Search PubMed⌕ Search

Biomedical subjects

Z Qu

Publications and source records attributed to Z Qu.

At least 127 records · Page 7Linked to original sources
PubMed1995

Effect of poly(ADP-ribose) synthetase on the expression of major histocompatibility complex (MHC) class II genes.

We have studied the effect of poly(ADP-ribose) synthetase on the interferon-gamma (IFN-gamma)-inducible expression of major histocompatibility complex (MHC) class II molecules. We constructed an expression plasmid capable of expressing either a sense RNA (MT-ARS) or an antisense RNA (pAS-FL or pAS-5') for poly(ADP-ribose) synthetase. We transfected the plasmid into mouse or human macrophage tumor cells and examined the effect on the expression of MHC class II molecules. The IFN-gamma-inducible expression of MHC class II gene was considerably reduced in transformant clones (A-2, B-2), in which the synthetase was highly expressed, whereas the depletion of the synthetase due to the expression of antisense RNA for the synthetase amplified the expression of MHC class II molecules. The results indicate that the level of the synthetase critically regulates the IFN-gamma-inducible MHC class II molecules. Next, we analyzed DNase I hypersensitive sites (DHS) of mouse MHC class II, I-A beta gene and found two sites, one in the promoter region and the other one in the first intron. The DHS in first intron was less sensitive towards DNase I attack in transformant clones (A-2, B-2) in which the synthetase was synthesized in a large quantity. Thus we constructed two beta-galactosidase reporter genes, one (A beta 2.0kb-lac z) containing the promoter region to a part of the second exon of the class II gene, and the other (A beta pro-lac z) containing the promoter region of the class II gene alone. The expression of the reporter gene was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and found that the expression of A beta 2.0kb-lac z was suppressed in the transformant clones (A-2, B-2) relevant to control cells but the expression of A beta pro-lac z was the same level among those cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma.

Mast cells play an essential role during development of inflammation after chemical and immunological insults and have been implicated in tissue fibrosis and angiogenesis. The exact contribution of mast cells to these conditions is largely unknown. In this study, we found that a potent angiogenic and mitogenic polypeptide, basic fibroblast growth factor (bFGF), is localized to the majority of mast cells from normal skin and lung and in tissue samples characterized by fibrosis, hyperplasia, and neovascularization. Using specific antibodies to mast cell tryptase, tissue macrophage, and bFGF, we demonstrate that cytoplasmic bFGF immunoreactivity is localized to 96.8 +/- 9.6% of tryptase-positive cells in human fibrotic lung tissue (n = 10), 82.3 +/- 6.9% of tryptase-positive cells in rheumatoid synovia (n = 6), and 93.1 +/- 4.8% of tryptase-positive cells in skin hemangioma (n = 5). Moreover, these tryptase-positive cells comprise a major portion (86 to 97%) of nonvascular cells exhibiting cytoplasmic bFGF staining in these tissues. In contrast, macrophage-like cells contribute less than 10% of the bFGF-positive cells in the same samples. The specificity of the immunostaining results was supported by the finding that cultured human mast cells (HMC-1) express both bFGF mRNA and protein. Our data indicate that mast cells, a primary source of heparin, also serve as a significant source of a heparin-binding growth factor, bFGF, in these disease processes. These observations suggest that mast cells may contribute to these pathological conditions by releasing this polypeptide.

Arthritis, Rheumatoid↗
PubMed1995

Expression of basic fibroblast growth factor in synovial tissue from patients with rheumatoid arthritis and degenerative joint disease.

