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J Lai

Publications and source records attributed to J Lai.

At least 19 recordsLinked to original sources
PubMed2002

Pronociceptive effects of spinal dynorphin promote cannabinoid-induced pain and antinociceptive tolerance.

Recent studies indicate that sustained opioid administration produces increased expression of spinal dynorphin, which promotes enhanced sensitivity to non-noxious and noxious stimuli. Such increased "pain" may manifest behaviorally as a decrease in spinal antinociceptive potency. Here, the possibility of similar mechanisms in the antinociception of spinal cannabinoids was explored. Response thresholds to non-noxious mechanical and noxious thermal stimuli were assessed. Antinociception was determined using the 52 degrees C tail-flick test. Mice received repeated WIN 55,212-2, its inactive enantiomer, WIN 55,212-3 or vehicle (i.th., bid, 5 days). WIN 55,212-2, but not WIN 55,212-3 or vehicle, produced a time-related increased sensitivity to non-noxious and noxious stimuli. WIN 55,212-2, but not WIN 55,212-3 or vehicle, elicited a significant increase in lumbar spinal dynorphin content at treatment day 5. Increased sensitivity to mechanical and thermal stimuli produced by WIN 55,212-2 was reversed to baseline levels by i.th. MK-801 or dynorphin antiserum; control serum had no effect. WIN 55,212-2, but not WIN 55,212-3 or vehicle, produced dose-related antinociception and repeated administration resulted in antinociceptive tolerance. While MK-801 and dynorphin antiserum did not alter acute antinociception produced by WIN 55,212-2, these substances significantly blocked antinociceptive tolerance when given immediately prior to WIN 55,212-2 challenge on day 5. Daily MK-801 pretreatments, prior to WIN 55,212-2 injection, also produced a significant block of antinociceptive tolerance. These data suggest that like opioids, repeated spinal administration of a cannabinoid CB1 agonist elicits abnormal pain, which results in increased expression of spinal dynorphin. Manipulations that block cannabinoid-induced pain also block the behavioral manifestation of cannabinoid tolerance.

Analgesics↗
PubMed2001

Distinct potassium channels on pain-sensing neurons.

Differential expression of ion channels contributes functional diversity to sensory neuron signaling. We find nerve injury induced by the Chung model of neuropathic pain leads to striking reductions in voltage-gated K(+) (Kv) channel subunit expression in dorsal root ganglia (DRG) neurons, suggesting a potential molecular mechanism for hyperexcitability of injured nerves. Moreover, specific classes of DRG neurons express distinct Kv channel subunit combinations. Importantly, Kv1.4 is the sole Kv1 alpha subunit expressed in smaller diameter neurons, suggesting that homomeric Kv1.4 channels predominate in A delta and C fibers arising from these cells. These neurons are presumably nociceptors, because they also express the VR-1 capsaicin receptor, calcitonin gene-related peptide, and/or Na(+) channel SNS/PN3/Nav1.8. In contrast, larger diameter neurons associated with mechanoreception and proprioception express high levels of Kv1.1 and Kv1.2 without Kv1.4 or other Kv1 alpha subunits, suggesting that heteromers of these subunits predominate on large, myelinated afferent axons that extend from these cells.

Animals↗
PubMed2001

Characterization and humanization of a monoclonal antibody that neutralizes human leukocyte interferon: a candidate therapeutic for IDDM and SLE.

We have developed a panel of murine monoclonal antibodies that recognize human interferon alpha. One of these mononclonal antibodies binds and neutralizes, with high affinity, all of seven tested recombinant human interferon alphas. This mononclonal antibody also neutralizes the interferon activity present in two independent pools of interferon alphas prepared following stimulation of human peripheral blood leukocytes. The complementary determining regions from this murine mononclonal antibody were transferred to a human IgG2 heavy chain and to a human kappa1 light chain. In addition, six (heavy chain) and two (light chain) amino acids were transferred from the framework regions. This generated a humanized mononclonal antibody that retained the specificity of the mouse parent. The humanized anti-interferon alpha antibody is a candidate therapeutic for those diseases, such as insulin-dependent diabetes, systemic lupus erythematosis, psoriasis and Crohn's disease, which are all characterized by pathological expression of interferon alpha.

