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Biomedical subjects

M G Bergeron

Publications and source records attributed to M G Bergeron.

At least 37 records · Page 2Linked to original sources

Sterically stabilized liposomes bearing anti-HLA-DR antibodies for targeting the primary cellular reservoirs of HIV-1.

The ability of liposomes bearing anti-HLA-DR Fab' fragments at the end termini of polyethyleneglycol chains (sterically stabilized immunoliposomes) to target HLA-DR expressing cells and increase the accumulation of liposomes into lymphoid organs has been evaluated and compared to that of conventional liposomes, sterically stabilized liposomes and conventional immunoliposomes after a single subcutaneous injection to mice. The accumulation of sterically stabilized liposomes in lymph nodes was higher than that of conventional liposomes. Sterically stabilized immunoliposomes accumulated much better than conventional immunoliposomes in all tissues indicating that the presence of PEG has an important effect on the uptake of immunoliposomes by the lymphatic system. Fluorescence microscopy studies showed that sterically stabilized liposomes are mainly localized in macrophage-rich areas such as the subcapsular region of lymph nodes and in the red pulp and marginal zone of the spleen. In contrast, sterically stabilized immunoliposomes mostly accumulated in the cortex in which follicles are located and in the white pulp of the spleen. As the human HLA-DR determinant of the major histocompatibility complex class II is expressed on activated CD4+ T lymphocytes and antigen presenting cells such as monocyte/macrophages and dendritic cells, known as the cellular reservoirs of HIV-1, liposomes bearing anti-HLA-DR antibodies constitute an attractive approach to concentrate drugs in HIV-1 reservoirs and improve their therapeutic effect.

Animals↗

Modulation of cytokines and chemokines, limited pulmonary vascular bed permeability, and prevention of septicemia and death with ceftriaxone and interleukin-10 in pneumococcal pneumonia.

Interleukin (IL)-10 is a biologically active anti-inflammatory and immunomodulatory cytokine. The respective effects or combined effect of ceftriaxone (Ctri) and IL-10 on host response was studied in a mouse model of lethal pneumococcal pneumonia. A once daily intraperitoneal (ip) injection of IL-10 (1 microg/mouse) for 2 days did not affect inflammation but accelerated bacterial dissemination to the bloodstream. Of mice treated with 1 ip 20 mg/kg Ctri injection, 40% developed septicemia, and only 52% survived. However, the addition of IL-10 to Ctri enhanced bacterial clearance, prevented septicemia, and yielded a 95% survival rate (P<.001). This approach also significantly (P<.05) decreased IL-1beta, IL-6, macrophage inflammatory protein-2, and myeloperoxidase levels in lungs and the production of nitric oxide in bronchoalveolar lavage fluid. Furthermore, Ctri plus IL-10 significantly (P<.05) reduced pulmonary vascular leakage and the appearance of red blood cells in alveoli. These data indicate a beneficial role for IL-10 as an adjunctive therapy to antibiotics against pneumococcal pneumonia.

Animals↗

A randomized controlled trial of filgrastim for the treatment of hospitalized patients with multilobar pneumonia.

This study assessed the safety and efficacy of filgrastim (r-metHuG-CSF [recombinant human methionine granulocyte colony-stimulating factor]), when combined with intravenous (IV) antibiotics, in the treatment of hospitalized adult patients with multilobar community-acquired pneumonia (CAP). Four hundred eighty patients were randomized to receive placebo (n=243) or filgrastim 300 microg/day (n=237), in addition to standard therapy. Treatment with study drug was continued for 10 days, until the peak white blood cell (WBC) count reached 75x109/L, until discharge from the hospital, until death, or until IV antibiotics were discontinued. Study-related observations continued through day 29. Filgrastim increased WBC counts (baseline median, 13.3x109/L; median peak, 43. 8x109/L). The 2 treatment groups were not statistically different with respect to the study end points; however, there was a trend toward reduction of mortality in patients with pneumococcal bacteremia. Although further studies will be required to validate this observation, filgrastim was safe and well tolerated when administered to patients with multilobar CAP.

