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A Gendron-Fitzpatrick

Publications and source records attributed to A Gendron-Fitzpatrick.

12 recordsLinked to original sources
PubMed2006

Characterizing a rat Brca2 knockout model.

Evidence exists that BRCA2 carriers may have an elevated risk of breast, ovarian, colon, prostate, and pancreatic cancer. In general, carriers are defined as individuals with protein truncating mutations within the BRCA2 gene. Many Brca2 knockout lines have been produced and characterized in the mouse. We previously produced a rat Brca2 knockout strain in which there is a nonsense mutation in exon 11 between BRC repeats 2 and 3, and a truncated protein is produced. Interestingly, while such a mutation in homozygous mice would lead to limited survival of approximately 3 months, the Brca2-/- rats are 100% viable and the vast majority live to over 1 year of age. Brca2-/- rats show a phenotype of growth inhibition and sterility in both sexes. Aspermatogenesis in the Brca2-/- rats is due to a failure of homologous chromosome synapsis. Long-term phenotypes include underdeveloped mammary glands, cataract formation and lifespan shortening due to the development of tumors and cancers in multiple organs. The establishment of the rat Brca2 knockout model provides a means to study the role of Brca2 in increasing cancer susceptibility and inducing a novel ocular phenotype not previously associated with this gene.

Animals↗
PubMed1998

Time course and host responses to Escherichia coli urinary tract infection in genetically distinct mouse strains.

Recurrent urinary tract infections (UTIs) are a significant clinical problem for many women; however, host susceptibility factors have not been completely defined. The mouse model of induced UTI provides an experimental environment in which to identify specific host characteristics that are important in initial bacterial colonization of the urinary tract and in resolution of an infection. This study examined initial susceptibility, bacterial clearance, and host defense mechanisms during induction and resolution of Escherichia coli UTIs in genetically distinct strains of mice. Of the ten inbred strains tested, six (BALB/c, C3H/HeN, C57BL/6, DBA.1, DBA.2, and AKR) showed progressive resolution of bladder infections over a 14-day period. A constant, low-level bladder infection was observed in SWR and SJL mice. High bladder infection levels persisted over the 14-day study period in C3H/HeJ and C3H/OuJ mice. Kidney infection levels generally correlated with bladder infection levels, especially in C3H/HeJ and C3H/OuJ mice, the two most susceptible strains, in which infections became more severe with time after challenge. The degree of inflammation in bladder and kidneys, as well as antibody-forming cell responses, positively correlated with infection intensity in all strains except C3H/HeJ, which had minimal inflammation despite high infection levels. These results demonstrate two important aspects of host defense against UTI. First, the innate immune response to an infection in the bladder or kidneys consists primarily of local inflammation, which is followed by an adaptive response characterized in part by an antibody response to the infecting bacteria. Second, a UTI will be spontaneously resolved in most cases; however, in mice with specific genetic backgrounds, a UTI can persist for an extended length of time. The latter result strongly suggests that the presence or absence of specific host genes will determine how effectively an E. coli UTI will be resolved.

Animals↗
PubMed1996

Lipopolysaccharide-responder and nonresponder C3H mouse strains are equally susceptible to an induced Escherichia coli urinary tract infection.

Host defense against bacterial urinary tract infections (UTI) includes both inflammatory and immune responses to infecting bacteria. The cellular events leading up to local inflammation are thought to be under genetic control and initiated by lipopolysaccharides (LPS) of gram-negative bacteria such as Escherichia coli. It has been previously reported that mice which lack functional Lps genes are more susceptible to induced E. coli UTI than mice with normal mitogenic responses to LPS. In contrast to these findings, data in this report demonstrate that LPS-responder and nonresponder C3H mouse strains are equally susceptible to E. coli UTI. When C3H/OuJ (Lps(n)/Lps(n)) and C3H/HeJ (Lps(d)/Lps(d)) were intravesically inoculated with equal numbers of uropathogenic E. coli organisms, neither strain was able to effectively resolve the induced UTI. The inability of C3H/OuJ mice to combat the infection was not due to an impaired response to LPS, nor could defect in the local inflammatory response be identified. The results indicate that factors other than LPS responsiveness are also important in determining hose resistance to UTI.

Animals↗
PubMed1992

In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3. Effects on spermatogenesis and reproductive capability.

