Biomedical subjects

J Y Xu

Publications and source records attributed to J Y Xu.

At least 37 records · Page 2Linked to original sources

PubMed1996

[Synergism of sobuzoxane in combination with doxorubicin against leukemia P388 in mice].

AIM: To study the antitumor activity of sobuzoxane (Sob) in combination with doxorubicin (Dox) and the effect of Sob on Dox-induced cardiotoxicity. METHODS: DBA/2 mice bearing transplanted leukemia P388 were given i.v. Dox 2 mg.kg-1.d-1 for 3 d, 4 mg.kg-1.d-1 for 1 d combined with ig Sob 20, 40 mg.kg-1.d-1 for 7 d. The increase in life span (ILS) of each group was recorded in 30 d. The myocardium of moribund mice was examined by transmission electron microscopy. RESULTS: The ILS of combination therapeutic groups of Sob with Dox was 48.7%, 57.3%, 59.0%, and 62.4% respectively, which were 30%-90% higher than the sum of ILS of two groups treated with Dox and Sob separately (P < 0.01). The ultrastructural injury of cardiomyocytes of P388-bearing mice caused by combination chemotherapy with Dox plus Sob was markedly attenuated compared with Dox alone. CONCLUSION: Sob with Dox exhibited an antitumor synergistic effect on leukemia P388, and the cardiotoxicity of Dox was reduced by Sob.

Animals↗

PubMed1996

N-cyclobutylmethyl analog of normorphinone, N-CBM-TAMO: a short-term opioid agonist and long-term Mu-selective irreversible opioid antagonist.

The antinociceptive and opioid binding properties of the N-cyclobutylmethyl analog of normorphinone, 14 alpha, 14' beta-[dithiobis[(2-oxo-2, 1-ethanediyl)imino]]bis[7,8-dihydro-N-(cyclobutylmethyl)-normor phinone] (N-CBM-TAMO) were investigated. This compound is a dimer, containing a disulfide capable of binding to thiol groups on the opioid receptor. Competition radioligand binding assays with bovine striatal membranes demonstrated that N-CBM-TAMO displayed a higher affinity for mu opioid receptors than for kappa and delta receptors. Incubation of membranes with N-CBM-TAMO resulted in wash-resistant inhibition of the binding of the mu-selective peptide [3H][D-Ala2,(Me)Phe4, Gly(ol)5]-enkephalin, the kappa-selective opioid [3H]U69,593 ((trans)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide+ ++ methanesulfonate hydrate)) and, to a lesser extent, the delta-selective peptide [D-Pen2, p-Cl-phenylalanine4, D-Pen5]enkephalin. Scatchard analysis of saturation binding data showed that N-CBM-TAMO decreased the Bmax value without affecting the Kd value for [3H][D-Ala2,(Me)Phe4, Gly(ol)5]enkephalin binding, whereas, N-CBM-TAMO increased the Kd value without altering the Bmax value for [3H]U69,593, which suggests that N-CBM-TAMO interacted covalently with the mu but not the kappa receptor. In the mouse 55 degrees C warm-water tail-flick test, N-CBM-TAMO given supraspinally acted as an agonist with low efficacy because only submaximal antinociception was observed at doses up to 100 nmol. The antinociception induced by N-CBM-TAMO in the tail-flick test was partially blocked by both the mu-selective antagonist beta-funaltrexamine and the kappa-selective antagonist nor-binaltorphimine. In the mouse acetic acid writhing test, N-CBM-TAMO acted as a full agonist with a D50 value of 0.08 (0.04-0.14) nmol, and the antinociception was blocked by coadministration of the kappa-selective antagonist nor-binaltorphimine. Pretreatment of mice with an i.c.v. dose of N-CBM-TAMO of 10 nmol, a dose that exhibited modest short-term antinociception in the tail-flick test, produced a time- and dose-dependent long-term antagonism of morphine-induced antinociception in an irreversible manner in this assay. Pretreatment of mice with i.c.v. N-CBM-TAMO at doses of 3 nmol and higher, which produced supermaximal short-term antinociception in the writhing test, produced a time- and dose-dependent long-term antagonism of U50,488 (trans)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methanesulfonate hydrate)-induced antinociception in a reversible manner, probably because of the development of tolerance. These in vivo data, together with the in vitro binding data, demonstrate that N-CBM-TAMO is a potent kappa agonist and at higher doses produces antinociception mediated by mu receptors. N-CBM-TAMO also produces long-term noncompetitive antagonism of antinociception mediated by mu opioid receptors.

