Biomedical subjects

Ashok Kumar

Publications and source records attributed to Ashok Kumar.

At least 163 records · Page 9Linked to original sources

PubMed2003

Synthesis of some newer derivatives of 2-amino benzoic acid as potent anti-inflammatory and analgesic agents.

Diazotization of N-benzylidene anthranilic acids 1a-1n at pH 9 yielded N-[alpha-(phenylazo) benzylidene] anthranilic acids 2a-2n and at pH 3 yielded N-benzylidene-5-(phenylazo) anthranilic acids 3a-3n. When compounds 3a-3n were treated with thioglycolic/thiolactic acid in the presence of anhydrous ZnCl(2), 2-(4-oxo-2-phenylthiazolidin-3-yl)-5-(phenylazo) benzoic acids 4a-4n were afforded. The newly synthesized compounds were screened for their anti-inflammatory and analgesic activities and were compared with standard drugs, aspirin and phenylbutazone. Out of the compounds studied, the most active compound 4n showed more potent activity than the standard drugs at all doses tested.

Analgesics↗

PubMed2003

Role of white light in reversing UV-B-mediated effects in the N2-fixing cyanobacterium Anabaena BT2.

The effects of various irradiances of artificial UV-B (280-315 nm) in the presence or absence of visible light (photosynthetically active radiation) on growth, survival, 14CO2 uptake and ribulose 1,5-bisphosphate carboxylase (RuBISCO) activity were studied in the N2-fixing cyanobacterium Anabaena BT2. We tested the hypothesis whether or not visible radiation offers any protection against UV-B-induced deleterious effects on growth and photosynthesis in Anabaena BT2. Attempts were also made to determine the irradiances of UV-B where inhibitory effects could be mitigated by simultaneous irradiation with visible light. Exposure of cultures to 0.2 W m(-2) or higher irradiance of UV-B caused inhibition of growth and survival and growth ceased above 1.0 W m(-2). 14CO uptake and RuBISCO activity were found to be more sensitive to UV-B and around 60% reduction in 14CO2 uptake and RuBISCO activity occurred after exposure of cultures to 0.4 W m(-2) for 1 h. However, growth, 14CO2 uptake and RuBISCO activity were nearly normal when UV-B (0.4 W m(-2)) and visible light (14.4 W m(-2)) were given simultaneously. Blue radiation (450 nm) was found to be the most effective in photoreactivation against UV-B, better than UV-A or any other light wavelength band. Our results demonstrate that the studied cyanobacterium possesses active photoreactivation mechanism(s) against UV-B-mediated damage which in turn probably allow survival under natural conditions in spite of being continuously exposed to the UV-B component present in the solar radiation. Continued growth of many algae and cyanobacteria in the presence of intense solar UV-B radiation under natural conditions seems to be due to the active role of photoreactivation.

Anabaena↗

PubMed2003

Study of the spread of a cold instantaneous heavy gas release with surface heat transfer and variable entrainment.

Air quality models help in developing relationships between the amount of pollutant released into the ambient atmosphere by a source and the corresponding incremental contribution in the atmospheric concentration. Of the various dispersion models, the heavy gas models help in predicting the concentrations due to release of gases heavier than air and the risks associated with the increased concentrations. Several differences exist among the various models developed to study the heavy-gas dispersion phenomena. These differences mainly arise because of the varied treatment given to physical processes involved in the dispersion mechanism. One of these processes, which have not been fully considered in many of the existing models, is the effect of ground heating on the movement of a cloud under windy conditions. In this study, the box model developed by Kunsch and Fannelop (J. Hazard. Mater. 43 (1995) 169) is extended to incorporate variable air entrainment on the dispersion of a heavy gas cloud spreading in a channel under windy conditions. The air entrainment was assumed to be proportional to the cloud frontal velocity. The semi-analytical equations developed were then solved by numerical methods to provide a heavy gas cloud dispersion profile. The popular Runge-Kutta fourth order technique was adopted to solve the differential equations numerically. The model was applied on a cold cloud released instantaneously and the results indicated that the model behavior follows closely the expected dispersion trends and observed cloud characteristics reported in a laboratory study. The trial run carried out in order to model the scenario of no heat transfer, by equating the source temperature to the ambient temperature, followed variations observed in the field. The analysis of cloud behavior indicated that the cloud length is strongly influenced by source density and initial cloud temperature.

