The experiment was performed to investigate changes of maternal immune status during the pregnancy. We observed the distribution of several immune cells [macrophage, activated B-cell, IgM+ B-cell, Lyt-2+ T-cell and L3T4+ T-cells] in the utero-placental interface and the peripheral blood of Balb/c mice. The experimental animals were divided into seven groups by the gestational ages ; virgin, 2nd, 5th, 8th, 10th, 14th and 19th day of pregnancy. In the utero-placental interface, the distribution patterns of the lymphocytes [both T and B] and macrophages were observed. Histochemical staining by naphthol-AS-MX phosphate sodium salt was used for the detection of activated B-cells. For the detection of macrophage, plasma cell, suppressor cell and helper cell, all the prepared samples reacted with Rat anti-mouse Mac-1, goat anti-mouse IgM, rat anti-Lyt2 and rat anti-L3T4 antibody first, and washed. Second reaction was done with biotinylated anti-rat or anti-mouse IgG anti-bodies, and washed. Avidin-biotin -peroxidase complex and 3, 3`-diamino-benzidine[DAB] were used for the visualization of specific cells. T-cells and B-cells were not observed during the all stages of pregnancy. By contrast, macrophages were observed a few at the perimetrium on the second day of gestation, and they were found at the outermost portion of the trophoblastic layer on the 8th day, and they were observed at the decidua basalis in late pregnancy after the 10th day when the placenta were well developed. In the peripheral blood, activated B-cells were not observed throughout the pregnancy. On the 8th day, the proportion of plasma cells to total mononuclear cells was decreased significantly to 16+/-2.4% compared with the virgin group[22+/-2.6%][p<0.01]. It increased again and it reached 42+/-5.8% on the 14th day and 37+/-4.9% on the 19th day. Helper T-cells were decreased on the 14th day[30+/-2.4%] compared with the normal control[47+/-5.1%]. But, Suppressor T-cells were increased on the 8th day[35+/-2.9%] and the 10th day[33+/-3.6%] compared with the normal controls[27+/-2.3%]. This decrement returned to the level of the normal controls on the 14th day and 19th day. Together with our previous data, we could find the synchronized changes of immune cells in utero-placental interface, uterus draining lymph nodes, peripheral blood and spleen. Therefore, we suggest that macrophages in utero-placental interface may play an important role for the immune responses against the fetal transplantation antigen.
Animals ; B-Lymphocytes* ; Decidua ; Female ; Gestational Age ; Goats ; Immunoglobulin G ; Immunoglobulin M ; Lymph Nodes ; Lymphocytes ; Macrophages* ; Mice* ; Placenta ; Plasma Cells ; Pregnancy ; Rats ; Sodium ; Spleen ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; Trophoblasts ; Uterus

It is well known that the spatial patterns of basement membrane[BM] components show a close correlation with the morphogenetic process in developing organs during pre- and postnatal period. But little is known about the chronological changes in BM components during the development of thyroid gland. To investigate the correlation of the distribution of BM components with the development of the thyroid gland, immunohistochemical localization of the BM components was performed, using rat fetuses[from 15 to 21 days of gestation] and pups[from 1 to 14 days]. According to the histological features with H.E. staining, prenatal development[El5-21] of the rat thyroid could be divided into 3 representative stages : 1] Undifferentiated primordium of thyroid epithelia, forming cell cords or cell nests [until El5 day]. 2] An intervening stage of cell proliferation with the pattern of lobulation[El6-17 days]. 3] Stage of maturing follicles[El8-21 days]. It could be concluded that differentiation of the thyroid follicle are terminated during the prenatal period and growth in size and number occurs during the first two weeks after birth. By the immunohistochemical localization of laminin[LM], fibronectin[FN], type IV collagen[CIV], the basement membranes investing thyroid follicles could be clearly delineated at 15 days of gestation. Reactivity for LN and CIV associated with BM increased with advancing development, while that of FH was apparently weakened during the 2 weeks after birth. On the other hand immunoreactivity for CIV in the same age group increased, compared to that of previous swage of development. These results indicate that BM components were expressed in distinct spatial patterns with advancing development of thyroid gland. Based on these observations, it could be concluded that these BM components are important determinants in epithelial growth and differentiation during thyroid development.
Animals ; Basement Membrane* ; Cell Proliferation ; Collagen Type IV ; Fibronectins ; Hand ; Humans ; Laminin ; Parturition ; Pregnancy ; Rats* ; Thyroid Gland*