Adult↗

Rapid detection of group B streptococci in pregnant women at delivery.

BACKGROUND: Group B streptococcal infections are an important cause of neonatal morbidity and mortality. A rapid method for the detection of this organism in pregnant women at the time of delivery is needed to allow early treatment of neonates. METHODS: We studied the efficacy of two polymerase-chain-reaction (PCR) assays for routine screening of pregnant women for group B streptococci at the time of delivery. We obtained anal, vaginal, and combined vaginal and anal specimens from 112 pregnant women; in 57 women, specimens were obtained before and after the rupture of the amniotic membranes. The specimens were tested for group B streptococci by culture in a standard selective broth medium, with a conventional PCR assay, and with a new fluorogenic PCR assay. RESULTS: Among the 112 women, the results of the culture of the combined vaginal and anal specimens were positive for group B streptococci in 33 women (29.5 percent). The two PCR assays detected group B streptococcal colonization in specimens from 32 of these 33 women: the one negative PCR result was in a sample obtained after the rupture of membranes. As compared with the culture results, the sensitivity of both PCR assays was 97.0 percent and the negative predictive value was 98.8 percent. Both the specificity and the positive predictive value of the two PCR assays were 100 percent. The length of time required to obtain results was 30 to 45 minutes for the new PCR assay, 100 minutes for the conventional PCR assay, and at least 36 hours for culture. CONCLUSIONS: Colonization with group B streptococci can be identified rapidly and reliably by a PCR assay in pregnant women in labor both before and after the rupture of membranes.

Anal Canal↗

Interaction between virion-bound host intercellular adhesion molecule-1 and the high-affinity state of lymphocyte function-associated antigen-1 on target cells renders R5 and X4 isolates of human immunodeficiency virus type 1 more refractory to neutralization.

The oligomeric nature of the viral envelope proteins has been partly held responsible for the observed differences in neutralization sensitivity between primary and laboratory-adapted strains of human immunodeficiency virus type 1 (HIV-1). However, recent evidence suggests that host factors can also modify the sensitivity of HIV-1 particles to neutralization. Having previously demonstrated that the acquisition of host-encoded intercellular adhesion molecule (ICAM)-1 proteins by newly formed viruses has a functional significance for the life cycle of HIV-1, we investigated whether the acquisition of host-derived ICAM-1 by HIV-1 could affect the virus sensitivity to neutralization. In this study, we have first shown that the physical presence of host cell membrane ICAM-1 on HIV-1 was not modifying virus sensitivity to neutralization by either two different anti-gp120 monoclonal antibodies (0.5beta and 4.8D) or soluble CD4. However, the ability of the F105 anti-gp120 monoclonal antibody (specific for the CD4-binding site) to neutralize ICAM-1-bearing virions was diminished when target cells were pretreated with an lymphocyte function-associated antigen-1 (LFA-1)-activating antibody. Interestingly, ICAM-1/POS progeny viruses were found to be slightly more resistant to neutralization by individual human sera in target cells expressing a low-affinity form of LFA-1 than viruses devoid of host-encoded ICAM-1 proteins. This resistance was markedly enhanced when target cells expressed an activated LFA-1 form on their surface. These results suggest that the interaction between virally embedded host ICAM-1 and target cell surface LFA-1 should be considered a factor modulating neutralization sensitivity of HIV-1 by human sera from HIV-1-infected individuals.

Adult↗

Novel genus-specific PCR-based assays for rapid identification of Neisseria species and Neisseria meningitidis.

