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Biomedical subjects

H A Lassiter

Publications and source records attributed to H A Lassiter.

At least 19 recordsLinked to original sources
PubMed2001

Complement inhibition does not reduce post-hypoxic-ischemic cerebral injury in 21-day-old rats.

Hypoxic-ischemic (HI) cerebral injury frequently follows resuscitation and is a recognized cause of permanent long-term neurologic disability in children. Complement activation has been shown to participate in post-ischemic injury to a variety of tissues and organs. To test the hypothesis that complement activation participates in post-HI cerebral injury in immature rats, 21-day-old rats were subjected to right common carotid artery ligation and 8% O(2). This combination of ischemia and hypoxia resulted in the development of significant neuronal loss, edema, and atrophy in the right cerebral hemisphere. However, intraperitoneal administration of the complement inhibitors soluble complement receptor type 1 or cobra venom factor did not reduce the neuronal loss, edema, or atrophy. Therefore, complement activation did not contribute significantly to the cerebral injury observed in this immature rat model.

Animals↗
PubMed2001

Nonspecific human IgG reduces survival in neonatal rats infected with Escherichia coli.

BACKGROUND: Human intravenous IgG (IVIG) containing specific antibodies protects neonatal rats from septic death. However, IVIG has immunosuppressive properties and clinical trials of IVIG in neonates at risk for sepsis have yielded conflicting results. HYPOTHESIS: This study was designed to test the hypothesis that nonspecific antibodies in IVIG reduce survival in neonatal rats infected with Escherichia coli. METHODS: Specific antibodies were adsorbed from IVIG with E. coli to produce IVIG/anti-E. coli-. After transthoracic administration of E. coli, survival was determined in neonatal rats injected intraperitoneally with phosphate-buffered saline, IVIG/anti-E. coli- (500 mg/kg) or IVIG containing anti-E. coli antibodies (IVIG/anti-E. coli+). Complement-mediated hemolytic activity of neonatal rat serum was quantified using sensitized sheep erythrocytes. RESULTS: Compared with placebo, intraperitoneal IVIG/anti-E. coli- reduced neonatal survival after E. coli infection. In contrast, IVIG/anti-E. coli+ protected infected animals. Both IVIG/anti-E. coli- and IVIG/anti-E. coli+ impaired the complement-mediated hemolytic activity of neonatal rat serum. CONCLUSIONS: IVIG contained (1) nonspecific antibodies that reduced survival in neonatal rats infected with E. coli and (2) protective anti-E. coli antibodies that enhanced survival in neonatal rats infected with E. coli. We speculate that in clinical trials of IVIG to treat or prevent neonatal sepsis, inconsistent results may be caused, in part, by lot-to-lot variations in the ratio of immunosuppressive, nonspecific antibodies to protective, specific antibodies.

Animals↗
PubMed1998

Complement component C9 enhances the capacity of beta-lactam antibiotics to kill Escherichia coli in vitro and in vivo.

Complement component C9 is required for rapid complement-mediated killing of Escherichia coli. In this report, the influence of supplemental C9 on the bactericidal and protective effects of beta-lactam antibiotics in neonates was assessed. By rocket immunoelectrophoresis, the intrinsic C9 concentrations of pooled serum from both human and rat neonates was less than 20% of adult levels. Supplemental C9 purified from human plasma enhanced the capacity of ampicillin-treated serum from human neonates to impair the survival of E coli O7:K1:NM (P < 0.02). Similarly, supplemental C9 enhanced the capacity of cefotaxime-treated neonatal rat serum to impair the survival of E coli O1:K1:NM (P < 0.05). Moreover, the intraperitoneal administration of C9 enhanced the survival of cefotaxime-treated neonatal rats that were septic with E coli (P < 0.05). These observations may contribute to the development of new strategies, such as augmentation of complement component serum concentrations, to reduce the morbidity and mortality of neonatal E coli sepsis.

Adult↗
PubMed1997

The administration of complement component C9 enhances the survival of neonatal rats with Escherichia coli sepsis.

To determine the significance of neonatal C9 deficiency, an animal model was developed in the rat. By rocket immunoelectrophoresis, the concentration of C9 in pooled adult rat serum was 224 +/- 7.2 microg/mL. In contrast, the concentration of C9 in pooled serum from 1-d-old rats was only 43 +/- 3.8 microg/mL and increased during the first 3 wk of life to 170 +/- 20 microg/mL. Similarly, the capacities of neonatal rat serum to kill two pathogenic strains of Escherichia coli and to lyse sensitized sheep erythrocytes were diminished compared with adult serum but increased during the first 3 wk of life. Supplemental human C9 significantly enhanced the bactericidal and hemolytic activity of neonatal rat serum. The capacity of neonatal rats to survive after the intrapulmonary injection of E. coli was positively correlated with the serum C9 concentration, bactericidal activity, and hemolytic activity. In 2-d-old rats infected with E. coli, the intraperitoneal administration of human C9 significantly enhanced survival and also enhanced the protective effect of intraperitoneal human IgG antibodies. The data indicate that C9 deficiency predisposed neonatal rats to invasion by E. coli. The neonatal rat appears to be a suitable model with which to investigate the significance of C9 deficiency.