Air Movements↗

PubMed2003

Tumor necrosis factor-alpha induces functionally active hyaluronan-adhesive CD44 by activating sialidase through p38 mitogen-activated protein kinase in lipopolysaccharide-stimulated human monocytic cells.

Interaction of CD44, an adhesion molecule, with its ligand, hyaluronan (HA), in monocytic cells plays a critical role in cell migration, inflammation, and immune responses. Most cell types express CD44 but do not bind HA. The biological functions of CD44 have been attributed to the generation of the functionally active, HA-adhesive form of this molecule. Although lipopolysaccharide (LPS) and cytokines induce HA-adhesive CD44, the molecular mechanism underlying this process remains unknown. In this study, we show that LPS-induced CD44-mediated HA (CD44-HA) binding in monocytes is regulated by endogenously produced tumor necrosis factor (TNF)-alpha and IL-10. Furthermore, p38 mitogen-activated protein kinase (MAPK) activation was required for LPS- and TNF-alpha-induced, but not IL-10-induced, CD44-HA-binding in normal monocytes. To dissect the signaling pathways regulating CD44-HA binding independently of cross-regulatory IL-10-mediated effects, IL-10-refractory promonocytic THP-1 cells were employed. LPS-induced CD44-HA binding in THP-1 cells was regulated by endogenously produced TNF-alpha. Our results also suggest that lysosomal sialidase activation may be required for the acquisition of the HA-binding form of CD44 in LPS- and TNF-alpha-stimulated monocytic cells. Studies conducted to understand the role of MAPKs in the induction of sialidase activity revealed that LPS-induced sialidase activity was dependent on p42/44 MAPK-mediated TNF-alpha production. Blocking TNF-alpha production by PD98059, a p42/44 inhibitor, significantly reduced the LPS-induced sialidase activity and CD44-HA binding. Subsequently, TNF-alpha-mediated p38 MAPK activation induced sialidase activity and CD44-HA binding. Taken together, our results suggest that TNF-alpha-induced p38 MAPK activation may regulate the induction of functionally active HA-binding form of CD44 by activating sialidase in LPS-stimulated human monocytic cells.

Cell Line, Tumor↗

PubMed2003

Distinct role of ZAP-70 and Src homology 2 domain-containing leukocyte protein of 76 kDa in the prolonged activation of extracellular signal-regulated protein kinase by the stromal cell-derived factor-1 alpha/CXCL12 chemokine.

Stimulation of T lymphocytes with the ligand for the CXCR4 chemokine receptor stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12), results in prolonged activation of the extracellular signal-regulated kinases (ERK) ERK1 and ERK2. Because SDF-1alpha is unique among several chemokines in its ability to stimulate prolonged ERK activation, this pathway is thought to mediate special functions of SDF-1alpha that are not shared with other chemokines. However, the molecular mechanisms of this response are poorly understood. In this study we show that SDF-1alpha stimulation of prolonged ERK activation in Jurkat T cells requires both the ZAP-70 tyrosine kinase and the Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) scaffold protein. This pathway involves ZAP-70-dependent tyrosine phosphorylation of SLP-76 at one or more of its tyrosines, 113, 128, and 145. Because TCR activates ERK via SLP-76-mediated activation of the linker of activated T cells (LAT) scaffold protein, we examined the role of LAT in SDF-1alpha-mediated ERK activation. However, neither the SLP-76 proline-rich domain that links to GADS and LAT, nor LAT, itself are required for SDF-1alpha to stimulate SLP-76 tyrosine phosphorylation or to activate ERK. Together, our results describe the distinct mechanism by which SDF-1alpha stimulates prolonged ERK activation in T cells and indicate that this pathway is specific for cells expressing both ZAP-70 and SLP-76.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Mechanisms by which angiotensin-converting enzyme inhibitors prevent diabetes and cardiovascular disease.

Angiotensin-converting enzyme (ACE) inhibitors are the first-line therapeutic agents for treating hypertension in patients with the cardiometabolic syndrome and those with diabetes. ACE inhibitor therapy reduces both microvascular and macrovascular complications in diabetes and appears to improve insulin sensitivity and glucose metabolism. Several recent studies indicate that ACE inhibitor therapy reduces the development of type 2 diabetes in persons with essential hypertension, a population with a high prevalence of insulin resistance. ACE inhibitor therapy has been shown to improve surrogates of cardiovascular disease (eg, vascular compliance, endothelial-derived nitric oxide production, vascular relaxation and plasma markers of inflammation, oxidative stress, and thrombosis) and reduce cardiovascular disease, renal disease progression, and stroke. This article explores potential mechanism by which ACE inhibition reduces the development of diabetes, improves these surrogate markers, and reduces cardiovascular disease and renal disease.

