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Biomedical subjects

C J Baker

Publications and source records attributed to C J Baker.

At least 109 records · Page 6Linked to original sources

Neutrophil Fc receptor participation in phagocytosis of type III group B streptococci.

Human peripheral blood neutrophils bear receptors for immunoglobulin G, FcRII, and FcRIII that differ structurally and functionally. We investigated the role of FcRII and FcRIII in the phagocytosis of group B streptococci (GBS) by measuring neutrophil uptake of radiolabeled type III GBS. The mean uptake of GBS opsonized with human serum containing complement and specific antibody was 76%, but when this serum was heated, the mean uptake was only 22%. A monoclonal antibody to FcRIII, Leu-11b, inhibited in a dose-dependent manner uptake of GBS opsonized with heated or intact serum to maxima of 40 and 30%, respectively. Conversely, a monoclonal antibody to FcRII, IV.3, inhibited by 77% the uptake of GBS opsonized with heated serum but had no effect when GBS was opsonized with intact serum. Leu-11b and IV.3 had an additive inhibitory effect with heated but not with intact serum. Neither monoclonal antibody inhibited the uptake of GBS opsonized with hypogammaglobulinemic serum. Therefore, FcRII is the primary mediator of the phagocytosis of GBS opsonized by antibody alone, whereas FcRIII plays a lesser role. Surprisingly, FcRII is not necessary for phagocytosis when complement is also present. FcRIII participates, to a limited extent, in phagocytosis of GBS opsonized with antibody whether or not complement is present. These findings suggest that the function of FcRII in triggering phagocytosis may be particularly important in host defense against type III GBS in the setting of complement deficiency of young infants.

Adult↗

Capsular polysaccharide regulates neutrophil complement receptor interactions with type III group B streptococci.

The capsular polysaccharide of type III group B streptococci contributes substantially to the virulence of this organism. We explored the extent to which capsular polysaccharide influences neutrophil complement receptor interactions by using a poorly encapsulated strain (COH 31r/s), two well-encapsulated strains (M732 and M912), and strains produced from COH 31r/s by transposon mutagenesis that lacked capsule (COH 31-15) or had capsular polysaccharide lacking terminal sialic acid residues (COH 31-21). When tested with normal human serum, each strain had initially high bactericidal indices (85 to 96%). Monoclonal antibody blockade of neutrophil complement receptor 3 (CD11b/CD18) inhibited opsonophagocytosis to a significantly greater extent for the well-encapsulated strain than for the poorly encapsulated, asialo, or unencapsulated mutant strain. The addition of antibody with specificity for capsular polysaccharide reduced the inhibitory effect significantly for the encapsulated but not for the mutant strains. Blockade of neutrophil complement receptor 1 (CD35) effected only low-level inhibition. However, simultaneous blockade of complement receptors 1 and 3 augmented the inhibitory effect. When hypogammaglobulinemic serum was used as an antibody-free complement source, the initial bactericidal index was low (30% +/- 15%) for an encapsulated strain and was not affected for the mutant strains. Blockade of either neutrophil complement receptor 1 or 3 or the combination fully inhibited killing of the encapsulated strain. These results demonstrate that the type III group B streptococcal capsular polysaccharide regulates interactions with neutrophil complement receptors. We conclude that efficient phagocytic killing of encapsulated group streptococci in nonimmune serum requires ligation of complement receptors 1 and 3.

Adult↗

Typing of group B streptococci: comparison of pulsed-field gel electrophoresis and conventional electrophoresis.

