• Title/Summary/Keyword: Antibody therapy

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Severe Anemia Due to Parvovirus Infection Following Treatment with Rituximab in a Pediatric Kidney Transplant Recipient : Anemia after Treatment of Rituximab in Kidney Recipient Patient

  • Kim, Seung Yun;Lee, Hyoung Jin;Park, Eujin;Ahn, Yo Han;Ha, Il-Soo;Cheong, Hae Il;Kang, Hee Gyung
    • Childhood Kidney Diseases
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    • v.19 no.2
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    • pp.176-179
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    • 2015
  • Rituximab (RTX), a monoclonal antibody against the B-cell marker CD20, is commonly used as a treatment for antibody-mediated diseases or B-lymphocyte-mediated diseases. Destruction of B cells may reverse the disease course in many conditions; however, patients who are treated with RTX cannot respond appropriately to de novo infection due to lack of B lymphocytes. Here, we report one such case. A 7-year-old renal allograft recipient presented with severe anemia due to parvovirus infection after RTX treatment. The patient had focal segmental glomerulosclerosis and had received cadaveric kidney transplantation 6 months previously. She was treated with high-dose steroid for acute rejection and RTX for Epstein Barr Virus infection 3 months previously. At presentation, her hemoglobin level was 5.4 g/dL and leukocyte and platelet counts were normal. She had microcytic normochromic anemia and high viral load of parvovirus B19(70,578 copies/mL). Intravenous immunoglobulin ($200mg/kg{\cdot}d$) treatment controlled the progression of anemia and parvovirus infection. De novo parvovirus infection during the B lymphocyte-depletion period may have precipitated the severe anemia in this case. Close monitoring of infection is required after RTX therapy.

Tumor Imaging by Monoclonal Antibodies Labeled with Radioactive Metal Ions

  • Endo, K.;Sakahara, H.;Nakashima, T.;Koizumi, M.;Kunimatsu, M.;Ohta, H.;Furukawa, T.;Ohmomo, Y.;Arano, Y.;Yokoyama, A.;Okada, K.;Yoshida, O.;Hosoi, S.
    • The Korean Journal of Nuclear Medicine
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    • v.18 no.2
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    • pp.77-85
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    • 1984
  • Monoclonal antibodies have become widely investigated in the Nuclear Oncology, especially in the radioimmunosassay of tumor markers and in vivo radioimmunoimaging of cancer. However, there are numerous factors as to whether radioimmunoimaging will ultimately successful. For imaging of tumors, metallic radionuclides such as In-111, Ga-67, Tc-99m have favorable nuclear properties than widely used I-131. These radioistopes have characteristics of the useful radiation for imaging, convenient short half-lives and the simple and rapid radiolabeling of monoclonal antibodies by using bifunctional chelaing agents. The obtained chelate-tagged antibodies are quite stable both in vitro and in vivo, without interfering antibody activities and animal experiments provided a good basis for its clinical applicability for the radioimmunoimaging of cancer. Much attention has also been given to the possibility, only beginning to be exploited, of the specific treatment of malignant neoplasms with these agents. Although specific antibody has not been developed that is uniquely specific for cancer alone and there are still many questions to be answered and problems to be overcome before radioimmunoimaging can be successfully used in ptients with cancer, these methods can be applied to the coupling of monoclonal antibodies with anti-neoplastic drugs or radionuclides suitable for internal radiation therapy of cancer.

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CD7-Specific Single Chain Antibody Mediated Delivery of siRNA to T Cells Inhibits HIV Replication in a Humanized Mouse Model

  • Ban, Hong-Seok;Kumar, Priti;Kim, Na-Hyun;Choi, Chang-Son;Shankar, Premlata;Lee, Sang-Kyung
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2008.05a
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    • pp.62-64
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    • 2008
  • A major hurdle to the development of RNA interference as therapy for HIV infection is the delivery of siRNA to T lymphocytes which are difficult cells to transfect even in vitro. We have employed a single chain antibody to the pan T cell surface antigen CD7 was conjugated to an oligo-9-arginine peptide (scFvCD7-9R) for T cell-specific siRNA delivery in NOD/SCIDIL2${\gamma}$-/- mice reconstituted with human peripheral blood lymphocytes (Hu-PBL). Using a novel delivery, we first show that scFvCD7-9R efficiently delivered CD4 siRNA into human T cells in vitro. In vivo administration to Hu-PBL mice resulted in reduced levels of surface CD4 expression on T cells. Mice infected with HIV-1 and treated on a weekly basis with scFvCD7-9R-siRNA complexes targeting a combination of viral genes and the host coreceptor molecule CCR5 successfully maintained CD4/CD3 T cell ratios up to 4 weeks after infection in contrast to control mice that displayed a marked reduction in CD4 T cell numbers. p24 antigen levels were undetectable in 3 of the 4 protected mice. scFvCD7-9R/antiviral siRNA treatment also helped maintain CD4 T cell numbers with reduced plasma viral loads in Hu-PBL mice reconstituted with PBMC from donors seropositive for HIV, indicating that this method can contain viral replication even in established HIV infections. Our results show that scFvCD7-9R could be further developed as a potential therapeutic for HIV-1 infection.

