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M Arditi

Publications and source records attributed to M Arditi.

At least 19 recordsLinked to original sources
PubMed1999

Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes.

Bacterial lipopolysaccharide (LPS)-mediated immune responses, including activation of monocytes, macrophages, and endothelial cells, play an important role in the pathogenesis of Gram-negative bacteria-induced sepsis syndrome. Activation of NF-kappaB is thought to be required for cytokine release from LPS-responsive cells, a critical step for endotoxic effects. Here we investigated the role and involvement of interleukin-1 (IL-1) and tumor necrosis factor (TNF-alpha) signal transducer molecules in LPS signaling in human dermal microvessel endothelial cells (HDMEC) and THP-1 monocytic cells. LPS stimulation of HDMEC and THP-1 cells initiated an IL-1 receptor-like NF-kappaB signaling cascade. In transient cotransfection experiments, dominant negative mutants of the IL-1 signaling pathway, including MyD88, IRAK, IRAK2, and TRAF6 inhibited both IL-1- and LPS-induced NF-kappaB-luciferase activity. LPS-induced NF-kappaB activation was not inhibited by a dominant negative mutant of TRAF2 that is involved in TNF signaling. LPS-induced activation of NF-kappaB-responsive reporter gene was not inhibited by IL-1 receptor antagonist. TLR2 and TLR4 were expressed on the cell surface of HDMEC and THP-1 cells. These findings suggest that a signal transduction molecule in the LPS receptor complex may belong to the IL-1 receptor/toll-like receptor (TLR) super family, and the LPS signaling cascade uses an analogous molecular framework for signaling as IL-1 in mononuclear phagocytes and endothelial cells.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Endotoxin-induced migration of monocytes and PECAM-1 phosphorylation are abrogated by PAF receptor antagonists.

The trafficking of monocytes across the endothelial lining of the blood vessel increases in response to bacterial infection at sites of inflammation. However, the molecular events involved in the diapedesis of monocytes in response to endotoxin are not completely understood. Our studies revealed that signaling by lipopolysaccharide (LPS) in human umbilical vein endothelial cells (HUVEC) resulted in a threefold increase in the transendothelial migration of monocyte-like HL-60 cells and a sevenfold increase in the phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1). The transmigration induced by LPS was inhibited by an antibody to PECAM-1. Both the phosphorylation of PECAM-1 and transendothelial migration of monocytes were inhibited by a platelet-activating factor (PAF) receptor antagonist, indicating the autocrine effect of PAF in these events. Treatment of HUVEC with LPS caused a fourfold increase in PAF receptor mRNA expression that was completely blocked by the PAF receptor antagonist. We conclude that PAF, generated by HUVEC in response to LPS or gram-negative bacterial infection, acts in an autocrine manner, causing PECAM-1 phosphorylation and thus the transendothelial migration of monocytes.

Azepines↗
PubMed1998

Three-year multicenter surveillance of systemic pneumococcal infections in children.

OBJECTIVE: To track antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from children with systemic infections and determine outcome of treatment. DESIGN: A 3-year (September 1993 through August 1996) prospective surveillance study of all invasive pneumococcal infections in children. PATIENTS: Infants and children cared for at eight children's hospitals in the United States with culture-proven systemic pneumococcal infection. RESULTS: One thousand two hundred ninety-one episodes of systemic pneumococcal infection were identified in 1255 children. An underlying illness was present in the children for 27% of the episodes. The proportion of isolates that were nonsusceptible to penicillin or ceftriaxone increased annually and nearly doubled throughout the 3-year period; for the last year the percentages of isolates nonsusceptible to penicillin and ceftriaxone were 21% and 9.3%, respectively. There was no difference in mortality between patients with penicillin-susceptible or nonsusceptible isolates. Only 1 of 742 patients with bacteremia had a repeat blood culture that was positive > 1 day after therapy was started. All 24 normal children with bacteremia attributable to isolates resistant to penicillin had resolution of their infection; the most common treatment regimen was a single dose of ceftriaxone followed by an oral antibiotic. CONCLUSIONS: The percentage of pneumococcal isolates nonsusceptible to penicillin and ceftriaxone increased yearly among strains recovered from children with systemic infection. Because empiric antibiotic therapy already has changed for suspected pneumococcal infections, antibiotic resistance has not been associated with increased mortality. Careful monitoring of antibiotic susceptibility and outcome of therapy is necessary to continually reassess current recommendations for treatment.

Adolescent↗
PubMed1998

Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use.