Angiotensin II↗

PubMed2003

CCAAT/enhancer-binding protein and activator protein-1 transcription factors regulate the expression of interleukin-8 through the mitogen-activated protein kinase pathways in response to mechanical stretch of human airway smooth muscle cells.

Here we investigated the mechanisms by which mechanical stretch regulates the production of IL-8 in primary human airway smooth muscle cells (HASMC). Bronchial HASMC were subjected to cyclic mechanical stretch (12%, 1 Hz) using the computer-controlled Flexcell Strain system. Mechanical stretch increased IL-8 mRNA expression and protein production. Cyclic stretch of HASMC also increased the kinase activities of ERK1/2, JNK1, p38, and the DNA binding activities of AP-1 and C/EBP transcription factors with little effect on NF-kappa B. The inhibition of AP-1 and C/EBP transcriptional activities blocked the production of IL-8 in culture supernatants. Furthermore, the inhibition of ERK1/2 and p38 but not JNK1 caused a significant down-regulation in the expression and production of IL-8 in response to cyclic stretch. Although protein tyrosine kinases were required for the activation of both ERK1/2 and p38 kinase, stretch-activated channels, small GTPase proteins, and extracellular Ca2+ influx were required only for the activation of p38 kinase whereas phosphoinositide 3-kinase was needed for ERK1/2 activation. In addition, the phosphorylation of ERK1/2 was essential for the activation of AP-1 whereas p38 MAP kinase was needed for the activation of C/EBP. Our data demonstrate that the cyclic stretch of HASMC causes the increased production of IL-8 by activating the AP-1 and C/EBP transcription factors through the activation of ERK1/2 and p38 kinase signaling pathways.

Binding Sites↗

PubMed2003

A randomized trial of eutectic mixture of local anesthetics during lumbar puncture in newborns.

OBJECTIVE: To determine the efficacy of a topical anesthetic cream, eutectic mixture of local anesthetics (EMLA), in alleviating pain associated with lumbar puncture in newborns. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Neonatal intensive care unit of a university teaching hospital. Patients Sixty consecutive newborns (gestational age, >or=34 weeks) undergoing diagnostic lumbar puncture. Intervention Topical application of 1 g of EMLA or placebo 60 to 90 minutes before lumbar puncture. MAIN OUTCOME MEASURES: Heart rate, transcutaneous oxygen saturation level, and total behavioral score recorded on a video camera and graded according to the Neonatal Facial Coding System. RESULTS: Compared with baseline, all newborns experienced pain as evidenced by increased heart rate, decreased oxygen saturation level, and total behavioral score (all within-groups differences were significant using repeated-measures analysis of variance; P<.001) during the procedure. Compared with placebo, EMLA significantly attenuated the pain response as shown by a lower mean +/- SE heart rate (per minute), particularly at needle insertion (EMLA: 159.3 +/- 2.3; placebo: 175.2 +/- 2.7; P<.001) and needle withdrawal (EMLA: 153.8 +/- 2.6; placebo: 167.3 +/- 2.5; P<.001), and a lower mean +/- SE total behavioral score, again at insertion (EMLA: 4.0 +/- 0.3; placebo: 5.0 +/- 0.0; P =.004) and withdrawal (EMLA: 1.8 +/- 0.3; placebo: 3.9 +/- 0.3; P<.001). There was no statistically significant difference between groups with regard to oxygen saturation level. CONCLUSIONS: Lumbar puncture in newborns produces pain responses. Eutectic mixture of local anesthetics is an efficacious agent for reducing the pain associated with needle insertion and withdrawal during lumbar puncture in newborns.

Anesthetics, Combined↗

PubMed2003

Inactivation of cyanobacterial nitrogenase after exposure to ultraviolet-B radiation.

