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Showing papers by "Banaras Hindu University published in 2002"


Journal ArticleDOI
TL;DR: Oral miltefosine is an effective and safe treatment for Indian visceral leishmaniasis and may also be helpful in regions where parasites are resistant to current agents.
Abstract: Background There are 500,000 cases per year of visceral leishmaniasis, which occurs primarily in the Indian subcontinent. Almost all untreated patients die, and all the effective agents have been parenteral. Miltefosine is an oral agent that has been shown in small numbers of patients to have a favorable therapeutic index for Indian visceral leishmaniasis. We performed a clinical trial in India comparing miltefosine with the most effective standard treatment, amphotericin B. Methods The study was a randomized, open-label comparison, in which 299 patients 12 years of age or older received orally administered miltefosine (50 or 100 mg [approximately 2.5 mg per kilogram of body weight] daily for 28 days) and 99 patients received intravenously administered amphotericin B (1 mg per kilogram every other day for a total of 15 injections). Results The groups were well matched in terms of age, weight, proportion with previous failure of treatment for leishmaniasis, parasitologic grade of splenic aspirate, and sple...

715 citations


Journal ArticleDOI
TL;DR: The group of diseases known as the leishmaniases are caused by obligate intracellular protozoa of the genus Leishmania.
Abstract: The group of diseases known as the leishmaniases are caused by obligate intracellular protozoa of the genus Leishmania ([39][1]). Natural transmission of leishmania is carried out by a certain species of sandfly of the genus Phlebotomus (Old World) or Lutzomyia (New World). These are present in

526 citations


Journal ArticleDOI
TL;DR: The essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore and all the active compounds showed greater protection than sodium valproate.

248 citations


Journal ArticleDOI
TL;DR: The chromate-reducing ability of Pseudomonas aeruginosa A2Chr was compared in batch culture, with cells entrapped in a dialysis sac, and with cells immobilized in an agarose-alginate film in conjunction with a rotating biological contactor to achieve maximum Cr(VI) reduction.
Abstract: The chromate-reducing ability of Pseudomonas aeruginosa A2Chr was compared in batch culture, with cells entrapped in a dialysis sac, and with cells immobilized in an agarose-alginate film in conjunction with a rotating biological contactor. In all three systems, the maximum Cr(VI) reduction occurred at 10 mg Cr(VI)/l. Whereas at 50 mg Cr(VI)/l concentration, only 16% of the total Cr(VI) was reduced, five spikings with 10 mg chromate/l at 2-h intervals led to 96% reduction of the total input of 50 mg Cr(VI)/l. Thus maximum Cr(VI) reduction was achieved by avoiding Cr(VI) toxicity to the cells by respiking with lower Cr(VI) concentrations. At 10 mg Cr(VI)/l, the pattern of chromate reduction in dialysis-entrapped cells was almost similar to that of batch culture and 86% of the bacterially reduced chromium was retained inside the dialysis sac. In electroplating effluent containing 100 mg Cr(VI)/l, however, the amount of Cr(VI) reduced by the cells immobilized in agarose-alginate biofilm was twice and thrice the amount reduced by batch culture and cells entrapped in a dialysis sac, respectively.

240 citations


Journal ArticleDOI
K. Adcox1, S. S. Adler2, N. N. Ajitanand3, Y. Akiba  +319 moreInstitutions (36)
TL;DR: In this article, the PHENIX experiment at RHIC was used to measure the transverse momentum spectra at mid-rapidity in collision centrality, and the average transverse momenta increase with the number of participating nucleons in a similar way for all particle species.
Abstract: Identified ${\ensuremath{\pi}}^{+/\ensuremath{-}}$, ${K}^{+/\ensuremath{-}}$, $p$, and $\overline{p}$ transverse momentum spectra at midrapidity in $\sqrt{{s}_{\mathrm{NN}}}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}130\phantom{\rule{0ex}{0ex}}\mathrm{GeV}\phantom{\rule{0ex}{0ex}}\mathrm{Au}+\mathrm{Au}$ collisions were measured by the PHENIX experiment at RHIC as a function of collision centrality. Average transverse momenta increase with the number of participating nucleons in a similar way for all particle species. Within errors, all midrapidity particle yields per participant are found to be increasing with the number of participating nucleons. There is an indication that ${K}^{+/\ensuremath{-}}$, $p$, and $\overline{p}$ yields per participant increase faster than the ${\ensuremath{\pi}}^{+/\ensuremath{-}}$ yields. In central collisions at high transverse momenta $({p}_{T}\ensuremath{\gtrsim}2\mathrm{GeV}/c)$, $\overline{p}$ and $p$ yields are comparable to the ${\ensuremath{\pi}}^{+/\ensuremath{-}}$ yields.