The SmaI restriction endonuclease digestion patterns of chromosomal DNAs from 35 group B streptococci were analyzed by pulsed-field gel electrophoresis (PFGE). Nineteen different patterns and four possible variants were identified. Twenty-four isolates were previously analyzed by conventional electrophoresis of HindIII-digested and/or BglII plus EcoRI double-digested chromosomal DNA. Although interpretations by both methods were essentially the same, PFGE identified as variants two isolates that were previously classified as the same isolate. More importantly, PFGE of the chromosomal DNA of group B streptococci digested with SmaI generated more easily defined patterns, since fewer and better separated bands were obtained, whereas digestion with HindIII or EcoRI plus BglII typically generated 100 or more bands. SalI digestion also yielded easily evaluable results, although the SalI fragments were somewhat smaller than those generated by SmaI. In our hands, PFGE patterns were more easily discerned and interpreted than were patterns previously generated by conventional electrophoresis.

Adult↗

Intravenous immune globulin for the prevention of nosocomial infection in low-birth-weight neonates. The Multicenter Group for the Study of Immune Globulin in Neonates.

BACKGROUND: Nosocomial infection is a major risk for premature infants with very low birth weights. One reason for their susceptibility to infection may be antibody deficiency, since there is little transfer of maternal IgG to the fetus before 32 weeks' gestation. METHODS: We conducted a multicenter, double-blind study of neonates weighing 500 to 1750 g at birth. A total of 588 neonates were randomly assigned, with stratification for birth weight, to receive periodic intravenous infusions of either immune globulin (500 mg per kilogram of body weight per day) or a placebo. Mortality, morbidity, and nosocomial infection during the next 56 days were assessed. RESULTS: The infusions were well tolerated; mild, reversible adverse reactions occurred in five infants in each group. There was a significant reduction in the risk of a first nosocomial infection in the recipients of immune globulin as compared with the placebo recipients (relative risk, 0.7; 95 percent confidence interval, 0.5 to 0.9). About 85 percent of the nosocomial infections were bacterial; the majority of these were caused by coagulase-negative staphylococci or Staphylococcus aureus. The neonates who received immune globulin had fewer mean days of hospitalization than the controls (62 vs. 68, P = 0.15); among the infants with infections, the difference in the mean length of the hospital stay was even greater (80 days vs. 101 days, P = 0.02). CONCLUSIONS: For premature infants weighing between 500 and 1750 g at birth, treatment with intravenous infusions of immune globulin is safe and reduces the risk of nosocomial infection.

Cross Infection↗

Wind-induced accidents of road vehicles.

This paper describes the results of a project that collected and collated data for wind-induced vehicle accidents that occurred in the United Kingdom during the major storm of 25 January 1990. The results of this data analysis are used to determine which vehicles are most at risk during windy periods, the nature of the accidents that were caused, and the likely values of accident wind speeds. Also the adequacy of a computer program that can predict such wind speeds (the program BLOWOVER) is assessed as far as the available data allows.

Accidents, Traffic↗

Sialylation and human neutrophil killing of group C Neisseria meningitidis.

This study describes the association of lipooligosaccharide (LOS) and capsule sialylation with the survival of 25 serogroup C meningococcal strains in phagocytosis assays. Eleven strains isolated from children were of diverse protein serotypes or were nontypeable; 14 were serotype 2b:P1.2 and were isolated from children during or immediately after a focal epidemic in Texas. Degree of endogenous LOS sialylation and amount of sialic acid capsule were associated with each other and with susceptibility to killing by neutrophils for the non-2b:P1.2 strains. The 2b:P1.2 strains as a group had significantly greater survival in the presence of neutrophils than did the non-2b:P1.2 strains. The susceptibility of these strains to killing by neutrophils was not associated with endogenous LOS sialylation or amount of capsule. These data suggest that many virulent strains evade neutrophil killing, either by sialylation or another mechanism. Evasion of neutrophil killing might enhance a strain's epidemic potential.

Child, Preschool↗

Description of an adenovirus type 8 outbreak in hospitalized neonates born prematurely.