Thyroid gland is composed of follicles surrounded by basement membrane, which is known to be related to the regenerative processes in several organs. This study was performed to observe the morphological details and changes of the basement membrane components, which are the presumtive factors in thyroid regeneration, with time sequences after partial thyroidectomy and then the relations between the components and thyroid regeneration were confirmed. Thyroid galnds of adult male rats were examined before and 1, 2, 3, 4, 5, 7 and 10 days after bilateral partial[50-60%] thyroidectomy. The basememnt membranes of follicles were prominent with high eosinophilicity at later stage when H & E stained. But in PAS and EM staining, the basement membrane of the operated groups didn`t show any specific changes comparing with control group but the dense collagenous fibers at the interfollicular space outside the membrane. Immunostaining of proliferating cell nuclear antigen[PCNA], which reflects the growth fraction, showed 2.3% positivity of total follicular cells in control group. The PCNA positive ratio in experimental groups were 10.3%, 15.9%, 19.9%, 12.2%, 10.5%, 1.9%, 2.7% on postoperative 1, 2, 3, 4, 5, 7, 10 days respectively. In unilaterally thyroidectomized rats, the resected lobe revealed 18.2% of PCNA positive ratio 3 days after operation, while that in the unresected lobe was only 5.9%. This suggested the predominence of local factors in thyroid regeneration. Meanwhile, with the double immunostaining of calcitonin and PCNA discriminate between follicular cells and C-cells among the PCNA positive cells, PCNA positive C-cells were very rare. The immunostaining of laminin, fibronectin, and collagen IV showed varying intensity with the progress of regeneration. Stainability for collagen IV was maintained in all groups with some increase in 5- and 7-day groups. Laminin was well localized to the basement membrane of the control follicle, and the staining intensity for laminin was markedly increased with additional cytoplasmic staining in follicular cells in 1- to 3-day groups and then decreased to attain the control level in 10-day group. In case of fibronectin, the control follicle showed scarce staining, but the resected group showed strong positivity for fibronectin with the most intense staining in 1- to 3-day groups. Immunostaining for fibronectin still showes in 10-day group with the gradual disappearance of immunoreactivity in the center of the lobe. This study revealed the accompaning changes of the basement membrane components during the regeneration process of partially resected thyroid glands. Among them, collagen IV seems to support the structural integrity of the basement membrane. Laminin and fibronectin were supposed to be related to the thyroid follicular regeneration.
Adult ; Animals ; Basement Membrane ; Calcitonin ; Collagen ; Collagen Type IV ; Cytoplasm ; Eosinophils ; Extracellular Matrix* ; Fibronectins ; Humans ; Laminin ; Male ; Membranes ; Proliferating Cell Nuclear Antigen ; Rats* ; Regeneration ; Thyroid Gland* ; Thyroidectomy

BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). METHODS: In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. RESULTS: The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. CONCLUSIONS: pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value.
Acute-Phase Proteins ; Adolescent ; Adult ; Aged ; Biomarkers/blood ; Biopsy ; Chi-Square Distribution ; Creatinine/blood ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications/pathology/physiopathology ; Humans ; Kidney/*metabolism/pathology/physiopathology ; Linear Models ; Lipocalins/*blood ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins/*blood ; Renal Insufficiency, Chronic/blood/etiology ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Young Adult