This study presents the development of polymerase chain reaction (PCR)-based tests for the identification and detection of Neisseria species and Neisseria meningitidis. Currently, isolating and identifying these pathogens using conventional biochemical methods require 48-72 h. To improve speed and accuracy in diagnosing Neisseria infections, simple PCR-based tests that are specific for the genus Neisseria and the species Neisseria meningitidis have been developed. The genus-specific and species-specific DNA sequences were chosen by selecting and analyzing available database sequences. Neisseria-specific and Neisseria meningitidis-specific primer pairs were derived from the genes asd (coding for the aspartate beta-semialdehyde dehydrogenase) and ctrA (coding for a conserved outer membrane protein), respectively. Both the Neisseria-specific and Neisseria meningitidis-specific PCR assays were specific (they amplified only DNA from the target genus or species, out of 84 bacterial species tested). In addition, the Neisseria-specific assay amplified DNA from 321 of 322 strains tested representing 13 species of Neisseria, while the Neisseria meningitidis-specific assay amplified DNA from all 256 strains tested representing nine serogroups of Neisseria meningitidis. These PCR assays, which can be combined in multiplex, have been adapted to ensure that they are simple and can be performed within approximately 90 min. The tests provide new diagnostic tools for identifying Neisseria infections.

Aspartate-Semialdehyde Dehydrogenase↗

Comparative efficacy of teicoplanin and cefazolin for cardiac operation prophylaxis in 3027 patients. The ESPRIT Group.

OBJECTIVE: Cephalosporins, especially cefazolin, are widely used in the prevention of postoperative wound infections after cardiac operations. As more and more Staphylococcus aureus and Staphylococcus epidermidis strains are becoming resistant to cephalosporins and other antibiotics, alternative agents, such as glycopeptides, are often used as prophylaxis. We performed a multicenter double-blind randomized controlled trial comparing teicoplanin, a glycopeptide antibiotic, with cefazolin. METHODS: A total of 3027 adult patients undergoing elective coronary artery bypass grafting, valve operations, or both were randomized to a single dose of teicoplanin (15 mg/kg) or a 2-day course of cefazolin (2 g initial dose, followed by 1 g every 8 hours for 6 more doses). Patients were followed up for a total of 6 months postoperatively. The primary objective was to compare, between groups, the incidence of surgical infections up to 30 days postoperatively. Secondary objectives were incidence of other infections, other complications, and death. RESULTS: A total of 3027 patients were randomized to receive either teicoplanin (n = 1518) or cefazolin (n = 1509). Thirty days postoperatively, there was a trend to more deep sternotomy wound infections in the teicoplanin group (31 vs 18, P =. 087), which became significant by 6 months (36 vs 19, P =.032). One hundred percent of the gram-positive strains infecting patients were susceptible to teicoplanin, whereas 8.3% were resistant to cefazolin. Pneumonia and urinary tract infections were more common in the teicoplanin group. Deep wound infections of the leg were more common in the cefazolin group. CONCLUSIONS: Cefazolin was more effective prophylaxis than teicoplanin against postoperative wound infections after elective cardiac operations. Infection rates were low with either treatment.

Adult↗

Multiplex PCR assays for the detection of clinically relevant antibiotic resistance genes in staphylococci isolated from patients infected after cardiac surgery. The ESPRIT Trial.

Multiresistant staphylococci (82 Staphylococcus aureus and 114 coagulase-negative staphylococci) were characterized by testing with rapid multiplex polymerase chain reaction (PCR) assays for species identification and detection of associated antibiotic resistance genes. These 196 staphylococci were isolated from 149 adult patients who developed wound infection after elective coronary artery bypass grafts and/or valve surgery. The multiplex PCR assays allowed identification of the most common staphylococcal species with S. aureus- and Staphylococcus epidermidis-specific primers as well as the detection of the erythromycin resistance genes ermA, ermB, ermC and msrA, the aminoglycoside resistance gene aac(6')-aph(2"), the oxacillin resistance gene mecA and the penicillin resistance gene blaZ. There was a very good correlation between the genotypic analysis by PCR and the phenotype determined by standard methods of susceptibility testing and identification of staphylococcal species: 100% for erythromycin resistance, 98.0% for gentamicin resistance, 99.0% for oxacillin resistance, 100% for penicillin resistance and 100% for S. aureus and S. epidermidis species identification. This study suggests that the incidence and distribution of the tested clinically relevant antibiotic resistance genes in staphylococci associated with infections after cardiac surgery do not differ from those in strains from other infections. These multiplex PCR assays may be used as diagnostic tools to replace or complement standard methods of susceptibility testing and identification of staphylococci.