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Association of p53 Protein Expression with Clinical Outcome in Advanced Supralottic Cancer (진행된 성문 상부암 환자에서 p53의 발현과 임상적 의의)

  • Kang, Jing-Oh;Hong, Seong-Eong
    • Radiation Oncology Journal
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    • v.16 no.1
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    • pp.1-6
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    • 1998
  • Purpose : To determine the incidence and prognostic effect of p53 expression in patients with advanced supralottic cancer. Materials : Twenty-one cases of total 48 advanced supraglottic cancer patients who received postoperative adjuvant radiation therapy were evaluated by immunohistochemical staining employing p53 monoclonal antibody. Result : Three out of six stage III patients and four out of fifteen stage IV patients showed p53 expression without statistically significant difference (p=0.608). Five year survival rates are $93\%$ in p53 negative, $80\%$ in p53 positive patients and there was no significant difference(p=0.776). p53 expression does not show statistically significant correlation with primary tumor status(p=0.877), lymph node status(p=0.874) and age(p=0.64). Conclusion : There was no statistically significant correlation between traditionally known risk factors and p53 expression.

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Effect of fractional ablative carbon dioxide laser with lidocaine spray on skin flap survival in rats

  • Choi, Manki;Park, Youngsoo;Kim, Yong-Ha;Chung, Kyu Jin
    • Archives of Craniofacial Surgery
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    • v.20 no.4
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    • pp.239-245
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    • 2019
  • Background: Lidocaine spray is a local anesthetic that improves random-pattern skin flap survival. The fractional ablative carbon dioxide laser (FxCL) produces vertical microchannels that delivers topically applied drugs to the skin. In this study, we hypothesized that FxCL therapy would enhance the lidocaine effect to improve random-pattern skin flap survival in rats. Methods: McFarlane random-pattern skin flaps were elevated in 48 rats, which were divided into four groups according to treatment: FxCL+lidocaine, FxCL, lidocaine, and nontreatment (control). On postoperative day 7, necrotic flap areas, the number of capillary vessels, and neutrophil count were evaluated. Anti-rat vascular endothelial growth factor (VEGF) and CD31 antibody activity were also evaluated by immunohistochemical staining. Results: Flap survival rate was $53.41%{\pm}5.43%$, $58.16%{\pm}4.80%$, $57.08%{\pm}5.91%$, and $69.08%{\pm}3.20%$ in the control, lidocaine, FxCL, and FxCL+lidocaine groups, respectively. Mean neutrophil count in the intermediate zone excluding the necrotic tissue was $41.70{\pm}8.40$, $35.43{\pm}6.41$, $37.23{\pm}7.15$, and $27.20{\pm}4.24cells/field$ in the control, lidocaine, FxCL, and FxCL+lidocaine groups, respectively. Anti-rat VEGF and CD31 antibody activity were the highest in the FxCL+lidocaine group. Conclusion: FxCL with lidocaine had a positive effect on random-pattern skin flap survival in rats. Thus, FxCL with lidocaine spray should be considered as a new treatment option to improve flap viability.

