Disease relevance of NKX6-2

• Cloning, expression and chromosomal location of NKX6B TO 10Q26, a region frequently deleted in brain tumors [1].
• However, the efficacy of these GTX in treating or preventing established neutropenic sepsis remains to be established in prospective controlled clinical trials [2].
• Infusion of G-CSF stimulated GTX results in measurable increases in the recipients' neutrophil count and may reduce the duration and severity of neutropenia [2].
• Early studies employing steroid mobilised GTX showed variable, dose-dependent results and significant pulmonary toxicity was reported [2].
• Bacterial meningoencephalitis occurring in the pre-engraftment period after bone marrow transplantation (BMT) is a rare complication, and the feasibility of granulocyte transfusion (GTX) in such cases remains to be elucidated [3].

High impact information on NKX6-2

• Mitral valve area in GTXP patients decreased from 2.5 +/- 0.4 to 2.1 +/- 0.3 cm2 (P < .05); however, mitral valve area in PTFE patients showed no significant change during follow-up (2.1 +/- 0.4 to 2.0 +/- 0.4 cm2, P = NS) [4].
• METHODS AND RESULTS: Between November 1986 and November 1993, 40 patients underwent mitral valve repair with artificial chordae using glutaraldehyde-tanned xenograft pericardium (GTXP) or polytetrafluoroethylene suture (PTFE) [4].
• Both glutaraldehyde-tanned xenograft pericardial chordae (GTXP) and extruded polytetrafluorethylene chordae (ePTFE) heal to papillary muscles and cusps [5].
• Wild-type channels from skeletal muscle (mu 1) were more sensitive to GTX modification than wild-type cardiac channels (rH1) by a factor of 1 [6].
• Introduction of specific mutations into a synthetic internal ribosome entry site (IRES(GTX)) derived from the GTX homeodomain protein revealed additional transcriptional activity [7].

Chemical compound and disease context of NKX6-2

• Results using pure concentrations of a sodium channel-specific toxin could be detected to inhibit hemolysis at a concentration of 0.3 microg/ml STX, 3.5 microg/ml for neo-STX, 3.0 microg/ml for GTX, and 5.0 microgl for TTX in the presence of ouabain and veratridine [8].
• Before GTX, all patients had fever despite antibiotic and antimycotic therapy, neutropenia (absolute neutrophil count ANC < 500/microl), increasing C-reactive protein (CRP) values, hypotension requiring dopamine infusion and three patients needed supplemental oxygen [9].
• The evolution of adjuvant and neoadjuvant chemotherapy and radiation for advanced pancreatic cancer: from 5-fluorouracil to GTX [10].
• On the other hand, spermine did not effect the growth of A. minutum T1, though it decreased the cell toxicity and the ratio of GTX 2 + GTX 3 (15.0 +/- 6.6%) [11].

Biological context of NKX6-2

• These results may implicate NKX6B as a candidate tumor suppressor gene for brain tumors, particularly for oligodendrogliomas [1].
• Finally, using STS content mapping and RH analyis, we demonstrated that NKX6B maps to the 10q26, a region where frequent loss of heterozygosity has been observed in various malignant brain tumors [1].
• Of particular interest was the regulated expression of Pax6 and Nkx6.1 mRNA and the absence of Pax7 transcription, indicating that neurons derived from NTERA2 pluripotent stem cells are characteristic of neuroectodermal cells of the ventral phenotype [12].
• A kinetics model is proposed to account for the behavior of GTX -modified sodium channels [13].

Anatomical context of NKX6-2

• A rapid increase of granulocytes in CSF was also observed, and cultures of blood and CSF became negative after GTX [3].
• Further studies are warranted to evaluate the clinical efficacy of GTX for the treatment of uncontrolled infections in granulocytopenic stem cell transplant recipients [3].
• CONCLUSION: Two necessary elements in the design of future trials of therapeutic GTX should be the transfusion of high doses of granulocytes and the provision of leukocytes that are crossmatch-compatible with the recipient's serum [14].

Associations of NKX6-2 with chemical compounds

• Toxin profiles of shellfish showed approximately the same composition as that of the dinoflagellate, although the shellfish contained several carbamate toxins (GTX I, GTX II, GTX IV and NEO) that were not detected in G. catenatum culture extracts [15].

Analytical, diagnostic and therapeutic context of NKX6-2

• Northern blot experiments showed that NKX6B expression is tightly controlled in a tissue-specific fashion with the highest site of expression being the brain [1].
• The expressed channels were measured using whole-cell patch-clamp techniques and examined for GTX sensitivity [6].
• Selected isolates from groups demonstrating 90% similarity were screened for their ability to metabolize a range of PST (gonyautoxins 1 and 4 [GTX 1/4], GTX 2/3, GTX 5, saxitoxin, and neosaxitoxin) using a novel screening method and confirming its results by high-performance liquid chromatography [16].
• We conducted a prospective, non-randomized study of granulocyte transfusions (GTX) to control acute life-threatening infections (44 episodes) and to prevent recurrence of severe fungal infections during HCT or intensive chemotherapy (23 episodes) [17].
• BACKGROUND: Meta-analysis was used to explain disagreements across controlled clinical studies of the efficacy of granulocyte transfusions (GTX) in the treatment of bacterial sepsis [18].

References