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Biomedical subjects

E Balish

Publications and source records attributed to E Balish.

At least 127 records · Page 7Linked to original sources

Modulation of the rats' immune status by monoassociation with anaerobic bacteria.

The capacity of a pure culture of anaerobic intestinal bacteria to influence the host's cellular and humoral immune systems was investigated with germfree, monoassociated, and conventionally reared rats. Monoassociation of germfree rats with Bacteroides fragilis stimulated the production of serum gamma globulin, agglutinating antibodies, and an apparent IgG (immunoelectrophoresis) band. A comparison of the in vitro blastogenic potential of lymphocytes (spleen cells and mesenteric lymph node cells) from germfree, monoassociated, and conventionally reared rats indicated the following: (1) the microbial flora had no obvious effect on the capacity of nonstimulated lymphocytes to incorporate [3H]thymidine; (2) spleen cells from conventionally reared rats responded to phytohemagglutinin, concanavalin A, or pokeweed mitogen better than splenocytes from germfree rats; (3) colonization of germfree rats with Fusobacterium necrophorum increased the responsiveness of splenocytes to photohemagglutinin and concanavalin A; and (4) monoassociation of germfree rats with B. fragilis, but not with F. necrophorum or propionibacterium acnes, increased splenocyte blastogenesis to homologous (i.e., colonizing) bacterial antigens. This study indicated that some intestinal bacteria can modulate the immune status of the host; the extent and nature of this modulation depended on the particular species of colonizing bacteria.

Animals↗

Inhibitors of bacterial adherence to urothelium.

We attempted to change the degree of bacterial adherence to rat urothelium by administering chemical and immunotropic agents as subcutaneous injections and as bladder instillations. Organic iodine instillations with an adjusted pH were effective. Levamisole and Freund adjuvant instillations were effective but were associated with excessive morbidity. AgNO3, inorganic iodide, and heparin instillations were not effective in the animal model used. Bladder instillations might be developed as a way to augment the antiadherence capacity of the bladder and prevent recurrent urinary tract infections.

Animals↗

Distribution of nitrogen-13 from labeled nitrate (13No3-) in humans and rats.

The body distribution of gavaged or intravenously administered nitrate labeled with nitrogen-13 was studied in humans and rats with the following results: (i) the labeled compound is not quickly absorbed from the stomach; (ii) the concentration of the label increases inside the lower intestinal tract (cercum and large intestine) when ingested or intravenously injected; and (iii) humans and rats have the capacity to store a portion of the label in their bodies. These observation indicate that depletion of body stores, the passage of nitrate down the gut, or the secretion of nitrate into the intestinal lumen may be a better explanation of the urinary, ileal, and fecal concentrations of nitrate and nitrite recently measured in humans that a bacterial nitrification reaction in the intestines, as suggested by Tannenbbaum et al.

Animals↗

Intestinal strangulation in germfree and monocontaminated dogs.

Earlier studies in the germfree rat demonstrated that the common intestinal bacteria vary greatly in their ability to cause death after intestinal strangulation. Some of these experiments were repeated in adult, germfree and monocontaminated beagles. Neither short closed-loop hemorrhagic nor long closed-loop ischemic strangulation killed the germfree dog. Either procedure rapidly killed the dog with a conventional bacterial flora or a dog monocontaminated with Clostridium perfringens. The dogs monocontaminated with Bacteroides fragilis died after several days, whereas Escherichia coli killed only one of three animals. These experiments demonstrate the usefulness of the germfree dog as a unique research subject, confirm our earlier studies on intestinal strangulation in germfree rats, and further emphasize the differing lethal potentials of the intestinal bacteria in intestinal strangulation.

Animals↗

Distribution and metabolism of ingested NO3- and NO2- in germfree and conventional-flora rats.

Germfree and conventional-flora Sprague-Dawley rats were fed sodium nitrate or sodium nitrite in their drinking water (1,000 microgram/ml), and various organs, tissues, and sections of the intestinal tract were assayed for nitrate (NO3-) and nitrite (NO2-) by a spectrophotometric method. When fed NO3-, germfree rats had chemically detectable levels of NO3- (only) in the stomach, small intestine, cecum, and colon. Conventional-flora rats fed NO3- had both NO3- and NO2- in the stomach, but only NO3- in the small intestine and colon. When fed NO2-, germfree rats had both NO3- and NO2- in the entire gastrointestinal tract. Conventional-flora rats fed NO2- had both ions in the stomach and small intestine, but only NO3- in the large intestine. Conventional-flora rats fed NO3- or NO2- had lower amounts of these ions in the gastrointestinal tract than comparably fed germfree rats. Control (non-NO3- or NO2--fed) germfree and conventional-flora rats had trace amounts of NO3- (only) in their stomachs and bladders. These results, in conjunction with various in vitro studies with intestinal contents, suggest that NO3- or NO2- reduction is a function of the normal bacterial flora, whereas NO2- oxidation is attributable to the mammalian host. In addition, the distribution of these ions after their ingestion appears more widespread in the body than previously thought.