Amino Acid Sequence↗
PubMed2001

Inhibition of neuropathic pain by selective ablation of brainstem medullary cells expressing the mu-opioid receptor.

Neurons in the rostroventromedial medulla (RVM) project to spinal loci where the neurons inhibit or facilitate pain transmission. Abnormal activity of facilitatory processes may thus represent a mechanism of chronic pain. This possibility and the phenotype of RVM cells that might underlie experimental neuropathic pain were investigated. Cells expressing mu-opioid receptors were targeted with a single microinjection of saporin conjugated to the mu-opioid agonist dermorphin; unconjugated saporin and dermorphin were used as controls. RVM dermorphin-saporin, but not dermorphin or saporin, significantly decreased cells expressing mu-opioid receptor transcript. RVM dermorphin, saporin, or dermorphin-saporin did not change baseline hindpaw sensitivity to non-noxious or noxious stimuli. Spinal nerve ligation (SNL) injury in rats pretreated with RVM dermorphin-saporin failed to elicit the expected increase in sensitivity to non-noxious mechanical or noxious thermal stimuli applied to the paw. RVM dermorphin or saporin did not alter SNL-induced experimental pain, and no pretreatment affected the responses of sham-operated groups. This protective effect of dermorphin-saporin against SNL-induced pain was blocked by beta-funaltrexamine, a selective mu-opioid receptor antagonist, indicating specific interaction of dermorphin-saporin with the mu-opioid receptor. RVM microinjection of dermorphin-saporin, but not of dermorphin or saporin, in animals previously undergoing SNL showed a time-related reversal of the SNL-induced experimental pain to preinjury baseline levels. Thus, loss of RVM mu receptor-expressing cells both prevents and reverses experimental neuropathic pain. The data support the hypothesis that inappropriate tonic-descending facilitation may underlie some chronic pain states and offer new possibilities for the design of therapeutic strategies.

Animals↗
PubMed2001

Pronociceptive actions of dynorphin maintain chronic neuropathic pain.

Whereas tissue injury increases spinal dynorphin expression, the functional relevance of this upregulation to persistent pain is unknown. Here, mice lacking the prodynorphin gene were studied for sensitivity to non-noxious and noxious stimuli, before and after induction of experimental neuropathic pain. Prodynorphin knock-out (KO) mice had normal responses to acute non-noxious stimuli and a mild increased sensitivity to some noxious stimuli. After spinal nerve ligation (SNL), both wild-type (WT) and KO mice demonstrated decreased thresholds to innocuous mechanical and to noxious thermal stimuli, indicating that dynorphin is not required for initiation of neuropathic pain. However, whereas neuropathic pain was sustained in WT mice, KO mice showed a return to baselines by post-SNL day 10. In WT mice, SNL upregulated lumbar dynorphin content on day 10, but not day 2, after injury. Intrathecal dynorphin antiserum reversed neuropathic pain in WT mice at post-SNL day 10 (when dynorphin was upregulated) but not on post-SNL day 2; intrathecal MK-801 reversed SNL-pain at both times. Opioid (mu, delta, and kappa) receptor density and G-protein activation were not different between WT and KO mice and were unchanged by SNL injury. The observations suggest (1) an early, dynorphin-independent phase of neuropathic pain and a later dynorphin-dependent stage, (2) that upregulated spinal dynorphin is pronociceptive and required for the maintenance of persistent neuropathic pain, and (3) that processes required for the initiation and the maintenance of the neuropathic pain state are distinct. Identification of mechanisms that maintain neuropathic pain appears important for strategies to treat neuropathic pain.

Animals↗
PubMed2001

Nerve injury-induced tactile allodynia is mediated via ascending spinal dorsal column projections.

