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Biomedical subjects

K Wicher

Publications and source records attributed to K Wicher.

At least 19 recordsLinked to original sources
PubMed1992

Experimental congenital syphilis: guinea pig model.

Neonates born to female guinea pigs of either a highly susceptible (C4D) or a resistant (Albany) strain, infected prior to or during pregnancy with a single dose of Treponema pallidum, showed in their sera from the first day of life immunoglobulin M (IgM) antibodies to T. pallidum, circulating immune complexes consisting of IgM antibodies and treponemal antigens, and IgM rheumatoid factor. Although the animals were asymptomatic for a 6-month observation period, several lines of evidence indicated that they were infected in utero. Molecular analysis of whole sera, purified serum IgM fraction, or dissociated immune complexes demonstrated IgM reactivity against one (47 kDa) or more of several T. pallidum peptides (15, 17, 37, 42, 45, and 87 kDa) recognized as integral membrane components. Sequential analysis of the neonates' sera by immunoblot and enzyme-linked immunosorbent assay, using alcohol-treated T. pallidum, T. phagedenis biotype Reiter, and T. vincentii, demonstrated early IgM antibodies followed 3 to 4 months later by IgG2- and IgG1-specific antibodies to T. pallidum. Moreover, an infectivity test done in five rabbits with pooled tissue extracts prepared from liveborn or stillborn animals evoked a seroconversion in two rabbits (reactive Venereal Disease Research Laboratory and fluorescent treponemal antibody tests), suggesting the presence of T. pallidum in the organs. Sera from neonates born to either T. phagedenis biotype Reiter-injected mothers or three normal pregnant females were all serologically negative. The model offers new possibilities for exploration of factors responsible for asymptomatic infection often observed in human congenital syphilis.

Animals↗
PubMed1992

Effect of passive immunization with purified specific or cross-reacting immunoglobulin G antibodies against Treponema pallidum on the course of infection in guinea pigs.

Whole immune serum or highly purified immunoglobulin G (IgG) antibodies to Treponema pallidum exhaustively adsorbed with three strains of nonpathogenic treponemes (TPI-IgG) were used for passive immunization of inbred strain 2 guinea pigs before and after intradermal challenge with 3.4 x 10(7) virulent T. pallidum Nichols organisms. Before challenge, control animals received a similarly purified IgG fraction containing either a cocktail of antibodies against three nonpathogenic treponemes (NPTI-IgG) or IgG prepared from normal guinea pig serum (NGPS-IgG). The purified fractions contained both IgG1 and IgG2 isotypes. The antibody levels (detected by fluorescent treponemal antibody test and enzyme-linked immunosorbent assay) and molecular specificities (immunoblot) of sera obtained from recipient animals before infection reflected those of the purified fractions used for immunization. Three protocols of passive immunization were used. Whole immune serum containing specific and cross-reacting antibodies afforded better protection than TPI-IgG even though asymptomatic animals were not fully protected. A single intradermal injection (0.1 ml) of TPI-IgG or NPTI-IgG into one hind leg 22 h before infection at the same site provided relatively higher protection than multiple intravenous injections (total, 15 ml) of the respective individual preparations. Since purified NGPS-IgG injected in the same animals, into the opposite hind leg, failed to protect against the challenging infection, it is reasonable to assume that specific and cross-reacting antitreponemal antibodies of the IgG1 subclass, which in guinea pigs are homocytotropic, play a relevant role in local protection.

Animals↗
PubMed1992

Detection of Treponema pallidum in early syphilis by DNA amplification.

By using experimentally infected rabbits as a model for early syphilis, the applicability of in vitro DNA amplification was explored for detection of Treponema pallidum. It was determined that whole blood in heparin or EDTA (but not serum), lesion exudate, and punch biopsy as well as swabs of lesions are useful specimens for examination by the polymerase chain reaction. Swabs do not require special diluents, and the specimens, whether kept at room temperature or frozen, are well suited for use in the polymerase chain reaction.

Animals↗
PubMed1992

Hepatic lesions in rabbits infected with Encephalitozoon cuniculi administered per rectum.

Microsporidia have been recognized recently as opportunistic pathogens in acquired immunodeficiency syndrome patients. In an attempt to develop an animal model of enteric microsporidiosis, adult (5 to 6 months old) male Flemish Giant rabbits from a closed New York colony were administered 5 x 10(3), 5 x 10(5), and 5 x 10(7) Encephalitozoon cuniculi per rectum. Rabbits given 5 x 10(5) and 5 x 10(7) E. cuniculi had moderate granulomatous periportal infiltrates, characterized by the presence of numerous macrophages, epithelioid cells and a few multinucleated giant cells, lymphocytes, and plasma cells. Inflammatory cells also were seen infiltrating the tunica adventitia and tunica media of hepatic portal veins and branches of the hepatic artery. This study demonstrates that administration of E. cuniculi per rectum to rabbits results in infection that is characterized by high frequency and severity of hepatic lesions.