Animals↗

Distribution of nitrogen-13 from labeled nitrate and nitrite in germfree and conventional-flora rats.

The in vivo distribution of physiological concentrations of NO3- and NO2- labeled with 13N was studied in germfree and conventional-flora Sprague-Dawley rats after gastric intubation (gavage), intravenous (cardiac or tail vein), or intraluminal (intestinal) injection. Some in vitro studies were performed to determine the influence of the bacterial flora on ion distribution. After gavage with 13NO3-, essentially all of the label passed into the upper small intestine, where most was absorbed; however, up to 24% of the 13N could reach the ileum within 1 h. Gavage with 13NO2- resulted in some gastric absorption of the label, but most seemed to exit the stomach via passage into the duodenum. The exit of 13NO2- from the stomach was slower, and less 13N appeared to be absorbed from the small intestine than with 13NO3-. Movement of label through the gastrointestinal tract could be enhanced by inducing diarrhea. Absorbed 13N was either excreted in the urine, reentered the gastrointestinal tract at various points, or was temporarily stored in the eviscerated carcass. The bacterial flora, either by incorporation or chemical alteration, appeared to have some influence on the distribution of 13N from 13NO3- or 13NO2-.

Animals↗

Effect of oral tetracycline, the microbial flora, and the athymic state on gastrointestinal colonization and infection of BALB/c mice with Candida albicans.

Scanning electron microscopy, light microscopy, and quantitative culture of microorganisms in intestinal contents were used to determine the effects of oral tetracycline, the bacterial flora of conventionally reared animals (conventional), and thymus-dependent immune competency on the capacity of Candida albicans to colonize and infect the gastrointestinal tract of four groups of mice: thymus-intact conventional mice, conventional athymic mice, flora-defined athymic mice, and thymus-intact bacteria-free mice. Thymus-intact conventional mice without antibiotic treatment began to shed C. albicans less than 48 h after oral yeast challenge and were devoid of detectable yeast by day 16. Tetracycline altered the bacterial flora qualitatively and quantitatively, allowing C. albicans to colonize in less than 48 h and to persist in the gut tract for 32 days. Only 2 of 72 of these conventional mice developed candidiasis (hyphal infection). Although tetracycline altered the bacterial flora of conventional athymic (nude) mice, it was not required to allow C. albicans to colonize their gut tract to levels significantly higher than those in thymus-intact conventional mice. All conventional nude mice were consistently colonized and 14 of 24 animals showed an increased yeast colonization of the keratinized stomach, but only 3 of 24 developed gastric candidiasis. Flora-defined athymic (nude) mice had significantly lower aerobic bacterial levels and significantly higher C. albicans levels in the gut contents than conventional athymic mice. The flora-defined nude mice, however, developed gastric candidiasis by day 5. Thymus-intact bacteria-free mice were uniformly colonized and infected with C. albicans less than 48 h after oral challenge regardless of tetracycline treatment. Populations of C. albicans in the gut of bacteria-free mice were significantly higher than in the gut tract of the thymus-intact conventional or athymic mice. Gastric mycelial infection was detected in 8 of 10 bacteria-free animals 2 days after oral challenge. By 32 days, 45 of 50 mice of both tetracycline-treated and control bacteria-free groups were infected with C. albicans. These data indicate that a competive bacteria flora is more effective than an intact immune system in preventing gastric candidiasis and that an immune deficiency may allow increased yeast colonization of the keratinized and glandular stomach epithelium. Tetracycline did not appear to enhance the invasiveness or pathogenicity of C. albicans in mice even though it facilitates yeast-phase gut colonization in conventionally reared mice.

Animals↗

Immune response modulation by colonization of germfree rats with Propionibacterium acnes.

Propionibacterium acnes (oral and/or parenteral administration) had a modulating effect on antibody-and cell-mediated immune responses of germfree (GF) and monoassociated (MA) rats. In conventionally reared rodents, parenteral injection of killed P. acnes stimulated the splenic plaque-forming cell response to sheep erythrocytes. However, in GF rats and in rats monoassociated with viable P. acnes, parenteral injection of killed P. acnes antigen inhibited the plaque-forming cell response to sheep erythrocytes. When compared with the responses of GF control rats, splenocytes from GF rats parenterally injected with P. acnes antigen had a decreased in vitro blastogenic response to phytohemagglutinin and concanavalin A and an increased blastogenic response to homologous bacterial antigens. Conversely, a parenteral injection of P. acnes antigen into P. acnes MA rats resulted in an increased splenocyte blastogenic response to phytohemagglutinin and concanavalin A but not to homologous (P. acnes) antigens. Thus the presence or absence of intestinal antigenic stimuli (in MA and GF rats) had a modulating effect on the immune response to a parenteral injection of P. acnes antigen.

