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    Jongyoun Kim

    This study explores a methodology solely dependent on remote sensing information to capture both the current climate signal and the spatial variability of daily potential evaporation (PE) by taking advantage of the new generation of Earth... more
    This study explores a methodology solely dependent on remote sensing information to capture both the current climate signal and the spatial variability of daily potential evaporation (PE) by taking advantage of the new generation of Earth Observation satellites (i.e., MODIS sensor). PE, a required input for most hydrologic models, is typically obtained from pan evaporation estimates, or in some cases,
    ABSTRACT The current study investigates a method to provide land surface parameters [i.e., land surface temperature (LST) and normalized difference vegetation index (NDVI)] at a high spatial (˜30 and 60 m) and temporal (daily and 8-day)... more
    ABSTRACT The current study investigates a method to provide land surface parameters [i.e., land surface temperature (LST) and normalized difference vegetation index (NDVI)] at a high spatial (˜30 and 60 m) and temporal (daily and 8-day) resolution by combining advantages from Landsat and moderate-resolution imaging spectroradiometer (MODIS) satellites. We adopt a previously developed subtraction method that merges the spatial detail of higher-resolution imagery (Landsat) with the temporal change observed in coarser or moderate-resolution imagery (MODIS). Applying the temporal difference between MODIS images observed at two different dates to a higher-resolution Landsat image allows prediction of a combined or fused image (Landsat+MODIS) at a future date. Evaluation of the resultant merged products is undertaken within the Southeastern Arizona region where data is available from a range of flux tower sites. The Landsat+MODIS fused products capture the raw Landsat values and also reflect the MODIS temporal variation. The predicted Landsat+MODIS LST improves mean absolute error around 5°C at the more heterogeneous sites compared to the original satellite products. The fused Landsat+MODIS NDVI product also shows good correlation to ground-based data and is relatively consistent except during the acute (monsoon) growing season. The sensitivity of the fused product relative to temporal gaps in Landsat data appears to be more affected by uncertainty associated with regional precipitation and green-up, than the length of the gap associated with Landsat viewing, suggesting the potential to use a minimal number of original Landsat images during relatively stable land surface and climate conditions. Our extensive validation yields insight on the ability of the proposed method to integrate multiscale platforms and the potential for reducing costs associated with high-resolution satellite systems (e.g., SPOT, QuickBird, IKONOS).
    Future operational frameworks for estimating surface turbulent fluxes over the necessary spatial and temporal scales will undoubtedly require the use of remote sensing products. Techniques used to estimate surface fluxes from radiometric... more
    Future operational frameworks for estimating surface turbulent fluxes over the necessary spatial and temporal scales will undoubtedly require the use of remote sensing products. Techniques used to estimate surface fluxes from radiometric surface temperature generally fall into two categories: retrieval-based and data assimilation approaches. Up to this point, there has been little comparison between retrieval- and assimilation-based techniques. In this note, the triangle retrieval method is compared to a variational data assimilation approach for estimating surface turbulent fluxes from radiometric surface temperature observations. Results from a set of synthetic experiments and an application using real data from the First International Satellite Land Surface Climatology Project (ISLSCP) Field Experiment (FIFE) site indicate that the assimilation approach performs slightly better than the triangle method because of the robustness of the estimation to measurement errors and parsimon...
    This paper outlines the development of a continuous, daily time series of potential evapotranspiration (PET) using Moderate Resolution Imaging Spectroradiometer (MODIS) sensor data from the Terra satellite platform. The approach is based... more
    This paper outlines the development of a continuous, daily time series of potential evapotranspiration (PET) using Moderate Resolution Imaging Spectroradiometer (MODIS) sensor data from the Terra satellite platform. The approach is based on the Priestley–Taylor equation, incorporating a daily net radiation model during cloudless days. A simple algorithm using “theoretical clear-sky” net radiation (incorporating daily cloud fraction and cloud optical thickness) and PET is then used to estimate net radiation and PET under cloudy conditions. The method requires minimal ground-based observations for initial calibration of regional radiation algorithm coefficients. Point-scale comparisons are undertaken at four flux-tower sites in North America covering a range of hydroclimatic conditions and biomes. Preliminary results at the daily time step for a 4-yr period (2001–04) show good correlation (R2 = 0.89) and low bias (0.34 mm day−1) for three of the more humid sites. Results are further i...
