Biomedical subjects

A Li

Publications and source records attributed to A Li.

At least 163 records · Page 9Linked to original sources

PubMed1999

[Instrumental analysis and systematic investigation on heavy oils from coal. II. Analysis of aromatic ring distribution by high performance liquid chromatography].

In this paper, the relationship of chromatographic retention index (I) and aromatic ring number (ARN) of 49 pure reagents in Zorbax-NH2 column/hepatane chromatographic system using high performance liquid chromatography(HPLC) have been studied. The results obtained were that log I values can be divided into several regions according to ARN. They were 0.672-1.089, 1.652-2.588, 2.629-3.241, 3.447-4.160 and 4.482-5.000 for ARN 1 through 5. Those were clear-cut and could be applied to the division of aromatic ring distribution (ARD) of heavy oil products. Hence the ARD method, which was based on the results from pure synthetic compounds, has been established. On the study of quantitation, the peak-area normalization method was used to quantify the aromatics with different ARN. The method has the features of high rapidity, high resolution and long life of column. In this paper heavy oil and pitch products from seven plants have been systematically analyzed for their ARD.

English Abstract↗

PubMed1998

Novel antineoplastic agents with efficacy against multidrug resistant tumor cells.

A novel series of pentafluorobenzenesulfonamides has been shown to inhibit the growth of a variety of human tumor cell lines. Among the cell types against which these agents were evaluated were the multidrug resistant (MDR) cell lines MCF-7/ADR and P388/ADR. The cytotoxic activity of members of this series of compounds was not affected by the multidrug resistant pump in MCF-7/ADR or P388/ADR cells.

Antineoplastic Agents↗

PubMed1998

Small espin: a third actin-bundling protein and potential forked protein ortholog in brush border microvilli.

An approximately 30-kD isoform of the actin-binding/ bundling protein espin has been discovered in the brush borders of absorptive epithelial cells in rat intestine and kidney. Small espin is identical in sequence to the COOH terminus of the larger ( approximately 110-kD) espin isoform identified in the actin bundles of Sertoli cell-spermatid junctional plaques (Bartles, J.R., A. Wierda, and L. Zheng. 1996. J. Cell Sci. 109:1229-1239), but it contains two unique peptides at its NH2 terminus. Small espin was localized to the parallel actin bundles of brush border microvilli, resisted extraction with Triton X-100, and accumulated in the brush border during enterocyte differentiation/migration along the crypt-villus axis in adults. In transfected BHK fibroblasts, green fluorescent protein-small espin decorated F-actin-containing fibers and appeared to elicit their accumulation and/or bundling. Recombinant small espin bound to skeletal muscle and nonmuscle F-actin with high affinity (Kd = 150 and 50 nM) and cross-linked the filaments into bundles. Sedimentation, gel filtration, and circular dichroism analyses suggested that recombinant small espin was a monomer with an asymmetrical shape and a high percentage of alpha-helix. Deletion mutagenesis suggested that small espin contained two actin-binding sites in its COOH-terminal 116-amino acid peptide and that the NH2-terminal half of its forked homology peptide was necessary for bundling activity.

Actins↗

PubMed1998

Low-Rate Dynamic Contact Angles on Poly(methyl methacrylate) and the Determination of Solid Surface Tensions.

Low-rate dynamic contact angles of nine liquids on a poly(methyl methacrylate) (PMMA) polymer are measured by an automated axisymmetric drop shape analysis-profile (ADSA-P). It is found that two liquids dissolved the polymer on contact. From the experimental contact angles of the other seven polar and nonpolar liquids, it is found that the liquid-vapor surface tension times cosine of the contact angle changes smoothly with the liquid-vapor surface tension (i.e., gammalnucos theta depends only on gammalnu for a given solid surface). The dependence of gammalnucos theta on gammasnu is explicitly illustrated by replacing the solid surface from the PMMA to other methacrylate polymers: such a procedure shifts the curves in a very regular manner. Thus, because of Young's equation, gammasl depends only on gammalnu and gammasnu. This contact angle pattern is in harmony with those from other inert and noninert (polar and nonpolar) surfaces. The solid-vapor surface tension of PMMA calculated from the equation of state approach for solid-liquid interfacial tensions is found to be 38.5 mJ/m2, with a 95% confidence limit of +/-0.5 mJ/m2 from the experimental contact angles of the seven liquids. Copyright 1998 Academic Press.