Analgesics, Opioid↗

PubMed1995

Nitric oxide/cyclic guanosine monophosphate system in the spinal cord differentially modulates intracerebroventricularly administered morphine- and beta-endorphin-induced antinociception in the mouse.

Our study was designed to study the modulatory role of nitric oxide/cyclic guanosine monophosphate in the spinal cord on the antinociception induced by morphine and beta-endorphin given supraspinally. The antinociception was assessed by the tail-flick test in male ICR mice. The antinociception induced by intracerebroventricularly (i.c.v.) administered morphine was potentiated by intrathecal (i.t) injection of N omega-nitro-L-arginine (2 micrograms), hemoglobin (120 micrograms) or methylene blue (5 micrograms), but was attenuated by i.t. administered L-arginine (20 micrograms) or 3-morpholino-sydnonimine (SIN-1, 5 micrograms). In contrast, the antinociception induced by i.c.v. administered beta-endorphin was attenuated by i.t. pretreatment with N omega-nitro-L-arginine (2 micrograms) and the attenuation of beta-endorphin-induced antinociception by N omega-nitro-L-arginine was reversed by i.t. administered L-arginine (20 micrograms). The antinociception induced by i.c.v. administered beta-endorphin was also attenuated by i.t. administration of hemoglobin (120 micrograms) or methylene blue (5 micrograms). Intrathecal pretreatment with L-arginine did not affect i.c.v. administered beta-endorphin-induced antinociception. It is concluded that the inhibition of nitric oxide/cyclic guanosine monophosphate system in the spinal cord potentiates i.c.v. administered morphine-induced antinociception but attenuates i.c.v. beta-endorphin-induced antinociception. The activation of nitric oxide/cyclic guanosine monophosphate system in the spinal cord attenuates i.c.v. administered morphine-induced antinociception but does not affect i.c.v. administered beta-endorphin-induced antinociception.

Analgesics↗

PubMed1994

Role of nitric oxide/cyclic GMP in i.c.v. administered beta-endorphin- and (+)-cis-dioxolane-induced antinociception in the mouse.

(+)-cis-Dioxolane (0.5-2 micrograms), a muscarinic receptor agonist, given intracerebroventricularly (i.c.v.) produced a dose-dependent inhibition of the tail-flick response in male ICR mice. (+)-cis-Dioxolane given i.c.v. at a subanalgesic dose (0.25 micrograms), selectively potentiated the antinociceptive response induced by i.c.v. administered beta-endorphin, an epsilon-opioid receptor agonist, but not morphine or [D-Ala2,NMePhe4,Gly5-ol]enkephalin (DAMGO), mu-opioid receptor agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE), a delta receptor agonist, or trans(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methane sulfonate (U50,488H), a kappa-opioid receptor agonist. The antinociceptive response induced by (+)-cis-dioxolane given i.c.v. was attenuated by i.c.v. treatment with N omega-nitro-L-arginine (1 microgram), hemoglobin (120 micrograms) or methylene blue (10 micrograms). The antinociception induced by carbachol given i.c.v. was also antagonized by the i.c.v. treatment with N omega-nitro-L-arginine (1 microgram). However, the same treatment with N omega-nitro-L-arginine, hemoglobin or methylene blue did not affect the beta-endorphin-induced antinociception. The potentiation of beta-endorphin-induced antinociception by (+)-cis-dioxolane was reversed by i.c.v. treatment with N omega-nitro-L-arginine (1 microgram), hemoglobin (120 micrograms) or methylene blue (10 micrograms). On the other hand, the antinociceptive response induced by (+)-cis-dioxolane (1 microgram) given i.c.v. was potentiated by i.c.v. administered L-arginine (20 micrograms) but not D-arginine (20 micrograms). Dibutyryl cyclic GMP at 0.5-2.0 micrograms given i.c.v. produced an antinociceptive response and at subanalgesic dose (0.1 microgram) potentiated i.c.v. beta-endorphin-induced antinociception.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1994

Effect of octreotide on dynamic excretion of bile in Chinese acromegalic patients assessed by [99mTc]EHIDA hepatobiliary scan.

