Biomedical subjects

S Hu

Publications and source records attributed to S Hu.

At least 37 records · Page 2Linked to original sources

PubMed2003

Root-parasitic nematodes enhance soil microbial activities and nitrogen mineralization.

Obligate root-parasitic nematodes can affect soil microbes positively by enhancing C and nutrient leakage from roots but negatively by restricting total root growth. However, it is unclear how the resulting changes in C availability affect soil microbial activities and N cycling. In a microplot experiment, effects of root-parasitic reniform nematodes ( Rotylenchulus reniformis) on soil microbial biomass and activities were examined in six different soils planted with cotton. Rotylenchulus reniformis was introduced at 900 nematodes kg(-1) soil in May 2000 prior to seeding cotton. In 2001, soil samples were collected in May before cotton was seeded and in November at the final harvest. Extractable C and N were consistently higher in the R. reniformis treatments than in the non-nematode controls across the six different soils. Nematode inoculation significantly reduced microbial biomass C, but increased microbial biomass N, leading to marked decreases in microbial biomass C:N ratios. Soil microbial respiration and net N mineralization rates were also consistently higher in the nematode treatments than in the controls. However, soil types did not have a significant impact on the effects of nematodes on these microbial parameters. These findings indicate that nematode infection of plant roots may enhance microbial activities and the turnover of soil microbial biomass, facilitating soil N cycling. The present study provides the first evidence about the direct role of root-feeding nematodes in enhancing soil N mineralization.

Animals↗

PubMed2003

Ginseng and aluminium hydroxide act synergistically as vaccine adjuvants.

The dry extract prepared from the Panax ginseng C.A. Meyer-root (total ginseng (T-ginseng)) contain ginsenosides (G-des) which were shown to have adjuvant properties as demonstrated by: (a) injecting guinea pigs with a mixture of T-ginseng and inactivated porcine parvovirus (PPV) as a conventional vaccine; (b)injecting PPV-antigen and T-ginseng simultaneously but separately at different sites on the animal and (c)injecting only the T-ginseng 1 or 2 weeks prior to immunisation with the PPV-antigen. Using a haemagglutination inhibition (HI) test in the antibody titration, it was found that the mean HI-titre for the animals injected with PPV-antigen only was 320 +/- 0. By comparison, the mean titre value was 2026 +/- 1206 for the sera from the animals injected with the same vaccine but adjuvanted with 4 mg of T-ginseng, while the antibody titre induced by a vaccine containing Al(OH)(3)-gel was 2986 +/- 1596. Interestingly, the T-ginseng and Al(OH)(3) acted synergistically and further improved the antibody response to the PPV-antigen to 6826 +/- 2413, i.e. more than 20 times the HI titre of the non-adjuvanted PPV-vaccine. Immunisations using PPV-vaccines adjuvanted with single purified G-des demonstrated that the ginseng fractions Rb1 and Rg1 are potent adjuvants inducing higher or similar antibody titres than the vaccine adjuvanted with Al(OH)(3), e.g. Rb1 tested at a concentration of 830 microg per dose induced a significantly (P = 0.009) higher antibody titre than the one adjuvanted with Al(OH)(3). Nevertheless, different than the mixture Al(OH)(3)-T-ginseng; Rb1 and Rg1 act antagonistically and partially inhibit each other. The G-des adjuvanted vaccines induced significantly (P = 0.0011) higher titres of IgG2 antibodies compared with IgG1.

Adjuvants, Immunologic↗

PubMed2003

Nonlinear theory of void formation in colloidal plasmas.

A nonlinear time-dependent model for void formation in colloidal plasmas is proposed. For experimentally relevant initial conditions, the model describes the nonlinear evolution of a zero-frequency linear instability that grows rapidly in the nonlinear regime and subsequently saturates to form a void. A number of features of the model are consistent with experimental observations under laboratory and microgravity conditions.

Journal Article↗

PubMed2003

Adjuvant effect of ginseng extracts on the immune responses to immunisation against Staphylococcus aureus in dairy cattle.

