Biomedical subjects

E Balish

Publications and source records attributed to E Balish.

At least 55 records · Page 3Linked to original sources

PubMed1994

Vaginal immunization of monkeys against urinary tract infection with a multi-strain vaccine.

Cynomolgus monkeys were treated with a vaccine containing 10 heat-killed uropathogenic bacteria including 6 Escherichia coli strains. The multi-strain vaccine was administered either as a vaginal surface immunogen or intramuscularly. Following an induced E. coli cystitis, bladder infections were significantly reduced compared with controls at 1 and 2 weeks (intramuscular route) or 1 week (vaginal route) after UTI. This vaccine has been shown to be efficacious against cystitis in humans when given parenterally and has now proved efficacious in nonhuman primates by the vaginal mucosal route.

Animals↗

PubMed1994

Candidacidal activity of macrophages from immunocompetent and congenitally immunodeficient mice.

The chemotactic, phagocytic, and candidacidal activities of peritoneal exudate macrophages from immunocompetent heterozygous (bg/+) and immunodeficient homozygous (bg/bg, bg/bg-nu/+, and bg/bg-nu/nu) beige mice were assessed. Overall, macrophages from all strains of mice tested not only were able to migrate into the peritoneal cavity in response to several eliciting agents but showed a comparable capacity to phagocytize fluorescein isothiocyanate-labeled, heat-killed Candida albicans. However, some populations of peritoneal exudate macrophages from homozygous beige mice (e.g., thioglycollate-elicited) and resident peritoneal macrophages from bg/bg mice incubated in vitro with supernatants from concanavalin A-stimulated splenocytes had poorer candidacidal activity than did control macrophages from bg/+mice. Interferon-gamma enhanced the in vitro candidacidal activity of macrophages from homozygous and heterozygous beige mice. As indicated by inhibitors, poor macrophage candidacidal activity seemed to correlate better with deficient nitric oxide--than with superoxide anion-mediated killing. These data suggest that impaired candidacidal activity of macrophages from homozygous beige mice may explain their enhanced susceptibility to candidiasis.

Analysis of Variance↗

PubMed1994

Humoral and cellular immune responses to enolase after alimentary tract colonization or intravenous immunization with Candida albicans.

Immune responses to defined antigens of the AIDS opportunistic pathogen Candida albicans that arise as a consequence of alimentary tract colonization or induced candidemia were assessed. Lymphocyte activation and antibody production to the abundant immunodominant antigen enolase were evident in germfree mice colonized with C. albicans. Lymphocytes from colonized or intravenously challenged mice responded to a recombinant C. albicans enolase fusion protein (EFP). The responses to EFP were significantly higher than the responses to a control protein, glutathione S-transferase. In immunoblotting experiments, enolase was the immunodominant humoral immunogen in these mice. These results demonstrate that enolase stimulates cellular and humoral responses and that specific immune responses to enolase are sensitive indicators of the presence of proliferating C. albicans in mice.

Animals↗

PubMed1994

The role of phagocytic cells in resistance to disseminated candidiasis in granulocytopenic mice.

This study assessed the involvement of phagocytic cells in murine resistance to disseminated candidiasis of endogenous origin. SCID mice and their immunocompetent CB.17 (BALB/c) counterparts were colonized with a pure culture of Candida albicans and treated with an antigranulocyte monoclonal antibody (anti-Gr-1), polyinosinic:polycytidylic acid (poly[I.C]), or both to impair macrophage function in vivo. Candida-colonized SCID mice were more susceptible to disseminated candidiasis after treatment with anti-Gr-1 or poly(I.C) than were CB.17 mice. Histopathology of orogastric tissues demonstrated that combined treatments with anti-Gr-1 and poly(I.C) also enhanced the susceptibility of SCID and CB.17 mice to orogastric candidiasis. These data indicate that macrophages as well as granulocytes play an important role in host resistance to mucosal and disseminated candidiasis of endogenous origin.

Abscess↗

PubMed1993

Congenital immunodeficiencies in mice increase susceptibility to urinary tract infection.

Severe combined immunodeficient (SCID), T cell deficient, and immunocompetent mice were challenged intravesically with viable uropathogenic Escherichia coli. In comparison to immunocompetent controls, SCID mice had significantly greater numbers of viable E. coli in their bladders and kidneys 7 days after inoculation. Splenic anti-E. coli antibody-forming cells (AFC) were virtually absent in SCID mice at 7.0 days after infection. Adoptive transfer of spleen cells from E. coli-immunized immunocompetent mice to SCID mice enhanced their resistance to urinary tract infection (UTI), as evidenced by lower bacterial counts in bladder and kidneys following an induced infection. Congenitally T cell deficient nude mice and immunocompetent heterozygous controls had equivalent bladder and kidney infection levels at 2 and 7 days after UTI. Immunocompetency thus appears to play a significant role in resistance to E. coli UTI in this animal model. Since mice deficient only in T cells did not show increased UTI susceptibility, T cell-independent antibody responses may be an important immunologic defense mechanism.

