Long-term effect of posterior nasal neurectomy for perennial allergic rhinitis.

BACKGROUND: Surgical treatment is recommended for patients with severe allergic rhinitis (AR) refractory to medical treatment. Endoscopic posterior nasal neurectomy (PNN) is primarily performed to improve rhinorrhea in severe perennial AR, however studies on its long-term prognosis are lacking. AIMS/OBJECTIVES: This study aimed to investigate the long-term prognosis of PNN. MATERIALS AND METHODS: A questionnaire survey was administered to 17 patients (12 men and 5 women) at least 1 year after PNN. Nasal symptoms and medications, as well as patient satisfaction with surgery at the time of survey, were scored. Furthermore, scores were compared between patients with postoperative periods of >5 years and <5 years. RESULTS: Nasal symptoms and medication scores significantly improved after surgery. There was no significant difference between patients with a postoperative period of >5 years and <5 years in both preoperative and postoperative nasal symptoms and medication scores. No correlation was found between patient satisfaction with surgery and postoperative period. CONCLUSIONS AND SIGNIFICANCE: PNN improved nasal symptoms and medication scores in patients with severe perennial AR. Furthermore, the study results suggest that the long-term effect of PNN for perennial AR lasts for >5 years. J. Med. Invest. 71 : 62-65, February, 2024.

Azidomethylation of Nucleobases and Related N-Heterocycles, Benzazoles, and Bis(arene)sulfonimides Using Azidomethyl Esters with Silyl Triflates.

An efficient method for the azidomethylation of amines using azidomethyl esters with silyl triflates is described. This protocol enables the azidomethylation of various amines that can be activated with silyl groups, including nucleobases.

Development and validation of equations for predicting appendicular skeletal muscle mass in male patients with head and neck cancer and normal hydration status.

OBJECTIVE: Muscle mass is typically assessed by abdominal computed tomography, magnetic resonance imaging, and dual-energy x-ray absorptiometry. However, these tests are not routinely performed in patients with head and neck cancer (HNC), making sarcopenia assessment difficult. The aim of this study was to develop and validate equations for predicting appendicular skeletal muscle mass (ASM) from data obtained in daily medical practice, with bioelectrical impedance analysis (BIA)-measured appendicular skeletal muscle mass (BIA-ASM) as a reference. METHODS: This cross-sectional study included 103 men with HNC who were randomly placed into development and validation groups. The prediction equations for BIA-ASM were developed by multiple regression analysis and validated by Bland-Altman analyses. The estimated skeletal muscle mass index (eSMI) was also statistically evaluated to discriminate the cutoff value for BIA-measured SMI according to the Asian Working Groups for Sarcopenia. RESULTS: Two practical equations, which included 24-h urinary creatinine excretion volume (24hUCrV), handgrip strength (HGS), body weight (BW), and body height (BHt), were developed: ASM (kg) = -39.46 + (3.557 × 24hUCrV [g]) + (0.08872 × HGS [kg]) + (0.1263 × BW [kg]) + (0.2661 × BHt [cm]) if available for 24hUCrV (adjusted R2 = 0.8905), and ASM (kg) = -42.60 + (0.1643 × HGS [kg]) + (0.1589 × BW [kg]) + (0.2807 × BHt [cm]) if not (adjusted R2 = 0.8589). ASM estimated by these two equations showed a significantly strong correlation with BIA-ASM (R > 0.900). Bland-Altman analyses showed a good agreement, and eSMI accuracy was high (>80%) in both equations. CONCLUSIONS: These two equations are a valid option for estimating ASM and diagnosing sarcopenia in patients with HNC in all facilities without special equipment.

The effects of continuous administration of diazepam on the recovery of lesion-induced nystagmus in unilaterally labyrinthectomised rats.

BACKGROUND: Diazepam, a gamma-aminobutyric acid type A receptor agonist, is classified as a vestibular suppressant and is effective in treating acute vertigo. However, its effects on vestibular compensation (VC) remain unclear. OBJECTIVES: We examined the effects of continuous administration of diazepam on the frequency of spontaneous nystagmus (SN) after unilateral labyrinthectomy (UL) as an index of the initial process of VC in rats. MATERIALS AND METHODS: Diazepam was continuously administered at doses of 3.5 and 7.0 mg/kg/day, intraperitoneally, via an osmotic minipump. The frequency of SN beating against the lesion side after UL was measured. Potassium chloride (KCl) solution (1 M) was injected intratympanically to induce SN beating to the injection side. RESULTS: Continuous administration of diazepam significantly and dose-dependently decreased the frequency of SN after UL, and also reduced the x intercept of the nonlinear regression curve of the decline in UL-induced SN with time in rats. However, the continuous administration of diazepam did not affect the frequency of intratympanic KCl-induced SN in the rats. CONCLUSION: These findings suggested that continuous administration of diazepam accelerates the initial process of VC; however, it does not suppress the nystagmus-driving mechanisms in rats.

