[Salmonella meningitis in an infant due to a pet turtle]. / Méningite à Salmonelle chez un nourrisson due à une tortue domestique.

In humans, Salmonella most often causes self-limiting gastroenteritis, but more severe symptoms such as sepsis and meningitis can also occur and can sometimes have a fatal outcome. Even if the meningitis is not fatal, sequelae such as epilepsy, cranial nerve palsies, and hydrocephalus can occur. In the United States, it has been estimated that approximately 6% of the human cases of salmonellosis can be attributed to contact with reptiles or amphibians. The infection may take place by direct contact between reptile and human or indirectly via contact with an environment contaminated with Salmonella from a reptile. Salmonella enterica subsp. enterica serotype Vitkin is a common gut inhabitant of reptiles. Though human cases due to this organism are exceedingly rare, it may infect young infants and immunocompromised individuals with a history of intimate associations with reptiles. Gastroenteritis is the most common presentation ; others include peritonitis, meningitis and bacteremia. We report a case of meningitis caused by S. enterica subsp. enterica serotype Vitkin in a 1-month-old child due to a pet turtle.

Structure, chromosome mapping, and expression of the mouse Lyl-1 gene.

The mouse Lyl-1 gene was cloned and shown to consist of four exons with extensive nucleotide and structural homology to the human LYL1 gene. The Lyl-1 gene was localized to the central region of mouse chromosome 8 which defines a new region of synteny with human chromosome 19p. The predicted mouse Lyl-1 protein is 78% identical to human LYL1. The region of highest similarity occurs in the basic DNA binding and helix-loop-helix dimerization motifs which are nearly identical in mouse and man differing by only one conservative amino acid substitution. Expression of the Lyl-1 gene was found to be low in murine spleen and undetectable in other tissues by Northern blot analysis. In lymphoid cell lines, Lyl-1 was expressed in most B lineage cells but downregulated during terminal differentiation and was not expressed in most T lineage cells. In a human T ALL cell line carrying a translocation that juxtaposed LYL1 with the beta TCR gene, the translocated LYL1 gene was transcriptionally active whereas the nontranslocated gene was transcriptionally silent. We conclude that LYL1 has the properties of a lineage- and differentiation-specific HLH protein that contributes to T-cell neoplasia through its deregulated expression following chromosomal translocation.

Mapping of translocation breakpoints on the short arm of chromosome 19 in acute leukemias by in situ hybridization.

Non-random translocation involving the short arm of chromosome 19 are frequently observed in acute leukemias. Recent studies have shown that the 19p13 genes E2A and LYLl, both of which encode helix-loop-helix proteins, lie at two different translocation breakpoints in acute lymphoblastic leukemias (ALL). The E2A gene is involved by the t(1;19)(q23;p13) in acute pre-B-cell leukemias and the LYL1 gene is structurally altered by a t(7;19)(q34;p13) in T-cell ALL. To assess the role of these genes in other leukemia-associated translocations we mapped their locations with respect to the t(11;19)(q23;p13) and t(4;19)(q21;p13) translocation breakpoints carried by T-ALL cell lines SUP-T13 and SUP-T8a, respectively. In situ hybridization studies indicated that the E2A and LYL1 genes are physically distinct from the t(4;19) and t(11;19) breakpoints. Using these and other 19p13 translocation breakpoints as landmarks, we established a partial physical map of 19p: 19pter-E2A-INSR-LYL1-[t(4;19)]-19cen. These data should help guide molecular studies to further characterize 19p13 breakpoints and mapping of genes in this chromosomal region.

Molecular analysis of the t(1;19) breakpoint cluster region in pre-B cell acute lymphoblastic leukemias.

The t(1;19) chromosomal translocation in acute lymphoblastic pre-B cell leukemias involves the gene E2A for helix-loop-helix (HLH) proteins E12 and E47, ubiquitous transcriptional proteins implicated in the regulation of various lymphoid and nonlymphoid genes. To characterize the molecular features of the t(1;19)(q23;p13) translocation, we molecularly cloned breakpoint DNA from t(1;19)-carrying pre-B cell leukemias. In all cases, breakpoints on chromosome 19 occurred within 2 kb of each other in a single intron of the E2A gene. This clustered arrangement resulted in specific truncation of the E2A gene and transcript, with loss of sequences encoding the basic DNA-binding and HLH dimerization motifs from the derivative 19 chromosome. In contrast, breakpoints on chromosome 1 were distributed over a large region and could not be linked to exonic sequences of the PBX1 gene, although identical chromosome 1 sequences are joined to E2A sequences in 1;19 fusion transcripts. These data show that the 1;19 translocation consistently results in exchange of 3' exons encoding the HLH motifs of E2A with DNA from chromosome 1 to form a fusion gene on the derivative 19 chromosome.

Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor.

The gene (E2A) for enhancer binding transcription factors E12 and E47 maps to the t(1;19) chromosomal translocation breakpoint in pre-B cell leukemias. Altered E2A transcripts lacking sequences coding for the helix-loop-helix DNA binding motif were detected in several t(1;19)-carrying cell lines. Fusion cDNAs that crossed the t(1;19) breakpoint were cloned and shown to code for an 85 kd protein consisting of the amino-terminal two-thirds of E2A fused to a chromosome 1-derived protein. The fusion protein has the features of a chimeric transcription factor in which the DNA binding domain of E2A is replaced by the putative DNA binding domain of a homeoprotein from chromosome 1 for which the name Prl (pre-B cell leukemia) is proposed. Identical E2A-prl mRNA junctions were detected by PCR in three t(1;19)-carrying cell lines, indicating that the fusion transcripts and predicted chimeric protein are a consistent feature of this translocation.

The gene for enhancer binding proteins E12/E47 lies at the t(1;19) breakpoint in acute leukemias.