We used [99mTc]EHIDA hepatobiliary scintigraphy to determine whether both hepatic bile secretion and gallbladder contractility are suppressed in acromegalic patients receiving long-term treatment with the somatostatin analogue octreotide. We studied three groups of patients: group 1, untreated patients; group 2, average dose of octreotide 500 +/- 100 micrograms/day for 33 +/- 4 months; and group 3, 1000 +/- 200 micrograms/day for 33 +/- 4 months. Images were taken at specified time intervals during the 120-min period following injection of EHIDA. After a single injection of octreotide, group 1 patients demonstrated delayed visualization of the radioisotope in the liver, gallbladder, and duodenum. At the end of long-term treatment, group 2 patients showed a delay in appearance of maximal radioactivity in the gallbladder. Two weeks following discontinuation of octreotide, this parameter had decreased significantly (P < 0.001). In group 3, visualization of the liver, gallbladder, and duodenum were prolonged, with delayed visualization of the gallbladder persisting two weeks after withdrawal (P < 0.005). These results indicate that gallbladder contractility is decreased after a single injection of octreotide and that during chronic octreotide therapy the rate of bile secretion is reduced. Impaired gallbladder contractility normalizes more rapidly after discontinuation of octreotide in patients receiving low doses of the analog.

Acromegaly↗

PubMed1993

Increase of nitric oxide by L-arginine potentiates beta-endorphin- but not mu-, delta- or kappa-opioid agonist-induced antinociception in the mouse.

L-Arginine pretreated i.c.v. produced a time- and dose-dependent potentiation of beta-endorphin-induced inhibition of the tail-flick response in ICR mice. However, the inhibition of the tail-flick response induced by morphine, DAMGO ([D-Ala2,NMePhe4,Gly5-ol]enkephalin), DPDPE ([D-Pen2,D-Pen5]enkephalin or U50,488H given i.c.v. was not potentiated by i.c.v. pretreated L-arginine. The results indicate that L-arginine selectively potentiates antinociception induced by epsilon-opioid receptor agonist, but not mu-, delta- or kappa-opioid receptor agonist. L-Arginine pretreated i.t. did not potentiate i.c.v. administered beta-endorphin-induced inhibition of the tail-flick response, indicating that the potentiating effect of L-arginine on beta-endorphin-induced antinociception is located at the supraspinal sites but not at the spinal sites.

Analgesics↗

PubMed1993

Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120.

HIV infection induces antibodies that mediate neutralization of cell-free virus and may protect against viral infection. Neutralizing human mAb that bind to the third hypervariable domain (V3) of gp120 have been generated from PBL of HIV-seropositive subjects. Twelve such mAb recognize 9 different epitopes spanning an 11 amino acid stretch at the tip of the V3MN loop. The epitopes of an additional two mAb have not been precisely determined but occur within a 15-mer peptide around the tip of the V3 loop. Eleven of 13 mAb are reactive with at least one other V3 peptide besides MN, indicating that cross-reactivity is a common phenomenon amongst anti-V3 antibodies. All the mAb achieved 50% neutralization of HIVMN at antibody concentrations of 12 to 4700 ng/ml. Two mAb, which recognized epitopes at the top of the V3 loop, GPGR and GRAF, neutralized strains as divergent as MN and IIIB. The affinities of all mAb tested were shown to be substantially higher for the rgp120 than for a 23-mer peptide from the V3 loop of the homologous strain. A significant inverse correlation was demonstrated between affinities and the 50% neutralizing doses for HIVMN.

Amino Acid Sequence↗

PubMed1993

Molecular mimicry accompanying HIV-1 infection: human monoclonal antibodies that bind to gp41 and to astrocytes.