The number of elderly patients with end-stage kidney disease has been increasing, but the outcomes of kidney transplants (KT) remain poorly understood in elderly patients. Therefore, we evaluated the clinical outcomes of elderly KT recipients and analyzed the impact of elderly donors. Methods: This retrospective cohort study included patients who underwent KT between 2000 and 2019. KT recipients were divided into four groups according to a combination of recipient and donor age (≥60 or <60 years); elderly recipients: old-to-old (n = 46) and young-to-old (n = 83); young recipients: old-to-young (n = 98) and young-to-young (n = 796). We compared the risks of mortality, graft failure, and acute rejection between groups using Cox regression analysis. Results: The incidence of delayed graft function, graft failure, and acute rejection was not different among groups. Annual mean tacrolimus trough level was not lower in elderly recipients than young recipients during 10-year follow-up. Mortality was significantly higher in elderly recipients (p = 0.001), particularly infection-related mortality (p < 0.001). In multivariable Cox regression analysis, old-toold and young-to-old groups had increased risk of mortality (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.14– 7.32; p = 0.03; aHR, 3.06; 95% CI, 1.51–6.20; p = 0.002). However, graft failure and acute rejection risks were not increased in elderly recipients. Conclusion: In elderly recipients, graft survival and acute rejection-free survival were not inferior to those of young recipients. However, mortality, especially risk of infection-related death, was increased in elderly recipients. Thus, low immunosuppression intensity might help decrease mortality in elderly recipients.

Background/Aims: Membranous nephropathy (MN) is a major cause of nephrotic syndrome in adults. This study aimed to evaluate the effect of rituximab (RTX) in patients with idiopathic MN (iMN) who have a high risk of progression. Methods: We retrospectively analyzed data of 13 patients with iMN, who received RTX treatments from January 2014 to July 2020. RTX was indicated in patients with iMN with severe proteinuria and decreasing estimated glomerular filtration rate (eGFR) in the previous 6 months despite other immunosuppressive therapies. Results: The patients were predominantly males (n = 11) and with a mean age of 55.3 years; median eGFR, 37.0 mL/min/1.73 m2 (interquartile range [IQR], 26.3 to 66.5); serum albumin level, 2.6 g/dL (IQR, 1.9 to 3.1); and spot urine protein-to-creatinine ratio at baseline, 6.6 g/g (IQR, 5.7 to 12.9). In a median follow-up of 22 months, eight patients (61.5%) achieved complete or partial remission. In responder group (n = 8), median eGFR increased from 31.5 to 61.5 mL/min/1.73 m2 (p = 0.049) and serum albumin level increased from 2.3 to 4.2 g/dL (p = 0.017) from RTX initiation to last follow-up. Antiphospholipase A2 receptor antibody (anti-PLA2R-Ab) was positive in six among seven tested patients, which markedly decreased in the responder group. There were no adverse events after RTX. Conclusions This study suggests that RTX is a safe and effective treatment option for patients with iMN who have a high risk of progression. Individualized therapy based on anti-PLA2R-Ab titer would be needed for better outcomes.

Background: Dermatophyte infection is one of the most common skin diseases affecting the skin, hair, and nails. Despite widespread recognition of the disease, missing details and misperceptions are commonplace in the general population. Objective: This study aimed to investigate the public perception and behavior regarding dermatophytosis of the hands and feet. Methods: This results from an online survey conducted between July 2022 and August 2022. The survey included 1,000 Korean participants aged 20 to 69 years, of whom 60% experienced symptoms of tinea pedis or onychomycosis. The questionnaire focused on the awareness and personal experience of tinea pedis and perception of the treatment of dermatophytosis. Results: Of the 1,000 participants, nearly 80% regarded tinea pedis as a common skin condition by which anyone can be affected. Furthermore, 88.4% had heard that the treatment of tinea pedis could be harmful, causing skin rash (60.4%) and worsening liver function (48.5%). Among 896 participants who noticed suspicious symptoms, 81.2% did not visit the clinic because it was not severe (50.1%) and seemed easily manageable (25.7%). Of the respondents, 84.4% preferred to meet dermatologists rather than non-dermatologist doctors regarding skin diseases, mainly because of trust in experts and belief in a faster cure. Conclusion Providing accurate and detailed information via online media, educational campaigns, and medical papers can rectify misconceptions and improve patient appliance, contributing to public skin health.