    Satellite-derived potential evapotranspiration (PET) estimates computed from Moderate Resolution Imaging Spectroradiometer (MODIS) observations and the Priestley–Taylor formula (M-PET) are evaluated as input to the Hydrology Laboratory... more
    Satellite-derived potential evapotranspiration (PET) estimates computed from Moderate Resolution Imaging Spectroradiometer (MODIS) observations and the Priestley–Taylor formula (M-PET) are evaluated as input to the Hydrology Laboratory Research Distributed Hydrologic Model (HL-RDHM). The HL-RDHM is run at a 4-km spatial and 6-h temporal resolution for 13 watersheds in the upper Mississippi and Red River basins for 2003–10. Simulated discharge using inputs of daily M-PET is evaluated for all watersheds, and simulated evapotranspiration (ET) is evaluated at two watersheds using nearby latent heat flux observations. M-PET–derived model simulations are compared to output using the long-term average PET values (default-PET) provided as part of the HL-RDHM application. In addition, uncalibrated and calibrated simulations are evaluated for both PET data sources. Calibrating select model parameters is found to substantially improve simulated discharge for both datasets. Overall average perc...
    ... BLU consists of many parts such as light sources, a light guide panel (LGP) for edge-lit type BLU, a diffuser plate for direct-lit type BLU, several optical films, mold frames, driving ... [ 8 ] Sumitomo 3M, in Liquid Crystal Display... more
    ... BLU consists of many parts such as light sources, a light guide panel (LGP) for edge-lit type BLU, a diffuser plate for direct-lit type BLU, several optical films, mold frames, driving ... [ 8 ] Sumitomo 3M, in Liquid Crystal Display Backlight, edited by S. Mikoshiba and S. Lim (Science & ...
    Silibinin has been known for its role in anti-cancer and radio-protective effect. Radiation therapy for treating lung cancer might lead to late-phase pulmonary inflammation and fibrosis. Thus, this study aimed to investigate the effects... more
    Silibinin has been known for its role in anti-cancer and radio-protective effect. Radiation therapy for treating lung cancer might lead to late-phase pulmonary inflammation and fibrosis. Thus, this study aimed to investigate the effects of silibinin in radiation-induced lung injury with a mouse model. In this study, we examined the ability of silibinin to mitigate lung injury in, and improve survival of, C57BL/6 mice given 13 Gy thoracic irradiation and silibinin treatments orally at 100 mg/kg/day for seven days after irradiation. In addition, Lewis lung cancer (LLC) cells were injected intravenously in C57BL/6 mice to generate lung tumor nodules. Lung tumor-bearing mice were treated with lung radiation therapy at 13 Gy and with silibinin at a dose of 100 mg/day for seven days after irradiation. Silibinin was shown to increase mouse survival, to ameliorate radiation-induced hemorrhage, inflammation and fibrosis in lung tissue, to reduce the number of inflammatory cells in the bronch...
    Although granulocyte-colony stimulating factor (G-CSF) is commonly used to support recovery from radiation-induced side-effects, the precise effects of G-CSF on colon cancer under radiotherapy remain poorly understood. In the present... more
    Although granulocyte-colony stimulating factor (G-CSF) is commonly used to support recovery from radiation-induced side-effects, the precise effects of G-CSF on colon cancer under radiotherapy remain poorly understood. In the present study, to investigate the effects of tumor growth following radiotherapy and G-CSF administration in a murine xenograft model of colon cancer, female BALB/c mice were injected with cells of a colon carcinoma cell line (CT26) with irradiation and G-CSF, alone or in combination. Mice received 2 Gy of focal radiation daily for 5 days and intraperitoneal injection of G-CSF (100 µg/kg/day) after irradiation for 7 days. Changes in the levels of myeloperoxidase (MPO), vascular endothelial growth factor (VEGF), matrix metalloproteinase type 9 (MMP-9) and CD31 were assessed in the mouse cancer induced by injection of colon cancer cells. We observed that G-CSF increased the number of circulating neutrophils, but facilitated tumor growth. However, G-CSF treatment ...
