Effector modeling of the action of GABA-receptor complex ligands. Functional interactions of subunits of the complex

The distribution of the minimum effective doses of bicuculline, corasole and picrotoxin was studied in intact mice and in mice administered different doses of 1.4-benzodiazepines (phenazepam and its 1,2,4,5-tetrahydroxy derivatives) and sodium barbital. The changes in the "dose-response" relationship for thiosemicarbazide have been observed with the administration of the increasing doses of phenazepam and sodium barbital. The effects registered correspond to the modifications of the GABA-receptor complex by exogenous ligands. The forms of the "dose-response" relationship observed, the types of the antagonism between pharmacological agents and the cooperation of their interaction correspond to the indices obtained from the "quartet" model of the receptor-channel complex.     

Poly(ADP-ribosylation) of nuclear proteins in rat thymocytes

Specific antibodies to poly(ADP-ribose) were obtained and characterized. Using these antibodies, the tissue specificity of poly(ADP-ribose) modified nuclear proteins from rat thymocytes and hepatocytes was studied. The differences in the levels of poly(ADP-ribosylation) of nuclear proteins from both tissues were found to be quantitative rather than qualitative. Analysis of intranuclear distribution of poly(ADP-ribose) acceptor proteins revealed that the bulk of them is localized in the nuclear sap and matrix. A comparison of spectral properties of poly(ADP-ribosylated) proteins, using specific antibodies and label incorporation from [14C]NAD showed the existence of two protein groups. Some of those were modified in a great degree but exchange poly(ADP-ribose) at a slow rate, whereas others (e.g., histones and HMG proteins) modified in a small degree exchanged poly(ADP-ribose) at a much higher rate. The results obtained by different methods are discussed.     

Asymmetric incorporation of [14C]cyanate and of fluorescein isothiocyanate in mamillary body of conditioned rats

A marked decrease in overall learning capacity has been observed in rats injected with cyanate. Therefore it was of interest to test whether learning influenced carbamylation of brain proteins. Incorporation of [¹⁴C]cyanate into proteins of the mamillary body was selectively modified following operant conditioning of the rat, so that trained rats showed an asymmetric image with higher levels of incorporation in the right side than in the left side, as compared to control rats. These results were confirmed using fluorescein isothiocyanate. The asymmetry persisted once the learning had been well established.     

Lampetra (Eudontomyzon) gracilis,a synonym of Eudontomyzon danfordi

Synopsis Evidence is presented which suggests that the nonparasitic lamprey, Lampetra (Eudontomyzon) gracilis Kux, 1965, is conspecific with the parasitic lamprey Eudontomyzon danfordi Regan, 1911. The diagnostic characters of the holotype and of the non-type material of E. gracilis are features found in E. danfordi specimens in their second and final year of adult life, thereby making the former a junior synonym of the latter.     

Localization, analysis and evolution of transposed human immunoglobulin V kappa genes

The localization of V kappa gene regions to chromosome 2, on which the kappa locus is located, and to other chromosomes is described. The V kappa genes that have been transposed to other chromosomes are called orphons. The finding of two new V kappa genes on chromosome 22 is reported. A V kappa II gene of this region and two V kappa I genes of the Chr1 and the cos 118 regions were sequenced. The two V kappa I orphon sequences and two others that had been determined previously were 97.5% identical, indicating that they may have evolved from a common ancestor by amplification. A model of the evolution of the human V kappa orphons is discussed.     

Intestinal parasites in the Camiri, Gutierrez and Boyuibe areas, Santa Cruz Department, Bolivia

A parasitological study was carried out on 381 apparently healthy subjects from Camiri, Boyuibe, Gutierrez. Intestinal parasites and non-pathogenic protozoa were present in 78.7% of the population sampled; multiple infections were observed in 67.7% of the parasitized individuals. The protozoon most commonly found was Entamoeba coli (in 40.7% of specimens), followed by Giardia intestinalis (30.7%), Iodamoeba bütschlii (10%), Chilomastix mesnili (8.7%). Other protozoon parasites also present were Enteromonas hominis (3.4%), Retortamonas intestinalis (2.4%), Cryptosporidium (2.1%), Endolimax nana (2.1%), Balantidium coli (1.8%) and Pentatrichomonas hominis (0.8%). The helminths observed were hookworms (28.6%), Trichuris trichiura (19.7%), Ascaris lumbricoides (9.7%), Hymenolepis nana (8.7%), Trichostrongylus (5.5%), Strongyloides stercoralis (1.8%), Taenia (5 cases) and Enterobius (6 cases). Prevalence for nematodes is probably underestimated in the 3-9 years age group because of a mebendazole treatment given 5 weeks before the survey, under a Program of P D C of the Ministry of Health. The sample from Camiri was found to be the most parasitized (84.1%). An extraordinarily high infection rate was found in two urban institutions, as well as in Itanambicua, a rural community close to Camiri. No significant differences were observed in parasitic prevalence between rural and urban environments. Exposure to contamination with human and animal faeces, overcrowding and poor sanitation habits are some of the factors responsible for the parasitic situation evidenced.     

Epidemiology of tegumentary leishmaniasis in Mérida, Venezuela. I. Diversity and dispersion of phlebotomine species at 3 altitude levels and its possible role in the transmission of the disease

As part of an epidemiological study on leishmaniasis in Merida, Venezuela, the diversity and dispersion of sandflies species found in 15 localities between 175 m and 1,960 m.a.s.l., are presented. From 7,126 collected sandflies (5,132 female and 1,994 male), 24 species were identified, 10 of them recognized as anthropophilic. The relation species-altitude is presented, and the species composition found in human dwellings, periodomestic and sylvatic areas, are recorded. The possible role of the identified species on the transmission of leishmaniasis in the andean region, is discussed.     

Identification of genes involved in growth autonomy of hematopoietic cells by analysis of factor-independent mutants

The factor-dependent myeloid precursor cell line D35 mutates spontaneously at a frequency greater than 2.4 x 10(-7) to growth factor autonomy. This frequency could be increased at least 20-fold by retrovirus insertional mutagenesis. The isolation and characterization of factor-independent mutants allowed the identification of genes involved in growth autonomy. Mutants could be subdivided into two sets: those that secreted a stimulating factor (10/11) and those that did not (1/11). In one case, the factor released was distinct from previously characterized growth factors. In most mutants (6/9), the activation of a growth factor gene was associated with rearrangement that could be attributed to the insertion of a transposable-like element either 5' or 3' of the factor coding region in all cases examined, excluding oncogene involvement. All factor-independent mutants were tumorigenic, consistent with the hypothesis that growth-factor independence initiated by aberrant growth factor gene activation is an important and early step in tumorigenesis.