Identification of a hereditary pancreatitis mutation in four West Virginia families.

Hereditary pancreatitis (HP) is the second most common cause of chronic childhood pancreatitis in the United States. Mutations in the cationic trypsinogen gene on chromosome 7 are known to cause HP. We identified four families in West Virginia with symptoms consistent with HP.

Expression and function of gamma delta- and alpha beta-T cell receptor heterodimers on human somatic T cell hybrids.

T cell somatic hybrids were obtained by fusion of human tetanus toxoid-specific gamma + delta + T cells and a T cell lymphoma cell line that expresses beta-chain but not alpha-chain transcripts. The hybrids simultaneously and independently expressed alpha beta and gamma delta TCR heterodimers on the cell surface without any significant differences in the level of expression. No heterodimers containing alpha delta-, beta delta-, beta gamma-, and alpha gamma-chains were transported to the cell membrane, indicating a chain specificity in dimer formation.

The chromosome 11 region flanking the t(11;14) breakpoint in human T-ALL is deleted in Wilms' tumor hybrids.

Human chromosomal band 11p13 has been implicated in T cell malignancies carrying t(11;14)(p13;q11) reciprocal translocations and has also been associated with Wilms' tumor and aniridia in a mechanism characterized by overlapping hemizygous constitutional deletions spanning this region. Using probes derived from the T cell receptor delta gene, we have cloned the chromosomal breakpoint in an acute T cell leukemia (T-ALL). Southern blotting analyses of mouse-human somatic cell hybrids from this human T-ALL sample and Chinese hamster-human somatic cell hybrids derived from Wilms' tumor lines have indicated that the 11p13 locus, tcl-2, juxtaposed to the TCR (T cell receptor) delta locus in T cell leukemia, is within the constitutional deletion of two Wilms' tumor-aniridia cases.

Sequence analysis of the MYC oncogene involved in the t(8;14)(q24;q11) chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered.

We have cloned the translocation-associated and homologous normal MYC alleles from SKW-3, a leukemia T-cell line with the t(8;14)(q24;q11) translocation, and determined the sequence of the MYC oncogene first exon and flanking 5' putative regulatory regions. S1 nuclease protection experiments utilizing a MYC first exon probe demonstrated transcriptional deregulation of the MYC gene associated with the T-cell receptor alpha locus on the 8q+ chromosome of SKW-3 cells. Nucleotide sequence analysis of the translocation-associated (8q+) MYC allele identified a single base substitution within the upstream flanking region; the homologous nontranslocated allele contained an additional substitution and a two-base deletion.

Identification of the Rts 1 DNA fragment responsible for temperature sensitive growth of host cells harboring a drug resistant factor Rts 1.

We have placed a kanamycin resistance SalI fragment (3.65 Kb) from the drug resistance factor Rts1 into pUC19 and pBR322. These chimeric plasmids containing the kanamycin resistance fragment from Rts1 cause temperature sensitive growth in E coli.