BACKGROUND: Recent studies have implicated polypeptide growth factors in the development of rheumatoid arthritis (RA), which is characterized by synoviocyte hyperplasia and neovascularization. One such polypeptide, basic fibroblast growth factor (bFGF), is of particular interest because of its potent mitogenic and angiogenic activities. We have previously reported that cultured human synoviocytes synthesize and bind bFGF and also proliferate in response to it (1). Recently, we found a close association between increased bFGF expression and destructive changes in arthritic joints from rats (2). Now we extend our study by detecting in vivo expression of bFGF in human synovial tissues obtained from patients with RA. EXPERIMENTAL DESIGN: Human synovial tissues from patients with RA, degenerative joint disease (DJD), and trauma were collected during joint surgery. The expression of bFGF protein and mRNA by the synovia was examined by immunolocalization, Western blot, Northern blot, and RNase protection assays. Synovium from patients with DJD and trauma was used to compare with rheumatoid synovium. Double immunostaining with cell type-specific antibodies was carried out to identify cellular sources of bFGF. RESULTS: Both polypeptide and mRNA for bFGF were detected in the synovial samples examined. Increased bFGF staining was found in synovium-cartilage interface where joint destruction occurred and in hyperplastic synoviocytes of a subset of rheumatoid synovium. Strong cytoplasmic bFGF staining was localized in the majority of mast cells and vascular cells. CONCLUSIONS: Synovial tissue from patients with RA, DJD, and trauma express bFGF. Increased bFGF staining in the hyperplastic lining synoviocytes and at the pannus-cartilage interface suggests that bFGF may play a role in synovial hyperplasia and joint destruction. Strong cytoplasmic bFGF staining found in mast cells and vascular cells indicates that these cells are the major sources of tissue bFGF.

Adult↗
PubMed1995

Effects of daurisoline on cytosolic free calcium in fetal rat cerebral cells.

Cytosolic free Ca2+ ([Ca2+]i) was measured in dissociated cerebral cells isolated from fetal rats with the fluorescent indicater fura-2. Increase in [Ca2+]i occurred rapidly following exposure of the cells to 50 mmol/L KCl, 10(-7) mol/L Bay K 8644 or 200 mumol/L glutamate (Glu). [Ca2+]i elevated by K(+)-depolarization was attenuated by pretreatment with 10(-7), 10(-6) mol/L daurisoline (Dau). The response of [Ca2+]i to K(+)-depolarization did not change when 10(-8) mol/L Dau was added. When 10(-8)-10(-6) mol/L Dau was added to the cell suspensions prior to exposure to Glu, the Glu-stimulated rises in [Ca2+]i were reduced significantly. However, Dau (10(-6), 10(-7) and 10(-8) mol/L) did not alter the response to Bay K 8644. These results indicate that Dau can inhibit the increase of [Ca2+]i in fetal rat cerebral cells induced by certain Ca2+ agonists, especially Glu, suggesting that this drug may have a protective effect against cerebral cellular injury.

Alkaloids↗
PubMed1994

Enhancement of interferon-gamma-induced major histocompatibility complex class II gene expression by expressing an antisense RNA of poly(ADP-ribose) synthetase.

We studied the effect of poly(ADP-ribose) synthetase on the interferon-gamma (IFN-gamma)-inducible expression of major histocompatibility complex (MHC) class II molecules by expressing an antisense RNA of poly(ADP-ribose) synthetase. We constructed two expression plasmids capable of expressing an antisense RNA for poly(ADP-ribose) synthetase, carrying 0.7-kilobase long fragment of 5'-coding region (pAS-5') and full-length cDNA (pAS-FL) of poly(ADP-ribose) synthetase in an antisense orientation under control of metallothionein I promoter. We transfected the plasmid into human leukemia THP-1 cells and isolated transformants. Metal-inducible reduction in poly(ADP-ribose) synthetase activity was observed in two pAS-5'-transfected clones out of 72 neo-resistant clones examined, and metal-independent reduction in the activity was exhibited in pAS-FL-transfected clones. The antisense RNA was induced in a metal-dependent manner in the clones transfected with pAS-5', as judged by hybridizing with a sense riboprobe of the synthetase gene. The mRNA of the synthetase decreased 1 day after an addition of metal ions, and the synthetase activity of the transformants decreased by more than 90% 3 days after an addition of metal ions. Thus, we incubated the transformant clones in the presence of metal ions for 3 days and then treated them with IFN-gamma. The IFN-gamma-inducible expression of MHC class II molecules was amplified in the transformant clones, as judged by RNA blot analysis and flow cytometry. These results indicate that the decrease in poly(ADP-ribose) synthetase makes THP-1 cells favorable to induce MHC class II molecules by IFN-gamma.

Gene Expression↗
PubMed1994

Local proliferation of fibroblast-like synoviocytes contributes to synovial hyperplasia. Results of proliferating cell nuclear antigen/cyclin, c-myc, and nucleolar organizer region staining.

