Biomedical subjects
Publications and source records attributed to N Ferrand.
Genetic polymorphism of plasma properdin factor B (BF) was detected in domestic rabbit, Oryctolagus cuniculus, by means of isoelectric focusing and immunoblotting. The analysis of 298 individuals, corresponding to one French and two Portuguese populations, revealed the existence of six alleles, of which BF*A, B and C were common alleles, and D, F and G were rare ones.
To study the formation of target specific afferents on brain stem motoneurones of the rat, we used an organotypic co-culture of embryonic rat (E18) brain stem explants containing the facial or hypoglossal motor nuclei together with a tongue explant. The brain stem explants also contained known dorsal premotor structures such as lateral reticular nuclei and vestibular or spinal trigeminal nuclei. In cultures maintained in vitro for over 3 weeks, silver impregnation studies identified neurones in the dorsal sensory structures with axons arborizing within the motor nucleus. A double fluorescent labelling procedure demonstrated that axons originating from dorsal sensory regions come in close contact with identified motoneurones. Electrical stimulation of neurones in the dorsal regions induced monosynaptic and polysynaptic EPSPs and spikes in identified motoneurones together with muscle contraction. This work demonstrates that premotor structures in slice cultures develop organotypic functional synaptic connections with embryonic brain stem motoneurones.
Genetic variation in the golden-striped salamander (Chioglossa lusitanica) was assessed in 231 individuals from four Portuguese populations by means of horizontal starch gel electrophoresis and isoelectric focusing. Three of 19 enzyme systems, representing 21 presumptive loci, were found to be polymorphic: phosphoglucomutase 1 (PGM1), peptidase B (PEPB), and peptidase D (PEPD). The observed average heterozygosity in Chioglossa lusitanica (0.027) is significantly lower than that observed for other amphibians, either urodeles or salamandrids. Differences in allele frequencies and the presence of private alleles are indicative of a high degree of population differentiation. PEPD, in particular, seems to be a diagnostic locus separating the southernmost population studied from the others.
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The E26 and avian erythroblastosis virus (AEV) avian retroviruses induce acute leukemia in chickens. E26 can block both erythroid and myeloid differentiation at an early multipotent stage. Moreover, E26 can block erythroid differentiation at the erythroid burst-forming unit/erythroid CFU (BFU-E/CFU-E) stage, which also corresponds to the differentiation stage blocked by AEV. AEV carries two oncogenes, v-erbA and v-erbB, whereas E26 encodes a single 135-kDa Gag-Myb-Ets fusion oncoprotein. v-ErbA is responsible for the erythroid differentiation arrest through negative interferences with both the retinoic acid receptor (RAR) and the thyroid hormone receptor (T3R/c-ErbA). We investigated whether Myb-Ets could block erythroid differentiation in a manner similar to v-ErbA. We show here that Myb-Ets inhibits both RAR and c-ErbA activities on specific hormone response elements in transient-expression assays. Moreover, Myb-Ets abrogates the inactivation of transcription factor AP-1 by RAR and T3R, another feature shared with v-ErbA. Myb-Ets also antagonizes the biological response of erythrocytic progenitor cells to retinoic acid and T3. Analysis of a series of mutants of Myb-Ets reveals that the domains of the oncoprotein involved in these inhibitory activities are the same as those involved in oncogenic transformation of hematopoietic cells. These data demonstrate that the Myb-Ets oncoprotein shares properties with the v-ErbA oncoprotein and that inhibition of ligand-dependent RAR and c-ErbA functions by Myb-Ets is responsible for blocking the differentiation of hematopoietic progenitors.
Four new alleles at the rabbit (Oryctolagus cuniculus) mannose-6-phosphate isomerase (E.C. 5.3.1.8, MPI) locus are proposed to account for phenotypes observed after starch gel electrophoresis and enzymatic staining of red cell lysates and tissues. Population data from various wild and domestic rabbit populations are presented.
Cellular processes underlying ontogenesis and regression of streptozotocin (STZ)-induced diabetes in newborn rats were investigated at the most severe stage of diabetes at day 3 and after recovery of normoglycemia at day 8 by immunocytochemistry and quantitative analysis. A previously unknown endocrine cell type subpopulation (PEPS) was identified. It was characterized by granule polymorphism, coexpression of insulin and glucagon immunoreactivity, and a proliferative capacity transiently higher than in B cells. In STZ-treated rats at day 3, B cell mass decreased 14-fold, whereas PEPS cells were unaffected. The islet mass was restored to 55.7% by day 8, with a concomitant appearance of numerous small islets contiguous to small ducts. B cell mass increased by 6.9-fold compared with 1.8-fold in control rats, although proliferative capacities remained similar. Proliferation dropped considerably by day 8, preventing complete B cell mass recovery in STZ-treated rats. STZ-induced neonatal diabetes thus stimulates neogenesis of islets close to ducts and proliferation of PEPS cells. Those partially differentiated islet cells appear to be on the differentiation pathway of stem cells to fully differentiated B cells.