OBJECTIVES: To evaluate the antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from the blood and cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment, and outcome of children with meningitis caused by S pneumoniae based on antimicrobial susceptibility of isolates and the administration of dexamethasone. DESIGN AND PATIENTS: Children with pneumococcal meningitis were identified from among a group of patients with systemic infections caused by S pneumoniae who were enrolled prospectively in the United States Pediatric Multicenter Pneumococcal Surveillance Study at eight children's hospitals in the United States. From September 1, 1993 to August 31, 1996, 180 children with 181 episodes of pneumococcal meningitis were identified and data were collected by retrospective chart review. OUTCOME: Clinical and laboratory characteristics were assessed. All pneumococcal isolates were serotyped and antibiotic susceptibilities for penicillin and ceftriaxone were determined. Clinical presentation, hospital course, and outcome parameters at discharge were compared between children infected with penicillin-susceptible isolates and those with nonsusceptible isolates and for children who did and did not receive dexamethasone. RESULTS: Fourteen (7.7%) of 180 children died; none of the fatalities were because of a documented failure of treatment caused by a resistant strain. Only 1 child, who had mastoiditis and a lymphangioma, experienced a bacteriologic failure with a penicillin-resistant (minimum inhibitory concentration = 2 microgram/mL) organism. Of the 166 surviving children, 41 (25%) developed neurologic sequelae (motor deficits) and 48 (32%) of 151 children had unilateral (n = 26) or bilateral (n = 22) moderate to severe hearing loss at discharge. Overall, 12.7% and 6.6% of the pneumococcal isolates were intermediate and resistant to penicillin and 4.4% and 2.8% were intermediate and resistant to ceftriaxone, respectively. Clinical presentation, cerebrospinal fluid indices on admission, and hospital course, morbidity, and mortality rates were similar for patients infected with penicillin- or ceftriaxone-susceptible versus nonsusceptible organisms. However, the relatively small numbers of nonsusceptible isolates and the inclusion of vancomycin in the treatment regimen for the majority of the patients limit the power of this study to detect significant differences in outcome between patients infected with susceptible and nonsusceptible isolates. Nonetheless, our results show that the nonsusceptible organisms do not seem to be intrinsically more virulent. Forty children (22%) received dexamethasone (>/=8 doses) initiated before or within 1 hour after the first dose of antibiotics. The incidence of any moderate or severe hearing loss was significantly higher in the dexamethasone group (46%) compared with children not receiving any dexamethasone (23%). The incidence of any neurologic deficits, including hearing loss, also was significantly higher in the dexamethasone group (55% vs 33%). However, children in the dexamethasone group more frequently required intubation and mechanical ventilation and had lower initial concentration of glucose in the cerebrospinal fluid than children who did not receive any dexamethasone. When we controlled for the confounding factor, severity of illness (intubation), the incidence of any deafness and of any neurologic sequelae, including deafness, were no longer significantly different between children who did or did not receive dexamethasone. CONCLUSIONS: Children with pneumococcal meningitis caused by penicillin- or ceftriaxone-nonsusceptible organisms and those infected by susceptible strains had similar clinical presentation and outcome. The use of dexamethasone was not associated with a beneficial effect in this retrospective and nonrandomized study. (ABSTRACT TRUNCATED)

Adolescent↗
PubMed1998

Clinical characteristics and outcome of children with pneumonia attributable to penicillin-susceptible and penicillin-nonsusceptible Streptococcus pneumoniae.