Exposure of the N(2)-fixing cyanobacterium Anabaena BT2 to ultraviolet-B radiation (2.5 W m(-2)) for 30 min resulted in complete loss of nitrogenase activity but 100% cell killing occurred only after a 90-min exposure. Inactivation of nitrogenase activity was not specific to Anabaena BT2; other species also showed a similar effect. The time required for 100% killing and inactivation of nitrogenase activity differed in various species, and this difference may be ascribed to the presence of different levels of UV-B protection mechanisms in individual species. Inhibition of nitrogenase activity was immediate, since exposure of cultures to UV-B for as little as 5 min elicited some inhibition of activity. The activity of UV-B-inhibited nitrogenase did not recover upon transfer of exposed cells to fluorescent light, suggesting that the inhibition may be due to specific inactivation of the enzyme. By employment of inhibitors of protein synthesis and PS-II activity, it was demonstrated that restoration of nitrogenase activity in a UV-B-treated culture occurred by fresh synthesis of nitrogenase polypeptide. Our findings suggest that estimation of nitrogenase activity in diazotrophic species may be used as a marker enzyme for assessing the impact of UV-B radiation.

Anabaena↗

PubMed2003

Compositional difference of the exopolysaccharides produced by the virulent and virulence-deficient strains of Xanthomonas oryzae pv. oryzae.

Xanthomonas oryzae pv. oryzae, the bacterial blight pathogen of rice, is known to produce phytotoxic polysaccharides. The extracellular polysaccharide (EPS) was isolated from virulent (BXO1) and virulence-deficient gum G mutant (BXO1002) strains of X. oryzae pv. oryzae and characterized using fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR). Data from the FT-IR suggested that the aldehyde (R-CHO) group and C=O of acid anhydride are present in BXO1 but absent in BXO1002. The (1)H-NMR spectra showed the presence of an acetyl amine of hexose or pentose, free amines of glucose, an beta-anomeric carbon of hexose and pentose, hydrogen next to hydroxyl group, an acetyl amine of hexose and pentose in the polysaccharides of both BXO1 and BXO1002, and the absence of alpha-anomeric carbon of hexose or pentose and the glucuronic acid in the polysaccharides produced by BXO1002. The test for glucuronic acid also confirmed the absence of glucuronic acid in the polysaccharides of BXO1002 and the presence glucuronic acid (32 microg/mg) in the polysaccharides produced by BXO1.

Bacterial Proteins↗

PubMed2003

Alterations in cholinergic and non-cholinergic neurotransmitter receptor densities in transgenic Tg2576 mouse brain with beta-amyloid plaque pathology.

Cholinergic deficits in Alzheimer's disease are accompanied by a number of alterations in other transmitter systems including glutamate, noradrenaline and serotonin, suggesting the involvement also of other neurotransmitter systems in the pathogenesis of the disease. To address the question whether beta-amyloid may contribute to these deficits, brain tissue from transgenic Tg2576 mice with Alzheimer plaque pathology at ages of 5 (still no significant plaque load) and 17 months (moderate to high cortical beta-amyloid plaque load) were examined for a number of cholinergic and non-cholinergic markers. Transgenic mice with no significant plaque load demonstrated reduced hemicholinium-3 (HCh-3) binding to choline uptake sites in anterior brain regions as compared to non-transgenic littermates, while in aged transgenic mice with high number of plaque deposits decreased HCh-3 binding levels were accompanied by increased vesicular acetylcholine transporter binding in selected cortical brain regions. In aged transgenic mice GABA(A), NMDA, AMPA, kainate, and beta-adrenergic as well 5-HT(1A)- and 5-HT(2A)-receptor binding levels were hardly affected, whereas alpha(1)- and alpha(2)-adrenoceptor binding was increased in selected cerebral cortical regions as compared to non-transgenic littermates. The development of changes in both cholinergic and non-cholinergic markers in transgenic Tg2576 mouse brain already before the onset of progressive plaque deposition provides in vivo evidence of a modulatory role of soluble beta-amyloid on cortical neurotransmission and may be referred to the deficits in learning and memory observed in these mice also before significant plaque load.

Acetylcholine↗

PubMed2003

Affinity fractionation of lymphocytes using a monolithic cryogel.