Peripheral nerve injury produces signs of neuropathic pain including tactile allodynia and thermal hyperalgesia, sensory modalities which may be associated with different neuronal pathways. Studies of spinally-transected, nerve-injured rats have led to suggestions that thermal hyperalgesia may be mediated predominately through local spinal circuitry whereas ascending input to supraspinal sites is critical to the manifestation of tactile allodynia. Here, the nature of ascending spinal input mediating tactile allodynia was explored using selective spinal lesions. Male Sprague-Dawley rats received L(5)/L(6) spinal nerve ligation (SNL) and ipsilateral or contralateral (relative to the SNL side) lesions including spinal hemisections and bilateral and unilateral dorsal column lesions. The rats were maintained in a sling and monitored for tactile allodynia by measuring withdrawal thresholds to probing with von Frey filaments 24 h after the hemisection. Rats receiving dorsal column lesions demonstrated no motor deficits while rats receiving spinal hemisection showed paralysis of the paw which nevertheless responded to strong noxious stimulation. Spinal hemisection ipsilateral, but not contralateral, to SNL completely abolished tactile allodynia while maintaining spinal nocifensive reflexes to noxious pinch. Bilateral and ipsilateral dorsal column lesions blocked tactile allodynia while contralateral dorsal column lesions did not. Administration of lidocaine into the nucleus gracilis ipsilateral to SNL also blocked tactile allodynia, but did not alter thermal hyperalgesia in SNL rats or increase thermal nociceptive responses in sham-operated rats. Lidocaine microinjected into the contralateral nucleus gracilis produced no changes in responses to tactile or thermal stimuli in either group. These results indicate that tactile allodynia after peripheral nerve injury is dependent upon inputs to supraspinal sites. Furthermore, it is apparent that afferent signals interpreted as tactile allodynia course through the ipsilateral dorsal columns and are relayed through the nucleus gracilis. This neuronal pathway is consistent with the interpretation that tactile allodynia pursuant to peripheral nerve injury is transmitted to the central nervous system by means of large diameter, myelinated fibers.

Anesthetics, Local↗
PubMed2001

Changes in the biomechanical properties of neutrophils and endothelial cells during adhesion.

This study examined changes in the biomechanical properties of cultured pulmonary microvascular endothelial cells (ECs) and neutrophils induced by adhesion of neutrophils to these ECs. The biomechanical properties of cells were evaluated using magnetic twisting cytometry, which measures the angular rotation of ferromagnetic beads bound to cells through antibody ligation on application of a specified magnetic torque. Adhesion of neutrophils to 24-hour tumor necrosis factor-alpha (TNF-alpha)-treated ECs, but not to untreated ECs, induced an increase in EC stiffness within 2 minutes, which was accompanied by an increase and a reorganization of F-actin in ECs. A cell-permeant, phosphoinositide-binding peptide attenuated the EC stiffening response, suggesting that intracellular phosphoinositides are required. The stiffening response was not inhibited by ML-7, a myosin light-chain kinase inhibitor, or BAPTA, an intracellular Ca2+ chelator. Moreover, the phosphorylation pattern of the regulatory myosin light chains was unaltered within 15 minutes of neutrophil adherence. These data suggested that the EC stiffening response appeared not to be mediated by myosin light-chain-dependent mechanisms. Concomitantly, neutrophil adhesion to 24-hour TNF-alpha-treated ECs also induced changes in the biomechanical properties of neutrophils compared to neutrophils bound to untreated ECs. Taken together, these results demonstrated that neutrophil adhesion to TNF-alpha-treated ECs induces changes in the biomechanical properties of both cell types through actin cytoskeletal remodeling. These changes may modulate neutrophil transmigration across the endothelium during inflammation.

Actins↗
PubMed2001

Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance.

Many clinical case reports have suggested that sustained opioid exposure can elicit unexpected, paradoxical pain. Here, we explore the possibility that (1) opioid-induced pain results from tonic activation of descending pain facilitation arising in the rostral ventromedial medulla (RVM) and (2) the presence of such pain manifests behaviorally as antinociceptive tolerance. Rats implanted subcutaneously with pellets or osmotic minipumps delivering morphine displayed time-related tactile allodynia and thermal hyperalgesia (i. e., opioid-induced "pain"); placebo pellets or saline minipumps did not change thresholds. Opioid-induced pain was observed while morphine delivery continued and while the rats were not in withdrawal. RVM lidocaine, or bilateral lesions of the dorsolateral funiculus (DLF), did not change response thresholds in placebo-pelleted rats but blocked opioid-induced pain. The intrathecal morphine antinociceptive dose-response curve (DRC) in morphine-pelleted rats was displaced to the right of that in placebo-pelleted rats, indicating antinociceptive "tolerance." RVM lidocaine or bilateral DLF lesion did not alter the intrathecal morphine DRC in placebo-pelleted rats but blocked the rightward displacement seen in morphine-pelleted animals. The subcutaneous morphine antinociceptive DRC in morphine-pelleted rats was displaced to the right of that in placebo-pelleted rats; this right shift was blocked by RVM lidocaine. The data show that (1) opioids elicit pain through tonic activation of bulbospinal facilitation from the RVM, (2) increased pain decreases spinal opioid antinociceptive potency, and (3) blockade of pain restores antinociceptive potency, revealing no change in antinociceptive signal transduction. These studies offer a mechanism for paradoxical opioid-induced pain and allow the development of approaches by which the loss of analgesic activity of opioids might be inhibited.

