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Biomedical subjects

D Bouley

Publications and source records attributed to D Bouley.

10 recordsLinked to original sources

Salmonella exploits caspase-1 to colonize Peyer's patches in a murine typhoid model.

Salmonella typhimurium invades host macrophages and induces apoptosis and the release of mature proinflammatory cytokines. SipB, a protein translocated by Salmonella into the cytoplasm of macrophages, is required for activation of Caspase-1 (Casp-1, an interleukin [IL]-1beta-converting enzyme), which is a member of a family of cysteine proteases that induce apoptosis in mammalian cells. Casp-1 is unique among caspases because it also directly cleaves the proinflammatory cytokines IL-1beta and IL-18 to produce bioactive cytokines. We show here that mice lacking Casp-1 (casp-1(-/)- mice) had an oral S. typhimurium 50% lethal dose (LD(50)) that was 1,000-fold higher than that of wild-type mice. Salmonella breached the M cell barrier of casp-1(-/)- mice efficiently; however, there was a decrease in the number of apoptotic cells, intracellular bacteria, and the recruitment of polymorphonuclear lymphocytes in the Peyer's patches (PP) as compared with wild-type mice. Furthermore, Salmonella did not disseminate systemically in the majority of casp-1(-/)- mice, as demonstrated by significantly less colonization in the PP, mesenteric lymph nodes, and spleens of casp-1(-/)- mice after an oral dose of S. typhimurium that was 100-fold higher than the LD(50). The increased resistance in casp-1(-/)- animals appears specific for Salmonella infection since these mice were susceptible to colonization by another enteric pathogen, Yersinia pseudotuberculosis, which normally invades the PP. These results show that Casp-1, which is both proapoptotic and proinflammatory, is essential for S. typhimurium to efficiently colonize the cecum and PP and subsequently cause systemic typhoid-like disease in mice.

Animals↗

Study of focused ultrasound tissue damage using MRI and histology.

This paper reports on an experimental study of in vivo tissue damage in the rabbit brain with focused ultrasound (FUS) using magnetic resonance imaging (MRI) and histopathological analysis. Ten ultrasonic lesions (tissue damage) were created in five rabbits using a focused ultrasound beam of 1.5 MHz, electrical power input to the transducer of 70-85 W, and an exposure duration of 15-20 seconds. T1- and T2-weighted fast spin-echo (FSE) and Fluid attenuated inversion recovery (FLAIR) sequences were used to detect the ultrasonic lesions after treatment. Imaging was performed for 4-8 hours after treatment, after which the animals were immediately sacrificed. Ultrasonic lesion diameter was measured on MRI and histological sections after correction for tissue shrinkage during the histological processing. The T1-weighted images showed lesions poorly, whereas both T2-weighted and FLAIR images showed lesions clearly. The lesion diameters on both T2 and FLAIR imaging correlated well with measurements from histology. The time delay before lesions appeared on T2-weighted imaging was 15 minutes to 1 hour, depending on the exposure location in the brain. J. Magn. Reson. Imaging 1999;10:146-153.

Animals↗

Partial tracheal obstruction due to chondromas in ball pythons (Python regius).

Over a 9-mo period, three adult ball pythons (Python regius) (one male, two females) were evaluated for severe dyspnea. Partial obstructions of the tracheal lumen were identified radiographically and/or visualized with a 3.0-mm rigid laparoscope inserted into the tracheal lumen in all three snakes. Administration of systemic antibiotics and nebulization resulted in partial improvement of the dyspnea. In two snakes, the tracheal lesions were removed with a rigid laparoscope and a flexible biopsy instrument inserted into the tracheal lumen. The other snake died and was necropsied. Histologically, the lesions from two snakes were determined to be benign chondromas. The chondromas were composed of a variably disorganized chondroid matrix populated by quiescent, normal-appearing chondrocytes within lacunae, although the chondrocytes were increased in density compared with normal hyaline cartilage and contained rare mitotic figures. The tracheal masses in one snake grew by expansion, not invasion, and were focally continuous with a mineralized cartilage tracheal ring, suggesting a benign nature. This is the second report of tracheal chondroma in ball pythons. Tracheal chondromas are exceedingly rare in humans and domesticated animals, suggesting a possible predisposition of ball pythons for this neoplasm.

Animals↗

Possible antibiotic-associated colitis in a dog.

