Regulation of B cell tolerance by the lupus susceptibility gene Ly108     

Kumar KR  Li L  Yan M  Bhaskarabhatla M  Mobley AB  Nguyen C  Mooney JM  Schatzle JD  Wakeland EK  Mohan C 《Science (New York, N.Y.)》2006,312(5780):1665-1669

The susceptibility locus for the autoimmune disease lupus on murine chromosome 1, Sle1z/Sle1bz, and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of Sle1z/Sle1bz impairs B cell anergy, receptor revision, and deletion. Members of the SLAM costimulatory molecule family constitute prime candidates for Sle1bz, among which the Ly108.1 isoform of the Ly108 gene was most highly expressed in immature B cells from lupus-prone B6.Sle1z mice. The normal Ly108.2 allele, but not the lupus-associated Ly108.1 allele, was found to sensitize immature B cells to deletion and RAG reexpression. As a potential regulator of tolerance checkpoints, Ly108 may censor self-reactive B cells, hence safeguarding against autoimmunity.  相似文献   

Prion-induced amyloid heart disease with high blood infectivity in transgenic mice     

Trifilo MJ  Yajima T  Gu Y  Dalton N  Peterson KL  Race RE  Meade-White K  Portis JL  Masliah E  Knowlton KU  Chesebro B  Oldstone MB 《Science (New York, N.Y.)》2006,313(5783):94-97

We investigated extraneural manifestations in scrapie-infected transgenic mice expressing prion protein lacking the glycophosphatydylinositol membrane anchor. In the brain, blood, and heart, both abnormal protease-resistant prion protein (PrPres) and prion infectivity were readily detected by immunoblot and by inoculation into nontransgenic recipients. The titer of infectious scrapie in blood plasma exceeded 10(7) 50% infectious doses per milliliter. The hearts of these transgenic mice contained PrPres-positive amyloid deposits that led to myocardial stiffness and cardiac disease.  相似文献   

Cell signaling. Protein kinases seek close encounters with active genes     

Edmunds JW  Mahadevan LC 《Science (New York, N.Y.)》2006,313(5786):449-451

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Climate change. Can we detect trends in extreme tropical cyclones?     

Landsea CW  Harper BA  Hoarau K  Knaff JA 《Science (New York, N.Y.)》2006,313(5786):452-454

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Urodynamic and morphologic changes in the lower portion of the urogenital tract after administration of estriol alone and in combination with phenylpropanolamine in sexually intact and spayed female dogs     

Hamaide AJ  Grand JG  Farnir F  Le Couls G  Snaps FR  Balligand MH  Verstegen JP 《American journal of veterinary research》2006,67(5):901-908

OBJECTIVE: To compare the urodynamic and morphologic effects of the administration of estriol alone and in combination with phenylpropanolamine on the lower portion of the urogenital tract in female dogs. ANIMALS: 3 sexually intact and 3 spayed female Beagles without urinary incontinence. PROCEDURE: Dogs received estriol (2 mg, PO) once daily for 7 days followed by estriol (2 mg, PO) and phenylpropanolamine (1.5 mg/kg, PO) once daily for 7 days. Urethral pressure profilometry, diuresis cystometry, and vaginourethrography were performed before treatment (day 0) and at days 7 and 14. The maximum urethral pressure (MUP) and closure pressure (MUCP), urethral functional and anatomic profile lengths, integrated pressure (IP), plateau, distance before MUP, maximum meatus pressure, threshold pressure, threshold volume, compliance, urethral length, and vaginal length and width were measured. RESULTS: Before treatment, no urodynamic differences were observed between the 2 groups; however, vaginal length and width were significantly shorter in spayed dogs. Compared with day 0 values, estriol treatment significantly increased MUP, MUCP, and IP values at day 7, but at day 14, this effect decreased despite phenylpropanolamine administration. No morphologic changes from baseline were detected after either treatment in any dog. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that estriol mainly acts on the urethral sphincter mechanism by increasing urethral resistance in sexually intact and spayed female dogs without urinary incontinence. Administration of estriol and phenylpropanolamine did not increase the urethral resistance more than estriol alone. The urodynamic effects of estriol in female dogs with urinary incontinence remain to be elucidated.  相似文献   

Comparison of various doses of carbon 13-labeled aminopyrine for a carbon 13-labeled aminopyrine demethylation blood test in healthy dogs     

Moeller EM  Steiner JM  Williams DA  Tetrick M  Burr J 《American journal of veterinary research》2006,67(7):1110-1114

OBJECTIVE: To determine an optimal dose of carbon 13 ((13)C)-labeled aminopyrine for use in a (13)C-aminopyrine demethylation blood test in healthy dogs. ANIMALS: 9 adult dogs. PROCEDURES: Food was withheld from each dog for 12 hours. A 2-mL baseline blood sample was obtained from each dog and placed into an evacuated tube containing sodium heparin. Carbon 13-labeled aminopyrine was administered IV at doses of 1, 2, 5, or 10 mg/kg. Additional blood samples (2 mL) were obtained and placed into evacuated tubes containing sodium heparin 30, 45, 60, and 75 minutes after (13)C-aminopyrine administration. Hydrochloric acid was used to extract CO(2) from blood samples. The extracted gas was analyzed by fractional mass spectrometry to determine the percentage dose of (13)C administered as (13)C-aminopyrine and recovered in extracted gas (PCD). RESULTS: Gross evidence of clinical adverse effects was not detected in any dog after administration of (13)C-aminopyrine. The mean coefficient of variation (CV) for PCD was significantly lower than the mean CV for the summation of PCD values up to a given sampling time (CUMPCD). Mean PCD values among the 4 doses for each sample time were not significantly different. Administration of (13)C-aminopyrine at a dose of 2 mg/kg resulted in the lowest interindividual variability. CONCLUSIONS AND CLINICAL RELEVANCE: The PCD is superior to CUMPCD for the quantification of aminopyrine demethylation. Administration of (13)C-(13)C-aminopyrine at a dose of 2 mg/kg is appropriate for use in the (13)C-aminopyrine demethylation blood test in healthy dogs.  相似文献   

