785–1.079, P = 0.305). No difference was found in minimum BMIs related to Val66Met in AN (one-way ANOVA, P > 0.05). Harm avoidance scores on the Temperament and Character Inventory were lower in the Met66 allele carriers (P = 0.0074) contrary to the previous report. Thus we were unable to replicate the previous findings that the Met66 allele of the BDNF is associated with AN and that the minimum BMI is lower or the harm avoidance score is higher in AN patients with the Met66 allele. © 2011 Wiley Periodicals, Inc.

Orbital complications in sinus infections occur due to the anatomical proximity of the paranasal sinuses and orbit. Delayed diagnosis and treatment may involve unfavorable morbidity and mortality. We report 10 cases—7 men and 3 women—of acute rhinosinusitis and acute exacerbation of chronic sinusitis complicating orbital symptoms in the last 5 years. Mean age at consultation was 64.6 years (54-75). Seven had undergone previous sinus surgery. The posterior ethmoid and sphenoid sinus were mainly affected. Mean preoperative visual acuity of 0.07 became 0.53 postoperatively. Restricted eye movement occurred in 1 case of good recovery. Of antibiotics, second- or third-generation cephem was used in 8 cases and carbapenem in 2. Corticosteroids were administered by pulse therapy in 5 and by tapering schedule in 4. Visual recovery occurred in 7. Unrecovered cases were likely to receive delayed surgery. We recommend initial 3-day steroid pulse therapy in subject with decreased vision, discontinued on vision recoveries. Pulse therapy should be continued in case of incomplete or poor recovery.

While oblique stripes have been observed in both laboratory and numerical experiments, their mechanism has not yet been theoretically understood. We investigate an orbital instability of plane Couette flow to infinitesimal disturbances using Lyapunov analysis, assuming the main flow to be a tessellation by identical copies of a minimal turbulence which reduces the numerical cost. Because of the periodicity of the linearized equations in the streamwise and spanwise directions, Bloch’s theorem is applicable and an orbital instability of disturbances with scales larger than the minimal flow unit can be investigated by a calculation within the minimal flow unit. By comparing Lyapunov exponents, we find that the most unstable mode has the Bloch wavenumber parallel to the streamwise direction, which however does not correspond to oblique patterns observed in laboratory experiments and numerical simulations. Therefore the infinitesimal orbital instability of minimal plane Couette turbulence does not explain the ...

Aim: Ezetimibe is known to target Niemann-Pick Type C1 Like1 (NPC1L1), a key protein in intestinal cholesterol absorption, and thus to decrease serum LDL-cholesterol (LDL-C) levels. The response of serum LDL-C levels to ezetimibe was reported to differe among NPC1L1 haplotypes.We analyzed NPC1L1 genotypes in Japanese and investigated differences in markers of cholesterol synthesis/absorption among the genotypes.Methods: Blood samples were collected from 42 adult volunteers to measure markers of cholesterol synthesis (lathosterol) and absorption (sitosterol and campesterol) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on a study by Hegele RA et al. in Canada, we selected three SNPs (1735 C>G, 25342 A>C and 27677 T>C (numbers relative to the transcription start site)) and analyzed them using PCR-RFLP.Results: The frequencies of genotypes were as follows: 1735 C/G (46%)>C/C (35%)>G/G (19%), 25342 A/A (97%)>A/C (3%)>C/C (0%) and 27677 T/T (97%)>T/C (3%)>C/C (0%). Serum campesterol levels were significantly higher in the 1735 G/G group than 1735 C/G+C/C group, but lathosterol levels showed no significant differences between the genotypes.Conclusion: Our results revealed differences in the frequency of the NPC1L1 polymorphism between Japanese and Canadians. In Japanese, the 1735 G/G group showed enhanced cholesterol absorption from the intestine, as compared to the 1735 C/G+C/C group.

