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Objective: To elucidate the effectiveness of a 30-degree anteriorly tilted coronal CT in visualizing the anterior wall of the sphenoid sinus., Methods: Medical records and CTs of patients who underwent septoplasty, inferior turbinectomy, or endoscopic sinus surgery were reviewed. We evaluated the visibility of the anterior wall of the sphenoid sinus on conventional coronal CT scans and categorized its orientation. We then created anteriorly tilted coronal CT images to evaluate its improved visibility., Results: A total of 129 patients were evaluated. While conventional coronal CT scans fully visualized the anterior wall of the sphenoid sinus in cases with an Onodi cell, 17.7% remained unidentified when the Onodi cell was absent. However, anteriorly tilted coronal CT scans consistently identified the anterior wall regardless of the presence of an Onodi cell., Conclusion: Our study highlights the effectiveness of anteriorly tilted coronal CT scans in consistently visualizing the anterior wall of the sphenoid sinus, regardless of the presence of an Onodi cell. It is possible that some other structures may become less identifiable on anteriorly tilted coronal CT., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: This study aims to evaluate the presence of residual Plus Moist HS-W (PM), a novel calcium alginate packing material, during the initial postoperative visit following endoscopic sinus surgery. The research aims to identify factors that influence the quantity of remaining PM., Methods: A retrospective review of medical records was conducted for patients who underwent middle meatus packing with PM., Results: A total of fifty-two patients (representing 92 sides of paranasal sinuses) were included in the analysis. The remaining PM was classified as follows: absent (0) in 41 out of 92 cases, minimal (1) in 22 out of 92 cases, moderate (2) in 15 out of 92 cases, and substantial (3) in 14 out of 92 cases. Notably, all three patients who underwent Draf III surgery exhibited a significant amount of PM during their initial visit, with two patients classified as grade 2 and one patient as grade 3. Other factors investigated were found to be unrelated to the persistence of PM. Removal of all PM was achieved effortlessly using suction under flexible endoscopy., Conclusion: This study highlights the efficacy of PM in post-endoscopic sinus surgery care. It is important to limit an amount of PM, particularly in Draf III procedures., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier B.V.)

Cyclic peptides are attracting attention as therapeutic agents due to their potential for oral absorption and easy access to tough intracellular targets. LUNA18, a clinical KRAS inhibitor, was transformed-without scaffold hopping-from the initial hit by using an mRNA display library that met our criteria for drug-likeness. In drug discovery using mRNA display libraries, hit compounds always possess a site linked to an mRNA tag. Here, we describe our examination of the Structure-Activity Relationship (SAR) using X-ray structures for chemical optimization near the site linked to the mRNA tag, equivalent to the C-terminus. Structural modifications near the C-terminus demonstrated a relatively wide range of tolerance for side chains. Furthermore, we show that a single atom modification is enough to change the pharmacokinetic (PK) profile. Since there are four positions where side chain modification is permissible in terms of activity, it is possible to flexibly adjust the pharmacokinetic profile by structurally optimizing the side chain. The side chain transformation findings demonstrated here may be generally applicable to hits obtained from mRNA display libraries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective/background: To clarify whether mobile sleep applications alleviate insomnia symptoms among adults from multi-community., Patients/methods: A literature search was conducted using the PubMed, Cochrane, PsycINFO, and Web of Science databases for articles related to mobile technology and sleep interventions published between database inceptions and March 27, 2023. We pooled relevant data using a random-effects model, and a meta-analysis was performed using a web version of the Cochrane Review Manager. The effect size was estimated and reported as the combined overall effect (weighted average). Forest plots were created, and the Cochrane risk-of-bias tool and Newcastle-Ottawa Scale were used to evaluate studies., Results: After an initial screening and full-text reviews, seven studies were identified with a total of 10,139 participants (females n = 8844, 87.2 %) recruited from multi-community and not diagnosed with sleep disorders or taking medications. These studies included one cross-sectional study investigating mindfulness meditation apps and six randomized-controlled trials (RCTs), including one with sleep-feedback messaging, one comparing sleep applications with or without a wearable device, and four with multicomponent interventions based on cognitive theory and subsequent behavioral change techniques. In a meta-analysis of three cognitive behavior therapy (CBT)-based RCTs, the intervention group showed statistically significant improvements in insomnia symptoms according to the Pittsburgh Sleep Quality Index but with high heterogeneity, while two CBT-based RCTs showed no significant improvements in the Insomnia Severity Index with low heterogeneity., Conclusions: A small body of evidence supports the use of CBT-based sleep applications to improve insomnia symptoms among adults from multi-community., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Head and neck surgeries may cause changes in the nasal airflow, and radiotherapy irreversibly damages paranasal sinus epithelial cells. Some chemotherapeutic drugs have been reported to negatively affect airway ciliary activity in mice, and chronic rhinosinusitis could be an adverse effect of head and neck cancer (HNC) treatment. To evaluate whether HNC treatment is a risk factor for developing sinonasal mucosal thickening that may reflect paranasal sinus inflammation, we compared pre- and post-treatment paranasal sinus computed tomography (CT) images of patients treated for HNC at a single university hospital., Methods: The patients who received curative treatment for HNC (oral, pharyngeal, and laryngeal cancers) and started receiving first-line therapy between January 2015 and December 2019 were included. Data on age, sex, primary lesion, clinical stage, treatment, smoking history, drinking history, comorbidities (diabetes and chronic lung disease), and pre- and post-treatment (three months and one year after the final treatment) paranasal sinus CT images were analyzed from medical records. Pre- and post-treatment paranasal sinus CT images were scored using the Lund-Mackay (LM) staging system., Results: In total, 245 patients participated in this study. Three months after the final treatment, 80.4% of patients had no change in their total LM scores (p=0.621). Almost 80% of patients who underwent total laryngectomy also had no change in their total LM scores (p=0.833). One-third of patients with nasopharyngeal cancer (NPC) had worse LM scores after treatment (5/15), although no significant difference was observed (p=0.171). None of the various factors collected were significantly related to changes in LM scores three months after the completion of treatment. One year after the final treatment, 211 patients were included and no significant changes in the pre-and post-LM scores were observed in the same analyses, while changes in LM scores were significantly different between T categories (T1-2 vs. T3-4) (p=0.020)., Conclusion: We found no significant changes in the LM scores after HNC treatment in all the patients, which implies that HNC treatment may not be an apparent risk factor for sinonasal mucosal inflammation., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022. Published by Elsevier B.V.)

