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1.
2.
DL-alpha-difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase (ODC), rapidly depletes cells of intracellular putrescine. When administered to animals and humans, DFMO cures acute infections of trypanosomiasis. In order to determine if the mechanism of drug action is related to initiation of transformation and biochemical alterations subsequent to polyamine depletion, trypanosome morphology and mitochondrial activation were studied in a monomorphic strain of Trypanosoma brucei brucei. Exposure of trypanosomes to DFMO in vivo in infected rodents or in vitro in culture resulted in a depletion of intracellular putrescine and a cessation of cell division without specific cytotoxicity. These events were followed by a transformation of the long slender bloodstream form to a short stumpy form via an intermediate morphology. Putrescine, the product of the ODC reaction, abrogates this effect. When introduced into SDM-79 medium, the intermediate form is capable of further transformation to an "insect" procyclic trypomastigote whereas the long slender form and short stumpy form are not. Short stumpy forms are incapable of binary fission and have lost their infectivity for the vertebrate host. In addition, the mitochondrial marker enzyme, NAD diaphorase, was found only in the short stumpy and intermediate forms. We hypothesize that the short stumpy phenotype may not be a viable stage in the natural transformation of the trypanosome from its mammalian host to the insect vector. 相似文献
3.
Lino Piccinini Paola Borella Annalisa Bargellini Cristina Incerti Medici Alessandra Zoboli 《Biological trace element research》1996,51(1):23-30
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. 相似文献
4.
Annalisa Pezzolo Giorgio Gimelli Amnon Cohen Antonella Lavaggetto Cesare Romano Giuseppina Fogu Orsetta Zuffardi 《Human genetics》1993,92(1):23-27
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. 相似文献
5.
E. Baldini Osvaldo Facini Fabrizio Nerozzi Federica Rossi Annalisa Rotondi 《Trees - Structure and Function》1997,12(2):73-81
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 相似文献
6.
Annalisa Botta Elizabeth A. Lindsay Vesna Jurecic Antonio Baldini 《Mammalian genome》1997,8(12):890-895
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 相似文献
7.
Mary C. O'Sullivan Qibing Zhou Zhili Li Timothy B. Durham Donna Rattendi Schennella Lane Cyrus J. Bacchi 《Bioorganic & medicinal chemistry》1997,5(12):2145-2155
Trypanothione reductase (TR) occurs exclusively in trypanosomes and leishmania, which are the etiological agents of many diseases. TR plays a vital role in the antioxidant defenses of these parasites and inhibitors of TR have potential as antitrypanosomal agents. We describe the syntheses of several spermine and spermidine derivatives and the inhibiting effects of these compounds on T. cruzi TR. All of the inhibiting compounds displayed competitive inhibition of TR-mediated reduction of trypanothione disulfide. The three most effective compounds studied were N4,N8-bis(3-phenylpropyl)spermine (12), N4,N8-bis(2-naphthylmethyl)spermine (14), and N1,N8-bis(2-naphthylmethyl)spermidine (21), with Ki values of 3.5, 5.5 and 9.5 μM, respectively. Compounds 12, 14, and 21 were found to be potent trypanocides in vitro with IC50 values ranging from 0.19 to 0.83 μM against four T. brucei ssp. strains. However, these compounds did not prolong the lives of mice infected with trypanosomes. This work indicates that certain polyamine derivatives which target a unique pathway in Trypanosomatidae have potential as antitrypanosomal agents. 相似文献
8.
Polyamines were determined by n-butanol extraction and thin-layer chromatography in four trypanosomatids: Trypanosoma brucei (rat infection) and cultures of Crithidia fasciculata, Leptomonas sp., and Trypanosoma mega. All had putrescine and spermidine but no detectable spermine. Putrescine and spermidine levels were quantitated for extracts of leptomonas during the normal growth cycle. Spermidine values peaked 18 h before peak cell populations. Spermidine-putrescine ratios for all organisms were related to the presumed phylogeny of the group. 相似文献
9.
C Lambros C J Bacchi S L Marcus S H Hutner 《Biochemical and biophysical research communications》1977,74(3):1227-1234
Antrycide and ethidium bromide — 2 cationic trypanocides — inhibited NAD-linked α-glycerophosphate dehydrogenase from sp. The kinetics of enzyme inhibition was determined by Lineweaver-Burk, Dixon, or direct linear plots. Inhibition by Antrycide was noncompetitive for dihydroxyacetone phosphate in the presence of saturating Mg2+ or spermidine. With dihydroxyacetone phosphate at saturation, Antrycide inhibition was also noncompetitive with respect to Mg2+ (Ki = 115 μM) and spermidine (Ki = 85 μM). Inhibition by ethidium in the presence of saturating dihydroxyacetone phosphate, was noncompetitive for Mg2+ (Ki = 400 μM) but mixed for spermidine (Ki = 495 μM); inhibition was noncompetitive for dihydroxyacetone phosphate in the presence of saturating Mg2+ or spermidine. Rabbit-muscle α-glycerophosphate dehydrogenase was inhibited at all concentrations of Antrycide and ethidium tested, but the enzyme was stimulated up to 3.5-fold by low concentrations of inhibitors in the absence of polyamine. New chemotherapeutic possibilities may thus be opened and an evolutionary distinction between trypanosomatid and mammalian enzyme. 相似文献
10.
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. 相似文献