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E Balish

Publications and source records attributed to E Balish.

At least 91 records · Page 5Linked to original sources

Pathogenesis of Campylobacter spp. in athymic and euthymic germfree mice.

Adult athymic (nu/nu) and euthymic (+/nu) germfree BALB/c mice were orally challenged with pure cultures of Campylobacter jejuni (human clinical fecal strains) and a human blood isolate of Campylobacter fetus subsp. fetus. After a period of adaptation to the mouse intestinal tract, all three C. jejuni strains caused disease in gnotobiotic mice. Mouse-adapted, weakly cytotoxic C. jejuni 45100 consistently induced disease symptoms (transient diarrhea, cecal shrinkage, and acute inflammatory changes with eosinophilia in the lower intestinal mucosa) in nu/nu mice 7 to 9 days after oral challenges. Conversely, no overt disease or histopathology was evident in +/nu mice challenged with the same strain (45100). After periods of adaptation in the murine alimentary tract, the two C. jejuni strains, 24 and INN 73-83, with greater cytotoxin-producing capacities, decreased cecal size and caused minor mucosal inflammatory changes in both nu/nu and +/nu BALB/c mice 1 to 2 weeks after intestinal colonization. A transient splenomegaly was also evident at 1 to 2 weeks after germfree nu/nu mice were colonized with each of the three C. jejuni strains used in this study. Occult blood was observed in a small percentage (approximately 11%) of nu/nu and +/nu BALB/c mice that were colonized with C. jejuni strains 45100 and INN 73-83. C. fetus subsp. fetus 255 colonized the alimentary tract of gnotobiotic mice, but neither morbidity nor mortality was evident. The disease we observed in the gnotobiotic mice, along with the histological changes in the intestinal tract after oral challenges, resembles symptoms of campylobacteriosis in humans. The gnotobiotic BALB/c mouse model of Campylobacter disease provides a unique opportunity to detail basic aspects of the acute and chronic pathogenesis of and immunity to this recently recognized disease.

Animals↗

Immune response of athymic and euthymic germfree mice to Campylobacter spp.

Pure cultures of several Campylobacter spp. induced a specific humoral immune response after they colonized and infected gnotobiotic mice; however, Campylobacter-immune mouse serum was not bactericidal (in vitro), manifested a weak agglutination reaction (in vitro), and showed specificity (strain 45100-immune mouse sera) for the homologous (infecting) Campylobacter strain, but was not able to passively protect germfree athymic (nu/nu) BALB/c mice against Campylobacter infection and diarrhea. Active immunization of germfree nu/nu mice with Formalin-killed C. jejuni also did not protect the gnotobiotic mice from Campylobacter infection and diarrhea. It appears from the results of our initial gnotobiotic studies that antibodies in serum against the infecting strain of C. jejuni may not play an essential role in resistance to Campylobacter disease in mice.

Animals↗

Antifungal therapy of dermatophytosis in guinea pigs and congenitally athymic rats.

Guinea pigs and athymic nude (RNU/RNU) rats were used to assess the efficacy of three orally administered antifungal agents--Tolciclate, Tolnaftate, and Ketoconazole--against Trichophyton mentagrophytes dermatophytosis. All three antifungal agents inhibited the test strain of T. mentagrophytes in vitro. Antifungal agents were tested in intervention (oral therapy started 5 days after challenge) or prophylaxis (oral therapy started 5 days before challenge) protocols. Oral treatment of dermatophytosis on guinea pig skin demonstrated that Tolciclate and Tolnaftate alleviated clinical symptoms and shortened the duration of the dermatophytosis, in comparison to nontreated controls. Assessment of antifungal efficacy in the guinea pig model was time consuming (30-35 days) and variability in the duration and severity of clinical symptoms on guinea pig skin was common. Oral therapy of chronically infected athymic rats demonstrated that Tolciclate, Tolnaftate, and ketoconazole were effective antifungal agents in vivo. Obvious improvement in clinical symptoms of dermatophytosis (i.e. less erythema and fewer lesions) was evident with all three antifungal agents within 10 days of starting oral therapy. By day 20, athymic rats that were treated with either Tolciclate or Ketoconazole showed marked clinical improvement of the chronic dermatophytosis. Chronically infected athymic rats, which lack thymus matured T-cells, are a promising new model to evaluate the efficacy of antifungal agents by culture, histology, and visual observations of clinical symptoms.

