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Biomedical subjects

C J Baker

Publications and source records attributed to C J Baker.

At least 127 records · Page 7Linked to original sources
PubMed1991

Transient hypothermia reduces focal ischemic brain injury in the rat.

The effect of transient hypothermia on focal cerebral ischemia was evaluated using a rat model of permanent middle cerebral artery (MCA) occlusion. MCA occlusion was performed on 10 rats at a temporalis muscle temperature of 24 degrees C (hypothermic group) and on 10 rats at 36 degrees C (normothermic group). Rats in the hypothermic group were maintained at 24 degrees C for 1 hour after MCA occlusion and then allowed to rewarm to 36 degrees C over the next 2 hours. Animals in both groups were killed 24 hours after MCA occlusion. Cerebral infarcts were visualized by staining of coronal brain sections with 2,3,5-triphenyltetrazolium chloride. Normothermic rats displayed an average infarct volume of 233.1 +/- 13.2 mm3 (standard error of the mean), whereas hypothermic rats had an average infarct volume of 166.2 +/- 22.8 mm3 (P less than 0.01). Expressed as a percentage of the volume of the right hemisphere, the normothermic group had an infarct volume of 22.1 +/- 1.5% and the hypothermic group an infarct volume of 16.0 +/- 2.2% (P less than 0.05). These results demonstrate that transient hypothermia to a temporalis muscle temperature of 24 degrees C significantly reduces subsequent infarct size in an experimental model of permanent arterial occlusion.

Animals↗
PubMed1991

Deposition and degradation of C3 on type III group B streptococci.

Antibody to the polysaccharide capsule of type III group B streptococci (GBS) and complement are essential to host defense against systemic infection in neonates. Interactions between C3 degradation products and specific neutrophil receptors mediate the attachment and ingestion of these organisms. To evaluate the influence of capsule on C3 disposition, we compared the C3 fragments released from a highly encapsulated clinical isolate (M861) with those from an unencapsulated mutant (COH 31-15) and an asialo mutant (COH 31-21) of type III GBS after opsonization with hypogammaglobulinemic serum. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) analysis, the three strains displayed similar patterns of C3 degradation; both C3b and iC3b were detectable. However, as the duration of opsonization increased, C3 fragment bands became more prominent on the encapsulated strain. The capsule, and specifically sialylation of the capsular polysaccharide of type III GBS, promotes C3 fragment deposition. However, C3 was deposited and degraded to iC3b in the absence of capsule. Opsonization of strain M861 with serum containing antibody specific for the polysaccharide capsule facilitated C3 fragment deposition in the early phases of opsonization. Because iC3b is one of the C3 fragments on an encapsulated strain of type III GBS, the relative deficiency of neonatal neutrophil receptors for this ligand may contribute to the virulence of this organism. Sufficient concentrations of antibody may enhance opsonization by facilitating C3 deposition as well as by interacting with Fc receptors on neutrophils.

Antibodies, Bacterial↗
PubMed1991

Role of neutrophil receptors in opsonophagocytosis of coagulase-negative staphylococci.

The role of neutrophil complement receptors in the opsonophagocytosis of 10 strains of coagulase-negative staphylococci was investigated. Polymorphonuclear leukocytes from adults as well as term and premature newborn infants were tested with normal human serum, adult hypogammaglobulinemic serum, and pooled premature infant serum in an opsonophagocytic assay. Neutrophils from premature infants demonstrated significantly lower killing capacity (62%) than neutrophils from adults (86%) or term infants (84%; P less than 0.02). Maximum inhibition of opsonophagocytosis by adult or infant neutrophils occurred with an FcIII receptor blockade (80%), whereas a blockade of complement receptors produced minimal inhibition. Opsonophagocytic activity for the coagulase-negative staphylococci was not influenced by the serum source but was influenced by reducing the serum concentration below 5%. Abrogation of the complement activity of normal human serum by heating or the addition of ethylenediamine tetraacetate reduced opsonophagocytosis by 100 and 96%, respectively, whereas selective inhibition of the classical complement pathway reduced opsonophagocytosis by only 40%. Thus, opsonophagocytosis of coagulase-negative staphylococci by human sera appears to be mediated primarily by neutrophil Fc receptors, but complement is also required. The inefficiency of these interactions with neutrophils from premature infants may partially explain the enhanced susceptibility of very-low-birth-weight neonates to disseminated, coagulase-negative staphylococcal infections.

Adult↗
PubMed1991

Phenotypic diversity in the alpha C protein of group B streptococci.

