Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group. After autoimmunization of the EAE mice with myelin oligodendrocyte glycoprotein, symptom severity scores, immunohistochemistry of the myelination of the spinal cord, and western blotting were used to evaluate the EAE mice. After the autoimmunization, the symptom scores of each EAE group significantly differed at times. The group treated with the larger tacrolimus dose had the lowest symptom scores. The tacrolimus-treated EAE groups exhibited less demyelination and inflammation and weak immunoreactivity for all of the immunization biomarkers. Our results revealed that oral-formulated tacrolimus inhibited the autoimmunization in MS pathogenesis by inactivating inflammatory cells.
Animals ; Autoimmune Diseases ; Biomarkers ; Blotting, Western ; Central Nervous System ; Demyelinating Diseases ; Encephalomyelitis, Autoimmune, Experimental* ; Humans ; Immunization ; Immunohistochemistry ; Inflammation ; Mice* ; Multiple Sclerosis ; Myelin Sheath ; Myelin-Oligodendrocyte Glycoprotein ; Neuromyelitis Optica ; Recurrence ; Spinal Cord ; Tacrolimus*

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by selective degeneration of motor neurons. Mutant superoxide dismutase 1 (SOD1) is often found as aggregates in the cytoplasm in motor neurons of various mouse models and familial ALS patients. The interplay between motor neurons and astrocytes is crucial for disease outcome, but the mechanisms underlying this phenomenon remain unknown. In this study, we investigated whether transient transfection with wild-type and mutant-type SOD1 may lead to amplification of mutant SOD1-mediated toxicity in cortical neurons and astrocytes derived from wild-type and mutant-type (human G93A-SOD1) mice. In transgenic mice expressing either wild- or mutant-type SOD1, we found that green fluorescent protein (GFP)-wtSOD1 was present in the cytoplasm and nuclei of wild-type cortical neurons and astrocytes, whereas GFP-mutant SOD1 was mainly cytoplasmic in wild- and mutant-type cortical neurons and astrocytes. These findings indicate that intracellular propagation of misfolding of GFP-wt or mtSOD1 are possible mediators of toxic processes involved in initiating mislocalization and aggregation. Here, we provide evidence that cytoplasmic aggregates induce apoptosis in G93A-SOD1 mouse cortical neurons and astrocytes and that the toxicity of mutant SOD1 in astrocytes is similar to the pathological effects of ALS on neurons in vitro. Collectively, our results indicate that mtSOD1 probably interacts with wtSOD1 via an unknown mechanism to produce augmented toxicity and may influence aggregate formation and apoptosis.
Amyotrophic Lateral Sclerosis ; Animals ; Apoptosis ; Astrocytes* ; Cytoplasm ; Humans ; Mice* ; Mice, Transgenic ; Motor Neurons ; Nervous System Diseases ; Neurons* ; Superoxide Dismutase ; Transfection*

BACKGROUND: The autophagy is the major route for lysosomal degradation of misfolded protein aggregates and oxidative cell components. We hypothesized that rapamycin (autophagy enhancer) would prolong the survival of motor neuron and suppress the disease progression in amyotrophic lateral sclerosis (ALS). METHODS: A total of 24 transgenic mice harboring the human G93A mutated SOD1 gene were used. The clinical status involving rotarod test and survival, and biochemical study of ALS mice model were evaluated. RESULTS: The onset of symptoms was significantly delayed in the rapamycin administration group compared with the control group. However, after the clinical symptom developed, the rapamycin exacerbated the disease progression and shortened the survival of ALS mice model, and apoptosis signals were up-regulated compared with control group. CONCLUSIONS: Even though further detailed studies on the relevancy between autophagy and ALS will be needed, our results revealed that the rapamycin administration was not effective for being novel promising therapeutic strategy in ALS transgenic mice and exacerbated the apoptosis.
Amyotrophic Lateral Sclerosis* ; Animals ; Apoptosis ; Autophagy ; Cellular Structures ; Disease Progression ; Humans ; Mice* ; Mice, Transgenic ; Motor Neurons ; Neuroprotective Agents* ; Rotarod Performance Test ; Sirolimus*