231 citations


Journal ArticleDOI
TL;DR: The present ethnobotanical exploration study presents the folk medicinal uses of certain plants by tribes of the Sonbhadra district in the Uttar Pradesh state of India.

185 citations


Journal Article
TL;DR: In this article, the authors discuss various approaches of ecosystem restoration on mine spoil, criteria for the selection of plantation species and future research needs in this regard, and discuss the criteria for selecting the best tree plantations.
Abstract: Because of large-scale destruction of natural areas due to mining operations, a restoration strategy is needed as a part of the overall mining management plan In restoration, emphasis is given first to build soil organic matter, nutrients and vegetation cover to accelerate natural recovery process Tree plantations can be used as a tool for mine spoil restoration as they have ability to restore soil fertility and ameliorate microclimatic conditions We discuss here various approaches of ecosystem restoration on mine spoil, criteria for the selection of plantation species and future research needs in this regard

178 citations


Journal ArticleDOI
TL;DR: The overall observations show the potential of the Cur EPS for its deployment in metal bioremediation.
Abstract: Extracellular polysaccharides (EPS) of a copper-sensitive (Cus) and a copper-resistant (Cur) Pseudomonas aeruginosa strain were investigated in terms of their production, chemical nature and response towards copper exposure. The extent of EPS synthesis by the resistant strain (4.78 mg mg−1 cell dry wt.) was considerably higher over its sensitive counterpart (2.78 mg mg−1 dry wt.). FTIR-spectroscopy and gas chromatography revealed that both the polymers were acidic in nature, containing alginate as the major component along with various neutral- and amino-sugars. Acid content in the Cur EPS (480.54 mg g−1) was greater than that in the Cus EPS (442.0 mg g−1). Presence of Cu2+ in the growth medium caused a dramatic stimulation (approximately 4-fold) in EPS synthesis by the Cur strain, while in a similar condition, the Cus failed to exhibit such response. The polymer of the resistant strain showed elevated Cu2+ binding (320 mg g−1 EPS) compared to that of the sensitive type (270 mg g−1). The overall observations show the potential of the Cur EPS for its deployment in metal bioremediation.

160 citations


Journal ArticleDOI
K. Adcox1, S. S. Adler2, N. N. Ajitanand3, Y. Akiba  +320 moreInstitutions (36)
TL;DR: Transverse momentum spectra of electrons from Au+Au collisions at square root[s(NN)] = 130 GeV have been measured by the PHENIX experiment at the Relativistic Heavy Ion Collider and are consistent with that expected from semileptonic decays of charm.
Abstract: Transverse momentum spectra of electrons from Au+Au collisions at roots(NN) = 130 GeV have been measured at midrapidity by the PHENIX experiment at the Relativistic Heavy Ion Collider. The spectra show an excess above the background from photon conversions and light hadron decays. The electron signal is consistent with that expected from semileptonic decays of charm. The yield of the electron signal dN(e)/dy for p(T) > 0.8 GeV/c is 0.025 +/- 0.004(stat) +/- 0.010( syst) in central collisions, and the corresponding charm cross section is 380 +/- 60(stat) +/- 200(syst ) mub per binary nucleon-nucleon collision.

147 citations


Journal ArticleDOI
K. Adcox1, S. S. Adler2, N. N. Ajitanand3, Y. Akiba  +319 moreInstitutions (35)
TL;DR: Two-particle azimuthal correlation functions are presented for charged hadrons produced in Au+Au collisions at the Relativistic Heavy Ion Collider, suggesting rapid thermalization and relatively strong velocity fields.
Abstract: Two-particle azimuthal correlation functions are presented for charged hadrons produced in Au+Au collisions at the Relativistic Heavy Ion Collider (sqrt[sNN]=130 GeV). The measurements permit determination of elliptic flow without event-by-event estimation of the reaction plane. The extracted elliptic flow values (v2) show significant sensitivity to both the collision centrality and the transverse momenta of emitted hadrons, suggesting rapid thermalization and relatively strong velocity fields. When scaled by the eccentricity of the collision zone e, the scaled elliptic flow shows little or no dependence on centrality for charged hadrons with relatively low pT. A breakdown of this e scaling is observed for charged hadrons with pT >1.0 GeV/c.

