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Biomedical subjects

R E Baughn

Publications and source records attributed to R E Baughn.

At least 55 records · Page 3Linked to original sources
PubMed1988

The effect of dietary fish oil supplementation on psoriasis. Improvement in a patient with pustular psoriasis.

An open study testing the effects of fish oil supplementation on psoriasis in 26 patients is described. None of the patients with plaque-type psoriasis vulgaris showed clinically significant improvement; however, a patient with generalized pustular psoriasis showed marked improvement with the fish oil supplementation. In this patient, scale leukotriene B4 levels were determined and shown to be significantly decreased after completion of the study, but the leukotriene B4 levels did not correlate with her clinical course. The results of our study are contrasted with those of a recent study that did show beneficial effects of fish oil supplementation on plaque-type psoriasis.

Adult↗
PubMed1988

Recognition of Treponema pallidum antigens by IgM and IgG antibodies in congenitally infected newborns and their mothers.

Immunoblotting techniques were used to examine the proteins of Treponema pallidum recognized by IgM and IgG antibodies in sera from infants with congenital syphilis and their mothers. Infected infants' serum IgM reactivity to treponemal antigens differed from that of control infants born to normal, serofast, and biologic false-positive mothers. Each of the infected infants' sera exhibited IgM reactions to the 47- and 37-kilodalton (kDa) proteins of T. pallidum. Although rheumatoid factor was detected in the sera of half of the infected infants, removing this factor did not alter the pattern of IgM blots. IgG reactions in infants were almost exclusively of the IgG1 and IgG3 subclasses and mirrored those of the mother, except for IgG1 and IgG3 reactions to the 83-kDa treponemal protein, which were unique to infants' sera. Our results suggest that the findings of IgM antibody directed against the 47- or 37-kDa antigens of T. pallidum may help to diagnose congenital syphilis at birth.

Antigens, Viral↗
PubMed1988

Characterization of the components in circulating immune complexes from infants with congenital syphilis.

Immunoglobulin class-specific Clq-solid-phase assays were used to detect circulating immune complexes in the sera of infants with congenital syphilis. Elevated levels of IgM complexes were present in the sera of all infants with overt disease and in two of 14 asymptomatic infants considered to be "at risk." The sera of infants born to normal, serofast, and biologic false-positive mothers did not contain immune complexes. Immunoblotting techniques revealed that complexes isolated from the sera of the infected infants contained endogenous host antigens, as well as a limited number of treponemal polypeptides. Consistent with earlier findings examining purified immune complexes from adults with secondary syphilis and from infected animals, an 83-kilodalton Treponema pallidum antigen was present in all of the isolated complexes from infants with congenital syphilis. Our findings emphasize the fact that current serological and clinical measures of infection are inadequate and that certain "at risk" infants should be treated despite normal cerebrospinal findings and the absence of clinical manifestations.

Antigen-Antibody Complex↗
PubMed1988

Vaccination of 18-month-old children with conjugated polyribosyl ribitol phosphate stimulates production of functional antibody to Haemophilus influenzae type b.

Eighteen-month-old children were immunized with polyribosyl ribitol phosphate (PRP) of Haemophilus influenzae type b or with PRP that had been conjugated to diphtheria toxoid. Conjugated vaccine stimulated significant mean increases in antibody titer as measured by radioimmunoassay and bactericidal effect, as well as a modest increase in opsonizing activity. In contrast unconjugated vaccine caused lesser albeit significant rises in antibody titer, but a negligible antibacterial effect. These results suggest that vaccinating infants with conjugated PRP is more likely to stimulate production of antibodies that are protective against systemic infection caused by H. influenzae type b than vaccinating with unconjugated PRP.

Antibodies, Bacterial↗
PubMed1988

Rabbit model of disseminated syphilis: immunoblot and immunohistologic evidence for a role of specific immune complexes in lesion pathogenesis.

