Intratumoral microdistribution of [131I]MB-1 in patients with B-cell lymphoma following radioimmunotherapy

Leprechaunism is a rare autosomal recessive disorder characterized by marked intrauterine and postnatal growth retardation, severe insulin resistance, and altered glucose homeostasis. This syndrome is related to mutations in the insulin receptor (IR) gene that impair the transmission of the insulin signal by several mechanisms. There is no effective therapy and patients usually die within the first months of life. Here we report the prenatal diagnosis of leprechaunism in two unrelated families in which affected children were compound heterozygotes with two different deficient IR alleles. In family Par-1, the disease IR alleles carried a missense mutation located in exon 18 (Arg1092-->Trp) and exon 20 (Glu1179-->Lys). In family Als, a 3-basepair deletion causing the loss of Asn281 in exon 3 and a major deletion of exons 10-13 were present in the maternal and paternal mutant IR alleles, respectively. Prenatal diagnosis was made in each family by a specific approach combining denaturing gradient gel electrophoresis (DGGE) and Southern blotting. This methodology allowed us to correctly predict the genotype of the two fetuses at the IR locus.     

V(D)J recombinase activity in a subset of germinal center B lymphocytes

Reexpression of the V(D)J recombinase-activating genes RAG1 and RAG2 in germinal center B cells creates the potential for immunoglobulin gene rearrangement and the generation of new antigen receptor specificities. Intermediate products of V(D)J recombination are abundant in a subset of germinal center B cells, demonstrating that the kappa immunoglobulin light-chain locus becomes a substrate for renewed V(D)J recombinase activity. This recombinationally active cell compartment contains many heavy-chain VDJ rearrangements that encode low-affinity or nonfunctional antibody. In germinal centers, secondary V(D)J recombination may be induced by diminished binding to antigen ligands, thereby limiting abrupt changes in receptor specificity to B cells that are usually eliminated from the germinal center reaction. This restriction preserves efficient antigen-driven selection in germinal centers while allowing for saltations in the somatic evolution of B cells.     

Cerebrosides alter the lyotropic and thermotropic phase transitions of DOPE:DOPC and DOPE:DOPC:sterol mixtures

An infectious cDNA of a highly myocarditic coxsackievirus B3 (CVB3m; Nancy strain) was cloned. Sequence data revealed 43 extra non-viral nucleotides upstream of the initial 5' sequence. However, the authentic 5' end sequence was maintained during replication of viral RNA transfected into HeLa cells, suggesting the RNA synthesizing complex edits the picornaviral 5' terminus sequence. Nucleotide sequences of the 5' nontranslated region and the capsid protein gene sequence of CVB3m were compared with the published sequences of five other CVB3 Nancy strains and two main lineages were found. In comparative assays for cardiovirulence, three of four CVB3 tested were cardiovirulent in adolescent male CD-1 mice. Only one of the three available CVB3 strains was neutralized with several anti-CVB3m monoclonal antibodies, suggesting that mutations in the surface epitopes of the capsid polypeptides contribute to antigenic drift within the serotype, perhaps in part through immunoselective pressures. Thus, phenotypic diversity of CVB3 within the prototype Nancy strain is an example of RNA viruses adapting to changing environments (cells, mice and humans) through mutations and selective pressure.     

N-methyl-D-aspartate-stimulated increases in intracellular calcium exhibit brain regional differences in sensitivity to inhibition by ethanol

To determine what effect ovariectomy and the accompanying sudden loss of circulating gonadal hormones has on spatial learning performance in the adult rat, two groups of rats were tested on the Lashley III simple alley maze following surgery. Ovariectomized animals were compared with a control group of animals that underwent laparotomy at the same time. The ovariectomized group evidenced superior performance on the maze task, as measured by latency to reach goal (running times) and error scores. It is suggested that this finding provides further evidence for the role of gonadal steroid hormones in the manipulation of functions related to learning and memory, especially in the hippocampus.