Age Factors↗
PubMed1994

Supplemental complement component C9 enhances the capacity of neonatal serum to kill multiple isolates of pathogenic Escherichia coli.

Previous studies demonstrated that, compared with adult serum, neonatal serum contained a diminished concentration of complement component C9 and that supplemental C9 enhanced the capacity of neonatal serum to kill an isolate of Escherichia coli. Therefore, experiments were designed to determine the mechanisms by which supplemental C9 enhances the bactericidal capacity of neonatal serum and to determine whether supplemental C9 enhances the capacity of neonatal serum to kill several different pathogenic strains of E. coli. A radiobinding assay and immunogold electron microscopy using a monoclonal anti-C9 antibody revealed that, compared with 40% adult serum, neonatal serum deposited a diminished quantity of C9 onto E. coli O7w:K1:NM. Supplemental C9 (75 mg/L) significantly enhanced the quantity of C9 deposited by the neonatal serum. Treatment with 10 mM MgEGTA (a mixture of 100 mM MgCl2 and 100 mM EGTA that blocks activation of the classic complement pathway but leaves the alternative pathway intact) abolished the capacity of neonatal serum to deposit C9 and to kill the bacteria. Supplemental C9 enhanced the capacity of neonatal serum to kill eight different blood isolates of E. coli. Therefore, supplemental C9 enhanced the capacity of neonatal serum to kill E. coli by increasing the total quantity of C9 deposited via activation of the classic complement pathway. Neonatal serum contained sufficient quantities of classic pathway components, other than C9, to deposit the supplemental C9 onto E. coli and to enhance bacterial killing. The bactericidal activity of neonatal serum against multiple isolates of pathogenic E. coli was increased after C9 supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Neonatal immune neutropenia following the administration of intravenous immune globulin.

BACKGROUND: In adults--but not neonates--neutropenia has been reported to complicate treatment with intravenous immunoglobulin, but the mechanism is unknown. PURPOSE: To describe for the first time the case of a newborn infant who, after intravenous immunoglobulin, demonstrated serum antineutrophil antibodies and neutropenia. PATIENTS AND METHODS: The 1,425-g, 36-week-gestation boy was healthy except for intrauterine growth retardation. Intravenous immunoglobulin (1g/dose x 3) was administered to treat alloimmune thrombocytopenia. Neutrophil-specific antibodies were detected by a granulocyte immunofluorescence assay. RESULTS: After the intravenous immunoglobulin, the platelet count normalized but the neutrophil count declined to 450/mm3. Neutrophil-specific antibodies were detected in the serum of the infant but not in the maternal serum. Furthermore, cross-matching revealed that the maternal serum did not react with the infant's granulocytes. Two of three random lots of intravenous immunoglobulin contained detectible anti-neutrophil antibodies. CONCLUSIONS: After intravenous immunoglobulin, the infant's serum contained one or more anti-neutrophil antibodies that were not maternal in origin. We speculate that the neutropenia resulted from the administration of intravenous immunoglobulin containing antineutrophil antibodies.

Adult↗
PubMed1992

Inefficient bacteriolysis of Escherichia coli by serum from human neonates.

To assess bacteriolysis in human neonates, Escherichia coli O7w:K1:NM were incubated with sera from eight healthy neonates, serum pooled from the eight neonates, and serum pooled from healthy adults. The adult serum killed E. coli. In contrast, the bacteria were not killed during incubation with sera from the eight neonates, the pooled neonatal serum, or with heat-inactivated adult serum. However, the combination of pooled neonatal serum and heat-inactivated adult serum killed the bacteria. Supplemental IgG-containing antibodies that bound to E. coli did not enhance the bactericidal activity of the neonatal serum. Ten of 12 blood isolates of E. coli from septic neonates but only 8 of 15 isolates from septic adults were serum-sensitive (killed during incubation with adult serum) (P less than .05). Therefore, neonatal serum killed E. coli inefficiently and was deficient in non-IgG heat-stabile component(s) required for bacterial killing. Compared with adults, neonates were more frequently septic with serum-sensitive strains of E. coli.

Adult↗
PubMed1992

Complement factor 9 deficiency in serum of human neonates.