PURPOSE: This study was to develop and prove the effects of aself management compliance promotion program for primary hypertension patients who reside in rural communities. METHOD: The content of the self management compliance promotion program developed by this study was as follows: A leader trains patients as a group or individually, in walking, education and green tea therapy from the first to twelfth week. From the thirteenth to twenty fourth week, the patients should perform walking and green tea therapy by themselves. One hundred twenty subjects volunteered to participate in the study, who were among those registered as hypertension patients in the 14 community health clinics located in Chungcheongbuk-do. RESULT: Systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglyceride, step width, and degree of obesity decreased significantly. High-density lipoprotein cholesterol, step length, knowledge of hypertension, and self management compliance significantly increased. CONCLUSION: A self management compliance promotion program for primary hypertensive patients enhances biophysical index and knowledge on hypertension, thus ultimately suggesting a nursing intervention for promoting self management compliance.
Adult ; Aged ; Aged, 80 and over ; Female ; Health Promotion ; Humans ; Hypertension/psychology/*therapy ; Life Style ; Male ; Middle Aged ; Patient Compliance ; *Patient Education as Topic ; Rural Population ; *Self Care

PURPOSE: Food allergies play a major role in childhood atopic dermatitis. Egg white is the most common causative allergen in IgE mediated food allergies, and the only treatment is complete elimination of egg white from diet. The purpose of this study is to evaluate the effect of an egg white elimination diet on clinical progress and egg white-specific IgE concentration in childhood atopic dermatitis. METHOD: In 20 children with mild to severe atopic dermatitis, clinical progress was monitored by Jakob's atopic dermatitis grading system, and serum specific-IgE levels to six common food allergens and two house dust mites were measured by CAP-FEIA. RESULTS: In the study subjects, eight patients had been exposed to egg before diagnosis. During the six to 48 months of egg white elimination diet, clinical symptoms and signs were improved in 15 out of 20 patients. However, egg white-specific IgE levels were reduced by less than 1.20 kU/L (the cut off level suggesting immunological tolerance) in only seven patients. In the five patients with clinically persistent atopic dermatitis, egg white-specific IgE levels were 10.6-100 kU/L and house dust mite-specific IgE levels were 25.9-100 kU/L at the time of final examination. CONCLUSION: After 6-48 months of the egg white elimination diet, 75% of egg allergic infants and children with atopic dermatitis showed clinical improvement of atopic dermatitis. However, it is suggested that the patients need more than 1-3 years of a complete elimination diet to obtain immunological tolerance determined by egg white-specific IgE levels.
Allergens ; Child* ; Dermatitis, Atopic* ; Diagnosis ; Diet* ; Dust ; Egg White* ; Food Hypersensitivity ; Humans ; Immunoglobulin E* ; Infant ; Ovum* ; Pyroglyphidae

PURPOSE: The exposure to domestic animals has been increased, but there is no systematic evaluation for the clinical importance of animal antigens in Korea. The purpose of this study is to evaluate the significance of animal epithelial antigens as the causative allergens in childhood asthma and rhinitis. METHODS: In 228 children with asthma and rhinitis, allergic skin tests were done with 72 extracts, including 5 animal epithelial antigens. RESULTS: According to the results of allergy skin tests, 208 out of 228 children showed positive skin reactions to more than one antigens, and 128(61.4%) showed positive reactions to animal epithelial extracts. Among them, 17(8.1%) were mites non-sensitive to house dust and sensitive to animal epithelium. The positive reaction to each antigens were as follows:D. farinae(72.6%), D. pteronyssinus(69.7%), rabbit(40.3%), cat(33.1%), dog(24.0%), horse(16.8 %), and cow(14.9%). The degree of skin reactions to animal epithelial antigens were weaker than those to house dust mites. The positive concordance rates between skin tests and specific IgE reactions to D. pteronyssinus and cat/dog were 89.1%, and 25.9%, respectively. We experienced six patients with asthma and rhinitis who suspected animal epithelium as a causative allergen. CONCLUSION: Up to 61.4% of children with respiratory allergy showed positive reactions to animal epithelial extracts and 8.1% of them were house dust mites non-sensitive cases. Therefore, animal epithelium should be investigated as a causative allergen when skin reactions were strong and showed positive specific IgE antibodies.
Allergens ; Animals* ; Animals, Domestic ; Antibodies ; Asthma* ; Child* ; Dust ; Epithelium* ; Humans ; Hypersensitivity ; Immunoglobulin E ; Korea ; Mites ; Pyroglyphidae ; Rhinitis* ; Skin ; Skin Tests