Journal Article↗

PubMed1998

Oxidation regulates cloned neuronal voltage-dependent Ca2+ channels expressed in Xenopus oocytes.

Functional modifications of neuronal P/Q-type voltage-dependent Ca2+ channels expressed in Xenopus oocytes by oxidation were examined electrophysiologically. Oxidation by external H2O2 enhanced the whole-oocyte currents through the Ca2+ channels composed of the alpha1A, alpha2/delta, and beta3 subunits at negative voltages (<0 mV) without markedly affecting the currents at more positive voltages. Single-channel analysis showed that oxidation accelerates the overall channel opening process. The effect of H2O2 to enhance the Ca2+ channel activity did not require heterologous expression of the alpha2/delta subunit, and it was not mimicked by a cysteine-specific oxidizing agent. The results suggest that oxidative stress may regulate the activity of neuronal Ca2+ channels and that regulation by oxidation may be important in some clinical situations, such as in reperfusion injury after ischemic episodes.

Animals↗

PubMed1998

Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein.

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcription factor that has been demonstrated to regulate fat cell development and glucose homeostasis. PPARgamma is also expressed in a subset of macrophages and negatively regulates the expression of several proinflammatory genes in response to natural and synthetic ligands. We here demonstrate that PPARgamma is expressed in macrophage foam cells of human atherosclerotic lesions, in a pattern that is highly correlated with that of oxidation-specific epitopes. Oxidized low density lipoprotein (oxLDL) and macrophage colony-stimulating factor, which are known to be present in atherosclerotic lesions, stimulated PPARgamma expression in primary macrophages and monocytic cell lines. PPARgamma mRNA expression was also induced in primary macrophages and THP-1 monocytic leukemia cells by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). Inhibition of protein kinase C blocked the induction of PPARgamma expression by TPA, but not by oxLDL, suggesting that more than one signaling pathway regulates PPARgamma expression in macrophages. TPA induced the expression of PPARgamma in RAW 264.7 macrophages by increasing transcription from the PPARgamma1 and PPARgamma3 promoters. In concert, these observations provide insights into the regulation of PPARgamma expression in activated macrophages and raise the possibility that PPARgamma ligands may influence the progression of atherosclerosis.

Animals↗

PubMed1998

Electrostatics, allostery, and activity of the yeast chorismate mutase.

The predicted active site of chorismate mutase of baker's yeast Saccharomyces cerevisiae has been studied by continuum electrostatics, molecular surface/volume calculations, and molecular modeling. Our study shows that despite being subject to an allosteric transition, the enzyme's active-site pocket neither decreased in volume nor deformed significantly in shape between the active R state and the inactive T state. We find that the polar atmosphere in the pocket is responsible for the enzyme's affinity. A single amino acid, Glu23, can adequately account for the atmospheric variation. This residue swings into the active-site pocket from the R state to the T state. In the R state, Glu23 on helix H2 doubly pairs with Arg204 and Lys208 of H11, which is packed against H2. In the T state, a slide occurs between H11 and H2 such that Glu23 can no longer interact with Lys208 and competes with Asp24 for interacting with Arg204. Consequently, Glu23 is found in the T state to couple with Arg157, an active-site residue critical to substrate binding. The tandem sliding of H11 in both monomers profoundly changes the interactions in the dimer interface. The loop between H11 and H12 demonstrates the largest conformational change. Hence, we establish a connection between the allosteric transition and the activity of the enzyme. The conformational change in the transition is suggested to propagate into the active-site pocket via a series of polar interactions that result in polarity reversal in the active-site pocket, which regulates the enzyme's activity.

Allosteric Regulation↗

PubMed1998

Integrin activation by dithiothreitol or Mn2+ induces a ligand-occupied conformation and exposure of a novel NH2-terminal regulatory site on the beta1 integrin chain.

