Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder due to clonal expansion of a pluripotent hematopoietic progenitor cell with secondary marrow fibrosis. No definitive treatment has as yet been devised for this condition, which shows a marked variability in clinical course. To evaluate whether excessive hematopoietic progenitor cell proliferation could be controlled by recombinant human interferon alpha (rIFN-alpha) and gamma (rIFN-gamma), we studied the effects of these agents on the in vitro growth of pluripotent and lineage-restricted circulating hematopoietic progenitor cells in 18 patients with MMM. A significant increase in the growth (mean +/- 1 SEM) per milliliter of peripheral blood of CFU-GEMM (594 +/- 253), CFU-Mk (1,033 +/- 410), BFU-E (4,799 +/- 2,020) and CFU-GM (5,438 +/- 2,505) was found in patients as compared with normal controls. Both rIFN-alpha and rIFN-gamma (10 to 10(4) U/mL) produced a significant dose-dependent suppression of CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM growth. Concentrations of rIFN-alpha and rIFN-gamma causing 50% inhibition of colony formation were 37 and 163 U/mL for CFU-GEMM, 16 and 69 U/mL for CFU-Mk, 53 and 146 U/mL for BFU-E, and 36 and 187 U/mL for CFU-GM, respectively. A marked synergistic effect was found between rIFN-alpha and rIFN-gamma: combination of the two agents produced inhibitory effects greater than or equivalent to those of 10- to 100-fold higher concentrations of single agents. These studies (a) confirm that circulating hematopoietic progenitors are markedly increased in MMM, (b) indicate that these presumably abnormal progenitors are normally responsive to rIFNs in vitro, and (c) show that IFNs act in a synergistic manner when used in combination. Because rIFN-gamma can downregulate collagen synthesis in vivo, this lymphokine could be particularly useful in the treatment of patients with MMM.
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PMID:Effects of recombinant alpha and gamma interferons on the in vitro growth of circulating hematopoietic progenitor cells (CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM) from patients with myelofibrosis with myeloid metaplasia. 311 31

A spectrum of tracheo-oesophageal malformations is seen in humans: oesophageal atresia, tracheal agenesis and laryngotracheo-oesophageal clefts. They are thought to share a common but unknown aetiology. These birth defects are frequently associated with other VACTERL anomalies. The adriamycin rat model (ARM) has proved to be a valuable model of the VACTERL anomalies, illustrating the dysmorphogenesis of oesophageal atresia and tracheal agenesis. As organogenesis relies on temporaspatially co-ordinated signalling systems, the next step would be to study the molecular pathogenesis of tracheo-oesophageal malformations. However, the mouse is the foremost mammal studied by developmental biologists, offering an expanding wealth of knowledge and scientific research techniques with which to investigate these anomalies. A limited dose response analysis of the teratogenicity of adriamycin in the mouse has identified a dose and timing of injections that produced tracheo-oesophageal malformations and other VACTERL anomalies. A clear account of the types and variability of the tracheo-oesophageal malformations produced by this dose is essential in order to be able to plan and interpret any future investigations of early gestation fetuses. CBA/Ca mice were accurately time-mated (n = 10). Nine dams received intraperitoneal injections of adriamycin (6 mg/kg) and one control dam received saline injections, on days 7 and 8. Fetuses were harvested on day 18, near term. Tracheo-oesophageal malformations were examined by dissecting microscope and serial transverse sections. Results are reported in the standard teratological manner as mean percentage per litter (+/-SEM). The resorption rate of the adriamycin treated fetuses was 50.4%. There were 29 adriamycin treated fetuses for inspection. Tracheo-oesophageal malformations were found in 29.2% (+/-10.3), affecting five out of nine litters. Oesophageal atresia occurred in 15.6% (+/-8.1), laryngotracheo-oesophageal cleft in 10.4% (+/-7) and tracheal agenesis in 3.1% (+/-3.1). All of these malformations occurred with a tracheo-oesophageal fistula. Unlike the ARM, the AMM can produce fetuses with complete laryngotracheo-oesophageal cleft as well as oesophageal atresia or tracheal agenesis. Their occurrence was found to be reproducible but variable. These are important considerations when planning and interpreting experiments using this model.
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PMID:Adriamycin mouse model: a variable but reproducible model of tracheo-oesophageal malformations. 1720 96

A recurrent specific JAK2 V617F mutation has been reported in bcr/abl-negative chronic myeloproliferative diseases (cMPD), including polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). The mutation is detectable in a variable proportion of neoplastic clones, depending on the molecular methods employed. In this study, we attempted to establish the JAK2 V617F mutation frequency in two partially overlapping cMPD patient series by two different PCR-based techniques. Using an allele-specific polymerase chain reaction assay (AS-PCR), the JAK2 V617F mutation was detected in 124/158 (78.5%) cMPD patients; in particular, 90.2, 72.1, 63.2 and 50% of PV, ET, IMF and unclassified (U)-MPD cases, respectively, showed the mutation. Employing a semiquantitative 5' fluorogenic TaqMan assay, the JAK2 V617F mutation was identified in a much larger percentage of cMPDs patients (118/127: 92.9%). Rates of mutation in PV, ET, IMF and U-MPD cases were 95.9, 85.7, 91.7 and 92.9%, respectively. Furthermore, a statistically higher percentage of JAK2 mutated alleles was detected by TaqMan assay in PV (68+/-3.5, mean value+/-SEM) and IMF (64+/-9.3) cases as compared with ET (35+/-5.4). Finally, a significant correlation between JAK2 V617F mutational status and hematocrit (Ht), white blood cell and platelet counts in PV patients, and Ht values in ET cases, was observed by AS-PCR. Overall, these data indicate that TaqMan technology significantly improved sensitivity in detecting the JAK2 mutation in cMPD patients and may be worth of further evaluations as a clinically useful tool for detection of small amounts of mutated clones.
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PMID:The incidence of JAK2 V617F mutation in bcr/abl-negative chronic myeloproliferative disorders: assessment by two different detection methods. 1872 Feb 12