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Biomedical subjects

G J Noel

Publications and source records attributed to G J Noel.

16 recordsLinked to original sources
PubMed1992

Type b capsule inhibits ingestion of Haemophilus influenzae by murine macrophages: studies with isogenic encapsulated and unencapsulated strains.

Phagocytosis may be important in clearing Haemophilus influenzae from the bloodstream. To define the effect of type b capsule on phagocytosis, binding and ingestion by macrophages was measured for 5 isogenic sets of capsule-sufficient strains (clinical isolates and type b transformants of capsule-deficient mutants) and capsule-deficient mutants (strains lacking a 9-kb EcoRI fragment of chromosomal DNA associated with type b capsule expression). Capsule-sufficient strains were not bound in the absence of serum, whereas capsule-deficient strains were bound and ingested (1.8-5.1 organisms/macrophage; 59%-97% ingested). In the presence of nonimmune serum, capsule-sufficient strains were largely bound but not ingested (4.7-7.2 organisms/macrophage; 7%-21% ingested), whereas capsule-deficient strains were nearly all ingested (6.2-10.5 organisms/macrophage; 93%-97% ingested). Strains resisting ingestion caused persistent bacteremia 24 h after intravenous challenge in mice and were more likely than readily ingested strains to cause persistent bacteremia or death in infant rats. Thus, type b capsule inhibits ingestion by macrophages; resistance to ingestion may be an important virulence determinant of type b organisms.

Agglutination Tests↗
PubMed1992

Multiple methicillin-resistant Staphylococcus aureus strains as a cause for a single outbreak of severe disease in hospitalized neonates.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial infection. Outbreaks of infection caused by these pathogens are generally considered to be traceable to introduction of single strains into a hospital population. A large outbreak of bacteremic disease that recently occurred in our neonatal intensive care unit (11 episodes in 10 patients) involved 9 low birth weight infants and was associated with serious infection (4 episodes of meningitis). To determine the role of a single point source in this outbreak, isolates were characterized based on phenotypic and genotypic analyses. Phenotypic analysis included assessing hemolytic activity, phage typing, antimicrobial susceptibility testing and methicillin resistance population analysis. Genotypic analysis included assessment of plasmid profiles, dot-blot hybridization, restriction enzyme fragment pattern analysis and hybridization analysis of chromosomal DNA using a panel of staphylococcal gene probes. This analysis established that at least two distinct strains of MRSA were responsible for disease during this outbreak. This experience demonstrates the potential for MRSA to cause severe disease in the neonatal intensive care unit and indicates that the epidemiology of MRSA outbreaks is more complex than the spread of a single strain of bacteria.

Cross Infection↗
PubMed1991

Host defense abnormalities associated with HIV infection.

Infection with human immunodeficiency virus (HIV) impairs immune function. Most abnormalities in host defense associated with HIV infection are due to helper T-cell dysfunction. Studies defining these abnormalities in the HIV-infected patient have largely been done in adults. A more complete understanding of the immunodeficiency that occurs in infants and young children congenitally infected with HIV awaits further study of their immune function and the effect this virus has on the developing immune system.

Adult↗
PubMed1991

In vivo stability of heterogeneous expression classes in clinical isolates of methicillin-resistant staphylococci.

To define the stability of methicillin-resistant Staphylococcus aureus (MRSA) in vivo, 22 isolates collected at one New York institution in 1989 and 1990 were studied. All 22 belonged to one of two distinct methicillin-resistant phenotypes (class 3 or 2), which were precisely identified as belonging to two distinct genotypes. Genotypic classification was based on restriction analysis of chromosomal DNA with EcoRI and HindIII and Southern analysis of ClaI digests using two DNA probes. One was specific for the mec gene; the other was specific for transposon Tn554. The findings suggest that the MRSA isolates studied were representative of two genetically distinct MRSA "clones," each with a unique strain-specific methicillin-resistant phenotype that is stable under the conditions of invasive disease, carriage, and spread from patient to patient.

Adult↗
PubMed1991

The role of C3 in mediating binding and ingestion of group B streptococcus serotype III by murine macrophages.

To understand how complement effects phagocytosis of type III group B streptococcus, we assessed the specific role of C3 in mediating binding and ingestion of these bacteria by macrophages. Phagocytosis of bacteria by resident mouse peritoneal macrophages was measured under conditions in which C3 deposition on bacteria was inhibited or after blockade of C3-ligands or of complement receptor type three (CR3) with specific antibodies. C3 depletion, incubation with F(ab')2 fragments of antibody to C3, or blockade of CR3 completely inhibited the binding of bacteria that was seen in the presence of nonimmune serum. Immune serum increased the number of associated organisms 6-fold compared to that seen with nonimmune serum. With this serum, 82% of organisms were ingested. C3 depletion or CR3 blockage had a modest effect, but this interaction could be ablated completely only after Fc receptors were blocked. Using varied concentrations of an IgG2a MAb against type III capsular antigen, it was possible to show that small amounts of antibody incapable of mediating bacterial binding by itself directed an interaction that also depended upon C3. Phagocytosis of group B streptococci by macrophages in the presence of little or no antibody requires complement and C3 opsonization specifically. C3-dependent binding may be important in determining mononuclear phagocyte-dependent clearance of these pathogens from blood, particularly in patients with little or no type-specific serum antibody.

Animals↗
PubMed1990

Role of complement in mouse macrophage binding of Haemophilus influenzae type b.

