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Pardridge, William M.; Kang, Young‐Sook; Buciak, Jody L.; Yang, Jing

doi:10.1023/a:1016244500596

Cited by 289 publications

(120 citation statements)

References 24 publications

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“…Multiple studies have shown that the presence of basic residues in the antibody hypervariable regions, mostly arginine residues in the HCDR3, may be responsible for the anti-DNA reactivity (21) and that cationization of otherwise irrelevant antibodies also appears to induce cellular uptake (49). Some distinct features of potential significance were found in the HCDR3 of the dual-specific mAb DSO (Fig.…”

Section: Discussionmentioning

confidence: 96%

Identification of a Lipid Peroxidation Product as the Source of Oxidation-specific Epitopes Recognized by Anti-DNA Autoantibodies*

Otaki

Chikazawa

Nagae

et al. 2010

Journal of Biological Chemistry

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Lipid peroxidation in tissue and in tissue fractions represents a degradative process, which is the consequence of the production and the propagation of free radical reactions primarily involving membrane polyunsaturated fatty acids, and has been implicated in the pathogenesis of numerous diseases, including systemic lupus erythematosus (SLE). We have found that bovine serum albumin incubated with peroxidized polyunsaturated fatty acids significantly cross-reacted with the sera from MRLlpr mice, a representative murine model of SLE. To identify the active substances responsible for the generation of autoantigenic epitopes recognized by the SLE sera, we performed the activity-guiding separation of a principal source from 13-hydroperoxy-9Z,11E-octadecadienoic acid and identified 4-oxo-2-nonenal (ONE), a highly reactive aldehyde originating from the peroxidation of 6 polyunsaturated fatty acids, as the source of the autoantigenic epitopes. When the age-dependent change in the antibody titer against the ONE-modified protein was measured in the sera from MRL-lpr mice and control MRL-MpJ mice, all of the MRL-lpr mice developed an anti-ONE titer, which was comparable with the anti-DNA titer. Strikingly, a subset of the anti-DNA monoclonal antibodies generated from the SLE mice showing recognition specificity toward DNA cross-reacted with the ONE-specific epitopes. Furthermore, these dual-specific antibodies rapidly bound and internalized into living cells. These findings raised the possibility that the enhanced lipid peroxidation followed by the generation of ONE may be involved in the pathogenesis of autoimmune disorders.

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Section: Discussionmentioning

confidence: 96%

Identification of a Lipid Peroxidation Product as the Source of Oxidation-specific Epitopes Recognized by Anti-DNA Autoantibodies*

Otaki

Chikazawa

Nagae

et al. 2010

Journal of Biological Chemistry

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“…However, the OX26 antibody vector is specific for rats (28), and to image brain amyloid, a BBB delivery vector must be available for the species under investigation. Recent studies show that the 83-14 mAb to the human insulin receptor is an active brain drug delivery vector in rhesus monkeys, but not squirrel monkeys (11). The 83-14 antibody is an active BBB transport vector, and the BBB PS product for the 83-14 mAb in the rhesus monkey is 8-fold greater than the BBB PS product for the 0X26 mAb in the rat (11).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies show that the 83-14 mAb to the human insulin receptor is an active brain drug delivery vector in rhesus monkeys, but not squirrel monkeys (11). The 83-14 antibody is an active BBB transport vector, and the BBB PS product for the 83-14 mAb in the rhesus monkey is 8-fold greater than the BBB PS product for the 0X26 mAb in the rat (11). The ability to semiquantitate and image amyloid in patients suspected of AD would not only provide a specific diagnostic test for this condition but also would provide a means of monitoring the effects of drug therapies aimed at reducing the A,B amyloid burden in AD brain.…”

Section: Discussionmentioning

confidence: 99%

“…The avidin analogue may consist of avidin (6), SA, as used in the present study, or neutral avidin (NLA), as used in previous studies (9). The BBB transport domain may consist of an mAb, such as the OX26 antibody to the transferrin receptor for studies in rats, or the 83-14 antibody to the insulin receptor for applications in either humans or Old World primates (11). If nous injection in anesthetized rats, as described previously (9).…”

mentioning

confidence: 99%

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Vector-mediated delivery of 125I-labeled beta-amyloid peptide A beta 1-40 through the blood-brain barrier and binding to Alzheimer disease amyloid of the A beta 1-40/vector complex.