A Poodle referred for renal disease developed severe colonic disease characterized by total mucosal collapse and necrosis. The onset of colonic disease was temporally related to administration of antibiotics. On 3 occasions, bacterial culture of fecal samples yielded only Streptococcus pyogenes, Pseudomonas aeruginosa, and Candida albicans, suggesting that the colonic bacterial flora was severely disrupted. Findings, although not conclusive, were suggestive of antibiotic-associated colitis that ultimately proved fatal. Colonoscopy should be considered for dogs with unduly severe large-bowel diarrhea associated with antibiotic treatment and can be done with minimal restraint and bowel preparation, if necessary. Nonselective bacterial culture of fecal samples should be considered for dogs with unduly severe large-bowel diarrhea associated with antibiotic treatment.

Ampicillin↗

Yersinia-induced apoptosis in vivo aids in the establishment of a systemic infection of mice.

Pathogenic Yersinia cause a systemic infection in mice that is dependent on the presence of a large plasmid encoding a number of secreted virulence proteins called Yops. We previously demonstrated that a plasmid-encoded Yop, YopJ, was essential for inducing apoptosis in cultured macrophages. Here we report that YopJ is a virulence factor in mice and is important for the establishment of a systemic infection. The oral LD50 for a yopJ mutant Yersinia pseudotuberculosis increases 64-fold compared with wild-type. Although the yopJ mutant strain is able to reach the spleen of infected mice, the mutant strain seldom reaches the same high bacterial load that is seen with wild-type Yersinia strain and begins to be cleared from infected spleens on day 4 after infection. Furthermore, when in competition with wild-type Yersinia in a mixed infection, the yopJ mutant strain is deficient for spread from the Peyer's patches to other lymphoid tissue. We also show that wild-type Yersinia induces apoptosis in vivo of Mac-1(+) cells from infected mesenteric lymph nodes or spleens, as measured by quantitative flow cytometry of TUNEL (Tdt-mediated dUTP-biotin nick-end labeling)-positive cells. The levels of Mac-1(+), TUNEL+ cells from tissue infected with the yopJ mutant strain were equivalent to the levels detected in cells from uninfected tissue. YopJ is necessary for the suppression of TNF-alpha production seen in macrophages infected with wild-type Yersinia, based on previous in vitro studies (Palmer, L.E., S. Hobbie, J.E. Galan, and J.B. Bliska. 1998. Mol. Microbiol. 27:953-965). We conclude here that YopJ plays a role in the establishment of a systemic infection by inducing apoptosis and that this is consistent with the ability to suppress the production of the proinflammatory cytokine tumor necrosis factor alpha.

Animals↗

Ambulatory visits to hospital emergency departments. Patterns and reasons for use. 24 Hours in the ED Study Group.

OBJECTIVES: To characterize the reasons ambulatory patients use hospital emergency departments (EDs) for outpatient care and to determine the proportion of ED patients who initially are assessed as having nonurgent conditions, but subsequently are hospitalized. DESIGN: Cross-sectional survey during a single 24-hour period of time. SETTING: Fifty-six hospital EDs nationwide. PATIENTS OR OTHER PARTICIPANTS: Consecutive ambulatory patients presenting for care. Patents who arrived by ambulance were excluded. RESULTS: Of 6441 ambulatory patients (79 percent of all ED visits) who were eligible for study, interviews were obtained from 6187 (96 percent). A total of 5323 patients (86 percent) had clinical reasons or preferences for seeking care at an ED, including 2799 (45 percent) who thought they had an emergency or an urgent condition or were too sick to go elsewhere. Nineteen percent (n=1199) reported that they were sent to the ED by a health care professional. Patients with a regular clinician or with insurance cited similar reasons for seeking care at an ED. A total of 3062 patients (50 percent) cited 1 or more nonfinancial barriers to care as an important reason for coming to the ED, and 949 (15 percent) cited financial considerations. A total of 3045 patents (49 percent of ambulatory patients and 37 percent of total ED visits) were assessed at triage as having a nonurgent condition; 166 of them (5.5 percent; 95 percent confidence interval, 4.7 percent-6.3 percent) were admitted to the hospital. CONCLUSIONS: Most ambulatory patients seek care in an ED because of worrisome symptoms or nonfinancial barriers to care. Although many ambulatory patients appear to have nonurgent conditions based on triage classification, a small but disturbing percentage of nonurgent patients are hospitalized.

Adolescent↗

Cryptosporidiosis, coccidiosis, and total colonic mucosal collapse in an immunosuppressed puppy.

An eight-week-old puppy with chronic diarrhea was diagnosed with simultaneous opportunistic pathogens (i.e., cryptosporidiosis, coccidiosis) and total colonic mucosal collapse. Lack of lymphoid follicles in the spleen and lymph nodes suggested a primary underlying immunosuppression that most likely permitted infection with these pathogens. Intensive antibiotic therapy was most likely responsible for the severe colonic lesion, and bismuth subsalicylate administration in this severely dehydrated puppy may have contributed to renal failure as the ultimate cause of death.

Animals↗