    Gene-targeted mice that contain a His6-tagged mouse c-Myc cDNA, Myc(His), inserted head to head into different sites of the mouse immunoglobulin heavy-chain locus, Igh, mimic the chromosomal T(12;15)(Igh-Myc) translocation that results in... more
    Gene-targeted mice that contain a His6-tagged mouse c-Myc cDNA, Myc(His), inserted head to head into different sites of the mouse immunoglobulin heavy-chain locus, Igh, mimic the chromosomal T(12;15)(Igh-Myc) translocation that results in the activation of Myc in the great majority of mouse plasmacytomas. Mice carrying Myc(His) just 5' of the intronic heavy-chain enhancer Emu (strain iMyc(Emu)) provide a specific model of the type of T(12;15) found in a subset (approximately 20%) of plasmacytomas that develop "spontaneously" in the gut-associated lymphoid tissue (GALT) of interleukin-6 transgenic BALB/c (C) mice. Here we show that the transfer of the iMyc(Emu) transgene from a mixed genetic background of segregating C57BL/6 x 129/SvJ alleles to the background of C increased the incidence of GALT plasmacytomas by a factor of 2.5 in first-generation backcross mice (C.iMyc(Emu) N1). Third-generation backcross mice (C.iMyc(Emu) N3, approximately 94% C alleles) were hypersu...
    Myc-induced lymphoblastic B-cell lymphoma (LBL) in iMycEmu mice may provide a model system for the study of the mechanism by which human MYC facilitates the initiation and progression of B cell and plasma cell neoplasms in human beings.... more
    Myc-induced lymphoblastic B-cell lymphoma (LBL) in iMycEmu mice may provide a model system for the study of the mechanism by which human MYC facilitates the initiation and progression of B cell and plasma cell neoplasms in human beings. We have recently shown that gene-targeted iMycEmu mice that carry a His6-tagged mouse Myc cDNA, MycHis, just 5' of the immunoglobulin heavy-chain enhancer, Emu, are prone to B cell and plasma cell tumors. The predominant tumor (approximately 50%) that arose in the iMycEmu mice on the mixed genetic background of segregating C57BL/6 and 129/SvJ alleles was LBL. The purpose of this study was to establish and characterize a cell line, designated iMycEmu-1, for the in-depth evaluation of LBL in vitro. The morphological features and the surface marker expression profile of the iMycEmu-1 cells were evaluated using cytological methods and FACS, respectively. The cytogenetic make-up of the iMycEmu-1 cells was assessed by spectral karyotyping (SKY). The ex...
    Eugenol is widely used in dentistry as a local analgesic agent, because of its ability to allay tooth pain. Interestingly, eugenol shares several pharmacological actions with local anesthetics which include inhibition of voltage-gated... more
    Eugenol is widely used in dentistry as a local analgesic agent, because of its ability to allay tooth pain. Interestingly, eugenol shares several pharmacological actions with local anesthetics which include inhibition of voltage-gated sodium channel (VGSC) and activation of transient receptor potential vanilloid subtype 1 (TRPV1). In the present study, we investigated the effects of eugenol on pain behaviors in orofacial area, and as an attempt to elucidate its mechanism we characterized inhibitory effects of eugenol on VGSCs in trigeminal ganglion (TG) neurons. TG neurons were classified into four types on the basis of their neurochemical and electrophysiological properties such as cell size, shapes of action potential (AP), isolectin-B(4) (IB(4)) binding, and were analyzed for the association of their distinctive electrophysiological properties and mRNA expression of Na(v)1.8 and TRPV1 by using single-cell RT-PCR following whole-cell recordings. Subcutaneous injection of eugenol r...
    Purpose: Micro-pinhole SPECT system with conventional multiple-head gamma cameras has the advantage of high magnification factor for imaging of rodents. However, several geometric factors should be calibrated to obtain the SPECT image... more
    Purpose: Micro-pinhole SPECT system with conventional multiple-head gamma cameras has the advantage of high magnification factor for imaging of rodents. However, several geometric factors should be calibrated to obtain the SPECT image with good image quality. We developed a simplified geometric calibration method for rotating triple-head pinhole SPECT system and assessed the effects of the calibration using several phantom and
    Glial activation is known to contribute to pain hypersensitivity following spinal sensory nerve injury. In this study, we investigated mechanisms by which glial cell activation in medullary dorsal horn (MDH) would contribute to tactile... more
    Glial activation is known to contribute to pain hypersensitivity following spinal sensory nerve injury. In this study, we investigated mechanisms by which glial cell activation in medullary dorsal horn (MDH) would contribute to tactile hypersensitivity following inferior alveolar nerve and mental nerve transection (IAMNT). Activation of microglia and astrocytes was monitored at 2 h, 1, 3, 7, 14, 28, and 60 days using immunohistochemical analysis with OX-42 and GFAP antibodies, respectively. Tactile hypersensitivity was significantly increased at 1 day, and this lasted for 28 days after IAMNT. Microglial activation, primarily observed in the superficial laminae of MDH, was initiated at 1 day, maximal at 3 days, and maintained until 14 days after IAMNT. Astrocytic activation was delayed compared to that of microglia, being more profound at 7 and 14 days than at 3 days after IAMNT. Both tactile hypersensitivity and glial activation appeared to gradually reduce and then return to the ba...