Integrins can be expressed in at least three functional states (i.e. latent, active, and ligand-occupied). However, the molecular bases for the transitions between these states are unknown. In the present study, changes in the accessibility of several beta1 epitopes (e.g. N29, B44, and B3B11) were used to probe activation-related conformational changes. Dithiothreitol or Mn2+ activation of integrin-mediated adhesion in the human B cell line, IM9, resulted in a marked increase in the exposure of the B44 epitope, while N29 expression levels were most sensitive to dithiothreitol treatment. These results contrasted with the epitope expression patterns of spontaneously adherent K562 cells, where N29 was almost fully accessible and B44 was low. Addition of a soluble ligand resulted in a marked increase in B44 levels, suggesting that this antibody detected a ligand-induced binding site. The N29 epitope was mapped to a cysteine-rich region near the NH2 terminus of the integrin chain, thus defining a novel regulatory site. These studies indicate that the activation of integrin function by different stimuli may involve related but nonidentical conformations. Both Mn2+ and dithiothreitol appear to induce localized conformational changes that mimic a ligand-occupied receptor. This differs from the "physiologically" activated integrins on K562 cells that display a marked increase in overall epitope accessibility without exposure of the ligand-induced binding site epitopes. The increased exposure of the N29 site on K562 cells may indicate a role for this region in the regulation of integrin function.

B-Lymphocytes↗

PubMed1998

Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype.

Despite the central role of human epidermal stem cells in tissue homeostasis, wound repair, and neoplasia, remarkably little is known about these cells, largely due to the absence of molecular markers that distinguish them from other proliferative cells within the germinative/basal layer. Epidermal stem cells can be distinguished from other cells in the basal layer by their quiescent nature in vivo and their greater overall proliferative capacity. In this study, we demonstrate enrichment and isolation of a subpopulation of basal epidermal cells from neonatal human foreskin based on cell surface phenotype, which satisfy these criteria. These putative stem cells are distinguished from other basal cells by their characteristic expression of high levels of the adhesion molecule alpha6, a member of the integrin family (alpha6bri), and low levels of a proliferation-associated cell surface marker recognized by recently described mAb 10G7 (10G7(dim)). We conclude that cells with the phenotype alpha6bri10G7(dim) represent the epidermal stem cell population based on the demonstration that these cells (i) exhibit the greatest regenerative capacity of any basal cells, (ii) represent a minor subpopulation (approximately 10%) of immature epidermal cells, which (iii) are quiescent at the time of isolation from the epidermis, as determined by cell cycle analysis.

Antigens, Surface↗

PubMed1998

Active site inhibited factor VIIa (DEGR VIIa) attenuates the coagulant and interleukin-6 and -8, but not tumor necrosis factor, responses of the baboon to LD100 Escherichia coli.

Antitissue factor antibody attenuated the coagulopathic and lethal responses to LD100 Escherichia coli, whereas active site inhibited factor Xa inhibited only the coagulopathic response. In this study, we wished to determine: (1) whether active site inhibited factor VIIa blocks the coagulopathic and/or attenuates the lethal effects of LD100 E coli and (2) whether these effects are accompanied by attenuation of the inflammatory cytokine response to LD100 E coli. Eight baboons infused for 2 hours with LD100 E coli also were given five bolus infusions of DEGR VIIa of 280 microg/kg at T = -10 minutes, +2, 4, 6, and 8 hours and observed for changes in vital signs, and the concentrations of hemostatic components (fibrinogen, platelets, fibrin degradation products) and inflammatory mediators (tumor necrosis factor [TNF], interleukin-6 [IL-6], IL-8) at T = 0, 1, 2, 4, 6, and 8 hours. Eight control baboons were also infused with LD100 E coli alone and followed as described above. Four of the eight baboons treated with DEGR VIIa were permanent 7-day survivors versus none in the control group. The mean survival times for the treated and control groups were 116 +/- 22 and 26 +/- 8 hours, respectively. These values differed significantly from each other, (P = .0008). The decrease in platelet and fibrinogen concentrations and the increase in fibrin degradation products observed in the control group were significantly attenuated in the treated group, as was thrombosis of renal glomerular capillaries. Treatment with DEGR VIIa showed no effect on the peak TNF response to LD100 E coli at T = 2 hours (170 +/- 32 v 120 +/- 35 ng/mL). DEGR VIIa, however, did attenuate the IL-6 and IL-8 responses at T = 8 hours (ie, the IL-6 concentrations were 81 +/- 10 for treated and 1,256 +/- 236 for the control groups and the IL-8 concentrations were 28 +/- 3.9 for the treated and 60 +/- 8.2 for the control group). These values for IL-6 and IL-8 differed significantly from each other between the treated and control groups (P = .0001 and .0074, respectively). It should be noted that the initial responses of IL-6 and IL-8 up to T = 4 hours were not attenuated. We concluded that DEGR VIIa treatment attenuates inflammatory, as well as hemostatic system responses to LD100 E coli. We hypothesize that this occurs through interference with the assembly and/or interactions of tissue factor/VIIa complexes.