Objective/background: Insomnia among truck drivers may contribute to traffic accidents. We previously reported that truck drivers had adverse lifestyle habits, including smoking and drinking alcohol, in addition to enforced sedentarism making them more vulnerable to lifestyle-related diseases. This study aimed to investigate the association between insomnia and diabetes, as well as the effect of anxiety related to driving tasks on this association., Patients/methods: A total of 755 male truck drivers under 65 years of age who belonged to Akita prefecture Truck Association in Japan were investigated. Insomnia and State-Trait Anxiety Inventory (STAI) score were assessed using a self-administered questionnaire in 2020. Insomnia was defined in accordance with International classification of sleep disorders-third edition. Diabetes was defined as a fasting blood glucose level of ≥126 mg/dL and/or use of anti-diabetic drugs using data obtained from health checkups in 2018., Results: The proportions of truck drivers with insomnia and diabetes were 13.9% and 9.7%, respectively, which were higher than those in the general working population in Japan. After adjusting for age, smoking, drinking, daily hours of driving and sleep, and hypertension, the STAI score (odds ratio [OR] for the highest quartile vs. the lowest: 3.88, 95% confidence interval [CI]: 1.84-8.18) and diabetes (OR: 2.49, 95% CI: 1.11-5.60) were found to be associated with insomnia. A statistical interaction with STAI scores was not observed between diabetes and insomnia., Conclusions: The present study demonstrated that diabetes and anxiety are independently and significantly associated with insomnia in male Japanese truck drivers., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Sinonasal inverted papilloma can be resected endoscopically, but has a risk of recurrence. This risk can be minimized by identifying the pedicle of the tumor and ensuring complete resection. Intraoperative bleeding, particularly from the tumor, decreases endoscopic visualization and contributes to failure to identify the tumor pedicle, and piecemeal resection with dissection of the non-tumoral mucosa makes it impossible to distinguish the tumor pedicle. Previously reported transseptal access with crossing multiple incisions (TACMI) increases mobility of an inverted papilloma within the otherwise restricted nasal cavity. This technique often allows en bloc resection complete with the pedicle and control of bleeding., Methods: We retrospectively reviewed our patients who underwent endoscopic resection of inverted papilloma with or without TACMI and compared the operating times, estimated blood loss, and en bloc resection and recurrence rates between the two groups., Results: Thirty-five patients underwent endoscopic resection of inverted papilloma (Krouse stage 2-4) with (n = 23) or without (n = 12) TACMI. The operating time was longer in the TACMI group (218±68 min) than in the non-TACMI group (129±33 min). Estimated blood loss was less in the TACMI group (72±103 mL vs. 120±136.5 mL) but this finding was not significant. En bloc resection was achieved in 19 patients (83%) in the TACMI group but not in any patient in the non-TACMI group. There were no recurrences in the TACMI group. Multivariate analysis showed significant relationships between estimated amount of blood loss and operating time according to Krouse stage and whether or not TACMI was performed., Conclusions: Endoscopic resection of inverted papilloma with TACMI may achieve better treatment results with less blood loss., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To investigate risk factors for dysgeusia after tonsillectomy., Methods: A retrospective survey of medical records identified 318 patients (163 male and 155 female subjects aged 12-75 years, average 41.7±16.1 years) who underwent tonsillectomy., Results: Thirty three patients (10.4%) and seven patients (2.2%) reported suffering from dysgeusia three and six months after tonsillectomy, respectively. Average age, serum level of Zn and operation time were not significantly different between positive and negative findings of dysgeusia. Women with positive findings of dysgeusia (72.7%) was significantly higher than men (27.3%) (Odds ratio: 3.276, 95% CI: 1.441-7.450, p<0.005). A chi-square test of independence was calculated comparing the frequency of dysgeusia in under 60 years old group (13-59 years-old) and 60 years old and over group (60-75 years-old). A significant interaction was found (χ2 (1)=5.238. p<0.05)., Conclusions: Women and under 60 years old patients had a significantly higher rate of dysgeusia after tonsillectomy. It is recommended that patients are informed of the potential postoperative complication of dysgeusia., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Optimization of manufacturing processes based on scientific evidence is important in the quality control of active pharmaceutical ingredients (APIs) and drug products, particularly when crystal forms change during production, which could affect subsequent drug performance. In this study, we verified crystalline states using various crystal faces and excipients during high-shear wet granulation based on non-contact low-frequency (LF) Raman probe monitoring. Four model drugs [indomethacin (IND), acetaminophen (APAP), theophylline (TP), and caffeine (CAF) polymorphs and cocrystals] were mixed with microcrystalline cellulose and hydroxypropyl cellulose with the addition of water over time. The LF Raman probe showed comparatively high sensitivity in monitoring 5-20% APAP and IND in a wet mass. Notably, as observed from the characteristic LF Raman peak shifts, form I TP and CAF and their cocrystals were more susceptible to transformation to the monohydrate form than form II. This method was also shown to be applicable in monitoring a commercial formulation of eight excipients and revealed crystalline transformations after 15 min of mixing. Therefore, probe-type LF Raman spectroscopy can be successfully employed to distinguish and monitor the crystalline state of APIs in real time during high-shear wet granulation, in which there is a risk of crystal transformation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: The Caldwell-Luc (CL) approach with a sublabial incision is used to manipulate the anterior wall of the maxillary sinus. Paresthesia is one of the major complications associated with the CL approach. We developed a new method, "direct approach to the anterior and lateral part of the maxillary sinus with an endoscope" (DALMA), that negates the need for a sublabial incision and minimizes dental paresthesia by reducing the risk of anterior superior alveolar nerve injury. This study aimed to describe how to perform the DALMA technique, and to review its effectiveness and associated complications., Methods: We retrospectively reviewed 10 patients who had received DALMA., Results: Ten patients underwent DALMA. The anterior superior alveolar nerve was identified in all patients. Access to the lateral side beyond the infraorbital canal and anterior wall of the maxillary sinus was achieved., Conclusions: DALMA is a simple, effective, and minimally invasive technique that can be used as an alternative to CL with sublabial incision., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Fibroblast growth factor 21 (FGF21), a member of the FGF subfamily that acts through the FGF receptor 1 with the co-receptor β-Klotho, functions as an important metabolic regulator of peripheral glucose tolerance and lipid homeostasis in an endocrine or autocrine and/or paracrine manner. Previous studies showed that FGF21 ameliorated and prevented the development of metabolic disorders, such as obesity and diabetes mellitus. In the present study, we demonstrated that berberine, a naturally occurring compound, stimulated FGF21 expression in brown adipose tissue (BAT). Furthermore, the up-regulated expression of FGF21 in brown adipocytes in response to berberine was due, at least in part, to the activation of the AMP-activated protein kinase pathway. We also found that berberine reversed high-fat diet-induced obesity concomitant with its regulation of the expression of Fgf21 and the core clock component brain and muscle Arnt-like 1 (Bmal1) in BAT. Berberine significantly up-regulated the gene expression and production of FGF21 in a dose-dependent manner in C3H10T1/2 brown adipocytes. Furthermore, the knockdown of Bmal1 prevented the up-regulated expression of FGF21 in response to berberine in C3H10T1/2 brown adipocytes, suggesting that Bmal1 links the regulatory mechanisms of FGF21 in response to berberine. The present results suggest that berberine stimulates the expression of FGF21 by modulating molecular clock Bmal1 in BAT, which may, in turn, attenuate diet-induced obesity. They also indicate the potential of berberine as a therapeutic agent for obesity and obesity-associated metabolic disorders related to circadian misalignments., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Breastfeeding rates in many countries fall short of the World Health Organization's recommendations. It has been reported that exclusive breastfeeding (EBF) is negatively associated with obesity; however, the association varies with ethnicity, and little information is available from Asia. We explored whether prepregnancy body mass index (BMI) and gestational weight gain (GWG) were associated with initiation of EBF., Methods: We investigated 6125 Japanese women with full-term (37-42 wk of gestation) singleton babies between January 2010 and June 2013, in a hospital with the largest annual number of deliveries in Tokyo, Japan., Results: Successful EBF initiation was observed in 72% of women 1 mo after delivery. The average GWG was 10 kg in underweight (BMI < 18.5 kg/m 2 ) and normal weight (BMI 18.5-24.9 kg/m 2 ) women; 7 kg in overweight (BMI 25-29.9 kg/m 2 ) women, and 4 kg in obese (BMI ≥ 30 kg/m 2 ) women. After adjusting for covariates, stepwise modeling revealed that compared with women of normal weight, obesity (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.16-0.53), and a single-unit increase in the GWG (OR, 0.98; 95% CI, 0.96-1.00) were significantly associated with unsuccessful EBF initiation. No statistical interaction was evident between prepregnancy BMI and GWG. Other significant risk factors for unsuccessful EBF initiation included older maternal age (P < 0.001), nulliparity (P < 0.001), cesarean delivery (P < 0.001), an earlier gestational week (P < 0.001), a light-for-date infant (P < 0.05), and mother-child separation for clinical reasons (P < 0.001)., Conclusions: This study suggested that prepregnancy obesity is a risk factor for EBF initiation among Japanese women., (Copyright © 2018 Elsevier Inc. All rights reserved.)