Adult↗

Efficacies of topical formulations of foscarnet and acyclovir and of 5-percent acyclovir ointment (Zovirax) in a murine model of cutaneous herpes simplex virus type 1 infection.

The topical efficacies of foscarnet and acyclovir incorporated into a polyoxypropylene-polyoxyethylene polymer were evaluated and compared to that of 5% acyclovir ointment (Zovirax) by use of a murine model of cutaneous herpes simplex virus type 1 infection. All three treatments given three times daily for 4 days and initiated 24 h after infection prevented the development of the zosteriform rash in mice. The acyclovir formulation and the acyclovir ointment reduced the virus titers below detectable levels in skin samples from the majority of mice, whereas the foscarnet formulation has less of an antiviral effect. Reducing the number of treatments to a single application given 24 h postinfection resulted in a significantly higher efficacy of the formulation of acyclovir than of the acyclovir ointment. Acyclovir incorporated within the polymer was also significantly more effective than the acyclovir ointment when treatment was initiated on day 5 postinfection. The higher efficacy of the acyclovir formulation than of the acyclovir ointment is attributed to the semiviscous character of the polymer, which allows better penetration of the drug into the skin.

Acyclovir↗

Correlation between the resistance genotype determined by multiplex PCR assays and the antibiotic susceptibility patterns of Staphylococcus aureus and Staphylococcus epidermidis.

Clinical isolates of Staphylococcus aureus (a total of 206) and S. epidermidis (a total of 188) from various countries were tested with multiplex PCR assays to detect clinically relevant antibiotic resistance genes associated with staphylococci. The targeted genes are implicated in resistance to oxacillin (mecA), gentamicin ¿aac(6')-aph(2"), and erythromycin (ermA, ermB, ermC, and msrA). We found a nearly perfect correlation between genotypic and phenotypic analysis for most of these 394 strains, showing the following correlations: 98% for oxacillin resistance, 100% for gentamicin resistance, and 98.5% for erythromycin resistance. The discrepant results were (i) eight strains found to be positive by PCR for mecA or ermC but susceptible to the corresponding antibiotic based on disk diffusion and (ii) six strains of S. aureus found to be negative by PCR for mecA or for the four erythromycin resistance genes targeted but resistant to the corresponding antibiotic. In order to demonstrate in vitro that the eight susceptible strains harboring the resistance gene may become resistant, we subcultured the susceptible strains on media with increasing gradients of the antibiotic. We were able to select cells demonstrating a resistant phenotype for all of these eight strains carrying the resistance gene based on disk diffusion and MIC determinations. The four oxacillin-resistant strains negative for mecA were PCR positive for blaZ and had the phenotype of beta-lactamase hyperproducers, which could explain their borderline oxacillin resistance phenotype. The erythromycin resistance for the two strains found to be negative by PCR is probably associated with a novel mechanism. This study reiterates the usefulness of DNA-based assays for the detection of antibiotic resistance genes associated with staphylococcal infections.

Anti-Bacterial Agents↗

In vivo activity and pharmacokinetics of ziracin (SCH27899), a new long-acting everninomicin antibiotic, in a murine model of penicillin-susceptible or penicillin-resistant pneumococcal pneumonia.

