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Biomedical subjects

G W Fischer

Publications and source records attributed to G W Fischer.

At least 73 records · Page 4Linked to original sources
PubMed1984

Intravenous immunoglobulin in neonatal group B streptococcal disease. Pharmacokinetic and safety studies in monkeys and humans.

Numerous studies have suggested that opsonic antibody is important in neonatal immunity to group B streptococci. Immunoglobulin G is primarily transferred from the mother to the fetus across the placenta in the last few weeks of pregnancy. Premature babies may, therefore, not acquire sufficient opsonic antibody to protect them from infection with group B streptococci. Although maternal immunization may provide adequate maternal opsonic antibody, premature infants with antibody deficiency may remain susceptible to infection. Intravenous immunoglobulin administered to term pregnant rhesus monkeys did not provide reliable levels of serum opsonic activity to group B streptococci in their offspring. Pharmacokinetic and safety studies were also performed in human neonates. Significant elevations in group B streptococcal-specific IgG did occur in human neonates given 500 mg/kg intravenous immunoglobulin and the infusions appeared safe and well tolerated. The availability of intravenous immunoglobulin with functional activity against group B streptococci may provide a rapid and effective method of delivering opsonic antibody to neonates.

Adult↗
PubMed1984

Improved detection of bacterial antigens by latex agglutination after rapid extraction from body fluids.

Nonspecific agglutination of antibody-coated latex particles, unrelated to the presence of specific bacterial antigens, is a major difficulty with commercial latex particle agglutination tests. Rheumatoid and other factors are known to interfere with latex tests. We studied the use of six chelating, reducing, and anticoagulatory reagents in a rapid extraction of antigen procedure to free heat-stable antigens of Haemophilus influenzae type b and group B streptococcus which had been added to human sera. We also screened sera for the incidence of nonspecific agglutination from the three following groups: 123 patients with positive serology tests, 112 hospitalized patients, and 87 blood donors. The rapid extraction of antigen procedure involved a 1:4 dilution of the sera with each of the six reagents, incubation at 100 degrees C for 3 min, and centrifugation at 13,000 X g for 5 min. Two commercial latex kits were tested (Bactigen and Wellcogen). Nonspecific agglutination was entirely eliminated by each of the six extraction reagents. Sera from 52% of the patients with positive serology tests, 29% of the hospitalized patients, and 28% of the blood donors showed nonspecific agglutination with Bactigen before extraction. Nonspecific agglutination was eliminated in all but one sample after the rapid extraction of antigen procedure. This simple, rapid extraction procedure eliminated nonspecific reactions in cerebrospinal fluids and amniotic fluids and reduced this problem in urines and sera with each commercial kit used on clinical specimens.

Agglutination↗
PubMed1984

Studies of short-term pulmonary and peripheral vascular responses induced in oophorectomized sheep by the infusion of a group B streptococcal extract.

Short-term (0-30 min) pulmonary and systemic vascular responses of oophorectomized ewes infused intravenously with a trichloroacetic acid (TCA) extract of a type III (strain 878) group B streptococcus (GBS) were studied. TCA-878 extract induced significant pulmonary hypertension, reduction in femoral artery pressure and reduced femoral artery PO2. These responses were similar to those observed after the infusion of sublethal doses of E. coli endotoxin and could be prevented by priming the animal with ibuprofen or indomethacin. Ewes rechallenged 48 h after their initial dose of TCA-878 extract experienced pulmonary arterial pressure significantly higher than those induced by the first infusion. Similar augmented responses were not seen after rechallenge with endotoxin. Larger doses of TCA-878 extract resulted in increasingly higher pulmonary arterial pressure. We conclude that the venous infusion of TCA extracts of GBS-878 induces significant pulmonary hypertension in sheep and that this response may be mediated by prostaglandins. The vasoactive substance extracted from these streptococci could play a role in promoting the vascular instability experienced by the human neonate with early onset GBS disease.

Animals↗
PubMed1983

Cat scratch disease: a bacterial infection.

Histopathologic examination of lymph nodes from 39 patients with clinical and pathological criteria for cat scratch disease revealed delicate pleomorphic Gram-negative bacilli in 34 of the 39 nodes. They were within the walls of capillaries in or near areas of follicular hyperplasia and within microabscesses. They were best seen with the Warthin-Starry silver impregnation stain. Organisms in lymph node sections exposed to convalescent serum from three patients and to immunoperoxidase stained equally well with all three samples. The organisms did not react with hyperimmune sera to Legionella pneumophila nor to several species of Rickettsia. These bacilli appear to be the causative agents of cat scratch disease.

