First nucleotide sequence of a human immunoglobulin variable lambda gene belonging to subgroup II.
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Amino Acid Sequence↗
Biomedical subjects
S Huck
Publications and source records attributed to S Huck.
Molecular mapping of the human T cell receptor gamma (TRG) genes and linkage of the variable and constant regions.
In the human T cell receptor gamma (TRG) locus, fourteen variable (TRGV) genes belonging to four subgroups have been identified upstream of two constant region (TRGC) genes. Three joining segments, JP1, JP and J1, have been localized upstream of TRGC1, and two others, JP2 and J2, upstream of TRGC2. In this report, we demonstrate that a unique Xho I fragment of 120 kilobases (kb) contains the fourteen TRGV genes and that the hybridization of that fragment in pulsed-field gel electrophoresis (PFGE) allows linkage of the variable region to the constant region locus. We also show that the variable and the constant regions are remarkably close to each other since the distance between V11, the most 3' V gamma gene, and JP1, the most 5' J gamma segment, is only 16 kb. With its 14 V gamma genes, spanning 100 kb, the two C gamma genes and 5 joining segments covering less than 40 kb and only 16 kb separating the most 3' V gene from the most 5' J segment, the human TRG locus spans 160 kb of genomic DNA and represents a particularly condensed locus compared to the other rearranging gene loci.
Amino Acid Sequence↗
Exon duplication and triplication in the human T-cell receptor gamma constant region genes and RFLP in French, Lebanese, Tunisian, and black African populations.
The human T-cell receptor gamma (TCRG) locus comprises 14 variable genes (TRGV), five joining segments (TRGJ), and two constant region genes (TRGC). The constant gamma 1 gene, TRGC1, consists of three exons, whereas the TRGC2 gene contains four or five exons due to the duplication or triplication of exon 2 and spans 9.5 kb or 12 kb, respectively. In this paper, we define the alleles of the T-cell receptor gamma J2 and C2 genes, and we show that two Hind III allelic fragments, 5.4 kb and 8 kb, characterize unambiguously the C2 gene with duplication or triplication of exon 2. We show also that the cDNA of the HPB-MLT cell line results from the transcription of an allelic TRGC2 gene with duplicated exon 2. We propose a model involving unequal crossing-overs to explain the organization and the evolution of the TRGC locus. Moreover, we analyze the TCRG haplotypes in four different populations (French, Lebanese, Tunisian, and Black African) to underline their interest for population genetics.
Alleles↗
A human immunoglobulin IGHG3 allele (Gmb0,b1,c3,c5,u) with an IGHG4 converted region and three hinge exons.
The five human IGHG genes consist of three constant domain exons plus one of or four hinge exon(s), the quadruplicated hinge region being characteristic of the IGHG3 gene. Besides this structural difference, the IGHG genes are polymorphic, as demonstrated by the restriction fragment length polymorphism and, at the protein level, by the Gm allotypic antigenic determinants. In this paper, we report the sequence of the G3m(b0, b1, c3, c5,u) IGHG3 allele, typical of the Black African populations and of populations with Negroid admixture, found in a homozygous Tunisian designated as LAT. We demonstrate that this G3 allele contains only three hinge exons instead of four (the probable result of an unequal crossing over) and that IGHG3 genes with triplicated hinge exons (and therefore encoding shorter gamma 3 chains) are present in healthy individuals from different populations. Moreover, we show that the LAT G3m (b0, b1, c3, c5, u) coding sequence results from the conversion, in the CH3 exon, of the G3m (b0, b1, b3, b4, b5, u, v) allele, the most frequent IGHG3 gene in the Negroid populations, by the homologous region of a IGHG4 gene. The structural features of the LAT IGHG3 allele, which are the lack of one hinge exon and its conversion by the IGHG4 gene, demonstrate that both crossing-over and gene conversion events occur in the evolution of the human IGHG genes.
Alleles↗
Deletion, insertion, and restriction site polymorphism of the T-cell receptor gamma variable locus in French, Lebanese, Tunisian, and black African populations.