Animals↗

PubMed1993

Mucosal and disseminated candidiasis in gnotobiotic SCID mice.

The alimentary tracts of germ-free SCID (severe combined immunodeficient) mice were susceptible to colonization with Candida albicans. Large viable populations (10(6)-10(8) colony forming units g-1) of C. albicans, in pure culture, were present in all sections of the intestinal tract. Candida-colonized SCID mice, sacrificed at various time intervals over a 16 week study, manifested chronic superficial mucosal candidiasis of keratinized epithelial surfaces (tongue and stomach). Despite the continuous presence of large viable populations of C. albicans in their intestinal tract, only superficial mucosal candidiasis and no progressive disseminated candidiasis of endogenous origin was evident in these mice. Treatment with cyclophosphamide (100 mg kg-1, intraperitoneally) enhanced the susceptibility of SCID mice to mucosal (tongue and stomach) candidiasis. Gnotobiotic (C. albicans-colonized) SCID mice were also found to be as resistant as immunocompetent BALB/c mice to acute (intravenous challenge) renal candidiasis. Colonization of the alimentary tract with a bacterial flora appeared to enhance the resistance of SCID mice to disseminated candidiasis. This study demonstrates that innate immune mechanisms (phagocytic and/or NK cells), in the absence of functional T- and B-cells, play an important role in the resistance of SCID mice to mucosal and disseminated candidiasis of endogenous (intestinal tract) or acute (intravenous challenge) origin.

Animals↗

PubMed1993

Resistance of SCID mice to Candida albicans administered intravenously or colonizing the gut: role of polymorphonuclear leukocytes and macrophages.

SCID mice, which lack functional T and B cells, and their immunocompetent counterparts were treated with a monoclonal antibody to murine granulocytes (anti-Gr-1), silica, or carrageenan to assess the role of phagocytic cells (Polymorphonuclear leukocytes and macrophages) in resistance to candidiasis. SCID mice treated with anti-Gr-1 showed enhanced susceptibility to acute systemic candidiasis, disseminated candidiasis of endogenous origin, and orogastric candidiasis. Immunocompetent CB.17 and BALB/c mice treated with anti-Gr-1 showed enhanced susceptibility to acute systemic candidiasis but not to either orogastric or disseminated candidiasis of endogenous origin. Impairment of phagocytic cell functions with silica or carrageenan also enhanced the susceptibility of SCID mice to acute systemic candidiasis. These data in SCID and CB.17 mice support clinical studies in patients that point out the important role that granulocytes play in resistance to candidiasis. The resistance of granulocyte-depleted CB.17 mice to orogastric and disseminated candidiasis of endogenous origin also demonstrates that functional T and B cells play a role in controlling candidiasis.

Animals↗

PubMed1993

Enhancement of susceptibility of CB-17 mice to systemic candidiasis by poly(I . C)-induced interferon.

Poly(I . C) enhanced the susceptibility of CB-17 (BALB/c) mice to acute systemic candidiasis. Poly(I . C), supernatants from poly(I . C)-treated macrophages, or alpha and beta interferons suppressed macrophage candidacidal activity in vitro. Thus, poly(I . C)-induced interferons may enhance the susceptibility of CB-17 mice to candidiasis by suppressing macrophage candidacidal activity in an autocrine fashion.

Animals↗

PubMed1993

Experimental mycoses in congenitally immunodeficient rodents.

Congenitally immunodeficient rodents are playing a major role in clarifying host defense mechanisms and elucidating the virulence factors of a variety of mycotic agents. These murine models are also being used to study the histopathology and chemotherapy of a variety of fungal infections. Recent development of immunodeficient transgenic mice will make these murine models even more valuable for studies on the diagnosis, pathogenesis, immunity, and chemotherapy of fungal infections.

Animals↗

PubMed1992

Poly(I.C)-induced interferons enhance susceptibility of SCID mice to systemic candidiasis.