To identify molecular signatures and establish a new diagnostic model for progressive oral squamous cell carcinoma (OSCC). Total RNAs were isolated from primary OSCCs from both node-positive and -negative patients and used in cDNA microarray analysis. To identify marker genes representing a malignant phenotype, their expression was further examined by quantitative reverse transcription-PCR (QRT-PCR) in 64 OSCC tissues. Using Fisher's linear discriminant analysis (LDA) fitted with a stepwise increment method, we created discriminatory predictor models. The stability of these models was examined using leave-one-out cross validation. Immunohistochemical analysis was performed. Among the 16,600 possible target cDNAs in the array analysis, 83 genes demonstrated significantly differential signals (>2-fold). We further identified 53 marker genes that can be implicated in the Yamamoto-Kohama's (YKs) mode of invasion for OSCCs (P < 0.06). Using LDA fitted with a stepwise increment method, we created four discriminatory predictor models based on 16- to 25-gene signatures which could best distinguish the five established grades of YKs mode of invasion. Leave-one out validation demonstrated that the stability of these models was 92-95%. For validation, we also examined an independent set of 13 primary OSCCs; the predictor models determined the invasion status from 77% to 100% (on average, 85%) fidelity with the pathological observations. TGM3 protein expression was markedly suppressed in highly invasive OSCCs. We reveal novel gene expression alterations during the progression of OSCC, and have constructed prediction models for the evaluation of the invasion status of these cancers.

Cyclic Cushing's disease is a rare clinical entity that is defined as a periodic excessive production of adrenocorticotropic hormone (ACTH) and cortisol. Only 42 cases with cyclic Cushing's disease have been reported in the literature. The diagnosis is very difficult because of the fluctuating secretion of ACTH and cortisol. We report a 78-year-old woman with a pituitary adenoma presenting with cyclic Cushing's disease. In the present case, several interesting issues are pointed out: 1) MRI study detected the presence of an adenoma and selective venous sampling in the cavernous sinus disclosed the hypersecretion of ACTH from a pituitary adenoma. These neuroimaging and endocrinological studies were helpful for the diagnosis, even in the remission phase. 2) The disease was in the long-term remission phase after transsphenoidal surgery despite the high recurrence rate in this clinical entity, although it recurred four years later. Even in the remission phase of cyclic Cushing's disease, meticulous endocrinological and neuroimaging examinations can reveal the presence of a pituitary adenoma, which should be treated surgically.

Previous reports including genome-wide association studies (GWASs) have described associations of serum lipids with genomic variations. In the present study, we examined the association of ∼2.5 million single-nucleotide polymorphisms (SNPs) from 3041 Japanese healthy volunteers obtained from the Japan Pharmacogenomics Data Science Consortium (JPDSC) database with serum lipids. We confirmed the previously reported associations of 14 SNPs in 5 regions for low-density lipoprotein (LDL) cholesterol, 23 SNPs in 12 regions for high-density lipoprotein (HDL) cholesterol, 16 SNPs in 6 regions for triglyceride and 5 SNPs in 1 region for phospholipid. Furthermore, we identified 16 possible novel candidate genes associated with LDL cholesterol, HDL cholesterol or triglycerides, where SNPs had P-values of

Previous investigations have suggested that ghrelin, an endogenous orexigenic peptide, is involved in the pathology of eating disorders. We conducted a study to determine whether any preproghrelin gene polymorphisms are associated with eating disorders. Three hundred thirty-six eating disorder patients, including 131 anorexia nervosa (AN)-restricting types (AN-R), 97 AN-binge eating/purging types (AN-BP) and 108 bulimia nervosa (BN)-purging types (BN-P), and 300 healthy control subjects participated in the study. Genotyping was performed to determine the polymorphisms present, and with this information, linkage disequilibrium (LD) between the markers was analyzed and the distributions of the genotypes, the allele frequencies, and the haplotype frequencies were compared between the groups. The Leu72Met (408 C > A) (rs696217) polymorphism in exon 2 and the 3056 T > C (rs2075356) polymorphism in intron 2 were in LD (D' = 0.902, r2 = 0.454). Both polymorphisms were significantly associated with BN-P (allele-wise: P = 0.0410, odds ratio (OR) = 1.48; P = 0.0035, OR = 1.63, for Leu72Met and 3056 T > C, respectively). In addition, we observed a significant increase in the frequency of the haplotype Met72-3056C in BN-P patients (P = 0.0059, OR = 1.71). Our findings suggest that the Leu72Met (408 C > A) and the 3056 T > C polymorphisms of the preproghrelin gene are associated with susceptibility to BN-P.