All regioisomeric di- and tetrahydrogeranylgeraniols possessing the C2C3 double bond were prepared as authentic samples. The synthetic C 20 -isoprenoid alcohols were separated well by gas chromatography. Based on the chromatographic analysis, the enzymatic reduction pathway of a geranylgeranyl group was investigated to identify the last stage of (bacterio)chlorophyll biosynthesis in phototrophs. The geranylgeranyl group was triply reduced to the phytyl group through the first regio- and stereospecific hydrogenation of C10C11 to C10HC11(S)H, the second of C6C7 to C6HC7(S)H, and the third of C14C15 to C14HC15H. The identification of the reduction sequence completes the biosynthetic pathways for naturally occurring chlorophyll-a and bacteriochlorophyll-a bearing a phytyl group as the esterifying moiety in the 17-propionate residues., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The biogenic amine histamine (HA) is not only the neurotransmitter of photoreceptors but also has important roles in mechanosensory reception, temperature preference, sleep and olfactory processing in insects. Two cDNAs (MdhclA and MdhclB) that encode HA-gated chloride channel subunits (MdHCLA and MdHCLB) were cloned from the housefly Musca domestica. The cRNAs were injected into Xenopus laevis oocytes to examine the functions and pharmacological characteristics of MdHCLA and MdHCLB channels using a two-electrode voltage clamp method. HA was used to activate MdHCLA and MdHCLB channels to evoke inward currents with EC 50 s of 33.1μM and 6.28μM, respectively. 2-(3-Trifluoromethylphenyl)histamine, an HA H 1 receptor agonist, was a partial agonist of MdHCLB receptors with an EC 50 of 49.4μM. MdHCLB channels were also activated by γ-aminobutyric acid (GABA) and monoamines, such as octopamine, serotonin (5-HT) and dopamine (DA); 5-HT and DA also acted as competitive antagonists. GABA acted as a full agonist of MdHCLB receptors with an EC 50 of 1.11mM. d-Tubocurarine, cimetidine and picrotoxinin were poor inhibitors of HA- and GABA-evoked currents in MdHCLB channels. Our data show that HCLB channels are more sensitive to agonists when compared with HCLA channels. HCLB channels are also affected by antagonists but insusceptible to known insecticides that target GABA- and glutamate-gated chloride channels., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, possesses many biological activities including anti-inflammatory and antioxidant activities. We aimed to investigate the protective effects of fucoidan on dyslipidemia and atherosclerosis in apolipoprotein E-deficient mice (ApoE(shl) mice) and to elucidate its molecular targets in the liver by using a transcriptomic approach. For 12weeks, ApoE(shl) mice were fed a high-fat diet (HFD) supplemented with either 1% or 5% fucoidan. Fucoidan supplementation significantly reduced tissue weight (liver and white adipose tissue), blood lipid, total cholesterol (TC), triglyceride (TG), non-high-density lipoprotein cholesterol (non-HDL-C) and glucose levels in HFD-fed ApoE(shl) mice but increased plasma lipoprotein lipase (LPL) activity and HDL-C levels. Fucoidan also reduced hepatic steatosis levels (liver size, TC and TG levels, and lipid peroxidation) and increased white adipose tissue LPL activity. DNA microarray analysis and quantitative reverse transcription-polymerase chain reaction demonstrated differential expression of genes encoding proteins involved in lipid metabolism, energy homeostasis and insulin sensitivity, by activating Ppara and inactivating Srebf1. Fucoidan supplementation markedly reduced the thickness of the lipid-rich plaque, lipid peroxidation and foaming macrophage accumulation in the aorta in HFD-fed ApoE(shl) mice. Thus, fucoidan supplementation appears to have anti-dyslipidemic and anti-atherosclerotic effects by inducing LPL activity and inhibiting the effects of inflammation and oxidative stress in HFD-fed ApoE(shl) mice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Human nasal epithelial cells (HNECs) are important in the tight junctional barrier and innate immune defense protecting against pathogens invading via Toll-like receptors (TLRs). MicroRNAs (miRNAs) regulate expression of tight junctions as direct or indirect targeting genes and maintain the barrier function. However, the roles of miRNAs in the epithelial barrier of HNECs via TLRs remain unknown. In the present study, to investigate the effects of miRNAs on the epithelial barrier of HNECs via TLRs, primary cultured HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs), were treated with the TLR3 ligand poly(I:C) and miRNA array analysis was performed. In the miRNA array of the cells treated with poly(I:C), upregulation of miR-187, -146a, -574, -4274, -4433, -4455 and -4750, and downregulation of miR-4785 by more than twofold compared to the control were observed. When control HNECs were treated with mimics and inhibitors of these miRNAs, an miR-146a mimic induced expression of tight junction proteins claudin-1, occludin and JAM-A together with an increase of the epithelial barrier function. The poly(I:C)-induced miR-146a was regulated via the distinct TLR3-mediated signal pathways PI3K, JNK and NF-κB. Furthermore, the miR-146a mimic prevented downregulation of claudin-1 and JAM-A and the secretion of proinflammatory cytokines IL-8 and TNF-α induced by poly(I:C) by targeting TRAF6. These findings indicate that, in HNECs, miRNA-146a plays crucial roles in maintenance of the tight junction barrier and innate immune defense protecting against invading pathogens., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Chest computed tomography (CT) is not performed routinely or worldwide as the initial diagnostic procedure for patients with head and neck cancer (HNC). The significance of the chest CT scan for HNC diagnosis has not been thoroughly defined. The present study reports findings in an effort to broaden the acceptance and application of CT for HNC., Methods: Using medical records, we assessed initial chest CT scans of the patients with new-onset HNC between April 2004 and March 2010. The results were classified into three groups: nodules ≥ 1 cm, small nodules (< 1 cm) that were indeterminate and normal lungs without nodules. Lung nodules that increased in size and/or number at follow-up were regarded as malignant. First, the sensitivity of X-ray and CT for detection of lung nodules in patients with HNC was compared. Second, the nodules were estimated to be malignant or not malignant by follow-up chest CT. Third, statistical analyses were performed to determine the association between variables and distant lung metastases in patients with head and neck squamous cell carcinoma., Results: In total, 332 patients underwent a chest CT scan as part of the initial examination. Lung nodules were detected on the initial chest CT in 77 patients: in contrast, lung nodules were detected on the initial chest X-ray in only five patients. On initial chest CT scans, lung nodules ≥ 1 cm were observed in 10 patients, small solitary lung nodules were observed in 67 patients, and lungs without nodules were observed in 255 patients. Lung nodules were detected in 77 (23.2%) patients, 25 (32.5%) of whom had malignant lung nodules. Moreover, in 18/67 patients (26.9%), small lung nodules initially classified as indeterminate were determined as malignant at follow-up. However, 30/255 patients (11.8%) without nodules at initial diagnosis developed lung nodules at follow-up. T3 or T4 disease (P = 0.006), N2 or N3 disease (P < 0.001) and stage 3 or 4 disease (P = 0.001) individually and significantly correlated with the development of lung metastases. In addition, lung nodules in initial CT scans (P = 0.004) and other distant metastases (P < 0.001) were significant predictors for the development of lung metastases at follow-up., Conclusion: Initial chest CT scan is recommended for patients with advanced HNC. Further, patients with advanced HNC with or without lung nodules, as detected on initial chest CT scans, should be followed up with additional scanning., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The acetyl-CoA (Ac-CoA) transporter, ACATN is a multiple (11 or 12) transmembrane protein in the endoplasmic reticulum. Ac-CoA is transported into the lumen of the endoplasmic reticulum/Golgi apparatus, where it serves as the substrate of acetyltransferases that modify a variety of molecules including the sialic acid residues of gangliosides and lysine residues of membrane proteins. The ACATN gene, assigned as SLC33A1, was cloned from human melanoma cells and encodes the ACATN/ACATN1 (Acetyl-CoA Transporter 1) protein. Although homologs of this family of proteins have been identified in lower organisms such as Escherichia coli, Drosophila