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S W Morris

Publications and source records attributed to S W Morris.

At least 91 records · Page 5Linked to original sources
PubMed1994

Molecular characterization of the gene for human interleukin-1 beta converting enzyme (IL1BC).

Interleukin-1 beta (IL-1 beta) mediates a wide range of immune and inflammatory responses. The active cytokine is generated by proteolytic cleavage of an inactive precursor by a protease called the IL-1 beta converting enzyme (ICE). A cDNA encoding this protease was recently isolated. A human genomic clone containing the ICE gene (IL1BC) was isolated using the cDNA as a probe. The gene consists of 10 exons spanning at least 10.6 kb. 5'-anchored polymerase chain reaction indicated a single transcription start site approximately 33 bp upstream of the initiator Met codon. The 5'-flanking region does not have an apparent TATA box but may contain an initiator (Inr) promoter element. However, transcriptional activity could not be detected with a fusion gene containing the 5'-flanking region linked to the bacterial chloramphenicol acetyltransferase gene (CAT) when transfected into the human acute monocytic leukemia cell line THP-1. Using the genomic IL1BC clone, we have confirmed the localization of the gene to chromosome 11 band q22.2-q22.3 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1994

Reverse transcriptase polymerase chain reaction for the Ki-1 anaplastic large cell lymphoma-associated t(2;5) translocation in Hodgkin's disease.

Hodgkin's disease (HD) and Ki-1 positive anaplastic large cell lymphoma (Ki-1 ALCL) appear pathologically and immunohistochemically related, and a common histogenesis has been postulated in at least some cases. The breakpoints of the t(2;5) (p23;q35) [corrected] translocation, which is reported in about 40% of Ki-1 ALCL, have recently been cloned. They involve a novel tyrosine kinase gene, ALK, at 2p23 and the nucleophosmin gene, NPM, at 5q35. Reverse transcriptase polymerase chain reaction (RT-PCR) using NPM and ALK primers consistently detects a fusion product in Ki-1 ALCL cases with the translocation. To determine if this tumor-specific genetic alteration also occurs in HD, we performed NPM-ALK RT-PCR on RNA samples extracted from 40 lymph node biopsies of HD (25 nodular sclerosis, 11 mixed cellularity, 2 lymphocyte depleted, 2 lymphocyte predominant). Using control samples, the sensitivity of the NPM-ALK RT-PCR assay was shown to be at least 1:10(4). Amplifiable template was confirmed in all samples by RT-PCR using beta-actin primers. None of the 40 cases showed the expected 177-bp RT-PCR product indicative of the translocation. We conclude that the most common primary genetic alteration in Ki-1 ALCL, the t(2;5), is absent or very infrequent in typical cases of HD. These results further support the concept that HD and Ki-1 ALCL are pathogenetically distinct entities.

Base Sequence↗
PubMed1994

t(5;14)(q33-34;q11), a new recurring cytogenetic abnormality in childhood acute leukemia.

A novel translocation, t(5;14)(q33-34;q11), was identified in the leukemic cells of four children presenting with acute lymphoblastic leukemia (ALL). The patients were 14 months, 2 years, 10 years, and 12 years old; each presented with one or more features of bulky disease, including lymphadenopathy, organomegaly or a mediastinal mass. The leukemic blasts were B lineage in two cases and T lineage in two cases. The patients with B-lineage ALL remain in continuous remission at 22 and 19 months following diagnosis. One patient with T-lineage ALL relapsed 6 months after diagnosis. The other patient with T-lineage ALL developed acute myelocytic leukemia (AML) 17 months after diagnosis; t(5;14)(q33-34;q11) was present in both the lymphoblasts at diagnosis and the myeloblasts at relapse, consistent with a lineage switch from ALL to AML. Rearrangement of the T-cell receptor delta chain (TCRD) gene at 14q11 was demonstrated in the three cases studied, suggesting its involvement in the pathogenesis of these leukemias by alteration of the structure or expression of an unidentified gene(s) on the long arm of chromosome 5.

Child↗
PubMed1993

Reassignment of the human ARH9 RAS-related gene to chromosome 1p13-p21.

