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Am J Physiol Lung Cell Mol Physiol. 2002 Jun;282(6):L1253-65.
Wild-type levels of the mouse Forkhead Box f1 gene are essential for lung repair.
Kalinichenko VV, Zhou Y, Shin B, Stolz DB, Watkins SC, Whitsett JA, Costa RH.
Department of Molecular Genetics, College of Medicine, University of Illinois at Chicago, 60607-7170, USA.
The Forkhead Box (Fox) family of transcription factors plays important roles in regulating expression of genes involved in cellular proliferation and differentiation. In a previous study, we showed that newborn foxf1(+/-) mice with diminished Foxf1 levels exhibited abnormal formation of pulmonary alveoli and capillaries and died postnatally. Interestingly, surviving newborn foxf1(+/-) mice exhibited increased pulmonary Foxf1 levels and normal adult lung morphology, suggesting that wild-type Foxf1 levels are required for lung development and function. The present study was conducted to determine whether adult foxf1(+/-) mice were able to undergo lung repair similar to that observed in wild-type mice. We demonstrated that adult foxf1(+/-) mice died from severe lung hemorrhage after butylated hydroxytoluene (BHT) lung injury and that this phenotype was associated with a 10-fold decrease in pulmonary Foxf1 expression and increased alveolar endothelial cell apoptosis that disrupted capillary integrity. Furthermore, BHT-induced lung hemorrhage of adult foxf1(+/-) mice was associated with a drastic reduction in expression of the Flk-1, bone morphogenetic protein-4, surfactant protein B, platelet endothelial cell adhesion molecule, and vascular endothelial cadherin genes, whereas the expression of these genes was either transiently diminished or increased in wild-type lungs after BHT injury. Because these proteins are critical for lung morphogenesis and endothelial homeostasis, their decreased mRNA levels are likely contributing to BHT-induced lung hemorrhage in foxf1(+/-) mice. Collectively, our data suggest that sustained expression of Foxf1 is essential for normal lung repair and endothelial cell survival in response to pulmonary cell injury.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12003781&dopt=Abstract hemorrhage
Theriogenology. 2002 Dec;58(9):1705-12.
Uterine prolapse with an interesting vascular anomaly in a cheetah: a case report.
Nothling JO, Knesl O, Irons P, Lane E.
Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa. jnothlip.up.ac.za
A 5-year-old cheetah suffered a complete prolapse of the left uterine horn after the birth of her second litter. Two attempts to reduce the prolapse transvaginally failed. The animal was hospitalized 13 days after the prolapse first occurred, and an ovariohysterectomy was performed to resolve the prolapse. The prolapsed uterine horn had been mutilated: its tip, together with the ipsilateral ovary was absent. Laparotomy revealed no sign of recent or past hemorrhage or adhesions, or any signs of the left ovarian artery or left ovarian vein in the remnants of the left mesovarium. A large vein crossed the uterine body from the left uterine horn to join the right uterine vein, presumably serving as the only route of venous drainage for the prolapsed uterine horn. A possible cause for the prolapse is excessive mobility of the uterus due to prior rupture of its mesial support. The animal died 24 days after surgery due to chronic renal failure, as a result of severe renal amyloidosis.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12472140&dopt=Abstract hemorrhage
Ann Diagn Pathol. 2002 Apr;6(2):100-5.
Primary mediastinal giant cell tumors: a clinicopathologic and immunohistochemical study of two cases.
Fu K, Moran CA, Suster S.
Department of Pathology, The University of Alabama at Birmingham, 35294, USA.