An adenovirus (Ad) type 8 outbreak was prospectively studied in a neonatal intensive care unit. Nasopharyngeal secretions were cultured weekly for viruses and clinical information was obtained daily in each infant. Eleven of 112 neonates were infected with Ad; 8 of 9 available isolates represented one variant of Ad 8. The median age at infection was 54 days and the median duration of virus shedding was 2 days. Seven of 11 infants had onset of new symptoms and/or required acute respiratory support; only 2 infants had eye disease. Maternal characteristics, race, gender, age at entry into study and respiratory distress syndrome at birth were similar for both groups. Ad-infected infants tended to have earlier gestations and lower birth weights. Ad-infected neonates stayed longer in the neonatal intensive care unit, required more days of respiratory support and were more likely to develop bronchopulmonary dysplasia. Thus an association was established between lung disease in premature neonates and Ad infection.

Adenovirus Infections, Human↗

Influence of serotype of group B streptococci on C3 degradation.

Serotype III strains of group B streptococci (GBS) are isolated from the majority of young infants with bacteremia or meningitis. We hypothesized that serotype-associated differences in structure of the type-specific capsular polysaccharide or the presence of c protein would influence the extent to which C3 degradation occurs on GBS and that type-specific antibody would alter C3 deposition or degradation patterns. When clinical isolates of GBS representing serotypes Ia, Ib/c, II (with or without c protein) and III were employed with hypogammaglobulinemic serum as an opsonic source, a remarkable similarity was observed in patterns of C3 deposition and degradation for each of the four GBS serotypes and between strains with or without c protein. Both C3b and iC3b were detected by 5 min and throughout a 90-min opsonization interval. Less deposition occurred at 5 min on serotypes Ia and Ib/c than on types II and III GBS. Minimal degradation to C3d or smaller fragments was observed. Type-specific antibody facilitated C3b deposition on GBS and C3b degradation to iC3b early in opsonization. Possibly, accessibility of C3 fragments to neutrophil receptors, rather than the extent to which the surface permits C3 degradation, accounts for differential virulence among GBS serotypes.

Antibodies, Bacterial↗

Complement and antibody participation in opsonophagocytosis of type IV and V group B streptococci.

Requirements for complement and antibody in neutrophil-mediated killing of serotype IV and V group B streptococci were investigated. Neutrophils from adults were tested in an opsonophagocytic assay with sera from healthy adults, healthy newborns, and hypogammaglobulinemic, agammaglobulinemic, and C4-deficient patients. For all serum sources, the bactericidal index for both serotypes exceeded 84% after 40 min of incubation. Heat inactivation of sera ablated killing. Blockade of neutrophil receptor FcIII effected a maximum of 16% inhibition of opsonophagocytosis, and FcII receptor blockade demonstrated negligible inhibition. When neutrophil complement receptor 1 or 3 blockade was employed, the maximum inhibition detected was 26%. Simultaneous blockade of complement receptors 1 and 3 effected maximum inhibition levels of 25 and 65% for serotypes IV and V, respectively. Blockade of complement receptor 3 and neutrophil receptor FcIII inhibited opsonophagocytosis by 56% for both serotypes. When serum complement concentrations were restricted, neutrophil-mediated killing diminished but was restored by the addition of hyperimmune rabbit antiserum. These findings suggest that complement and antibody are major participants in the opsonophagocytosis of serotypes IV and V group B streptococci. A low prevalence of carriage or mediation of efficient phagocytosis by interactions of neutrophil complement and Fc receptors may contribute to the rarity of human infections caused by these two serotypes.

Adult↗

Contributions of complement and immunoglobulin to neutrophil-mediated killing of enterococci.