The human ARH9 gene (originally rhoC), a member of the RAS gene superfamily, was initially isolated on the basis of cross-hybridization with a RAS-related cDNA from the marine snail Aplysia. The ARH9 gene locus was previously assigned to the telomeric region of chromosome 5q by isotopic chromosomal in situ hybridization and Southern analysis of somatic cell hybrid DNAs; the gene was noted to cosegregate with the CSF1 gene locus in human-rodent somatic cell hybrids carrying partial chromosomes 5, together with other human chromosomes. With the recent reassignment of the human CSF1 locus to chromosome 1, region p13-p21, it seemed important to reexamine the localization of the ARH9 gene, since it segregates 100% concordantly with the CSF1 locus in hybrid cells. Results of our investigation demonstrate that the ARH9 locus is also present in hybrids retaining chromosome 1, but not 5. Using hybrids carrying partial 1p, we mapped the ARH9 locus relative to other 1p loci, localizing the gene to the region 1p13-p31. Fluorescence in situ hybridization to metaphase chromosomes with a genomic ARH9 clone refined the gene's localization to chromosome 1, bands p13-p21.

Animals↗
PubMed1993

The gene for PAX7, a member of the paired-box-containing genes, is localized on human chromosome arm 1p36.

The murine Pax-7 gene and the cognate human gene, formerly designated HuP1, are members of the multigene paired-box-containing class of developmental regulatory genes first identified in Drosophila. By analysis of somatic cell hybrids segregating human chromosomes, the gene encoding PAX7 was localized to human chromosome 1. Fluorescence in situ hybridization confirmed this assignment and allowed mapping of the gene to the terminal region of the short arm (1p36) of the chromosome. Additionally, these results confirm the extensive homology between human chromosome 1p and the distal segment of mouse chromosome 4, extending from bands C5 through E2.

Animals↗
PubMed1992

Sublocalization of the chromosome 5 breakpoint of the 3;5 translocation in myelodysplastic syndromes and acute myeloid leukemia.

A t(3;5)(q25.1;q34) reciprocal translocation identifies a subset of cases of myelodysplastic syndrome or acute myeloid leukemia (AML) that are characterized by increased numbers of megakaryocytes and severe trilineage dysplasia. As a first step in characterizing the t(3;5) breakpoints, we asked whether the translocation involves the CSFIR/PDGFRB locus at 5q33-q35. Pulsed-field gel electrophoretic analysis of a region extending 580 kb 5' to the PDGFRB gene and 120 kb 3' to the CSFIR gene did not reveal aberrant restriction fragments in leukemic cell DNA, confirming that the breakpoint does not occur in the vicinity of these genes. To sublocalize the breakpoint, we performed Southern blot hybridizations using DNA from human x hamster somatic cell hybrids containing the normal 3, the normal 5, the derivative 3, or the derivative 5 human chromosome. Using a series of polymorphic DNA probes from the long arm of chromosome 5, which have been linked by genetic recombination, we bracketed the breakpoint to within a region that spans approximately 13 centimorgans (sex average) and is flanked by the q34-qter markers cKK5.19 and L1200 (D5S62). This analysis places the chromosome 5 breakpoint of the t(3;5) considerably telomeric to the CSFIR/PDGFRB locus, confirming our studies with pulsed-field electrophoresis. Future efforts to identify the genes affected by the t(3;5) should focus on the 5q segment described in this study.

Animals↗
PubMed1992

Assignment of the genes encoding human interleukin-8 receptor types 1 and 2 and an interleukin-8 receptor pseudogene to chromosome 2q35.

Two human cDNA clones that encode different interleukin-8 (IL8) receptors have recently been isolated. The interleukin-8 receptor type 1 (IL8R1) binds IL8 only, whereas the interleukin-8 receptor type 2 (IL8R2) (previously designated IL8RA) also binds growth regulated gene (GRO), and neutrophil activating protein-2 (NAP-2) with high affinity. In the process of screening a genomic library with these cDNAs to obtain large clones for use in chromosomal localization studies, we isolated an interleukin-8 receptor pseudogene (IL8RP) that bears greatest similarity to IL8R2. Using Southern hybridization analysis of human x rodent somatic cell hybrid DNAs with cDNA probes for IL8R1 and IL8R2 and probes from the IL8RP locus, we assigned the three loci to chromosome 2; fluorescence in situ hybridization (FISH) to metaphase chromosome preparations using genomic clones from each locus refined this localization to chromosome 2, band q35, for all three. By virtue of their chromosomal location, IL8R1 and IL8R2 may be considered candidate genes for several human disorders in which the involved locus has been mapped to distal 2q or that are associated with structural abnormalities of this segment, including van der Woude syndrome and the neoplastic diseases rhabdomyosarcoma and uterine leiomyomata. In addition, because this region of chromosome 2q is homologous to proximal mouse chromosome 1 in the segment containing the Lsh-Ity-Bcg locus involved in mediating host resistance to infection with intracellular pathogens, examination for abnormalities of the murine homologues of the IL8R genes should be considered in mice affected by mutations of this locus.