The human T-cell receptor gamma region spans 160 kb of genomic DNA and is densely populated by coding sequences. Restriction fragment length polymorphisms have been previously documented for the constant region genes, the joining segments, and the variable genes belonging to subgroups I and IV. Here we further define the polymorphism of the V gamma I subgroup genes. based on complete mapping of the Eco RI and Taq I allelic restriction fragments. We describe seven haplotypes; five result from polymorphic restriction sites, the sixth corresponds to a deletion of about 10 kb encompassing V4 and V5, and the seventh results from an insertion of an additional gene, V3P, between V3 and V4. As a consequence of the deletion or insertion polymorphism, the number of V gamma I subgroup genes vary from seven in haplotype TRGVI*3 to ten in haplotype TRGVI*4, whereas the most common haplotype, TRGVI*1, has nine V genes, five of them being functional. Frequencies of the different TRGVI haplotypes in French, Lebanese, Tunisian, and Black African populations are given.
Black People↗
The human immunoglobulin pseudo-gamma IGHGP gene shows no major structural defect.
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Amino Acid Sequence↗
Restriction fragment haplotypes in the human immunoglobulin IGHG locus and their correlation with the Gm polymorphism.
Of the four human IgG subclass heavy chain (IGHG) genes, three--IGHG1, IGHG2 and IGHG3--have allelic forms which encode antigenic determinants called G1m, G2m and G3m allotypes for markers of the IgG1, IgG2 and IgG3 molecules. The alleles at these three closely linked loci are transmitted as Gm haplotypes, together with the IGHG4 and the IGHGP (or pseudo gamma) genes. Restriction Fragment Length Polymorphisms (RFLPs) have been described for all these IGHG genes, allowing us to define at least 15 RFLP alleles (N. Ghanem et al., Eur. J. Immunol. 1988. 18:1059). In this article, we determine unambiguously the Gm alleles and haplotypes and the associated RFLPs in French, Lebanese and Tunisian families, chosen for the various Gm phenotypes of their members, in order to correlate both these polymorphisms and to know the evolution of the IGHG multigene family. We were able to assign all the IGHG alleles to the Gm alleles and to their linked IGHG4 and IGHGP genes allowing us to define restriction fragment haplotypes of the IGHG gene family.
Alleles↗
Variable region genes in the human T-cell rearranging gamma (TRG) locus: V-J junction and homology with the mouse genes.
The locus of the human T cell rearranging gamma (TRG) or T cell receptor gamma chain genes comprises at least 14 variable genes (TRGV) belonging to four subgroups, five joining segments (TRGJ) and two constant region genes (TRGC). Nine V gamma genes belong to subgroup I, whereas subgroups II, III and IV each consists of a single gene respectively designated V9, V10 and V11. T cells expressing the gamma chain (TRG+) and recognized by the anti-Ti gamma A monoclonal antibody have been shown to rearrange the V9 gene. In order to assess the N diversity at the V-J junction in the TRG+ cells, the germline sequences of the segments involved in the V-J rearrangements must be known. In this paper, we report the sequences of the germline V9 and V10 genes. Comparison of the V-J junction and N region from transcripts or rearranged TRG genes belonging to the different subgroups shows no evidence of D segments in the human TRG locus. Sequences of the rearranged V11 gene from the JM cell line and those of the VA and VB pseudogenes, located upstream of V9 and V11 respectively, are given. Our results bring the number of human V gamma genes whose sequence is known to 13 and reveal unexpected homology with the mouse V gamma genes.
Amino Acid Sequence↗
Development of inward currents in chick sensory and autonomic neuronal precursor cells in culture.
The development of ionic inward currents was studied in cultured neuronal precursors from chick sensory dorsal root ganglia (DRG) and compared with neuronal precursors from the cholinergic ciliary ganglia (CG) using whole cell patch-clamp recording. Neuronal precursors devoid of neuron-specific surface markers were isolated during the period of neuronal birth, i.e., at embryonic day (E) 6 from DRG and at E4.5 from CG. All neuronal precursor cells from DRG, as well as CG, showed outward K+ currents directly after they had attached to the substrate. During the first 5 hr in culture, half of the DRG cells had no inward currents at all, whereas the other half displayed a rapidly and fully inactivating Ca2+ current, which was activated with small depolarizing pulses from a holding potential of -80 mV to a -50 mV membrane potential (low-voltage-activated current, LVA). At these early stages, no other inward currents were resolved. TTX-blockable Na+ currents and slowly inactivating classical Ca2+ currents, which were activated with larger depolarizing pulses to a -20 mV membrane potential (high-voltage-activated currents, HVA) appeared concurrently after 15-20 hr in culture. In contrast, more than half of the CG cells showed LVA currents, as well as Na+ currents, as early as during the first 5 hr in culture. The HVA Ca2+ currents from the majority of the cells could be recorded only after 10-15 hr in culture. In both types of precursor-derived neurons, the LVA Ca2+ current preceded the classical HVA Ca2+ current. However, the temporal relation of the first Na+ currents to the first HVA Ca2+ currents seemed to be different in the 2 preparations. In DRG cells, Na+ and HVA Ca2+ currents appeared at the same time, whereas in CG cells, the HVA Ca2+ current showed a time lag with respect to the Na+ current. In addition, the relative amplitudes of the currents differed in the CG and DRG cells. This shows that as early as E4-6, shortly after their terminal mitosis, neurons from distinct peripheral ganglia in chick vary in the development of their basic ionic currents.