When administered in overtly toxic doses to postweanling male rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces adverse effects on the reproductive system including a decrease in spermatogenesis. Because the male reproductive system may be particularly susceptible to toxic insult during the perinatal period, the effects of in utero and lactational TCDD exposure on its development were examined. Male rats born to dams given TCDD (0.064, 0.16, 0.40, or 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation were evaluated at various stages of development; effects on spermatogenesis and male reproductive capability are reported herein. Testis, epididymis, and cauda epididymis weights were decreased in a dose-related fashion at 32, 49, 63, and 120 days of age, that is, when males were at the juvenile, pubertal, postpubertal, and mature stages of sexual development, respectively. When measured on Days 49, 63, and 120, daily sperm production by the testis was reduced at the highest maternal TCDD dose to 57-74% of the control rate. Cauda epididymal sperm reserves in 63- and 120-day-old males were decreased to as low as 25 and 44%, respectively, of control values, although the motility and morphology of these sperm appeared to be unaffected. The magnitude of the effects described above tended to lessen with time; nevertheless, the decreases in epididymis and cauda epididymis weights, daily sperm production, and cauda epididymal sperm number were statistically significant at the lowest maternal dose tested (0.064 micrograms TCDD/kg) on Day 120 and at most earlier times. To determine if in utero and lactational TCDD exposure also affects male reproductive capability, rats were mated at approximately 70 and 120 days of age with control females. Little if any effect on fertility was seen, and the survival and growth of offspring was unaffected. These results are not inconsistent with the pronounced reductions in daily sperm production and cauda epididymal sperm reserves caused by perinatal TCDD exposure since rats produce and ejaculate far more sperm than are required for normal fertility. The TCDD-induced reduction in spermatogenesis cannot be accounted for by concurrent effects on plasma follicle-stimulating hormone or androgen concentrations or by undernutrition. To investigate the nature of the spermatogenic lesion, leptotene spermatocyte to Sertoli cell ratios were determined.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1992

Determination of virulence of different strains of Listeria monocytogenes and Listeria innocua by oral inoculation of pregnant mice.

A pregnant mouse model was developed to follow the course of infection after peroral inoculation with six different strains of Listeria monocytogenes and one strain of Listeria innocua. Tissues were sampled and analyzed by microbiologic and histologic methods for 5 days postinoculation. In gnotobiotic pregnant BALB/c mice, L. monocytogenes Scott A (SA), serotype 4b, colonized the gastrointestinal tract, translocated to the livers and spleens of mice by day 1 postinoculation, and multiplied in these tissues until day 4. Infection of the placental tissues occurred by days 3 and 4 and was followed by infection of the fetuses. Little damage of colonic and cecal tissues was evident by histologic examination. Livers and spleens showed a cellular immune response; a similar immune response was not detected in the placentas or fetuses. A rough variant of L. monocytogenes SA which was as virulent as the parent strain in mice when injected intraperitoneally was less virulent perorally and did not consistently infect the fetuses. L. monocytogenes ATCC 19113, serotype 3a, did not colonize the gastrointestinal tract, nor was it isolated from any internal tissue. L. monocytogenes strains of serotypes 1/2a and 1/2b behaved like the SA strain in this mouse model. L. innocua colonized the gastrointestinal tract and translocated to the livers and spleens but did not survive in these organs and rapidly disappeared without infecting placental and fetal tissues. In comparison with gnotobiotic mice, conventional pregnant mice inoculated with L. monocytogenes strains showed less consistent infection. These results suggest that the gnotobiotic pregnant mouse is a useful model for detecting differences in virulence relating to colonization, invasiveness, and uteroplacental infection which cannot be detected by intraperitoneal inoculation of mice.

Animals↗
PubMed1990

Probable paratuberculosis in a Sicilian ass.

A presumptive diagnosis of paratuberculosis was made in a Sicilian ass on the basis of a history of chronic diarrhea and weight loss, pasture exposure to a heifer with paratuberculosis confirmed by bacterial culture of feces, postmortem identification of granulomatous inflammation of the intestine containing acid-fast organisms, the absence of acid-fast organisms in extraenteric tissues, and the absence of exposure to tuberculosis. The literature on paratuberculosis in equids is reviewed. The potential for cross-species transmission is emphasized. Justification for consideration of Mycobacterium paratuberculosis infection in the differential diagnoses of equine granulomatous enteritis is discussed.

Animals↗
PubMed1990

Dietary olive and safflower oils in promotion of DMBA-induced mammary tumorigenesis in rats.