Two cases of posterior mediastinal giant cell tumors are presented. The patients are a woman and a man, 31 and 18 years old, respectively. One of the patients had symptoms of paresthesias while the other was completely asymptomatic. Complete physical examination did not disclose evidence of tumor elsewhere. Neither patient had a previous history of malignancy. Surgical resection was performed. Histologically, both tumors were composed of a proliferation of osteoclast-like giant cells associated with a mononuclear cell population composed of oval and spindle cells. Mitotic activity and mild cellular atypia were present in the mononuclear cell component. No evidence of necrosis or hemorrhage could be demonstrated in either case. Immunohistochemically, both tumors showed strong positive reaction in the mononuclear component for antibodies against vimentin and CD68, while keratin, epithelial membrane antigen, CD45, S-100 protein, and desmin were negative. On clinical follow-up, both patients are alive and well without evidence of recurrence or metastasis 6 and 108 months after surgery. The present cases highlight the ubiquitous distribution of soft tissue giant cell tumors and the importance of considering these tumors in the differential diagnosis of posterior mediastinal neoplasms. 2002, Elsevier Science (USA). All rights reserved.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12004357&dopt=Abstract hemorrhage
Xenotransplantation. 2002 Jan;9(1):36-44.
HDAF transgenic pig livers are protected from hyperacute rejection during ex vivo perfusion with human blood.
Luo Y, Levy G, Ding J, Qi J, Chakbrati S, Garcia BM, Phillips MJ, Kumar N, Friend P, Noble L, Macdonald J, Zhong R, Grant D.
Transplantation Technologies Inc, London, Ontario, Canada.
The aim of this study was to determine if human decay-accelerating factor (hDAF) protects against hyperacute rejection in an ex vivo liver perfusion system using human blood. Pig livers were perfused ex vivo via the portal vein for an average of 5-6 h using a membrane oxygenator. Three groups were studied. Group I: Wild-type pig livers were alloperfused with fresh pig blood (n = 5). Group II: Wild-type pig livers were xenoperfused with fresh human blood (n = 5). Group III: hDAF transgenic pig livers were xenoperfused with fresh human blood (n = 5). The graft ischemic time, ratio of perfusate volume to liver weight, flow rate, and perfusate hematocrit were similar in each group. The hDAF livers perfused with human blood (Group III) had a lower ALT level, less protein and albumin losses, lower bilirubin levels in the perfusate, less weight gain, and greater bile production than the wild-type livers perfused with human blood. Histology showed classic features of hyperacute rejection in Group II, including massive hemorrhage, severe vasculitits, fibrin and C5b-9 deposition, and endothelial damage within 1 h of perfusion, whereas liver histology studies in Groups I and III were near normal. IgG and IgM deposits were seen in the xenoperfused livers. Electron microscopy (EM) and immuno-EM showed loss of endothelial cells, trapping of white blood cells and platelets, and diffuse fibrin deposits in Group II only. hDAF pig livers perfused with human blood showed superior function and histology when compared with wild-type pig livers. These data suggest that (1) hyperacute rejection may contribute to the inconsistent results using wild-type pig livers for extracorporeal liver support and (2) genetically modified pigs that express hDAF may provide a better donor source than wild-type pigs for extracorporeal liver support.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12005103&dopt=Abstract hemorrhage
Life Sci. 2002 Mar 8;70(16):1901-8.
Role of MAPK in chronic cerebral vasospasm.
Aoki K, Zubkov AY, Tibbs RE, Zhang JH.
Department of Neurosurgery, University of Mississippi Medical Center, Jackson 39216-4505, USA.
This study was undertaken to investigate the role of p44/42 MAPK in a dog double hemorrhage model of subarachnoid hemorrhage (SAH), and whether MEK inhibitors can alter the degree of SAH-induced vasoconstriction. The diameter of the basilar artery, which was compared with day 0 angiogram, decreased gradually in a time-dependent manner from day 3 (80%), day 5 (68%) through day 7 (53.5%). The level of MAPK (p44/42) immunoprecipitation peaked on day 3 and remained enhanced through day 7 (P < 0.05). MEK inhibitor PD98059 significantly reduced p44/42 MAPK immunoprecipitation and significantly reversed vasospasm and increased residual diameter to 79.0% on day 7. These results demonstrated that p44/42 MAPK kinase is involved in the pathogenesis of cerebral vasospasm. The MEK inhibitor PD98059 might be useful in the treatment of vasospasm.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12005175&dopt=Abstract hemorrhage
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