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Factor VII Deficiency
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1. Delayed diagnosis of congenital factor IX deficiency (Christmas disease) in a girl with Turner's Syndrome.
Match Strength: 6.642

Patients with Turner's syndrome are at risk of X-linked recessive disorders. We report a case of a young girl with Turner's syndrome with persistent mildly abnormal coagulation studies associated with a mild to moderate bleeding diathesis. The abnormalities were initially attributed to intrahepatic cholestasis and were partially responsive to vitamin K. After an interval of several years an episode of unexplained iron deficiency anaemia prompted re-investigation of the mild coagulopathy. Disproportionate reduction in the factor IX concentration and restoration of haemostasis with factor IX ... Read More »
» Published in Clin Lab Haematol. 2006 Oct;28(5):355-6.

2. In-vitro and in-vivo consequences of mutations in the von Willebrand factor cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpura.
Match Strength: 4.612

Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by microvascular thrombosis, often associated with deficiency of the vonWillebrand factor (VWF) cleaving protease ADAMTS13. We investigated the spectrum of ADAMTS13 gene mutations in patients with TTP and congenital ADAMTS13 deficiency to establish the consequences on ADAMTS13 processing and activity. We describe five missense (V88M, G1239V, R1060W, R1123C and R1219W), 1 nonsense (W1016Stop) and 1 insertion (82_83insT) mutations. In two patients no mutation was identified despite undetectable protease activity. Expression in ... Read More »
» Published in Thromb Haemost. 2006 Oct;96(4):454-64.

3. Methotrexate-induced mucositis in mucin 2-deficient mice.
Match Strength: 4.339

The mucin Muc2 or Mycin2 (Muc2), which is the main structural component of the protective mucus layer, has shown to be upregulated during chemotherapy-induced mucositis. As Muc2 has shown to have protective capacities, upregulation of Muc2 may be a counter reaction of the intestine protecting against mucositis. Therefore, increasing Muc2 protein levels could be a therapeutic target in mucositis prevention or reduction. Our aim was to determine the role of Muc2 in chemotherapy-induced mucositis. Mucositis was induced in Muc2 knockout (Muc2(-/-)) and wild type (Muc2(+/+)) mice by injecting ... Read More »
» Published in J Cell Physiol. 2007 Jan;210(1):144-52.

4. Immune-mediated etiology of acquired von Willebrand syndrome in systemic lupus erythematosus and in benign monoclonal gammopathy: therapeutic implications.
Match Strength: 4.237

The most common nonimmune etiology of acquired von Willebrand syndrome (AvWS) includes hypothyroidism, Wilms' tumor, thrombocythemia, or congenital heart defects, and the use of various drugs. AvWS type 1 in patients with hypothyroidism is due to decreased Willebrand factor (vWF) synthesis and is reversible by treatment with thyroxin. AvWS type 1 or 3 in children with Wilms' tumor disappears after successful chemotherapy or tumor resection but the mechanism of the vWF deficiency is unknown. The AvWS type 2 in patients with thrombocythemia of various myeloproliferative disorders is caused by ... Read More »
» Published in Semin Thromb Hemost. 2006 Sep;32(6):577-88.

5. Leptin deficiency unmasks the deleterious effects of impaired peroxisome proliferator-activated receptor gamma function (P465L PPARgamma) in mice.
Match Strength: 4.179

Peroxisome proliferator-activated receptor (PPAR)gamma is a key transcription factor facilitating fat deposition in adipose tissue through its proadipogenic and lipogenic actions. Human patients with dominant-negative mutations in PPARgamma display lipodystrophy and extreme insulin resistance. For this reason it was completely unexpected that mice harboring an equivalent mutation (P465L) in PPARgamma developed normal amounts of adipose tissue and were insulin sensitive. This finding raised important doubts about the interspecies translatability of PPARgamma-related findings, bringing into ... Read More »
» Published in Diabetes. 2006 Oct;55(10):2669-77.

6. JNK2 is a positive regulator of the cJun transcription factor.
Match Strength: 4.023

The cJun NH(2)-terminal kinase (JNK) signal transduction pathway is established to be an important mechanism of regulation of the cJun transcription factor. Studies of Jnk1(-/-) and Jnk2(-/-) mice suggest that the JNK1 and JNK2 isoforms have opposite effects on cJun expression and proliferation. Here, we demonstrate, using a chemical genetic approach, that both JNK1 and JNK2 are positive regulators of these processes. We show that competition between JNK1 and JNK2 contributes to the opposite phenotypes caused by JNK1 and JNK2 deficiency. Our analysis illustrates the power of a chemical ... Read More »
» Published in Mol Cell. 2006 Sep 15;23(6):899-911.