A crude ginseng extract (GS) and the purified ginsenoside R(b1) (R(b1)) were evaluated for their adjuvant effects in dairy cattle at immunisation with ovalbumin (OVA) and/or a Staphylococcus aureus bacterin used for prevention of bovine mastitis. To evaluate a suitable dose of GS as an adjuvant, 36 lactating cows were randomly divided into six groups. The cows were inoculated twice intramuscularly with a 2-week interval, with saline solution, OVA in saline, or OVA in combination with 4, 16 or 64 mg GS, or Al(OH)(3). The level of specific antibodies to OVA in serum and milk whey was measured before immunisations and 1-5 weeks after the second immunisation. The antibody response in serum was significantly higher in animals immunised with OVA and GS than in animals immunised with OVA alone. A significant increase in milk antibody titres compared with OVA only was only found 2 weeks after the second immunisation in the group immunised with OVA and 4 mg GS. In the second part of the study, 18 heifers were randomly divided into three groups and were immunised twice intramuscularly with a two week interval, with the S. aureus bacterin (control), or with the bacterin in combination with 4 mg GS or 1mg R(b1). The specific antibody response to S. aureus and the lymphocyte proliferation after stimulation with PWM, concanavalin A (Con A) or a specific S. aureus antigen was evaluated in blood samples taken before and after immunisations as specified above. Addition of R(b1) resulted both in significantly higher antibody production and lymphocyte proliferation in response to PWM, Con A and S. aureus antigens than in the control group. Addition of GS induced a significantly higher lymphocyte proliferation in response to PWM and Con A than the control, but had no additional effect on the antibody production. In conclusion, both GS and R(b1) were safe adjuvants, and R(b1) had the strongest adjuvant effects, when used for immunisation against S. aureus in dairy cattle. Field trials are warranted to test the ability of GS and R(b1) to enhance the efficacy of mastitis vaccines in protection against intramammary infections.

Adjuvants, Immunologic↗

PubMed2003

Ginseng extract in aluminium hydroxide adjuvanted vaccines improves the antibody response of pigs to porcine parvovirus and Erysipelothrix rhusiopathiae.

Ginseng, the dry extract prepared from the Panax ginseng C.A. Mayer-root contain immunomodulators named ginsenosides, which in the pig enhance the antibody response to viral and bacterial antigens. The enhancing effect of ginseng was demonstrated vaccinating pigs against porcine parvovirus (PPV) and Erysipelothrix rhusiopathiae infections, using commercially available vaccines. The potency of the licensed, aluminium hydroxide adjuvanted; vaccines were compared with those supplemented with ginseng. The antibody response to PPV was measured by the haemagglutination inhibition (HI) test whereas the mouse potency test and ELISA evaluated the immune response to E. rhusiopathiae. Antibodies to the 64-66 kDa glycoprotein of the E. rhusiopathiae were demonstrated by immunoblotting. The qualitative antibody responses were evaluated by means of ELISA(s) using monoclonal antibodies to swine IgG1 and IgG2. The addition of 2mg ginseng per vaccine dose, potentiate the antibody response of the commercial vaccines without altering their safety. Significantly higher (P<0.001) antibody titres were achieved to both PPV and to E. rhusiopathiae by the supplementation with ginseng. Aluminium hydroxide adjuvanted vaccines favoured the production of IgG1 antibodies. Interestingly, the vaccines supplemented with ginseng favoured IgG2. The vaccines used in the evaluations varied in their immunogenic potency. However, after the addition of ginseng the less immunogenic vaccine proved to be as potent as the better one without ginseng. Thus, the use of ginseng as a co-adjuvant provides a simple, safe and cheap alternative for improving the potency of aluminium hydroxide adjuvanted vaccines.

Adjuvants, Immunologic↗

PubMed2003

Association of interleukin 1B gene polymorphism and gastric cancers in high and low prevalence regions in China.