Cat-Scratch Disease↗
PubMed1983

Effect of dimethoate and O-demethyldimethoate on bone marrow cells of CFLP mice.

The organophosphorus pesticide dimethoate and its nonalkylating O-demethyl derivative were tested for their ability to induce chromosomal alterations in bone marrow cells of CFLP mice after ip administration. A single dose of 20 mg/kg dimethoate proved to be ineffective. However, doses of 60 mg/kg dimethoate or 69 mg/kg O-demethyldimethoate sodium salt significantly increased the aberration rates above those of the controls. The same effect was observed after a nontoxic dose of 690 mg/kg O-demethyldimethoate sodium salt. Considering the distribution of the several aberration types, these findings suggest that the alkylating properties of dimethoate only in part may be responsible for its cytogenetic activity.

Alkylation↗
PubMed1983

Functional antibacterial activity of a human intravenous immunoglobulin preparation: in vitro and in vivo studies.

The functional antibacterial activity of an intravenous immunoglobulin preparation (Swiss Red Cross Immunoglobulin, SRK-Ig) was tested both in vitro and in vivo. Using type III group B streptococci as a model system, the intravenous immunoglobulin preparation was shown to enhance phagocytosis and killing of the bacteria by human neutrophils. There was good activity to several type III strains, and for efficient opsonization both antibody and complement were required. In an animal model of neonatal group B streptococcal sepsis, passively administered immunoglobulin enhanced survival with 27/37 (73%) treated animals surviving compared to only 3/16 (19%) controls. These studies demonstrate that the intravenous immunoglobulin preparation SRK-Ig has retained functional activity and may have potential value for prophylaxis or therapy of certain bacteria infections.

Animals↗
PubMed1983

Detection of group B streptococcal antigens in amniotic fluid of rhesus monkeys.

To simulate group B streptococci (GBS) amniotic fluid infections common in humans and to examine bacterial growth and the appearance of GBS antigens in vivo, GBS were injected into the amniotic cavity of 19 near-term rhesus monkeys. Transabdominal aspirates of amniotic fluid were obtained before bacterial challenge, after 2 and 6 h, and during cesarean section delivery (24 h). Each fluid was quantitatively cultured for GBS. Specimens of amniotic fluid and gastric aspirate from each infant were tested for the presence of GBS antigens with a commercial latex particle agglutination test (Wellcogen Strep B; Wellcome Diagnostics, Dartford, England). To eliminate nonspecific latex particle agglutination reactivity, presumably caused by proteins, a processing procedure was required. Despite active proliferation of bacteria, only 12% of the 2-h amniotic specimens were latex particle agglutination positive. In contrast, 94% of th3 6-h and 100% of the 24-h specimens had detectable antigens, as did 89% of the gastric fluid specimens aspirated from the 19 newborns. Latex particle agglutination tests, after proper processing, will readily detect GBS antigens in amniotic or gastric aspirate fluid from experimentally infected rhesus monkeys.

Amniotic Fluid↗
PubMed1982

Antibacterial activity of a human monoclonal antibody to haemophilus influenzae type B capsular polysaccharide.

Human splenic lymphocytes were fused with a new mutant human myeloma cell line (HFB-1) to produce hybridomas that secrete human monoclonal antibodies. A cloned hybridoma line was selected that secretes IgG antibodies reactive with Haemophilus influenzae type b polyribosylribitolphosphate (PRP) capsular polysaccharide. This human monoclonal antibody was active in an in-vitro neutrophil-mediated bactericidal assay, and provided significant protection in an animal model of H. influenzae type b disease. Human monoclonal antibody to H. influenzae type b may have prophylactic value in man, particularly in infants who do not produce protective antibody after active immunisation with PRP.

Antibodies, Monoclonal↗
PubMed1982

Functional characteristics of a modified immunoglobulin preparation for intravenous administration: summary of studies of opsonic and protective activity against group B streptococci.

Group B streptococci (GBS) remains a major cause of morbidity and mortality in newborn babies, despite antibiotic therapy, Recent studies suggest that phagocytosis and killing of GBS is ineffective due to a deficiency in anti-GBS antibody. Using an opsonophagocytic bacterial assay and a suckling rat model of GBS sepsis, we analyzed a modified human immunoglobulin for opsonic and protective antibody. Immune globulin (IGIV) prepared for intravenous use (Gamimune, Cutter Laboratories, Inc.) was highly protective in this experimental GBS model. Using the opsonophagocytic assay, antibody activity to several strains of types Ia, II, and III GBS were also demonstrated with IGIV. To ensure that the IGIV activity was in fact antibody, globulin from IGIV was isolated and analyzed. Purified IgG retained opsonic activity in vitro and also provided protection in experimental GBS disease. Variation in the quantity of IgG necessary for protection was observed in different GBS strains. Since IGIV has opsonic and protective activity against several strains and serotypes of GBS, its intravenous administration may provide a valuable adjunct to standard antibiotic therapy for neonatal GBS infections.

