guanosine-triphosphate and Acute-Disease

The authors have shown previously that surgical specimens from infants with acute necrotizing enterocolitis (NEC) show upregulation of inducible nitric oxide (NO) synthase (iNOS) and interferon-gamma mRNA. However, the contribution of other inflammatory cytokines such as interleukin-8 (IL-8), IL-11, and IL-12 has not been defined. Likewise, the role of GTP-cyclohydrolase, the rate-limiting enzyme in tetrahydrobiopterin synthesis, and thus NO production by iNOS is unclear. In this study, the authors sought to further define the pattern of cytokine expression seen in infants with acute NEC.. The authors measured intestinal cytokine mRNA expression by semiquantitative reverse transcriptase polymerase chain reaction in 21 infants with histologically confirmed NEC, 18 with other inflammatory conditions, and in 9 patients without intestinal inflammation. Guanosine triphosphate-cyclohydrolase (GTP-CH) activity was measured by specific enzyme assay. Univariate exact logistic regression analysis was performed to identify predictors of outcome.. IL-8 and IL-11 mRNA were upregulated in patients with acute NEC compared with those with other inflammatory conditions or those without disease; these levels returned to baseline at the time of stoma closure. Increased IL-11 mRNA decreased the likelihood of pan-necrosis (odds ratio, 0.93; P =.002). Increased IL-12 levels (but not IL-8) seemed to protect against pan-necrosis (odds ratio, 0.70; P =.06).. Local upregulation of IL-11 may represent an adaptive response designed to limit the extent of intestinal damage in NEC. Decreased IL-12 levels may contribute to the pathogenesis of NEC by allowing bacteria to escape host defenses.

Topics: Acute Disease; Analysis of Variance; Culture Techniques; Cytokines; Enterocolitis, Necrotizing; Female; Gene Expression Regulation; Genetic Markers; Guanosine Triphosphate; Humans; Immunohistochemistry; Infant; Infant, Newborn; Interleukin-11; Interleukin-12; Interleukin-8; Logistic Models; Male; Prognosis; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity; Severity of Illness Index

The Ras signal transduction pathway is often deregulated in human myeloid leukaemia. For example, activating point mutations in RAS genes are found in some patients with juvenile chronic myelogenous leukaemia (JCML), while other patients with JCML show loss of the neurofibromatosis type 1 (NF1) gene, a Ras GTPase activating protein. By generating mice whose haematopoietic system is reconsituted with Nf1 deficient haematopoietic stem cells we show that Nf1 gene loss, by itself, is sufficient to produce the myeloproliferative symptoms associated with human JCML. We also provide evidence to indicate that Nf1 gene loss induces myeloproliferative disease through a Ras-mediated hypersensitivity to granulocyte/macrophage-colony stimulating factor (GM-CSF). Finally, we describe a genetic screen for identifying genes that cooperate with Nf1 gene loss during progression to acute myeloid leukaemia.

Topics: Acute Disease; Animals; Bone Marrow; Cell Differentiation; Cell Line, Transformed; Crosses, Genetic; Disease Models, Animal; Disease Progression; Female; Genes, Neurofibromatosis 1; Granulocyte-Macrophage Colony-Stimulating Factor; Guanosine Triphosphate; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Liver; Male; Mice; Mice, Inbred C57BL; ras Proteins; Signal Transduction

Serum hepatocyte growth factor (HGF) levels in patients with acute hepatic failure has been reported to increase. However, possible mechanisms responsible for HGF elevation in this syndrome remains to be determined. To explore the possible mechanisms, we measured serum HGF in patients with acute hepatic failure and self-limited acute hepatitis, using an immunoradiometric assay. Serum HGF levels in acute hepatic failure were 36-fold higher compared with those in acute hepatitis. Serum HGF values in acute hepatitis were significantly correlated with serum bilirubin and gamma-GTP levels, whereas those in acute hepatic failure were not. These clinical findings suggest that serum HGF levels in acute hepatic failure may be regulated by different mechanisms from those in self-limited acute hepatitis.

Topics: Acute Disease; Bilirubin; Female; Guanosine Triphosphate; Hepatitis; Hepatocyte Growth Factor; Humans; Immunoradiometric Assay; Liver; Liver Failure, Acute; Male; Organ Size

A marked diurnal variation in high-affinity binding of 2-[125I]iodomelatonin ([125I]MEL) in rat brain sections containing the suprachiasmatic nuclei (SCN) was observed. Binding was highest late in the light phase and lowest during darkness, in inverse correlation to the serum melatonin rhythm. Interestingly, only high-affinity sites were present during most of the light phase while both high- and low-affinity sites were detected just before and during darkness. Guanosine triphosphate (GTP) in combination with sodium converted all high affinity sites to a low affinity state suggesting that the two sites observed during darkness represent the two states of the melatonin receptor. Acute swim-stress caused a significant elevation of serum melatonin, together with a decrease in the density of [125I]MEL binding in the SCN. The inverse relationship between circulating melatonin levels and binding, under two different physiological conditions, indicates that this hormone is involved in regulating its own receptors in the SCN.

Topics: Acute Disease; Animals; Circadian Rhythm; Guanosine Triphosphate; Male; Melatonin; Protein Binding; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Receptors, Melatonin; Sodium; Stress, Physiological; Suprachiasmatic Nucleus

A case of erythropoietic protoporphyria (EPP) with severe acute abdominal pain and jaundice was reported. Erythrocyte protoporphyrin (PP) levels were constantly high, and liver histology showed a slight fibrosis with inflammatory infiltration. During the investigation period of 18 months, erythrocyte PP levels closely paralleled those of serum gamma-GTP.

Topics: Acute Disease; Adult; Biopsy; Erythrocytes; Erythropoiesis; Fibrosis; Guanosine Triphosphate; Humans; Liver Diseases; Male; Porphyrias; Porphyrins

Topics: Acute Disease; Alkaline Phosphatase; Aspartate Aminotransferases; Chronic Disease; Female; Guanosine Triphosphate; Hepatitis; Humans; Liver Cirrhosis; Male