OBJECTIVE: To test the hypothesis that local proliferation contributes significantly to the hyperplasia of rheumatoid synovium. METHODS: Immunohistologic and chemical staining was used to identify 3 markers of cell proliferation: proliferating cell nuclear antigen, c-myc proto-oncogene, and nucleolar organizer regions. Synovium from 21 patients with rheumatoid arthritis, 34 with degenerative joint disease, and 7 with joint trauma was examined. RESULTS: All 3 markers indicated substantial, active proliferation of synovial lining cells in synovium with hyperplasia. Proliferating cells showed type I procollagen immunoreactivity but were negative for CD68, a monocyte/macrophage marker. Proliferation was greater in rheumatoid arthritis than in the other conditions evaluated. CONCLUSION: In situ proliferation of fibroblast-like synoviocytes in the synovium lining contributes considerably to the increase in cell numbers in rheumatoid synovium.

Adult↗
PubMed1994

Analysis of the humoral response elicited in mice by a chimeric peptide representing variable segments I and IV of the major outer membrane protein of Chlamydia trachomatis.

A synthetic chimeric peptide representing the variable segments I (VS I) and IV of the major outer membrane protein (MOMP) of Chlamydia trachomatis, serovars C and E respectively, was studied to determine its ability to elicit a neutralizing humoral response in mice. Antibody responses varied to the peptide in the five inbred strains of mice, A/J(H-2a), DBA/1(H-2q), C57BL/10(H-2b), CBA/J(H-2k), Balb/c(H-2d), that were immunized. There was a spectrum of antibody responses which ranged from high ELISA and IFA titres by the C57BL/10 mice to little or no response by Balb/c mice. Antisera from C57BL/10 mice recognized all 15 serovars of C. trachomatis in a dot blot assay. A pepscan of the antisera from C57BL/10 mice showed strong reactivity to both neutralizing epitopes VAGLQNDPT in VS I of serovar C and the species-conserved peptide, TLNPTIA, in the VS IV. This antiserum neutralized, in vitro, the infectivity of serovars representing the B complex (B, D and E), C complex (C and J), B-related (F) and C-related (L3) complexes. In an attempt to elicit a stronger response to the peptide in the weakly reactive Balb/c and the DBA/1 strains, the peptide was conjugated to the carrier, keyhole limpet haemocyanin (KLH). All mice immunized with the KLH-peptide produced high-titred antisera that recognized neutralizing epitopes in VS I and VS IV and strongly neutralized the infectivity of both serovars C and E.

Amino Acid Sequence↗
PubMed1994

Comparison of innervation and agrin-induced tyrosine phosphorylation of the nicotinic acetylcholine receptor.

Studies of the regulation of tyrosine phosphorylation at the neuromuscular junction during development and following denervation suggest that tyrosine phosphorylation of the nicotinic acetylcholine receptor is regulated by neuronal innervation of muscle. The finding that agrin, a neuronally derived extracellular matrix protein also induces tyrosine phosphorylation of the nicotinic receptor, suggests that nerve-induced tyrosine phosphorylation may be mediated by agrin. To study this further, we have examined the regulation of tyrosine phosphorylation of the nicotinic receptor by innervation in vitro using muscle-neuron cocultures. Innervation of chick myotubes by chick ciliary ganglia neurons induced tyrosine phosphorylation of the nicotinic receptor with the same subunit specificity seen with bath applied purified agrin. Both innervation and agrin-induced phosphorylation of the nicotinic receptor resulted in an increase in tyrosine and serine phosphorylation. In addition, thermolysin phosphopeptide maps of the subunits after innervation or agrin-treatment were identical. The similarity in the agrin- and nerve-induced phosphorylation of the acetylcholine receptor suggests that agrin mediates the nerve-induced phosphorylation during development in vivo and that phosphorylation of the acetylcholine receptor may play an important role in the development of the neuromuscular junction.

Agrin↗
PubMed1994

Immunolocalization of basic fibroblast growth factor and platelet-derived growth factor-A during adjuvant arthritis in the Lewis rat.