Monoclonal antibodies that bound to HIV gp41 and cross-reacted with astrocytes were recovered from the blood of three patients infected with HIV-1. Mapping of the specificity of these monoclonal antibodies, using synthetic gp41 peptides, located their epitope to amino acids 644-663 and established their conformation dependence. Six other human monoclonal anti-HIV antibodies were found to bind to HIV gp41 or gp120 but not to reactive astrocytes in brain tissue. Sharing of linear or conformational protein determinants between disparate viral and host proteins is termed molecular mimicry. The consequences of such mimicry by anti-viral antibodies interacting with astrocytes may play a role in the dementia of AIDS patients since a major function of astrocytes is to maintain the appropriate milieu for neuronal function. The finding of such cross-reactive antibodies adds to the evidence for a possible autoimmune pathogenesis in some of the disease manifestations accompanying HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed1993

[Characterization of a fluorouracil-resistant human gastric carcinoma cell line and its morphological behavior].

A fluorouracil (FU)-resistant human carcinoma cell line (SGC-7901/R) was established in culture by progressively increasing the concentration of FU from 50 ng.ml-1 to 2.5 mg.ml-1. The cell line has been successfully subcultured for more than 150 passages during more than 2 years. Its degree of FU resistance was 139-fold vs that of FU sensitive cell line (SGC-7901/S), and the resistant phenotype was stable when cells were cultured for 23 passages in FU-free medium. The doubling time was 17.3 and 25.6 h for resistant cells and parental cells, respectively. Swiss (nu/nu) nude mice were used for the in vivo experiment, the FU-resistant cell line also exhibited resistance to FU and cross-resistance to mitomycin C. FU inhibited markedly the incorporation of [3H]UR into sensitive cells and only showed a 31.6% inhibition with FU 100 micrograms.ml-1 in resistant cells. For the incorporation of [3H]TdR into DNA, inhibitory rates were seen with different concentrations of FU in resistant cells. By morphologic observation, SGC-7901/R cells showed little secretion but without any tendency to glandular pattern. Their nuclei were allotype with enlarged perinuclear space and a few intranuclear pseudoinclusions. The mitotic phase of cells was found frequently. The phenotype of resistant cell line can be deduced more malignant than that of parental cell line.

Animals↗

PubMed1993

[Therapeutic effects and mechanisms of tetramethylpyrazine on lung injury in acute haemorrhagic necrotizing pancreatitis in rats].

To evaluate the therapeutic effects and mechanisms of tetramethylpyrazine (TMP), a Chinese herbal medicine, on the lung injury in bile-induced acute haemorrhagic necrotizing pancreatitis (AHNP) in the SD rats, the rats were randomly divided into three groups: sham-operative, untreated and TMP treated. AHNP model were induced by ligation with 5% taurocholate. The changes of lung index, serum lipid peroxide (LPO), TXB2, 6-keto-PGF1 alpha, and lung pathology at light and electron microscope were all investigated at 1, 6, 12 hours after induction of AHNP model. Survival rate of AHNP in rats were recorded also. Results of the study showed that in untreated group, the time-related progressive pancreatic haemorrhage and necrosis, accompanied by pancreatitis-associated lung injury, such as pronounced pulmonary congestion, alveolar and interstitial edema, polymorphonuclear granulocytes infiltration, transparent membrane formation, the density of layer body in type II endothelial cells decreasing, with some vacuole formation, mitochondria, endoplasmic reticulum swollen, basal membrane of endothelial cells rupture were observed. The level of LPO elevated at 1 hour after induction of AHNP and peaked at 12 hours. TXB2 and 6-keto-PGF1 alpha was increased. Using TMP treatment, survival rate increased, and lung at light and electron microscope were much improved and lung index, value of LPO, TXB2 decreased significantly, 6-keto-PGF1 alpha increased slightly, the ratio of TXB2/6-keto-PGF1 alpha was stabilized. It was suggested that TMP has definite therapeutic effects on AHNP-related lung injury in rats, and exerted by scavenging oxygen free radical, inhibiting synthesis of TXA2, augmenting production of PGI2 and maintaining balance between TXA2 and PGI2.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Increase of nitric oxide production by L-arginine potentiates i.c.v. administered beta-endorphin-induced antinociception in the mouse.

Pretreatment (i.c.v.) of mice with L-arginine but not D-arginine potentiated beta-endorphin-induced (i.c.v. administered) inhibition of the tail-flick response. The potentiation was attenuated by N omega-nitro-L-arginine methyl ester, a selective inhibitor of nitric oxide synthase. This observation suggests that increased production of nitric oxide from L-arginine mediates the potentiation of beta-endorphin-induced antinociception.

