Tumor promoter chloroform is a potent protein kinase C activator

The major interaction site for tumor-promoting phorbol esters is the calcium-activated, phospholipid-dependent protein kinase (protein kinase C), a key-element in signal transduction. Binding of phorbol esters results in enzyme activation which mediates, at least in part, the action of these agents. We have investigated the effects of tumor promoter chloroform on protein kinase C activity. Like thrombin and 12-O-tetradecanoylphorbol-13-acetate (TPA), chloroform was able to activate protein kinase C in intact rabbit platelets. In addition, chloroform stimulated enzyme activity as well as TPA binding capacity in cell-free system. Scatchard analysis of the data has shown that chloroform increased the number of phorbol ester binding sites. Structurally related compounds, carbon tetrachloride and methylene chloride, activated the enzyme similarly.     

A case-control study on selenium,zinc, and copper in plasma and hair of subjects affected by breast and lung cancer

The purpose of our study was to investigate the relationship between plasma and hair levels of Se, Zn, and Cu, and cancer. We selected a total of 66 patients affected by either breast (38) or lung (28) cancer. They entered into the study at the onset of disease, and before any chemical or radiotherapy. Controls were randomly selected among healthy people and were matched for sex, age, smoking habits, and residence. In the group of breast cancer, a significant decrease in hair Se was found compared to controls (p<0.01), whereas plasma Se was only slightly decreased. No difference between cases and controls was detected in both hair and plasma levels of Zn and Cu. Subjects who developed lung cancer were significantly lower in hair Zn (p<0.05) and Cu (p<0.01) than controls, whereas there was no difference with regard to Se. In addition, plasma Cu of these patients was increased as compared to controls.     

Presence of telomeric and subtelomeric sequences at the fusion points of ring chromosomes indicates that the ring syndrome is caused by ring instability

In situ hybridization of a telomeric (TTA-GGG) _n sequence to metaphases from three cases of ring chromosome, involving respectively chromosomes 4, 16, and 20, showed the presence of the cognate sequences in all three rings. To investigate whether these ring chromosomes originated by telomere-telomere fusion, we determined, by in situ hybridization, whether telomere-associated sequences and/or specific distal sequences were still present in the ring chromosomes. The finding that these sequences were preserved in all the ring chromosomes strongly indicates that they originated by telomere-telomere fusion. All three subjects carrying the ring chromosomes are affected by the so-called ring syndrome, with failure to thrive, minor dysmorphic signs and no major anomalies. The r(4) patient has the ring in mosaic form with a normal cell line and has normal intelligence. The r(16) and the r(20) patients have moderate mental retardation and suffer from seizures. We conclude that the ring syndrome, even in its more severe manifestation, is caused by ring chromosome instability.     

Leaf characteristics and optical properties of different woody species

 Light partition has been examined and evaluated on five woody species (Olea europaea, Ficus carica, Pittosporum tobira, Hedera helix maculata, Persica vulgaris) in relation to their leaf morpho-histological characteristics, water and chlorophyll contents. Leaf parameters and optical properties (reflectance, transmittance, absorbance) in PAR, FR and NIR wavebands (400–1100 nm) were preliminarily submitted to a canonical correlation analysis where lamina thickness and water content showed a leading role in determining all the optical properties, while chlorophyll, influential in the PAR region, was remarkably effective only in an extreme pigment situation when green and albino patches of ivy leaves were compared. Transmittance appeared inversely related to lamina thickness in accordance with the Lambert Beer law. Significant correlations were found also between mesophyll water content and both transmittance (positive) and reflectance (negative). Olive leaves showed peculiar optical patterns because of the dense and continuous trichome layer on their abaxial surface. Received: 3 January 1997 / Accepted: 5 May 1997     

Comparative mapping of the DiGeorge syndrome region in mouse shows inconsistent gene order and differential degree of gene conservation