melanogaster and Caenorhabditis elegans, only one member of this SLC33A1 family has been identified. Although acetylated gangliosides are synthesized in the luminal Golgi membrane and show a highly tissue-specific distribution, ACATN1 is enriched in the ER membrane and is ubiquitously expressed. Phylogenetically, the SLC33A1 gene is highly conserved, suggesting that it is particularly significant. In fact, ACATN1 is essential for motor neuron viability. SLC33A1 is associated with neurodegenerative disorders such as sporadic amyotrophic lateral sclerosis (ALS) and Spastic Paraplegia 42, in the Chinese population., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: The sphenoid sinus is situated at the most posterior part of the nasal cavity and opens at the sphenoethmoidal recess located between the nasal septum and the superior turbinate. The correlation between anatomical structures surrounding the sphenoid sinus and sphenoid sinusitis is poorly understood. This study investigated possible factors that correlate to opacification of the sphenoid sinus on computed tomography., Methods: Review of computed tomography images of 200 patients who underwent endoscopic sinus surgery and/or septoplasty. The total lengths of the anterior sphenoid wall and the part medial to the superior turbinate were measured. The correlations were analyzed between the occurrence of sphenoiditis and these values, as well as age, sex, presence or absence of Onodi cell, opacification of the paranasal sinuses other than the sphenoid sinus, and shadow at the olfactory cleft., Results: The length of the part medial to the superior turbinate was significantly (odds ratio=1.36, P=0.001) associated with sphenoiditis, but the total length of the anterior wall of the sphenoid was not. Advanced age and disease of the olfactory cleft, posterior ethmoid cells, and frontal sinus were also correlated with sphenoiditis., Conclusions: Certain characteristics of the anatomical structures surrounding the sphenoid sinus are associated with sphenoiditis., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Chronic sclerosing sialadenitis, which clinically resembles a salivary gland tumor, is considered a salivary gland lesion of the IgG4-related inflammatory disease. Corticosteroids are effective for the treatment of chronic sclerosing sialadenitis, but the natural clinical course of this disease is not fully understood. We report a 67-year-old man with chronic sclerosing sialadenitis who showed lung lesions, which spontaneously regressed without steroid therapy after excision of the submandibular gland. He presented with several weeks' history of continuous swelling in the right submandibular region. Physical examination showed a hard swelling of the right submandibular gland; the cytological finding was Papanicolaou class III. A chest X-ray demonstrated bilateral infiltration of the right middle and left lower lobes. The right submandibular gland was excised under general anesthesia for definite diagnosis, and histopathological examination revealed an IgG4-positive plasmacytic infiltration accompanied by periductal fibrosis and interlobular sclerosis, consistent with chronic sclerosing sialadenitis. Five months after operation, the lung lesions regressed spontaneously., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) currently affects 20%-30% of adults and 10% of children in industrialized countries, and its prevalence is increasing worldwide. Although NAFLD is a benign form of liver dysfunction, it can proceed to a more serious condition, nonalcoholic steatohepatitis (NASH), which may lead to liver cirrhosis and hepatocellular carcinoma. NAFLD is accompanied by obesity, metabolic syndrome and diabetes mellitus, and evidence suggests that fructose, a major caloric sweetener in the diet, plays a significant role in its pathogenesis. Inflammatory progression to NASH is proposed to occur by a two-hit process. The first "hit" is hepatic fat accumulation owing to increased hepatic de novo lipogenesis, inhibition of fatty acid beta oxidation, impaired triglyceride clearance and decreased very-low-density lipoprotein export. The mechanisms of the second "hit" are still largely unknown, but recent studies suggest several possibilities, including inflammation caused by oxidative stress associated with lipid peroxidation, cytokine activation, nitric oxide and reactive oxygen species, and endogenous toxins of fructose metabolites., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Male and female teleost seabream (Pagrus major) were examined for seasonal variation of eumelanin, pheomelanin, 11-ketotestosterone (11KT, fish androgen), lightness (L* value) and Gonad Somatic Index (GSI: gonad mass/body massx100). In males, levels of pyrrole-2,3,5-tricarboxylic acid (a marker of eumelanin), 11KT and the GSI increased sharply from September and plateaued in March and April when the fish are sexually mature. These results are consistent with the lightness of their body color. Using the data from males, a high correlation was observed for all combinations of those four variables (PTCA, 11KT, lightness and GSI). In females, little change was observed in those variables except for the GSI. 4-Amino-3-hydroxyphenylalanine (a marker of pheomelanin) was also analyzed, but it was below the detection limit at all times. Oral treatment of juvenile red seabream with synthetic androgen methyl-testosterone for 2 months induced eumelanin accumulation about 3 times higher than the control. These data show that there is a close relationship between androgen levels and eumelanin accumulation in teleosts. This is the first report that androgen affects melanin accumulation in a dose-dependent manner., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: Lactic acid bacteria (LAB) contribute to human health; however, the probiotic properties vary among strains classified into the same species. The primary objective of this study was to evaluate the effects of yogurts made by different types of LAB on the gastrointestinal system. The yogurts were also evaluated by measuring serum lipid contents and liver functional indicators as a secondary objective., Methods: Healthy human adults (n = 68) with some complaints with regard to intestinal health, including constipation and diarrhea, were randomly assigned to receive one of three types of yogurt in a double-blind manner: type A, a yogurt made by plant-derived LAB (mainly Lactobacillus [Lb.] plantarum SN35N); type B, a yogurt made by plant-derived LAB (mainly Lb. plantarum SN13T); and type C, a yogurt made by animal-derived LAB (mainly Lactococcus lactis A6 and Streptococcus thermophilus 510) as a control. The subjects consumed 100 g of yogurt daily for 6 wk. Data were collected from clinical visits at 2-wk intervals and by diaries used to record defecation and health conditions., Results: Drastic and constant increments of defecation frequency in subjects with constipation were observed with type A and B yogurts but not with type C yogurt. Type B and C yogurts resulted in decreases in total and low-density lipoprotein cholesterol. The serum concentrations of liver functional parameters were improved by the type B yogurt (12-25% reduction)., Conclusion: The present study suggests that Lb. plantarum SN13T exhibits a superior probiotic effect on constipation in addition to improving the serum lipid contents and liver function., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: To assess the relationship between job stress and insomnia among office workers., Methods: This cross-sectional study examined 1209 male workers (mean age 43 years) at periodic health checkups in 2007. Insomnia was defined as consistently experiencing any of three sleep disorder symptoms (i.e., difficulty initiating sleep, difficulty maintaining sleep, and early-morning awakening) in a recent two-week period. Job stress indices included job demand, control, strain (job demand/control), and social support, as measured by the Job Content Questionnaire., Results: The prevalence of insomnia was 4.7%. After adjusting for age, perceived daily stress, sleep dissatisfaction, lifestyle factors, and physical comorbidities, the risk of insomnia increased with a higher degree of job strain (odds ratio 2.3, 95% confidence intervals 1.3-4.0) and decreased with a higher degree of job control (0.5, 0.3-0.8). The combination of high job strain with low degree of control or social support had an approximately three times higher risk of insomnia than that of low job strain with high degree of control or support., Conclusions: Both job strain and job control had an independent effect on insomnia, and the association between job strain and insomnia was mediated by the buffering effects of control and support.