Analgesics↗
PubMed2001

Opioid peptide receptor studies. 14. Stereochemistry determines agonist efficacy and intrinsic efficacy in the [(35)S]GTP-gamma-S functional binding assay.

Previous data obtained with the cloned rat mu opioid receptor demonstrated that stereochemistry affects the four parameters of the ligand-receptor interaction: potency (ED(50)), efficacy (maximal stimulation), intrinsic efficacy (effect as a function of receptor occupation), and binding affinity. This study evaluated the activities of structurally diverse opioid receptor ligands in the [(35)S]GTP-gamma-S binding assay, comparing the relationship between receptor binding, activation, efficacy, and intrinsic efficacy. The data, obtained with cloned rat mu receptors, demonstrated that an analgetic, (-)-5-m-hydroxyphenyl-2-methylmorphan (NIH8508), and its (+)-isomer (NIH8509), behave as partial agonists, but had different intrinsic efficacy in the [(35)S]GTP-gamma-S binding assay. Replacement of the methyl group with the phenethyl group on the piperidine nitrogen of NIH8508 and NIH8509 [(1R,5S)-AH019 and (1S, 5R)-AH019] increased affinity for the mu receptor and eliminated any agonist effect, supporting the hypothesis that certain structural features make these compounds antagonists. These study also show that all of the fully efficacious mu agonists studied here had high levels of intrinsic efficacy, producing a 50% response at about 10% receptor occupancy. Comparison of the binding K(i) in competitively inhibiting [(125)I]IOXY binding to the functional K(i) for opioid antagonists [K(i)(IOXY)/K(i)(GTP-gamma-S)] provides more detailed evidence that the [(35)S]GTP-gamma-S binding assay can be used to reliably determine apparent functional antagonist K(i) values in addition to agonist ED(50), efficacy and intrinsic efficacy.

Analgesics, Opioid↗
PubMed2001

Effect of photodynamic therapy (PDT) on the expression of pro-apoptotic protein Bak in nasopharyngeal carcinoma (NPC).

BACKGROUND AND OBJECTIVE: To investigate the effect of photodynamic therapy (PDT) on expression of the pro-apoptotic gene Bak in nasopharyngeal carcinoma (NPC). STUDY DESIGN/MATERIALS AND METHODS: Apoptosis and expression of the pro-apoptotic gene Bak on the tumor tissues from both pre- and post-PDT were determined using the in situ end labeling (ISEL), standard immunohistochemistry technique and western blot, respectively, in 24 patients with either persistent or recurrent NPC after radiotherapy. RESULTS: Before PDT, apoptotic index (AI) in tumor tissue was 1.2 +/- 0.6. At 6, 12, 24 and 48 hours after PDT, AI were 6.5 +/- 3.1, 23.6 +/- 8.3, 67.2 +/- 14.2 and 89.3 +/- 8.1, respectively. PDT caused apoptosis in a time-dependent fashion. Immunohistochemical assay indicated that 75% (18/24) of the patients had an upgrade expression of Bak protein in their tumor tissues after PDT. Increases in expression of Bak from PDT were also confirmed by western blot analysis. CONCLUSIONS: PDT probably causes NPC cell apoptosis through an upregulation of the pro-apoptotic protein Bak expression.

Adult↗
PubMed2001

CYP gene polymorphisms and early menarche.