Circulating immune complexes (CIC) containing Treponema pallidum proteins have been preliminarily implicated as inducers of a neutrophilic vascular reaction in early human cutaneous lesions of secondary syphilis. To clarify the role of specific CIC in producing cutaneous and renal lesions, 12 rabbits were studied at the following intervals after induction of disseminated syphilis: 20 days (4 rabbits: biopsies of normal and lesional skin for direct immunofluorescence (IMF) for (IgG, IgM, IgA, Clq, C3, C4), fibrin, and T. pallidum proteins; routine histology; and immunoblots of serum for CIC containing T. pallidum proteins); 21 days (4 rabbits: as at 20 days without IMF for T. pallidum protein); 23 days (4 rabbits: as at 20 days without IMF); 30 days (same 12 rabbits restudied with routine histology of normal and lesional skin; kidneys from 4 rabbits removed for routine, IMF, and electron microscopy (EM). Treponemal polypeptide antigen (MW-87 kd) was demonstrated in CIC from rabbits. Routine cutaneous histology showed evolution of lesions from an early neutrophilic vascular reaction to the typical lymphoplasmacytic reaction. IMF showed vessel-based immunoreactants in 3 of the 4 rabbits tested at 20 days and 1 of 4 at 21 days, and T. pallidum proteins in 3 of 4 rabbits at 20 days. Routine histology, IMF, and EM studies of glomeruli showed glomerular abnormalities, but no evidence of immune deposits containing specific T. pallidum protein. Skin and kidney studies of 4 controls were all negative. These data indicate a role for specific immune complexes in the pathogenesis of cutaneous lesions in this rabbit model.

Animals↗
PubMed1987

Humoral response in Treponema pallidum-infected guinea pigs. II. Circulating immune complexes and autoimmune responses.

Guinea pigs of inbred strain 2 and of a strain deficient in complement component 4 (C4D) responded to intradermal infection with Treponema pallidum by production of antibodies to treponemal antigens, normal rabbit serum proteins, fibronectin, and creatine kinase and with formation of circulating immune complexes (IC). IC started to appear at low concentrations 1 mo after infection and increased between 3 and 5 mo post-infection. Antibodies to fibronectin appeared after the second month but were not detectable 30 days later. Antibody activity to creatine kinase was detectable at the fourth month and became significantly higher at 5 mo post-infection. Reinoculation with a dose similar to that used for primary infection caused a significant increase in all antibodies and IC. Dissociation products of IC formed after primary infection consisted predominantly of treponemal antibodies and antigens, whereas IC detected after reinfection consisted predominantly of antibodies and normal rabbit serum proteins. Antibodies to fibronectin and creatine kinase are considered autoantibodies, and the underlying mechanism responsible for their production in syphilis is discussed.

Animals↗
PubMed1986

Characterization of the antigenic determinants and host components in immune complexes from patients with secondary syphilis.

Sera from patients with secondary syphilis were evaluated for abnormal levels of circulating immune complexes (IC), immunoglobulins (Ig), and complement components. Clq-solid-phase assays (Clq-SPA) that made use of monoclonal and polyclonal antibodies directed against IgG subclasses indicated that human IC were composed primarily of IgG3 and IgG1; these findings appeared consistent with subclass profile responses of electrophoretically transferred blots (Western blots) of Treponema pallidum reacted with syphilitic sera. Complexes were isolated from reactive sera by polyethylene glycol precipitation followed by either anti-Clq column chromatography or protein A-Sepharose chromatography. Although qualitative and quantitative differences were noted, all purified materials contained a treponemal polypeptide antigen with a m.w. of approximately 87,000. Subsequent analysis of this polypeptide, which was also present in purified IC from rabbits with experimental syphilis, suggests that it may represent the fibronectin receptor of the organism. The 76,000 and 66,000 materials, earlier identified in purified rabbit IC, appeared to represent C-terminal degradation products of fibronectin presumably of host origin, rather than treponemal antigens. Although fibronectin binds avidly to Clq and could represent a co-precipitable contaminant throughout the isolation procedure, anti-fibronectin antibodies in the sera of patients detectable by radioimmunoassay and the present of antibodies to 76,000 and 66,000 dalton fibronectin fragments in the globulin fractions of disassociated complexes argues against such a conclusion.