Risk factors of first bite syndrome after surgical resection of parapharyngeal space tumors.

OBJECTIVE: First bite syndrome is a complication of surgical resection of parapharyngeal space tumors and the development of cramping pain in the parotid region with the first bite of a meal. The present study aimed to identify the potential risk factors for the development of first bite syndrome. METHODS: We retrospectively reviewed 30 consecutive patients with parapharyngeal space tumors who had been surgically treated between August 2003 and December 2015 at our department. RESULTS: The tumor site (prestyloid or retrostyloid) and surgical approach (transcervical-parotid, transparotid, or transcervical) were not correlated with the development of first bite syndrome. Ligation and mobilization of the external carotid artery was significantly correlated with the development of first bite syndrome. Moreover, patients with complete resection of the parotid gland did not experience first bite syndrome. DISCUSSION: The present findings suggest that concomitant surgical settings of 1) sympathetic denervation of the parotid gland with ligation of the external carotid artery or injury of the sympathetic nerve plexus around the external carotid artery during its mobilization, and 2) residual parotid gland tissue are risk factors for the development of first bite syndrome after surgical resection of parapharyngeal space tumors. J. Med. Invest. 70 : 150-153, February, 2023.

Repetitive postoperative extubation failure due to dynamic inspiratory airway collapse concomitant with subglottic stenosis in a patient who previously underwent tracheostomy.

BACKGROUND: This report describes a case of dynamic inspiratory airway collapse concomitant with subglottic stenosis in a patient who previously underwent tracheostomy that led to repeated post-operative extubation failure. CASE PRESENTATION: A 43-year-old woman who had undergone tracheostomy 25 years previously was admitted to our intensive-care unit (ICU) after coronary artery bypass graft surgery. On postoperative day (POD) 0, she was extubated, but stridor was observed. We suspected upper airway obstruction and she was therefore reintubated. Before reintubation, urgent laryngotracheoscopy revealed dynamic inspiratory airway collapse and obstruction concomitant with subglottic stenosis. Preoperative computed tomography showed mild subglottic stenosis. Although intravenous corticosteroids were administered to prevent tracheal mucosal edema and a cuff leak test was confirmed to be negative, she developed extubation failure on POD6. On POD12, we performed tracheostomy to reduce mechanical irritation from the endotracheal tube. Mechanical ventilation was withdrawn and she discharged from the ICU. On POD33, her tracheostomy tube was removed and she remained clinically asymptomatic. CONCLUSIONS: We should be aware of the history of tracheostomy, especially at high tracheostomy sites, even in the absence of respiratory symptoms as risk factors for dynamic inspiratory airway collapse concomitant with subglottic stenosis contributing to repeated respiratory failure after extubation. J. Med. Invest. 70 : 301-305, February, 2023.

A Diversifiable Synthetic Platform for the Discovery of New Carbasugar SGLT2 Inhibitors Using Azide-Alkyne Click Chemistry.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are clinically available to control blood glucose levels in diabetic patients via an insulin-independent mechanism. It was found that some carbasugar analogs of known SGLT2 inhibitors exert a high inhibiting ability toward SGLT2 and have a prolonged blood glucose lowering effect. In this study, we designed new candidates of carbasugar SGLT2 inhibitor that can be synthesized using copper-catalyzed azide-alkyne cycloaddition (CuAAC) into an aromatic ring, which is a part of the pharmacophore at the final stage in the synthetic protocol for the easier discovery of superior SGLT2 inhibitors. Based on the results of molecular docking studies, some selected compounds have been synthesized. Evaluation of these compounds using a cell-based assay revealed that the majority of these compounds had SGLT2 inhibitory activity in a dose-dependent manner. The SGLT2 inhibitory activity of 7b and 7c was almost equal to that of SGLT2 inhibitors in current use. Furthermore, molecular dynamics simulations also revealed that 7c is a promising novel SGLT2 inhibitor.

Muscle mass, quality, and strength; physical function and activity; and metabolic status in cachectic patients with head and neck cancer.

