1.IL-2 Pathway Blocking in Combination with Anti-CD154 Synergistically Establishes Mixed Macrochimerism with Limited Dose of Bone Marrow Cells and Prolongs Skin Graft Survival in Mice.
Jeong Hoon LEE ; Jongwon HA ; Shi Hwa KIM ; Sang Joon KIM
Journal of Korean Medical Science 2006;21(6):1005-1011
To facilitate the establishment of mixed chimerism with limited dose of bone marrow (BM) cells, and to achieve tolerance in skin graft model, combined blocking of costimulatory pathway and IL-2 pathway was used in minimally myeloablative model using busulfan. BM cells (2.5 x 10(7)) of BALB/c were injected into C57BL/6 mice at day 0 with full thickness skin graft after single dose injection of busulfan (25 mg/kg) on day-1. Recipients were grouped and injected the anti-CD154, CTLA4-Ig, anti-IL-2R at days 0, 2, 4, and 6 according to protocol. Mixed macrochimerism were induced in groups treated with anti-CD154+anti-CTLA4-Ig, anti-CD154+anti-IL-2R, and anti-CD154+anti-CTLA4 Ig+anti-IL-2R. Three groups having chimerism enjoyed prolonged graft survival more than 6 months. Superantigen deletion study revealed deletion of alloreactive T cells in combined blockade treated groups. In graft versus host disease model using CFSE staining, CD4+ T cell and CD8+ T cell proliferation were reduced in groups treated with CTLA4-Ig or anti-IL-2R or both in combination with anti-CD154. However, anti-IL-2R was not so strong as CTLA4-Ig in terms of inhibition of T cell proliferation. In conclusion, IL-2 pathway blocking combined with anti-CD154 can establish macrochimerism with limited dose of BM transplantation and induce specific tolerance to allograft.
Skin Transplantation/*immunology/methods
;
Mice, Inbred BALB C
;
Mice
;
Male
;
Interleukin-2/*immunology
;
Immunoconjugates/*administration & dosage
;
Graft Survival/*immunology
;
Drug Combinations
;
CD40 Ligand/*immunology
;
Bone Marrow Transplantation/*immunology/methods
;
Antibodies/*administration & dosage/immunology
;
Animals
2.IL-2 Pathway Blocking in Combination with Anti-CD154 Synergistically Establishes Mixed Macrochimerism with Limited Dose of Bone Marrow Cells and Prolongs Skin Graft Survival in Mice.
Jeong Hoon LEE ; Jongwon HA ; Shi Hwa KIM ; Sang Joon KIM
Journal of Korean Medical Science 2006;21(6):1005-1011
To facilitate the establishment of mixed chimerism with limited dose of bone marrow (BM) cells, and to achieve tolerance in skin graft model, combined blocking of costimulatory pathway and IL-2 pathway was used in minimally myeloablative model using busulfan. BM cells (2.5 x 10(7)) of BALB/c were injected into C57BL/6 mice at day 0 with full thickness skin graft after single dose injection of busulfan (25 mg/kg) on day-1. Recipients were grouped and injected the anti-CD154, CTLA4-Ig, anti-IL-2R at days 0, 2, 4, and 6 according to protocol. Mixed macrochimerism were induced in groups treated with anti-CD154+anti-CTLA4-Ig, anti-CD154+anti-IL-2R, and anti-CD154+anti-CTLA4 Ig+anti-IL-2R. Three groups having chimerism enjoyed prolonged graft survival more than 6 months. Superantigen deletion study revealed deletion of alloreactive T cells in combined blockade treated groups. In graft versus host disease model using CFSE staining, CD4+ T cell and CD8+ T cell proliferation were reduced in groups treated with CTLA4-Ig or anti-IL-2R or both in combination with anti-CD154. However, anti-IL-2R was not so strong as CTLA4-Ig in terms of inhibition of T cell proliferation. In conclusion, IL-2 pathway blocking combined with anti-CD154 can establish macrochimerism with limited dose of BM transplantation and induce specific tolerance to allograft.
Skin Transplantation/*immunology/methods
;
Mice, Inbred BALB C
;
Mice
;
Male
;
Interleukin-2/*immunology
;
Immunoconjugates/*administration & dosage
;
Graft Survival/*immunology
;
Drug Combinations
;
CD40 Ligand/*immunology
;
Bone Marrow Transplantation/*immunology/methods
;
Antibodies/*administration & dosage/immunology
;
Animals
3.A Clinical Analysis of Treatment of Cervical Fracture and Dislocation.