A simple, rapid, and precise HPLC method using ultrafiltration to remove plasma protein was developed to determine cefozopran concentrations in human plasma for real-time therapeutic drug monitoring. Plasma was separated by centrifugation at 4 degrees C from blood collected in heparinized vacuum tubes. Cefozopran and an internal standard were detected by ultraviolet absorbances at 235 nm with no interfering plasma peak. The calibration curve of cefozopran in human plasma was linear from 0.2 to 200 microg/ml. The limit of detection was 0.05 microg/ml. The assay was applied to febrile neutropenia patients in a clinical setting.

Circadian rhythms are endogenous cycles with periods close to, but not exactly equal to, 24 h. In mammals, circadian rhythms are generated in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as several peripheral cell types, such as fibroblasts. Protein kinases are key regulators of the circadian molecular machinery. We investigated the role of the c-Jun N-terminal kinases (JNK), which belong to the mitogen-activated protein kinases family, in the regulation of circadian rhythms. In rat-1 fibroblasts, the p46 kDa, but not the p54 kDa, isoforms of JNK expressed circadian rhythms in phosphorylation. The JNK-inhibitor SP600125 dose-dependently extended the period of Period1-luciferase rhythms in rat-1 fibroblasts from 24.23+/-0.17-31.48+/-0.07 h. This treatment also dose-dependently delayed the onset of the bioluminescence rhythms. The effects of SP600125 on explant cultures from Period1-luciferase transgenic mice and Period2(Luciferase) knockin mice appeared tissue-specific. SP600125 lengthened the period in SCN, pineal gland, and lung explants in Period1-luciferase and Period2(Luciferase) mice. However, in the kidneys circadian rhythms were abolished in Period1-luciferase, while circadian rhythms were not affected by SP600125 treatment in Period2(Luciferase) mice. Valproic acid, already known to affect period length, enhanced JNK phosphorylation and, as predicted, shortened the period of the Period1-bioluminescence rhythms in rat-1 fibroblasts. In conclusion, our results showed that SP600125 treatment, as well as valproic acid, alters JNK phosphorylation levels, and modulates the period length in various tissues. We conclude that JNK phosphorylation levels may help to set the period length of mammalian circadian rhythms.