BACKGROUND & AIMS: Cancer cachexia is commonly associated with poor prognosis in patients with head and neck cancer (HNC). However, its pathophysiology and treatment are not well established. The current study aimed to assess the muscle mass/quality/strength, physical function and activity, resting energy expenditure (REE), and respiratory quotient (RQ) in cachectic patients with HNC. METHODS: This prospective cross-sectional study analyzed 64 patients with HNC. Body composition was measured via direct segmental multifrequency bioelectrical impedance analysis, and muscle quality was assessed using echo intensity on ultrasonography images. Muscle strength was investigated utilizing handgrip strength and isometric knee extension force (IKEF). Physical function was evaluated using the 10-m walking speed test and the five times sit-to-stand (5-STS) test. Physical activity was examined using a wearable triaxial accelerometer. REE and RQ were measured via indirect calorimetry. These parameters were compared between the cachectic and noncachectic groups. RESULTS: In total, 23 (36%) patients were diagnosed with cachexia. The cachectic group had a significantly lower muscle mass than the noncachectic group. Nevertheless, there was no significant difference in terms of fat between the two groups. The cachectic group had a higher quadriceps echo intensity and a lower handgrip strength and IKEF than the noncachectic group. Moreover, they had a significantly slower normal and maximum walking speed and 5-STS speed. The number of steps, total activity time, and time of activity (<3 Mets) did not significantly differ between the two groups. The cachectic group had a shorter time of activity (≥3 Mets) than the noncachectic group. Furthermore, the cachectic group had a significantly higher REE/body weight and REE/fat free mass and a significantly lower RQ than the noncachectic group. CONCLUSIONS: The cachectic group had a lower muscle mass/quality/strength and physical function and activity and a higher REE than the noncachectic group. Thus, REE and physical activity should be evaluated to determine energy requirements. The RQ was lower in the cachectic group than that in the noncachectic group, indicating changes in energy substrate. Further studies must be conducted to examine effective nutritional and exercise interventions for patients with cancer cachexia.

Design of supramolecular hybrid nanomaterials comprising peptide-based supramolecular nanofibers and in situ generated DNA nanoflowers through rolling circle amplification.

The artificial construction of multicomponent supramolecular materials comprising plural supramolecular architectures that are assembled orthogonally from their constituent molecules has attracted growing attention. Here, we describe the design and development of multicomponent supramolecular materials by combining peptide-based self-assembled fibrous nanostructures with globular DNA nanoflowers constructed by the rolling circle amplification reaction. The orthogonally constructed architectures were dissected by fluorescence imaging using the selective fluorescence staining procedures adapted to this study. The present, unique hybrid materials developed by taking advantage of each supramolecular architecture based on their peptide and DNA functions may offer distinct opportunities to explore their bioapplications as a soft matrix.

Imaging features of a myoepithelial carcinoma of the nasal cavity: A case report and literature review.

Myoepithelial carcinoma of the nasal cavity is extremely rare. We report the case of a 66-year-old man with myoepithelial carcinoma of the nasal cavity. Computed tomography (CT) and magnetic resonance imaging revealed a lobulated soft tissue mass with central necrosis and hemorrhage, as well as an invasion of the skull base and left orbit. The patient presented with continuous nasal congestion and heavy head and had no elevated level of squamous cell carcinoma-related antigen. CT, magnetic resonance imaging, or 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT revealed no evidence of a metastatic lesion. 18F-FDG accumulation in the tumor was inhomogeneous and moderate. Histopathological examination of the resected specimen confirmed a well-circumscribed solid tumor with septa, a small area of hemorrhage, and necrosis. The subsequent diagnosis was a myoepithelial carcinoma of the left nasal cavity. This case shows that nasal myoepithelial carcinoma might appear as a well-defined lobulated mass with hemorrhagic necrosis and intense contrast enhancement in the solid component. We conjecture that hemorrhagic necrosis and intense enhancement values may be potential markers of nasal myoepithelial carcinoma.

Betuletol, a Propolis Component, Suppresses IL-33 Gene Expression and Effective against Eosinophilia.