AIM: Our aim was to study the relationship between interleukin 1B (IL-1B) polymorphism, Helicobacter pylori infection, and gastric cancer in high prevalent (Shanxi) and low prevalent (Guangdong) regions in China. METHOD: Genomic DNA was extracted from peripheral blood of 192 healthy volunteers, 84 gastric cancer patients from Guangdong and 169 healthy volunteers, and 86 gastric cancer patients from Shanxi. Polymorphisms in IL-1B that encodes IL-1beta and IL-1RN that encodes IL-1 receptor antagonist were analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). These polymorphic sites include promoter regions of IL-1B at positions +3954, -511 (C-T transition), and -31 (T-C transition), and IL-1RN variable tandem repeats. RESULTS: In the low prevalence region, the frequencies of the IL-1B +3954 T/T and IL-1RN *2/*2 genotypes were similar. IL-1B -511T/T genotype frequency was significantly higher among patients with gastric cancer (25.0%) than control subjects (12.5%) (chi2=6.7, p=0.01). In the high prevalence region, the frequencies of the IL-1B +3954T/T and -511T/T genotypes and the IL-1RN *2/*2 genotype in the cancer and control groups were similar. IL-1B -31C/C genotype frequency was significantly higher among patients with gastric cancer (90.0%) than controls (78.0%) (chi2=5.0, p=0.025). Compared with the low prevalence region, control subjects from the high prevalence region had a higher frequency of the IL-1B -511T/T genotype (23.0% v 12.5%; chi2=7.0, p<0.008). While H pylori infection alone had only a modest effect on the risk of gastric cancer development (odds ratio (OR) 5.0 (95% confidence interval (CI) 1.5-16.3)), combined with the IL-1B -511T/T genotype the risk was markedly elevated (OR 17.1, 95% CI 3.8-76.4). CONCLUSION: IL-1B -511T/T genotypes are associated with gastric cancer in China. The effect of IL-1B polymorphism is less obvious in areas of high prevalence for gastric cancer.

Adult↗

PubMed2003

Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms.

METHODS: The 22q13 deletion syndrome (MIM 606232) is characterised by moderate to profound mental retardation, delay/absence of expressive speech, hypotonia, normal to accelerated growth, and mild dysmorphic features. We have determined the deletion size and parent of origin in 56 patients with this syndrome. RESULTS: Similar to other terminal deletion syndromes, there was an overabundance of paternal deletions. The deletions vary widely in size, from 130 kb to over 9 Mb; however all 45 cases that could be specifically tested for the terminal region at the site of SHANK3 were deleted for this gene. The molecular structure of SHANK3 was further characterised. Comparison of clinical features to deletion size showed few correlations. Some measures of developmental assessment did correlate to deletion size; however, all patients showed some degree of mental retardation and severe delay or absence of expressive speech, regardless of deletion size. CONCLUSION: Our analysis therefore supports haploinsufficiency of the gene SHANK3, which codes for a structural protein of the postsynaptic density, as a major causative factor in the neurological symptoms of 22q13 deletion syndrome.

Base Sequence↗

PubMed2003

Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro.

We have found that the ubiquitin-proteasome pathway exerts exquisite control of osteoblast differentiation and bone formation in vitro and in vivo in rodents. Structurally different inhibitors that bind to specific catalytic beta subunits of the 20S proteasome stimulated bone formation in bone organ cultures in concentrations as low as 10 nM. When administered systemically to mice, the proteasome inhibitors epoxomicin and proteasome inhibitor-1 increased bone volume and bone formation rates over 70% after only 5 days of treatment. Since the ubiquitin-proteasome pathway has been shown to modulate expression of the Drosophila homologue of the bone morphogenetic protein-2 and -4 (BMP-2 and BMP-4) genes, we examined the effects of noggin, an endogenous inhibitor of BMP-2 and BMP-4 on bone formation stimulated by these compounds and found that it was abrogated. These compounds increased BMP-2 but not BMP-4 or BMP-6 mRNA expression in osteoblastic cells, suggesting that BMP-2 was responsible for the observed bone formation that was inhibited by noggin. We show proteasome inhibitors regulate BMP-2 gene expression at least in part through inhibiting the proteolytic processing of Gli3 protein. Our results suggest that the ubiquitin-proteasome machinery regulates osteoblast differentiation and bone formation and that inhibition of specific components of this system may be useful therapeutically in common diseases of bone loss.

Animals↗

PubMed2002

The mechanisms underlying the unique pharmacodynamics of nateglinide.