Animals↗
Rearrangements to the JP1, JP and JP2 segments in the human T-cell rearranging gamma gene (TRG gamma) locus.
In the human T-cell rearranging gamma (TRG gamma) locus, five joining (J) segments have been identified: J1, J2 and three additional segments JP, JP1 and JP2. We report the sequence of the germline JP1 segment and compare it with the other human and mouse J gamma segments. We also demonstrate that rearrangements to the three additional J gamma segments can be identified by hybridization of the KpnI digests to the J gamma 1 probe pH60. Since rearrangements to J1 or J2 can be assigned, using the same pH60 probe, to one of the nine variable (V) gamma genes known to rearrange [(1987) EMBO J. 6, 1945-1950], our results show that a unique probe can detect all the TRG gamma rearrangements and be particularly useful for assessing the preferential usage of V gamma and J gamma segments in the TRG gamma-expressing cells.
Amino Acid Sequence↗
Patch-clamp study of ion channels activated by GABA and glycine in cultured cerebellar neurons of the mouse.
gamma-Aminobutyric acid (GABA) and glycine receptor channels have been investigated using the patch-clamp technique. Six out of 12 membrane patches exposed to GABA as well as to glycine responded to both substances, 3 to only GABA, two to only glycine and one was insensitive to both transmitters which were applied in micromolar concentrations. Channel currents reversed at the potential predicted by the constant field equation (using Cl- activities), indicating that the charge was carried by Cl-. Although multiple-conductance states were induced by GABA as well as by glycine, the phenomenon was much more pronounced after glycine applications. GABA channel permeabilities ranged from 3.7 X 10(-14) to 6.0 X 10(-14) cm3 s-1. With Cl- distributed symmetrically at 145 mM, these values would correspond to conductances of 19 and 31 pS, respectively. Glycine channel permeabilities ranged from 3.3 X 10(-14) to 14.7 X 10(-14) cm3 s-1 (corresponding conductances 17 and 76 pS).
Animals↗
New subgroups in the human T cell rearranging V gamma gene locus.
Two new V gamma genes in humans are described from rearrangement in T cell lines, which constitute single members of new V gene subgroups of the T-cell rearranging gamma (TRG gamma) locus. These two genes (herein designated as belonging to V gamma III and V gamma IV subgroups) are located between V gamma I/V gamma II subgroups and the constant (C) gamma genes. The existence of these new genes brings the number of different, potentially useable, human TRG V gamma genes to eight (excluding at least five pseudo V gamma genes) and the number of distinct subgroups to four. Polymorphism in the sequence of the V gamma II subgroup gene is also described and rearranged fragment sizes which make possible an unequivocal assignment of a V gamma rearrangement are given. These results extend previous conclusions of the inherited diversity of the human TRG V gamma locus.
Amino Acid Sequence↗
A gamma 3 hinge region probe: first specific human immunoglobulin subclass probe.
We report the first specific human immunoglobulin subclass probe which was obtained by subcloning the gamma 3 hinge region. This specific gamma 3 probe allowed us to identify with certainty the C gamma 3 gene on Southern genomic blots, to describe the first C gamma 3 restriction fragment length polymorphism (EZZ gamma 3 RF) and to show that an IgG3 selective deficiency, previously described serologically, was not due to a deletion of the C gamma 3 gene. Such a probe should be particularly useful for screening libraries from individuals with IgG3 immunodeficiencies or presenting unusual C gamma 3 genes and, consequently, for studying the C gamma gene evolution.