Animals↗
PubMed1982

Pneumococcal sepsis with false-negative blood cultures.

Most physicians recognize the false-positive blood cultures (generally due to contamination) are common. Bacteria such as pneumococci, however, may rapidly die in broth cultures, and viable bacteria may not be identified. Several patients were observed with pneumococcal infections that had false-negative blood cultures 24 hours after inoculation. Hemolysis and methemoglobin formation in the bottle suggested bacterial growth within 12 hours after incubation, and blind subcultures at that time yielded pneumococci. Pneumococcal antigen could be detected in the blood culture bottles using counter-immunoelectrophoresis, even though subculture at 24 hours yielded no growth. Physicians and laboratory personnel should be aware that false-negative blood cultures may occur, particularly with certain bacteria such as Streptococcus pneumoniae, and that the blood culture bottles should be observed visually for the presence of brown sediment or hemolysis.

Adult↗
PubMed1982

Modified human immune serum globulin for intravenous administration: in vitro opsonic activity and in vivo protection against group B streptococcal disease in suckling rats.

Human immune serum globulin (ISG) preparations were tested in an in vivo suckling rat protection assay and an in vitro opsonophagocytic assay against various types and strains of Group B streptococci (GBS). Standard ISG provided minimal protection in suckling rats against type III GBS sepsis, whereas preparations of ISG modified for intravenous administration (MISG) provided significant protection against all strains of type III, type II and type Ia GBS tested. Although less protection was obtained against type Ia strains, the survival in suckling rats challenged with all types of GBS varied from 73% to 91% with MISG therapy, as compared with 5% to 12% survival in untreated animals. In this in vivo model, MISG was protective even when administered after bacterial challenge, but had to be administered within 5 h of infection. MISG also had high in vitro opsonic activity against GBS types III and II, but was less effective with some type Ia strains. Just as MISG was more protective than ISG in vivo, it also was more opsonic in vitro. A detailed comparison of one lot of MISG with its parent ISG revealed that the modified preparation actually contained less IgG. When equivalent concentrations of affinity-purified IgG from both preparations were tested, the IgG from MISG was significantly more opsonic. Since the affinity purification procedure eliminated the possibility that IgM or substances introduced in the modification process were actually responsible for the enhanced bactericidal activity, it appears that the individual IgG molecules in MISG may be more effective. These studies suggest that MISG which has been modified by reduction and alkylation for intravenous administration may provide a valuable adjunct to chemotherapy in the treatment of GBS disease in the neonate.

Animal Population Groups↗
PubMed1981

Levamisole: potentiation of primary immunoglobulin M antibody responses in suckling rats.

The influence of levamisole (LMS) on the primary immunoglobulin M (IgM antibody response of suckling rats was investigated. Although suckling rats did make a direct plaque-forming cell (PFC) response to sheep red blood cells (SRBC), the magnitude of this response was much lower than that of adult rats. LMS treatment (2.5 mg/kg) markedly potentiated the anti-SRBC response in 10-day-old rats, but this enhanced PFC response never attained adult levels. In contrast, LMS failed to boost the anti-SRBC response of adult rats, although the adult response to suboptimal antigenic stimuli was enhanced. The ontogeny of immunological responsiveness to SRBC was not influenced by LMS; only existing responses could be modulated. The potentiating effect of LMS was dose-dependent, with high doses causing suppression. The influence of LMS did not involve the earlier appearance of PFC. Since LMS augmented the PFC response to SRBC when administered before or after antigen, it appears that both the inductive phase and the proliferative phase of antibody production can be modulated. Finally, the PFC responses to a more thymus-independent antigen (2,4,6-trinitrophenyl-Ficoll) was boosted, suggesting that LMS may be capable of directly influencing B lymphocytes. These findings indicate that the functional immunodeficiency of the neonatal antibody response can be improved by LMS treatment.

Adjuvants, Immunologic↗
PubMed1981

Type III group B streptococcal strain differences in susceptibility to opsonization with human serum.