Amino Acid Sequence↗
PubMed1991

Reassignment of the human CSF1 gene to chromosome 1p13-p21.

Human macrophage colony-stimulating factor (CSF-1 or M-CSF) is encoded by a single gene that was previously assigned to the long arm of chromosome 5, band q33.1, in a region adjacent to the gene encoding its receptor (Pettenati MJ, et al, Proc Natl Acad Sci USA 84:2970, 1987). Using fluorescence in situ hybridization with genomic probes to examine normal metaphase chromosomes, we reassigned the human CSF1 gene to the short arm of chromosome 1, bands p13-p21. We confirmed this result by hybridizing a CSF1 cDNA probe to filters containing flow-sorted chromosomes and by identifying CSF1 sequences in DNAs extracted from human x rodent somatic cell hybrids that contained human chromosome 1 but not human chromosome 5. Our findings are consistent with studies that have shown tight linkage between the murine CSF1 and amylase genes, as part of a conserved linkage group between mouse chromosome 3 and the short arm of human chromosome 1, which also includes the genes encoding the beta subunits of thyrotropin and nerve growth factor. Assignment of the CSF1 gene to chromosome 1 at bands p13-p21 raises the possibility that it may be altered by certain nonrandom chromosomal abnormalities arising in human hematopoietic malignancies and solid tumors.

Cell Line↗
PubMed1990

Relationship of bcr breakpoint to chronic phase duration, survival, and blast crisis lineage in chronic myelogenous leukemia patients presenting in early chronic phase.

Strong evidence implicates fusion of control elements and 5' sequences of the bcr gene of chromosome 22 with 3' sequences of the c-abl gene of chromosome 9 in the pathogenesis of Ph-positive and certain cases of Ph-negative chronic myelogenous leukemia (CML). Since this fusion gene gives rise to a chimeric tyrosine protein kinase with transforming potential, and since the bcr exon contribution to this chimeric protein is variable, the question has arisen as to whether bcr breakpoint location and bcr exon contribution could influence the clinical course of CML. Prior studies have yielded conflicting results on this point. Here we have looked, in a manner approximating a prospective analysis, at the relation of bcr breakpoint localization to the duration of chronic phase, total survival, and blast crisis phenotype in 81 patients presenting in the chronic phase of CML. We have found no significant differences in chronic phase duration or total survival among patients with breakpoints in the three major subregions of a breakpoint cluster region within the bcr gene. These findings indicate that chronic phase duration and total survival cannot be predicted from bcr breakpoint for CML patients presenting in chronic phase and suggest that unknown oncogenic events determining the onset of blast crisis are the prime determinants of prognosis. Combined analysis of blast crisis cell lineage in our patients and patients presented in a previous study has revealed an overall ratio of myeloid:lymphoid (M:L) crisis of 3.4:1, but a striking predominance of myeloid crisis in patients with breakpoints in subregion 2 (M:L of 9:1), and a lower than expected M:L ratio (1.6:1) among patients with breakpoints in subregion 3 (P for subregion 2 versus 3 = .012; subregions 0,1,2 versus 3 = .012; subregions 0,1,3 versus 2 = .032). The molecular basis for this divergence from the anticipated M:L ratio in patients with breakpoints in bcr subregions 2 and 3 is unknown.

Adult↗
PubMed1989

DNA restriction fragment length polymorphisms as markers of familial coronary heart disease.

246 of 713 men aged 30 to 59 years had first-degree relatives who had had coronary heart disease (CHD) by the age of 60; men with a family history of CHD were twice as likely to have CHD themselves, compared with those without such a family history. At least 75% of the difference was accounted for by CHD in men with minor alleles of 4 restriction fragment length polymorphisms (RFLPs) in the region of the apolipoprotein (apo) AI and apo CIII genes. The RFLPs were identified with the restriction enzymes XmnI, PstI, MspI, and SacI. Each polymorphism has two alleles (major and minor), designated X1 and X2, P1 and P2, M1 and M2, and S1 and S2, respectively. In men with any one of the minor alleles, a family history of CHD was associated with a 234% increase in CHD prevalence. In men with major alleles only, a family history of CHD was not associated with any significant increase in CHD. The effect of the minor alleles was not significantly altered when plasma lipids and other variables except for age were taken into account. The association between the minor RFLP alleles and polymorphic gene variants (probably the apo AI, apo CIII, or both genes) which enhance liability to CHD accounted for almost 20% of total CHD in this population.

Adult↗