Tae Sup LEE ; Won Hyuck LEE ; Shi Hyun CHO ; Jae Oh KIM ; Ki Won SUNG ; Hwa Yong RHEE
Journal of Korean Neurosurgical Society 1986;15(4):681-690
Recently, the authors experienced the thirty-one cases of cervical fracture and dislocation. Among them, nineteen cases underwent surgical treatment and remained conservative treatment. There are three ways in operation ; 1) anterior approach(Cloward, Smith-Robinson method). 2) posterior approach. 3) combined approach(modified Smith-Robinson and posterior fusion). We did a combined approach and the results were excellent.
Dislocations*
4.Incidence and Clinical Characteristics of Patients with Tinnitus According to Diagnostic Classification.
Hwa Jong YOO ; Shi Nae PARK ; Dong Kee KIM ; Kyoung Ho PARK ; Min Ji KIM ; Ji Eun KIM ; A Ri KIM ; Sang Won YEO
Korean Journal of Otolaryngology - Head and Neck Surgery 2011;54(6):392-398
BACKGROUND AND OBJECTIVES: Knowledge about the incidence and clinical characteristics of tinnitus can be useful for diagnostic approach and treatment plan. We analyzed the incidence and clinical characteristics of each case of tinnitus according to the classification of tinnitus. SUBJECTS AND METHOD: The study recruited 211 tinnitus patients who visited tinnitus clinic from March 2009 to August 2009. First, patients were diagnosed and classified as sensorineural tinnitus and somatosounds. Somatosounds were subdivided to vascular tinnitus, muscle origin tinnitus and patulous Eustachian tube. Patients were evaluated by history taking by means of having them fill out tinnitus questionnaires and psychoacoustic questionnaires. Audiologic findings of each type of tinnitus have also been analyzed. RESULTS: Incidences of sensorineural tinnitus and somatosounds were 82.9% and 17.1% respectively. Among somatosounds, vascular tinnitus occupied 7.6%, muscle origin tinnitus, 4.3% and patulous Eustachian tube, 5.2%. The mean age of the patients with sensorineural tinnitus was older than somatosounds. Patients with muscle origin tinnitus had higher scores of tinnitus loudness, effect on life, tinnitus handicap inventory, stress and depression than those with other types of tinnitus. Overall compliance of the treatment was 66.7% and their tinnitus had been significantly improved after treatment. CONCLUSION: With the knowledge of incidence, clinical characteristics and treatment approach for each tinnitus, clinicians can be more confident in providing proper diagnosis and management of patients with tinnitus. Somatosounds, which showed relatively high incidence in this study, should not be neglected but properly treated with early diagnosis.
Compliance
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Depression
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Early Diagnosis
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Eustachian Tube
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Humans
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Incidence
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Muscles
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Psychoacoustics
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Surveys and Questionnaires
;
Tinnitus
5.Immune Correlates of Resistance to Trichinella spiralis Reinfection in Mice.
Ki Back CHU ; Sang Soo KIM ; Su Hwa LEE ; Dong Hun LEE ; Ah Ra KIM ; Fu Shi QUAN
The Korean Journal of Parasitology 2016;54(5):637-643
The immune correlate of host resistance induced by reinfection of Trichinella spiralis remains unclear. In this study, we investigated immune correlates between the resistance and serum IgG antibody level, CD23⁺ IgM⁺ B cells, and eosinophil responses induced by T. spiralis reinfection. Mice were primarily infected with 10 or 100 T. spiralis larvae (10 TS, 100 TS), respectively, and after 4 weeks, they were challenge infected with 100 T. spiralis larvae (10–100 TS, 100-100 TS). Upon challenge infections, 10–100 TS mice induced significantly higher levels of T. spiralis-specific total IgG antibody responses in sera and antibody secreting cell responses in spleens compared to 100-100 TS mice, resulting in significantly reduced worm burdens in 10–100 TS mice (60% and 70% reductions for adult and larvae, respectively). Higher levels of eosinophils were found in mice primarily infected with 10 TS compared to those of 100 TS at week 8 upon challenge. CD23+ IgM+ B cells were found to be increased significantly in mice primarily infected with 10 TS. These results indicate that primary infection of 10 larvae of T. spiralis, rather than 100 larvae, induces significant resistance against reinfection which closely correlated with T. spiralis-specific IgG, eosinophil, and CD23+ IgM+ B cell responses.
Adult
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Animals
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Antibody Formation
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B-Lymphocytes
;
Eosinophils
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Humans
;
Immunoglobulin G
;
Larva
;
Mice*
;
Spleen
;
Trichinella spiralis*
;
Trichinella*
6.A Case of Nonspecific Interstitial Pneumonia in a Patient with Ulcerative Colitis.