The serum concentration of complement factor C9 (C9) was 260 +/- 47 micrograms/ml (+/- SE) in 14 mothers and less than 42 micrograms/ml in each of their 14 neonates. During incubation for 60 min, 11 of 14 maternal sera and 3 of 14 neonatal sera reduced the survival of Escherichia coli O7w:K1:NM to less than 20% of the original inoculum (P less than .03). Eleven neonatal sera did not kill the bacteria. Supplemental C9 (60 micrograms/ml) enhanced the bactericidal capacity of 10 neonatal sera. 125I-labeled C9 was deposited onto E. coli by neonatal sera, but less efficiently than by pooled adult sera. Supplemental IgG enhanced 125I-labeled C9 deposition and potentiated the bactericidal activity of exogenous C9. Therefore, neonatal sera contained diminished concentrations of C9 and killed E. coli inefficiently. In neonatal sera, supplemental C9 was deposited onto E. coli and enhanced bactericidal activity. These effects of C9 were potentiated by supplemental IgG.

Adult↗
PubMed1992

Intravenous immunoglobulin in the prevention and treatment of neonatal bacterial sepsis.

IVIG has been shown in vitro to enhance many antibody-dependent immunologic functions. In animal models, IVIG enhanced the survival of septic neonates. In humans, preliminary data indicate that prophylactic IVIG may diminish the incidence of bacterial sepsis in VLBW neonates if sufficient doses of the immunoglobulin are administered repeatedly. IVIG administered after the onset of clinical symptoms may improve the survival of septic human neonates. However, the studies designed to assess the efficacy of IVIG to treat established sepsis have employed a small number of subjects and have, overall, provided inconclusive data. IVIG has been tolerated well by neonates, but the safety and long-term consequences of administering IVIG to newborn infants are not yet defined. IVIG will likely serve as a useful adjunct to enhance the antibacterial defenses of newborn infants. Use of IVIG in human neonates remains experimental at this time; therefore, the clinical application of IVIG for the prevention or treatment of neonatal bacterial sepsis should await the development of guidelines to be derived from ongoing multicentered, placebo-controlled clinical trials.

Animals↗
PubMed1991

Effect on neutrophil kinetics and serum opsonic capacity of intravenous administration of immune globulin to neonates with clinical signs of early-onset sepsis.

This study was designed to test the hypothesis that administration of immune globulin to human neonates with early-onset bacterial sepsis would (1) facilitate neutrophil egress from the marrow, (2) improve serum opsonic capacity, and (3) facilitate recovery from the infectious illness. Twenty-two newborn infants with clinical signs of early-onset sepsis were given an intravenous infusion of either 750 mg of immune globulin (IVIG) per kilogram of body weight or the same volume of a vehicle control (albumin). All 22 infants survived, but significant hematologic, immunologic, and respiratory differences were observed after the IVIG and not after the control infusion. Eleven of the patients had neutropenia; 24 hours after the infusions, the neutropenia had resolved in all six IVIG recipients but persisted in all five control recipients (p less than 0.001). Ten patients had I/T neutrophil ratios (a measure of immature neutrophils to total neutrophils on the leukocyte differential count) of less than 0.2. One hour after completion of the infusions, all five IVIG recipients had elevated I/T ratios (mean +/- SEM:0.10 +/- 0.05 before vs 0.43 +/- 0.03 after infusion; p less than 0.001), suggesting a prompt release of neutrophils from the marrow neutrophil storage pool into the circulation; no increase in the I/T ratio was observed in the control recipients. Six hours after the IVIG infusions, the ratio of arterial oxygen tension to fraction of inspired oxygen increased; no increase was observed after control infusions. Serum concentrations of IgG, IgG1, IgG2, IgG3, IgG4, and total hemolytic complement and the capacity of serum to support opsonophagocytosis of type II and type III group B streptococci increased markedly in the IVIG recipients but not in the control subjects. We conclude that administration of 750 mg IVIG per kilogram to neonates with clinical signs of early-onset sepsis was associated with immunologic, hematologic, and physiologic improvement.

Bacterial Infections↗
PubMed1991

Diminished IgG, but not complement C3 or C4 or factor B, precedes nosocomial bacterial sepsis in very low birth weight neonates.