144 citations


Journal ArticleDOI
K. Adcox1, S. S. Adler2, N. N. Ajitanand3, Y. Akiba  +320 moreInstitutions (36)
TL;DR: Two-pion correlations in roots(NN) = 130 GeV Au+Au collisions at RHIC have been measured over a broad range of pair transverse momentum k(T) by the PHENIX experiment as discussed by the authors.
Abstract: Two-pion correlations in roots(NN) = 130 GeV Au+Au collisions at RHIC have been measured over a broad range of pair transverse momentum k(T) by the PHENIX experiment at RHIC. The k(T) dependent transverse radii are similar to results from heavy-ion collisions at roots(NN) = 4.1 , 4.9, and 17.3 GeV, whereas the longitudinal radius increases monotonically with beam energy. The ratio of the outwards to sidewards transverse radii (R-out/R-side) is consistent with unity and independent of k(T) .

Journal ArticleDOI
TL;DR: Explant age, preculture period, bacterial strain and density were found to be critical determinants of transformation efficiency and indicated the effectiveness of the transgene against infestation by diamondback moth (Plutella xylostella) larvae.
Abstract: A number of factors that are known to influence genetic transformation were evaluated to optimizeAgrobacterium-mediated transformation of hypocotyl explants of cauliflower variety Pusa Snowball K-1. The binary vector p35SGUSINT mobilized intoAgrobacterium strain GV2260 was used for transformation and transient GUS expression was used as the basis for identifying the most appropriate conditions for transformation. Explant age, preculture period, bacterial strain and density were found to be critical determinants of transformation efficiency. Using the optimized protocol, the syntheticcryIA(b) gene was mobilized into cauliflower. Molecular analyses of transgenics established the integration and expression of the transgene. Insect bioassays indicated the effectiveness of the transgene against infestation by diamondback moth (Plutella xylostella) larvae.

Journal ArticleDOI
TL;DR: If applied in a practical clinical setting (on symptomatic patients in whom active VL is suspected and other common infections have been excluded), strip testing of serum for anti-K39 antibody should be both sensitive and specific for diagnosing VL in India.
Abstract: Stored sera from 429 Indian subjects were assayed to extend the analysis of the accuracy of immunochromatographic strip-test detection of anti-K39 antibody in the non-invasive diagnosis of visceral leishmaniasis (VL). All 225 samples from patients with proven Leishmania infection tested positive [estimated sensitivity=100%; 95% confidence interval (CI)=98%-100%]. Sera from 99 of the 100 symptomatic patients with other diseases were non-reactive (estimated specificity=99%; CI=94%-100%). However, samples from 13 of the 104 apparently healthy controls showed positive strip-test results (estimated specificity=88%; CI=79%-93%), yielding an overall specificity of 93% (190/204; CI=88%-96%). If applied in a practical clinical setting (on symptomatic patients in whom active VL is suspected and other common infections have been excluded), strip testing of serum for anti-K39 antibody should be both sensitive and specific for diagnosing VL in India.

Journal ArticleDOI
TL;DR: Lifetime measurements of the 5D0 level as a function of Eu3+ concentration have been used to explore the concentration quenching process and the mechanism of quench is found to be of a dipole-dipole type.

Journal ArticleDOI
TL;DR: Low-dose liposomal amphotericin B given for 5 days can cure most patients with Indian kala-azar, according to posttreatment apparent cure and definite cure rates.
Abstract: In this randomized, double-blind, dose-ranging, multicenter trial, 84 patients with visceral leishmaniasis refractory to antimony therapy were administered liposomal amphotericin B (AmBisome) at cumulative doses of 3.75, 7.5, and 15.0 mg/kg for 5 consecutive days. Posttreatment apparent cure and definite cure were assessed at 2 weeks and 6 months after the end of therapy, respectively. Mild to moderate infusion-related fever and rigors were seen in 29 and 44% of patients, respectively. One patient each in the 3.75- and 7.5-mg groups had detectable parasites on splenic smear at posttreatment evaluation. At 6 months' follow-up, however, 2, 1, and 1 patients relapsed in the 3.75-, 7.5-, and 15.0-mg groups, resulting in definite cure rates of 89, 93, and 97%, respectively. There was no significant difference in the cure rates of the 3 groups. Low-dose liposomal amphotericin B given for 5 days can cure most patients with Indian kala-azar.

