The goblet cell population of the conjunctiva reflects the degree of the differentiation or maturation of the conjunctival epithelium, which in turn reflects the overall health of the ocular surface. The authors observed the conjunctival goblet cell counts in the 25 eyes with pterygium stained with Periodic acid-Schiff(PAS) and Hematoxylin-Eosinophil(H-E) stain for the evaluation of the conjunctival health state in the presence of pterygium, and compared conjunctival goblet celli counts in the eyes with pterygium with that in the normal 20 eyes. The distribution of conjunctival goblet cells was evaluated in observing the bulbar conjunctival cell counts at 12, 3, 6, 9 o'clock site in enucleated eyes due to phthisis bulbi. There was significant decrease(P<0.01) in the conjunctival goblet cell counts in the eye with pterygium, and was many difference in the individual cases. Mean goblet cell counts in the normal subjects was 6.6/mm. The number of goblet cells was highest in the nasal side, followed by inferior, superior, and temporal side.
Biopsy* ; Cell Count ; Conjunctiva ; Epithelium ; Goblet Cells* ; Pterygium*

Mucus hypersecretion is a common response to chronic inflammation in the lower airways and is a hallmark of chronic rhinosinusitis. It contributes to their morbidity and mortality by plugging airways and causing recurrent infections in lower airway. At present there is no specific treatment for mucus hypersecretion. However, it has been discovered that epithelial growth factor receptor (EGFR) expression and activation causes mucin production in airways. An EGFR pathway is implicated in mucus cell differentiation induced by various stimuli; therefore, inhibition of the EGFR transduction cascade may provide effective new treatments for hypersecretory airway diseases. EGFR pathways have also been implicated in the regranulation of goblet cell in the airway epithelium. Proving this theory will require the use of selective EGFR inhibitors in clinical studies of nasal hypersecretory states.
Cell Differentiation ; Epidermal Growth Factor* ; Epithelium* ; Goblet Cells ; Inflammation ; Mortality ; Mucins* ; Mucus ; Receptor, Epidermal Growth Factor*

To study the basic pathological changes of small intestine in metagonimiasis, light- and electron microscopic studies were made, using a total of 21 cats which were experimentally infected with metacercariae of Metagonimus yokogawai. The metacercariae were obtained from naturally infected sweetfish (Plecoglossus altivelis) by digestion technique. The cats were divided in control, light-infection(10,000 metacercariae infected) and heavy-infection(50,000 metacercariae infected) groups. Cats were killed at the 5th, 10th, 15th day, and 4th, 8th and 10th week after the infection. And the small intestine was prepared for the study. Pathological studies comprised gross examination, worm distribution pattern, light microscopic examination and both transmission and scanning electron microscopic examinations. The results obtained were summarized as follows. Gross morphologic changes were the most marked during the first 2 weeks after infection. The gross abnormalities were severer in the heavily infected animals. The changes were dryness and listlessness of serosal surface due to dehydration, mushy and/or watery intestinal content, effacement of transverse nodes and enlargement of mesenteric lymph folds and Peyer's patches. After 4 weeks of infection, these changes became less marked showing a tendency to return to normal. The sectioned flukes were distributed from duodenum to proximal ileum. However, individual variation was marked in distribution. In the heavy-infection group, the locality of parasitism tended to extend more distally. The locality of M. yokogawai in the intervillous space was mostly in the lower-most portion of intervillous space, where they compressed and eroded epithelial cells probably due to mechanical damage to the structure. Very rarely the worms were found in lumen of Lierberkuehn's crypt, and reaching, in two occasions, into proprial lymphoid tissue. Light-microscopically the lesion was restricted in mucosa: Early mucosal changes were shortening, blunting, fusion, and thickening of the villi, crypt hypertrophy with consequent decrease of villus/crypt ratio, as well as stromal changes of edema, capilliary ectasia and marked inflammatory cell infiltration of lymphocytes and plasma cells. Goblet cells were markedly reduced in number as with depletion of its cytoplasmic content. In the later stages of infection, mucosa restored its normal configuration in spite of persistent parasitism of the worms. At the infection stage of 5-15 days, there was significant shortening of the microvillous height with varible destruction of glycocalyx in electron microscopic examination. With lapse of infection time, microvilli became to restore the normal pattern. With these morphological changes, it appears that diarrhea in experimental metagonimiasis would be related to the decrease of absorptive surface of the small intestine particularly in the early phase of infection. The significant changes seen in villi and microvilli might be due to massive intrusion or invasion of Metagonimus worms into the crypts, causing direct mechanical and possible host-immune response to the small bowel mucosa.
parasitology-helminth-trematoda ; metagonimiasis ; Metagonimus yokogawai ; pathology ; cat-intestine ; edema ; lymphocytes ; plasma cells ; goblet cell