The annual changes in Japanese chestnut (Castanea crenata Sieb. et Zucc.) agglutinin (CCA) were investigated by both protein and RNA blotting analyses, to clarify whether CCA has a function as storage protein. In the woody part of shoots and leaves, CCA expression was only detected at both the protein and RNA levels in May and June. In buds, the CCA protein and mRNA expressions were both restricted to April. However, the amount of accumulated CCA was too low to act as a nitrogen reserve. No expression was observed in the bark at any time point, suggesting that bark does not contain either CCA or CCA-like proteins. These results suggest that CCA may be required in young organs as a defense protein, rather than as a storage protein. In addition, CCA was not related to dormancy, unlike some other woody plant bark lectins. In contrast to CCA, a 28kDa polypeptide was observed to accumulate during dormancy. Sequence analysis indicated that this polypeptide was a glutathione transferase. After cDNA cloning, RNA blot analyses indicated that this glutathione transferase was strongly expressed in woody parts during mid-winter. In shoots, this protein represented approximately 10% of the total soluble protein content. Therefore, in Japanese chestnut trees, glutathione transferase may play a nitrogen storage role in addition to its intrinsic defensive role against stresses during dormancy.

Angiofibromas are nasopharyngeal tumors mostly seen in adolescent males. They account for less than 0.5% of all head and neck neoplasms. Extranasopharyngeal angiofibromas, although rare, have been reported. We report a case of extranasopharyngeal angiofibroma arising from the inferior turbinate of a 62-year-old male. The tumor was excised using the Denker approach. The patient is currently free of relapse 10 months after surgery. Previous extranasopharyngeal angiofibromas research was reviewed.

A new series of 1,4-benzoxazepine derivatives was designed, synthesized, and evaluated for binding to 5-HT1A receptor and cerebral anti-ischemic effect. A lot of compounds exhibited nanomolar affinity for 5-HT1A receptor with good selectivity over both dopamine D2 and alpha1-adrenergic receptors. Among these compounds, 3-chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-yl]butyl]-1, 4-benzoxazepin-5(4H)-one (50: SUN N4057 (Piclozotan) as 2HCl salt) showed remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model.

In this paper, we describe an effective method for constructing a micro-library enriched with chromosomal DNA replication origins. Carrot (Daucus carota L.) somatic embryos at early globular stage were incubated for 15 min in the presence of bromodeoxyuridine (BrdU) to pulse label newly synthesized DNA strands. Nuclei were isolated from the cells, and the DNA was extracted on microscopic slides. DNA fibers spread on slides were visualized using anti-BrdU and FITC-conjugated secondary antibodies. DNA regions where BrdU was incorporated were clearly visualized under a fluorescent microscope as dots on DNA fibers. Regions of DNA fiber containing many fluorescent dots should contain replicons in them. DNA fibers showing many fluorescence dots, or replicons were easily cut and collected using a laser microdissection system equipped with a pulse laser beam. DNA fragments containing many replicons were able to be collected with an efficiency of 20-30 DNA fragments per 1 h. Using degenerate oligonucleotide primed PCR, fragments were randomly amplified from the microdissected fragments, and subcloned to construct a micro-library. This is the first report of the application of a laser microdissection technique for constructing a micro-library enriched with replication origins of chromosomal DNA, although there were some reports on laser microdissection of chromosomes. The simple procedure established here should open up a new application of laser optics.

A double-stranded (ds) RNA (2411 bp) from a strain V18 of the violet root rot basidiomycetous fungus, Helicobasidium mompa was sequenced. Using the fungal mitochondrial genetic code in which UGA codes for tryptophan, the positive strand of V18 dsRNA was found to contain a long open-reading frame with the potential to encode a protein of 700 amino acids (molecular mass 79,805 Da), including conserved motifs characteristic of RNA-dependent RNA polymerase (RDRP). This putative RDRP was shown to be related to putative RDRPs of several fungal mitochondrial viruses. It is proposed that V18 dsRNA is assigned to the genus Mitovirus in the family Narnaviridae and designated as H. mompa mitovirus 1-18 (HmMV1-18). Like other mitoviruses, HmMV1-18 RNA can be folded into potentially stable stem-loop structures at both the 5'- and 3'-termini, and both terminal sequences have inverted complementarity with the potential to form panhandle structure. BLAST analysis indicates that the RDRP encoded by HmMV1-18 is more closely related to those encoded by mitochondrial viruses of some ascomycetes than to that of the unassigned RsM2-1A1 dsRNA in the basidiomycetous Rhizoctonia solani. HmMV1-18 is the first member of the genus Mitovirus from basidiomycete fungi.

Chronic caffeine exposure during pregnancy has an effect on fetal growth; however, the adverse effects of caffeine on embryogenesis are not well understood and controversial. We used cDNA microarray technology to determine whether caffeine alters gene expressions in a human cytotrophoblast-like cell line, BeWo. We found that the expression of the B-cell CLL/lymphoma 2 (Bcl-2) gene in BeWo cells was down-regulated by caffeine, suggesting that chronic exposure during the gestational period could exert an influence on embryogenesis. We then focused on the Bcl-2- and Bcl-2-associated X protein gene, Bax, to study the responsive gene expression in BeWo cells as well as placentas of pregnant rats fed a diet supplemented with caffeine (2 mg/100 g body weight) during gestation, and analyzed the gene expressions using LightCycler-based quantitative real-time polymerase chain reaction assays. We found a significantly decreased level of Bcl-2 mRNA expression, which demonstrated the influence of caffeine on placental function.

Recent glycobiology studies have suggested fundamental biological functions for chondroitin, chondroitin sulfate and dermatan sulfate, which are widely distributed as glycosaminoglycan sidechains of proteoglycans in the extracellular matrix and at cell surfaces. They have been implicated in the signaling functions of various heparin-binding growth factors and chemokines, and play critical roles in the development of the central nervous system. They also function as receptors for various pathogens. These functions are closely associated with the sulfation patterns of the glycosaminoglycan chains. Surprisingly, nonsulfated chondroitin is indispensable in the morphogenesis and cell division of Caenorhabditis elegans, as revealed by RNA interference experiments of the recently cloned chondroitin synthase gene and by the analysis of mutants of squashed vulva genes.