Nateglinide, a D-phenylalanine derivative, belongs to a new group of insulinotropic agents with rapid onset and short duration of action. These agents have been developed to reduce the risk of hypoglycaemia associated with pharmacological control and to decrease the likelihood of pancreatic beta-cell exhaustion. Nateglinide mediates the release of insulin from beta-cells by binding to the sulphonylurea receptors, which leads to the closure of ATP-sensitive K(+) channels. Increasing evidence from receptor binding, mechanistic and in vitro and in vivo insulin studies indicate unique pharmacodynamic and pharmacokinetic properties with nateglinide that are distinct from those of sulphonylureas. The time required by nateglinide to close beta-cell K(ATP) channels is comparable to that of glyburide but threefold and fivefold faster than repaglinide and glimepiride, respectively. Furthermore, its effects are rapidly reversed with an off-rate at the K(ATP) channel twice as fast as that of glyburide and glimepiride and five times faster than repaglinide. This results in a rapid and short insulin response characteristic of the physiological pattern of post-mealtime insulin release. Internalisation into beta-cells is not required for the action of nateglinide. Given that the kinetic profile of the agent is associated with selective enhancement of early-phase insulin secretion, nateglinide is expected to minimise post-meal hyperglycaemia with minimal propensity for hypoglycaemia.

ATP-Binding Cassette Transporters↗

PubMed2002

Phonon spectrum in a plasma crystal.

The Fourier spectra of longitudinal and transverse waves corresponding to random particle motion were measured in a two-dimensional plasma crystal. The crystal was composed of negatively charged microspheres immersed in a plasma at a low gas pressure. The phonons were found to obey a dispersion relation that assumes a Yukawa interparticle potential. The crystal was in a nonthermal equilibrium, nevertheless phonon energies were almost equally distributed with respect to wave number over the entire first Brillouin zone.

Journal Article↗

PubMed2002

Dispersion relations of longitudinal and transverse waves in two-dimensional screened Coulomb crystals.

Dispersion relations of longitudinal and transverse waves in two-dimensional (2D) screened-Coulomb crystals were investigated. The waves were excited in 2D crystals made from complex plasmas, i.e., dusty plasmas, by applying radiation pressure of laser light. The dependencies of the dispersion relation on the shielding parameter, the damping rate, and the wave propagation direction were experimentally measured. The measured dispersion relations agree reasonably with a recently developed theory, and the comparison yields the shielding parameter and the charge on particles.

Journal Article↗

PubMed2001

Increased pituitary and adrenal reactivity in premenopausal women with posttraumatic stress disorder.

BACKGROUND: Limited studies of hypothalamic-pituitary-adrenal axis regulation in posttraumatic stress disorder have been performed in premenopausal women. We therefore undertook a study of hypothalamic-pituitary-adrenal axis regulation in this population. METHODS: Outpatient posttraumatic stress disorder subjects were compared with healthy, age- and weight-matched nontraumatized subjects. Subjects were free from psychotropic medications, alcohol and other illicit substances for at least 4 weeks before study. Menstrual cycle phase was determined by monitoring the LH surge and plasma progesterone levels. Corticotropin releasing factor and adrenocorticotropin stimulation tests, as well as 24-hour urinary-free cortisol measurements were performed. RESULTS: Corticotropin releasing factor test: Baseline adrenocorticotropic hormone and cortisol levels did not differ between the 12 PTSD and 11 comparison subjects, but the posttraumatic stress disorder group had greater adrenocorticotropic hormone and cortisol responses to corticotropin releasing factor, as well as a later cortisol peak. Adrenocorticotropic hormone test: Baseline cortisol levels did not differ between the 10 posttraumatic stress disorder subjects and seven controls, but the posttraumatic stress disorder group showed greater cortisol responses to adrenocorticotropic hormone. Peak cortisol responses to corticotropin releasing factor and adrenocorticotropic hormone were correlated with each other and with 24-hour urinary-free cortisol excretion. CONCLUSIONS: Pituitary and adrenal hyperreactivity to exogenous corticotropin releasing factor and adrenocorticotropic hormone is demonstrated in premenopausal women with chronic posttraumatic stress disorder. Cortisol hyperreactivity thus may play a role in the pathophysiology of posttraumatic stress disorder in women.

Adrenocorticotropic Hormone↗

PubMed2001

IL-18-binding protein protects against lipopolysaccharide- induced lethality and prevents the development of Fas/Fas ligand-mediated models of liver disease in mice.