Saito

Buciak

Yang

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

100

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The brain amyloid of Alzheimer disease (AD) may potentially be imaged in patients with AD by using neuroimaging technology and a radiolabeled form of the 40-residue 18-amyloid peptide A81-40 that is enabled to undergo transport through the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo.Transport of 125I-labeled A31-40 (125I-A31B-40) Alzheimer disease (AD) is a severe neurodegenerative disorder, and presently there is no premortem diagnostic test for this disease (1). The dementia of AD correlates with the deposition in brain of amyloid (2), which is principally composed of the 42-to 43-amino acid (3-amyloid peptide, A1(3'42/43 (3,4). One possible diagnostic approach to AD is the development of a premortem brain scan that would allow for semiquantitation of the AP3 amyloid burden in human brain. Previous studies have shown that 125I-labeled A(31-40 (125I-A3'-40) binds to preexisting amyloid plaques in frozen sections of AD brain (5). The delivery to brain of radiolabeled A,f1-40 in conjunction with the use of standard neuroimaging modalities such as single photon emission computed tomography (SPECT) may allow for quantitation of AB3 amyloid in AD brain. Therefore, the present studies examine whether 125I-A3l-40 undergoes significant transport through the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo, by using both intravenous/pharmacokinetic and internal carotid artery perfusion techniques. These studies then measure the extent to which BBB transport of 125I-AI3-40 is enhanced with the use of a vector-mediated drug delivery system (6). The latter is composed of a conjugate of streptavidin (SA) and the OX26 monoclonal antibody (mAb) to the transferrin receptor (7), which undergoes receptor-mediated transcytosis through the BBB (6); 125I-A31-40 is monobiotinylated (bio), and 125I,bio-Af140 is then conjugated to the SA-OX26 vector. Since conjugation of 125I-Af3'-40 to the vector-mediated delivery system may inhibit binding of A1'-40 to amyloid plaques, the present studies also examine the saturable binding of 125I-A31-40 to amyloid in AD brain after conjugation to the delivery system. Conjugate Synthesis. The OX26 was conjugated to SA by a thioether linkage as described previously (7,8 Abbreviations: Af31-40, 13-amyloid peptide residues 1-40; BBB, bloodbrain barrier; AD, Alzheimer disease; SA, streptavidin; mAb, monoclonal antibody; 0X26, murine mAb to the rat transferrin receptor; NHS, N-hydroxysuccinimide; SPECT, single photon emission computed tomography; bio, biotinylated; VD, brain volume of distribution; PS, permeability-surface area; AUC, area under the plasma concentration curve; TCA, trichloroacetic acid; TFA, trifluoroacetic acid; %ID, percent of the injected dose. MATERIALS AND METHODS

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“…In contrast, the immunogenicity of the PIL is restricted to the targeting mAb, and the antibody immunogenicity can be eliminated with the use of genetically engineered ''humanized'' mAbs. A mAb to the human insulin receptor (HIR) is an active BBB delivery system in Old World primates and humans and delivers 4% of the injected dose to the primate brain (17). This murine HIR mAb has been genetically engineered for use in humans (18).…”

mentioning

confidence: 99%

Brain-specific expression of an exogenous gene after i.v. administration

Shi

Zhang

Zhu

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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269

195

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Abstract: These studies demonstrate an unexpected high degree of transcytosis of a monoclonal antibody through the primate BBB in vivo.

Cited by 289 publications

References 24 publications

Identification of a Lipid Peroxidation Product as the Source of Oxidation-specific Epitopes Recognized by Anti-DNA Autoantibodies*

Identification of a Lipid Peroxidation Product as the Source of Oxidation-specific Epitopes Recognized by Anti-DNA Autoantibodies*

Vector-mediated delivery of 125I-labeled beta-amyloid peptide A beta 1-40 through the blood-brain barrier and binding to Alzheimer disease amyloid of the A beta 1-40/vector complex.

Brain-specific expression of an exogenous gene after i.v. administration

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