The mucus secretion of airway glands is known to be controlled by the various autonomic neurotransmitters such as noradrenalin and acetylcholine. However, a recent study suggests that non-adrenergic, non-cholinergic (NANC) nerves may contribute to the secretory activity of glands. Substance P (SP) has been proposed as a neurotransmitter of the NANC nervous system. SP is present within nerve fibers innervating the airway mucosa and is known to be released from sensory nerves via an axonal reflex. SP activity is controlled by neutral endopeptidase (NEP) which degrades SP. In this study, we evaluated the effects of NEP inhibitor (thiorphan) and substance P on nasal mucosa and histamine on the nasal mucosa in healthy males. In the thiorphan-substance P experimental group, the nasal volume decreased after nebulization of substance P in proportion to the concentration of histamine. In the thiorphan-substance P experimental group, the frequency of sneezing increased in proportion to the concentration of histamine, but there was no increased frequency of sneezing from thiorphan, SP and normal saline. The results of this study suggest that axonal reflexes can play a role in the pathogenesis of nasal mucosal hypersensitivity and neurogenic inflammation.
Acetylcholine ; Axons* ; Histamine ; Humans ; Hypersensitivity* ; Male ; Mucous Membrane ; Mucus ; Nasal Mucosa ; Neprilysin ; Nerve Fibers ; Nervous System ; Neurogenic Inflammation ; Neurotransmitter Agents ; Reflex* ; Sneezing ; Substance P* ; Thiorphan

BACKGROUND & OBJECTIVES: Some components of ground substances are known to be involved in developing nasal polyp. The fibroblasts are a major component of the ground substances in nasal polyp and have many immunologic roles. Heterogeneity of fibroblasts has been observed in other anatomical sites including the nasal mucosa. The aim of this study was to investigate the heterogeneity of fibroblasts of nasal polyps in non-allergic rhinitis and allergic rhinitis. MATERIALS & METHODS: Using the third passage of the fibroblasts taken from polyps of allergic and non-allergic patients, we measured the proliferating potential by comparing the cell growth in the culture system of fibroblasts and calculated the doubling time of the cell growth. We also compared the proliferating potentials between the two groups after stimulation with histamine or IL-4. RESULTS: Morphologic differences were examined by transmission electron microscopy. In the non-stimulated experiment, proliferation of fibroblasts was increased in the non-allergic polyp group (NAPG). When the fibroblasts were stimulated with histamine, the proliferation was not significantly changed on day 6 in both groups. When the fibroblasts were stimulated with IL-4, the proliferation was significantly increased in NAPG. Morphologic differences were demonstrated between the NAPG and the APG. CONCLUSION: The differences in cell proliferation potentials and morphological changes between both groups suggest that there is a heterogeneity of fibroblasts between them.
Cell Proliferation ; Fibroblasts* ; Histamine ; Humans ; Interleukin-4 ; Microscopy, Electron, Transmission ; Nasal Mucosa ; Nasal Polyps* ; Polyps ; Population Characteristics* ; Rhinitis*

BACKGROUND AND OBJECTIVES: Smoking is regarded as one of the factors that bring about nonspecific hypersensitivity in allergic nasal mucosa. But it is uncertain how chronic smoking affects hypersensitivity in nasal mucosa. This study was designed to evaluate the relationship between smoking and nasal hypersensitivity. In this study, histamine is used since it is commonly used to evaluate nasal hypersensitivity. MATERIAL AND METHODS: Twelve smokers and 9 nonsmokers were participated in this study. Nasal mucosae of each subjects were stimulated by thiorphan followed by substance P. After stimulation, several dilutions of 10 to 5X104 ng/ml of histamine was instilled to both nasal cavity at intervals of 10 minutes. We measured the volume of nasal cavity by acoustic rhinometry in each step and counted the number of sneezing and nasal blowing at every 10 minute intervals. Changes in volume after each dillutions of histamine instillations were compared with the values measured after the stimulation by thiorphan and substance P., and this value was expressed as the percentage volume change. RESULTS: The nasal volume of smoker group was increased upto 100 ng/ml of histamine and decreased from 1000 ng/ml of histamine. The nasal volume of nonsmoker group decreased more than the smoker group with each dilution of histamine. The number of sneezing and nasal blowing increased in each group with each dilution of histamine. CONCLUSIONS: Chronic smoking may decrease susceptibility of hypersensitivity to histamine in nasal mucosa.
Histamine ; Hypersensitivity* ; Nasal Cavity ; Nasal Mucosa ; Rhinometry, Acoustic ; Smoke ; Smoking ; Sneezing ; Substance P ; Thiorphan