Interpretation of studies comparing the efficacy of different dietary fat sources in promoting 7,12-dimethylbenz[a]-anthracene (DMBA)-induced rat mammary tumorigenesis often ignores the fact that about 4% (wt/wt) linoleic acid (18:2n-6) is required for optimal tumor promotion. We therefore fed DMBA-intubated or placebo-intubated female, Sprague-Dawley rats 20% fat diets containing 18:2n-6 (wt/wt) from either high-linoleic safflower oil (SL, 14.6% 18:2n-6), high-oleic safflower oil (SO, 3.4% 18:2n-6), olive oil (OO, 1.1% 18:2n-6), or OO supplemented with 18:2n-6 (OL, 3.4% 18:2n-6) for 16 weeks. Results indicated that OO-fed rats had longer tumor-free time, fewer tumors per rat, and lower tumor incidence compared with SO and OL. Addition of 2.3% 18:2n-6 to OO enhanced tumor promotion (p less than 0.04); SL, SO, and OL demonstrated similar tumor-enhancement effect. About 74% of observed mammary tumors were adenocarcinomas; a greater number of tumors appeared in the thoracic and inguinal than in the cervical and abdominal regions irrespective of diet. These results indicate that once an optimal amount of linoleic acid is provided in the diet, oleic- or linoleic-rich oils have similar effects on promotion of mammary tumors in the rat.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Systemic disease in Peromyscus leucopus associated with Borrelia burgdorferi infection.

Sixteen wild Peromyscus leucopus, trapped for the establishment of a breeding colony, developed signs of neurological damage (trembling, incoordination, circling, head tilt, and lameness of the rear legs) 2-47 days after capture in southern Wisconsin. Spirochetes were cultured from the brain of 5/11 mice, and Borrelia burgdorferi was cultured from 1 brain. A spirochete was isolated from the bladder of 1 mouse. The spirochete was identified by fluorescent antibody staining with the monoclonal antibody specific for B. burgdorferi, H5332. Serum antibodies to the spirochete were found in 14/15 mice. Negative results were obtained in all tests for viruses and bacteria, including Listeria (2/2), Mycoplasma (2/2), mouse hepatitis virus (10/10), Theilers's encephalomyelitis virus (GD VII) (8/8), REO 3 virus (2/2), and lymphocytic choriomeningitis virus (4/4). There was no bacterial growth from brains cultured on eosin methylene blue or blood agar (3/3). Histologic lesions included nonsuppurative cellular infiltrates in the brain, kidney, liver, and lung. Three outbred Swiss-Webster mice were inoculated orally with a suspension of the brain in BSKII medium, and 3 were inoculated with unpassed B. burgdorferi cultured from the brain of a P. leucopus with motor dysfunction. Five of the inoculated mice developed antibody titers of 1:128; one mouse was positive at 1:256. Motor signs of neurologic damage developed in 3/6 mice 2-24 weeks post-inoculation, and B. burgdorferi was detected in the brains of 2 mice by isolation and by fluorescent antibody.

Animals↗
PubMed1987

Arthritis and systemic disease caused by Borrelia burgdorferi infection in a cow.

Infection with Borrelia burgdorferi caused arthritis, myocarditis, glomerulonephritis, and pneumonitis in a cow. Spirochetes were detected by use of immunofluorescent staining in liver and lung specimens and were isolated from the liver. The carpal, stifle, and tarsal joints had marked synovial proliferation, and synovial fluid obtained from these joints had high antibody titers against B burgdorferi. The cow was from an area of Wisconsin that is not endemic for borreliosis.

Animals↗
PubMedDate not supplied

"Double-muscle" trait in cattle: a possible model for Wiedemann-Beckwith syndrome.

The Wiedemann-Beckwith syndrome (WBS) was first described in 1963 as a group of anomalies involving primarily macrosomia, macroglossia, and omphalocele. Histologic studies of WBS show nesidioblastosis of the pancreas, adrenocortical cytomegaly, and persistent metanephric blastema of the kidney. Multiple lines of evidence indicate that the human 11p15.5 region is the locus of abnormality in WBS. Insulin-like growth factor II (IGF-2) frequently has been considered a candidate gene, and expression of IGF-2 is known to be significantly delayed in fetal skeletal muscle of double-muscle (DM) cattle. Other candidate genes recently have been proposed for WBS. A number of recessive alleles in the bovine myostatin gene (GDF8, mapped to bovine chromosome 2 and apparently orthologous to the human 2q22 region) have been shown to be responsible for DM. Recently the first human case of deficient GDF8 function has been reported, confirming the importance of this gene. Bovine IGF-2 has been sequenced and localized to chromosome 25. The primary purpose of this study was to compare and contrast histologic findings in DM and WBS. Immunohistochemical staining confirms changes similar to nesidioblastosis in the pancreas. Other dysplastic changes of a cystic nature are seen in the adrenal. The renal histology of DM fetuses did not appear significantly different than controls.

Adrenal Cortex↗