Group B streptococci (GBS) is the leading cause of neonatal sepsis and meningitis. C proteins are an immunologically important group of surface-associated antigens in GBS that remain incompletely characterized. Two C proteins have been designated alpha and beta on the basis of protease susceptibility. We recently used a monoclonal antibody to describe a protective epitope of the GBS alpha (or trypsin-resistant) C protein in the prototype Ia/c GBS strain. In the present study, we examined 51 GBS isolates for expression of C-protein alpha and beta antigens. The alpha antigen, as detected with monoclonal antibody in sodium dodecyl sulfate (SDS) extracts, appears as a heterogeneous series of proteins spaced 8 kDa apart on SDS-polyacrylamide gel electrophoresis, but has a maximum molecular mass that varies among strains from 62.5 to 167 kDa. By immunoblotting with human immunoglobulin A, polyclonal antiserum, or monoclonal antibody, the beta antigen, in contrast, appears as a single protein of molecular mass between 124 and 134 kDa. The amount of alpha antigen expressed by each strain was quantified by enzyme immunoassay inhibition and was found to vary markedly from strain to strain. The susceptibility of strains of GBS to opsonization and killing by human polymorphonuclear leukocytes in the presence of either complement alone or complement with alpha-specific monoclonal antibody was examined. Strains expressing the alpha antigen were less readily killed in the absence of specific antibody than were alpha-negative strains. Killing in the presence of alpha-specific monoclonal antibody was found to correlate directly with the maximum molecular mass of the alpha antigen and with the quantity of antigen on the bacterial cell surface. Isolates of GBS that express the alpha C protein vary widely in the quantity and molecular mass of the alpha antigen produced, and this heterogeneity appears to have biologic importance.

Antibodies, Bacterial↗
PubMed1990

New uses of intravenous immune globulin in newborn infants.

Preterm infants are hypogammaglobulinemic at birth, a condition that worsens during the first several weeks of life. It has been postulated that periodic infusions of intravenous immune globulin in preterm infants might prevent systemic infections after age 7 days, but clinical trials have been inconclusive. To test this hypothesis in neonates weighing 500 to 1750 g at birth, a multicenter, randomized, double-blind, placebo-controlled trial was initiated. Either intravenous immune globulin (500 mg/kg) (284 infants) or placebo (5% albumin-normal saline, 10 ml/kg) (293 infants) was infused periodically for 8 weeks. Infusions were well tolerated. Mortality (4%) was similar in both groups. However, the incidence of systemic infection was significantly reduced in the treatment group, but only in those weighing less than 1500 g. More than 80% of infections were bacterial; half were caused by staphylococci. Standard use of intravenous immune globulin in preterm infants looks promising but must await full analysis of data from this and another ongoing multicenter trial.

Bacterial Infections↗
PubMed1990

Patterns of immune response among survivors of group B streptococcal meningitis.

Serum samples from 10 infants surviving type III, group B streptococcal (GBS) meningitis were collected acutely and longitudinally for 6 months to determine patterns of antibody response to the capsular polysaccharide and their in vitro functional correlates. Five infants who failed to develop specific antibody at a mean of 3.8 weeks after diagnosis had an increase of greater than or equal to 1.0 microgram/ml after another 4-8 weeks. This IgM-predominant type-specific antibody declined to baseline 2-4 months later. Opsonophagocytosis of type III GBS increased from 0 to 88% in parallel with peak antibody response. Three infants developed increased antibody and opsonophagocytosis at 15-31 weeks after diagnosis, while two had no detectable response. Despite increasing complement levels, opsonophagocytosis of type III GBS was poor with low specific antibody levels These results suggest that survivors of GBS meningitis transiently develop specific antibody and associated efficient opsonophagocytosis, but functional competence does not persist despite maturation to adult levels of complement proteins.

Aging↗
PubMed1990

Role of complement receptors in opsonophagocytosis of group B streptococci by adult and neonatal neutrophils.

The role of complement receptors in bactericidal activity for types III and Ia group B streptococci (GBS) by adult or neonatal polymorphonuclear leukocytes (PMNL) was explored using polyclonal and monoclonal antibodies to complement receptors one (CR1) and three (CR3). In an opsonophagocytic assay, selective blockade of the CR3 sugar or lectin-like binding site on adult or neonatal PMNL effected a significant reduction in killing of both GBS serotypes that was more pronounced for type III. In contrast, blockade of the iC3b binding site effected greater inhibition of bactericidal activity for type Ia than for type III GBS. When both the CR3 sugar or lectin-like binding site and CR1 were blocked, inhibition was enhanced for type Ia GBS by adult PMNL and for both serotypes by neonatal PMNL. These results demonstrate a role for both CR1 and CR3 in the opsonophagocytosis of GBS. Possibly, differences in CR3 epitope utilization contribute to the differential virulence among GBS serotypes in neonates.