Endoglin (also known as CD105 or TGF-beta type III receptor) is a co-receptor involved in TGF-beta signaling. In atherosclerosis, TGF-beta signaling is crucial in regulating disease progression owing to its anti-inflammatory effects as well as its inhibitory effects on smooth muscle cell proliferation and migration. Endoglin is a regulator of TGF-beta signaling, but its role in atherosclerosis has yet to be defined. This review focuses on the roles of the various forms of endoglin in atherosclerosis. The expression of the two isoforms of endoglin (long-form and short-form) is increased in atherosclerotic lesions, and the expression of the soluble forms of endoglin is upregulated in sera of patients with hypercholesterolemia and atherosclerosis. Interestingly, long-form endoglin shows an atheroprotective effect via the induction of eNOS expression, while short-form and soluble endoglin enhance atherogenesis by inhibiting eNOS expression and TGF-beta signaling. This review summarizes evidence suggesting that the different forms of endoglin have distinct roles in atherosclerosis.
Atherosclerosis* ; Disease Progression ; Humans ; Hypercholesterolemia ; Myocytes, Smooth Muscle ; Protein Isoforms ; Transforming Growth Factor beta

BACKGROUND: It is well known that IgA isotype switching is induced by TGF-beta1. LPS-activated mouse normal B cells well differentiate into IgA secreting plasma cells under the influence of TGF-beta1. Nevertheless, there are lots of difficulties in studying normal B cells in detail because it is not simple to obtain highly purified B cells, showing low reproducibility and transfection efficacy, moreover impossible to keep continuous culture. To overcome these obstacles, it is desperately needed to develop B cell line which acts like normal B cells. In the present study, we investigated whether CH12F3-2A lymphoma cells are appropriate for studying IgA isotype switching event. METHODS: CH12F3-2A B cell line was treated with LPS and TGF-beta1, then levels of germ-line (GL) transcripts were measured by RT-PCR, and GLalpha promoter activity was measured by luciferase assay. In addition, membrane IgA (mIgA) expression and IgA secretion were determined by FACS and ELISA, respectively. RESULTS: TGF-beta1, regardless of the presence of LPS, increased level of GLalpha transcripts but not GLgamma2b transcripts. However, IgA secretion was increased dramatically by co-stimulation of LPS and TGF-beta1. Both mIgA and IgA secretion in the presence of TGF-beta1 were further increased by over-expression of Smad3/4. Finally, GLalpha promoter activity was increased by TGF-beta1. CONCLUSION: CH12F3-2A cell line acts quite similarly to the normal B cells which have been previously reported regarding IgA expression. Thus, CH12F3-2A lymphoma cell line appears to be adequate for the investigation of the mechanism(s) of IgA isotype switching at the cellular and molecular levels.
Animals ; B-Lymphocytes ; Cell Line ; Enzyme-Linked Immunosorbent Assay ; Immunoglobulin A* ; Immunoglobulin Class Switching* ; Luciferases ; Lymphoma* ; Membranes ; Mice* ; Plasma Cells ; Transfection ; Transforming Growth Factor beta1

Osteoma of the tongue is a rare entity of unknown origin. Clinically, the majority of the osteoma are described as growth of pedunculated mass on the posterior dorsum of the tongue without symptoms. The mechanism for its formation is unknown, but various theories have been proposed. Surgery is an appropriate treatment and no recurrence after surgery has been reported. We experienced a 68 year old man with undiagnosed osteoma of the tongue, incidentally detected during gastroscopy. We report this case with a review of literature.
Aged ; Gastroscopy ; Humans ; Osteoma ; Recurrence ; Tongue

The aim of this study was to evaluate effects of leukotriene D4(LTD4) on the nasal airway. Fifteen guinea pigs were divided into two groups;10 for experimental group and 5 for control group. Two l of 10(-5)mol LTD4 was administered to both nasal cavities in experimental group and same volume of normal saline in control group. Transmission electron microscopy was performed to investigate ultrastructural change of the nasal mucosal membrane in LTD4 administered guinea pigs. Infiltration of neutrophils and eosinophils from the capillaries were seen in the perivascular space. In the capillaries, some endothelial cells degenerated and intercellular spaces of the cells were widened, especially 6 hours later. Degranulated mast cells and neutrophils were found in the lumen of the capillaries. Several red blood cells with low electron density were seen in the shrunken vessels. The giant mitochondriae with inclusion bodies were observed. The results of this study suggest that leukotriene may be a potent mediator to induce biphasic response in the nasal passage of guinea pigs.
Animals ; Capillaries ; Endothelial Cells ; Eosinophils ; Erythrocytes ; Extracellular Space ; Guinea Pigs* ; Guinea* ; Inclusion Bodies ; Leukotriene D4* ; Mast Cells ; Membranes ; Microscopy, Electron, Transmission ; Mitochondria ; Mucous Membrane* ; Nasal Cavity ; Neutrophils