    Signaling through the T cell antigen receptor (TCR) is important for the homeostasis of naïve and memory CD4(+) T cells. The significance of TCR signaling in regulatory T (Treg) cells has not been systematically addressed. Using an... more
    Signaling through the T cell antigen receptor (TCR) is important for the homeostasis of naïve and memory CD4(+) T cells. The significance of TCR signaling in regulatory T (Treg) cells has not been systematically addressed. Using an Ox40-cre allele that is prominently expressed in Treg cells, and a conditional null allele of the gene encoding p56(Lck), we have examined the importance of TCR signaling in Treg cells. Inactivation of p56(Lck) resulted in abnormal Treg homeostasis characterized by impaired turnover, preferential redistribution to the lymph nodes, loss of suppressive function, and striking changes in gene expression. Abnormal Treg cell homeostasis and function did not reflect the involvement of p56(Lck) in CD4 function because these effects were not observed when CD4 expression was inactivated by Ox40-cre.The results make clear multiple aspects of Treg cell homeostasis and phenotype that are dependent on a sustained capacity to signal through the TCR.
    A uridine diphosphate glucosyltransferase from Bacillus licheniformis was overexpressed, purified and incubated with nucleotide diphosphate (NDP) d- and l-sugars to produce glucose, galactose, 2-deoxyglucose, viosamine, rhamnose, and... more
    A uridine diphosphate glucosyltransferase from Bacillus licheniformis was overexpressed, purified and incubated with nucleotide diphosphate (NDP) d- and l-sugars to produce glucose, galactose, 2-deoxyglucose, viosamine, rhamnose, and fucose sugar-conjugated resveratrol glycosides. A significantly higher (90%) bioconversion of resveratrol was achieved with αd-glucose as the sugar donor to produce four different glucosides of resveratrol, resveratrol 3-O-β-d-glucoside, resveratrol 4□-O-β-d-glucoside, resveratrol 3,5-O-β-d-diglucoside, and resveratrol 3,5,4□-O-β-d-triglucoside. The conversion rates and number of products formed were found to vary with the other NDP-sugar donors. Resveratrol 3-O-β-d-2-deoxyglucoside, resveratrol 3,5-O-β-d-di-2-deoxyglucoside were found to be produced while using TDP-2-deoxyglucose as donor, however, monoglycosides resveratrol 4□-O-β-d-galactoside, resveratrol 4□-O-β-d-viosaminoside, resveratrol 3-O-β-l-rhamnoside, resveratrol 3-O-β-l-fucoside were produ...
    Optic neuritis is frequently the first symptom of multiple sclerosis (MS), an inflammatory demyelinating neurodegenerative disease. Impaired axonal transport has been considered as an early event of neurodegenerative diseases. However,... more
    Optic neuritis is frequently the first symptom of multiple sclerosis (MS), an inflammatory demyelinating neurodegenerative disease. Impaired axonal transport has been considered as an early event of neurodegenerative diseases. However, few studies have assessed the integrity of axonal transport in MS or its animal models. We hypothesize that axonal transport impairment occurs at the onset of optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice. In this study, we employed manganese-enhanced MRI (MEMRI) to assess axonal transport in optic nerves in EAE mice at the onset of optic neuritis. Axonal transport was assessed as (a) optic nerve Mn(2+) accumulation rate (in % signal change/h) by measuring the rate of increased total optic nerve signal enhancement, and (b) Mn(2+) transport rate (in mm/h) by measuring the rate of change in optic nerve length enhanced by Mn(2+). Compared to sham-treated healthy mice, Mn(2+) accumulation rate was significantly decreased by 19% and 38% for EAE mice with moderate and severe optic neuritis, respectively. The axonal transport rate of Mn(2+) was significantly decreased by 43% and 65% for EAE mice with moderate and severe optic neuritis, respectively. The degree of axonal transport deficit correlated with the extent of impaired visual function and diminished microtubule-associated tubulins, as well as the severity of inflammation, demyelination, and axonal injury at the onset of optic neuritis.