Animals↗

PubMed1998

Femoral neck metaphyseal osteopathy in the cat.

This paper describes 17 cats that developed an idiopathic necrosis of the femoral neck. In four cats the lesions were bilateral when they were first examined and five cats developed lesions in the other limb within five months. They were all male cats, two years old or younger, and 15 had been neutered. The initial sign was a vague lameness which typically progressed, often acutely, to a more severe lameness. Radiography demonstrated radiolucency and loss of definition within the proximal femoral metaphysis, the femoral neck. In 12 cases there was a complete radiolucent line across the femoral neck. An excision arthroplasty was carried out on all the affected hips and the lameness resolved in all cases. The clinical and radiological signs suggest a primary bone resorption with secondary fracture of the femoral neck. The lesions have some similarities with Legg-Calve-Perthes' disease, traumatic fracture of the femoral neck, canine metaphyseal osteopathy, bacterial osteomyelitis and experimental feline herpes virus osteomyelitis.

Animals↗

PubMed1998

Molecular dynamics simulation of the unfolding of barnase: characterization of the major intermediate.

The folding/unfolding pathway of barnase has been studied extensively using the protein engineering method, which has provided indirect structural information for the transition state and the major folding intermediate. To further characterize the structural properties of the intermediate, we have simulated the thermal denaturation of barnase beginning from the average NMR structure. Our results indicate that there are at least two intermediates on the unfolding pathway. The three hydrophobic cores are partially formed in the major intermediate (I1), with core1 and core3 being slightly stronger than core2. Helix alpha 1 is substantially formed, with the center being stronger than the termini. The first turn of alpha 2 is lost and alpha 3 is unfolded. The center of the beta-sheet is substantially formed, but the edges are disrupted. These structural characteristics are in good qualitative agreement with the experimental data. For semi-quantitative comparison with experimental data, the extent of native structure of individual residues is characterized by a structure index, S, that reflects both secondary and tertiary structure. There is good agreement between S and the experimentally measured phi values, which are based on energetics, except for three residues. These residues are polar and non-conservative mutations were made to obtain phi values, which can complicate structural interpretations. These residues make strong side-chain interactions in I1, but the backbone structure is disrupted, leading to low S values. Thus, this discordance highlights possible limitations in both the phi value and S value analyses: strong polar interactions in the intermediate may give rise to high phi values that are not reflective of structure per se; however, due to sampling limitations, any one simulation is not expected to capture all of the features of the true conformational ensemble. In any case, these simulations provide an experimentally testable, atomic-level structural model for the major folding intermediate of barnase, as well as the detailed pathway from the native to the intermediate state.

Bacterial Proteins↗

PubMed1998

Effect of aluminum on long-term potentiation and its relation to L-arg-NO-pathway in hippocampal CA3 area of rats.

Experiments were performed on 64 Sprague-Dawley rats under urethane anesthesia. Extracellular recording method was used to investigate the effect of aluminum(Al) microinjected into CA3 on long-term potentiation(LTP) in this area. The relationship between the inhibitory effect of Al and L-arginine-NO pathway was also studied. Microinjection of Al (0.5 mol/L, 1 microliter) into CA3 could block the induction of LTP in CA3. Microinjection of Al (0.5 mol/L, 1 microliter) into CA3 after LTP was induced could also decrease the amplitude of population spike (PS). The inhibitory effect of Al on LTP in CA3 could be enhanced by preinjection of NG-nitro-L-arginine (0.3 mol/L, 1 microliter). Preinjection of L-arginine (0.3 mol/L, 1 microliter) into CA3 could antagonize the inhibitory effect of Al on LTP. These results suggest that Al could block the induction of LTP and decrease the amplitude of PS potentiated in CA3. The effect of Al might be antagonized by L-arginine-NO pathway.