Adult↗
PubMed1990

Evaluation of an intravenous immunoglobulin preparation for the prevention of viral infection among hospitalized low birth weight infants.

An intravenous immunoglobulin (IVIG) preparation was evaluated prospectively in hospitalized low birth weight infants for the prevention of respiratory virus infection. Premature neonates were evaluated from October 19, 1987, through July 31, 1988. Nasopharyngeal secretions were cultured weekly for viruses and clinical information was obtained daily on each infant. Ninety-one infants with birth weights between 500 and 1750 g were randomized to receive either IVIG, 500 mg/kg (46 infants), or 5% albumin-normal saline (placebo), 10 ml/kg (45 infants), between Days 3 and 7 of life, 7 days later and every 14 days thereafter for a maximum of 5 doses. Demographic and life event data during pregnancy were similar for IVIG and placebo groups. Birth weight, gestational age, gender, age at entry into the study and incidence of respiratory distress syndrome at birth were also similar in both groups of premature infants. Twenty-six viruses were isolated from 25 infants. There were 13 and 12 infections in the IVIG and placebo groups, respectively. Severity of disease, as measured by clinical factors and outcomes of virus-infected infants were no different in IVIG-treated and placebo groups. Adenoviruses and cytomegalovirus accounted for 57.7 and 23.1%, respectively, of the viral isolates. In this study the use of IVIG did not prevent or modify adenovirus and cytomegalovirus infections in premature infants.

Adenoviridae Infections↗
PubMed1990

Involvement of plasma membrane calcium influx in bacterial induction of the k/h and hypersensitive responses in tobacco.

An early event in the hypersensitive response of tobacco to Pseudomonas syringae pv syringae is the initiation of a K(+)/H(+) response characterized by specific plasma membrane K(+) efflux, extracellular alkalinization, and intracellular acidification. We investigated the role of calcium in induction of these host responses. Suspension-cultured tobacco cells exhibited a baseline Ca(2+) influx of 0.02 to 0.06 micromole per gram per hour as determined from (45)Ca(2+) uptake. Following bacterial inoculation, uptake rates began to increase coincidently with onset of the K(+)/H(+) response. Rates increased steadily for 2 to 3 hours, reaching 0.5 to 1 micromole per gram per hour. This increased Ca(2+) influx was prevented by EGTA and calcium channel blockers such as La(3+), Co(2+), and Cd(2+) but not by verapamil and nifedipine. Lanthanum, cobalt, cadmium, and EGTA inhibited the K(+)/H(+) response in both suspension-cultured cells and leaf discs and prevented hypersensitive cell death in leaf discs. We conclude that increased plasmalemma Ca(2+) influx is required for the K(+)/H(+) and hypersensitive responses in tobacco.

Journal Article↗
PubMed1990

Enterococcal sepsis in neonates: features by age at onset and occurrence of focal infection.

Fifty-six neonates with enterococcal septicemia in a single hospital from 1977 through 1986 were studied. The incidence was low and constant until 1983, when an increase, attributable to infections in infants older than 7 days of age (late-onset), was noted. These infants were more premature (mean gestational age 29.5 vs 36.9 weeks) and had lower birth weights (mean 1250 vs 2700 g) than those with early-onset enterococcal sepsis, and in most the infections were characterized by a nosocomial origin. Infants with early-onset infection had a mild illness with respiratory distress typical of other etiologic agents or diarrhea without focal infection. By contrast, late-onset enterococcal sepsis was heralded by severe apnea, bradycardia, circulatory collapse, and increased ventilatory requirements. Focal infections, including scalp abscess or catheter-related infection (23% each), meningitis or pneumonia (15% each), were common. Rapid clinical improvement and clearance of bacteremia resulted from therapy with an aminoglycoside and either ampicillin or vancomycin, but only if abscesses were drained and intravascular catheters were removed. Mortality rates for early-onset, late-onset, and necrotizing enterocolitis-associated infection were 6, 8, and 17%, respectively. Enterococcus is a frequent cause of late-onset septicemia in premature neonates, and empiric therapy should include appropriate antimicrobial agents.

Birth Weight↗