    Wiskott-Aldrich syndrome (WAS) is an X-linked congenital immune-deficiency syndrome, and bone marrow transplantation (BMT) has become a curative modality. However, the transplant with the alternative donor needed more intensive... more
    Wiskott-Aldrich syndrome (WAS) is an X-linked congenital immune-deficiency syndrome, and bone marrow transplantation (BMT) has become a curative modality. However, the transplant with the alternative donor needed more intensive conditioning with increased treatment-related toxicities. Recently, fludarabine-based reduced toxicity myeloablative conditioning regimens have been developed for adult myeloid malignancies with promising results of good engraftment and low treatment-related toxicities. To increase the engraftment potential without serious complications, a boy with WAS received successful unrelated BMT with a reduced toxicity myeloablative conditioning regimen composed of fludarabine (40 mg/m2) on days -8, -7, -6, -5, -4, -3), busulfan (0.8 mg/kg i. v. q 6 hr on days -6, -5, -4, -3), and thymoglobulin (2.5 mg/kg on days -4, -3, -2). This novel conditioning regimen could improve the outcome of allogeneic transplantation for other non-malignant diseases such as congenital immun...
    ABSTRACT
    An operationally simple colorimetric way for measuring hyaluronidase activity was developed using cysteamine-bound gold nanoparticles. The addition of gold nanoparticles into hyaluronidase-containing solutions resulted in color changes,... more
    An operationally simple colorimetric way for measuring hyaluronidase activity was developed using cysteamine-bound gold nanoparticles. The addition of gold nanoparticles into hyaluronidase-containing solutions resulted in color changes, which could easily be observed with the naked eye or a UV/Vis spectrophotometer.
    To describe the frequency and clinical characteristics of chorioretinal lesions as a complication of chronic granulomatous disease (CGD). Seventeen patients with CGD examined at Seoul National University... more
    To describe the frequency and clinical characteristics of chorioretinal lesions as a complication of chronic granulomatous disease (CGD). Seventeen patients with CGD examined at Seoul National University Children's Hospital between 1996 and 1999 were recruited for this study. A review of their historical, clinical, and fluorescein angiographic features was performed, and the prevalence and demographic and clinical features of the chorioretinal lesions were summarized. Chorioretinal lesions were identified in 11 eyes of six patients with CGD, an overall prevalence of 35.3%. Patients' ages ranged from 6 months to 10 years, with a median of 47.0 months. Three of the six patients were boys. The lesions included RPE atrophy or pigment clumping, chorioretinal atrophy. Among the six patients, two had vision loss because of ischemia in the peripheral retina, neovascular membrane, and macular edema, which had not been previously reported. Chorioretinal lesions are not uncommon in patients with CGD and they may affect vision. Regular screening of patients with CGD and long-term follow-up of CGD chorioretinopathy patients should be performed to define the lesion, natural history, and pathogenesis.
    Pyrimidine nucleosides fused with... more
    Pyrimidine nucleosides fused with 3',4'-tetrahydrofuran ring were synthesized, starting from 1,2;5,6-di-O-isopropylidene-D-glucose and assayed for antiviral activities. Thymine analogue 1 and its corresponding 2'-deoxy analogue 3 exhibited high cytotoxicity instead of giving antiviral activities.
    Halogenated analogues of neplanocin A were synthesized from the key intermediate 1, among which fluoro-neplanocin A was found to be novel mechanism-based irreversible inhibitor of S-Adenosylhomocysteine hydrolase.
    It has been demonstrated previously that water diffusion anisotropy in vivo is equivalent to that observed ex vivo after perfusion fixation in the mouse brain. This finding supports the practice of ex vivo diffusion tensor imaging (DTI)... more
    It has been demonstrated previously that water diffusion anisotropy in vivo is equivalent to that observed ex vivo after perfusion fixation in the mouse brain. This finding supports the practice of ex vivo diffusion tensor imaging (DTI) measurement on perfusion-fixed tissues. However, the validity of extrapolating ex vivo DTI measurements from immersion-fixed autopsy specimens to the in vivo state is questionable because of variable postmortem delays often encountered before fixation. In this study, we investigated the effect of postmortem delay on the water diffusion anisotropy of ventrolateral spinal cord white matter from mice. Mouse spinal cords, each from the same animal, were examined using DTI in vivo, in situ after death before fixation, and ex vivo immersion fixed 10 h after death. Our results suggest that diffusion anisotropy in mouse spinal cord is preserved up to 10 h after death. Regional characteristics of diffusion anisotropy in mouse spinal cord white matter are equivalent in vivo, in situ after death (up to 10 h before fixation), and ex vivo 15 weeks after immersion fixation.