7. Vitamin C deficiency increases the lung pathology of influenza virus-infected gulo-/- mice.
Match Strength: 3.775

This study was designed to determine the effects of vitamin C deficiency on the immune response to infection with influenza virus. l-Gulono-gamma-lactone oxidase gene-inactivated mice (gulo-/- mice) require vitamin C supplementation for survival. Five-wk-old male and female gulo-/- mice were provided water or water containing 1.67 mmol/L vitamin C for 3 wk before inoculation with influenza A/Bangkok/1/79. There were no differences in lung influenza virus titers between vitamin C-adequate and -deficient mice; however, lung pathology in the vitamin C-deficient mice was greater at 1 and 3 d after ... Read More »
» Published in J Nutr. 2006 Oct;136(10):2611-6.

8. CD18 in Monogenic and Polygenic Inflammatory Processes of the Skin.
Match Strength: 3.602

The beta(2) integrin family (CD11/CD18) of leukocyte adhesion molecules plays a key role in inflammation. Absence of the common beta chain (CD18) leads to leukocyte adhesion deficiency-1 (LAD1) in humans. We here summarize data of two genetically defined mice models of beta(2) integrin deficiency, one with a CD18 null mutation (CD18(-/-)), and the other one with a hypomorphic CD18 mutation (CD18(hypo)). Firstly, we focus on the underlying mechanism of a severely impaired wound healing in CD18(-/-) mice, outlining a scenario in which a defective extravasation and phagocytosis of CD18(-/-) ... Read More »
» Published in J Invest Dermatol. 2006 Sep;126 Suppl:7-15.

9. Omega-3 fatty acids and rodent behavior.
Match Strength: 3.478

This paper reviews the role of the n-3 fatty acids in the regulation of cognitive functions, locomotor and exploratory activity and emotional status in rodents. There are disparate data on the performance of n-3 fatty acid deficient animals in the open field test and elevated plus maze. Results obtained in our laboratory indicated slower habituation to the open field in deficient mice, which affects total locomotor and exploratory parameters. We also observed no change in plus maze performance of deficient mice under low-stress but elevated anxiety under high-stress conditions. There is some ... Read More »
» Published in Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):271-89. Epub 2006 Sep 14.

10. Prostate cancer: serum and tissue markers.
Match Strength: 3.415

The detection of prostate cancer, its clinical staging, and the prediction of its prognosis remain topics of paramount importance in clinical management. The digital rectal exam, although once the "gold standard," has been largely supplanted by a variety of techniques including serum and tissue-based assays. This article reviews recent progress in the development of prostate-specific antigen assays with greater specificity; molecular markers for prostate cancer (DNA ploidy, nuclear morphometry, markers of proliferation, and cell adhesion molecules); the link between vitamin D deficiency and ... Read More »
» Published in Rev Urol. 2001;3 Suppl 2:S11-9.

11. Calcineurin/Nfat signaling is required for perinatal lung maturation and function.
Match Strength: 3.345

Pulmonary surfactant proteins and lipids are required for lung function after birth. Lung immaturity and resultant surfactant deficiency cause respiratory distress syndrome, a common disorder contributing to morbidity and mortality in preterm infants. Surfactant synthesis increases prior to birth in association with formation of the alveoli that mediate efficient gas exchange. To identify mechanisms controlling perinatal lung maturation, the Calcineurin b1 (Cnb1) gene was deleted in the respiratory epithelium of the fetal mouse. Deletion of Cnb1 caused respiratory failure after birth and ... Read More »
» Published in J Clin Invest. 2006 Oct;116(10):2597-609. Epub 2006 Sep 21.

12. Less is more: pathophysiology of dopaminergic-therapy-related augmentation in restless legs syndrome.
Match Strength: 3.152

Therapy-related augmentation of the symptoms of restless legs syndrome (RLS) is an important clinical problem reported in up to 60% of patients treated with levodopa and, to a lesser extent, with dopamine agonists. The efficacy of low-dose dopaminergic drugs for RLS has been established, but the mode of action is unknown. Here, we review the existing data and conclude that augmentation is a syndrome characterised by a severely increased dopamine concentration in the CNS; overstimulation of the dopamine D1 receptors compared with D2 receptors in the spinal cord may lead to D1-related pain and ... Read More »
» Published in Lancet Neurol. 2006 Oct;5(10):878-86.