Adolescent↗
PubMed1986

Role of circulating immune complexes in human secondary syphilis.

Studies in animal models and in the glomerulonephritis of human secondary syphilis and results from in vitro assays have suggested a role for circulating immune complexes (CICs) in human secondary syphilis. Nine adult subjects with early secondary syphilis were studied. All patients tested had CICs on C1q-binding or Raji cell assays. Proteins previously described as Treponema pallidum-specific antigens were detected by radioimmunoblot techniques in CICs from all five subjects tested. Biopsy of early cutaneous lesions revealed immunoreactants (IgG, C3, and/or C1q) in three of nine subjects and treponemal antigen in six of eight subjects tested. Histamine was injected intradermally as a trap for CICs, and biopsy of these injection sites revealed immunoreactants in four of nine subjects and treponemal antigen in five of eight subjects tested. A neutrophilic vascular reaction consistent with CIC-mediated vessel damage was seen in three of nine lesions and six of nine histamine injection sites. Normal controls did not show these changes.

Antigen-Antibody Complex↗
PubMed1986

Natural and vaccine-related immunity to Streptococcus pneumoniae.

To investigate the protective effects of pneumococcal vaccine, we assayed serum from healthy adults and from elderly bronchitics for antibody and opsonic activity against nine serotypes of S. pneumoniae. Before vaccination, there was no relation between opsonization and the level of antibody measured by RIA. Some serotypes were well opsonized in the absence of detectable antibody to capsular polysaccharide; others were not, despite modest levels of antibody. These in vitro studies did not support the concept that a certain level of antibody (e.g., greater than or equal to 250 ng of antibody nitrogen/ml) was specifically associated with the capacity to opsonize pneumococci. Nearly all postvaccination sera had increased antibody and opsonic activity against all serotypes, but the lack of correlation in any individual serum persisted. RIA showed that pre- and postvaccination levels of antibody in elderly adults with chronic lung disease were similar to those of younger adults. In elderly bronchitics, opsonizing activity for six of the nine serotypes was lower after vaccination, a result of suggesting a possible explanation for the failure of pneumococcal vaccine to be fully protective in these subjects. Elderly subjects had higher levels of antibody to phosphocholine, but when isolated, this antibody did not opsonize any of the vaccine strains of pneumococci. These results suggest that alternative strategies are needed to maximize the protective effect of pneumococcal vaccine in the population at greatest risk.

Adult↗
PubMed1986

Antibody-independent interactions of fibronectin, C1q, and human neutrophils with Treponema pallidum.

Although recent evidence suggests that fibronectin may be involved in the attachment of treponemes to mammalian cells, its possible role in promoting phagocytosis of Treponema pallidum has not been investigated. In the present study, we examined the antibody-independent interactions of fibronectin, C1q, and human polymorphonuclear leukocytes with T. pallidum. Binding of [125I]fibronectin was specific and saturable with an affinity constant of approximately 2 X 10(7) M-1. The number of binding sites per treponeme at 37 degrees C, irrespective of the mammalian source of fibronectin, was between 2,500 and 7,500, with a mean of approximately 4,700. Binding of [125I]C1q to T. pallidum, in the absence of antibodies to the organism, also was saturable and specific. Pretreatment of treponemes with C1q enhanced binding of soluble [125I]fibronectin two- to threefold and also increased attachment of 125I-surface-labeled treponemes to fibronectin-coated surfaces. Treatment of 125I-labeled T. pallidum with fibronectin alone, or together with C1q, however, did not enhance surface phagocytosis by neutrophils.

Bacterial Proteins↗
PubMed1986

Emergence of bactericidal and opsonizing antibody to Vibrio vulnificus following bacterial infection.