BACKGROUND AND OBJECTIVE: Murine system for studying allergic diseases has been popular in the fields of food allergy and development of their therapeutic strategies. However, there has been no information about the age-dependent changes of natural immune responses of naive C3H/HeJ mice. The purpose of this study was to evaluate the age-dependent changes of B and T-cell mediated immunologic parameters in naive C3H/HeJ mice, which can provide information for experimental planning and analysis of research results. SUBJECTS AND METHODS: Eight naive, female, 5-week-old C3H/HeJ mice were grown under the regular mouse chow feeding conditions for 6 weeks. Sera were obtained at week (w) 5, w6, w8 and w10 for measuring total and chow-specific IgE, IgG1 and IgG2a antibodies. Splenocyte proliferation (at w8 and w10) and cytokine production (at w6, w8 and w10) were evaluated with or without Con A stimulation with pooled splenocytes from two mice of each age group. Serum antibodies and cytokines (IL-4, IL-5, IL-12, INF-gamma, TGF-beta1) were measured by ELISA. Using RT-PCR, IL-4 and INF-gamma mRNA expressions were measured in Peyer's patch and spleen tissue at w10. RESULTS: The levels of total IgE and IgG1 were increased by age while the level of IgG2a was decreased. Chow-specific IgE and IgG2a responses were neglectable through out the whole experimental period (20-30 ng/ml or less). Chow-specific IgG1 levels were measured in the significant concentrations (200-300 ng/ml) but there was no age-dependent change through out the experiment. Con A stimulated-splenocyte proliferation indexes were variable according to the culture-durations and ages of mice. The higher proliferation indexes were observed in the wells receiving thymidine pulse at 48-hour culture, especially in the mice at w10. Con A stimulated IL-4 production in the 72-hour splenocyte culture supernatant was significantly increased at w8, and w10 while INF-gamma production increased only at w10. The changes in the production of IL-5, IL-12 and TGF-beta did not provide significant information in the present study. The ratio of IL-4/IFN-gamma mRNA expression was higher in Peyer's patch than in the spleen. CONCLUSION: The changes of B-cell and T-cell mediated immunologic parameters were complex and variable according to the age in naive C3H/HeJ mice under regular chow feeding conditions. For that reason, the information from the present study needs to be considered in the course of planning or analysing research/data using murine systems.
Animals ; Antibodies ; B-Lymphocytes ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Female ; Food Hypersensitivity ; Humans ; Immunoglobulin E ; Immunoglobulin G ; Interleukin-12 ; Interleukin-4 ; Interleukin-5 ; Mice* ; RNA, Messenger ; Spleen ; T-Lymphocytes ; Thymidine ; Transforming Growth Factor beta

We have previously demonstrated that transferrin binding protein (TfBP) is a reliable marker for mature oligoden-drocytes (OLGs) in the avian central nervous system (CNS). Unlike mammalian CNS in which OLGs are generated largely postnatally, avian OLGs are differentiated during embryonic development of CNS. In this study, several aspects of TfBP(+/-) OLG development were immunohistochemically examined in the embryonic chick cerebellum : (1) change in shapes of immature cells with respect to time and to location within the cerebellum, (2) possible sites of origin, and (3) pathways of precursor cell migration. Our results indicate that TfBP expression gradually increases and extends from the deep portion of the white matter to gray matter with proportion to progress of cerebellar development. A few TfBP? cells were first observed in the deep portion of the cerebellum at E9. At E13, TfBP(+/-) cells were distributed evenly within the white matter. At E17, many TfBP(+/-) OLGs were located at granular layer and at the near place of Purkinje cell layer. At E20, a large number of TfBP cells appeared at the granular layer with a few in the molecular layer. Our data demonstrated distinct patterns of morphology and location of TfBP(+/-) OLGs in the cerebellum during development and suggest a role of TfBP in OLG development.
Animals ; Carrier Proteins ; Cell Movement ; Central Nervous System ; Cerebellum* ; Chick Embryo ; Embryonic Development ; Female ; Oligodendroglia ; Pregnancy ; Transferrin