OBJECTIVE: To compare the clinical characteristics, treatment, and outcome of pediatric patients with pneumonia attributable to isolates of Streptococcus pneumoniae that were either susceptible or nonsusceptible to penicillin. DESIGN: Multicenter, retrospective study. SETTING: Eight children's hospitals in the United States. PARTICIPANTS: Two hundred fifty-four children with pneumococcal pneumonia identified from patients enrolled in the United States Pediatric Multicenter Pneumococcal Surveillance Study during the 3-year period from September 1, 1993 to August 31, 1996. OUTCOME MEASURES: Demographic and clinical variables including necessity for and duration of hospitalization, frequency of chest tube placement, antimicrobial therapy, susceptibility of isolates, and clinical outcome. RESULTS: There were 257 episodes of pneumococcal pneumonia that occurred in 254 patients. Of the 257 isolates, 22 (9%) were intermediate and 14 (6%) were resistant to penicillin; 7 (3%) were intermediate to ceftriaxone and 5 (2%) were resistant to ceftriaxone. There were no differences noted in the clinical presentation of the patients with susceptible versus nonsusceptible isolates. Twenty-nine percent of the patients had a pleural effusion. The 189 (74%) hospitalized patients were more likely to have an underlying illness, multiple lung lobe involvement, and the presence of a pleural effusion than nonhospitalized patients. Fifty-two of 72 hospitalized patients with pleural effusions had a chest tube placed, and 27 subsequently underwent a decortication drainage procedure. Eighty percent of the patients treated as outpatients and 48% of the inpatients received a parenteral second or third generation cephalosporin followed by a course of an oral antimicrobial agent. Two hundred forty-eight of the patients (97.6%) had a good response to therapy. Six patients died; however, only 1 of the deaths was related to the pneumococcal infection. CONCLUSION: The clinical presentation and outcome of therapy did not differ significantly between patients with penicillin-susceptible versus those with nonsusceptible isolates of S pneumoniae. Hospitalized patients were more likely to have underlying illnesses, multiple lobe involvement, and the presence of pleural effusions than patients who did not require hospitalization. In otherwise normal patients with pneumonia attributable to penicillin-resistant pneumococcal isolates, therapy with standard beta-lactam agents is effective.

Adolescent↗
PubMed1998

Pediatric pneumococcal bone and joint infections. The Pediatric Multicenter Pneumococcal Surveillance Study Group (PMPSSG).

OBJECTIVE: To describe the clinical and microbiological characteristics of infants and children with bone and joint infections caused by penicillin-susceptible and penicillin-nonsusceptible strains of Streptococcus pneumoniae. DESIGN: Multicenter, prospective patient accrual; retrospective chart review of identified patients. SETTING: Eight children's hospitals in the United States. PARTICIPANTS: Forty-two children with bone and/or joint infections prospectively enrolled in the United States Pediatric Multicenter Pneumococcal Surveillance Study from September 1, 1993 to August 31, 1996. OUTCOME MEASURES: Data were collected on multiple variables, including age, gender, race, days of symptoms before and during hospitalization, antibiotic and surgical therapy, laboratory and imaging studies. RESULTS: Of the 42 children enrolled (21 bone, 21 joint infections), 14 had isolates that were not susceptible to penicillin. Eight of 16 (50%) strains isolated from children who received antibiotics within 4 weeks before hospitalization were not susceptible to penicillin, compared with 4 of 15 (27%) strains isolated from children without previous antibiotic exposure. Clinical response to therapy was similar between children infected by penicillin-susceptible strains compared with those infected by penicillin-nonsusceptible strains, including duration of hospitalization (9.1 days vs 11.2 days), days of intravenous antibiotic therapy (25.3 days vs 24.6 days), days of fever (3.6 days vs 3.1 days), and sequelae (14% vs 7%). The most commonly prescribed single agents for parenteral therapy in definitive treatment were ceftriaxone (36%), penicillin (15%), and clindamycin (15%). Oral therapy followed parenteral therapy in 56% of children. The mean (+/- standard deviation) duration of total antibiotic therapy in children with osteomyelitis was 57.5 +/- 48.6 days (range, 23-196 days) and 29.2 +/- 11.8 days (range, 12-67 days) for arthritis. Late sequelae (long-term destructive changes of the bone or joint) were documented in 5 (12%) children, 4 with osteomyelitis, and 1 with arthritis. Sequelae occurred in 30% of children with long bone osteomyelitis associated with infection in the adjacent joint. The age of children with sequelae was younger than those without sequelae (6.4 months vs 18.6 months). CONCLUSIONS: The demographic characteristics and anatomic sites of infection in our patients were similar to previously published series collected from single institutions before the emergence of significant antibiotic resistance in S pneumoniae. Our analysis suggests that children infected by penicillin-nonsusceptible strains have a similar clinical response to therapy when compared with children infected by penicillin-susceptible strains.

Anti-Bacterial Agents↗
PubMed1997

Preliminary study in differential contrast echography.