13. Emerging targets and novel strategies in the treatment of AIDS-related Kaposi's sarcoma: bidirectional translational science.
Match Strength: 3.068

Through the mentorship process, Dr. Arthur Pardee emphasized the critical importance of bidirectional translational research-not only advancing drug development from bench to bedside, but also bringing back precious clinical material to the laboratory to assess the biologic effects of therapeutic agents on their targets. This mini-review focuses on the signal transduction pathways of Kaposi's sarcoma (KS) and on how the knowledge of such pathways has led to the rational development of molecularly targeted pathogenesis-driven therapies. Acquired immune deficiency syndrome (AIDS) related-KS ... Read More »
» Published in J Cell Physiol. 2006 Dec;209(3):659-62.

14. Receptor-mediated clearance of factor VIII: implications for pharmacokinetic studies in individuals with haemophilia.
Match Strength: 2.959

Summary The present review discusses the current concept of receptor-mediated clearance of coagulation factor VIII (FVIII) from the circulation in vivo, which is one of the mechanisms regulating FVIII level in plasma. Several lines of experimental evidence suggest that two receptors from the low-density lipoprotein (LDL) receptor family, low-density lipoprotein receptor-related protein (LRP) and LDL receptor (LDLR), cooperate in this process. Administration of receptor-associated protein, a classical antagonist of these receptors, leads to prolongation of FVIII half-life in mice. The elevation ... Read More »
» Published in Haemophilia. 2006 Nov;12 Suppl 4:15-22.

15. Vitamin D status and glucose homeostasis in the 1958 British birth cohort: the role of obesity.
Match Strength: 2.674

OBJECTIVE: Obesity is a well-known risk factor for vitamin D deficiency. We evaluated the interrelationship between vitamin D status, body size, and glucose homeostasis, measured by HbA1c (A1C). RESEARCH DESIGN AND METHODS: Data are from the survey of the 45-year-old 1958 British birth cohort (2002-2004). Information on A1C, 25-hydroxyvitamin D [25(OH)D; an indicator of vitamin D status], and BMI was collected from 7,198 Caucasian subjects. RESULTS: 25(OH)D was < 75 nmol/l in 80% of the obese subjects (BMI > or = 30 kg/m2) versus 68% of the other subjects (P < 0.0001). Serum 25(OH)D ... Read More »
» Published in Diabetes Care. 2006 Oct;29(10):2244-6.

16. The paradox of platelet activation and impaired function: platelet-von Willebrand factor interactions, and the etiology of thrombotic and hemorrhagic manifestations in essential thrombocythemia and polycythemia vera.
Match Strength: 2.668

Patients with essential thrombocythemia (ET) and polycythemia vera (PV), complicated by microvascular ischemic or thrombotic events, have shortened platelet survival, increased beta-thromboglobulin, platelet factor 4, and thrombomodulin levels, and increased urinary thromboxane B2 excretion. These are all reversible by inhibition of platelet cyclooxygenase 1 with aspirin, and are therefore indicative of platelet activation and platelet-mediated thrombotic processes. The thrombotic tendency persists as long as platelet counts are above the upper limit of normal (400 x 10 (9)/L). Despite strong ... Read More »
» Published in Semin Thromb Hemost. 2006 Sep;32(6):589-604.

17. The dynamics of the LPS triggered inflammatory response of murine microglia under different culture and in vivo conditions.
Match Strength: 2.287

Overall, the inflammatory potential of lipopolysaccharide (LPS) in vitro and in vivo was investigated using different omics technologies. We investigated the hippocampal response to intracerebroventricular (i.c.v) LPS in vivo, at both the transcriptional and protein level. Here, a time course analysis of interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) showed a sharp peak at 4 h and a return to baseline at 16 h. The expression of inflammatory mediators was not temporally correlated with expression of the microglia marker F4/80, which did not peak until 2 days after LPS injection ... Read More »
» Published in J Neuroimmunol. 2006 Nov;180(1-2):71-87. Epub 2006 Sep 20.

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