Amino Acid Oxidoreductases↗

PubMed1992

Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody.

The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is thought to induce potent neutralizing antibodies which are generally defined as type specific and reactive with individual viral isolates. In contrast, the CD4-binding domain is thought to induce neutralizing antibodies that are group specific and capable of neutralizing all isolates of HIV-1. However, in this study, we used a panel of human monoclonal antibodies to these regions of gp120 which displays specificities and neutralizing activities that challenge these tenets. In particular, we used a human monoclonal antibody to the V3 domain with exceptionally potent and broad neutralizing activity against many diverse HIV-1 isolates. The anti-CD4-binding domain antibodies, on the other hand, showed a more restricted pattern of activity.

Amino Acid Sequence↗

PubMed1992

[Short-term effects of Angelica sinensis and nifedipine on chronic obstructive pulmonary disease in patients with pulmonary hypertension].

UNLABELLED: 40 COPD cases with pulmonary hypertension (PH) in remission stage were equally divided into four groups, 10 cases in each. Group 1-4 were treated with 25% Angelica sinensis (250 ml, iv. drip, qd), nifedipine (10 mg, po, tid), both Angelica sinensis+nifedipine and blank control respectively. The study was designed to investigate the changes of hemodynamics, pulmonary function and blood gas before and after the treatments by impedance rheopneumogram, lung function examination and blood gas analysis. RESULTS: Mean pulmonary arterial pressure was decreased and cardiac output, PaO2 were increased significantly (P < 0.05 or P < 0.01) in group 3. The effects of group 3 appeared to be better than in other groups. The side effect of PaO2 lowering in group 2 was overcome in adding Angelica sinensis.

Aged↗

PubMed1992

Involvement of supraspinal epsilon and mu opioid receptors in inhibition of the tail-flick response induced by etorphine in the mouse.

Etorphine, a potent opioid agonist, has been reported to bind to both mu and epsilon opioid receptors. The present studies were designed to determine what types of opioid receptors and neurotransmitters for descending pain control systems were involved in antinociception induced by etorphine in mice. Morphine, a typical mu opioid receptor agonist, and beta-endorphin, an epsilon opioid receptor agonist, were used for comparison. Antinociceptive response induced by etorphine (20 ng) given i.c.v was blocked by i.c.v administration of D-Phe-Cys-Tyr-D-Tyr-Orn-Thr-Pen-Thr-NH2 (CTOP, 25 ng) and beta-endorphin-(1-27) [beta-EP-(1-27)] (6 micrograms), but not ICI 174,864 (ICI, 5 micrograms) or norbinaltorphimine (N-BNI, 5 micrograms). The antinociception induced by i.c.v. etorphine was also antagonized by the i.c.v. pretreatment of beta-funaltrexamine (beta-FNA, 50 ng, 24 hr). Intracerebroventricular administration of beta-EP-(1-27) (3 micrograms) caused a further attenuation of the i.c.v. etorphine-induced antinociception in mice pretreated with beta-FNA. The antinociceptive response induced by morphine (2 micrograms) given i.c.v. was blocked by i.c.v. administration of CTOP (25 ng) or beta-FNA (50 ng), but not beta-EP-(1-27) (6 micrograms), ICI (5 micrograms) or N-BNI (5 micrograms). These results indicate that the antinociception induced by etorphine given i.c.v. is mediated by the stimulation of both mu and epsilon opioid receptors whereas the antinociception induced by morphine given i.c.v. is mediated by the stimulation of mu, but not epsilon opioid receptors at supraspinal sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

PubMed1992

[The determination of serum hepatitis B virus DNA by polymerase chain reaction in hepatitis B patients treated with alpha-interferon].