Microbubble-based contrast agents have backscattering properties that differ greatly from those of soft tissues. These agents exhibit nonlinear scattering properties in response to incident acoustic energy, causing harmonic components in reflected energy. Even in linear scattering conditions, an important difference is observed in the frequency dependence of their backscatter coefficient, when compared to that of tissues. In this situation, any such differential behaviour can be exploited by imaging instrumentation to enhance the detection of agent-containing vessels against background tissue. The resulting B-mode image brightness (or pixel level) can thus be the representation of a local parameter computed from radio frequency (rf) signal processing of the raw echoes. The object of this article is to report on parametric imaging studies performed with Sonovue (formerly code named BR1, Bracco Research SA), aimed at assessing the contrast-enhancing potential of spectral rf signal processing. The technique used, termed here "differential contrast echography" (DCE), is applicable in real-time B-mode imaging. It is based on an on-line subtractive approach, using dual-channel signal processing to implement differential filtering and demodulation. In this preliminary work, DCE was implemented off-line, on rf echo signals digitised from commercial B-mode scanners. Data acquisition, DCE processing and complete B-mode image reconstruction were programmed on a personal computer. The images presented were produced from test phantoms as well as animal phased array scanning. The phantom included a flow channel, background scattering material, fixed echogenic targets and echo-free regions. Animal scanning was performed on rabbit liver. The results obtained from DCE show promising contrast-enhancing properties. The regions containing no contrast agent are significantly suppressed from the image, preferentially leaving the regions perfused by the contrast agent. This property was favourable to experimenting with image-overlay presentations, superimposing colour-coded DCE imaging with standard log-compressed grey-scale B-mode, in a way analogous to duplex imaging combining colour Doppler and B-mode.

Algorithms↗
PubMed1997

Differential antibiotic-induced endotoxin release and interleukin-6 production by human umbilical vein endothelial cells (HUVECs): amplification of the response by coincubation of HUVECs and blood cells.

The activation of human vascular endothelial cells (ECs), as assessed by interleukin (IL)-6 production, was investigated in response to antibiotic-induced lipopolysaccharide release from Escherichia coli. Antibiotic-induced killing of E. coli resulted in the activation of human umbilical vein endothelial cells (HUVECs). Imipenem and meropenem induced faster killing of E. coli than ceftriaxone at 2 and 6 h. However, imipenem-induced bacterial killing resulted in significantly less IL-6 release compared with meropenem or ceftriaxone. When HUVECs were coincubated with diluted (4%) human blood, bacterial killing-induced total IL-6 release was significantly higher than that produced by HUVECs or by 4% blood cells alone. These observations suggest that antibiotic-induced lipopolysaccharide release activates both endothelial cells and monocytes and that the effect is significantly amplified when endothelial cells and monocytes are coincubated. Imipenem, which has a greater affinity for penicillin-binding protein (PBP) 2, induced less IL-6 release from blood and endothelial cells than did PBP 3-specific ceftriaxone and meropenem.

Anti-Bacterial Agents↗
PubMed1995

Lipopolysaccharide stimulates the tyrosine phosphorylation of mitogen-activated protein kinases p44, p42, and p41 in vascular endothelial cells in a soluble CD14-dependent manner. Role of protein tyrosine phosphorylation in lipopolysaccharide-induced stimulation of endothelial cells.

Vascular endothelial cell (EC) injury or activation by LPS plays a critical role in the pathogenesis of Gram-negative meningitis and endotoxic shock. EC do not express membrane CD14, but respond to LPS in a soluble CD14-dependent manner. The signal transduction mechanisms involved in LPS-induced EC responses are largely unknown. We used bovine and human brain microvessel EC (BBMEC, and HBMEC) to study LPS-induced protein tyrosine phosphorylation. LPS rapidly induced the tyrosine phosphorylation of several proteins in BBMEC and HBMEC, which was detectable by 5 to 15 min, reached a maximum by 30 min, and declined by 60 to 90 min. The increase in tyrosine phosphorylation was apparent following stimulation with LPS at 0.1 ng/ml and was dose dependent up to 100 ng/ml. Similar changes in tyrosine phosphorylation were induced by smooth and rough LPS as well as lipid A, but not by the inactive lipid A analogue, Rhodopseudomonas sphaeroides diphosphoryl lipid A. Pretreatment of EC with the tyrosine kinase inhibitor, herbimycin A, inhibited LPS-stimulated protein tyrosine phosphorylation and LPS-mediated lactic dehydrogenase release from BBMEC and IL-6 release from HBMEC in a dose-dependent manner. Three proteins with apparent m.w. of 44, 42, and 41 kDa were predominant among the LPS-induced tyrosine phosphoproteins, and they were identified as mitogen-activated protein kinase isoforms ERK1, ERK2, and p38, respectively. LPS-induced protein tyrosine phosphorylation in HBMEC and BBMEC was soluble CD14 dependent, since pretreatment of these cells with anti-hCD14 mAb inhibited the LPS-induced tyrosine phosphorylation of p44, p42, and p41. Additionally, LPS induced a mobility shift in p44 and p42 mitogen-activated protein kinase isozymes, which was inhibited by herbimycin A pretreatment of the EC. These findings demonstrate for the first time that increased protein tyrosine phosphorylation and activation of mitogen-activated protein kinases occur rapidly after LPS stimulation of EC in the presence of soluble CD14. Our data also suggest that a herbimycin-sensitive step, presumably a tyrosine kinase, is involved in mediating LPS-induced human EC activation and IL-6 secretion.