Young Wook NOH ; Eun Kyung BAIK ; Yon Ju RYU ; Seong Eun KIM ; Jin Hwa LEE ; Sung Shin SIM ; Shi Nae LEE ; Eun Mi CHUN
Tuberculosis and Respiratory Diseases 2007;62(1):56-61
Pulmonary complications of ulcerative colitis are relatively uncommon and may present as a variety of disorders. Ulcerative colitis-related interstitial lung disease is extremely rare. There are a few case reports of nonspecific interstitial pneumonia in ulcerative colitis worldwide but none in Korea. We report a patient with ulcerative colitis related biopsy-proven nonspecific interstitial pneumonia, who responded to prednisolone (1 mg/kg) and mesalazine therapy
Colitis, Ulcerative*
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Humans
;
Korea
;
Lung Diseases, Interstitial*
;
Mesalamine
;
Prednisolone
;
Ulcer*
7.Virus-like Particle Vaccine Containing Toxoplasma gondii Rhoptry Protein 13 Induces Protection against T. gondii ME49 Infection in Mice
Hae Ji KANG ; Ki Back CHU ; Su Hwa LEE ; Min Ju KIM ; Hyunwoo PARK ; Hui JIN ; Fu Shi QUAN
The Korean Journal of Parasitology 2019;57(5):543-547
Toxoplasma gondii can infect humans worldwide, causing serious diseases in pregnant women and immunocompromised individuals. T. gondii rhoptry protein 13 (ROP13) is known as one of the key proteins involved in host cell invasion. In this study, we generated virus-like particles (VLPs) vaccine expressing T. gondii rhoptry ROP13 and investigated VLPs vaccine efficacy in mice. Mice immunized with ROP13 VLPs vaccine elicited significantly higher levels of T. gondii-specific IgG, IgG1, IgG2a, and IgA antibody responses following boost immunization and challenge infection, whereas antibody inductions were insignificant upon prime immunization. Differing immunization routes resulted in differing antibody induction, as intranasal immunization (IN) induced greater antibody responses than intramuscular immunization (IM) after boost and challenge infection. IN immunization induced significantly higher levels of IgG and IgA antibody responses from feces, antibody-secreting cells (ASCs), CD4⁺ T, CD8⁺ T cells and germinal center B cell responses in the spleen compared to IM immunization. Compared to IM immunization, IN immunization resulted in significantly reduced cyst counts in the brain as well as lesser body weight loss, which contributed to better protection. All of the mice immunized through either route survived, whereas all naïve control mice perished. These results indicate that the ROP13 VLPs vaccine could be a potential vaccine candidate against T. gondii infection.
Animals
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Antibody Formation
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Antibody-Producing Cells
;
Body Weight
;
Brain
;
Feces
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Female
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Germinal Center
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Humans
;
Immunization
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Immunoglobulin A
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Immunoglobulin G
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Mice
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Pregnant Women
;
Spleen
;
T-Lymphocytes
;
Toxoplasma
8.Maternal and Neonatal Outcomes in Pregnant Women With Coronavirus Disease 2019 in Korea
Youseung CHUNG ; Eun Jin KIM ; Hee-Sung KIM ; Kyung-Hwa PARK ; Ji Hyeon BAEK ; Jungok KIM ; Ji Yeon LEE ; Chang-Seop LEE ; Seungjin LIM ; Shin-Woo KIM ; Eu Suk KIM ; Hye Jin SHI ; Shin Hee HONG ; Jae-Bum JUN ; Kyung-Wook HONG ; Jae-Phil CHOI ; Jinyeong KIM ; Kyung Sook YANG ; Young Kyung YOON
Journal of Korean Medical Science 2022;37(41):e297-
Background:
This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19.
Methods:
This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021.
Results:
A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04–1.15) and parity (OR, 1.703, 95% CI, 1.13–2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns’ amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2.
Conclusion
At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.
9.Induction of Myeloma Cell Line-specific Cytotoxic T Lymphocytes using Monocyte-derived Dendritic Cells Pulsed with Myeloma Cell Line Lysates.