Administration, Oral↗

A quantitative in vivo assay for bacterial adherence to the urethra.

Bacterial adherence to urinary tract mucosal surfaces is thought to be the initiating event in ascending urinary tract infection. To study this process, we have developed a physiologic, quantitative, in vivo assay for bacterial adherence to the urethra. The effect of local (vaginal mucosa) immunization on the adherence of E. coli to the urethra was studied. Local immunization with a formalinized E. coli vaccine significantly reduced the capacity of viable cells of the immunizing strain to adhere to the urethra. Immunization-induced decrease in bacterial adherence to urethral mucosa is in agreement with our previous observations that immunization of the vaginal mucosa decreases the adherence of E. coli to the rat bladder. These data provide further evidence of a protective effect from local immunization against ascending urinary tract infection. No obvious change in indigenous urethral flora occurred after mucosal immunization.

Animals↗

Immunization against urinary tract infections.

Over the last few years there has been increasing emphasis placed on the importance of the role of bacterial adhesion, both in the initial stage and the clinical manifestations of urinary infection. It has been clearly demonstrated that all urinary infections are accompanied by an immunity response usually related in degree to the severity of the infectious lesion. Moreover, various in vitro and in vivo studies have demonstrated that bacterial adhesion to uro-epithelial cells can be inhibited immunologically. A study was conducted to analyze and compare results of different immunization procedures, in an animal model (female rat), on in vivo inhibition of adhesion to bladder epithelium of various bacterial strains. The bacteria selected were E. coli (075) and E. coli (06) with respectively a mannose-resistant (MR) hemagglutinin (HA) and a Klebsiella pneumoniae. The three immunization procedures were: intravaginal instillation, oral doses completed by intraperitoneal injection and subcutaneous administration. The instilled or injected antigen was made up of a formalized bacterial suspension emulsified in Freund's incomplete adjuvant: only the orally administered antigen was composed of live bacteria. Quantitative in vivo test of bacterial adhesion was by radioactive labelling of bacteria instilled into the bladder. Of the three immunization routes, only vaginal instillation significantly inhibited bacterial adhesion to bladder mucosa whatever the HA type involved. Furthermore, although E. coli (075), which possesses an HAMR, adhered more than E. coli (06) to the bladder wall, a marked and comparable inhibition of its adhesion was noted after immunization by the homologous (E. coli (075)) as by the E. coli (06) strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesiveness↗

The effect of microbial flora, diet, and age on the tumoricidal activity of natural killer cells.

This study examined the effects of diet (chemically defined vs natural-ingredient), age, and microbial flora on the tumoricidal activity of natural killer (NK) cells from the spleens of mice. Results from a 4-h 51Cr-release assay indicate the following: Germfree C3H/HeCr mice raised on a chemically defined diet had significantly greater NK cell activity than their germfree or "clean-conventional" (i.e., barrier-maintained) counterparts who were raised on a sterilized natural-ingredient diet. The NK activity of germfree mice was dramatically increased after their alimentary tract was colonized with a complex intestinal flora. Conventional mice raised under clean (barrier) conditions had significantly less NK cell activity than nonbarrier-maintained mice. Switching germfree mice from a chemically defined diet to a sterile natural-ingredient diet did not enhance NK cell activity. No significant differences in NK activity were evident with C3H/HeCr mice of different (6-10 wk vs 29-36 wk) ages. These results indicate that diet and microbial flora can modulate the NK cell activity of mice.

Aging↗

Enhanced immune response in the urinary tract of the rat following vaginal immunization.