We have constructed a comparative map in mouse of the critical region of human 22q11 deleted in DiGeorge (DGS) and Velocardiofacial (VCFS) syndromes. The map includes 11 genes potentially haploinsufficient in these deletion syndromes. We have localized all the conserved genes to mouse Chromosome (Chr) 16, bands B1-B3. The determination of gene order shows the presence of two regions (distal and proximal), containing two groups of conserved genes. The gene order in the two regions is not completely conserved; only in the proximal group is the gene order identical to human. In the distal group the gene order is inverted. These two regions are separated by a DNA segment containing at least one gene which, in the human DGS region, is the most proximal of the known deleted genes. In addition, the gene order within the distal group of genes is inverted relative to the human gene order. Furthermore, a clathrin heavy chain-like gene was not found in the mouse genome by DNA hybridization, indicating that there is an inconsistent level of gene conservation in the region. These and other independent data obtained in our laboratory clearly show a complex evolutionary history of the DGS-VCFS region. Our data provide a framework for the development of a mouse model for the 22q11 deletion with chromosome engineering technologies. Received: 8 July 1997 / Accepted 11 August 1997     

Metabolism of N6,O2'-[3H]dibutyryl cyclic adenosine 3',5'-monophosphate and macromolecular interactions of the products perfused rat liver.

Mitochondria from liver, kidney, brain, and skeletal muscle metabolized acetaldehyde. Acetaldehyde oxidation by liver and kidney mitochondria was maximal at low levels of acetaldehyde and was sensitive to rotenone, suggesting the involvement of a NAD⁺-dependent aldehyde dehydrogenase with a high affinity for acetaldehyde. Acetaldehyde oxidation was stimulated 50% by ADP, suggesting that, in state 4, reoxidation of NADH is rate limiting for acetaldehyde oxidation. In state 4, acetaldehyde oxidation was decreased by NAD⁺-dependent substrates, as well as by succinate and ascorbate. The inhibition by the latter two substrates was prevented by ADP, dinitrophenol, valinomycin, and gramicidin, but not by oligomycin. Since these compounds are linked to energy transduction and utilization, the data suggest that the inhibition is mediated via energy-dependent reversed electron transport. In state 3, all of these substrates caused considerably less inhibition of acetaldehyde oxidation, suggesting that the activity of aldehyde dehydrogenase, and not of NADH reoxidation, is probably rate limiting for acetaldehyde oxidation. The ionophores valinomycin and gramicidin stimulated acetaldehyde oxidation to a greater extent than ADP. These ionophores also stimulated acetaldehyde oxidation in the presence of ADP. Stimulation by valinomycin occurred in the presence of monovalent cations transported by this ionophore, e.g., K⁺, Rb⁺, Cs⁺. Stimulation by gramicidin also occurred in the presence of these cations, but did not occur with Na⁺ or Li⁺. Na⁺ prevents the stimulation of acetaldehyde oxidation, which occurs in the presence of gramicidin and K⁺. The stimulation by valinomycin and gramicidin was energy dependent and required the presence of a permeant anion. In the absence of an ionophore, potassium phosphate had no effect on acetaldehyde oxidation. These data suggest that the oxidation of acetaldehyde by rat liver and kidney mitochondria is influenced by the oxidation-reduction state of the mitochondria and by the cationic environment. With brain and muscle mitochondria, the rate of acetaldehyde oxidation increased two- to threefold as the concentration of acetaldehyde was raised from 0.167 to 0.50 mm. Acetaldehyde oxidation in these mitochondria was also sensitive; to rotenone, indicating dependence on NAD⁺. ADP, valinomycin, gramicidin, and succinate, compounds which either increased or decreased the rate of acetaldehyde oxidation by liver and kidney mitochondria, had no effect on acetaldehyde oxidation by muscle or brain mitochondria. In state 4, mitochondria from Becker-transplantable hepatocellular carcinoma HC-252 oxidized acetaldehyde at the same rate as liver mitochondria. However, in the presence of ADP, dinitrophenol, valinomycin and gramicidin, the rate of acetaldehyde oxidation by the tumor mitochondria was two to three times greater than that of liver mitochondria, suggesting the presence of a more active; acetaldehyde-oxidizing system in tumor than in liver mitochondria.     

Nuclear protein synthesis in regenerating rat liver : Selective histone inhibition by α-amanitin

Nuclear protein synthesis has been studied in regenerating rat hepatocytes after partial hepatectomy and α-amanitin treatment. The toxin induced a marked and precocious inhibition of histone synthesis without affecting the acidic nuclear proteins. This inhibition preceded the inhibition of DNA synthesis. The modification of polyribosome profile and of [¹⁴C]lysine incorporation on synthesized polypeptides were consistent with a reduction of specific mRNAs.