The effectiveness of ziracin (SCH27899), a novel everninomicin, was at first investigated against lethal pneumonia caused by a penicillin-susceptible Streptococcus pneumoniae strain. A single intravenous injection of ziracin at a dose of 60 mg/kg of body weight given at 18 h postinfection protected 100% mice and led to the complete clearance of bacteria from their lungs. The activity of ziracin was observed to be the same as that of ceftriaxone: the 50% protective doses (PD(50)s) of ziracin and ceftriaxone were 24.8 and 24.6 mg/kg, respectively. Evaluation of this therapy with leukopenic mice showed that a single injection of ziracin protected 75% of these mice. A delay in therapy with ziracin, which was initiated at 48 h postinfection with 30 mg/kg given once daily for 3 days, resulted in an 83% survival rate of immunocompetent mice. The efficacy of ziracin was further compared to that of vancomycin against lethal pneumonia caused by a penicillin-resistant S. pneumoniae strain in leukopenic mice. The PD(50)s of ziracin and vancomycin were 40.5 and 44.2 mg/kg, respectively. Treatment with ziracin at 30 mg/kg once daily for 2 days (initiated 18 h postinfection) yielded an 83% survival rate and achieved complete eradication of the bacteria. The results were the same as those obtained with vancomycin administered at 15 mg/kg twice daily for 2 days. It is notable that the high survival rates for mice treated with ziracin were associated with effective eradication of the bacteria and rapid recovery of pulmonary tissues from pneumonia. The pharmacokinetic properties of ziracin, ceftriaxone, and vancomycin were estimated following intravenous administration of a single dose of 30 mg/kg to immunocompetent mice. The half-life of ziracin was observed to be longer than those of ceftriaxone and vancomycin (2.3 h versus 1.0 and 0.36 h in the bloodstream and 3 h versus 1.9 and 0. 45 h in lung tissues). The areas under the concentration-time curves (AUCs) in lung tissue for ziracin versus those for ceftriaxone and vancomycin were 36 microg. h/g versus 20 and 9.5 microg. h/g. The prolonged half-life and high AUC for ziracin in tissue contributed to its excellent in vivo activities.

Aminoglycosides↗

Sodium lauryl sulfate increases the efficacy of a topical formulation of foscarnet against herpes simplex virus type 1 cutaneous lesions in mice.

The influence of sodium lauryl sulfate (SLS) on the efficacies of topical gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous infection has been evaluated in mice. A single application of the gel formulation containing 3% foscarnet given 24 h postinfection exerted only a modest effect on the development of herpetic skin lesions. Of prime interest, the addition of 5% SLS to this gel formulation markedly reduced the mean lesion score. The improved efficacy of the foscarnet formulation containing SLS could be attributed to an increased penetration of the antiviral agent into the epidermis. In vitro, SLS decreased in a concentration-dependent manner the infectivities of herpesviruses for Vero cells. SLS also inhibited the HSV-1 strain F-induced cytopathic effect. Combinations of foscarnet and SLS resulted in subsynergistic to subantagonistic effects, depending on the concentration used. Foscarnet in phosphate-buffered saline decreased in a dose-dependent manner the viability of cultured human skin fibroblasts. This toxic effect was markedly decreased when foscarnet was incorporated into the polymer matrix. The presence of SLS in the gel formulations did not alter the viabilities of these cells. The use of gel formulations containing foscarnet and SLS could represent an attractive approach to the treatment of herpetic mucocutaneous lesions, especially those caused by acyclovir-resistant strains.

Administration, Topical↗

Evidence for horizontal gene transfer in evolution of elongation factor Tu in enterococci.

