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N Qureshi

Publications and source records attributed to N Qureshi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Inhibition of lipopolysaccharide-induced transcription factor Sp1 binding by spectrally pure diphosphoryl lipid A from Rhodobacter sphaeroides, protein kinase inhibitor H-8, and dexamethasone.

The transcription factor Sp1 plays a crucial role in the monocyte-specific expression of CD14, a binding site (or putative receptor) for lipopolysaccharide (LPS) complexes with LPS-binding protein (LBP). By using RAW 264.7 macrophages treated with spectrally pure deep-rough-chemotype hexa-acyl LPS from Escherichia coli D31m4, three inhibitors were found to block the binding activity of transcription factor Sp1, as measured by electrophoretic mobility shift assays. These inhibitors were diphosphoryl lipid A from Rhodobacter sphaeroides (10 microg/ml); the isoquinoline-sulfonamide H-8 (10 and 100 microM), which is thought to be a cGMP-dependent protein kinase inhibitor; and the anti-inflammatory agent dexamethasone (10 microM).

Animals↗
PubMed1997

Diphosphoryl lipid A from Rhodobacter sphaeroides inhibits complexes that form in vitro between lipopolysaccharide (LPS)-binding protein, soluble CD14, and spectrally pure LPS.

An early event in septic shock is the activation of macrophages by a complex consisting of lipopolysaccharide (LPS), LPS-binding protein (LBP), and the cell surface antigen CD14. The complexes that form between [3H]ReLPS (ReLPS is deep-rough-chemotype hexacyl LPS from E. coli D31m4), soluble CD14 (sCD14), and LBP were analyzed by two independent methods, native (nondenaturing) gel electrophoresis and size-exclusion high-performance liquid chromatography (HPLC). This is the first reported use of HPLC to purify and study LPS-protein complexes. The binding of [3H]ReLPS to LBP and sCD14 was inhibited by preincubation with diphosphoryl lipid A from Rhodobacter sphaeroides (RsDPLA), a potent LPS antagonist. In addition, [3H]ReLPS bound to LBP and to a truncated form of sCD14 [sCD14(1-152)] that contained the LPS binding domain. Binding to both proteins was blocked by RsDPLA. Thus, RsDPLA competes in a 1:1 ratio for the same or nearby binding sites on ReLPS complexes. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of aggregated ReLPS eluting from the HPLC indicated that only LBP, not sCD14, was bound to the aggregated ReLPS. This finding supports the binary model of LPS complex formation with LBP and sCD14.

Acute-Phase Proteins↗
PubMed1997

The Falconª Eccentric Coronary Balloon Angioplasty Catheter: A Randomized Safety and Efficacy Study.

Percutaneous coronary angioplasty (PTCA) is usually performed using concentric shaped balloon catheters with the guidewire passing through the center of the shaft. The Falconª balloon catheter features a guide wire lumen on the outside of the balloon so that an eccentric balloon catheter profile is obtained concentrating the dilating force on the wire supported side, allowing lower inflation pressures and potentially causing less vessel injury. The aim of this study was to evaluate the safety and efficacy of this new balloon catheter in patients with stable and unstable angina. In 95 prospectively randomized patients, 57 lesions were dilated with a concentric balloon and 51 with the eccentric balloon. Technical success in the two groups was similar (73.3% vs. 74.5% control vs. Falcon respectively). Procedural success was 96.5% vs. 96.1% in the control and Falcon groups respectively. The mean increase in minimum luminal diameter (MLD) was 1.01 +/- 0.41 mm in the control vs 0.85 +/- 0.45 mm in Falcon (p = 0.053). There was an increase in type A dissections in the Falcon group 18 (36.75%) vs. 10 (19.23%) in the control group (p = 0.07) with no difference in stent implantation, myocardial infarction, CABG or death between the two groups. All patients with a technically successful PTCA were followed up. Seventeen (43.6%) in the control and 11 (32.4%) in the Falcon had repeat coronary angiography (p = 0.38), 12 (30.8%) vs. 7 (20.6%) had repeat PTCA (p = 0.37) and time to PTCA was 116 +/- 70 days vs. 154 +/- 103 days respectively (p = 0.36). The Falcon performed technically as well as the concentric balloons. Despite a smaller MLD and increase in Type A dissections there was no associated increase in complications or reintervention for restenosis. Further investigation is required to evaluate the role of this mechanism of dilatation in restenosis.

Journal Article↗
PubMed1996

Paclitaxel (Taxol)-induced NF-kappaB translocation in murine macrophages.