To clarify the status of HBV in serum of chronic hepatitis B (CHB) patients who were treated with alpha-interferon, we determined the serum HBV DNA before and after treatment in 15 CHB patients with polymerase chain reaction (PCR). Before treatment all the 15 patients were HBsAg and HBeAg positive. HBV DNA was also positive with dot-blot hybridization (DB), PCR, ethidium bromide (PCR-EB) and PCR Southern-blot hybridization (PCR-SBH). HBeAb was negative in all the 15 patients. 12 patients has the determination repeated 2 to 39 weeks after treatment, 7 out of the 12 patients became HBeAg negative and HBV DNA also negative with DB and PCR-EB. However, in 5 of the 7 patients HBV DNA was still positive with PCR-SBH. Seroconversion of HBeAb from negative to positive occurred in 4 of the 12, but HBV DNA of the 4 patients remained positive with PCR-SBH. After an interval of one and half year or more following treatment 12 patients repeated the examination, only 5 of the 12 patients became seronegative for HBeAg and HBV DNA with DB and PCR-EB, but in 4 of the 5 HBV DNA was positive with PCR-SBH. Two of the 5 were seropositive for HBeAb and HBV DNA with PCR-SBH. The mechanism of residual viraemia after alpha-interferon treatment in CHB patients is uncertain.

Adult↗

PubMed1992

[Antitumor effect of Tripterygium wilfordii].

A new component of antitumor action TG has been isolated from the ethyl acetate extract of Tripterygium wilfordii (besides Triptolide, Tripdiolide and Triptonide). TG was shown in this study to have obvious antitumor effects. The average life span of H22, S180, EAC and breast carcinoma-bearing mice treated with TG ip x 2 days were 100% more than those of the control mice (P less than 0.01) TG was able to inhibit tumor growth of S37-bearing mice at the dose of 150 mg/kg per day, ig x 3, its inhibitory rate was 42% (P less than 0.01). TG could also inhibit squamous epithelial lung carcinoma induced by 3-methylcholanthrene. The inhibitory rate was 65.13% (P less than 0.05). TG had remarkable killing effect on human HL60 and Daudi cells and two direction effects on function M phi of mouse abdominal cavity in vitro.

Animals↗

PubMed1991

Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein.

Cell lines secreting IgG1 human monoclonal antibodies (mAb) to the envelope glycoprotein, gp120, of human immunodeficiency virus (HIV) have been produced by transformation of peripheral blood cells from HIV-infected individuals and by fusion of transformed cells to a human-mouse heteromyeloma cell line (SHM-D33). Two human mAbs were site-selected by means of a 23-mer synthetic peptide spanning a portion of the third variable domain of gp120 from the MN strain of HIV. The two heterohybridomas produce three times more IgG than do their parent lymphoblastoid cell lines. The specificities of these mAbs have been mapped to sequences near the tip of the disulfide loop of the gp120 third variable domain, Lys-Arg-Ile-His-Ile and His-Ile-Gly-Pro-Gly-Arg, respectively. The mAbs have dissociation constants of 3.7 x 10(-6) M and 8.3 x 10(-7) M, neutralize HIVMN in vitro at nanogram levels, and bear the characteristics of antibodies associated with protective immunity in vivo.

Antibodies, Monoclonal↗

PubMed1991

Two immunodominant domains of gp41 bind antibodies which enhance human immunodeficiency virus type 1 infection in vitro.

Four of eight human monoclonal antibodies (huMAbs) to gp41 were identified which could enhance human immunodeficiency virus type 1 (HIV-1) infection in vitro by complement-mediated antibody-dependent enhancement (C'-ADE). These enhancing huMAbs were mapped to two distinct domains on the HIV-1 gp41 transmembrane glycoprotein by using synthetic peptides. The first domain, amino acids 579 to 613 (peptide AA579-613), was recognized by three of the four enhancing huMAbs. The AA579-613 peptide blocked C'-ADE of HIV-1 infection in vitro whether it was mediated by these three huMAbs or by human polyclonal anti-HIV serum. The second domain, amino acids 644 to 663, bound the remaining enhancing huMAb. This peptide weakly blocked C'-ADE mediated by the huMAb and by an HIV immune globulin fraction but did not block C'-ADE mediated by a patient's serum. The patient's serum did react with the peptide in an enzyme immunoassay. The huMAbs to the two domains could interact in vitro to enhance HIV-1 infection in a synergistic manner. These two domains, which bind enhancing antibodies, are conserved between HIV-1 isolates as well as between HIV-2 and simian immunodeficiency virus isolates. These data demonstrate the existence of two conserved regions within the HIV-1 gp41 which bind enhancing antibodies; these two domains, amino acids 579 to 613 and 644 to 663, may prove important in HIV-1 vaccine development and in immunopathogenesis of HIV-1 infection.

Amino Acid Sequence↗