Propolis, a resinous substance produced by honeybees, has been used in folk medicine since ancient times due to its many biological benefits such as antitumor, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory effects. Propolis contains flavonoids, terpenoids, aromatic aldehydes, and alcohols, which vary with different climate and environmental conditions. In our study, we examined the antiallergic activity of Brazilian green propolis (BGP) and isolated the active compound that can suppress an allergy-sensitive gene, IL-33, expression and eosinophilia. Ethanolic extract of BGP freeze-dried powder was fractionated with several solvent systems, and the active fractions were collected based on activity measurement. The single active compound was found by thin-layer chromatography. Using column chromatography and NMR, the active compound was isolated and identified as 3,5,7-trihydroxy-6,4'-dimethoxyflavone, also known as betuletol. Further, the antiallergic activity of that has been examined in PMA-induced up-regulation of IL-33 gene expression in Swiss 3T3 cells. Our data showed the IL-33 gene suppression both by BGP and the isolated active compound, betuletol. We also found that betuletol suppressed ERK phosphorylation, suggesting it could be effective in suppressing IL-33 mediated eosinophilic chronic inflammation and will provide new insights to develop potent therapeutics against allergic inflammations.

Effects of sublingual immunotherapy with tablets or drops containing Japanese cedar pollen antigens on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis.

OBJECTIVE: We examined the effects of SLIT with tablets containing JCP antigens on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis during pollen dispersal season. METHODS: A total of 128 patients with Japanese cedar pollinosis were categorized into four groups:19 one-year SLIT with tablets group, 16 two-year SLIT with drops group, 19 antihistamine group, and 74 untreated group. The scores of nasal symptoms and sleep disturbance were evaluated based on the Japanese guidelines for allergic rhinitis and the Athens Insomnia Scale. RESULTS: The scores of nasal symptoms and sleep disturbance at the peak cedar pollen period in the two-year SLIT with drop group and the one-year SLIT with tablets group were significantly lower than those in untreated group. Additionally, these scores were significantly lower in the one-year SLIT with tablets group than those in the antihistamine group. CONCLUSION: It is suggested that SLIT with JCP tablets improved both nasal symptoms and sleep disturbances at peak pollen period in patients with Japanese cedar pollinosis. SLIT with JCP tablets for one year was more effective than SLIT with JCP drops for two years and prophylactic treatment with antihistamines. J. Med. Invest. 69 : 97-100, February, 2022.

New method to evaluate sequelae of static facial asymmetry in patients with facial palsy using three-dimensional scanning analysis.

OBJECTIVE: During the process of neural recovery after facial palsy, distressing sequelae of static and dynamic facial asymmetry develop in patients with facial palsy. A pronounced nasolabial fold is mainly responsible for static facial asymmetry, which leads to many psychological and social problems in patients. Objective and qualitative assessment of facial appearance is critical to determine the severity of sequelae of static facial asymmetry and whether an intervention is effective for treatment. In the present study, an attempt was made to develop three-dimensional analysis method to assess sequelae of static facial asymmetry after facial palsy. METHODS: Eight patients with sequelae of facial asymmetry after facial palsy and ten healthy volunteers were enrolled. We used three-dimensional scanning analysis with a portable non-contact optical scanner to obtain three-dimensional surface data from a patient's face and produced a three-dimensional digital model of the face. We then identified a reference plane fixed with the patient's face, and measured the depth of the nasolabial fold of the face. RESULTS: The nasolabial fold of the face on the affected side was significantly deeper than that on the unaffected side in patients with sequelae of static facial asymmetry after facial palsy. However, the depth of the facial nasolabial fold on the right side was not different from that on the left side in healthy volunteers. Affected-unaffected side differences in the depth of the nasolabial fold in patients with sequelae of static facial asymmetry after facial palsy were significantly larger than left-right differences in the depth of the nasolabial fold in healthy volunteers. Two weeks after treatment with botulinum toxin injection to the affected zygomaticus muscles, affected-unaffected side differences in the depth of the nasolabial fold were significantly decreased in the patients. In the patients who received botulinum toxin, the absolute values of affected-unaffected side differences in the depth of the nasolabial fold measured using the three-dimensional scanning analysis showed a significant positive correlation with the visual analog scale scores of facial asymmetry marked by independent doctors. CONCLUSION: The present findings suggest that affected-unaffected side differences in the depth of the nasolabial fold of the measured using three-dimensional scanning analysis can be used as an index of sequelae of static facial asymmetry. It is also suggested that the index can evaluate whether interventions are effective for the treatment of sequelae.

Efficacy of dual sublingual immunotherapy with Japanese cedar pollen and house dust mite allergens in patients with allergic rhinitis sensitized to multiple allergens.