In AEV-transformed erythroleukemic cells the v-erbA gene product is likely to antagonize the function of triiodothyronine (T3) and retinoic acid (RA) receptors and thereby to block cell differentiation. We have thus investigated the effects of T3 and RA on normal early erythrocytic progenitor cells. Here we show: (1) that either RA or T3 play an essential role during the early commitment to erythrocytic differentiation, (2) that both T3 and RA induce death by apoptosis and a strong inhibition of self-renewal in progenitor cells grown in the absence of differentiation-inducing agents and (3) that the v-erbA oncogene renders erythrocytic progenitor cells insensitive to apoptosis and to self-renewal inhibition induced by RA or T3. The behaviour of a non-transforming mutant of v-erbA suggests that this v-erbA-induced protection is related to its transforming potential.
Genetic polymorphism in transferrin (TF) and in the haemoglobin alpha chain (HBA) was detected in the brown hare (Lepus europaeus) from Austria and Czechoslovakia by means of horizontal agarose and starch gel electrophoresis, respectively. Genetic analyses of complete families suggest that the TF and the HBA systems are each controlled by one autosomal gene locus with two codominant alleles. The distribution of both polymorphisms among some free-ranging Austrian brown hare populations was examined and the observed genotypes were in good agreement with the Hardy-Weinberg expectations. A comparison between the brown hare and the rabbit revealed no bands in common. The HB beta-chain was monomorphic in all specimens investigated.
Genetic polymorphism of serum albumin was demonstrated by isoelectric focusing in wild rabbit populations from Portugal and England. Gene frequencies were estimated to be (1) ALB*1 = 0.47, ALB*2 = 0.49, ALB*3 = 0.04, in Portugal, and (2) ALB*1 = 0.60 and ALB*2 = 0.40, in England. One hundred Portuguese domestic rabbits of mixed breeds were all of ALB 1 type.
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A technique for the separation of human alloalbumin variants by means of isoelectric focusing in the presence of 8M urea and 60 mM L-serine is described. The potential usefulness of this technique in the detection and classification of genetic heterogeneity at the albumin locus is demonstrated by the differentiation of three human alloalbumin variants of European origin.
The minimal gene diversity at a locus of the antibody constant region, as estimated in natural populations of rabbit, revealed levels of heterozygosity similar to those reported for the major histocompatibility complex in human and murine populations. Sera of 416 wild rabbits were collected on the Iberian peninsula and on three islands of the Azorean archipelago and analyzed for the occurrence of the serological markers of the b locus of the immunoglobulin light chain. All four serotypes present in domestic rabbits were found in Portugal. They represented less than 50% of the gene pool. In Andalusia this was less than 15% and on the Azorean islands less than 10%. The pronounced and systematic hierarchy in allele frequencies, previously found in populations from the more recent distribution area of the species, was not observed. On the peninsula, the frequencies of the "domestic" alleles were similar, averaging 10%. The Portuguese sample revealed a total heterozygosity of at least 87%. This high value was supported by at least 11 serologically different alleles, none of them occurring at frequencies above 20%. These data are in agreement with an Iberian origin of the European rabbit and strongly suggest the coalescence of b locus allelic lines drawn from Iberian and western populations. The role of balancing selection in the evolution of the b locus polymorphism was further emphasized.
A genetic polymorphism of rabbit (Oryctolagus cuniculus) hemoglobin alpha chain is demonstrated by means of acid starch gel electrophoresis. The polymorphism is not detected by isoelectric focusing and may be based upon neutral for neutral amino acid substitutions in accordance with previous findings by means of amino acid sequencing. Segregation analysis was performed on 15 matings with 49 offspring and confirmed the initial genetic hypothesis of three common codominant alleles at an autosomal locus. The calculated gene frequencies in a random sample of 86 unrelated individuals are HBA*1 = 0.73, HBA*2 = 0.22, and HBA*3 = 0.05.
A genetic polymorphism of delta-aminolaevulinic acid dehydratase (ALAD) in the domestic rabbit, Oryctolagus cuniculus, was detected by starch gel electrophoresis. Family data (15 matings with 49 offspring) support the genetic model of two common codominant alleles at an autosomal locus. Gene frequencies were calculated in a random sample of 55 mixed breed, unrelated domestic rabbits: ALAD1 = 0.31 and ALAD2 = 0.69.
A statistical study has been conducted in order to study the efficiency of an "R.C.M. apex locator" in endodontometry. The study is based on 97 electronic measurements in vivo, all samples being controlled in vitro by X-Ray examination after extraction of the teeth, the instrument remaining in the canal. Results showed that the "R.C.M. apex locator" allows a success rate of 85% length recorded being short of beyond the apex by 0.5 mm.
A genetic polymorphism of beta-chain rabbit (Oryctolagus cuniculus) hemoglobin is demonstrated by means of acid starch gel electrophoresis. The biochemical evidence presented suggests that a previously reported substitution of a neutral amino acid for a histidine is responsible for the detected genetic variation. Segregation analysis was performed in a sample of 15 matings with 49 offspring and confirmed the genetic hypothesis: two common alleles at an autosomal locus. The calculated gene frequencies in a random sample of 125 individuals are HBB*1 = 0.48 and HBB*2 = 0.52.