In the absence of any demonstrable T- or B-cell responses, gnotobiotic CB-17 SCID (severe combined immunodeficient) mice not only show innate resistance to acute systemic (intravenous challenge) candidiasis but also manifest innate resistance to systemic candidiasis of endogenous (gastrointestinal tract) origin. Poly(I. C), a potent inducer of interferons (IFNs) in vivo, enhanced the susceptibility of CB-17 SCID mice to acute systemic candidiasis and to systemic candidiasis of endogenous origin, as demonstrated by increased numbers of viable Candida albicans in internal organs after poly(I. C) treatment. The poly(I. C)-enhanced susceptibility of mice to candidiasis was abrogated by in vivo treatment with antibodies to IFN-alpha, -beta, and -gamma. In vivo depletion of natural killer cells from SCID mice did not significantly enhance their susceptibility to systemic candidiasis or abrogate poly(I. C)-enhanced susceptibility. In vivo and in vitro, treatment with poly(I. C) impaired the candidacidal and phagocytic activity of thioglycollate-elicited macrophages from SCID mice. Antibody to IFN-alpha/beta or IFN-beta alone interfered with the ability of poly(I. C) to impair the candidacidal activity of macrophages from SCID mice in vitro. These data suggest that poly(I. C)-induced interferons can impair the candidacidal activity of macrophages in SCID mice and decrease their innate resistance to acute systemic candidiasis and to systemic candidiasis of endogenous origin.

Animals↗

PubMed1992

The relative lethality of intestinal bacteria for gnotobiotic rats with experimental intestinal strangulation.

In eight experiments utilizing 28 animals each, germfree rats with and without ischemically or hemorrhagically strangulated closed loop intestinal segments were contaminated with either one of four common intestinal anaerobic bacteria, or a combination of two or three bacteria previously found to be innocuous in pure culture. The results showed that: a) in pure culture, Bacteroides fragilis, Bacteroides melaninogenicus, and Peptostreptococcus anaerobius were innocuous; b) Fusobacterium necrophorum alone was a very lethal organism that produced intense, confluent, intraperitoneal, fibrous adhesions after four to six days; and c) mixed inoculum of Klebsiella pneumoniae, Bacteroides fragilis, and/or Streptococcus faecalis was found to be lethal for gnotobiotic rats with intestinal strangulation. It is concluded that Fusobacterium necrophorum is so patent that it should be specifically treated with antibiotics when suspected or known to be present in clinical specimens. This gnotobiotic animal model will be useful to delineate the lethality of known combinations of intestinal bacteria.

Animals↗

PubMed1992

The natural course of Clostridium perfringens--induced pneumatosis cystoides intestinalis.

Primary pneumatosis cystoides intestinalis (PCI) is an uncommon, usually benign condition whose natural course is poorly understood and which can sometimes produce significant changes in a patient's cecum and sigmoid colon. In this study, PCI was produced by monocontaminating the peritoneal cavities of adult germfree rats with Clostridium perfringens. These animals were then observed for up to 26 weeks. PCI took up to two weeks to develop, lasted at least ten weeks in most animals, and presumably disappeared from 42% of 26 animals killed during the final 16 weeks. PCI was usually benign, but in some animals produced extensive and persistent subserosal and submucosal air cysts of the cecum and sigmoid colon without evidence of intra-abdominal sepsis. These profound segmental colonic lesions suggest a possible etiology for other segmental inflammatory bowel diseases.

Animals↗

PubMed1991

Inflammatory responses to cryptococcosis in congenitally athymic mice.

Histopathology revealed that nu/nu mice developed both acute and chronic inflammatory responses following infection with Cryptococcus neoformans. In comparison to inflammatory responses in nu/+ mice, the responses in nu/nu mice were delayed, less intense, contained predominantly more polymorphonuclear leukocytes (PMNs) than macrophages (M phi s), and did not develop into granulomas. In addition, nu/nu mice developed cryptococcal skin lesions demonstrating that C. neoformans is dermatotropic in a T-cell deficient host. Quantitative culturing of infected organs confirmed that delayed and incomplete inflammatory responses observed in nu/nu mice correlated with their enhanced susceptibility to C. neoformans.

Animals↗

PubMed1991

Role of natural killer cells in resistance to systemic cryptococcosis.

These studies demonstrate that Cryptococcus neoformans infection induced a dose-dependent augmentation of splenic natural killer (NK) cell activity by bg/+, but not bg/bg mice. To directly assess the role of NK cells in resistance to C. neoformans, bg/+ and bg/bg mice were treated with anti-NK-1.1 monoclonal antibody (mAb). Anti-NK-1.1-treatment abrogated the augmented NK cell activity observed during C. neoformans infection in bg/+ mice. Anti-NK-1.1-treated bg/+ mice had higher C. neoformans colony forming units (CFU) in their lungs on days 3 and 7 after intravenous (i.v.) challenge than control bg/+ mice. Moreover, the number of C. neoformans CFU in the lungs of anti-NK-1.1-treated bg/+ mice on days 3 and 7 were similar to those observed for infected bg/bg mice. By day 14, however, no differences in C. neoformans CFU were evident in the lungs of anti-NK-1.1-treated and control bg/+ mice. Anti-NK-1.1-treatment did not alter either the growth of C. neoformans in the spleens, livers, kidneys, or brain of bg/+ mice or the susceptibility of bg/bg mice to systemic cryptococcosis. These studies suggest that NK cells do not play a role in resistance to systemic cryptococcosis in the spleen, but do appear to play an early, but transient role in resistance to C. neoformans in the lungs. Overall, congenital defects in polymorphonuclear neutrophils (PMNs) and macrophages (M phi s), in addition to defects in NK cells, contribute to the enhanced susceptibility of bg/bg mice to systemic cryptococcosis.