Aluminum Chloride↗

PubMed1998

Effect of prednisone on prostate-specific antigen in patients with hormone-refractory prostate cancer.

OBJECTIVES: To evaluate the effects of prednisone on prostate-specific antigen (PSA) in a cohort of patients with "hormone-refractory" prostate cancer. METHODS: Data were collected from 29 consecutive patients with hormone-refractory progressive prostate cancer who were treated with 10 mg of prednisone orally two times a day. Patients were included in this analysis only if other factors known to influence PSA levels (antiandrogen withdrawal, radiation, and/or other concomitant anticancer therapies) were definitively excluded as potentially confounding variables. RESULTS: The mean and median PSA decline after initiating prednisone was 33% (95% confidence interval [CI] 20% to 46%) and 24% (range 0% to 99%), respectively. Ten patients (34%) had a PSA decline of more than 50% and 4 patients (14%) had PSA declines of more than 75%. The average and median time for progression-free survivals were 2.8 (95% CI 1.7 to 3.8) and 2.0 (range 0 to 11) months. Four (14%) patients had PSA declines lasting 6 months or more. Median survival was 12.8 months. Additional analyses indicated that a PSA decline of more than 50%, compared with less than 50%, was associated with a longer survival. Toxicities included steroid myopathy (n = 4), new-onset diabetes (n = 1), and dyspnea (n = 1). CONCLUSIONS: Prednisone (10 mg orally two times a day) can decrease PSA by more than 50% in approximately one third of patients with hormone-refractory progressive prostate cancer. On the basis of comparisons with other data sets, we hypothesize a dose-response relationship between glucocorticoid dose and PSA decline.

Aged↗

PubMed1998

Serial experimental and clinical studies on the pathogenesis of multiple organ dysfunction syndrome (MODS) in severe burns.

These serial clinical and experimental studies were designed to clarify the pathogenesis of postburn MODS. Both animal and clinical studies were performed. In animal experiments, 46 male cross-bred dogs were cannulated with Swan-Ganz catheters and 39 of them were inflicted with 50% TBSA third degree burns (7 were used as controls). The burned dogs were randomly divided into 4 groups: immediate infusion, delayed infusion, delayed fast infusion and delayed fast infusion combined with ginsenosides. All dogs were kept under constant barbiturate sedation during the whole study period. Hemodynamics, visceral MDA, mitochondrial respiratory control rate (RCR) and ADP/O ratio, ATP, succinic dehydrogenase (SDH), organ water content as well as light and electron microscopy of visceral tissues were determined. In the clinical study, 61 patients with extensive deep burns were chosen, of which 16 sustained MODS. Plasma TXB2/6-keto-PGF1alpha ratio, TNF, SOD, MDA, circulatory platelet aggregate ratio (CPAR), PGE2, interleukin-1, total organ water content and pathological observations of visceral tissues from patients who died of MODS were carried out. Results demonstrated that ischemic-reperfusion damage due to severe shock, sepsis and inhalation injury are three main causes of postburn death. All inflammatory mediators increased markedly in both animals and patients who sustained organ damage or MODS. SDH, RCR, ADP/O and ATP decreased significantly. These findings suggested that ischemic damage and systemic inflammatory response syndrome (SIRS) initiated by mediators or cytokines might be important in the pathogenesis of postburn MODS.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

Levamisole and interleukin-2 for advanced malignancy.

