The effect of the adrenal cortex and diet composition on the rate of acetoacetate formation by liver slices from infant and adult rats

Zusammenfassung Hoher Acetoacetatanteil in Leber junger Ratten wird durch Kortikosteronverabreichungin vivo am 10. Tag nach Geburt erniedrigt. Bei erwachsenen Ratten kein Hormoneinfluss. Adrenalektomie (14. Tag nach Geburt) führt zu hoher Produktion (19. Tag). Nur bei erwachsenen, nicht hungernden Ratten ist dies weniger ausgeprägt.     

The activities of citrate cleavage enzyme,acetyl-CoA synthetase and lipoprotein lipase in white and brown adipose tissue and the liver of the rat during development

Zusammenfassung Während der Rattenontogenese wurde die Aktivität des Citrat-Cleavage-Enzyms und der Acetyl-CoA-Synthetase in der Leber und im braunen und weissen Fettgewebe bestimmt. In allen Geweben wird die Aktivität vor der Geburt höher als nach der Geburt, wobei die Adultwerte nach dem 30. postnatalen Tag erreicht werden. Die Aktivität der Lipoproteinlipase ist im Säuglingsalter gross und sinkt nach der Entwöhnung ab.     

Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells

Betel quid (BQ) chewing shows a strong correlation to the incidence of oral submucous fibrosis (OSF), leukoplakia and oral cancer. BQ contains mainly areca nut, lime, Piper betle leaf (PBL) and the inflorescence of P. betle (IPB). Hydroxychavicol (4-allyl-catechol, HC), as a major phenolic compound in PBL and IPB, is shown to induce oxidative stress, glutathione (GSH) depletion and cell cycle deregulation. Using bivariate BrdU/PI flow cytometry, KB cells in DNA synthesis (S phase) are shown to be sensitive to the toxic effect of HC and show cell cycle arrest and apoptosis following exposure to 0.1 and 0.3 mM HC. HC-induced apoptosis and cell cycle arrest are associated with mitochondrial membrane potential (m) depolarization as revealed by a decrease in rhodamine fluorescence. N-acetyl-L-cysteine (1 mM), superoxide dismutase (100 U/ml) and catalase (1000 U/ml) were effective in prevention of HC-induced GSH depletion (as indicated by chloromethylfluorescein fluorescence), reactive oxygen species (ROS) production (by dichlorofluorescein fluorescence), cell cycle arrest and apoptosis. However, dimethylthiourea (2 mM), neocuproine (1 mM), 1,10-phenanthroline (200 M) and desferrioxamine (0.5 mM) showed little effect on HC-induced cell changes. HC elevated the cellular and mitochondrial GSH levels at moderate concentrations (0.05–0.1 mM), whereas at a concentration of 0.3 mM, inhibitory effects were noted. These results indicate that HC consumption may be associated with BQ-chewing-related oral mucosal diseases via GSH depletion, ROS production, mitochondrial dysfunction, cell cycle disturbance and the induction of apoptosis. These events are related to the production of superoxide radicals and hydrogen peroxide.Received 9 July 2003; received after revision 28 September 2003; accepted 24 October 2003     

Biologically diverse molecular variants within a single HIV-1 isolate

AIDS is a disorder characterized by a slow progressive impairment of immune function and by infection of human immunodeficiency viruses (HIV-1, HIV-2). Our knowledge of how these viruses cause disease in man, or how the related lentiviruses (visna and equine infectious anaemia virus) cause disease in animals, is still fragmentary. In particular, the significance of genetic variation in HIV-1, occurring within populations, within individuals and over periods of time, and the mechanisms of viral persistence remain unclear. To address these issues we prepared a series of proviral clones of HIV-1 originating from a single patient and compared their biological properties. Here we show that hybrid genomes (in which the envelope region of six viral clones were separately substituted into a prototype HIV-1 genome) generated viruses with widely differing capacity to grow in human T cells, cell lines and monocytoid cultures. These data suggest that extensive biological variation exists in vivo within an infected individual and is in part determined at the level of the viral envelope.     

Aktivierung einer alkalischen Phosphatase

Summary -Glycerophosphatase prepared from the intestinal mucosa of the calf was purified by fractionated precipitation with alcohol. A further concentration of the enzyme activity was attained by electrophoresis.The activity of the purified enzyme solution was reduced to of its original value when dialysed for 48 hours atp _H 4.5. Atp _H 6 and atp _H 10.5 only a less pronounced decrease of the activity occurred.By addition of heat-inactivated-glycerophosphatase to the enzyme solution which was partly inactivated by dialysis atp _H 4.5 the activity of the latter was increased by about 100%.     

Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion

Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events.     

Human immunodeficiency viruses: SIV infection in wild gorillas

Chimpanzees (Pan troglodytes troglodytes) from west central Africa are recognized as the reservoir of simian immunodeficiency viruses (SIVcpzPtt) that have crossed at least twice to humans: this resulted in the AIDS pandemic (from human immunodeficiency virus HIV-1 group M) in one instance and infection of just a few individuals in Cameroon (by HIV-1 group N) in another. A third HIV-1 lineage (group O) from west central Africa also falls within the SIVcpzPtt radiation, but the primate reservoir of this virus has not been identified. Here we report the discovery of HIV-1 group O-like viruses in wild gorillas.     

Spliceosome mutations in hematopoietic malignancies

Recent studies, including two in this issue, report heterozygous missense mutations in the U2AF1 and SF3B1 genes that encode spliceosome subunits. U2AF1 is frequently mutated in myeloid hematopoietic malignancies, especially in myelodysplastic syndrome (MDS), and SF3B1 is frequently mutated in both MDS and chronic lymphocytic leukemia (CLL).