PURPOSE: Paclitaxel is a chemotherapeutic agent with a potent microtubule stabilizing activity that arrests mitosis at G2-M phase of cell cycle which is the most radiosensitive period. Therefore paclitaxel is considered as a cell cycle-specific radiosensitizer. This study investigates the effect of paclitaxel on the radiation response of the normal large bowel mucosa of the rat. MATERIALS AND METHODS: The rats were divided into the three groups i.e., single intraperitoneal infusion of paclitaxel (10 mg/kg), a single fraction of irradiation (8 Gy, x-ray) to the whole abdomen, and a combination of irradiation (8 Gy, x-ray) given 24 hours after paclitaxel infusion. The histological changes as well as kinetics of mitotic arrest and apoptosis were evaluated on the large bowel mucosa at 6 hours, 1 day, 3 days and 5 days after treatment with paclitaxel alone, radiation alone and combination of paclitaxel and radiation. RESULTS: The incidence of the mitotic arrest was not increased by paclitaxel infusion. The apoptosis appeared in 24 hours after paclitaxel infusion, and the histopathologic changes such as vesiculation, atypia and reduction of the goblet cell of the mucosa of the large bowel were demonstrated during the period from 6 hours to 3 days after, and returned to normal in 5 days after paclitaxel infusion. In irradiated group, the apoptosis was increased in 6 and 24 hours after irradiation, and the histopathologic changes of the mucosa were appeared in 24 hours and markedly increased in 3 days and returned to normal in 5 days. In combined group of irradiation and paclitaxel infusion, the apoptosis was appeared in 3 days and the histopathologic changes appeared during the period from 6 hours to 3 days after infusion. On the basis of the incidence of apoptosis and the degree of the histopathologic changes of the large bowel mucosa, there seemed to be additive effect by paclitaxel on radiation rather than sensitizing effect. CONCLUSION: The histopathological changes of large bowel mucosa in combined group compared to radiation alone group suggested an additive effect of paclitaxel on radiation response in the large bowel of rat.
Abdomen ; Animals ; Apoptosis ; Cell Cycle ; Goblet Cells ; Incidence ; Infusions, Parenteral ; Kinetics ; Microtubules ; Mitosis ; Mucous Membrane* ; Paclitaxel* ; Rats*

PURPOSE: To evaluate the possibility of short-term dry eye model in rabbits by injection of concanavalin A (conA) to the lacrimal and haderian gland of rabbits. METHODS: We injected conA (10 mg/ml, 0.05 ml) to the lacrimal and haderian gland of rabbits twice to induce inflammation of lacrimal gland and compared with saline-injected control by lacrimal gland biopsy with H&E staining for identification of inflammation. The ratio of lacrimal secretion was evaluated by Schirmer test (preinjection vs. postinjection of conA) for 10 days and the number of goblet cells was counted in 10 consecutive high power field using impression cytology with PAS staining. The corneal & conjunctival apoptotic cell deaths were investigated with TUNEL staining 10 days after injection. RESULTS: Infiltration of inflammatory cells and destructed normal architecture of lacrimal gland was found only in conA injected group till 10 days. The Schirmer test showed marked reduction (0.56+/-0.26) by 5days after injection compared with control group (1.07+/-0.35) (p=0.02) and its significant difference was maintained till 10days. The number of goblet cell was 9.70+/-5.03/x200HPF, which was statistically significant decreased compared to control (47.50+/-17.13/x200HPF) at 10 days (p=0.00). Apoptotic cells were increased in injected eye (26.20+/-4.27) compared with those in control (16.60+/-2.70). CONCLUSIONS: Injection of conA to lacrimal glands in rabbit shows decrease of lacrimal secretion and similar cytological changes of the cornea and conjunctiva in human dry eye patients. It suggests its possible feasibility of short-term dry eye animal model for the 10 days.
Animals* ; Biopsy ; Cell Death ; Concanavalin A* ; Conjunctiva ; Cornea ; Goblet Cells ; Humans ; In Situ Nick-End Labeling ; Inflammation ; Lacrimal Apparatus ; Models, Animal* ; Rabbits