Myong Suk PARK ; Jung Sun PARK ; Hyun Kyu KANG ; Sang Ki KIM ; Jong Ho WON ; Bo Hwa CHOI ; Shi Won SHIN ; Xiao Wei ZHU ; Chun Ji JIN ; Thanh Nhan Nguyen PHAM ; Duck CHO ; Jong Hee NAM ; Young Jin KIM ; Yeo Kyeoung KIM ; Deok Hwan YANG ; Ik Joo CHUNG ; Hyeoung Joon KIM ; Je Jung LEE
Korean Journal of Hematology 2006;41(3):186-193
BACKGROUND: In multiple myeloma (MM), the idiotype (ID) determinant of the paraprotein has been used for immunotherapy using dendritic cells (DCs). However, ID-specific immune responses showed limited clinical responses after the Id vaccination. Therefore, an alternative approach using DCs pulsed with other tumor antigens is required. METHODS: We investigated the possibility of immunotherapy for MM using myeloma cell line-specific cytotoxic T lymphocytes (CTLs), that were stimulated in vitro by monocyte-derived DCs pulsed with the myeloma cell line ysates. CD14+ cells isolated from the peripheral blood of HLA-A0201+ healthy donors were cultured in the presence of GM-CSF and IL-4. On day 6, the immature DCs were pulsed with the myeloma cell line lysates (IM-9: HLA0201+ and ARH-77: HLA0201+), and then maturation of DCs was induced by the addition of TNF- alpha for 2 days. CTL lines were generated by a 2 time stimulation with DCs to the autologous CD3+ T cells. RESULTS: DCs pulsed with myeloma cell lysates showed the production of IL-12p70, but less than that of unpulsed DCs. CTLs lines stimulated with the DCs pulsing, for the myeloma cell line lysates, showed potent cytotoxic activities against autologous target cells, but not against HLA-A2-cell lines (RPMI-8226). Mature DCs pulsed with the myeloma cell line lysates showed a higher stimulatory capacity for autologous CTL when compared with mature non-pulsed DCs. CONCLUSION: These results suggest that DCs pulsed with the myeloma cell line lysates can generate potent myeloma cell line-specific CTLs for the myeloma cell-based immunotherapeutic approach in MM.
Antigens, Neoplasm
;
Cell Line*
;
Dendritic Cells*
;
Granulocyte-Macrophage Colony-Stimulating Factor
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Humans
;
Immunotherapy
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Interleukin-4
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Multiple Myeloma
;
T-Lymphocytes
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T-Lymphocytes, Cytotoxic*
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Tissue Donors
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Vaccination
10.Results of Active Middle Ear Implantation in Patients With Mixed Hearing Loss After Middle Ear Surgery: A Prospective Multicenter Study (the ROMEO Study)
Chan Il SONG ; Hyong-Ho CHO ; Byung Yoon CHOI ; Jae Young CHOI ; Jin Woong CHOI ; Yun-Hoon CHOUNG ; Jong Woo CHUNG ; Won-Ho CHUNG ; Sung Hwa HONG ; Yehree KIM ; Byung Don LEE ; Il-Woo LEE ; Jong Dae LEE ; Jun Ho LEE ; Kyu-Yup LEE ; Il Joon MOON ; In Seok MOON ; Seung-Ha OH ; Hong Ju PARK ; Shi Nae PARK ; Ji Won SEO
Clinical and Experimental Otorhinolaryngology 2022;15(1):69-76
Objectives:
. This study was conducted to evaluate the user satisfaction, efficacy, and safety of round window (RW) vibroplasty using the Vibrant Soundbridge (VSB) in patients with persistent mixed hearing loss after mastoidectomy.
Methods:
. The study included 27 patients (mean age, 58.7 years; age range, 28–76 years; 11 men and 16 women) with mixed hearing loss after mastoidectomy from 15 tertiary referral centers in Korea. The VSB was implanted at the RW. The Korean translation of the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire and the Korean version of the International Outcome Inventory for Hearing Aids (K-IOI-HA) questionnaire were used to evaluate user satisfaction as the primary outcome. The secondary outcome measures were audiological test results and complication rates.
Results:
. The mean scores for ease of communication (61.3% to 29.7% to 30.2%), reverberation (62.1% to 43.1% to 37.4%), and background noise (63.3% to 37.7% to 34.3%) subscales of the APHAB questionnaire significantly decreased after VSB surgery. The mean K-IOI-HA scores at 3 and 6 months after surgery were significantly higher than the mean preoperative score (18.6 to 27.2 to 28.1). The postoperative VSB-aided thresholds were significantly lower than the preoperative unaided and hearing aid (HA)-aided thresholds. There was no significant difference between preoperative unaided, preoperative HA-aided, and postoperative VSB-aided maximum phonetically balanced word-recognition scores. None of the 27 patients experienced a change in postoperative bone conduction pure tone average. One patient developed temporary facial palsy and two developed surgical wound infections.
Conclusion
. RW vibroplasty resulted in improved satisfaction and audiological test results in patients with mixed hearing loss after mastoidectomy, and the complication rate was tolerable.