Selective tyrosine conjugation with a newly synthesized PCB -TE2A-luminol bifunctional chelator

  • Subramani Rajkumar;Hyun Park;Abhinav Bhise;Seong Hwan Cho;Jung Young Kim;Kyo Chul Lee;Jeongsoo Yoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.7 no.2
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    • pp.85-91
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    • 2021
  • Selective amino acid conjugation of bulky antibodies is a valuable asset for real-time diagnosis and therapy. However, selective conjugation incorporating a chelate-bearing radioactive atom into an antibody without affecting its immunoreactivity is a challenging task. A bifunctional chelator (BFC), a selective amino acid-targeting probe, and a linker have been developed to overcome this problem. Here, we report the synthesis of a novel propylene cross-bridged chelator (PCB)-1,8-N,N'-bis-(carboxymethyl)-1,4,8,11-tetraazacyclotetradecane (TE2A)-luminol BFC via a click reaction and radiolabel it with a 64Cu ion for tyrosine-selective conjugation of trastuzumab. In the initial optimization study, we tried different oxidative addition conditions such as electro-oxidation, hemin, horseradish peroxidase, iodogen tube, chloramine-T, and iodo beads. In this study, up to 82% of 64Cu-PCB-TE2A-luminol was conjugated with the antibody in an iodo bead-catalyzed oxidative addition reaction with an isolated yield of 24.4%.

Incidence of Low Seroimmunity to Hepatitis B Virus in Children with Inflammatory Bowel Disease: A Single Center Experience

  • Hala H. Mansour ;Ayman E. Eskander;Sara M. Osman;Normeen H. Rady
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.27 no.2
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    • pp.104-112
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    • 2024
  • Purpose: Immunosuppressive therapy is frequently administered to patients with inflammatory bowel disease (IBD), which may make them more susceptible to infections like hepatitis B. Methods: A cross-sectional study was conducted on patients aged 5-18 years diagnosed with IBD who visited a gastroenterology clinic along with controls who were the same age as the patients with IBD and were healthy overall. A logistic regression analysis using the independent variables of age, sex, race, disease phenotype, surgery, and medications and the dependent variable of adequate hepatitis B surface antibody (HBsAb) titers (>10 mIU/mL) was performed on quantitative serum HBsAb titers. Results: The study enrolled 62 patients, including 37 males and 25 females. Crohn's disease, ulcerative colitis, and indeterminate colitis were diagnosed in 16, 22, and 24 patients, respectively. Thirty-nine patients were taking corticosteroids at the time of the study, 42 were taking immunomodulators, and four were taking biologics. Compared to 44.7% of the control group, 9.3% of the patients had protective titers. Only 12 out of 62 patients had HBsAb titers greater than 10 million IU/mL. None of the patients who received biologics or corticosteroids and 3.2% of those who received immunomodulators were found to be seroimmuned. Conclusion: The younger patients had the highest titers. Patient-specific factors that may impact these low titers include the length of the patient's illness and the use of immunosuppressants.

Evaluation of Protective Immune Response Induced by a DNA Vaccine Encoding GRA8 against Acute Toxoplasmosis in a Murine Model

  • Chu, Jia-Qi;Huang, Shuai;Ye, Wei;Fan, Xuan-Yan;Huang, Rui;Ye, Shi-Cai;Yu, Cai-Yuan;Wu, Wei-Yun;Zhou, Yu;Zhou, Wei;Lee, Young-Ha;Quan, Juan-Hua
    • Parasites, Hosts and Diseases
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    • v.56 no.4
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    • pp.325-334
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    • 2018
  • Toxoplasma gondii is an apicomplexan zoonotic protozoan parasite that infects most species of warm-blooded animals, including humans. The heavy incidence and severe or lethal damage caused by T. gondii infection clearly indicate a need for the development of an effective vaccine. T. gondii GRA8 is a member of the dense granules protein family and is used as a marker of acute infection. In the present study, we evaluated the protective immunity induced by DNA vaccination based on a recombinant eukaryotic plasmid, pDsRed2-GRA8, against acute toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with the pDsRed2-GRA8 plasmid and then challenged by infection with the highly virulent GFP-RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii of this vaccine were analyzed by measuring cytokine and serum antibody titers, splenocyte proliferation assays, and the survival times of mice after challenge. Our results showed that mice immunized with pDsRed2-GRA8 demonstrated specific humoral and cellular responses, induced higher IgG antibody titers with predominant IgG2a production; increased levels of IL-10, IL-12 (p70), $IFN-{\gamma}$, $TNF-{\alpha}$, and splenocyte proliferation; and prolonged survival times compared to those of control mice. The present study showed that DNA immunization with pDsRed2-GRA8 induced humoral and cellular immune responses, and all immunized mice showed greater Th1-type immune responses and longer survival times than those of control mice. These results indicated that T. gondii GRA8 DNA immunization induces a partial protective effect against acute toxoplasmosis.