BACKGROUND: All tissue components in the nasal mucosa, including the epithelium, goblet cells, excretory glands, and blood capillaries participate in nasal secretory response. In vivo studies have suggested that, of these components, submucosal glands are thought to play an important role in nasal mucus secretion. These studies, however, are limited in dealing with pure secretory activity of submucosal glands. Therefore, in vitro study using cultured nasal submucosal glands is required to evaluate the pathophysiological mechanisms of nasal mucus secretion. The present study draws on experience obtained from the culture of human submucosal glands isolated from nasal mucosa. MATERIALS AND METHODS: To obtain isolated submucosal gland cells, the uncinate process mucosa was stripped of surface epithelum by stroking the luminal surface with cotton tip applicator and minced into small fragments. By enzymatic treatment, thereafter, the submucosal gland cells were isolated and plated on culture flasks containing media. Using millipore inserts and cover slide, culuted cell was stained AB-PAS to identify that confluent monolayer cells were submucosal gland cell. RESULTS: The uncinate process mucosa were appropriate for the isolation of submucosal gland cell. An average of 1.2X106 cells were obtained in every preparation of cells. The exclusion ratio of trypan blue was 95%. The isolated cells were strongly stained in AB-PAS, suggesting that cells are of glandular origin. Plated gland cell formed colony on the 3rd day and became confluent after 5-7 days. The proportion of the stained cells to the total cells decreased depending the duration of cell culture. CONCLUSION: We succeeded in isolation and culture of submucosal gland cells which can provide model systems for studying the mechanisms of nasal glandular cell secretion in vivo.
Capillaries ; Cell Culture Techniques* ; Epithelium ; Goblet Cells ; Humans* ; Mucous Membrane ; Mucus ; Nasal Mucosa ; Phenobarbital ; Stroke ; Trypan Blue

PURPOSE: Live Mycobacterium bovis Bacille Calmette-Guerin (BCG) has a suppressive effect on asthma, but its use in clinical practice may be limited due to adverse reactions. To develop a product that is effective for suppressing asthma with minimal adverse reactions, we investigated whether the heat-killed body or culture supernatants of mycobacteria could also prevent asthma development. METHODS: Female BALB/c mice were treated with live BCG, the heat-killed body, or culture supernatants of BCG or Mycobacterium tuberculosis intraperitoneally, while sensitizing and provoking with ovalbumin. Then they underwent a methacholine bronchoprovocation test, and the peribronchial inflammatory cell numbers and cytokine levels in splenocyte culture supernatants were assessed. RESULTS: The airway sensitivity to methacholine decreased significantly after treatment with not only live BCG (30.8 versus 10.0 mg/mL, P<0.001) but also with the culture supernatant (BCG, 23.0 mg/mL, P<0.05; M. tuberculosis, 20.5 mg/mL, P<0.05). In contrast, heat-killed mycobacteria did not effectively decrease airway sensitivity. The peribronchial eosinophil counts and the goblet cell proportions in total epithelial cells decreased significantly in most of the groups. The interferon-gamma/interleukin-5 ratios increased significantly in most of the treatment groups except for the heat-killed groups, and were significantly related to airway sensitivity (r=0.312, P<0.01) and peribronchial eosinophil counts (r=-0.416, P<0.001). Interleukin-17A level was inversely related to airway sensitivity (r=-0.212, P<0.05) and was significantly lower in the live BCG group than in the control (137+/-20 versus 308+/-57 pg/mL, P<0.05). CONCLUSIONS: BCG and mycobacteria culture supernatants may effectively prevent the development of asthma associated with altered Th1/Th2 cytokines and interleukin-17A levels.
Animals ; Asthma ; BCG Vaccine ; Cell Count ; Cytokines ; Eosinophils ; Epithelial Cells ; Female ; Goblet Cells ; Humans ; Interferons ; Interleukin-17 ; Interleukins ; Methacholine Chloride ; Mice ; Mycobacterium ; Mycobacterium bovis ; Mycobacterium tuberculosis ; Ovalbumin ; Tuberculosis

BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a recently discovered TGF-beta superfamily cytokine. But localization and functions of NAG-1 have not been thoroughly studied. So, we wanted to investigate its expression and localization in human nasal mucosa and also wanted to investigate the change of NAG-1 expression as a function of mucociliary and squamous differentiation. MATERIALS AND METHODS: Anterior and middle portion of human inferior turbinate were used and immunohistochemistry with NAG-1 antibody was done. Passage-2 normal human nasal epithelial cell culture using air-liquid interface method was performed for 14 days and the cells were divided as retinoic acid (RA)-sufficient and RA-deficient group. Hematoxylin and eosin staining was done on each group to study the degree of differentiation. Western blot analysis for NAG-1 expression was performed on each group on 0, 7, and 14 days. RESULTS: NAG-1 expression of muco-ciliated epithelium was noted in ciliated cells and serous acini, but was not found in goblet cells and mucous acini. In the squamous epithelium, its expression was weaker than in the mucociliated epithelium. In the RA-sufficient culture, NHNE cells were differentiated into ciliated epithelium, but in the RA-deficient culture, keratinizing squamous epithelium was noted. In the Western blot analysis, NAG-1 expression was significantly higher in the RA-sufficient culture than in the RA-deficient culture and this expression was time-dependent. CONCLUSION: NAG-1 may be related to differentiation and apoptotic process of nasal epithelial cells. However, it is still unclear whether NAG-1 is an inducer or a byproduct of differentiation or apoptosis. The role of NAG-1 protein remains to be solved.
Anti-Inflammatory Agents ; Apoptosis ; Blotting, Western ; Cell Differentiation ; Eosine Yellowish-(YS) ; Epithelial Cells* ; Epithelium ; Goblet Cells ; Hematoxylin ; Humans* ; Immunohistochemistry ; Nasal Mucosa* ; Transforming Growth Factor beta ; Tretinoin ; Turbinates

PURPOSE: Live/killed mycobacteria and culture supernatants can suppress asthmatic reactions. This study investigated whether mycobacterial secretory proteins have therapeutic effects on asthma. METHODS: Mycobacterium bovis bacille Calmette-Guerin (BCG; 2x105 CFUs) and mycobacterial secretory proteins (Ag85 complex, 38-kDa protein or MPB70; 4 or 20 microg) were administered intraperitoneally to female BALB/c mice with established airway hyperresponsiveness. One week after treatment, the mice underwent a methacholine challenge test, and then inflammatory cell numbers in bronchoalveolar lavage fluid (BAL) and around bronchi (<500 microm), and cytokine levels in splenocyte supernatants, were assessed. RESULTS: BCG and all of the tested secretory proteins significantly improved airway sensitivity compared to baseline values (P<0.05). The secretory protein Ag85 complex significantly suppressed airway reactivity also (P<0.05), while 38-kDa protein significantly suppressed reactivity and maximal narrowing (P<0.05). The number of eosinophils in BAL and around bronchi, and the goblet cell proportion, were also significantly reduced in mice in both the BCG and secretory protein groups compared to the asthma control group. IFN-gamma/IL-5 ratios were significantly higher in mice treated with BCG, 4 microg MPB70 or 4 microg 38-kDa protein than in asthma control mice (P<0.05), and were negatively associated with airway hyperresponsiveness, peribronchial eosinophil numbers and goblet cell proportion (all P<0.05). IL-17A was positively correlated with IL-5 (r=0.379, P<0.001), maximal airway narrowing, peribronchial eosinophil numbers and goblet cell proportion (all P<0.05). CONCLUSIONS: Secretory proteins from BCG and M. tuberculosis and live BCG were effective against established asthma, their effects being accompanied by increased IFN-gamma/IL-5 ratios. Thus, allergic asthma could be effectively treated with mycobacterial secretory proteins.
Animals ; Asthma ; Bronchi ; Bronchoalveolar Lavage Fluid ; Cell Count ; Eosinophils ; Female ; Goblet Cells ; Humans ; Indoles ; Interleukin-17 ; Interleukin-5 ; Methacholine Chloride ; Mice ; Mycobacterium bovis ; Proteins ; Tuberculosis

BACKGROUND/AIMS: The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. METHODS: High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. RESULTS: HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. CONCLUSIONS: These results suggest that the IL-17–leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.
Adipokines ; Adipose Tissue ; Animals ; Asthma* ; Bronchoalveolar Lavage Fluid ; Cell Differentiation ; Diet, High-Fat ; Goblet Cells ; Humans ; Inflammation* ; Interleukin-17 ; Mice ; Obesity ; Ovalbumin ; Ovum ; Oxidoreductases ; Pravastatin ; Respiratory Hypersensitivity ; Spleen