The elongation factor Tu, encoded by tuf genes, is a GTP binding protein that plays a central role in protein synthesis. One to three tuf genes per genome are present, depending on the bacterial species. Most low-G+C-content gram-positive bacteria carry only one tuf gene. We have designed degenerate PCR primers derived from consensus sequences of the tuf gene to amplify partial tuf sequences from 17 enterococcal species and other phylogenetically related species. The amplified DNA fragments were sequenced either by direct sequencing or by sequencing cloned inserts containing putative amplicons. Two different tuf genes (tufA and tufB) were found in 11 enterococcal species, including Enterococcus avium, Enterococcus casseliflavus, Enterococcus dispar, Enterococcus durans, Enterococcus faecium, Enterococcus gallinarum, Enterococcus hirae, Enterococcus malodoratus, Enterococcus mundtii, Enterococcus pseudoavium, and Enterococcus raffinosus. For the other six enterococcal species (Enterococcus cecorum, Enterococcus columbae, Enterococcus faecalis, Enterococcus sulfureus, Enterococcus saccharolyticus, and Enterococcus solitarius), only the tufA gene was present. Based on 16S rRNA gene sequence analysis, the 11 species having two tuf genes all have a common ancestor, while the six species having only one copy diverged from the enterococcal lineage before that common ancestor. The presence of one or two copies of the tuf gene in enterococci was confirmed by Southern hybridization. Phylogenetic analysis of tuf sequences demonstrated that the enterococcal tufA gene branches with the Bacillus, Listeria, and Staphylococcus genera, while the enterococcal tufB gene clusters with the genera Streptococcus and Lactococcus. Primary structure analysis showed that four amino acid residues encoded within the sequenced regions are conserved and unique to the enterococcal tufB genes and the tuf genes of streptococci and Lactococcus lactis. The data suggest that an ancestral streptococcus or a streptococcus-related species may have horizontally transferred a tuf gene to the common ancestor of the 11 enterococcal species which now carry two tuf genes.

Amino Acid Sequence↗

In vitro and in vivo evaluations of sodium lauryl sulfate and dextran sulfate as microbicides against herpes simplex and human immunodeficiency viruses.

The efficacy of sodium lauryl sulfate (SLS), a sulfated anionic chaotropic surfactant, and dextran sulfate (DS), a polysulfated carbohydrate, against herpes simplex virus (HSV) and human immunodeficiency virus (HIV) infections was evaluated in cultured cells and in different murine models of HSV infection. Results showed that both SLS and DS were potent inhibitors of the infectivities of various HSV-1 and HSV-2 strains. Pretreatment of HIV-1 (strain NL4-3) with SLS also reduced its infectivity to 1G5 cells. DS prevented the binding of HSV to cell surface receptors and therefore its entry into cells. Pretreatment of HSV-1 (strain F) with 50 microM SLS resulted in a complete loss of virus infectivity to Vero cells. However, viruses were able to enter into cells and to produce in the nuclei capsid shells devoid of a DNA core. The amount of the glycoprotein D gene produced in these cells remained unchanged compared to controls, suggesting that SLS could interfere with the maturation of the virus. At a higher SLS concentration (100 microM), HSV was highly damaged by SLS pretreatment and only a few viral particles could enter into cells to produce abnormal capsids. Although DS was a more potent inhibitor of HSV infectivity in vitro, it was unable to provide any protection in murine models of HSV infection. However, SLS conferred a complete protection of animals infected cutaneously with pretreated viruses. In addition, skin pretreatment of mice with a polymer formulation containing SLS completely prevented the development of cutaneous lesions. More interestingly, intravaginal pretreatment of mice with SLS in a buffered solution also completely protected against lethal HSV-2 infection. Taken together, our results suggest that SLS could thus represent a candidate of choice as a microbicide to prevent the sexual transmission of HIV, HSV, and possibly other pathogens that cause sexually transmitted diseases.

Animals↗

Development of a rapid PCR assay specific for Staphylococcus saprophyticus and application to direct detection from urine samples.