Therapy for cancer patients with biologically active immune modulators is attractive but has met with limited clinical success. Interleukin-2 (IL2) stimulates T-cells and natural killer (NK) cells to kill tumor cells and levamisole (LMS) is an immunostimulant which has been shown to increase NK cells and activated T-cells in patients receiving this adjuvantly along with 5FU for Stage III colon cancer. This study was designed to evaluate whether treatment with LMS prior to IL2 would provide synergistic activity and improve response rates. Four patients with advanced malignancies were treated with LMS at 50 mg p.o. TID for 3 days followed on day 4 with 600,000 units/kg IL2 as a single i.v. bolus. This treatment was repeated weekly until progression. Serum soluble IL2 receptor (sIL2R) and interferon-gamma levels were monitored throughout the treatment course as markers of immune activation. All patients had eventual progression of disease. Toxicity was minimal with Grade II orthostatic hypotension the major consequence of therapy. The pattern of sIL2R levels in 3/4 patients revealed a steady increase over the several weeks of therapy, indicating ongoing immunostimulation (r=0.53 , p=0.001). Short-term treatment with LMS, however, resulted in a significant and consistent decreases in sIL2R levels (2198 U/ml vs. 1969 U/ml, p=0.001) in all patients. In conclusion, LMS/IL2 in the dose and schedule utilized here was not clinically effective. However, LMS reduced sIL2R levels immediately following a three-day course. This reduction in sIL2R by LMS may improve the possibility of response to IL2 by facilitating a decrease in inhibitory sIL2R. Combinations of these two agents should continue to be investigated as potential synergistic anti-tumor agents.

Adjuvants, Immunologic↗

PubMed1998

Molecular basis for hypertension in the "type II variant" of apparent mineralocorticoid excess.

The syndrome of apparent mineralocorticoid excess (AME) is a heritable form of hypertension in which cortisol acts as a potent mineralocorticoid. The type I variant results in a severe clinical and biochemical phenotype and arises because of mutations in the gene encoding the type 2 isozyme of 11beta-hydroxysteroid dehydrogenase (11beta-HSD2), an enzyme responsible for the peripheral inactivation of cortisol to cortisone. Only mild abnormalities of cortisol metabolism have been found in the type II variant of AME, suggesting that it may be a separate gene defect. In an extensive consanguineous Sardinian pedigree affected with "type II" AME, a novel homozygous point mutation (C945T) was found in the human 11beta-HSD2 gene in four affected individuals. Thirteen family members were heterozygous for the resultant R279C amino acid substitution. The LOD score of linkage of the mutation to the disease was 3.23. Expression of the 11beta-HSD2 mutant cDNA resulted in an enzyme with reduced maximum velocity, but similar substrate affinity, compared with activity of the wild-type cDNA. Affected individuals were >30 years of age and had both mineralocorticoid hypertension and evidence of impaired metabolism of cortisol to cortisone. The heterozygote state was phenotypically normal but was associated with subtle defects in cortisol metabolism. AME represents a spectrum of mineralocorticoid hypertension with severity reflecting the underlying genetic defect in the 11beta-HSD2 gene; classification into distinct subtypes is inappropriate. Hypertensive populations should be screened to identify the prevalence of milder defects in 11beta-HSD2 in patients currently labeled as having "essential" hypertension.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1998

Synergistic neutralization of simian-human immunodeficiency virus SHIV-vpu+ by triple and quadruple combinations of human monoclonal antibodies and high-titer anti-human immunodeficiency virus type 1 immunoglobulins.

We have tested triple and quadruple combinations of human monoclonal antibodies (MAbs), which are directed against various epitopes on human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, and a high-titer anti-HIV-1 human immunoglobulin (HIVIG) preparation for their abilities to neutralize a chimeric simian-human immunodeficiency virus (SHIV-vpu+). This virus encodes the HIV-1 strain IIIB env, tat, rev, and vpu genes. The quantitative nature of the Chou-Talalay method (Adv. Enzyme Regul. 22:27-55, 1984) allows ranking of various combinations under identical experimental conditions. Of all triple combinations tested, the most potent neutralization was seen with MAbs 694/98D plus 2F5 plus 2G12 (directed against domains on V3, gp41, and gp120, respectively) as measured by the total MAb concentration required to reach 90% neutralization (90% effective concentration [EC90], 2.0 microg/ml). All triple combinations involving MAbs and/or HIVIG that were tested yielded synergy with combination index values of < 1; the dose reduction indices (DRIs) ranged from 3.1 to 26.2 at 90% neutralization. When four MAbs (the previous three plus MAb F105, directed against the CD4 binding site) were combined, higher neutralization potency (EC90 1.8 microg/ml) and a higher degree of synergy compared to any triple combination were seen. The mean DRIs of the quadruple combination were approximately twice that of the most synergistic triple combination. We conclude that human MAbs targeting different HIV-1 envelope glycoprotein epitopes exhibit strong synergy when used in combination, a fact that could be exploited clinically for passive immunoprophylaxis against HIV-1.

Animals↗