Previous in vivo studies demonstrated that clearance of encapsulated Haemophilus influenzae from blood is associated with the deposition of C3 on these bacteria and is independent of the later complement components (C5-C9). Since clearance of encapsulated bacteria is determined by phagocytosis of bacteria by fixed tissue macrophages, we studied the interaction of H. influenzae type b with macrophages in vitro. Organisms bound to macrophages in the presence of nonimmune serum. Binding was not evident in heat-treated serum or in serum from complement depleted animals and was inhibited by F(ab')2 fragments of antibody to C3 and by blockade of the macrophage complement receptor type 3. The majority of organisms bound in the presence of complement alone remained extracellular. Antibody in the form of convalescent serum or an IgG1 monoclonal to type b capsule did not increase the total number of organisms associated with macrophages, but did increase the number of organisms ingested. Furthermore, complement enhanced antibody-mediated ingestion. This in vitro study demonstrates that complement largely mediates binding of H. influenzae to macrophages. This binding may be critical in determining the early clearance of these bacteria from blood and may be an important mechanism of defense in the nonimmune, as well as the immune host.

Animals↗
PubMed1989

Resistance to serum bactericidal activity distinguishes Brazilian purpuric fever (BPF) case strains of Haemophilus influenzae biogroup aegyptius (H. aegyptius) from non-BPF strains. Brazilian Purpuric Fever Study Group.

We studied the ability of normal human serum to lyse H. influenzae biogroup aegyptius (H. aegyptius) isolates recovered from patients with Brazilian purpuric fever (BPF clone) or non-BPF clone strains. BPF clone isolates, although similar to non-BPF clone isolates with regard to the ability to fix C3 to their surfaces, could be distinguished from non-BPF clone strains by their resistance to lysis in vitro following incubation with normal adult human serum.

Blood Bactericidal Activity↗
PubMed1988

Complement-mediated early clearance of Haemophilus influenzae type b from blood is independent of serum lytic activity.

The role of complement-mediated serum lytic activity in the clearance of encapsulated Haemophilus influenzae type b was studied by comparing clearance of bacteria from blood in normal mice with that in congeneic C5-deficient animals and mice depleted of complement by using cobra-venom factor. The clearance of organisms from blood by C5-deficient and C5-sufficient normal animals was similar. C3 depletion and the inability to fix C3 to the surface of bacteria were, however, associated with impaired clearance of organisms during the first 24 h after intravenous bacterial challenge. These studies suggest that complement-mediated opsonization rather than bacteriolysis is important in determining early clearance of H. influenzae type b from the bloodstream.

Animals↗
PubMed1988

Anaerobic bacteremia in a neonatal intensive care unit: an eighteen-year experience.

A review of anaerobic bacteremia in the Neonatal Intensive Care Unit identified 29 episodes of clinically significant bacteremia occurring over the past 18 years. This experience suggested that certain clinical settings were associated with specific anaerobic infections. Although Gram-positive and Gram-negative anaerobes were isolated with similar frequency, 8 of 12 infants bacteremic within the first 48 hours of life were infected with Gram-positive, penicillin G-susceptible organisms whereas 11 of 17 infants older than 2 days were bacteremic with Gram-negative, penicillin G-resistant anaerobes. Eleven of 17 infants with anaerobic bacteremia associated with necrotizing enterocolitis were bacteremic with Gram-negative anaerobes. Five of 6 infants with anaerobic bacteremia associated with chorioamnionitis were bacteremic with Gram-positive anaerobes. These observations should be considered in making decisions regarding empiric therapy for the newborn at highest risk for anaerobic bacteremia.

Anti-Bacterial Agents↗
PubMed1988

Neonatal Staphylococcus epidermidis right-sided endocarditis: description of five catheterized infants.

Coagulase-negative staphylococci are important causes of bacteremia and focal infections in infants hospitalized in neonatal intensive care units. The medical records and echocardiograms of 58 newborns with persistent Staphylococcus epidermidis bacteremia who were hospitalized in the neonatal intensive care unit at The New York Hospital during the past 5 1/2 years were reviewed, and five infants were identified as having S epidermidis right-sided infective endocarditis. These episodes were associated with placement of umbilical venous catheters in the right atrium, slow resolution of bacteremia, and persistent thrombocytopenia. This experience suggests the role of endocardial trauma resulting from the placement of umbilical venous catheters in the pathogenesis of endocarditis. The increasing importance of coagulase-negative staphylococci as a cause of bacteremia in the newborn may explain the emergence of S epidermidis as an important cause of infective endocarditis in the neonatal intensive care unit. These cases underscore the potential severity of S epidermidis infection in the premature newborn.

Catheterization↗
PubMed1986

In vitro activities of selected new and long-acting cephalosporins against Pasteurella multocida.

The activities of six agents commonly used in treating infections of the skin and soft tissues and the action of selected cephalosporins against 15 isolates of Pasteurella multocida were assessed by a macro-broth dilution method. Broad-spectrum cephalosporins, including ceftriaxone and cefixime, had excellent in vitro activities (MIC less than or equal to 0.098) against the isolates tested.

Cefaclor↗
PubMed1985

Newborn sepsis following antepartum group B streptococcal maternal infection in rats.

Group B streptococcus is an important pathogen in man and infection due to this bacteria is responsible for significant mortality and morbidity in neonates. An animal model of neonatal infection caused by group B streptococcus that results from vertical transmission is described. Nine pregnant Sprague-Dawley rats received intraperitoneal inoculation of 10(9)-10(10) colony forming units of group B streptococcus on day 20 or 21 of gestation. Four of nine rats died following inoculation. A total of 51 pups was born to the surviving five mothers. Pups were sacrificed at 4- to 8-h intervals and cultures of blood, brain, liver, and spleen were obtained. Nineteen of 51 pups (37%) had group B streptococcus isolated from blood or tissues within the first 48 h of life. Results suggest that antepartum systemic infection in rats can result in vertical transmission of disease. This animal model can be used to further study the mechanisms of transmission of group B streptococcus and the pathogenesis and treatment of neonatal sepsis caused by this pathogen.

Animals↗