Interaction of bacterial lipopolysaccharide (LPS) with macrophages results in the induction of a cascade of cytokines that mediate the varied effects of LPS. An early intracellular signaling event that follows receptor engagement is the activation of transcription factor NF-kappaB. Nf-kappaB has been shown to be important for the induction of many LPS-inducible cytokine genes, including tumor necrosis factor alpha, interleukin-1beta, and interleukin-6. Previously, we and others have shown that the antitumor agent paclitaxel (Taxol) is able to mimic bacterial LPS in its ability to activate murine macrophages. In this report, we have extended these findings by demonstrating that paclitaxel, like LPS, is able to stimulate the translocation of primarily p50-p65 heterodimers of NF-kappaB to the nucleus. This activation is dose dependent and requires a concentration of > or =5 microM paclitaxel. The kinetics of NF-kappaB activation by paclitaxel are slower than those of LPS: by 15 min poststimulation, LPS-induced NF-kappaB activation was readily detected, whereas the paclitaxel-induced NF-kappaB activation was minimal. Moreover, paclitaxel- and protein-free LPS-induced translocation of NF-kappaB was seen only in macrophages derived from LPS-responsive C3H/OuJ mice and not from the LPS-hyporesponsive C3H/HeJ mice, a finding that is consistent with those of previous genetic studies linking paclitaxel responsiveness to the Lps gene. Finally, the LPS structural antagonist Rhodobacter sphaeroides diphosphoryl lipid A inhibited both LPS-and paclitaxel-induced NF-kappaB activation, suggesting a common receptor component in this activation.

Animals↗
PubMed1996

Predicting outcome following surgical treatment of unruptured intracranial aneurysms: a proposed grading system.

Surgical treatment of unruptured aneurysms is gaining increased support owing to the recently defined poor long-term natural history of these aneurysms. The benefit of treatment ultimately depends on the relative risk of subsequent aneurysm rupture in untreated patients versus the risk of surgery. To identify those patients at a higher risk from surgery, the authors reviewed the management of 172 patients with unruptured intracranial aneurysms treated at their institution. The size of the aneurysms ranged from 3 to 45 mm (mean 13.7 mm). Twenty-two patients (12.8%) had aneurysms in the posterior circulation, and 32 (18.6%) of these were giant aneurysms. Major morbidity occurred in 12 patients (6.9%) and five patients (2.9%) died. Multivariate logistic analysis of several risk factors revealed that aneurysm size and location had an independent correlation with surgical outcome and that patient age approached statistical significance. Patients presenting with ischemic cerebrovascular disease, in particular, did not have a higher risk of a poor outcome. A simple classification for predicting patients at high risk from surgical morbidity and mortality is proposed. Preoperative grading is based on the size and location of the aneurysm and patient's age. The lowest grade is given to young patients with small anterior circulation aneurysms, and the highest grade includes elderly patients with complex giant posterior circulation aneurysms. A retrospective analysis of this classification demonstrated a strong correlation with postoperative outcome. The incidence of poor outcome progressively increased with a higher grade, ranging from 0% in Grade 0 to 66.6% in Grade VI. An analysis of this classification on 50 consecutive surgically treated patients with unruptured aneurysms not included in the analysis also validated the predictive value of this system. Along with predicting outcome, this classification should provide a standardized format for comparison of results from different clinical centers as well as different therapeutic techniques (surgical vs. endovascular) without omission of significant risk factors found to influence outcome.

Adult↗
PubMed1995

CD14 is not involved in Rhodobacter sphaeroides diphosphoryl lipid A inhibition of tumor necrosis factor alpha and nitric oxide induction by taxol in murine macrophages.