OBJECTIVE: In the present study, we examined the effects of dual sublingual immunotherapy (SLIT) with Japanese cedar pollen (JCP) and house dust mite (HDM) allergens on nasal symptoms during the peak pollen period (PPP) and in late fall (LF) in patients with allergic rhinitis (AR) sensitized to both JCP and HDM. We then compared the efficacy of dual-SLIT with JCP and HDM to that of mono-SLIT with JCP at PPP. METHODS: Twenty-five bisensitized patients with AR who showed positive serum specific immunoglobulin E (IgE) against both JCP and HDM were enrolled. In dual-SLIT, 16 patients received JCP drops/tablets and HDM tablets concurrently. In mono-SLIT with JCP, nine patients received JCP drops/tablets. Nasal symptoms were scored on a 0-4 point scale. RESULTS: The nasal scores at PPP and in LF in the bisensitized patients with AR who received dual-SLIT with JCP and HDM in 2019 were significantly lower than those in the same patients who received antihistamines only in 2018. The decrease in scores of nasal obstruction at PPP from 2018 to 2019 in patients who received dual-SLIT was significantly greater than those in patients who received mono-SLIT with JCP. Dual-SLIT was well tolerated and only had mild adverse effects. CONCLUSION: These findings suggest that dual-SLIT suppressed both JCP-induced seasonal and HDM-induced perennial nasal symptoms in bisensitized patients with AR. Dual-SLIT was more effective in suppressing nasal obstruction at PPP than mono-SLIT with JCP with limitation of baseline characteristics not to be controlled between the two groups, suggesting that dual-SLIT suppressed HDM-induced priming effects, thus resulting in further suppression of nasal obstruction at PPP. LEVEL OF EVIDENCE: 3b, a case-controlled study.

Long-term changes in serum squamous cell carcinoma antigen levels after surgery in patients with sinonasal inverted papilloma.

OBJECTIVES: This study aimed to examine whether serum SCCA levels can be used as clinical markers for monitoring recurrence of sinonasal inverted papilloma (IP) during the follow-up period after surgery. We measured long-term changes in serum levels of SCCA after surgery in patients with IP and examined whether postoperative SCCA levels were associated with IP recurrence. METHODS: Twenty-five consecutive patients (13 with primary IPs and 12 with recurrent IPs after their previous surgery) were included in this study. All patients underwent endoscopic or external surgery. Postoperative serum SCCA levels were measured 3 months after surgery and every 3 - 12months during the follow-up. The optimal cut-off values of postoperative SCCA levels to predict subsequent recurrence of IP were evaluated using ROC analysis. RESULTS: Preoperative serum levels of SCCA were higher than the upper limit of normal range in most patients with both primary and recurrent IP, and significantly decreased after surgery. Thus, the presence of IP was closely associated with elevated serum SCCA levels. Moreover, postoperative elevation of SCCA levels was closely associated with subsequent recurrence of IP. Postoperative SCCA levels in 5 patients with recurrence were significantly higher than those in 20 patients without recurrence. The optimum cut-off value of SCCA levels to predict subsequent recurrence of IP 3 months after surgery was 1.85 ng/ml, with a sensitivity of 100.0 % and a specificity of 90.0 %. CONCLUSIONS: These findings suggest that SCCA can be a tumor marker of IP. It is also suggested that postoperative elevation of SCCA levels is a clinical marker for monitoring the recurrence of IP during the follow-up period. A SCCA cut-off value of 1.85 ng/ml postoperatively may predict the subsequent recurrence of IP with high sensitivity and specificity.

Formation of Supramolecular Nanostructures through in Situ Self-Assembly and Post-Assembly Modification of a Biocatalytically Constructed Dipeptide Hydrazide.

Aqueous self-assembly of short peptides has attracted growing attention for the construction of supramolecular materials for various bioapplications. Herein, we describe how the thermolysin-assisted biocatalytic construction of a dipeptide hydrazide from an N-protected amino acid and an amino acid hydrazide leads to the formation of thermally stable supramolecular hydrogels. In addition, we demonstrate the post-assembly modification of the supramolecular architectures constructed in situ tethering hydrazide groups as a chemical handle by means of fluorescence imaging.

Patho-Pharmacological Research of Anti-allergic Natural Products Targeting Antihistamine-Sensitive and -Insensitive Allergic Mechanisms.