The immune response in the rat urinary tract was assessed by an enzyme-linked immunosorbent assay for immunoglobulins following vaginal immunization and subsequent intravesical challenge with live E. coli 06. Vaginally immunized rats showed a strong and rapid bladder immune response following intravesical challenge, in contrast to nonimmunized control rats. The immune response was localized to the urinary tract in that antibody to E. coli 06 was not detected in serum, saliva and vaginal washes from immunized rats.

Animals↗

Colonization of congenitally athymic, gnotobiotic mice by Candida albicans.

Colony counts, scanning electron microscopy, and light microscopy were used to assess the capacity of Candida albicans to colonize (naturally) and infect the alimentary tract of adult and neonatal (athymic [nu/nu] or heterozygous [+/nu] littermates) germfree BALB/c mice. When exposed to yeast-phase C. albicans, the alimentary tract of adult germfree mice (nu/nu or +/nu) is quickly (within 24 to 48 h) colonized with yeast cells. Neither morbidity nor mortality was evident in any mice that were colonized with a pure culture of C. albicans for 6 months. Yeast cells of C. albicans predominated on mucosal surfaces in the oral cavities and vaginas of adult athymic and heterozygous mice. In both genotypes, C. albicans hyphae were observed in keratinized tissue on the dorsal posterior tongue surface and in the cardial-atrium section of the stomach. Conversely, neonatal athymic or heterozygous mice, born to germfree or C. albicans-colonized mothers, do not become heavily colonized or infected with C. albicans until 11 to 15 days after birth. Although yeast cells adhered to some mucosal surfaces in vivo, neither widespread mucocutaneous candidiasis, i.e., invasion of mucosal surfaces with C. albicans hyphae, nor overwhelming systemic candidiasis was evident in neonatal (nu/nu or +/nu) mice. Thus, even in the absence of functional T-cells and a viable bacterial flora, athymic and heterozygous littermate mice (adult or neonatal BALB/c) that are colonized with a pure culture of C. albicans manifest resistance to extensive mucocutaneous and systemic candidiasis.

Animals↗

The thymus dependency of acquired resistance to Trichophyton mentagrophytes dermatophytosis in rats.

Congenitally athymic "nude" (RNU/RNU) rats and euthymic (+/RNU) rats were cutaneously inoculated with Trichophyton mentagrophytes. Dermatophytosis, as evidenced by erythema and scaling, was observed in both athymic and euthymic rats by day 7 postinfection. Macroscopic lesions in +/RNU rats became intensely erythematous (climax days 10-14), were limited in spread and alopecia (days 16-20), and healed with hair regrowth by day 35. In nude rats, however, erythema peaked early (days 8-10) and a persistent, mild erythema and scaling spread over the animals' backs. Viable T. mentagrophytes was cultured from the skin of all infected nude rats for the duration of each experiment (90 days), while +/RNU rats became culture-negative by day 35. Following clearance of primary lesions, +/RNU rats manifest a delayed-type hypersensitivity skin test response to soluble trichophytin and an accelerated cutaneous inflammation and enhanced resistance to reinfection. Although T. mentagrophytes primarily invaded the keratinized layers of the epidermis in both nude and +/RNU rats, hyphae and arthrospores were also observed within the nucleated layers of the internal root sheath of hair follicles. Our observations are consistent with the hypothesis that thymus-dependent cell-mediated immunity is required to limit cutaneous spread and terminate cutaneous T. mentagrophytes infection. This acquired immunity against T. mentagrophytes in +/RNU rats was characterized histologically by: (1) an intense inflammatory migration of lymphocytes, monocytes, and macrophages into the epidermis, dermis, and follicular epithelium; (2) hyperplasia of the epidermis and follicular epithelium; and (3) elimination of arthrospores and hyphae from T. mentagrophytes-infected skin.

Animals↗

Pseudomembranous colitis in Clostridium difficile-monoassociated rats.