Although group IIA phospholipase A(2) has been suggested to be implicated in inflammatory bowel disease, its pathophysiological role in colitis remains unclear. We investigated whether group IIA phospholipase A(2) had pro-inflammatory roles in dextran sulfate sodium-induced colitis in the rat. Secretory phospholipase A(2) activity was markedly increased in the distal colon with two peaks. Strong immunostaining for group IIA phospholipase A(2) was found in subepithelial tissue and lamina propria at early stage and in deeper tissues of the erosion area at later stage. Treatment with a specific group IIA phospholipase A(2) inhibitor, S-3013/LY333013 (methyl[[3-(aminooxoacetyl)-2-ethyl-1-(phenylmethyl)]-1H-indol-4yl]oxy) acetate), reduced erosion area, shortening of colon and colonic inflammation, and strongly inhibited the increase in secretory phospholipase A(2) activity and moderately reduced myeloperoxidase activity in the colon in vivo, while eicosanoid levels were not affected. Marked group IIA phospholipase A(2) expression in the erosion area and the improvement of colitis by the group IIA phospholipase A(2) inhibitor strongly suggest that this enzyme plays pro-inflammatory roles in this colitis model.

Rhythmical activity in trigeminal motoneurons (TMNs) was studied in an in vitro neonatal rat brainstem preparation that retains functionally active circuits for oral-motor behaviors. Whole-cell current-clamp recording from TMNs demonstrated rhythmical activities during both spontaneously generated respiratory activity and neurochemically induced rhythmical oral-motor activity. TMNs showed spontaneous rhythmical (0.08 +/- 0.04 Hz) activities of burst-firing pattern during inspiration synchronized with inspiratory activities recorded in hypoglossal nerves. During rhythmical oral-motor activity induced by bath application of N-methyl-d,l-aspartic acid and the GABA(A) receptor antagonist bicuculline methiodide, TMNs showed only a rhythmical (5.6 +/- 0.8 Hz) pattern of single-spike discharge. TMNs never showed a burst-firing pattern during rhythmical oral-motor activity even when membrane potentials were shifted either to depolarized or hyperpolarized levels. Rhythmical activity in TMNs exhibited different discharge patterns between rhythmical oral-motor activity and respiratory activity generated in vitro., (Copyright 2002 Elsevier Science Inc.)

A large number of constituents, such as growth factors, cytokines, and vasoregulatory molecules, contribute a network of cellular interactions to atherosclerotic lesions, and current evidence suggests that granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of these constituents. We conducted this study to determine whether GM-CSF has an effect on the fate and function of macrophages. We examined the effect of GM-CSF on macrophages in vitro with a highly inducible HL60 subclone (HL60/DU-1) that we recently established. HL60 cells have been reported to preserve functional GM-CSF receptors, but a GM-CSF allele was rearranged and partially deleted. HL60/DU-1 cells were devoid of GM-CSF immunoreactivity and of autocrine stimulation of GM-CSF. HL60/DU-1 cells fated to die soon after terminal differentiation of macrophages by 1, 25-dihydroxy vitamin D(3) treatment. We found cell death to be mediated mainly by necrosis, not apoptosis, as confirmed by DNA fragmentation in agarose gel electrophoresis, morphological observation under a fluorescence microscope, and assay of lactate dehydrogenase release. Exogeneously administered GM-CSF rescued cells from necrotic death and caused them to survive and generate superoxide anions. We also conducted immunohistochemical analysis on an atherosclerotic human artery. Macrophages, endothelial cells, and smooth muscle cells were found to be GM-CSF positive in an atherosclerotic lesion. In summary, GM-CSF, which is produced by macrophages, endothelial cells, and smooth muscle cells, is thought to act in an autocrine and a paracrine fashion as a necrosis-inhibiting factor against arterial macrophages. This unique function may play an important role in ensuring survival and promoting function in atherosclerotic lesions.

We examined peripheral insulin sensitivity in 32 patients with cancer (17 with stomach cancer, 7 with colorectal cancer, and 8 with lung cancer) and 6 normal control subjects by the euglycemic hyperinsulinemic glucose clamp technique. The relationships between insulin resistance and tumor factors (type and stage), malnutrition, and inflammatory reaction were evaluated. Insulin sensitivity often was reduced in patients with cancer; however, the amount of glucose metabolized was not related to tumor site or stage. The decreased glucose uptake was negatively correlated with the acute-phase response but was not correlated with body-weight loss, serum albumin, or resting energy expenditure. Our results suggest that insulin resistance in cancer patients was not induced by malnutrition. Although the qualitative presence of tumor might be the major factor inducing insulin resistance, other factors such as inflammatory reactions might be involved in the development of insulin resistance.

The importance of vitamin K in bone metabolism has been suggested previously. The binding protein of vitamin K2 (menatetrenone, 2-methyl-3-all-trans-tetraphenyl-1,4-naphthoquinone, menaquinone-4), found in nuclear extract of human osteoblasts, binds to vitamin K1 and K2, but not K3. Since the binding protein does not bind to other steroids or vitamins, such as hydrocortisone, vitamin A, 1,25(OH)2vitamin D3, trolox (a derivative of vitamin E), and warfarin, a specific binding protein to vitamin K1 and vitamin K2 in osteoblasts was suggested. The size of the specific binding protein was revealed to be 6S by sucrose density gradient and about 40,000 daltons by SDS-PAGE. Twenty amino acid residues from the N-terminal were the same as human glyceraldehyde-3-phosphate dehydrogenase (GAPDH), but the 21st residue, alanine, was replaced with serine. The binding protein was precipitated with anti-human GAPDH antibody, and authentic human GAPDH could bind vitamin K2. We propose that the nuclear binding protein for vitamin K2 exists in nuclei similarly to other vitamin receptors and that the molecular structure is very close to human GAPDH.

An enzymatic method was proposed for measuring acetylpolyamine (AcPA) alone, even when non-acetylated polyamine co-exists. The method consisted of four enzymatic reactions. First, AcPA was hydrolysed by acylpolyamine amidohydrolase to yield acetate; followed by the other three reactions coupled with three enzymes, respectively, acetate kinase, pyruvate kinase, and lactate dehydrogenase; the acetate formation caused a decrease in NADH. The quantity of AcPA was then evaluated as the change in absorbance at 340 nm. The reagent composition of the reaction mixture was determined, and characteristics of the method were investigated. The validation tests produced satisfactory results. The co-existence of non-acetylated polyamine gave no effect on the measurement. The present method was found to be used easily, rapidly and reliably for the selective determination of AcPA itself.