IL-18-binding protein (IL-18BP) is a natural IL-18 inhibitor. Human IL-18BP isoform a was produced as fusion construct with human IgG1 Fc and assessed for binding and neutralizing IL-18. IL-18BP-Fc binds human, mouse, and rat IL-18 with high affinity (K(D) 0.3-5 nM) in a BIAcore-based assay. In vitro, IL-18BP-Fc blocks IL-18 (100 ng/ml)-induced IFN-gamma production by KG1 cells (EC(50) = 0.3 microg/ml). In mice challenged with an LD(90) of LPS (15 mg/kg), IL-18BP-Fc (5 mg/kg) administered 10 min before LPS blocks IFN-gamma production and protects against lethality. IL-18BP-Fc administered 10 min before LPS blocks IFN-gamma production induced by LPS (5 mg/kg) with ED(50) of 0.005 mg/kg. Furthermore, IL-18BP-Fc (5 mg/kg) abrogates LPS (5 mg/kg)-induced IFN-gamma production even when administered 6 days before LPS but shows no effect when administered 9 or 12 days before LPS. Given 10 min before LPS challenge to mice primed 12 days in advance with heat-killed Propionibacterium acnes, IL-18BP-Fc prevents LPS-induced liver damage and IFN-gamma and Fas ligand expression. Given at the moment of priming with P. acnes, IL-18BP-Fc decreases P. acnes-induced granuloma formation, macrophage-inflammatory protein-1alpha and macrophage-inflammatory protein-2 production and prevents sensitization to LPS. IL-18BP-Fc also prevents Con A-induced liver damage and IFN-gamma and Fas ligand expression as well as liver damage induced by Pseudomonas aeruginosa exotoxin A or by anti-Fas agonistic Ab. In conclusion, IL-18BP can be engineered and produced in recombinant form to generate an IL-18 inhibitor, IL-18BP-Fc, endowed with remarkable in vitro and in vivo properties of binding and neutralizing IL-18.

Animals↗

PubMed2001

Effect of insulinotropic agent nateglinide on Kv and Ca(2+) channels in pancreatic beta-cell.

Novel insulinotropic agent nateglinide stimulates insulin via binding to sulfonylurea receptor and closing the ATP-dependent K+ (K(ATP)) channels in pancreatic beta-cells, leading to an increase in [Ca(2+)](i) for exocytosis. The voltage-dependent Ca(2+) channel and the delayed rectifier K+ (Kv) channels are also present in beta-cells and their activities determine the configuration of action potential and hence contribute to the regulation of [Ca(2+)](i) and insulin secretion. This study, by using the patch-clamp method in whole cell configuration, comparatively characterized the direct effects of sulfonylurea receptor ligands including nateglinide, glyburide, and repaglinide on Kv and Ca(2+) channels. Each agent inhibited Kv currents in a concentration-dependent manner with effective concentration range two to three orders higher than that for blocking K(ATP) channels. A marginal stimulation of Ca(2+) current was observed with all drugs, while repaglinide at concentration greater than 300 nM inhibited Ca(2+) current. The direct effects of these antidiabetic agents on Kv and Ca(2+) channels may act concertedly with their primary action on K(ATP) channels in regulating [Ca(2+)](i) and the stimulus-secretion coupling.

Animals↗

PubMed2001

Sequence analysis of the Spodoptera litura multicapsid nucleopolyhedrovirus genome.

The complete Spodoptera litura multicapsid nucleopolyhedrovirus (SpltMNPV) genome contained 139,342 bp with a G+C content of 42.7%, and 141 putative open reading frames (ORFs) or genes of 150 nucleotides or greater that showed minimal overlap. Ninety-six ORFs had homologues in Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), 16 had homologues in other baculoviruses, and 29 were unique to SpltMNPV. The homologues of ubiquitin and gp37 are fused in SpltMNPV. The genome lacked a homologue of the major budded virus glycoprotein gene gp64, but it contained a homologue of ORF130 of Lymantria dispar multicapsid nucleopolyhedrovirus (LdMNPV). There were two homologues of AcMNPV ORF2 (bro gene), and a DnaJ protein gene (SpltORF39) in which the N-terminus showed homologies with the J domain of DnaJ family proteins. Seventeen homologous regions (hrs) were identified, each containing 2-29 palindromic repeats, with an average length of 534 bp and base content (G+C%) of 33.0.

Amino Acid Sequence↗

PubMed2001

Characterization of the interaction between phospholipid and protein by capillary electrophoresis with laser-induced fluorescence detection.