Animals↗

PubMed1991

Immunization against urinary tract infection with a multi-valent vaginal vaccine.

Systemic and local immune responses are thought to play an important role in susceptibility to urinary tract infection. In an attempt to boost local immunity, a vaccine was administered parenterally or vaginally to two mouse strains. Both routes of immunization increased the number of splenic antibody-forming cells against the bacterial strains in the vaccine. Following vaginal or parenteral immunization and subsequent induction of cystitis with live E. coli, immunized animals had fewer viable bladder E. coli than non-immunized animals.

Animals↗

PubMed1991

Acquired immunity to systemic candidiasis in immunodeficient mice.

Twenty-seven percent of beige-athymic (bg/bg nu/nu) mice died of systemic candidiasis 7-20 weeks after gastrointestinal tract colonization with Candida albicans. Conversely, beige-euthymic (bg/bg nu/+) mice colonized with C. albicans for a similar time period did not die or develop systemic candidiasis. C. albicans-colonized bg/bg nu/+ mice, but not bg/bg nu/nu mice, developed C. albicans-specific T cell-dependent antibody- and cell-mediated immune responses, indicating that T cell-dependent responses might explain the acquired resistance of bg/bg nu/+ mice to systemic candidiasis. Colonization with C. albicans enhanced the resistance of T cell-competent bg/bg nu/+ mice, but not bg/bg nu/nu mice, to systemic candidiasis. T cell-mediated immunity activated after mucosal colonization with C. albicans plays an important role in resistance to systemic candidiasis.

Animals↗

PubMed1991

A monoclonal antibody to gamma interferon blocks augmentation of natural killer cell activity induced during systemic cryptococcosis.

These studies demonstrate that the cytotoxic activity of splenic natural killer (NK) cells is augmented in both nu/nu and nu/+ mice during systemic cryptococcosis. Both the kinetics and the regulation of NK cell activity differed in Cryptococcus neoformans-infected nu/nu and nu/+ mice. Greater augmentation was observed following challenge with 10(5) cells than with smaller inocula, and augmented NK cell activity was not always associated with enhanced control of systemic cryptococcosis. Infection with a nonencapsulated strain of C. neoformans induced an early but transient increase in splenic NK cell activity in nu/nu and nu/+ mice. Injection of capsular polysaccharide induced a transient augmentation of splenic NK cell activity in nu/+ mice but caused a persistent increase in splenic NK cell activity in nu/nu mice. In vivo treatment with monoclonal antibody to gamma interferon abrogated the augmentation of splenic NK cell activity induced during cryptococcal infections in both nu/nu and nu/+ mice and enhanced the susceptibility of nu/+ mice to C. neoformans to a greater extent than it did that of nu/nu mice. These results suggest that gamma interferon is an important mediator of resistance to C. neoformans.

Animals↗

PubMed1991

Cutaneous cryptococcosis in athymic and beige-athymic mice.

The dermotropism of Cryptococcus neoformans SLHA in congenitally athymic (nu/nu) and doubly immunodeficient beige-athymic (bg/bg-nu/nu) mice is described. Both bg/bg-nu/nu and nu/nu mice developed cutaneous cryptococcosis within 7 to 12 days following intravenous challenge with 10(4) encapsulated yeast cells. Macroscopically, cutaneous lesions appeared as small subcutaneous nodules without ulceration. Cryptococcal skin lesions were observed primarily on the flank of nu/nu mice, whereas skin lesions in bg/bg-nu/nu mice were distributed over the trunk, abdomen, and face. While bg/bg-nu/nu mice had four times as many macroscopic skin lesions as nu/nu mice on day 14 after intravenous challenge, the skin lesions in nu/nu mice were larger. Histopathology revealed large foci of encapsulated yeasts extending from the basement membrane of the epidermis through the dermis to the underlying musculature. Yeasts in these lesions evoked a minimal inflammatory response that consisted primarily of macrophages. Interestingly, yeast cells appeared to be degrading collagen bundles located in the dermis. The dermotropic strain used in this study produced gelatinase and other proteases in vitro. These results indicate that C. neoformans can be dermotropic in a T-cell-deficient host and that proteases may be a virulence factor(s).

Animals↗