Early age at menarche is a risk factor for breast cancer. A previous study reported a significant positive association between the CYP3A4*1B variant allele and early puberty. We investigated whether polymorphisms of the CYP3A4, CYP17, CYP1B1, and CYP1A2 genes predict the age at onset of menarche. Five hundred eighty-three nulliparous women between ages 17 and 35, of various ethnic backgrounds, completed a questionnaire that included information about menstrual history. Samples of DNA were provided and used to genotype these women for polymorphic variants in the four genes. There was no significant difference in mean age at menarche between women who carried two variant CYP17 A2 alleles (12.5 years) and women who carried one or no variant allele (12.5 years) (P = 0.8, adjusted for ethnic group and year of birth). Similar results were found for the CYP1B1*3 variant allele and for the CYP1A2*1F variant allele. Women who carried two variant CYP3A4*1B alleles had an earlier mean age at menarche (12.0 years) than women who carried one or no variant allele (12.6 years) (P = 0.02). However, after adjusting for ethnic group and year of birth, no significant differences in mean age at menarche were found. The polymorphic variants of the CYP3A4, CYP17, CYP1B1, and CYP1A2 genes are unlikely to influence age of menarche.

Adolescent↗
PubMed2001

Muscarinic versus nicotinic modulation of a visual task. a pet study using drug probes.

Little is known about acetylcholine (ACh) modulation of central visual processing in humans. Receptor densities in visual brain regions are differentially distributed suggesting that receptor subtypes have different functions. Using PET, we have previously described the brain regions activated by a simple pattern-flash stimulus in healthy elderly subjects. To evaluate muscarinic and nicotinic contributions to ACh modulation of visual processing, we scanned elderly subjects watching the pattern-flash stimulus during no drug, during physostigmine augmentation, and during scopolamine antagonism of physostigmine's action. These manipulations of ACh significantly altered regional cerebral blood flow (rCBF) in brain regions activated by the task. The pattern of rCBF values across drug conditions suggested that muscarinic and nicotinic effects were dissociated. Muscarinic action predominated in striate cortex (Brodmann Area, BA 17) and lateral visual association areas (BA 18, 19), while nicotinic action predominated in the thalamus and inferior parietal regions (BA 39/40). Both muscarinic and nicotinic actions increased rCBF in some regions while decreasing it in others. A parsimonious reconciliation of these results with functional anatomy suggests that muscarinic action modulates visual attribute processing, while nicotinic action modulates arousal and selective attention to the visual task.

Aged↗
PubMed2001

A motif-based profile scanning approach for genome-wide prediction of signaling pathways.

The rapid increase in genomic information requires new techniques to infer protein function and predict protein-protein interactions. Bioinformatics identifies modular signaling domains within protein sequences with a high degree of accuracy. In contrast, little success has been achieved in predicting short linear sequence motifs within proteins targeted by these domains to form complex signaling networks. Here we describe a peptide library-based searching algorithm, accessible over the World Wide Web, that identifies sequence motifs likely to bind to specific protein domains such as 14-3-3, SH2, and SH3 domains, or likely to be phosphorylated by specific protein kinases such as Src and AKT. Predictions from database searches for proteins containing motifs matching two different domains in a common signaling pathway provides a much higher success rate. This technology facilitates prediction of cell signaling networks within proteomes, and could aid in the identification of drug targets for the treatment of human diseases.

Algorithms↗
PubMed2001

RT-PCR reveals muscarinic acetylcholine receptor mRNA in the pre-Bötzinger complex.

Muscarinic receptors mediate the postsynaptic excitatory effects of acetylcholine (ACh) on inspiratory neurons in the pre-Bötzinger complex (pre-BötC), the hypothesized site for respiratory rhythm generation. Because pharmacological tools for identifying the subtypes of the muscarinic receptors that underlie these effects are limited, we probed for mRNA for these receptors in the pre-BötC. We used RT-PCR to determine the expression of muscarinic receptor subtypes in tissue punches of the pre-BötC taken from rat medullary slices. Cholinergic receptor subtype M(2) and M(3) mRNAs were observed in the first round of PCR amplification. All five subtypes, M(1)-M(5), were observed in the second round of amplification. Our results suggest that the majority of muscarinic receptor subtypes in the pre-BötC are M(2) and M(3), with minor expression of M(1), M(4), and M(5).

Animals↗
PubMed2001

A double-blind, placebo-controlled study of the use of amphetamine in the treatment of aphasia.