The significance of low serum IgG and complement proteins in very low birth weight (VLBW; less than 1500 g) neonates is not known. Therefore serum IgG, C3, C4 and Factor B were quantitated weekly by rate nephelometry in 15 VLBW neonates who developed proven nosocomial bacterial or candidal sepsis (Group A) and 27 VLBW neonates who did not develop sepsis (Group B). In the first week of life the serum IgG of neonates in Group A was 295 +/- 33 mg/dl (mean +/- SEM) and in Group B it was 440 +/- 21 mg/dl (P less than 0.01). In the second week, the IgG of Group A was 270 +/- 32 mg/dl and that of Group B was 473 +/- 38 mg/dl (P less than 0.01). If the IgG was less than 350 mg/dl in the first week or less than 230 mg/dl in the second week, the relative risk of acquiring sepsis was greater than or equal to 5 (95% confidence interval in the first week, 1.7 to 11.2). The serum IgG was measured before the onset of sepsis in 14 of the 15 neonates in Group A. In the week before sepsis the IgG of the 14 neonates was less than 440 mg/dl (range, 45 to 433 mg/dl) in all cases, was below the mean IgG of Group B in 12 of 14 cases (P = 0.006 vs. Group B) and was greater than 2 SD below the mean IgG of Group B in 4 of 14 cases (P = 0.0003 vs. Group B).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗
PubMed1990

Complement C3 deposition onto bacteria by neonatal serum is not enhanced after the infusion of intravenous immunoglobulin.

To determine the effect of intravenous immunoglobulin (IVIG) on the capacity of serum from septic neonates to deposit complement C3 and IgG onto the bacteria isolated from their blood, 500 mg/kg of IVIG was administered to 18 neonates suspected of being septic. Blood was obtained just before the infusion, and again 15 minutes after its completion. Group B streptococcus type II, group B streptococcus type III, Staphylococcus aureus, and Staphylococcus epidermidis were isolated from the pre-infusion blood of four neonates. Bacteria were incubated with the appropriate serum, washed, and the amount of C3 and IgG subsequently bound to the organisms was quantified by radioimmunobinding assay. Sera from the four septic neonates and sera from four neonates of similar gestational age but whose blood cultures were negative were compared with pooled sera from healthy adults. Before the administration of IVIG, C3 deposition onto the bacteria by sera from five of the seven neonates tested was significantly less than that observed for adult sera. Following the infusion, no increase in C3 deposition was observed for any of the seven sera assayed, and in two cases C3 deposition fell significantly. In contrast, in seven of eight cases, IVIG enhanced the IgG deposition to levels greater than or equal to those observed for adult sera. Therefore, following the infusion of IVIG into neonates with proven or suspected sepsis, the deposition of C3 onto invasive bacteria by their serum was not enhanced even though IgG deposition was increased.

Antibodies, Viral↗
PubMed1989

Immunologic regulation of E. coli K1 by serum from neonatal rats is enhanced following intraperitoneal administration of human IgG.

The effect of 1500 mg/kg intraperitoneal human IgG on the capacity of neonatal rat serum to opsonize and to kill Escherichia coli K1 and to deposit IgG and C3 onto this organism was investigated. Unlike serum from neonatal rats injected with albumin, serum from neonatal rats injected with human IgG opsonized and killed E. coli K1 efficiently. Heat treatment abolished the bactericidal effect of serum from IgG recipients, suggesting a role for complement. A radioimmunobinding assay demonstrated that the capacity of neonatal rat serum to deposit IgG and C3 onto E. coli K1 was impaired. However, intraperitoneal human IgG enabled serum from neonatal rats to deposit human IgG onto the bacteria and enhanced C3 deposition to a level equivalent to that observed with adult rat serum. Therefore, neonatal rats have a functionally competent classic pathway of complement. Human IgG ameliorates the opsonic and bacteriolytic inadequacies of neonatal rat serum that result primarily from a deficiency of antibodies to E. coli.

Animals↗
PubMed1988

Neutrophil-mediated killing, opsonization, and serum-mediated killing of Escherichia coli K1 by neonatal rats.

Neonates are particularly susceptible to infection with Escherichia coli K1. To investigate the mechanisms which lead to this susceptibility, we examined: (a) the bactericidal activity of neutrophils; (b) opsonization, and (c) the bactericidal activity of serum in developing rats. Neutrophils from adult rats killed E. coli K1 more efficiently than did neutrophils from young animals. Opsonization of E. coli by serum of prematurely delivered rats was poor. Serum from prematurely delivered and term rats promoted growth of E. coli K1, while serum from adult rats killed greater than 95% of the organisms within 90 min. However, the mixture of heat-inactivated serum from adult rats plus serum from prematurely delivered rats killed E. coli K1.

Animals↗
PubMed1983

Neonatal appendicitis.

We report a case of neonatal appendicitis with right flank edema and abdominal wall cellulitis. These findings suggest retrocecal appendicitis, especially in conjunction with hematuria, proteinuria, and thickening of the right abdominal wall. When these signs are present, immediate surgical exploration must be considered. With attention to clinical information, physical signs, ancillary tests, and abdominal x-ray films, it may be possible to lower the unacceptably high mortality of 80%.

Appendicitis↗