A prerequisite in defining the role of a growth factor in a disease is knowledge of its expression kinetics during the natural course of the disease. We, therefore, used immunohistochemical and immunoblot analyses to examine tissue distribution of basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF-A) during the development of destructive arthropathy in the rat adjuvant arthritis model. In normal joints, bFGF was primarily localized in endothelial cells. In inflamed joints, increased staining for bFGF was found in the invading panni, hyperplastic synovium, and thickened periosteum where bFGF was also co-localized with two cell proliferation markers. Staining for bFGF began to increase at the onset of arthritis (days 11 to 13), reached peak level on days 17 to 24, and gradually declined afterward. In contrast, PDGF-A staining did not change until day 17 and the increased staining was restricted to areas of newly formed bone. The district temporal and spatial distribution pattern of these two growth factors during the destructive arthropathy strongly suggests that they play different roles during arthritis. Although PDGF-A seems to be exclusively related to osteogenesis, bFGF may have a more extensive impact on synovial proliferation and bone destruction as well as bone formation.

Animals↗
PubMed1993

Characterization of a neutralizing monoclonal antibody directed at variable domain I of the major outer membrane protein of Chlamydia trachomatis C-complex serovars.

A monoclonal antibody (MAb), C10, that neutralized in vitro the infectivity of serovars C, I, J, and L3 (members of the C and C-related complexes) of Chlamydia trachomatis was identified. Of the 15 major serovars and the mouse pneumonitis strain of C. trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae, which were used as nontreated and heat-treated (56 degrees C, 30 min) antigens in a dot blot assay, only serovars C, I, J, and L3 were recognized with both the native and treated antigens. Western blot (immunoblot) results showed that MAb C10 recognized the major outer membrane protein of these four serovars. Overlapping hexameric peptides corresponding to variable domains (VDs) I, II, III, and IV of the major outer membrane protein of C. trachomatis serovar C were synthesized, and peptide screening showed that MAb C10 mapped to the VD I amino acid sequence VAGLQNDPT. Results of an in vitro neutralization assay correlated with those of the indirect immunofluorescence assay, Western blot, and dot blot assay in that only serovars C, I, J, and L3 were neutralized by MAb C10. In vitro competitive neutralization experiments, using a peptide representing VD I of serovar C to compete with C. trachomatis serovar C for MAb C10 binding, revealed that both serological and neutralizing activities of MAb C10 were inhibited by the VD I peptide. In an in vivo toxicity/infectivity assay using serovar L3 pretreated with MAb C10, there was 100% survival of mice infected with a lethal dose at 48 h. In contrast, the control group, consisting of mice injected with the same dose of L3 pretreated with a MAb that does not recognize L3, had no survivors during a 48-h observation period. In summary, since the surface-exposed contiguous epitope recognized by MAb C10 binds neutralizing antibodies that are subspecies specific for the C and C-related complexes, it should be considered for inclusion in the development of a chlamydial vaccine.

Amino Acid Sequence↗
PubMed1991

Agrin induces phosphorylation of the nicotinic acetylcholine receptor.

Agrin causes acetylcholine receptors (AChRs) on chick myotubes in culture to aggregate, forming specializations that resemble the postsynaptic apparatus at the vertebrate skeletal neuromuscular junction. Here we report that treating chick myotubes with agrin caused an increase in phosphorylation of the AChR beta, gamma, and delta subunits. H-7, a potent inhibitor of several protein serine kinases, blocked agrin-induced phosphorylation of the gamma and delta subunits, but did not prevent either agrin-induced AChR aggregation or phosphorylation of the beta subunit. Experiments with anti-phosphotyrosine antibodies demonstrated that agrin caused an increase in tyrosine phosphorylation of the beta subunit that began within 30 min of adding agrin to the myotube cultures, reached a plateau by 3 hr, and was blocked by treatments known to block agrin-induced AChR aggregation. Anti-phosphotyrosine antibodies labeled agrin-induced specializations as they do the postsynaptic apparatus. These results suggest that agrin-induced tyrosine phosphorylation of the beta subunit may play a role in regulating AChR distribution.

Agrin↗
PubMed1990

[Analysis of trace elements in cataractous lenses and environmental samples in Tibet].

Trace elements of Cu, Fe, Zn, Mg, and Se in Tibetan cataractous lenses and also in local samples of earth, drinking water, and staple foods were analyzed to estimate the possible relationship between environmental factors and primary cataract formation in Tibet. The Fe, Mg and Se contents in Tibetan cataracts were significantly lower in comparison with levels in those of Chengdu area, particularly the Se contents were low in both cataracts and local environment, suggesting a probable correlation between cataract formation and low Se contents in food and water.