Virulent isolates of Vibrio vulnificus resist the bactericidal and opsonizing effects of normal human serum, in contrast to environmental isolates, which are highly serum susceptible. Immune responses to bacteremic V. vulnificus infections in human subjects have not been characterized. Serum from a patient who survived sepsis caused by V. vulnificus had substantial bactericidal and opsonizing immunoglobulin G (IgG) for his own bloodstream isolate. Killing was mediated by the classical complement pathway, whereas opsonization was effected by either the classical or the alternative pathway. IgG that reacted strongly with 55-, 58-, and 68-kilodalton outer membrane proteins was present in the patient's convalescent-phase serum but was absent from normal human serum. These findings suggest that humoral immunity to V. vulnificus, mediated by bactericidal and opsonizing antibody, emerges during infection and may be due, in part, to IgG directed against identifiable outer membrane proteins.

Antibodies, Bacterial↗
PubMed1985

Outer membrane proteins of nontypable Haemophilus influenzae and reactivity of paired sera from infected patients with their homologous isolates.

Normal human serum and acute or convalescent serum from patients infected with nontypable Haemophilus influenzae were tested for reactivity with electroblotted outer membrane proteins obtained from the homologous nontypable H. influenzae isolates. Of 12 patients, 8 had immunoglobulin G antibodies to outer membrane proteins from their own infecting nontypable H. influenzae isolates that were not present in normal human serum. Three patients had immunoglobulin antibody in convalescent serum that had been absent in acute serum, but no consistent outer membrane protein was involved in the sets of patient sera with outer membrane proteins examined.

Antibodies, Bacterial↗
PubMed1985

Radioimmunoassays for the detection of antibodies to treponemal polypeptide antigens in serum.

Cross-reacting treponemal antigens are potentially important candidates for serodiagnostic assays in syphilitic infections. Based on the idea that the organelles for locomotion in virulent and avirulent treponemes might be composed of similar subunits, we attempted to purify the flagellar antigens of Treponema phagedenis biotype Reiter and Treponema refringens for use in radioimmunoassays. With a combination of physical and chemical methods, the major protein subunit of purified flagellar preparations exhibited a mass of approximately 37 kilodaltons (kd) on sodium dodecyl sulfate-polyacrylamide gels. These 37-kd materials, with weight estimates comparable to those of other flagellin molecules, were further purified by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroelution. Human and rabbit sera, alone or subjected to DEAE Affi-Gel blue chromatography, were subsequently tested in radioimmunoassays employing each of the purified preparations. Even though sera from patients with secondary syphilis and from experimentally infected animals at 3 to 4 weeks postinfection were reactive in radioimmunoassays employing the 37-kd flagellar antigens, the assays were relatively insensitive for detection of immunoglobulin G responses in the early stages of human infection. Detection of immunoglobulin G antibodies in sera obtained early in the course of natural or experimental infection was possible with electroeluted 33- to 64-kd materials from both avirulent and virulent treponemes.

Animals↗
PubMed1984

Evaluation of Sch 29482 in experimental syphilis and comparison with penicillin G benzathine in disseminated disease and localized infection.

The present study was designed to assess the in vivo activity of Sch 29482, a new penem antibiotic, against disseminated and localized Treponema pallidum infections in rabbits. Animals were inoculated either intravenously or intradermally. Randomized groups then received 25 or 50 mg of Sch 29482 per kilogram of body weight twice a day for 7 days, two weekly injections of 200,000 U of penicillin G benzathine for comparative purposes, or no antibiotic therapy. In both infection models, striking differences were noted between the untreated control rabbits and rabbits receiving penicillin G benzathine or high-dose Sch 29482. Intravenously infected rabbits did not develop disseminated lesions or orchitis, and chancres produced by intradermal infection regressed and healed rapidly after both treatment regimens. Infectivity studies also suggested that high-dose Sch 29482 and penicillin G benzathine were effective since the testes and lymph nodes of treated animals were free of infectious organisms. Treatment of animals with the lower dose of Sch 29482 represented borderline or suboptimal therapy, with a failure rate of one in four for each infection model.