Enterococci have become a frequent causative agent in neonatal sepsis. The relative contributions of antibody and complement and their interactions in the neutrophil-mediated bacterial killing of 11 Enterococcus strains from neonates were investigated. Polymorphonuclear leukocytes (PMNL) from adult and term newborn infants were tested with normal human serum, adult hypogammaglobulinemic serum, and normal newborn serum in a neutrophil bactericidal assay. Neutrophil bactericidal activity for enterococci was not influenced by the serum source but was essentially ablated after heat inactivation of complement in all sera. No differences were observed in the killing capacity of healthy newborn versus adult PMNL regardless of serum source. Representative Enterococcus strains were then tested with agammaglobulinemic serum or C4-deficient serum, resulting in neutrophil bactericidal activities consistently exceeding 90%. A neutrophil bactericidal assay performed with normal rabbit serum and hyperimmune rabbit serum against enterococci showed that antibodies to enterococci enhanced neutrophil-mediated killing of this organism. Thus, neutrophil killing of enterococci appears to be mediated primarily by complement, with antibody playing a less essential but potentially important role. PMNL from adult and healthy term infants functioned with equal efficiency in the neutrophil killing of enterococci.

Adult↗

Reduction by delayed hypothermia of cerebral infarction following middle cerebral artery occlusion in the rat: a time-course study.

The effect of hypothermia on neuronal injury following permanent middle cerebral artery (MCA) occlusion in the rat was examined. Moderate hypothermia (body temperature 24 degrees C) was induced before MCA occlusion (0-minute delay group) in six rats, at 30 minutes in eight rats, and at 1 (seven rats), 2 (seven rats), and 3 (nine rats) hours after occlusion. The rats were kept at a 24 degrees C body temperature for 1 hour, then allowed to rewarm over 90 minutes. The animals were sacrificed 24 hours after MCA occlusion, and infarction was visualized by staining of coronal sections with 2,3,5-triphenyltetrazolium chloride. Infarct volumes were compared to matched normothermic control rats (body temperature 36 degrees C). Additional groups of 0-minute delay hypothermic (10 rats) and control animals (nine rats) were sacrificed 72 hours after MCA occlusion to examine the effects of prolonged survival. A significant reduction in the percentage of infarcted right hemisphere was seen in the animals sacrificed after 24 hours with 0-minute, 30-minute, and 1-hour delays in inducing hypothermia (mean +/- standard error of the mean: 2.2% +/- 0.7%, 4.4% +/- 0.9%, and 3.6% +/- 1.1%, respectively) as compared to normothermic control rats (10.8% +/- 1.5%, p less than 0.01 by Student's t-test). In the 2- and 3-hour delay groups, the percentage of infarcted right hemisphere was 17.1% +/- 2.4% and 12.0% +/- 2.7%, respectively, and no decrease in infarct volume was observed. The 0-minute delay hypothermia group sacrificed after 72 hours also displayed a significant reduction in right hemisphere infarct compared to their respective controls (4.8% vs. 11.7%, p less than 0.05). These findings indicate that, in the setting of permanent MCA occlusion, hypothermia markedly decreases brain injury even when its induction is delayed for up to 1 hour after the onset of ischemia. Ischemic damage does not appear to be merely retarded but permanently averted.

Animals↗

Prevention of group B streptococcal infection.

Group B streptococci continue to be major perinatal pathogens, both for mothers and their infants, and are associated with significant morbidity, mortality, and its attendant cost to society. Approaches to prevention are directed toward either eliminating exposure to the organism or enhancing host resistance, that is, chemoprophylaxis and immunoprophylaxis. Intrapartum chemoprophylaxis has been shown to effectively interrupt vertical transmission of group B streptococci from the genitally colonized mother to the infant and to decrease the incidence of both maternal and early-onset neonatal group B streptococcal disease. To avoid unnecessarily exposing large numbers of colonized women to antibiotics, only those with defined risk factors should be selected for intrapartum chemoprophylaxis. This regimen is ampicillin given intravenously, 2 g initially at onset of labor or rupture of membranes, followed by 1 g every 4 hours until delivery. Risk factors include premature onset of labor or rupture of membranes before 37 weeks' gestation, rupture of membranes of more than 12 hours, intrapartum fever, group B streptococcal bacteriuria, or having previously delivered an infant with group B streptococcal disease. Detection of anogenital colonization is accomplished either by culture late in the second or early in the third trimester or by intrapartum group B streptococcal antigen testing of vaginal swabs from those previously culture-negative or not cultured. Although this approach combines the advantages of several proposed strategies, it will still miss those cases of group B streptococcal disease developing in the absence of discernible risk factors. Intrapartum prophylaxis does not prevent late-onset group B streptococcal disease. Prenatal and postnatal chemoprophylaxis have not been shown to be effective. Symptomatic infants born to mothers given chemoprophylaxis should be evaluated for neonatal sepsis and treated accordingly. This approach is also suggested for asymptomatic premature infants, those whose mothers have not received adequate prophylaxis or have previously delivered infants with group B streptococcal disease, and for twin siblings of infants developing group B streptococcal disease. Successful implementation of this approach may be limited by the availability and sensitivity of the rapid antigen test used. Immunoprophylaxis, and active immunization in particular, is the most promising method of preventing perinatal group B streptococcal disease in mothers and their infants, including late-onset disease. Immunization of pregnant women with type III polysaccharide vaccine has resulted in adequate provision of functional antibody to the infants born to responders.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Vaccines↗