Journal Article
TL;DR: This work examined female remating with respect to sperm competition and sexual selection in Drosophila and addressed the possible benefits for females, and reviewed the role of accessory gland fluid in remating.
Abstract: Female remating is fundamental to evolutionary biology as it determines the pattern of sexual selection and sexual conflict. Remating in females is an important component of Drosophila mating systems because it affects sperm usage patterns and sexual selection. Remating is common in females of many species of Drosophila in both natural and laboratory populations. It has been reported in many insect species and also in vertebrates. Female remating is a prerequisite for sperm competition between males, and the consequences of this competition, such as sperm precedence or sperm displacement, have been reported for many species of Drosophila. Female remating is dependent on the amount of sperm stored, the male seminal fluid components, nutrition, the quantity of eggs laid, experimental design and density of flies in laboratory. Remating by a female is an insurance against male sterility and sub-fertility and increases genetic heterogeneity of female offspring. Remating gives greater female productivity in many species of Drosophila. We examined female remating with respect to sperm competition and sexual selection in Drosophila and addressed the possible benefits for females. We also reviewed the role of accessory gland fluid in remating, costs associated with remating, the genetic basis of female remating and some possible mechanisms of sperm competition in the light of last male sperm priority and paternity assurance in Drosophila and other insects. We also suggest future areas of research.

Journal ArticleDOI
TL;DR: The structure and activity of the methane-oxidising microbial community in a wet meadow soil in Germany were investigated using biogeochemical, cultivation, and molecular fingerprinting techniques, and calculations based on kinetic data suggested that this cell density was sufficient to account for the observed methane oxidation activity in the soil.

Journal ArticleDOI
TL;DR: In this article, it was shown that for the model proposed by Ranjan et al., the correct space group of the high-temperature monoclinic phase should be Ω(Cc).
Abstract: Ranjan et al. [Phys. Rev. B 65, 060102(R) (2002)] have recently presented results of a powder neutron-diffraction study of the high-temperature monoclinic ${(F}_{M}^{\mathrm{HT}})$ to low-temperature monoclinic ${(F}_{M}^{\mathrm{LT}})$ phase transition in $\mathrm{Pb}({\mathrm{Ti}}_{1\ensuremath{-}x}{\mathrm{Zr}}_{x}){\mathrm{O}}_{3}$ discovered by Ragini et al. [Phys. Rev. B 64, 054101 (2001)]. They attribute the presence of superlattice reflections in the diffraction data to tilting of oxygen octahedra and propose a monoclinic space group $\mathrm{Pc}$ for the ${F}_{M}^{\mathrm{LT}}$ phase. It is shown that for the model proposed by Ranjan et al., the correct space group of the ${F}_{M}^{\mathrm{LT}}$ phase should be $\mathrm{Cc}.$ This has also been corroborated by a group-theoretical approach to the problem. A different set of refined structural parameters for the $\mathrm{Cc}$ space group obtained from the Rietveld analysis of the powder neutron-diffraction data of Ranjan et al. is also presented.

Journal ArticleDOI
TL;DR: The N-terminal sequence of pigeonpea urease, determined up to the 20th residue, was homologous to that of jack bean and soybean seed ureases.

Journal Article
TL;DR: Compound 6-chloroisatin-3- (4-bromophenyl)-semicarbazone has emerged as the most active analogue of the series showing good activity in all the three tests and was more active than phenytoin and valproic acid.
Abstract: Purpose: A series of substituted isatin semicar- bazones and related bioisosteric hydrazones were designed and synthesised to meet the structural requirements essen- tial for anticonvulsant properties. Methods: The struc- tures of all synthesised compounds were confirmed by means of infrared, proton magnetic resonance spectros- copy and by elemental analyses. All compounds were eval- uated for their anticonvulsant activity by maximal electroshock (MES), subcutaneous metrazol (ScMet) and subcutaneous strychnine (ScSty) induced seizure methods and their neurotoxic effects were determined by rotorod test. Results: A number of isatin semicarbazones exhib- ited significant protection after intraperitoneal administra- tion at the dose of 100 and 300mg/kg. Some of them showed good anticonvulsant activity in MES test in rats after per oral administration at the dose of 30mg/kg. The bioisosteric hydrazone derivatives were inactive in all tests. Compound 6-chloroisatin-3- (4-bromophenyl)-semicarba- zone has emerged as the most active analogue of the series showing good activity in all the three tests and was more active than phenytoin and valproic acid. Conclusions: The results evidenced the importance of hydrogen bond- ing and suggested a new pharmacophore model with four binding sites essential for anticonvulsant activity.