Administration, Oral↗

Suppression of in vitro lymphocyte transformation during an experimental dermatophyte infection.

During primary Trichophyton mentagrophytes infection of strain 2 guinea pigs, the colony-forming units (CFU) of fungi present within the lesion peaked between days 7 and 14, whereas the severity of the lesion itself peaked between days 11 and 16. Concomitant with the latter peak, a pronounced depression in the in vitro mitogenic activity of spleen cells (SPC) and lymph node cells (LNC) was observed. Only after resolution of the primary infection (day 21) did LNC show increased deoxyribonucleic acid (DNA) synthesis in the presence of fungal antigens. During cutaneous reinfection, there was no distinct peak fungal load and CFU appeared to decrease steadily during the accelerated course of a reinfection disease. LNC from guinea pigs with severe, ulcerated reinfection lesions generally exhibited a heightened response to fungal antigen in vitro. LNC from guinea pigs with mild reinfection dermatophytosis had depressed in vitro reactivity to mitogens and dermatophyte antigen. The suppression of blastogenic activity during dermatophyte infection appeared to be associated with autologous serum components, since increased DNA synthesis resulted when SPC or LNC were cultured with fetal calf serum. The depressed in vitro DNA synthesis of lymphocytes (cultured with dermatophyte antigens) that were harvested during reinfection was not accompanied by an impaired ability of infected guinea pigs to respond with a delayed-type hypersensitivity skin test in vivo. These results support the hypothesis that experimental T. mentagrophytes dermatophytosis is a cell-mediated hypersensitivity disease that can be modified by immunosuppressive control mechanisms elaborated or induced by the fungus.

Animals↗

The mitogenic activity of lipopolysaccharide for spleen cells from germfree, conventional, and gnotobiotic rats.

Spleen cells from germfree rats, conventionally reared rats, and gnotobiotic rats associated with two Pseudomonas species gave no positive blastogenic response when incubated with each of four lipopolysaccharide (LPS) preparations from Escherichia coli, with glycolipid extracted from Salmonella minnesota R595 or with S. minnesota R595 lipid A. However, spleen cell preparations from athymic mice demonstrated a positive blastogenic response when incubated with E. coli LPS. Removal of adherent cells from germfree and conventional-flora rat spleen cells did not increase the mitogenic activity of LPS for nonadherent cells (less than 0.5% esterase-positive cells). All rat spleen cell preparations gave positive blastogenic responses to phytohemagglutinin and concanavalin A. This study indicates that LPS may not be a mitogenic agent for rat spleen cells.

Animals↗

The use of a laminar airflow isolation system for the treatment of major burns.

A laminar airflow isolation burn ward was designed which would maintain a sterile environment and also allow unrestricted burn care and rehabilitation to be performed. A very low rate of sepsis and sepsis-related complications have been found in the 115 patients treated in the unit. Patient cross contamination has been completely controlled under laminar airflow conditions. The incidence of burn colonization and infection by virulent gram-negative organisms, namely pseudomonas, serratia, klebsiella, and proteus, in these patients has been extremely low, particularly in comparison with burn patients managed in a non-laminar flow intensive care environment.

Adolescent↗

Gastrointestinal microecology of BALB/c nude mice.

The aerobic, facultative, and anaerobic microorganisms cultivable from the stomachs, ilea, ceca, and colons of BALB/c athymic (nu/nu) mice (normal and wasting), thymus-implanted normal nude mice, and their heterozygous (nu/+) littermates were investigated. Ninety-one species representing 23 genera of bacteria and yeasts were isolated from the 27 mice. The wasting nude mice showed significantly lower numbers of lactobacilli in their stomach microbiota than did mice from the other three groups. The littermate animals appeared unique among the four groups in having corynebacteria as a major constituent of their stomach and ileal flora. The normal nude mice appeared to have a more diverse anaerobic stomach flora than their heterozygous littermates. These minor differences are discussed with respect to possible immunological, physiological, and environmental factors as their cause. Because the gastrointestinal microfloras of the mice from the four groups were not radically divergent from each other, it was concluded that loss of T-cell function does not dramatically alter the makeup of the cultivable gastrointestinal microflora in these mice.

Aerobiosis↗

Immunity to experimental renal candidiasis in rats.

Germfree rats were found to be more susceptible to intravenous challenge with Candida albicans than were conventional rats. The resistance of conventional rats could be overcome by increasing the challenge dose. The resistance of the germfree rat was enhanced by vaccination with Formalin-killed C. albicans in complete Freund adjuvant, complete Freund adjuvant, or incomplete Freund adjuvant. These results, and histological evidence obtained from infected gnotobiotic rats, provided further information on the mechanism of resistance to the disseminated form of candidiasis.

Animals↗