BACKGROUND AND PURPOSE: A number of studies suggest that drugs which increase the release of norepinephrine promote recovery when administered late (days to weeks) after brain injury in animals. A small number of clinical studies have investigated the effects of the noradrenergic agonist dextroamphetamine in patients recovering from motor deficits following stroke. To determine whether these findings extend to communication deficits subsequent to stroke, we administered dextroamphetamine, paired with speech/language therapy, to patients with aphasia. METHODS: In a prospective, double-blind study, 21 aphasic patients with an acute nonhemorrhagic infarction were randomly assigned to receive either 10 mg dextroamphetamine or a placebo. Patients were entered between days 16 and 45 after onset and were treated on a 3-day/4-day schedule for 10 sessions. Thirty minutes after drug/placebo administration, subjects received a 1-hour session of speech/language therapy. The Porch Index of Communicative Ability was used at baseline, at 1 week off the drug, and at 6 months after onset as the dependent language measure. RESULTS: Although there were no differences between the drug and placebo groups before treatment (P=0.807), by 1 week after the 10 drug treatments ended there was a significant difference in gain scores between the groups (P=0.0153), with the greater gain in the dextroamphetamine group. The difference was still significant when corrected for initial aphasia severity and age. At the 6-month follow-up, the difference in gain scores between the groups had increased; however, the difference was not significant (P=0.0482) after correction for multiple comparisons. CONCLUSIONS: Administration of dextroamphetamine paired with 10 1-hour sessions of speech/language therapy facilitated recovery from aphasia in a small group of patients in the subacute period after stroke. Neuromodulation with dextroamphetamine, and perhaps other drugs that increase central nervous system noradrenaline levels, may facilitate recovery when paired with focused behavioral treatment.

Adrenergic Uptake Inhibitors↗
PubMed2001

Generation of a humanized, high affinity anti-tissue factor antibody for use as a novel antithrombotic therapeutic.

Blocking the cofactor function of human tissue factor may be beneficial in various coagulation-mediated diseases. The murine antibody D3 binds to the membrane proximal substrate interaction region of human tissue factor and blocks tissue factor function even in the presence of bound factor VIIa. The cloned murine D3 antibody was humanized and affinity matured by exchanging amino acids in the complementarity determining regions as well as in the antibody framework. The humanized antibody, D3H44, bound to tissue factor with a 100-fold increased affinity (KD 0.1 nM) as compared to the original murine and chimeric versions. Depending on the particular disease, different pharmacokinetic properties of the antibody may be required and, therefore, several antibody variants-- F(ab), F(ab')2, IgG2, IgG4 and IgG4b-were generated. In vitro, the humanized D3 antibodies displayed potent inhibition of plasma clotting and tissue factor: factor VIIa-mediated activation of factors IX and X (e.g. D3H44-F(ab')2, IC50(F.X) 47 pM). In addition, D3H44-F(ab')2 completely prevented fibrin deposition in a human ex vivo thrombosis model under venous blood flow conditions (IC50 37 nM). The humanized D3 antibodies may be utilized for treatment of cardiovascular diseases which involve tissue factor activity, e.g. acute coronary syndrome and venous thrombosis.

Amino Acid Sequence↗
PubMed2000

High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R.

Immunoglobulin G (IgG) Fc receptors play a critical role in linking IgG antibody-mediated immune responses with cellular effector functions. A high resolution map of the binding site on human IgG1 for human Fc gamma RI, Fc gamma RIIA, Fc gamma RIIB, Fc gamma RIIIA, and FcRn receptors has been determined. A common set of IgG1 residues is involved in binding to all Fc gamma R; Fc gamma RII and Fc gamma RIII also utilize residues outside this common set. In addition to residues which, when altered, abrogated binding to one or more of the receptors, several residues were found that improved binding only to specific receptors or simultaneously improved binding to one type of receptor and reduced binding to another type. Select IgG1 variants with improved binding to Fc gamma RIIIA exhibited up to 100% enhancement in antibody-dependent cell cytotoxicity using human effector cells; these variants included changes at residues not found at the binding interface in the IgG/Fc gamma RIIIA co-crystal structure (Sondermann, P., Huber, R., Oosthuizen, V., and Jacob, U. (2000) Nature 406, 267-273). These engineered antibodies may have important implications for improving antibody therapeutic efficacy.

Antibody-Dependent Cell Cytotoxicity↗