Taxol, a microtubule stabilizer with anticancer activity, mimics the actions of lipopolysaccharide (LPS) on murine macrophages in vitro. Recently, it was shown that taxol-induced macrophage activation was inhibited by the LPS antagonist Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA). To investigate the mechanisms of taxol-induced macrophage activation, the present study focused on the interaction of LPS, RsDPLA, and taxol in the activation of and binding to macrophages. Taxol alone induced murine C3H/He macrophages to secrete tumor necrosis factor alpha (TNF) and to produce nitric oxide (NO) with kinetics similar to that of LPS. Macrophages from LPS-hyporesponsive C3H/HeJ mice, in contrast, did not yield any detectable TNF and NO production in response to LPS or taxol. RsDPLA inhibited taxol-induced TNF and NO production from C3H/He macrophages in a dose-dependent manner. The inhibition by RsDPLA was specific for LPS and taxol in that RsDPLA did not inhibit heat-killed Listeria monocytogenes- or zymosan-induced TNF production. Polymyxin B blocked the inhibitory effect of RsDPLA on taxol-induced TNF production. The inhibitory activity of RsDPLA appeared to be reversible since macrophages still responded to taxol in inducing TNF production after the RsDPLA was washed out with phosphate-buffered saline prior to the addition of taxol. Taxol-induced TNF production was not inhibited by colchicine, vinblastine, or 10-deacetylbaccatine III. A mutant cell line, J7.DEF3, defective in expression of a CD14 antigen, responded equally well to taxol by producing TNF as did the parent J774.1 cells. This suggested that the activation of macrophages by taxol does not require CD14. Taxol-induced TNF production by the mutant cells was also inhibited by RsDPLA. 125I-labeled LPS and 3H-labeled taxol was reported to bind to J774.1 cells predominantly via CD14 and microtubules, respectively. The binding of 125I-labeled LPS to J7.DEF3 cells was about 30 to 40% of that to J774.1 cells. The binding of 125I-LPS to J774.1 cells was inhibited by unlabeled LPS and RsDPLA but not by taxol. On the other hand, 3H-labeled taxol bound to both J774.1 cells and J7.DEF3 cells in similar time- and dose-dependent manners. The binding of [3H]taxol to these cells was inhibited by taxol but not by LPS or RsDPLA. Although the binding studies failed to examine cross competition for binding to macrophages, a possible explanation of these results is that LPS, RsDPLA, and taxol share the same molecule(s) on murine macrophages for their functional receptor(s), which is neither CD14 nor tubulin.

Animals↗
PubMed1995

Diphosphoryl lipid A from Rhodobacter sphaeroides transiently activates NF-kappa B but inhibits lipopolysaccharide induction of kappa light chain and Oct-2 in the B-cell lymphoma line 70Z/3.

Lipopolysaccharide (LPS) is implicated in much of the pathophysiology associated with gram-negative septic shock. One approach to this serious clinical problem is to develop new drugs that antagonize the action of toxic LPS. A model system to study LPS action and test for potential antagonists is readily provided by LPS regulation of the kappa gene in the murine B-cell line 70Z/3. Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) effectively blocked toxic LPS induction of kappa light-chain immunoglobulin expression in 70Z/3 cells. Induction of kappa expression by LPS is dependent on the activation of at least two transcription factors, Oct-2 and NF-kappa B. RsDPLA completely repressed the long-term activation of NF-kappa B observed after 24 h of Salmonella typhosa LPS treatment and antagonized activation of oct-2 mRNA expression. However, RsDPLA was not an inert competitor of LPS. RsDPLA alone strongly activated NF-kappa B binding activity by 30 min but not beyond 9 h of treatment. It also induced a small increase in oct-2 mRNA levels. RsDPLA is not simply a weak agonist; we found no graded increase in kappa expression with increasing RsDPLA concentrations up to 50 micrograms/ml. The NF-kappa B complexes activated by RsDPLA and S. typhosa LPS were both composed of the p50-p65 heterodimer. These results suggest that the physiological LPS receptor(s) on B cells transmits qualitatively different signals depending on the nature of the binding ligand and that the fatty acyl groups of LPS play an important role in activating signal transduction.

Animals↗
PubMed1995

The inflammatory cytokine response to Chlamydia trachomatis infection is endotoxin mediated.

Chlamydia trachomatis is a major etiologic agent of sexually transmitted diseases. Although C. trachomatis is a gram-negative pathogen, chlamydial infections are not generally thought of as endotoxin-mediated diseases. A molecular characterization of the acute immune response to chlamydia, especially with regard to the role of its lipopolysaccharide (LPS), remains to be undertaken. We extracted 15 mg of LPS from 5 x 10(12) C. trachomatis elementary bodies (EB) for analysis of structure and biological activity. When methylated lipid A was subjected to high-pressure liquid chromatography followed by mass spectrometry, the majority of the lipid A was found to be pentaacyl. The endotoxin activities of whole C. trachomatis EB and purified LPS were characterized in comparison with whole Salmonella minnesota R595 and with S. minnesota R595 LPS and lipooligosaccharide from Neisseria gonorrhoeae. Both C. trachomatis LPS and whole EB induced the release of tumor necrosis factor alpha from whole blood ex vivo, and C. trachomatis LPS was capable of inducing the translocation of nuclear factor kappa B in a Chinese hamster ovary fibroblast cell line transfected with the LPS receptor CD14. In both assays, however, C. trachomatis was approximately 100-fold less potent than S. minnesota and N. gonorrhoeae. The observation that C. trachomatis is a weak inducer of the inflammatory cytokine response correlates with the clinical observation that, unlike N. gonorrhoeae infection, genital tract infection with C. trachomatis is often asymptomatic. The ability of specific LPS antagonists to completely inhibit the tumor necrosis factor alpha-inducing activity of whole C. trachomatis EB suggests that the inflammatory cytokine response to chlamydia infection may be mediated primarily through LPS. This implies that the role of other surface protein antigens, at least in terms of eliciting the proinflammatory cytokine response, is likely to be minor.