Human serum opsonins to type III Group B streptococci (GBS) were studied in an in vitro opsonophagocytic assay. Two type III GBS test strains were susceptible (893 and IIINor) and two resistant (891 and 892) to opsonization by the majority of sera from 15 healthy adults. Four individuals with undetectable or low opsonic titers to the test strains were immunized with pneumococcal vaccine; immunization with pneumococcal vaccine induced a titer rise in all but one instance when susceptible GBS strains were tested. In contrast, only a single titer rise was detected when resistant GBS strains were employed in the test. These results indicate that immunization with a cross-reacting antigen (identical to core antigen of type III GBS) fails to induce opsonic antibody to all strains of type III GBS. A resistant strain was made highly susceptible to neutrophil killing in vitro by exposure to neuramindase prior to incubation with opsonic serum. Using a fluorescent lectin-binding assay, this enzyme appeared to remove surface sialic acid, suggesting that sialic acid is an antiphagocytic factor. However, the possibility that other surface moieties may act as antiphagocytic factors cannot be ruled out. Both opsonic susceptible and resistant strains absorbed opsonic antibody from serum, which suggests that the GBS antiphagocytic factors do not prevent binding of antibody to resistant bacteria. These findings indicate that demonstration of serum opsonic activity to one strain of type III GBS may not accurately depict opsonic activity to other strains. In addition, immunization with core antigen did not enhance opsonic activity against all GBS strains. These data also point out the need to use assays which measure functional antibody, since demonstration of antibody binding may not reflect its ability to facilitate bacterial phagocytosis and killing.

Adult↗
PubMed1980

Diminished bacterial defences with intralipid.

'Intralipid', a lipid emulsion used in parenteral nutrition, impaired bacterial clearance and enhanced bacterial virulence in mice. In addition it inhibited the chemotaxis of human neutrophils in vitro. Intralipid may enhance the risk of bacterial sepsis in certain patients.

Animals↗
PubMed1980

Pulmonary paragonimiasis in childhood. A cause of persistent pneumonia and hemoptysis.

A 4-year-old Filipino girl, a recent immigrant to Hawaii, had hemoptysis, and a chest roentgenogram disclosed diffuse infiltrates of the right lung. Microscopic examination of a morning gastric aspirate showed numerous golden-brown, operculated ova, and microscopic examination of sputum and stool specimens confirmed these ova to be those of the lung fluke, Paragonimus westermani. She responded favorably to bithionol therapy and was asymptomatic and growing normally 2 1/2 years after therapy.

Bithionol↗
PubMed1980

Acute and cutaneous toxicity of beta-chlorovinyl ketones and aldehydes in rodents.

The acute toxicity (LD50, intraperitoneal in the mouse) of beta-chlorovinyl ketones and aldehydes used as intermediates for organic syntheses was determined and their action on the skin of rodents investigated. Ketones of the type Cl-CH-CH-COR prove to be relatively toxic and display a markedly necrotic action after percutaneous absorption. In comparison with this the isomeric aldehydes Cl-CR-CH-CHO have a lower acute and less markedly cutaneous toxicity. As therapeutic counter action after skin contamination by beta-chlorovinyl carbonyl compounds the immediate treatment with an aqueous ethanolic solution of hexamethylenetetramine is recommendable.

Administration, Topical↗
PubMed1980

Decreased phytohemagglutinin-induced aggregation and C5a-induced chemotaxis of human newborn neutrophils.

Phytohemmagglutinin (PHA)-induced lectin aggregation, chemotactic response to C5a, and random migration were measured on paired samples of neutrophils obtained from human peripheral blood and cord blood of normal newborn infants. The mean aggregation rate (+/- 1 SD) of adult neutrophils with PHA was 16.8 +/- 4.4 vs. 12.0 +/- 3.6 for newborn neutrophils (P less than 0.005), and the mean percent aggregation of adult neutrophils was 56.2 +/- 9.2 vs. 45.6 +/- 8.3 for newborn neutrophils (P less than 0.005). Exposure to newborn plasma had no affect on adult neutrophil aggregation. Whereas vinblastine (VBL) decreased both the percent and rate of PHA-induced adult neutrophil aggregation, only the rate of newborn neutrophil aggregation was reduced by VBL. Newborn neutrophil chemotactic response to C5a, was reduced by 80% (P less than 0.0025), and showed a positive correlation with percent PHA-induced aggregation (r = 0.6037, P less than 0.05). On the other hand, random migration was not significantly reduced and did not correlate with PHA-induced aggregation. These observations suggest that the decreased chemotactic responsiveness of newborn neutrophils may be due to developmental membrane differences which adversely affect the number and/or availability of C5a resceptors. Lectin-induced aggregation studies of other chemotactic defects may identify similar differences.

Cell Aggregation↗