PURPOSE: Severe asthma and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) are difficult to control and are often associated with poor clinical outcomes. However, much is not understood regarding the diagnosis and treatment of severe asthma and ACOS. To evaluate the current perceptions of severe asthma and COPD among asthma and COPD specialists, we designed an e-mail and internet-based questionnaire survey. METHODS: Subjects were selected based on clinical specialty from among the members of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Academy of Tuberculosis and Respiratory Diseases. Of 432 subjects who received an e-mail invitation to the survey, 95 subjects, including 58 allergists and 37 pulmonologists, responded and submitted their answers online. RESULTS: The specialists estimated that the percentage of severe cases among total asthma patients in their practice was 13.9%±11.0%. Asthma aggravation by stepping down treatment was the most common subtype, followed by frequent exacerbation, uncontrolled asthma despite higher treatment steps, and serious exacerbation. ACOS was estimated to account for 20.7% of asthma, 38.0% of severe asthma, and 30.1% of COPD cases. A history of smoking, persistently low forced expiratory volume in 1 second (FEV1), and low FEV1 variation were most frequently classified as the major criteria for the diagnosis of ACOS among asthma patients. Among COPD patients, the highly selected major criteria for ACOS were high FEV1 variation, positive bronchodilator response, a personal history of allergies and positive airway hyperresponsiveness. Allergists and pulmonologists showed different assessments and opinions on asthma phenotyping, percentage, and diagnostic criteria for ACOS. CONCLUSIONS: Specialists had diverse perceptions and clinical practices regarding severe asthma and ACOS patients. This heterogeneity must be considered in future studies and strategy development for severe asthma and ACOS.
Allergy and Immunology ; Asthma* ; Diagnosis ; Electronic Mail ; Forced Expiratory Volume ; Humans ; Hypersensitivity ; Lung Diseases, Obstructive ; Population Characteristics ; Pulmonary Disease, Chronic Obstructive ; Smoke ; Smoking ; Specialization* ; Tuberculosis

PURPOSE: Although mild to moderate asthma is much more common, the morbidity and mortality of severe asthma are much higher. This study was performed to identify and analyze the clinical characteristics of severe asthma in Korea. METHODS: We registered patients with severe refractory asthma into the Severe Asthma Registry supported by the Severe Asthma Work Group of the Korean Academy of Asthma, Allergy and Clinical Immunology. Patients were enrolled since 2010 from the 15 university hospitals nationwide in Korea. Severe asthma was defined according to modified European Respiratory Society/American Thoracic Society criteria. Information on demographics, medical history, pulmonary function tests and skin prick tests was collected; the clinical characteristics of severe asthmatics were analyzed from the collected data. RESULTS: A total of 489 patients were enrolled with a mean age of 62.3; 45% are male. Sixty percent of patients received Global Initiative for Asthma step 4 treatment, and 30% received step 5 treatment. The most common comorbidities were allergic rhinitis (58.7%). Aspirin hypersensitivity was observed in 14.0%. Approximately half (53.9%) are non-smokers. Atopy was proven in 38.5% of the patients. Regarding asthma medications, inhaled corticosteroids and long-acting β-agonist combination inhalers were most commonly prescribed (96.5%), followed by leukotriene antagonists (71.0%). A recombinant anti-immunoglobulin E monoclonal antibody (omalizumab) has been used in 1.8% of the patients. The mean forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC were 78.7%, 67.5% and 67.9% of predicted values, respectively. The mean Asthma Control Test and quality of life questionnaire scores were 16.5 out of 25 and 59.5 out of 85, respectively. CONCLUSIONS: The baseline characteristics of severe asthma patients in the Korea Severe Asthma Registry were analyzed and reported for the first time. With this cohort, further prospective studies should be performed to search for ways to improve management of severe refractory asthma.
Adrenal Cortex Hormones ; Adult* ; Allergy and Immunology ; Aspirin ; Asthma* ; Cohort Studies ; Comorbidity ; Demography ; Forced Expiratory Volume ; Hospitals, University ; Humans ; Hypersensitivity ; Korea* ; Leukotriene Antagonists ; Male ; Mortality ; Nebulizers and Vaporizers ; Prospective Studies ; Quality of Life ; Respiratory Function Tests ; Rhinitis, Allergic ; Skin ; Vital Capacity