Chronic sinusitis with eosinophils easily recurs after endoscopic sinus surgery. The condition is usually complicated by asthma, and many eosinophils are present in the sinus mucosa. One conservative treatment method is the administration of glucocorticoids locally or systematically. To evaluate the efficacy and tolerability of intranasal fluticasone propionate for the treatment of chronic sinusitis with eosinophils, seven patients with chronic sinusitis with eosinophils were treated over a 12-week period using a fluticasone propionate aqueous nasal spray (800 microg per day in each nostrilz). The Symptons of 7 patients, especially nasal discharge and nasal obstructions, improved and an expanded air space was observed on paranasal CT images. The percent of drug systemically available after intranasal administration varied by less than 1% for intranasal fluticasone propionate. Therefore, even if intranasal fluticasone propionate is administerved at double the usual dose, it is unlikely to cause systemic side effects. Fluticasone propionate aqueous nasal spray at double the usual dose is effective for the treatment of chronic sinusitis with eosinophils.

The classical pathway for estrogen receptor (ER) signaling is mediated by ER binding to an estrogen response element (ERE) in DNA. ERalpha can also act via a nonclassical pathway by altering the activities of other transcription factors (e.g., Sp1, AP-1, or NF-kappaB) at their cognate sites on DNA. We previously generated a mutant form of ERalpha (E207A/G208A) that does not bind to EREs, and therefore lacks signaling via the classical pathway but retains signaling via the nonclassical pathway. In the current study, we introduce this mutant ERalpha into MDA-MB231 ERalpha-negative breast carcinoma cells to identify nonclassical pathway genes that respond to 17beta-estradiol (E2), selective estrogen receptor modulators (SERMs) tamoxifen (TAM) or raloxifene (RAL), or the estrogen antagonist ICI 182,780 (ICI). Consistent with a role for nonclassical signaling in SERM action, microarray analyses identify 268 responsive nonclassical ERalpha pathway target genes. ICI elicits the largest number of nonclassical genes, followed by RAL, TAM, and E2. Custom microarrays containing identified nonclassical ERalpha responsive genes are used to compare gene expression in human breast tumor (n = 34) and normal mammary epithelial cell (n = 9) samples. A subset of nonclassical genes (n = 32) are differentially expressed in breast tumors. In summary, we show that nonclassical ERalpha pathway target genes exhibit a range of transcriptional responses to SERMs and identify targets of this pathway as potentially relevant to breast cancer. The identification of nonclassical ERalpha target genes offers new insight into estrogen receptor signaling and cross talk with pathways that mediate breast tumor response to SERM therapy.

Social support is supposed to have a positive health effect via alteration of immunity. In this study, associations between perceived social support and immune systems were examined. Immunological assessments, e.g. T cell count, Natural Killer cell count, Interferon-gamma, Interleukin-4, and psychological assessments, e.g. Generic Job Stress Questionnaire were conducted on male employees. Two-way (social support x job stressor) analyses of covariance controlling for age, smoking, alcohol consumption, and exercise revealed that there were main effects of perceived social support on NK cell counts, IL-4, and Th1/Th2 balance. On the other hand, interaction effects were observed on T cell counts and INF-gamma production in vitro. Social support affects immune function in a way that is consistent with both the direct and buffering hypotheses depending on the sources of support and the immune parameter.