Administration, Rectal↗
PubMed1992

Production of rheumatoid factor in adoptively immune guinea-pigs after challenge with Treponema pallidum.

Guinea-pigs of inbred strains 2 and C4D were infused with various concentrations (1 x 10(8) to 4 x 10(8) of syngeneic nylon wool-purified Treponema pallidum-immune T lymphocytes (TPI-T) and challenged 24 hr later with virulent T. pallidum (10(8) organisms). The degree of protection depended on the number of infused T cells and was associated with an accelerated production of IgM rheumatoid factor (RF). Fully protected animals (4 x 10(8) TPI-T) did not produce treponemal antibodies or circulating immune complexes (CIC) but produced IgM RF detectable 10 days after infection. Partially protected animals (< or = 2 x 10(8) TPI-T) produced, 30 days post-infection, relatively low levels of treponemal antibodies but high levels of CIC and RF. Control animals infused with 2 x 10(8) TPI-T lymphocytes but not infected with T. pallidum, when monitored for a period of 6 weeks, did not produce treponemal antibodies, CIC, or RF, excluding the possibility that IgM RF could be generated by the donor's B cells contaminating (circa 3%) the TPI-T lymphocytes. Moreover, unprotected syngeneic control animals infused, prior to infection, with T. phagedenis biotype Reiter-immune T cells or with T. pallidum-free testicular inflammatory fluid-immune T cells responded with increasing levels of treponemal antibodies; only a few animals produced RF and CIC 5 months after infection similarly to control guinea-pigs infected only. The production of RF in partially protected animals responding to infection with treponemal antibodies and CIC was apparently associated with the presence of the CIC; but the mechanism of RF production in fully protected animals in which no antibodies or CIC were detected is currently unknown.

Animals↗
PubMed1992

Strain- and age-associated differences in lymphocyte phenotypes and immune responsiveness in C4-deficient and Albany strains of guinea-pigs.

Spleen lymphocytes from C4-deficient (C4D) and Albany strains of guinea-pigs, 1-7 days, 3-6 and 12-16 months old, genetically related to inbred strains 13 and 2 respectively, were analysed in terms of their expression of cell surface markers, allogenic and T- and B-cell mitogenic responses, and interleukin-1 (IL-1) and IL-2 production. There were strain- and age-associated differences in phenotypic expression and immune responsiveness levels. In both strains a significant shift in immunocompetence apparently occurs postnatally before 3-6 months of age, with no further significant changes noticed in animals 12-16 months old. Phenotypic changes in cell surface markers did not always correlate with functional capability of lymphoid cells. H159+ (pan T) and H155+ (CD4) lymphocyte number and levels of T-cell responsiveness (mitogenic and allogenic responses, and IL-2 production) were higher in C4D neonates compared with age-matched Albany guinea-pigs or with young animals of the same strain. On the other hand, 31D2+ (B) lymphocytes in a significantly higher proportion in Albany neonates compared with similarly aged C4D, did not correlate at this age or at any other time with their proliferative response to lipopolysaccharide (LPS) or dextran sulphate (DS), two B-cell-specific mitogens.

Aging↗
PubMed1991

Immunization of guinea pigs with recombinant TmpB antigen induces protection against challenge infection with Treponema pallidum Nichols.

Treponema pallidum-susceptible guinea pigs of strain C4D were immunized with recombinant T. pallidum antigens TmpA, TmpB, TmpC, and TmpA plus TmpB plus TmpC; with Escherichia coli membranes; or with adjuvant alone. Animals in groups of five received six immunizing injections, each of 100 micrograms of antigen incorporated in RIBI adjuvant. After the sixth immunization, all experimental and nonimmunized controls were intradermally challenged with 3 x 10(6) T. pallidum Nichols freshly extracted from infected rabbit testes. Although high titers of antitreponemal antibodies in the fluorescent-treponemal-antibody test or an enzyme-linked immunosorbent assay were evoked in all animals immunized with recombinant antigens, only guinea pigs receiving TmpB antigen demonstrated protection expressed by the development of significantly (P less than 0.01) smaller, atypical lesions of significantly (P less than 0.01) shorter duration and devoid of or containing fewer T. pallidum organisms than lesions in the remaining immunized and control animals.

Animals↗
PubMed1991

Enteric infection with an obligate intracellular parasite, Encephalitozoon cuniculi, in an experimental model.