Forkhead box P3-positive (Foxp3 + )-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1–mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1–mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1–mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF–mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.

NF-kappaB activation has been implicated as a key signaling mechanism for pancreatic beta-cell damage. Sulfuretin is one of the main flavonoids produced by Rhus verniciflua, which is reported to inhibit the inflammatory response by suppressing the NF-kappaB pathway. Therefore, we isolated sulfuretin from Rhus verniciflua and evaluated if sulfuretin could inhibit cytokine- or streptozotocin-induced beta-cell damage. Rat insulinoma RINm5F cells and isolated rat islets were treated with IL-1beta and IFN-gamma to induce cytotoxicity. Incubation of cells and islets with sulfuretin resulted in a significant reduction of cytokine-induced NF-kappaB activation and its downstream events, iNOS expression, and nitric oxide production. The cytotoxic effects of cytokines were completely abolished when cells or islets were pretreated with sulfuretin. The protective effect of sulfuretin was further demonstrated by normal insulin secretion of cytokine-treated islets in response to glucose. Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was further evidenced by immunohistochemical staining of islets. However, the diabetogenic effects of streptozotocin were completely prevented when mice were pretreated with sulfuretin. The anti-diabetogenic effects of sulfuretin were also mediated by suppression of NF-kappaB activation. Collectively, these results indicate that sulfuretin may have therapeutic value in preventing beta-cell damage.
Animals ; Benzofurans/*pharmacology/therapeutic use ; Cell Line ; Cytokines/*adverse effects ; Diabetes Mellitus, Experimental/drug therapy/*prevention & control ; Flavonoids/pharmacology/therapeutic use ; Hypoglycemic Agents/pharmacology/therapeutic use ; Insulin-Secreting Cells/*drug effects ; Male ; Mice ; Mice, Inbred ICR ; NF-kappa B/*metabolism ; Rats ; Rats, Sprague-Dawley ; Rhus/chemistry

OBJECTIVE: The purpose of this study was to evaluate the risk of cesarean section in nulliparous women who undergone induction at postterm pregnancy. METHODS: The retrospective study was conducted from March, 1997 to March, 2005 by reviewing 331 nulliparous patients more than 41 weeks' gestation delivered after induction at our Hospital. The evaluated variables to assess the risk of cesarean section were maternal age, body mass index (BMI), gestational age (GA), Bishop scores (BS), fetal body weight (FBW), fetal head circumference (FHC) and fetal sex. t-test and x2-test were used to compare these categorical variables. RESULTS: The study included 331 nulliparous singleton pregnant women undergoing elective induction for postterm pregnancy: 127 (38.4%) delivered babies by cesarean section due to induction failure, progression failure and fetal distress, whereas 204 (61.6%) delivered vaginally. The mean maternal ages were 27.59+/-2.57 in cesarean delivery group and 26.99+/-2.61 in vaginal delivery group. The average values of BMI at postterm in cesarean and vaginal delivery groups were 26.70+/-2.82 and 25.75+/-2.67 kg/m2. GA was 41.36+/-0.27 weeks in cesarean delivery group, whereas 41.20+/-0.19 weeks in vaginal delivery group. The average FBW and FHC were 3460.31+/-358.22 g and 34.59+/-1.18 cm in cesarean delivery group, compared to 3363.95+/-361.22 g and 34.03+/-1.34 cm in vaginal delivery group. CONCLUSION: The BMI, FBW and FHC have linked to the risk of cesarean delivery in nulliparous women who underwent elective induction. Thus, these information would provide the useful tools to assess the risk of cesarean section in postterm nulliparous patients for planning an induction.
Body Mass Index ; Cesarean Section* ; Female ; Fetal Distress ; Fetal Weight ; Gestational Age ; Head ; Humans ; Maternal Age ; Pregnancy ; Pregnancy* ; Pregnant Women ; Retrospective Studies