Germfree rats were monoassociated with either a toxin-producing strain of Clostridium difficile (Tox+) or a variant of this strain (ToxR) which produced much less toxin (1/10,000) in vivo and in vitro. Monoassociation of germfree rats with C. difficile Tox+ resulted in mortality (17%) and in pathology to the small and large intestines, livers, and lungs. Cecal filtrates from the Tox+-monoassociated rats were cytotoxic for tissue culture cells. The cytotoxicity of cecal filtrates could be blocked by sera from Tox+-monoassociated rats. Monoassociation of rats with C. difficile ToxR resulted in no deaths or pathology, and much less toxin was detected in the cecal filtrates of these animals than in those of rats colonized with the Tox+ strain. This gnotobiotic model may be useful for investigating the etiology, prophylaxis, therapy, and exacerbation of C. difficile-induced pseudomembranous colitis.

Animals↗

Clostridium tetani growth and toxin production in the intestines of germfree rats.

Germfree rats were challenged orally and intrarectally with spores of Clostridium tetani. Although C. tetani spores remained viable in the intestinal tract, they were unable to germinate. Germfree rats were then challenged orally with vegetative cells of C. tetani. Vegetative cells were able to colonize the intestinal tract, replicate, and produce toxin. Tetanus antitoxin, but no tetanus toxin, was detected in the sera of monoassociated rats.

Animals↗

Systemic candidosis in silica-treated athymic and euthymic mice.

Intravenous silica injections were used to assess the role of macrophages in the resistance of BALB/c nude and euthymic mice to systemic candidosis. CFU of Candida albicans in the kidneys, livers, and spleens of saline- or silica-treated mice were enumerated at various times after inoculation with 10(4) viable yeast cells. The number of C. albicans organisms recovered from the kidneys of silica-treated euthymic mice was similar to the number recovered from saline-treated controls during the first 3 days of infection; however, at every assay period thereafter, the number of organisms recovered from the kidneys of silica-treated mice was dramatically reduced (100- to 1,000-fold). Conversely, silica-treated nude mice were no more susceptible to systemic candidosis than were saline-injected nude mice. Silica treatment did not alter the ability of treated or control mice to clear C. albicans from the liver and spleen. These results demonstrate that macrophages play an important role in susceptibility to Candida infections.

Animals↗

The influence of a gastrointestinal microflora on natural killer cell activity.

These studies demonstrate that the natural cytotoxicity of BALB/c mouse spleen cells for 51Cr-labeled YAC-1 cells can be significantly enhanced by microorganisms in the alimentary tract. Spleen cells from germfree BALB/c mice, euthymic, athymic, or non-nude background (+/+), had natural cell-mediated cytotoxicity for YAC-1 cells. Intestinal colonization with a few (flora-defined) or many (complex flora-conventionalized) microorganisms significantly enhanced natural cell-mediated cytotoxicity of athymic and euthymic mice over their germfree counterparts. Conversely, colonization of the alimentary tract of athymic and euthymic germfree mice with a pure culture of Candida albicans or colonization with Candida and a Bacillus sp. did not enhance natural cell-mediated cytotoxic activity over germfree levels. Spleen cells from germfree athymic mice were significantly more cytotoxic than spleen cells from germfree BALB/c mice that did not carry the nude gene (ie, +/+). In the germfree or gnotobiotic state, no difference in natural killer cell activity was evident between athymic (nu/nu) and heterozygous (+/nu) littermate mice; however, athymic (nu/nu) flora-defined or conventionalized mouse spleen cells were significantly more cytotoxic for YAC-1 cells than splenocytes from flora-defined or conventionalized heterozygous (+/nu) littermates. Spleen cells from BALB/c mice that were athymic (nu/nu) and colonized with a complex microbial flora (ie, conventionalized) had the highest percentage of cytotoxicity, at three different effector to target ratios, for YAC-1 cells. These studies indicate that the intestinal microflora can alter murine natural cell-mediated cytotoxicity.

Animals↗