PURPOSE: Buckwheat flour (BF) is known as a potent food allergen. Its sensitization usually occurs by ingestion, but also by inhalation due to occupational or domestic exposure. We underwent this study to identify an effect of buckwheat chaff stuffed pillow (BCP) exposure on sensitization to BF and clinical BF allergy in asthmatic children. METHOD: We obtained detailed history of BCP exposure in 36 asthmatic children (aged 0.7-14.2 years). We also performed RIA for specific IgE, BCP-elimination-provocation test. All subjects were divided into 3 groups, Group I (continuous BCP exposurers, n=13), Group II (previous exposurers, n=11), and Group III (non-exposurers to BCP, n=12) and all subjects had no history of ingestion of BF containing foods. RESULTS: In the 13 Group I cases, the durations of BCP exposure were 1-6 years, and 8 of them were users of BCP themselves, 5 were indirect exposurers by family members' BCP. The positive rates of BF specific IgE were 92.3, 36.4% and 8.3% in the Group I, II and III, respectively (Chi-square test, P<0.05). While the positive rates of house dust mites specific IgE were not significantly different among three groups. Twelve out of 13 Group I cases sensitized to BF, and 9 of those 12 were not sensitized to house dust mites. Eight out of 13 Group I cases were positive in BCP elimination-provocation test, during 6-24 month follow-up periods, 7 of them were managed effectively by BCP elimination only. CONCLUSION: Taken together, a small amount of BF attached to BCP can induce BF sensitization and BCP can be a major cause of childhood nocturnal asthma.
Asthma ; Child* ; Eating ; Fagopyrum* ; Flour ; Follow-Up Studies ; Humans ; Hypersensitivity ; Immunoglobulin E ; Inhalation ; Pyroglyphidae

Retina, a part of CNS, has served valuable and accessible tissue for elucidating the cellular properties of neurons and glia due to its similarity to brain. Unlike mammalian counterpart, avian retina is devoid of vessels and astrocytes. However little is known about glial reaction to neuronal injuries in this species. Therefore, this study was performed to investigate the microglial responses in the quail retina following neuronal injuries. The retinae from normal and optic nerve transected adult quails were studied immunohistochemically with anti-QH1, a marker known to be specific for microglia. In the normal retina, QH1-labeled microglial cells displayed typical feature of ramified (resting) form and were localized mainly in the inner plexiform layer. After optic nerve transection (ONT) morphology of microglial cells changed from the ramified to the amoeboid form. This feature of microglial cells maintained throughout the post operational periods until 28 days after ONT. Particularly, at 14 and 21 days after ONT amoeboid microglia displayed cell bodies with stout and bushy processes, suggesting active phagocytosis. The distribution pattern of microglia also changed in accord to ganglion cell degeneration: they gradually moved to layers of ganglion cells and optic nerve fibers where ganglion cell bodies and axons were under degeneration. This change of microglial distribution was most prominent at 14 days of ONT. The result of this study is generally consistent with that reported in mammalian counterpart and this similarity between the avascular avian retina and the vascularized mammalian counterpart suggests that processes of microglial activation, such as migration and phagocytosis, can occur in the vessel-free CNS tissue.
Adult ; Astrocytes ; Axons ; Brain ; Ganglion Cysts ; Humans ; Microglia* ; Neuroglia ; Neurons ; Optic Nerve Injuries* ; Optic Nerve* ; Phagocytosis ; Quail ; Retina ; Retinaldehyde*