Journal ArticleDOI
TL;DR: In this article, carbon, oxygen and strontium isotope compositions of carbonate rocks of the Proterozoic Vindhyan Supergroup, central India suggest that they can be correlated with the isotope evolution curves of marine carbonates during the latter Proteozoic.

Journal ArticleDOI
K. Adcox1, S. S. Adler2, N. N. Ajitanand3, Y. Akiba  +318 moreInstitutions (35)
TL;DR: In this paper, the authors measured the distribution of event-by-event fluctuations of the mean transverse momentum and mean transversal energy near mid-rapidity in Au+Au collisions at roots(NN)=130 GeV at the Relativistic Heavy-Ion Collider.
Abstract: Distributions of event-by-event fluctuations of the mean transverse momentum and mean transverse energy near mid-rapidity have been measured in Au+Au collisions at roots(NN)=130 GeV at the Relativistic Heavy-Ion Collider. By comparing the distributions to what is expected for statistically independent particle emission, the magnitude of nonstatistical fluctuations in mean transverse momentum is determined to be consistent with zero. Also, no significant nonrandom fluctuations in mean transverse energy are observed. By constructing a fluctuation model with two event classes that preserve the mean and variance of the semi-inclusive p(T) or e(T) spectra, we exclude a region of fluctuations in roots(NN)=130 GeV Au+Au collisions.

Journal ArticleDOI
TL;DR: In this article, a ternary ferrite with molecular formula, CoFe2−xCrxO4 (0≤x≤1.0) has been synthesized at 70°C by a precipitation method and were transformed into the film form at the pretreated Ni support (1.5× 1.0 cm2) using an oxide-slurry painting technique.

Journal ArticleDOI
TL;DR: In this article, the formation of new ternary hydride Mg 2 FeH 6 (K 2 PtCl 6 type) in a single-step procedure following the process of mechanical alloying of initial stoichiometric ingredients Mg and Fe under hydrogen.

Journal ArticleDOI
TL;DR: In this article, low cycle fatigue behavior of the Ti alloy IMI 834 was studied, for a bimodal microstructure with ≈14 vol.% primary α (α p ) in the matrix of transformed β, at different total strain amplitudes (Δ e t /2) from ± 0.75 to ± 1.7%, at room temperature.
Abstract: Low cycle fatigue behavior of the Ti alloy IMI 834 was studied, for a bimodal microstructure with ≈14 vol.% primary α (α p ) in the matrix of transformed β, at different total strain amplitudes (Δ e t /2) from ±0.75 to ±1.7%, at room temperature. TEM examination revealed silicide particles at the interface of secondary α platelets in the transformed β, at the boundary of α p and transformed β, and extremely fine precipitates of ordered Ti 3 Al in the matrix. Cyclic softening was observed at all the above strain amplitudes. However, the degree as well as the rate of softening increased markedly at Δ e t /2⩾1%. Cyclic softening was much less at low strain amplitude (Δ e t /2⩽0.8%). The increase in the degree and the rate of softening at higher strain amplitudes is associated with increase in the number and more complete shearing of the ordered Ti 3 Al precipitates, from increase in the number of slip bands and glide dislocations. The increase in the number of glide dislocations in each cycle, with increase in strain amplitude occurs from increase in the effective strain rate to maintain the cyclic frequency at constant level. Bi-linearity was observed in the Coffin–Manson relationship and it was found to be associated with change in the deformation behavior from low to high strain amplitude.

Journal ArticleDOI
TL;DR: In this article, the authors showed that partial substitution of La by Sr in the LaCoO3 matrix increased the electrochemically effective area (RF), as well as the apparent electrocatalytic activity (ia) but it decreased the true catalytic efficiency (it).

Journal ArticleDOI
TL;DR: The high chemical oxygen demand (COD) and the dark brown colour of the distillery spentwash even after anaerobic treatment indicates that conventional treatment methods are far from optimal in attaining the safe limits of disposal.