Cataract↗
PubMed1989

[Fundus examination of newborns on Tibet plateau].

Fundus examination of 255 newborns in high altitude Tibet revealed that the optic discs were of orange-pink colour with clear margin and over ten small vessels. The C/D ratio in 500 eyes (98.04%) was 0.3 or less, and none was 0.6 or over. The C/D ratio in both eyes of 242 babies (94.90%) was symmetrical and in only 1 case (0.39%) it differed by 0.2. The macula of all infants was dark red with no foveal reflection. Some of the veins were engorged. Retinal hemorrhages were found in 64 cases (25.10%), 12 cases in the macular region and 1 case on the optic disc. Retinal edema was present in 30 cases, cotton wool exudates in 30 cases, vitreous artery in 6 cases, and congenital cataracts in 1 case. The mechanism of retinal changes were discussed.

Altitude↗
PubMed1989

[Correlation of SPECT, EEG and CT in patients with epilepsy. A preliminary report].

Single photon emission computed tomography (SPECT) were performed in 14 patients with epilepsy. Among 6 patients with GTC, five had no focal abnormalities in EEG and CT scan, SPECT also showed no changes of regional cerebral perfusion. In another one patient EEG was normal, CT scan showed hypodensity in right frontal area, SPECT showed decreased regional cerebral perfusion in right frontotemporal area. AVM in frontal lobe was found at operation. In 3 patients with complex partial seizures and 5 patients with complex partial seizures and GTC, SPECT showed regional cerebral perfusion coincided with the area of focal epileptic form discharges in EEG. In one patient with complex partial seizures and GTC EEG showed right antero-temporal focal sharp wave discharges, discrete calcification in superior suprasella cisterna on CT, SPECT showed decreased regional perfusion in right temporal area, pathological examination revealed hematoma in right temporal lobe. SPECT is useful for localizing epileptogenic foci in epileptics.

Adolescent↗
PubMed1982

Insect immunity: isolation and structure of cecropins B and D from pupae of the Chinese oak silk moth, Antheraea pernyi.

The immune system in the Chinese oak silk moth, Antheraea pernyi, has been compared with that of the Cecropia moth which has been characterized earlier. Antibacterial activity against Escherichia coli was induced in diapausing pupae by injection of viable E. coli or Enterobacter cloacae. The activity reached a maximum on day 7-8 after which the response gradually declined. The pupae produced a set of immune proteins with P4 and P5 as major labelled components similar to that earlier found in Cecropia. The major antibacterial factor in A. pernyi was cecropin D. A procedure is described for the isolation of cecropin B and D, which is in principle similar to the one used for the isolation of the corresponding cecropins from Cecropia pupae. Amino acid sequence analyses of the A. pernyi cecropins show the D form to contain 36 amino acid residues and that both cecropins have blocked C-termini. The general structure of cecropins having a charged N-terminal region (residues 1-21) followed by a long hydrophobic stretch (residues 22-32) is well conserved. Cecropin B and D from A. pernyi differ from the corresponding proteins in Cecropia by four and three conservative amino acid replacements, respectively. The homology between the cecropins from the two insects suggests that they orginate from a single ancestral gene. The antibacterial activity was tested against nine different bacterial species. Evolutionary aspects of the cecropins are discussed.

Amino Acids↗
PubMedDate not supplied

The effect of orientation within a chimeric peptide on the immunogenicity of Chlamydia trachomatis epitopes.

Peptides representing the Chlamydia trachomatis major outer membrane protein variable domains (VD) 1 and 4 of serovars C and E, respectively, have been shown to elicit a neutralizing antibody response in mice. To assess whether the position within a chimeric peptide influences the immunogenicity of the epitopes, two constructs, VD 1-4 and VD 4-1, were made in which the position of the VD relative to the amino and carboxy terminals were rotated. C57BL/10 mice were immunized with 100 micrograms of peptide in complete Freund's adjuvant (FA) on day 0, followed by an immunization with peptide (100 micrograms) in complete FA on day 14. By day 21 the immunodominant epitope in both chimeras as measured by ELISA was the one located at the carboxy terminus. A pepscan of the VD 1-4 antisera revealed a main peak in VD 4 which had been previously identified by neutralizing MAbs. The VD 4-1 antisera gave a peak in the VD 1 region which did not correspond to regions previously mapped with neutralizing MAbs. The VD 1-4 antisera but not the VD 4-1 antisera was able to neutralize in vitro serovar E. In summary, the position of these chlamydial epitopes within a chimeric peptide greatly influenced the resulting immune response.