Factors associated with umbilical catheter-related sepsis in neonates.

To determine factors associated with risk for umbilical catheter-related sepsis, we studied neonates with one or more catheters in place for more than 3 days. Among 225 infants with 357 umbilical catheters, catheter-related sepsis occurred in 14 infants (6%). Catheter-related sepsis occurred in 5% of infants with umbilical arterial catheters and in 3% of infants with umbilical venous catheters. Staphylococcal species accounted for 71% of cases of catheter-related sepsis. Multiple logistic regression analysis revealed that very low birth weight and longer duration of antibiotic therapy were significantly associated with risk for umbilical arterial catheter-related sepsis. Increased risk for umbilical venous catheter-related sepsis was best predicted by the simultaneous occurrence of higher birth weight and infusion of hyperalimentation solution. Catheter duration correlated with duration of antibiotic therapy and with infusion of hyperalimentation solution for both types of catheters; however, in the multivariable analysis, duration of catheterization was not found to be a significant independent predictor of risk for catheter-related sepsis for either type of catheter.

Anti-Bacterial Agents↗

Hypothermic protection following middle cerebral artery occlusion in the rat.

The effects of deep hypothermia on ischemic neuronal injury were examined using a permanent middle cerebral artery occlusion model in the rat. Animals were maintained at temporalis temperatures of either 24 degrees C or 36 degrees C and killed 6 hours after arterial occlusion. Normothermic rats displayed an average infarct volume of 25.1% +/- 1.6% of the right hemisphere, whereas hypothermic rats had an average infarct volume of 4.1% +/- 1.3% (p less than 0.001). The right/left hemispheric ratio was 1.05 +/- 0.02 in the normothermic group and 1.00 +/- 0.02 in the hypothermic group (p less than 0.05). These results suggest that hypothermia to 24 degrees C may reduce cerebral infarction and edema formation following middle cerebral artery occlusion in the rat.

Animals↗

Pooled human IgG hyperimmune for type III group B streptococci: evaluation against multiple strains in vitro and in experimental disease.

Because rates of morbidity and mortality due to newborn sepsis are unacceptably high, adjunctive therapies must be investigated. In the current studies, after healthy adults were immunized with type III group B streptococcal (III-GBS) capsular polysaccharide vaccine, serum was obtained from "vaccine-responders" from which a pooled human IgG preparation hyperimmune for III-GBS was prepared by ion-exchange column chromatography. This preparation, containing 549 micrograms/ml III-GBS antibody was very active functionally when evaluated against multiple III-GBS strains both in vitro in an opsonophagocytic assay using newborn sera and in a newborn rat model of III-GBS disease. The level of functional activity was dramatically higher than that of commercially available human IgG preparations for intravenous use demonstrated previously in identical assays. Human IgG preparations hyperimmune for GBS offer promise for use as adjunctive therapy of sepsis in newborns.

Animals↗