Amino Acid Sequence↗
PubMed1995

BR1: a new ultrasonographic contrast agent based on sulfur hexafluoride-filled microbubbles.

RATIONALE AND OBJECTIVES: The basic characteristics of BR1, a novel echo contrast agent based on stabilized sulfur hexafluoride (SF6) microbubbles have been evaluated. METHODS: The authors determined the physicochemical properties (bubble concentration, bubble size distribution, resistance to pressure, and stability) and the acoustic properties (backscatter and attenuation coefficients) of BR1. The diagnostic value of BR1 was evaluated further in minipigs. Left heart images were recorded before and after injection of different doses of BR1. RESULTS: BR1 is formulated as a lyophilized product, which after addition of saline, provides a suspension containing 2 x 10(8) SF6 microbubbles/mL with a number mean diameter of 2.5 microns. More than 90% of the bubbles are below 8 microns. The use of SF6 rather than air provides an improved resistance to pressure increases such as the ones occuring in the left heart during systole. After reconstitution, the echogenicity and the bubble characteristics are unchanged for more than 8 hours. The high echogenicity remains almost constant over the entire medical frequency range (1-10 MHz). BR1 injections in animals resulted in a homogenous, dose-dependent opacification of the left heart. CONCLUSIONS: Considering its high echogenicity, outstanding stability, and resistance to pressure changes, BR1 is a very promising ultrasound contrast agent.

Animals↗
PubMed1995

Dexamethasone therapy for children with bacterial meningitis. Meningitis Study Group.

OBJECTIVE: To determine whether treatment with dexamethasone and ceftriaxone for children with bacterial meningitis reduces the frequency of either sensorineural hearing loss or other neurologic sequelae. DESIGN: This was a prospective, multicentered, placebo-controlled clinical trial. Subjects were followed for 1 year. SETTING: The study was conducted in six children's hospitals located in Pittsburgh, Houston, Los Angeles, Chicago, Washington, D.C., and Columbus, Ohio. PATIENTS: Enrolled were 173 children, 8 weeks to 12 years of age, with suspected bacterial meningitis; 143 children were evaluable. Eighty-seven percent of patients were followed for at least 6 weeks to 3 months, and 67% were followed for 1 year. INTERVENTIONS: Subjects were randomized to receive ceftriaxone with or without dexamethasone (0.15 mg/kg every 6 hours for 4 days). Auditory brainstem responses (ABR) were measured within 24 hours of admission. MAIN OUTCOME MEASURES: Hearing, development, and neurologic sequelae were assessed at the time of discharge and 6 weeks and 1 year later. MAIN RESULTS: One hundred forty-three patients (69 received dexamethasone and 74 received placebo) with bacterial meningitis were evaluable: Haemophilus influenzae type b (83), Streptococcus pneumoniae (33), Neisseria meningitidis (24), and three others. Overall, there was no significant difference in auditory outcome between dexamethasone and placebo recipients. Twenty-two children had bilateral moderate or more severe hearing loss at the time of the first ABR. At follow-up, the resolution of hearing impairment was nearly identical for each group. Nine of ten children who remained persistently deaf were deaf at the time of the first ABR. There were no differences in neurologic or developmental outcome between groups. CONCLUSION: All but one child with persistent bilateral moderate or more severe hearing loss had demonstrable deafness at the time of the first ABR. Dexamethasone did not significantly improve audiologic, neurologic, or developmental outcome in children with bacterial meningitis.

Ceftriaxone↗
PubMed1994

Bactericidal/permeability-increasing protein protects vascular endothelial cells from lipopolysaccharide-induced activation and injury.