Rabbits were intrarectally infected with 3 doses (5 x 10(3), 5 x 10(5), and 5 x 10(7] of an obligate intracellular parasite, Encephalitozoon cuniculi, with or without prior colonic lavages. Although chronic administration of enemas seems to interfere to some degree with the intestinal translocation of the parasite, systemic infection was observed in both manipulated and nonmanipulated animals. The animals responded with antibodies of immunoglobulin A (IgA) and IgG isotypes, reflecting the route of infection. They also produced significant amounts of circulating immune complexes composed of IgA and IgG antibodies and E. cuniculi antigens. Lesions compatible with encephalitozoonosis were seen in the liver, kidney, lung, and brain. In all instances, nonmanipulated animals had more severe lesions than manipulated rabbits given the same dose of parasites. Levels of serum antibodies, circulating immune complexes, and histopathologic changes were associated with the infection dose. The presented data suggest that human microsporidiosis may also be transmitted via the rectal route. It is, therefore, of clinical relevance in view of several reports of microsporidian infections in patients with acquired immunodeficiency.

Administration, Rectal↗
PubMed1991

Pathogen-specific humoral response in Treponema pallidum-infected humans, rabbits, and guinea pigs.

Molecular analysis of the humoral response to pathogen-specific polypeptides was done using sera from patients at different stages of syphilis and sera from Treponema pallidum-infected rabbits and guinea pigs collected at various times after infection. The sera were examined by ELISA, fluorescent treponemal antibody absorption test (FTA-ABS), and immunoblot before and after sequential adsorption with cyanogen bromide-activated Sepharose 4B coupled individually to five sonicated nonpathogenic treponemes. Guinea pig antisera were also adsorbed with rabbit proteins. After adsorption, sera from all three species reacted neither by ELISA nor by immunoblot with nonpathogenic treponemes, nor did guinea pig sera react with rabbit proteins. Regardless of the species of treponema used for initial adsorption, none by itself could effectively remove all cross-reactivities. Nine pathogen-specific polypeptides (15, 17, 33, 37, 39, 43, 45, 47, 97 kDa), eight (15-47 kDa) known as integral membrane or endoflagellar components, were commonly recognized by the tree species when chancre immunity developed. The substantial reduction in immune reactivity after adsorption suggests that most of these peptides consist of specific and common treponemal epitopes. Throughout the various stages of the human disease, pathogen-specific antibodies were exclusively of the IgG isotype.

Animals↗
PubMed1990

Experimental neonatal syphilis in a susceptible (C4D) and a resistant (Albany) strain of guinea pig.

Despite similar levels of natural antibodies and treponemicidal activity, 83% of fourth complement component-deficient (C4D) mother guinea pigs developed ulcerative lesions to a challenge of 5 x 10(7) Treponema pallidum, whereas 75% of offspring 1 to 5 days old were temporarily (2-3 months) resistant to development of dermal lesions. In contrast, only 17% of Albany-strain mothers developed small papular lesions, while 68% of 1- to 5-day-old newborns developed large papular or ulcerative lesions within 9-15 days postinfection. These findings, together with the late development of both dermal lesions and antibodies in C4D neonates, preclude the concept of an antibody-associated natural resistance. T. pallidum infection in either C4D or Albany neonates was not associated with depletion of any particular cell population in lymphoid tissue. However, marked age- and strain-dependent histologic differences were noted. Histologic examination of lymph nodes and spleens from 17-day-old and 3- to 4-month-old animals showed that maturation of lymphoid tissues in C4D animals lagged behind the Albany strain at either age. Moreover, 75% of C4D newborns contained significantly higher levels of immunomodulatory alpha 1 fetoprotein than Albany neonates. The possibility that differences in susceptibility to T. pallidum infection between C4D and Albany guinea pigs as neonates and again as adults is the result of genetically associated changes in immunologic recognition is discussed.

Animals↗
PubMed1990

Immunocompetence of inflammatory cells in rabbit testes infected with Treponema pallidum.

Systematic studies were conducted in rabbits to delineate factors favoring the predilection for multiplication of T. pallidum in testes. The results strongly suggest that, in addition to the mucoid material produced during lesion development regardless of the site of infection, a whole array of testicular substances with immunomodulatory activity may largely contribute to the propagation and delayed clearance of the pathogen from the testicular environment and most likely from the host.

Animals↗
PubMed1990

Autoimmunity in syphilis.