Animals↗
PubMed1984

Immunoglobulin A from bronchopulmonary secretions blocks bactericidal and opsonizing effects of antibody to nontypable Haemophilus influenzae.

Patients with chronic bronchitis are colonized by and may develop acute bronchopulmonary infection due to nontypable Haemophilus influenzae (NTHI) despite the presence of bactericidal and opsonizing antibody to the infecting organism. To test the hypothesis that secretory immunoglobulin A (IgA) interferes with host defense mechanisms, we extracted secretory IgA from bronchopulmonary secretions of five patients with NTHI pneumonia. NTHI was incubated with IgA before or during incubation with each patient's own serum or normal human serum. IgA from four of these individuals blocked the bactericidal and opsonizing effects of normal human serum and/or their own serum against their own and/or other NTHI. IgA from bronchopulmonary secretions of patients not infected with NTHI or from the serum of a patient with an IgA myeloma had no such effect. Blocking appeared to result from a direct interaction between IgA and the bacteria. The presumed mechanism is an interaction with bacterial surface antigens, although it is not known whether this occurs at antigenic sites responsible for bactericidal and opsonizing activity or whether interaction with adjacent antigenic sites and subsequent steric interference is responsible. This blocking effect of IgA may be one mechanism that allows for the development of NTHI colonization or pneumonia in an individual who already has seemingly adequate antibody against the infecting organism.

Antibodies, Bacterial↗
PubMed1983

The interaction between Treponema pallidum and human polymorphonuclear leukocytes.

The interaction between polymorphonuclear leukocytes (PMNLs) and Treponema pallidum was studied. Intradermal injection of greater than or equal to 10(6) T. pallidum into rabbits caused a rapid accumulation of PMNLs. Human serum released chemotaxigenic factor (C5a) during incubation in vitro with T. pallidum. Incubation of T. pallidum with human PMNLs in vitro (ratio, 100:1) stimulated chemiluminescence. These responses were dependent upon the presence of both antibody and complement and were greatest when serum from a patient with late secondary syphilis was used as a chemotaxigenic source or for opsonization. Electron microscopic studies documented the rapid uptake of T. pallidum into membrane-bound vacuoles in the human PMNLs in vitro after incubation for as little as 5 min, with leukocyte degranulation and loss of treponemal integrity observed after 4 hr. T. pallidum were found within PMNLs 3 hr after intradermal inoculation of rabbits. These data show that PMNLs are attracted to, and appear to ingest, T. pallidum, but they fail to explain why inoculation of these organisms is not followed by eradication.

Animals↗
PubMed1983

Opsonizing and bactericidal effects of normal human serum on nontypable Haemophilus influenzae.

The observation that nontypable (NT) Haemophilus influenzae causes serious infection in adults has stimulated interest in mechanisms that may protect the human host against NT H. influenzae infection. Incubating NT H. influenzae with normal human serum (NHS) caused dose- and time-dependent killing that varied with the individual NHS and NT H. influenzae. Adsorption of NHS with NT H. influenzae removed bactericidal activity against the adsorbing isolate but not necessarily that against others, suggesting antigenic diversity and supporting recent studies that show different outer membrane protein profiles among NT H. influenzae. Heating NHS to 56 degrees C for 30 min abolished bactericidal activity; this activity was not restored by complement-rich guinea pig serum or NT H. influenzae-adsorbed NHS. This is analogous to the "third factor" needed for intraleukocytic killing of pneumococci. Optimal opsonization of NT H. influenzae for phagocytosis by human polymorphonuclear leukocytes required antibody and complement, but other serum factors also played a role. Bactericidal activity generally, but not uniformly, correlated with opsonizing activity of individual NHS. Humoral factors may be important in host defenses against NT H. influenzae infection; their emergence during convalescence warrants further study.

Blood Bactericidal Activity↗