A new type of continuous, supermacroporous, monolithic, cryogel affinity adsorbent was developed, allowing specific fractionation and separation of human peripheral blood lymphocytes in a chromatographic format. The affinity adsorbent was used to design a novel cell separation strategy, which was based on the interaction of protein A from Staphylococcus aureus with cells bearing IgG antibodies on the surface. After treating lymphocytes with goat anti-human IgG(H+L), the IgG-positive B-lymphocytes were efficiently separated from T-lymphocytes. Protein A covalently coupled to epoxy activated dimethylacrylamide (DMAA) cryogel matrix specifically bound IgG-bearing B-lymphocytes through the Fc region, while non-bound T-lymphocytes passed through the column. More than 90% of the B-lymphocytes were retained in the column while the cells in the breakthrough fraction were enriched in T-lymphocytes (81%). The viability of the T-lymphocytes isolated was greater than 90%. The bound lymphocytes released by human or dog IgG recovered 60-70% of the B-cells without significantly impairing the cell viability. The technique can be applied in general to cell separation systems where IgG antibodies against specific cell surface markers are available.

Blood Proteins↗

PubMed2003

Effect of lycopene on pre-eclampsia and intra-uterine growth retardation in primigravidas.

OBJECTIVES: To observe the effect of the antioxidant lycopene on the occurrence of pre-eclampsia and intrauterine growth retardation in primigravida women. METHODS: A total of 251 primigravida women were enrolled in this prospective, randomized controlled study in the second trimester. A total of 116 women were given oral lycopene (Group I) in a dose of 2 mg twice daily while 135 women were given a placebo (Group II) in the same dose until delivery. The criteria for recruitment included gestational age of 16-20 weeks, singleton pregnancy, absence of any medical complication and willingness on the part of the women to participate in the study. The women were followed-up until delivery for development of pre-eclampsia, mode of delivery and fetal outcome. RESULTS: The two groups were comparable in their maternal characteristics. Pre-eclampsia developed in significantly less women in the lycopene group than in the placebo group (8.6% vs. 17.7%, P=0.043 by chi-square test). Mean diastolic blood pressure was significantly higher in the placebo group (92.2+/-5.98 mmHg vs. 86.7+/-3.80 mmHg, P=0.012). Mean fetal weight was significantly higher in the lycopene group (2751.17+/-315.76 g vs. 2657+/-444.30 g, P=0.049). The incidence of intrauterine growth retardation was significantly lower in the lycopene group than in the placebo group (12% vs. 23.7%, P=0.033). CONCLUSIONS: The results of the present study suggest that the antioxidant lycopene reduces the development of pre-eclampsia and intrauterine growth retardation in primigravida women.

Adult↗

PubMed2003

Interaction of age and chronic estradiol replacement on memory and markers of brain aging.

The current study examined effects of chronic estradiol replacement on cognition and biomarkers of aging. Young, middle-aged, and aged rats were ovariectomized and implanted with blank capsules, or capsules containing high or low doses of estradiol benzoate (EB). Three weeks later, animals were tested on inhibitory avoidance and cue and spatial discrimination on the Morris water maze. High plasma estradiol levels were associated with slower swim speed and impaired retention of inhibitory avoidance. No effect of EB treatment was observed for acquisition of the spatial discrimination task, however, a dose by age interaction was observed for retention of spatial discrimination such that higher retention scores were observed for young, middle-aged and aged animals under blank, low and high dose conditions, respectively. EB treatment reversed several hippocampal markers of age-related memory impairment, blocking induction of long-term depression and decreasing cytosolic calcineurin activity. Results indicate that the level of chronic hormone replacement interacts with age to influence hippocampal function.

Aging↗

PubMed2003

Augmentation of B7 expression by herpes simplex virus antigen.

B7 costimulation plays a major role in herpes simplex virus (HSV) immunity. Effects of immunoregulatory cytokines (interferon-gamma [IFN-gamma] and interleukin-10 [IL-10]) and HSV antigens on B7-1 (CD80) and B7-2 (CD86) expression on monocytes during HSV-2 infection were investigated using flow cytometry. Our results demonstrate that HSV-2 infection effects the expression of B7 isoforms (B7-1 and B7-2) on monocytes in two ways, with opposing outcomes. It abrogates the IFN-gamma upregulation of B7-1 and B7-2 and also augments expression of B7-1 and B7-2 on monocytes through an IFN-gamma independent mechanism. The clinical significance of these opposing effects may be related to the pathogenesis of recurrent HSV disease in immunocompetent hosts.

Antigens, CD↗

PubMed2003

Evaluation of anti-diarrhoeal activity in seed extracts of Mangifera indica.