    Nociceptin is a non-opioid peptide that modulates pain response. One of mechanism underlying its analgesic action is the inhibition of voltage-dependent calcium current (ICa), similar to that of opioids. We investigated the molecular... more
    Nociceptin is a non-opioid peptide that modulates pain response. One of mechanism underlying its analgesic action is the inhibition of voltage-dependent calcium current (ICa), similar to that of opioids. We investigated the molecular mechanism by which nociceptin inhibits ICa using sensory neurons and a heterologous expression system. ICa inhibition by nociceptin was voltage-dependent, exhibited the slowing of activation kinetics and prepulse facilitation, and was blocked by N-ethylmaleimide, indicating the involvement of Gi/Go protein. ICa inhibition by nociceptin was primarily mediated through binding to its own receptor, ORL-1, but not through affecting other mu-opioid receptors. Thus, our results strongly demonstrate that heterologous cross-talk between ORL1 and muOR is not involved in the ICa inhibition by nociceptin.
    We have recently demonstrated that inferior alveolar nerve and mental nerve (branches of the mandibular nerve) injury from rats serves as a valid trigeminal neuropathic pain model. In these animals, we found that neuronal loss of... more
    We have recently demonstrated that inferior alveolar nerve and mental nerve (branches of the mandibular nerve) injury from rats serves as a valid trigeminal neuropathic pain model. In these animals, we found that neuronal loss of trigeminal ganglion (TG) was not correlated with pain hypersensitivity. In this study, we examined changes of transient receptor potential vanilloid 1 (TRPV1) expression in the injured and uninjured TG neurons using immunohistochemical analysis at 3 days after surgery, the time point where we observed significant pain hypersensitivity. Injured neurons were identified by positive immunoreactivity for activating transcription factor 3 (ATF3). ATF3 immunoreactivity was exclusively observed in the nuclei of subpopulation of ipsilateral mandibular TG neurons, whereas no ATF3 expression was found in the naive and contralateral TG neurons. Interestingly, the expression of TRPV1 was increased in the uninjured ipsilateral maxillary TG neurons as well as in the uninjured ipsilateral mandibular TG neurons. The upregulation of TRPV1 and ATF3 expression returned to the basal level at 60 days after surgery. Our results demonstrate that trigeminal sensory nerve injury induced differential changes in TRPV1 expression of the injured and uninjured TG neurons. The upregulation of TRPV1 in uninjured TG neurons may play an important role in pain hypersensitivity after trigeminal nerve injury. The TRPV1 is a well-known pain transducer molecule and plays crucial roles in the perception of inflammatory and thermal pain. This article presents that TRPV1 expression was increased in uninjured neurons rather than injured neurons after peripheral nerve injury. The upregulation of TRPV1 in uninjured neurons may be associated with the development of neuropathic pain. TRPV1 might be a potential target for the treatment of neuropathic pain.
    The interaction of 4-1BB and its ligand plays an important role in the regulation of T-cell-mediated immune responses. In this study, the authors examined the effect of a humanized anti--4-1BB monoclonal antibody (H4B4) on... more
    The interaction of 4-1BB and its ligand plays an important role in the regulation of T-cell-mediated immune responses. In this study, the authors examined the effect of a humanized anti--4-1BB monoclonal antibody (H4B4) on ovalbumin-induced immune responses in baboons. Previously, a mouse monoclonal antibody, 4B4 against the human 4-1BB molecule, was generated and characterized. Based on this antibody, a humanized version of 4B4 monoclonal antibody was constructed and the resultant antibody, H4B4, showed full recovery of the binding activity of the original antibody 4B4: a 1.5-fold increase in affinity for 4-1BB. In addition, H4B4 mediated antibody-dependent cellular cytotoxicity of activated human peripheral blood T cells and CEM cells in a dose-dependent manner. Weekly administration of H4B4 at doses of 1 or 4 mg/kg could suppress immunoglobulin G production against ovalbumin. This was not a result of the overall immune suppression, because the numbers of B and T cells and the total immunoglobulin G production were not altered during treatment with H4B4. These findings suggest that treatment with H4B4 may be a valid therapeutic approach to control unwanted immune responses in persons with autoimmune diseases.

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