The gene (E2A) that codes for proteins with the properties of immunoglobulin enhancer binding factors E12/E47 was mapped to chromosome region 19p13.2-p13.3, a site associated with nonrandom translocations in acute lymphoblastic leukemias. The majority of t(1;19)(q23;p13)-carrying leukemias and cell lines studied contained rearrangements of E2A as determined by DNA blot analyses. The rearrangements altered the E2A transcriptional unit, resulting in the synthesis of a transcript larger than the normal-sized E2A mRNAs in one of the cell lines with this translocation. These observations indicate that the gene for a transcription factor is located at the breakpoint of a consistently recurring chromosomal translocation in many acute leukemias and suggest a direct role for alteration of such factors in the pathogenesis of some malignancies.

lyl-1, a novel gene altered by chromosomal translocation in T cell leukemia, codes for a protein with a helix-loop-helix DNA binding motif.

We have characterized a transcription unit at chromosome band 19p13 that lies at the site of a chromosomal translocation breakpoint in T cell acute lymphoblastic leukemia. The lyl-1 gene is structurally altered following a t(7;19) translocation, resulting in its head-to-head juxtaposition with the T cell receptor C beta gene and truncation of lyl-1 RNA. The predicted protein product of the lyl-1 gene contains a potential helix-loop-helix DNA binding motif also found in several proteins involved in the control of cellular proliferation and differentiation: all members of the Myc family, MyoD1, myogenin, the Drosophila achaete-scute, twist, and daughterless proteins, and two recently described immunoglobulin enhancer binding proteins. The implication of lyl-1 in cellular transformation suggests that other proteins containing similar DNA binding motifs may also be involved with neoplastic transformation in various cellular lineages.

Lack of involvement of the c-fms and N-myc genes by chromosomal translocation t(2;5)(p23;q35) common to malignancies with features of so-called malignant histiocytosis.

We report the molecular, cytogenetic, and immunologic characterization of three hematologic malignancies that contained characteristic t(2;5) chromosomal translocations. The clinicopathologic features in all three cases fit the disease spectrum of so-called malignant histiocytosis (MH). All cases expressed activation antigens including Ki-1 (CD 30), but no lineage-restricted pattern of cellular antigen expression was observed. Cell lines SUP-M2 and SU-DHL-1 established from two of the cases showed rearranged beta T-cell receptor (beta TCR) genes nonproductive of full-length beta TCR mRNA and therefore not helpful in unequivocal establishment of lineage derivation. The common cytogenetic feature was a reciprocal translocation between chromosomes 2 and 5, involving bands 2p23 and 5q35 near the reported chromosomal locations of the N-myc and c-fms genes, respectively. Normal-sized and truncated c-fms RNAs were observed in both cell lines, whereas no N-myc transcripts were detected. Sequence analysis of the truncated fms RNA showed that it consisted of the 3' half of the c-fms mRNA, but its derivation was not the result of a structural alteration of the c-fms gene. Our studies show that the t(2;5) does not involve the N-myc and c-fms protooncogenes and that this cytogenetic abnormality may be characteristic of a subset of primitive malignancies with an indeterminate lineage but with clinicopathologic features of so-called MH.

Mesolimbic dopaminergic supersensitivity following electrical kindling of the amygdala.

Limbic seizures developed in rats following daily electrical stimulation of the basolateral nucleus of the amygdala. Animals were designated as "kindled" after five complete (stage 5) behavioral seizures were observed. A subgroup, designated as "superkindled," received three additional weeks of electrical stimulations. Kindled rats were significantly subsensitive to the stereotypy-inducing effects of apomorphine, a direct dopamine agonist, compared to controls. Superkindled rats were supersensitive to the effects of apomorphine. However, both kindled and superkindled rats demonstrated an increase in 3H-spiperone Bmax values, reflecting dopamine D2-receptor densities, in the nucleus accumbens ipsilateral to the stimulating electrode. The number of interictal spikes recorded from the stimulating amygdaloid electrode during the last week of kindling was correlated with changes in apomorphine sensitivity in individual animals.

Chromosomal translocation involving the beta T cell receptor gene in acute leukemia.

DNA spanning a t(7;19) chromosomal translocation breakpoint was isolated from the human T cell line SUP-T7 established from an acute lymphoblastic leukemia. Nucleotide sequence analysis showed that the point of crossover on chromosome 7 occurred immediately adjacent to joining segment J beta 1.1 within the TCR-beta gene, suggesting that this translocation resulted from an error in TCR gene rearrangement. On chromosome 19, the translocation occurred within a previously uncharacterized transcriptional unit for which we propose the name lyl-1. An approximately 1.5-kb RNA is transcribed from this gene in a wide variety of hematolymphoid cell lines. The t(7;19) results in truncation of the lyl-1 gene and production of abnormal-sized RNAs, suggesting a role for lyl-1 in the pathogenesis of this leukemia.

Differential effects of proglumide on mesolimbic and nigrostriatal dopamine function.

Cholecystokinin octapeptide (CCK-8) is prevalent as a co-transmitter in the mesolimbic dopamine pathway. The effect of proglumide, a CCK-8 antagonist, on two acute and one chronic behavioral models of dopamine function was tested. First, haloperidol was used to inhibit stereotypies induced by apomorphine in rats. Pre-administration of proglumide significantly shifted the haloperidol dose response curve to the left. Second, rats were injected in the left caudate nucleus with kainic acid. Three weeks later, haloperidol was used to inhibit apomorphine-induced circling. Pre-administration of proglumide had no effect on this haloperidol dose response curve. Third, either proglumide, haloperidol, or combined treatment was administered to rats for 2 weeks. In proglumide-treated animals, a significant increase in 3H-spiperone binding sites in the nucleus accumbens was observed.