The autoimmune response in natural and experimental syphilis, apparently triggered as a secondary reaction to T. pallidum infection, is represented by the production of various antibodies to self-antigens. In addition to the classic Wassermann (cardiolipin) antibodies, the following autoantibodies are associated with the disease: (1) biphasic hemolysin (known also as Donath-Landsteiner antibody), (2) antilymphocytic antibodies, (3) rheumatoid factor, (4) cryoglobulins, (5) antifibronectin, (6) anticollagen, (7) antilaminin, and (8) anticreatine kinase. Although less explored, the autoimmune reaction seems also to involve the cellular arm of the immune response. Transient sensitization of lymphocytes to homologous organ antigens have been reported in T. pallidum-infected rabbits. Questions of whether the humoral and cellular autoimmune responses--which are apparently harmless and of transient nature--play a role in immunoregulation and consequently affect the course of infection remain to be answered.

Animals↗
PubMed1989

Treponema pallidum-immobilizing antibodies in guinea pig experimental syphilis.

Treponema pallidum-immobilizing (TPI) antibodies were examined in intradermally infected inbred strain 13 and adoptively immune inbred strain 2 guinea pigs. Both strains of animals produced TPI antibodies at or after 90 days of infection. TPI antibodies were not associated with the protective mechanism(s) operative after challenge in adoptively immune animals.

Animals↗
PubMed1989

Immunogenicity of three recombinant Treponema pallidum antigens examined in guinea pigs.

The immunogenicity of recombinant treponemal antigens TmpA, TmpB and TmpC incorporated in RIBI adjuvant and injected into inbred strain 2 guinea pigs has been examined. The immune status of these animals has been challenged by infection with Treponema pallidum, Nichols. The immune response evaluated by the fluorescent-antibody test, microhemagglutination test and ELISA demonstrated high titers of antibodies to the T. pallidum antigens. The immunoblot analysis proved that the antibodies were directed to the 43-(Tmp A) 34- (Tmp B) and 35-kdalton (Tmp C) polypeptides. Antibodies cross-reacting with Treponema phagedenis biotype Reiter were, however, also detected. In spite of high titers of antibodies the animals were not protected against challenging infection with 10(8) organisms of T. pallidum.

Adjuvants, Immunologic↗
PubMed1989

Experimental syphilis in guinea pig.

The infrequent use of guinea pig in experimental syphilis, the not well genetically and immunologically characterized strains of animals originating from places with unspecified conditions of husbandry, and the various strains of Treponema pallidum used for infection provided inconsistent and discouraging results. For eight decades the rabbit has been the major animal model in studies of syphilis. However, the lack of readily available inbred strains of rabbits--necessary for adoptive transfer experiments--has been a stumbling block in revealing the mechanisms responsible for immunity, susceptibility, and resistance to T. pallidum infection. These difficulties have recently been overcome by demonstration of inbred strains susceptible to T. pallidum infection, paving the way to studies of adoptive immunity. The guinea pig may also be a better model than the rabbit for immunomanipulations (irradiation, injection with antibodies specific to various cell populations), allowing a closer insight into the immunopathologic mechanism operating during the course of syphilitic infection. The "rediscovery" of the guinea pig as a model for experimental syphilis and recent years of intensive studies justify a review summarizing older data and providing the most recent information. The authors, having first-hand experience with this model, will provide detailed information on (1) historical background; (2) course of infection with T. pallidum in inbred and outbred strains of guinea pigs; (3) the ID50 for various strains; (4) various routes of infection; (5) age and sex-dependent susceptibility to infection; (6) kinetic of the humoral response to specific and non-specific treponemal antigens; (7) appearance of autoantibodies and immune complexes; (8) cellular response, including lymphoproliferative response, macrophage inhibitory factor(s) production, chemotaxis and adoptive transfer of immunity by purified T cells; and (9) a complete list of references.

Animals↗
PubMed1989

Kinetics of pathogen-specific humoral response in Treponema pallidum-infected young and old inbred strain 2 guinea pigs.

The kinetics of the humoral response to pathogen-specific polypeptides was examined in Treponema pallidum-infected young (3-5 months old) and old (10-20 months old) inbred strain-2 guinea pigs. Sera collected before and at various times after infection were pooled and examined by immunoblotting and two serologic tests (ELISA and FTA) before and after sequential adsorption with CNBr-activated sepharose coupled to normal rabbit proteins and antigens from five nonpathogenic treponemal species. Prior to adsorption the kinetics of the humoral response to T. pallidum antigens did not seem to differ significantly between the two groups. After adsorption, however, a delay in the appearance of detectable antibodies and a milder response to various pathogen-specific polypeptides was observed in the older group. After adsorption, a sharp drop in ELISA-TP, ELISA-TR and FTA titres occurred in both groups. Six months post-infection, between 9 and 10 pathogen-specific polypeptides (97, 57, 47, 45, 43, 39, 37, 33, 17 and 15 kD) were recognized by both groups. The effect of age and levels of natural treponemal antibodies on the clinical symptoms of primary lesions and humoral response to pathogen-specific polypeptides is discussed.

Aging↗