Mangifera indica is commonly grown in many parts of the world. Its seeds have been used for anti-diarrhoeal activity in Indian traditional medicine. This study evaluates the potential anti-diarrhoeal activity of methanolic (MMI) and aqueous (AMI) extracts of seeds of M. indica in experimental diarrhoea, induced by castor oil and magnesium sulphate in mice. Both MMI and AMI were given orally in the dose of 250 mg/kg, showed significant anti-diarrhoeal activity comparable with that of the standard drug loperamide. However, only MMI significantly reduced intestinal transit in charcoal meal test as compared with atropine sulphate (5 mg/kg; im). The in vitro antimicrobial activity of MMI and AMI showed variable results. While, AMI significantly inhibited growth of Streptococcus aureus and Proteus vulgaris, both MMI and AMI did not show any significant effect on growth of E. coli and Klebsiella. The results illustrate that the extracts of M. indica have significant anti-diarrhoeal activity and part of the activity of MMI may be attributed to its effect on intestinal transit.

Animals↗

PubMed2003

Longterm survival after extended resections in patients with gallbladder cancer.

BACKGROUND: Surgery is the treatment of choice for gallbladder cancer, but the extent of resection and its benefits remain unclear. STUDY DESIGN: Survival analysis of 42 patients who underwent extended resections for gallbladder cancer was performed. Resections were labeled R0 (curative) or R1 (noncurative) based on histopathologic evaluation. Survival curves were constructed using the Kaplan-Meier method, and survival data were analyzed by univariate and multivariate analyses to identify factors associated with longterm (>2 years) survival. RESULTS: R0 status was achieved in 18 patients (43%): 100%, 100%, 45%, and 0% in stages I, II, III, and IV, respectively. Patients with R0 resections had a significantly better survival than those with R1 resections (median 25.8 months versus 17.0 months; p = 0.03). R0 status was achieved in only 3 of 20 patients (15%) with node positive (N1) disease compared with 14 of 17 patients (82%) with node negative (N0) disease. Patients with N0 disease had a significantly better survival than those with N1 disease (median not reached versus 17 months; p = 0.01). None of the patients with N1 disease survived 5 years; 5-year survival for N0 patients was 58%. Adjuvant therapy did not have a significant effect on survival. CONCLUSIONS: In patients with gallbladder cancer, R0 status could be achieved in only 43% of patients undergoing extended resections. R0 status and N0 disease were associated with better longterm survival.

Adult↗

PubMed2003

Monocyte-derived IL12, CD86 (B7-2) and CD40L expression in relapsing and progressive multiple sclerosis.

Multiple sclerosis has been postulated to be an autoimmune disease in which Th1 immune responses predominate. This response is associated with an increased production of IFNgamma and IL12 produced by T cells and by cells of the monocyte (MO) lineage, respectively. An increased expression of costimulatory molecules by T cells and antigen-presenting cells is also observed. We hypothesized that in relapsing-remitting MS (RRMS) (with or without of IFNbeta treatment) and in secondary progressive patients (SPMS) IL12 and costimulatory molecules (CD80 [B7-1], CD86 [B7-2], CD28, CD40, CD40L) would be differentially produced or expressed by MO or T cells. We performed cross-sectional and longitudinal flow cytometric studies (at monthly intervals) on peripheral blood mononuclear cells (PBMC) or on MO from SPMS or untreated and IFNbeta-treated patients with RRMS. We determined that CD86 and CD40L expression was highest on MO derived from SPMS patients compared to those from RRMS or from healthy controls (HC). In vitro culture of PBMC with recombinant human IL10, a cytokine that may be increased in response to treatment with IFNbeta and that down-regulates CD86 expression, reduced the expression of CD86 on MO derived from RRMS patients to a much higher degree compared to cells derived from SPMS or HC. In vitro secreted IL12 levels from freshly isolated MO from SPMS patients were more than 10-fold higher than either the treated or the untreated RRMS or HC. RRMS patients treated with IFNbeta demonstrated slightly lower levels of MO IL12 secretion. Our data suggest that a key mechanism in the pathogenesis of MS is the increased expression of CD86 and CD40L and the increased production of IL12 during disease progression. Part of the mechanism of action of IFNbeta may be to reduce MO CD86 and CD40L expression and IL12 secretion; failure to do so might signify either a lack of response or a transition to a more progressive phase of illness.

Adjuvants, Immunologic↗