Antigens, CD↗
PubMed1994

Endotoxin-induced early gene expression in C3H/HeJ (Lpsd) macrophages.

C3H/HeJ (Lpsd) macrophages have been shown to respond to certain LPSs, especially from rough mutant bacteria. C3H/OuJ (Lpsn) macrophages are induced by wild-type LPS, rough LPS, or lipid A to express many genes, including TNF-alpha, TNFR-2, IL-1 beta, IP-10, D3, and D8. C3H/HeJ macrophages failed to induce any of these genes when cultured with wild-type LPS or synthetic lipid A, even when pretreated with IFN-gamma. However, rough mutant Salmonella minnesota Ra, Rc, and Rd LPS, and Escherichia coli D31 m3 Rd LPS induced Lpsd macrophages to express a subset of genes within the gene panel. Because bioactive preparations contained trace quantities of endotoxin protein(s), a deoxycholate-modified, phenol-water method was used to repurify rough LPS into an aqueous phase, and extract endotoxin proteins into a phenol phase. Repurified LPS failed to stimulate Lpsd macrophages; however, phenol fractions were approximately 10% as potent in Lpsd macrophages as crude rough LPS. Full potency was restored in C3H/HeJ macrophages when aqueous phase LPS and phenol-phase proteins were co-precipitated, suggesting that LPS and endotoxin proteins interact synergistically. Endotoxin proteins alone induced TNF-alpha, TNFR-2, and IL-1 beta, but not IP-10, D3, and D8 genes in both Lpsd and Lpsn macrophages. Tyrosine phosphorylation of three 41- to 47-kDa proteins was induced by endotoxin proteins, but not by LPS, in Lpsd macrophages. Thus, endotoxin proteins seem to activate a signaling pathway(s) that converges (distal to the Lps gene product) with a subset of LPS-signaling pathways.

Animals↗
PubMed1994

Craniocerebral epidermoid and dermoid tumours: a review of 32 cases.

We reviewed 22 epidermoid and 10 dermoid tumours of the skull and brain from patients operated on consecutively at Henry Ford Hospital between 1975 and 1991. There were 19 intradural (16 epidermoid, 3 dermoid) and 13 extradural (6 epidermoid, 7 dermoid) lesions. The average age at presentation was 35 years for patients with epidermoids and 15 years for those with dermoids. Common clinical presentations for patients with intradural lesions included headache, visual deficits, and seizures, whereas patients with extradural lesions harbored asymptomatic scalp masses. All patients with intradural lesions were investigated with computed tomography (CT) and cerebral angiography, and 8 patients underwent magnetic resonance imaging (MRI). Total resection was possible in 12 (92%) of 13 extradural tumours, all with excellent outcomes. Eight (42%) of the intradural tumours were completely resected. Overall, with the intradural tumours we had good to excellent results in 17 patients (90%), poor results in 1 (5%), and 1 death (5%). Re-operation was needed in 5 intradural recurrences (26%) with deterioration in only one patient's neurologic status postoperatively. From a review of ours and others' data, we conclude that 1) these tumours have an insidious onset despite significant size and mass effect as demonstrated by imaging studies; 2) CT, angiography, and particularly MRI help to define the extent of subarachnoid tumour spread and involvement of neurovascular structures, thus permitting better surgical planning; 3) a significant number of intradural tumours are difficult to excise because of their adherence to neurovascular structures, and thus are related to higher morbidity and mortality; and 4) because of extremely slow growth, complete tumour resection should not be the goal at the risk of injury to neurovascular structures.