Type I immune-mediated polyarthritis with azathioprine therapy in a Shih-tzu dog

  • Jung, Dong-In;Park, Chul;Kang, Byeong-Teck;Kim, Ju-Won;Kim, Ha-Jung;Lim, Chae-Young;Ko, Ki-Jin;Lee, So-Young;Cho, Sue-Kyung;GU, Su-Hyun;Heo, Ra-Young;Park, Hyo-Jin;Jeon, Hyo-Won;Kim, Jung-Hyun;Han, Sung-Kuk;Yoon, Ah-Ram;Sung, Ju-Heon;Yoo, Jong-Hyun;Park, Hee-Myung
    • Korean Journal of Veterinary Research
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    • v.46 no.4
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    • pp.395-398
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    • 2006
  • A 2-month-old female Shih-tzu dog was referred because of lameness, exercise intolerance, depression, elbow and stifle joint swelling. Physical examination, complete blood counts, serum-chemistry, radiography, synovial fluid analysis, antinuclear antibody test, and rheumatoid factor measurement were initiated. On radiography, soft tissue swelling of elbow and stifle joints without erosiveness were founded. The results of synovial fluid analysis revealed severe neutrophilic pleocytosis (nondegenerative), decreased viscosity, increased turbidity, positive on mucin-clot test, and negative on bacterial culture. The results of rheumatoid factor measurement and antinuclear antibody test were negative and below 1 : 40, respectively. Based on all tests, we diagnosed this case as juvenile onset type I immune-mediated polyarthritis. Azathioprine (1 mg/kg body weight, per os q 24 h, for 4 weeks) was then administered and clinical signs improved gradually. Four weeks after azathioprine administration, clinical signs were disappeared. This report describes the clinical findings, imaging characteristics, synovial fluid findings, and other laboratory results of type I immune-mediated polyarthritis and successful management with azathioprine therapy.

The Significance of Serum Thyroid Peroxidase as a New Tumor Marker in Papillary Thyroid Carcinoma after Thyroidectomy (유두상 갑상선암의 수술후 재발예측인자로서 혈청 Thyroid Peroxidase의 의의)

  • Chang Hang-Seok;Na Jae-Wung;Chung Woong-Youn;Park Cheong-Soo
    • Korean Journal of Head & Neck Oncology
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    • v.15 no.1
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    • pp.46-51
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    • 1999
  • Background: Total thyroidectomy and postoperative radiodiodine ablation therapy in differentiated thyroid carcinomas enhance the reliability of serum thyroglobulin(Tg) levels and radioiodine scan in detecting recurrence or distant metastasis. There have been, however, some limitations in using these methods under certain conditions. Recently, several reports have indicated that thyroid peroxidase(TPO) could be used as an alternative tumor marker. We aimed to estimate the significance of serum TPO levels in differentiated thyroid carcinoma. Materials and Methods: Forty-eight patients who had undergone total thyroidectomy due to papillary thyroid carcinomas and who had been followed-up for at least 3 years were classified into two groups: 27 patients without any evidence of recurrence in group 1; and 20 patients with recurrence or distant metastasis in group 2. All patients were examined by radioiodine scans. Serum Tg, TSH, antithyroglobulin antibody, and TPO were measured and the relationships were statistically analyzed. The sensitivity and specificity of $^{131}I$ scan, serum Tg, and serum TPO were evaluated. Results: Serum Tg levels were $3.81{\pm}5.16ng/mL$ in group 1 and $147.02{\pm}193.75ng/mL$ in group 2. Only 2 patients in group 1 showed Tg levels exceeding 10ng/mL. In contrast, 4 patients in group 2 were under 10ng/mL. Serum antithyroglobulin antibody and TSH levels showed no statistical difference between the two groups. In group 1, 16 patients showed negative serum TPO results, and 4 patients in group 2 showed negative results. There was no correlation among serum Tg levels, antithyroglobulin antibody titers, and serum TPO levels in each group. In group 2, 4 patients with negative serum Tg levels showed positive TPO results and positive whole body scans. Two cases with false negative $^{131}I$ scans showed positive serum TPO and Tg results. In 4 cases showing false negative serum TPO levels, serum Tg levels and $^{131}I$ scans were positive. Conclusion: Serum Tg levels, radioiodine scans, and serum TPO levels can be clinically used as complementary methods in the diagnosis of recurrent or metastatic thyroid carcinomas. Serum TPO levels may be helpful when other methods fail to detect recurrences or distant metastasis in highly suspected patients.

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