Histamine H1 receptor (H1R) has a special up-regulation mechanism by the stimulation of H1R, mediated by protein kinase C-delta (PKCδ) signaling and H1R gene expression, resulting increase in H1R signaling. Increase in H1R mRNA in nasal mucosa was induced after the provocation of nasal hypersensitivity model rats and suppressed by the pre-treatment of antihistamines. Improvement of nasal symptoms and suppression of H1R mRNA expression in nasal mucosa were also observed by the pre-treatment of antihistamines in pollinosis patients. Elucidation of a correlation between symptoms and H1R mRNA level suggests that H1R gene is an allergic disease (AD)-susceptibility gene, targeted by antihistamines. Similar to antihistamines, pre-treatment of Kujin extract, an anti-allergic Kampo medicine improved nasal symptoms and suppressed H1R mRNA expression in nasal hypersensitivity model rats. (-)-Maackiain targeting heat shock protein 90 (Hsp90) was isolated as an inhibitor of PKCδ signaling-mediated H1R gene expression from Kujin extract. In addition to H1R-mediated activation of H1R gene expression as the first mechanism, nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression is suggested to participate to allergic symptoms as the second mechanism insensitive to antihistamines. Pyrogallol and proanthocyanidin suppressing IL-9 gene expression were discovered from Awa-tea and lotus root knots, respectively. Combination therapy using medicines suppressing both H1R gene expression and IL-9 gene expression is promising for outstanding alleviation of AD. Multifactorial diseases involving H1R gene expression may be treated by the combination therapy with antihistamine and complementary drugs, and diseases involving PKCδ signaling may be treated by drugs targeting Hsp90.

Development of receptive vocabulary and verbal intelligence in Japanese children with unilateral hearing loss.

OBJECTIVE: In the past, it was believed that unilateral hearing loss has a minimal impact on the speech and language development in children. However, several studies have suggested that some school-age children with unilateral hearing loss have learning impairments in language. In the present study, we first examined whether preschool-age children with unilateral severe-to-profound hearing loss (UHL) have delays in the development of receptive vocabulary and verbal intelligence. In the follow-up study, we tested the children again after school admission. The objective of the present study was to reveal the development of receptive vocabulary and verbal intelligence from preschool to school years in children with UHL. METHODS: Fifteen Japanese preschool-age children with UHL and a control group of 20 age-matched Japanese children with bilateral normal hearing (NH), who were examined because articulation disorder was suspected, were enrolled in this study. The development of receptive vocabulary and verbal intelligence was evaluated using the Picture Vocabulary Test-Revised (PVT-R) and the Wechsler Intelligence Scale, respectively. The present retrospective study was approved by the Committee for Medical Ethics of Tokushima University Hospital (#3801). RESULTS: The scaled score (SS) of the PVT-R and verbal intelligence quotient (VIQ)/verbal comprehension index (VCI), but not performance intelligence quotient/perceptual reasoning index in children with UHL were significantly lower than those in the control children with NH at preschool-age. The SS of the PVT-R and VIQ/VCI in children with UHL significantly improved after school admission. In the subgroup analysis, the SS of the PVT-R in the lower receptive vocabulary group of children with UHL at preschool-age was significantly increased after school admission, but the SS in the normal and higher receptive vocabulary group of children with UHL at preschool-age were still around the standardized mean of SS after school admission. CONCLUSION: These findings suggest that the development of receptive vocabulary and verbal intelligence was delayed in preschool-age children with UHL and that most of them caught up to exhibit normal language ability after school admission.

Molecular Signaling and Transcriptional Regulation of Histamine H1 Receptor Gene.

Histamine-activated histamine H1 receptor (H1R) signaling regulates many gene expressions, mainly through the protein kinase C (PKC)/extracellular signal-regulated kinases (ERK) signaling. Involvement of other signaling, including NF-κB, Wnt, RUNX-2, and Rho A signaling was also demonstrated. In addition, cAMP production through the activation of H1R signaling was reported. H1R gene itself is also up-regulated by the activation of H1R signaling with histamine. Here, we review our recent findings in the molecular signaling and transcriptional regulation of the H1R gene. Stimulation with histamine up-regulates H1R gene expression through the activation of H1R in HeLa cells. The PKCδ/ERK/poly(ADP)ribosyl transferase-1 (PARP-1) signaling was involved in this up-regulation. Heat shock protein 90 also plays an important role in regulating PKCδ translocation. Promoter analyses revealed the existence of two promoters in the human H1R gene in HeLa cells. H1R-activated H1R gene up-regulation in response to histamine was also observed in U373 astroglioma cells. However, this up-regulation was mediated not through the PKCδ signaling but possibly through the PKCα signaling. In addition, the promoter region responsible for histamine-induced H1R gene transcription in U373 cells was different from that of HeLa cells. These findings suggest that the molecular signaling and transcriptional regulation of the H1R gene are different between neuronal cells and non-neuronal cells.