Adolescent↗
PubMed1994

Diphosphoryl lipid A derived from the lipopolysaccharide (LPS) of Rhodobacter sphaeroides ATCC 17023 is a potent competitive LPS inhibitor in murine macrophage-like J774.1 cells.

Pentaacyl diphosphoryl lipid A derived from the nontoxic lipopolysaccharide (LPS) of Rhodobacter sphaeroides ATCC 17023 (RsDPLA) did not induce tumour necrosis factor-alpha nor interleukin-6 release in the murine macrophage-like cell line J774.1. However, it effectively inhibited the induction of these two cytokines by LPS of Salmonella minnesota Re mutant R595 (ReLPS) in a concentration-dependent manner. Maximal inhibition and half-maximal inhibition occurred when the ReLPS to RsDPLA mass ratio was 1:30 and 1:1, respectively. A binding study was performed in the presence of serum to determine whether RsDPLA is competing with ReLPS for LPS binding sites on J774.1 cells. This assay allows the determination of LPS binding to J774.1 cells via a mechanism involving CD14, a receptor for complexes of LPS with LPS binding protein (LBP), and its possible inhibition. The results show that RsDPLA strongly inhibits the binding of 125I-labelled ReLPS to J774.1 cells. Maximal and one-half maximal inhibition of binding occurred when the ReLPS to RsDPLA mass ratios were 1:2.5 and 1:0.5, respectively. It was found that the inhibition of binding by RsDPLA was much stronger than that by unlabelled ReLPS. These results suggest that RsDPLA is competing with ReLPS for CD14-dependent recognition of LPS on J774.1 cells.

Animals↗
PubMed1993

Lipopolysaccharide antagonists block taxol-induced signaling in murine macrophages.

Taxol is the prototype of a new class of microtubule stabilizing agents with promising anticancer activity. Several studies show that taxol mimics the actions of lipopolysaccharide (LPS) on murine macrophages. To investigate the mechanism of taxol-induced macrophage stimulation, we evaluated the ability of Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) and SDZ 880.431 to block taxol-induced effects. RsDPLA and SDZ 880.431 are lipid A analogues that lack LPS-like activity, but inhibit the actions of LPS, presumably by blocking critical cellular binding sites. We report that RsDPLA and SDZ 880.431 potently inhibited taxol-induced TNF secretion, gene activation, and protein-tyrosine phosphorylation. The role of microtubules in taxol signaling was investigated. Taxol-induced microtubule bundling in primary and transformed RAW 264.7 macrophages was not blocked by RsDPLA or SDZ 880.431. Taxotere, a semisynthetic taxoid, was more potent than taxol as an inducer of microtubule bundling, but did not induce tumor necrosis factor alpha secretion and gene activation. These data dissociate the microtubule effects of taxol from macrophage stimulation and suggest that taxol stimulates macrophages through an LPS receptor-dependent mechanism. The results underscore the potential of taxol as a tool for studying LPS receptor activation and provide insights into possible therapeutic actions of this new class of drugs.

Animals↗
PubMed1993

Lipopolysaccharide (LPS) binding to 73-kDa and 38-kDa surface proteins on lymphoreticular cells: preferential inhibition of LPS binding to the former by Rhodopseudomonas sphaeroides lipid A.

Using a photoactivable, radioiodinated lipopolysaccharide probe, [125I]ASD-LPS (derivatized from purified E. coli 0111:B4 S-LPS), we earlier reported the presence of a 73-kDa (p73) predominant LPS-binding protein on mouse lymphocytes and macrophages with specificity for the lipid A region of LPS. Both Re-LPS from Salmonella minnesota and purified lipid A will inhibit the binding of LPS to the p73 LPS receptor. In the studies reported here, we have found that non-toxic diphosphoryl lipid A purified from Rhodo-pseudomonas sphaeroides has the capability to inhibit the binding of [125I]ASD-LPS to the p73 protein. However, using the same LPS probe and photoaffinity cross-linking techniques, our data suggest that a less dominant 38-kDa (p38) LPS-specific binding protein identified on mouse splenocytes, J774.1 macrophage-like cell line, and 70Z/3 pre B-cell line by SDS-PAGE is not inhibited by purified lipid A, even at a concentration in 50-fold excess of that of [125]ASD-LPS. The binding of the LPS probe to the 38 protein could be inhibited in a dose-dependent manner by underivatized native S. minnesota Re-LPS (composed only of Kdo and lipid A). We speculate that this p38 LPS-binding protein may manifest a specificity for inner core oligosaccharide determinants on LPS.

Acute-Phase Proteins↗