ABSTRACT
BACKGROUND: High hyperdiploid (HeH) pre-B pediatric acute lymphoblastic leukemia (B-pALL) is known to be heterogeneous by prognosis, but the stratification principals according to conventional cytogenetic analysis (CCA) are equivocal. PROCEDURE: Untreated bone marrow samples of 214 B-pALL patients were previously classified according to the modal numbers (iMN8) based on the gains of the chromosomes 4, 6, 10, 14, 17, 18, 21, and X as revealed by consecutive and correlated 2×4 color interphase fluorescence in situ hybridization, and at least five years of follow up data were analyzed. RESULTS: Data from 48 of the 53 HeH (iMN8>50) B-pALL patients indicated that among the age, gender, WBC, and iMN8 parameters, only the last was significantly associated with overall survival (pOS), which allowed the cases to be classified as iMN8 51-54 (75%) and iMN8 ≥ 55 (95%). Among the specific chromosomal gains of +4, +4/+6, +4/+17 and +4/+18, the first exhibited the most significance in terms of beneficial outcomes. The better prognostic group according to the iMN8 was associated with a significantly reduced complexity of the subclonal landscape. However, iMN8 did not prove to be an independent variable but was instead overridden by isolated trisomy of chromosome 4. CONCLUSIONS: These data indicate that the better outcomes in the HeH B-pALL group arose from the gain of a specific chromosome that always ranks at the same position in the sequential acquisition of the affected chromosomes.
Subject(s)
Chromosomes, Human, Pair 4/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Trisomy , Child , Child, Preschool , Chromosome Aberrations , Diploidy , Female , Follow-Up Studies , Humans , Infant , Male , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Survival AnalysisABSTRACT
UNLABELLED: We aimed to test two hypotheses: (1) isolated small veins develop substantial myogenic tone in response to elevation of intraluminal pressure, (2) H2O2 contributes to the mediation of myogenic response via activation of arachidonic acid (AA) cascade and release constrictor prostaglandins. METHODS: Small veins were isolated from gracilis muscle of male rats, then cannulated. Changes of diameter to increases in intraluminal pressure, H2O2 and arachidonic acid in the presence and absence of various inhibitors were measured by videomicroscope and microangiometer. At the end of experiments the passive diameter were obtained in Ca2+ -free PSS solution. RESULTS: Isolated rat gracilis muscle small veins developed a substantial myogenic tone in response to increases in intraluminal pressure (1-12 mmHg). Calculated maximum myogenic tone was 70 ± 5% at 10 mmHg. Presence of catalase or indomethacin or SQ 29,548 reduced significantly the pressure-induced myogenic response. Also, H2O2 (10-9-10-5 M) and arachidonic acid (10-7-10-4 M) elicited concentration dependent constrictions, which were inhibited by the presence of indomethacin or SQ 29,548. CONCLUSION: We propose that both myogenic response and pressure-induced release of H2O2 play important roles in regulating the vasomotor function of venules both in physiological and pathological conditions.
Subject(s)
Hydrogen Peroxide/metabolism , Muscle, Skeletal/blood supply , Receptors, Thromboxane A2, Prostaglandin H2/metabolism , Animals , Bridged Bicyclo Compounds, Heterocyclic , Fatty Acids, Unsaturated , Hydrazines/pharmacology , In Vitro Techniques , Indomethacin/pharmacology , Male , Pressure , Rats , Rats, Wistar , Receptors, Thromboxane A2, Prostaglandin H2/antagonists & inhibitors , Thromboxane A2/metabolism , Veins/drug effects , Veins/metabolismABSTRACT
The basic patterns of thyroid hormones [thyroxine (T4) and 3,3',5-triiodothyronine (T3)] and the T4 and T3 responses induced by thyrotropin releasing hormone (TRH) are reported in captive female barn owls (Tyto alba) during the non-breeding period. The main findings of the study, conducted on a total of 10 owls, are as follow: (1) The thyroid gland of barn owl can be stimulated by the classical TRH stimulation test. (2) T3 response was much more pronounced both under cold (around 10 degrees C) and warm (around 20 degrees C) conditions, whereas T4 response ranged so widely that we could not point out any significant change in it. (3) Basal T3 plasma level was significantly (p = 0.036) higher in birds exposed to cold temperature, and they responded to TRH treatment with a lower plasma T3 elevation than the birds kept in a warm chamber. This pattern, however, cannot be explained by increased food intake, but is in agreement with the fact that enhanced T3 level may account for higher avUCP mRNA expression, which results in higher heat production on the cell level. From the results it is concluded that altering T3 plasma level plays a significant role in cold-induced thermoregulation.