Amino Acid Sequence↗
PubMedDate not supplied

Pretargeting for cancer radioimmunotherapy with bispecific antibodies: role of the bispecific antibody's valency for the tumor target antigen.

The use of a divalent effector molecule improves bispecific antibody (bsMAb) pretargeting by enabling the cross-linking of monovalently bound bsMAb on the cell surface, thereby increasing the functional affinity of a bsMAb. In this work, it was determined if a bsMAb with divalency for the primary target antigen would improve bsMAb pretargeting of a divalent hapten. The pretargeting of a (99m)Tc-labeled divalent DTPA-peptide, IMP-192, using a bsMAb prepared by chemically coupling two Fab' fragments, one with monovalent specificity to the primary target antigen, carcinoembryonic antigen (CEA), and to indium-loaded DTPA [DTPA(In)], was compared to two other bsMAbs, both with divalency to CEA. One conjugate used the whole anti-CEA IgG, while the other used the anti-CEA F(ab')(2) fragment to make bsMAbs that had divalency to CEA, but with different molecular weights to affect their pharmacokinetic behavior. The rate of bsMAb blood clearance was a function of molecular weight (IgG x Fab' < F(ab')(2) x Fab' < Fab' x Fab' conjugate). The IgG x Fab' bsMAb conjugate had the highest uptake and longest retention in the tumor. However, when used for pretargeting, the F(ab')(2) x Fab' conjugate allowed for superior tumor accretion of the (99m)Tc-IMP-192 peptide, because its more rapid clearance from the blood enabled early intervention with the radiolabeled peptide when tumor uptake of the bsMAb was at its peak. Excellent peptide targeting was also seen with the Fab' x Fab' conjugate, albeit tumor uptake was lower than with the F(ab')(2) x Fab' conjugate. Because the IgG x Fab' bsMAb cleared from the blood so slowly, when the peptide was given at the time of its maximum tumor accretion, the peptide was captured predominantly by the bsMAb in the blood. Several strategies were explored to reduce the IgG x Fab' bsMAb remaining in the blood to take advantage of its 3-4-fold higher tumor accretion than the other bsMAb conjugates. A number of agents were tested, including those that could clear the bsMAb from the blood (e.g., galactosylated or nongalactosylated anti-id antibody) and those that could block the anti-DTPA(In) binding arm [e.g., DTPA(In), divalent-DTPA(In) peptide, and DTPA coupled to bovine serum albumin (BSA) or IgG]. When clearing agents were given 65 h after the IgG x Fab' conjugate (time of maximum tumor accretion for this bsMAb), (99m)Tc-IMP-192 levels in the blood were significantly reduced, but a majority of the peptide localized in the liver. Increasing the interval between the clearing agent and the time the peptide was given to allow for further processing of the bsMAb-clearing agent complex did not improve targeting. At the dose and level of substitution tested, galacosylated BSA-DTPA(In) was cleared too quickly to be an effective blocking agent, but BSA- and IgG-DTPA(In) conjugates were able to reduce the uptake of the (99m)Tc-IMP-192 in the blood and liver. Tumor/nontumor ratios compared favorably for the radiolabeled peptide using the IgG x Fab'/blocking agent combination and the F(ab')(2) x Fab' (no clearing/blocking agent), and peptide uptake 3 h after the blocking agent even exceeded that of the F(ab')(2) x Fab'. However, this higher level of peptide in the tumor was not sustained over 24 h, and actually decreased to levels lower than that seen with the F(ab')(2) x Fab' by this time. These results demonstrate that divalency of a bsMAb to its primary target antigen can lead to higher tumor accretion by a pretargeted divalent peptide, but that the pharmacokinetic behavior of the bsMAb also needs to be optimized to allow for its clearance from the blood. Otherwise, blocking agents will need to be developed to reduce unwanted peptide uptake in normal tissues.

Animals↗