Stabilized enzymatic reagents for measuring some components in biological fluids have been successfully developed based on two kinds of thermostable enzymes derived from Bacillus stearothermophilus with separation of the reagent into two complementary solutions. The thermostable glucokinase produced was applied to the measurement of glucose and creatine kinase activity, while the alanine dehydrogenase produced was used for the measurement of gamma-glutamyltransferase activity. The enzymatic reagents were also stabilized by developing two separate reagents with an optimum pH for the main reagent components. The stability of the reagents in liquid form was examined at 10 degrees C. It was clearly shown that the reagents for measuring glucose and creatine kinase activity were stable and retained their full capability for accurate measurement in biological fluids for over one year. The alanine dehydrogenase product was stable for at least 40 days.

A clinical investigation was carried out on patients with uric acid stones in order to study the frequency and pathogenesis of uric acid nephrolithiasis. Of 652 patients with stones in the upper urinary tract in whom the stone composition could be examined, 36 patients and uric acid stones (5.5%). The male to female ratio was 11:1. The average age of the 33 male subjects was 49 +/- 11 years (mean +/- SD), and the 3 females were 22, 37 and 42 years old, respectively. Two of the females showed hypouricemia. With regard to stone composition, pure uric acid stones were present in 26 cases (72%), a mixed uric acid and calcium oxalate stones were found in 6 cases (17%), both pure uric acid and mixed uric acid and calcium oxalate stones were observed in 3 cases (8%), and a mixed uric acid and sodium acid urate stone in 1 (3%). Biochemical studies on male patients showed that the blood uric acid level was higher in the uric acid stone group and the pure uric acid stone group compared to the calcium stone group. The blood uric acid levels of the former 2 groups did not differ from the control group. With respect to urine chemistry, the excretion of calcium in the uric acid stone group was significantly lower than that in the control group. In the uric acid stone group and the pure uric acid stone group the excretion of calcium tended to be lower than that in the calcium stone group. The amounts of oxalic acid excreted in the uric acid stone group and in the pure uric acid stone group were low compared to the calcium stone group. Oxalic acid elimination in these 2 groups did not differ from the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

A novel compound, FR64822(N-(4-pyridylcarbamoyl)amino 1,2,3,6,-tetrahydropyridine), displays antinociceptive activities in a variety of assays with mice and rats. It has a strong antinociceptive activity in the acetic acid writhing test (ED50 = 1.8 mg/kg p.o.), whereas it has little antinociceptive activity in the tail flick test. The antinociceptive profile is similar to that of nefopam but different from that of anti-inflammatory agents. The involvement of monoamines in the mechanism of action of FR64822 was investigated. Pretreatment with reserpine (2 mg/kg) significantly reduced the antinociceptive activity of FR64822, when tested against acetic acid writhing. A similar reduction of activity was found in mice pretreated with sulpiride (10 mg/kg), a dopamine D2 receptor antagonist, but not with Sch23390 (0.25 mg/kg), a dopamine D1 receptor antagonist. Pretreatment with p-chlorophenylalanine, yohimbine and naloxone hardly affected the antinociceptive activity of FR64822. These results were compared with those for nefopam and clonidine. It is suggested that FR64822 induces antinociceptive activity through a novel mechanism of action, indirect stimulation of dopamine D2 receptors, which differs from that of nefopam in that no specific neurotransmission could be determined in nefopam analgesia.

This article presents a brief review on the electrophysiological analysis of the structural aspects of the voltage-dependent SR (sarcoplasmic reticulum) K+ channel. In the first half, early attempts to determine the physical dimensions of the ion conducting mechanism such as the mouth, narrow tunnel, or ion selective filter of the channel, are reviewed. The depicted cartoon of the SR K+ channel, as an extremely short, busy district with a big mouth on each side, is quite similar to the recently-obtained reconstructed structural image of the acetylcholine receptor channel. In the latter half, we introduce our recent attempts to draw a physical image of the gating mechanism of the SR K+ channel. We examined, for example, the location of the gate and the voltage sensor, and the relationship between them. It is suggested that the gate and the sensor are connected tightly and that the sensor would be exposed to the surface of the lumen side of SR when the gate opens. Finally, the issue of substates in SR K+ channel is discussed. It is implied that the substrate-conductances reflect a partial occlusion of the pore by an intermediate-open gate.

1. A species-specific sperm-activating peptide was isolated from the egg jelly of the sea urchin Diadema setosum and the amino acid sequence was determined as follows: (formula; see text). 2. The peptide caused significant increases of respiration rates and cyclic nucleotide concentrations in D. setosum spermatozoa as low as 10(-9) M. 3. The addition of the peptide to D. setosum spermatozoa resulted in the appearance of a newly stained protein (mol. wt 128,000) on sodium dodecyl sulfate-polyacrylamide gels.

1. Six new sperm activating peptides were purified from the egg jelly of the sea urchin Glyptocidaris crenularis and their amino acid sequences were determined as follows: Ser-Ala-Lys-Leu-Cys-Pro-Gly-Gly-Asn-Cys-Val, Lys-Leu-Cys-Pro-Gly-Gly-Asn-Cys-Val, Leu-Cys-Pro-Gly-Gly-Asn-Cys-Val, Ser-Phe-Lys-Leu-Cys-Pro-Gly-Gly-Gln-Cys-Val, Lys-Leu-Cys-Pro-Gly-Gly-Gln-Cys-Val and Leu-Cys-Pro-Gly-Gly-Gln-Cys-Val. 2. The peptides were specific for G. crenularis spermatozoa and caused significant increases of sperm respiration rates and sperm cyclic nucleotide concentrations at concentrations as low as 10(-10) M. 3. The addition of the peptides to intact spermatozoa resulted in the change of the apparent mol. wt of a sperm protein from 195,000 to 200,000.

1. Fourteen peptides were isolated from the egg jelly of sea urchins, Pseudocentrotus depressus, Strongylocentrotus purpuratus, Hemicentrotus pulcherrimus and Anthocidaris crassispina and their amino acid sequences were determined. 2. The peptides stimulated H. pulcherrimus sperm respiration one half-maximally at about 8-60 pM. 3. Addition of speract to intact spermatozoa of P. depressus, H. pulcherrimus and A. crassispina resulted in the appearance of a newly stained protein (Mr 128,000 for P. depressus, Mr 128,000 for H. pulcherrimus and Mr 131,000 for A. crassispina) on sodium dodecyl sulfate-polyacrylamide gels.