Liver lobe torsion in dogs: 13 cases (1995-2004)     

Schwartz SG  Mitchell SL  Keating JH  Chan DL 《Journal of the American Veterinary Medical Association》2006,228(2):242-247

OBJECTIVE: To determine history, results of diagnostic testing, surgical findings, complications, and outcome for dogs with liver lobe torsion (LLT). DESIGN: Retrospective case series. ANIMALS: 12 dogs (1 with 2 episodes). PROCEDURE: Signalment, clinical signs, clinicopathologic findings, radiographic and ultrasonographic findings, surgical and histologic findings, complications, and hospitalization time were evaluated. RESULTS: The most common clinical signs were nonspecific abnormalities (eg, vomiting, lethargy, and anorexia) of acute or chronic duration. All dogs were large-breed dogs (median body weight, 37.2 kg [82 lb]). Biochemical abnormalities included high alanine amino-transferase (n = 12) and aspartate aminotransferase (11) activities. Results of abdominal ultrasonography were supportive of the diagnosis in 5 of 8 cases. Affected lobes included the left medial lobe (n = 4), left lateral lobe (3), papillary process of the caudate lobe (2), caudate lobe (1), and right lateral lobe (1). Exploratory celiotomy and liver lobectomy were performed in 12 of 13 cases, and in 11 of those 12 cases, the dog survived. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that development of nonspecific clinical signs of vomiting, lethargy, and anorexia in conjunction with high serum hepatic enzyme activities and mature neutrophilia in a medium-sized or large-breed dog should increase the index of suspicion for LLT. Abdominal ultrasonography with Doppler assessment may be useful in establishing the diagnosis. The long-term outcome for dogs that survive the hospitalization period is excellent.  相似文献   

Age-dependent seroprevalence of antibodies against a Helicobacter pylori-like organism and Helicobacter pylori in commercially reared swine     

Ellis JA  Waldner CL  McIntosh KA  Rhodes C  Harding JC  Ringler SS  Krakowka S 《American journal of veterinary research》2006,67(11):1890-1894

OBJECTIVE: To determine the prevalence of antibodies against a swine-origin Helicobacter pylori-like organism (HPLO) and H pylori in conventionally reared swine. ANIMALS: 640 conventionally reared swine of various ages from 16 high-health farms in Canada, 20 sows from Ohio, and 35 gnotobiotic swine. PROCEDURES: Blood was collected from the cranial vena cava. Sera were collected and tested via ELISA for antibodies against antigen prepared from a swine-origin HPLO and human H pylori strain 26695. RESULTS: Antibodies reactive with a swine HPLO, H pylori, or both were detected in 483 of 640 swine from all 16 farms in western Canada. Seroprevalence varied with age and was low (5.6%) in suckling ( 4 weeks old to adulthood. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that colonization by a swine-origin HPLO, H pylori, or both and resultant seroconversion, like that of H pylori infection in humans, were common in commercial swine operations. Furthermore, data indicated that gastric infection was acquired at an early age. The relationships to gastric colonization by HPLOs and clinical manifestations of disease such as gastritis and gastroesophageal ulceration remain to be determined.  相似文献   

Pharmacokinetics of intravenously administered caffeine in healthy alpacas (Lama pacos) and llamas (Lama glama)     

Lakritz J  Middleton JR  Anderson DE  Linden DR  Sams RA  Tessman RK  Tyler JW 《American journal of veterinary research》2006,67(6):1063-1069

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Use of a flow-mediated vasodilation technique to assess endothelial function in dogs     

Puglia GD  Freeman LM  Rush JE  King RG  Crawford SL 《American journal of veterinary research》2006,67(9):1533-1540

OBJECTIVE: To develop and assess the reproducibility of a protocol to noninvasively test endothelial function in dogs on the basis of the flow-mediated vasodilation (FMD) procedure used in humans. ANIMALS: 5 healthy spayed female dogs. PROCEDURES: Luminal arterial diameter and blood flow velocity in the brachial and femoral arteries were measured with ultrasonography. The within-dog reproducibility of these ultrasonographic measurements was tested. An occlusion period of 1, 3, or 5 minutes with an inflatable cuff was used to create the FMD response. Measurements made at 15, 30, and 60 seconds following release of the occlusion were compared with measurements made immediately prior to each occlusion to assess the FMD response. RESULTS: Within-dog reproducibility of measurements revealed moderate to high correlations. Change from baseline in luminal arterial diameter was most substantial when measured at 30 seconds following release of occlusion, whereas blood flow velocity changes were maximal when measured at 15 seconds following release. The brachial imaging site provided a larger number of significant FMD responses than the femoral site. The 3-minute occlusion period provided equal or better responses than the 5-minute occlusion period. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonographic measurement of the FMD responses was a feasible and reproducible technique and significant changes from baseline were detected. The FMD responses in dogs were most substantial when performed at the brachial artery with blood flow velocity and luminal arterial diameter changes from baseline measured at 15 and 30 seconds, respectively, following release of a 3-minute occlusion period.  相似文献