Staphylococcus saprophyticus is one of the most frequently encountered microorganisms associated with acute urinary tract infections (UTIs) in young, sexually active female outpatients. Conventional identification methods based on biochemical characteristics can efficiently identify S. saprophyticus, but the rapidities of these methods need to be improved. Rapid and direct identification of this bacterium from urine samples would be useful to improve time required for the diagnosis of S. saprophyticus infections in the clinical microbiology laboratory. We have developed a PCR-based assay for the specific detection of S. saprophyticus. An arbitrarily primed PCR amplification product of 380 bp specific for S. saprophyticus was sequenced and used to design a set of S. saprophyticus-specific PCR amplification primers. The PCR assay was specific for S. saprophyticus when tested with DNA from 49 gram-positive and 31 gram-negative bacterial species. This assay was also able to amplify efficiently DNA from all 60 strains of S. saprophyticus from various origins tested. This assay was adapted for direct detection from urine samples. The sensitivity levels achieved with urine samples was 19 CFU with 30 cycles of amplification and 0.5 CFU with 40 cycles of amplification. This PCR assay for the specific detection of S. saprophyticus is simple and rapid (approximately 90 min, including the time for urine specimen preparation).

DNA, Bacterial↗

Development of conventional and real-time PCR assays for the rapid detection of group B streptococci.

BACKGROUND: Group B streptococci (GBS), or Streptococcus agalactiae, are the leading bacterial cause of meningitis and bacterial sepsis in newborns. Currently available rapid methods to detect GBS from clinical specimens are unsuitable for replacement of culture methods, mainly because of their lack of sensitivity. METHODS: We have developed a PCR-based assay for the rapid detection of GBS. The cfb gene encoding the Christie-Atkins-Munch-Petersen (CAMP) factor was selected as the genetic target for the assay. The PCR primers were initially tested by a conventional PCR method followed by gel electrophoresis. The assay was then adapted for use with the LightCycler(TM). For this purpose, two fluorogenic adjacent hybridization probes complementary to the GBS-specific amplicon were designed and tested. In addition, a rapid sample-processing protocol was evaluated by colony-forming unit counting and PCR. A total of 15 vaginal samples were tested by both standard culture method and the two PCR assays. RESULTS: The conventional PCR assay was specific because it amplified only GBS DNA among 125 bacterial and fungal species tested, and was able to detect all 162 GBS isolates from various geographical areas. This PCR assay allowed detection of as few as one genome copy of GBS. The real-time PCR assay was comparable to conventional PCR assay in terms of sensitivity and specificity, but it was more rapid, requiring only approximately 30 min for amplification and computer-based data analysis. The presence of vaginal specimens had no detrimental effect on the sensitivity of the PCR with the sample preparation protocol used. All four GBS-positive samples identified by the standard culture method were detected by the two PCR assays. CONCLUSION: These assays provide promising tools for the rapid detection and identification of GBS.

Animals↗

Targeting lymph nodes with liposomes bearing anti-HLA-DR Fab' fragments.

The ability of liposomes bearing anti-HLA-DR Fab' fragments to target cells expressing the human HLA-DR determinant of the major histocompatibility complex class II (MHC-II) has been evaluated and compared to that of conventional liposomes. Anti-HLA-DR immunoliposomes did not bind to HLA-DR-negative cells. In contrast, a high level of binding was observed following incubation of immunoliposomes with cells bearing important levels of human HLA-DR. The accumulation of conventional and murine anti-HLA-DR immunoliposomes in different tissues has been investigated following a single subcutaneous injection given in the upper back of C3H mice. Anti-HLA-DR immunoliposomes resulted in a much better accumulation in the cervical and brachial lymph nodes when compared to conventional liposomes. The accumulation in the liver was similar for both liposomal preparations, whereas an approximately twofold decrease in accumulation was observed for immunoliposomes in the spleen. Given that HLA-DR surface marker is expressed on monocyte/macrophages and activated CD4+ T lymphocytes, the primary cellular reservoirs of the human immunodeficiency virus (HIV), the use of liposomes bearing surface-attached anti-HLA-DR could constitute a convenient strategy to more efficiently treat this debilitating retroviral disease. Moreover, the reported incorporation of high amounts of host-encoded HLA-DR proteins by HIV particles renders the use of liposomes bearing anti-HLA-DR antibodies even more attractive.

Animals↗