Journal ArticleDOI
TL;DR: It was concluded that solid-dispersion formulations of Clofazimine can be used to design a solid dosage form of the drug, which would have significant advantages over the currently marketed soft gelatin capsule dosage form.
Abstract: Clofazimine (CLF) was formulated with polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) as a solid solid dispersion (SSD) to increase the aqueous solubility and dissolution rate of the drug. Different molecular weights of PEG (1500, 4000, 6000, and 9000 Da) and PVP (14,000 and 44,000 Da) were used in different drug:carrier weight ratios (1:1, 1:5, and 1:9) and their effect on the dissolution performance of the drug was evaluated in USP Type 2 apparatus using 0.1 N HCl medium. The dissolution rate was compared with corresponding physical mixtures, a currently marketed soft gelatin capsule product, and free CLF. The effect of different methods of preparation (solvent/melt) on the dissolution rate of CLF was evaluated for PEG solid dispersions. Saturation solubility and phase solubility studies were carried out to indicate drug:carrier interactions in liquid state. Infrared (IR) spectroscopy and X-ray diffraction (XRD) were used to indicate drug:carrier interactions in solid state. Improvement in the drug dissolution rate was observed in solid dispersion formulations as compared to the physical mixtures. The dissolution rate improved with the decreasing weight fraction of the drug in the formulation. Polyvinyl pyrrolidone solid dispersion systems gave a better drug release profile as compared to the corresponding PEG solid dispersions. The effect of molecular weight of the PEG polymers did not follow a definite trend, while PVP 14,000 gave a better dissolution profile as compared to PVP 44,000. Improvement in saturation solubility of the drug in the solid dispersion systems was noted in all cases. Further, IR spectroscopy indicated drug:carrier interactions in solid state in one case and XRD indicated reduction in the crystallinity of CLF in another. It was concluded that solid-dispersion formulations of Clofazimine can be used to design a solid dosage form of the drug, which would have significant advantages over the currently marketed soft gelatin capsule dosage form.

Journal ArticleDOI
TL;DR: The D-Pro-Xxx segment can in principle adopt both II’ and I’ turn conformations as si (D-Pro) values of +30 deg.
Abstract: Recent progress in the design of beta-hairpin peptides[1] and beta-sheet models has been based on the ability to nucleate reverse turns of the appropriate stereochemistry. D-Pro-Gly[2] and to a lesser extent Asn-Gly[3] segments have been shown to facilitate formation of type I’ and II’ beta-turns, which are most often found at the site of sharp polypeptide chain reversal, that is, beta-hairpins in proteins.[4, 5] The prime turns, I’ and II’, can exert differing influences on the relative twist of the antiparallel strands. The I’ turn has the sense of twist that matches the twisting of adjacent beta-strands in proteins. In contrast, the II’ turn results in a more planar arrangement with the hairpin flattening to a considerable degree.[4a,e] The D-Pro-Xxx segment can in principle adopt both II’ and I’ turn conformations as si (D-Pro) values of +30 deg. and –120 deg. are energetically favorable.[1a, 5]

Journal ArticleDOI
TL;DR: The ability of MCP-1 to activate murine peritoneal macrophages in vitro for enhanced expression of CD11b, macrophage-mediated cytotoxicity, and production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) is reported.
Abstract: The CC chemokine monocyte chemotactic protein-1 (MCP-1) is a major mediator of monocyte/macrophage infiltration at the inflammatory sides under both physiologic and pathologic conditions. We report the ability of MCP-1 to activate murine peritoneal macrophages in vitro for enhanced expression of CD11b, macrophage-mediated cytotoxicity, and production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). The macrophages treated with MCP-1 in vitro displayed significant cytolytic activity toward TNF-alpha-sensitive L929 cells in a dose-dependent manner. The macrophage-mediated L929 cytotoxicity was blocked in the presence of anti-TNF-alpha antibodies, suggesting the involvement of TNF-alpha. Production of TNF-alpha and IL-1 macrophages on MCP-1 treatment was maximum at 24 h of incubation with 100 ng/ml MCP-1. Enhanced TNF-alpha and IL-1beta mRNA expression was also demonstrated by RT-PCR, which revealed transcription of interferon gamma (IFN-gamma), IL-12, and related T cell-specific chemokine genes, KC and IP-10, in the MCP-1-treated macrophages. The pharmacologic inhibitors pertussis toxin (100 ng/ml), wortmannin (200 ng/ml), H-7 (10 microM), PD98059 (25 microM), and genistein (10 microg/ml) significantly inhibited TNF-alpha and IL-1 production in the MCP1-treated macrophages, suggesting the involvement of G-proteins, phosphoinositol-3-kinase (PI3K), protein kinase C, p42/44 MAPK, and tyrosine kinases in this process.