We report an electrophoretic mobility shift-based method to study the interactions between phospholipids and proteins by capillary electrophoresis with laser-induced fluorescence detection. A fluorogenic dye, 3-(2-furoyl)quinoline-2-carboxaldehyde (FQ), was used to label phosphatidylserine (PS). Then the FQ labeled PS (FQ-PS) was used as the fluorescent probe for monitoring the association between PS and bovine serum albumin (BSA). Two conjugates were observed to form between each PS species and BSA, indicating that two interactions exist between these PS species and BSA. We can also detect the competitive association with BSA between labeled PS and unlabeled PS. This method only needs a minute volume of sample. It is highly sensitive and can be used to detect the interaction between phospholipids and nanomolar concentrations of proteins, such as BSA.

Electrophoresis, Capillary↗

PubMed2001

Voltage-dependent flickery block of an open cystic fibrosis transmembrane conductance regulator (CFTR) channel pore.

1. Fast flickery block of the cystic fibrosis transmembrane conductance regulator (CFTR) was studied with cell-attached and whole-cell patch-clamp recordings from mouse NIH3T3 cells stably expressing a mutant CFTR channel, K1250A-CFTR. This mutant CFTR channel, once open, can stay open for minutes. Within a prolonged opening, the kinetics of fast flickery closures can be readily quantified. 2. Flickering block of K1250A-CFTR channels was voltage dependent since the open probability within an opening burst decreased as the membrane was hyperpolarized. 3. Mean open time (tau(o)) and mean closed time (tau(c)), obtained from single-channel kinetic analysis, were corrected for missed events. Our data show that corrected tau(c) was voltage dependent while corrected tau(o) exhibited little voltage dependence. Results from whole-cell current relaxation upon voltage jump further indicate that tau(c) at a membrane potential of -100 mV was at least 10-fold longer than that at +100 mV. 4. tau(c), but not tau(o), was sensitive to external permeant anions. After complete replacement of external Cl(-) with impermeant anions, tau(c) showed little voltage dependence and approximated a value observed under strong hyperpolarization in the presence of high external permeant anions. These results suggest that the resident time of the blocker is prolonged by conditions (i.e. hyperpolarization or the absence of external permeant anions) that deplete Cl(-) in the CFTR pore. 5. Results from macroscopic current noise analysis of both wild-type CFTR and K1250A-CFTR channels further confirm the voltage dependence and Cl(-) sensitivity of the fast flickery block observed with single-channel analysis. 6. We conclude that the voltage dependence of the flickery block in CFTR is mainly due to the voltage-dependent occupancy of an anion-binding site in the channel pore by trans-anions. The blocker acquires a voltage-dependent off rate through an electrostatic interaction with Cl(-) in the pore.

3T3 Cells↗

PubMed2001

U50488 inhibits HIV-1 expression in acutely infected monocyte-derived macrophages.

Opioids may play an immunomodulatory role in the pathogenesis of human immunodeficiency virus-1 (HIV-1) infection. Recently, synthetic kappa-opioid receptor (KOR) ligands have been found to have anti-human immunodeficiency virus type 1 activity in acutely infected brain macrophages. In the present study, we investigated whether the selective KOR ligand U50488 would exert such an anti-HIV-1 effect in acutely infected blood monocyte-derived macrophages (MDM). Treatment of acutely infected MDM with U50488 induced a concentration-dependent inhibition of HIV-1 expression. The dose--response relationship of U50488 was U-shaped with a peak effect observed at 10(-13) M, which was evident at both 7 and 14 days post-infection. The KOR antagonist nor-binaltorphimine blocked the anti-HIV-1 effect of U50488 by 73%, indicating involvement of a KOR-mediated mechanism. Also, expression of KOR mRNA and binding activity with a fluorescence-labeled KOR ligand supported the existence of KOR on MDM. Antibodies to the beta-chemokine, RANTES (regulated on activation normal T-cell expressed and secreted), but not to various other cytokines, blocked U50488 inhibition by 56% suggesting that the anti-HIV-1 effect of U50488 involved, in part, the production of RANTES by MDM. Taken together, these in vitro findings support the anti-HIV-1 property of U50488, and suggest that KOR ligands may have therapeutic potential for treating patients with acquired immunodeficiency syndrome.

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