Amino Acid Sequence↗
Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C gamma genes.
We report the first and complete nucleotide sequence of a human gamma 3 heavy chain constant region gene (C gamma 3). This gene displays the same organization than the others C gamma genes and exhibits normal RNA splice and polyadenylation sites. A comparison of its primary sequence with those of C gamma 1, C gamma 2 and C gamma 4 genes confirms the high degree of homology (95%) of the human family in both coding and non-coding regions, and the divergence of the hinge region. The C gamma 3 gene we sequenced codes for a Gm(b) gamma 3 chain (EZZ). Comparison with other known protein sequences reveals that only two specific aminoacids are involved in the Gm(b) and Gm(g) allotypes, which suggests an important part of the spatial configuration in the allotypic specificities.
Amino Acid Sequence↗
Differentiation of drug-induced rhythmical activities in the rabbit's brain by a benzodiazepine antagonist.
The effect of a benzodiazepine antagonist, ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazol[1,5a] [1,4]benzodiazepine-3-carboxylate (Ro 15-1788), on the cerebello-rubral rhythm induced by a water soluble benzodiazepine derivative (medazepam hydrochloride) or by a barbiturate (pentobarbital sodium) was investigated in the rabbit. The frequency of this rhythm which depends on the depth of the central depression caused by either of these agents was used for the drug interaction study. Ro 15-1788 when given alone up to 10 mg/kg did not cause any changes in the cerebello-rubral and the neocortical electrical activities. Ro 15-1788 (0.5 and 2.0 mg/kg) was effective in antagonizing the medazepam-induced cerebello-rubral rhythm and the rhythmic discharges of Purkinje cells in a dose-dependent manner. The antagonistic effect was also observed in the electrocorticogram. The pentobarbital-induced cerebello-rubral rhythm and the neocortical activity were not influenced by Ro 15-1788 up to 5 mg/kg. Thus, the similar effect of barbiturates and benzodiazepine derivatives on the cerebello-rubral system seems to be mediated by different pharmacodynamic actions. The findings are in line with previous studies indicating a selective antagonism of Ro 15-1788 and benzodiazepine derivatives.
Animals↗
Failure of 6-aminonicotinamide in selectively damaging astrocytes in vitro.
The present study investigates cytotoxic effects of 6-amino-nicotinamide (6-AN), a nicotinamide antagonist, in primary cultures of the dissociated postnatal mouse cerebellum. Initial effects were seen with 1.5 microM 6-AN of this substance included in the culture medium at plating. Established cultures responded to concentrations higher than 3.1 microM. The relative number of astrocytes (identified immunohistochemically) was not reduced in cultures exposed to low, but effective concentrations of 6-AN. We therefore conclude that 6-AN is no suitable agent to regulate the number of astrocytes in cell cultures. Thus, at the present alpha-aminoadipic acid remains the only substance which can be considered a selective gliotoxin in vivo and in vitro.
6-Aminonicotinamide↗
Scoring system to improve cost effectiveness of open access endoscopy.
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Cost-Benefit Analysis↗
Drug-induced rhythmic burst activity of cerebellar neurons.
The discharge of cerebellar neurons was investigated in the rabbit and the rat under the influence of pentobarbital, diazepam or medazepam. In the rabbit, these drugs are known to induce a rhythm ranging between 4 and 25 Hz in the red nucleus (RN) and the cerebellum (Cb). Purkinje cells (P cells) in the intermediate zone of the cerebellar cortex as well as neurons of the interposed nucleus (IPN) were found to discharge with burst patterns fully synchronized with the drug-induced RN rhythm. In contrast, P cells in the medial cerebellar zone responded to these drugs only with changes in their discharge rate. Since P cells of the intermediate longitudinal zone project to the RN mainly via the IPN, the present findings complement our previous results, indicating that the rhythmic electrical activity in the RN is initiated by the cerebellum. The three drugs had similar effects on the activity of cerebellar units in the rabbit and the rat. The investigation also shows that, in spite of the uniform morphological structure of the cerebellar cortex, P cells do not respond uniformly to a given drug: the diversity of findings published on the P cell response to barbiturates or benzodiazepine derivatives may be explained by differences in the recording sites.
Animals↗