Bactericidal/permeability-increasing protein (BPI), a human neutrophil granule protein, has been shown to bind lipopolysaccharide (LPS) and neutralize LPS-mediated cytokine production in adherent monocytes and the whole-blood system. In this study we investigated the ability of recombinant human BPI (rBPI) to inhibit LPS-induced vascular endothelial cell (EC) injury and activation. rBPI inhibited significantly both rough and smooth LPS-mediated injury for cultured bovine brain microvessel ECs, as measured by lactic dehydrogenase release, and blocked the LPS-induced interleukin-6 (IL-6) release from human umbilical vein ECs in a dose-dependent manner. BPI was able to inhibit LPS-mediated EC injury or activation whether it was added before or at the same time with LPS, but delaying the time of addition of rBPI resulted only in a partial inhibition. BPI also inhibited LPS-induced tumor necrosis factor alpha, IL-1 beta, and IL-6 release from human whole blood. This inhibition of tumor necrosis factor alpha, IL-1 beta, and IL-6 release from whole blood was maximal when BPI was premixed with LPS before addition to blood and was partial when BPI was added simultaneously with LPS, but no inhibition was observed when the addition of rBPI was delayed for 5 min. These findings suggest that rBPI is a potent inhibitor of LPS-mediated responses in ECs and whole blood and underscore the potential use of BPI in treatment or prevention of endotoxic shock. In contrast, the anti-lipid A monoclonal antibodies HA-1A and E5 were ineffective in inhibiting LPS-mediated EC injury and activation as well as LPS-induced cytokine release in whole blood.

Animals↗
PubMed1993

Antibiotic-induced bacterial killing stimulates tumor necrosis factor-alpha release in whole blood.

Rapid lysis of gram-negative bacteria is associated with considerable release of free endotoxin. Production of tumor necrosis factor (TNF) from adult whole blood ex vivo in response to bacterial products generated during antibiotic killing of Haemophilus influenzae type b (Hib) was investigated. Heparinized whole blood released TNF in a dose-dependent fashion in response to purified lipooligosaccharide of Hib. Bacteria (10(4)-10(7) cfu/mL) were placed into a Transwell filter insert (0.1 microns) and incubated with whole blood in the presence of various antibiotics. Exposure to ceftriaxone resulted in significantly greater release of TNF during killing of Hib than did exposure to imipenem, despite similar degrees of bacterial killing at 6 h. Polymyxin B inhibited the ceftriaxone-induced TNF release by 97%-99%, indicating that free endotoxin was the predominant stimulus for the increase in TNF release in this system. These observations suggest that ceftriaxone-induced killing of Hib results in bacterial cell wall products that are more proinflammatory than those produced by imipenem.

Adult↗
PubMed1993

Endotoxin-mediated endothelial cell injury and activation: role of soluble CD14.

Vascular endothelial cell (EC) injury by lipopolysaccharides (LPS) plays a major role in the pathogenesis of gram-negative bacterial sepsis and endotoxic shock. The studies described here were performed to define further the molecular mechanisms involved in the EC responses to LPS. We showed that serum was required for LPS-mediated cytotoxicity for bovine brain microvessel, pulmonary, and aortic ECs and that anti-human CD14 antibodies completely blocked LPS-mediated cytotoxicity for ECs in the presence of human serum. The addition of a recombinant soluble form of human CD14 to serum-free medium restored the LPS-mediated cytotoxicity, whereas the addition of LPS binding protein (LBP), a serum protein that potentiates LPS-induced responses to monocytes, had no effect. A similar dependency on serum or recombinant soluble CD14 (under serum-free conditions) was observed for LPS-induced secretion of interleukin-6 by human umbilical vein ECs. These findings indicate that soluble CD14 is required for LPS-mediated EC responses independently of LPB, suggesting that serum soluble CD14 represents a naturally occurring agonist for EC responses to LPS.

Acute-Phase Proteins↗
PubMed1992

Polymeric microballoons as ultrasound contrast agents. Physical and ultrasonic properties compared with sonicated albumin.

Air-filled polymeric microballoons were prepared with number-mean diameters of approximately 3 microns, volume-mean diameters of approximately 5 microns, and narrow particle-size distributions (standard deviation [SD] = 1.2 microns in number and SD = 2.0 microns in volume). More than 99% of the particles were below 8 microns. These particles were found to be highly echogenic for ultrasound, showing backscatter coefficients at 7.5 MHz, similar to the ones obtained with sonicated albumin microspheres. However, at 2.25 MHz, microballoons were less echogenic than albumin microspheres. These results are consistent with ultrasound attenuation measurements, which showed a maximum at 8 to 9 MHz for the microballoons compared with a reported value of 3.5 to 4.5 MHz for albumin microbubbles. Polymeric microballoons were found to be stable in plasma or under applied pressure as evidenced by unchanged particle concentration and echogenicity. Albumin microspheres were particularly unstable to applied pressure (150 mm Hg) and showed a rapid decrease in both particle counts and echogenicity.

Air↗