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Biomedical subjects

M Dean

Publications and source records attributed to M Dean.

At least 361 records · Page 20Linked to original sources
PubMed1988

A short exercise and living course for asthmatics.

A 5-day, non-residential exercise and living course for children with asthma is described as a feature of a programme of outpatient physiotherapy. Eleven children undertaking such a course were compared with 10 asthmatic children in a control group. The subject group showed, in the short term at least, an improvement in bronchial lability, peak flow rates, nocturnal and daytime wheeze, and activity compared with the controls. These findings were statistically significant. There was no difference between the groups in the number of days on which extra medication was taken. A short, sharp course is of benefit physically, socially and psychologically to children with asthma.

Activities of Daily Living↗
PubMed1988

Physical mapping of the cystic fibrosis region by pulsed-field gel electrophoresis.

The gene for cystic fibrosis (CF) is known to be flanked by the closely linked DNA markers met and J3.11 on chromosome 7. Using the technique of pulsed-field gel electrophoresis, we have constructed a complete overlapping restriction map of approximately 3000 kb of DNA in this region. The met and J3.11 probes are found to be between 1300 and 1800 kb apart, which compares well with their genetic distance of 1-2 cM. The CF gene must be located within this interval, and the availability of this physical map should be of considerable utility in mapping additional clones as the search for the gene proceeds.

Cell Line↗
PubMed1988

Refined linkage map of chromosome 7 in the region of the cystic fibrosis gene.

The genetic map in the region of human chromosome 7 that harbors the gene for cystic fibrosis (CF) has been refined by multilocus linkage studies in an expanded database including a large set of normal families. Six loci known to be linked to CF were examined: MET, an oncogene; COL1A2, collagen, TCRB, T-cell-receptor beta polypeptide; and three arbitrary loci--D7S8, D7S13, and D7S16--defined by probes pJ3.11, pB79a, and p7C22, respectively. The gene order with greatest statistical support is COL1A2-D7S13-D7S16-MET-D7S8-TCRB. Linkage analysis in families segregating for CF suggested that the most likely location of the CF gene on this map is between MET and D7S8.

Chromosome Mapping↗
PubMed1988

HTLV-I infection and chronic lymphocytic leukemia.

We have captured the immunoglobulin genes of CLL cells by fusing the peripheral blood lymphocytes from CLL cells with the B lymphoblastoid line. The hybridoma cell line established from the fusion of CLL cell from two patients who were HTLV-I seropositive produced antibody directed against HTLV-I proteins. The antibody activity of the immunoglobulin produced by the fused cells is different in the two patients in one case being directed against a gag protein and in the other against the viral large envelope protein. In an attempt to explore possible mechanisms whereby HTLV-I may contribute indirectly to the pathogenesis of B cell CLL, we have determined that B cell lines infected with HTLV-I produce growth factor(s) which stimulate and expand populations of normal B cells as well as CLL cells. These results suggest that HTLV-I infection may contribute in several ways to the development of a malignancy in cell where the virus is not present in the cellular genome.

HTLV-I Infections↗
PubMed1987

Chromosomal localization of the met proto-oncogene in the mouse and cat genome.

The met proto-oncogene was mapped in the mouse and cat genomes with the use of mouse X hamster and cat X rodent somatic cell hybrid DNA panels. Based on these analyses we assigned the met gene to mouse chromosome 6 and to cat chromosome A2. We also assigned the cat raf-1 proto-oncogene to the A2 chromosome; met and raf-1 are the first cloned DNAs mapped to this linkage group. Using an interspecies backcross we further localized met on mouse chromosome 6 to a position proximal to the beta chain of the T-cell receptor. This places met near the obese locus in a region of mouse chromosome 6 that appears to be homologous with the long arm of human chromosome 7. The close linkage of met to the gene responsible for cystic fibrosis in humans suggests that further genetic analysis of mouse chromosome 6 may be useful in developing a mouse model for the disease.

Animals↗
PubMed1987

Three additional DNA polymorphisms in the met gene and D7S8 locus: use in prenatal diagnosis of cystic fibrosis.

We have used cloned DNA sequences from the 5' end of the met locus and the D7S8 locus to locate new restriction fragment length polymorphisms. TaqI and MspI polymorphisms with frequencies of 0.34/0.66 and 0.10/0.90, respectively, for met and a PvuII polymorphism (0.15/0.85) at D7S8 are described. We used these new markers to analyze our reference panel of cystic fibrosis pedigrees and found that they provided additional information in several families. No evidence for recombination was observed between the 5' end of met and previously described met markers. We present examples of the use of the met markers in the clinical diagnosis of cystic fibrosis and summarize our analysis of 29 clinical cases including eight prenatal diagnoses. We conclude that DNA-based prediction of cystic fibrosis is an effective clinical diagnostic procedure.

Alleles↗
PubMed1987

Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors.

We isolated overlapping cDNA clones corresponding to the major MET protooncogene transcript. The cDNA nucleotide sequence contained an open reading frame of 1408 amino acids with features characteristic of the tyrosine kinase family of growth factor receptors. These features include a putative 24-amino acid signal peptide and a candidate, hybrophobic, membrane-spanning segment of 23 amino acids, which defines an extracellular domain of 926 amino acids that could serve as a ligand-binding domain. A putative intracellular domain 435 amino acids long shows high homology with the SRC family of tyrosine kinases and within the kinase domain is most homologous with the human insulin receptor (44%) and v-abl (41%). Despite these similarities, however, we found no apparent sequence homology to other growth factor receptors in the putative ligand-binding domain. We conclude from these results that the MET protooncogene is a cell-surface receptor for an as-yet-unknown ligand.

Amino Acid Sequence↗
PubMed1987

Characterization of the rearranged tpr-met oncogene breakpoint.

We determined the nucleotide sequence of the rearranged trp-met genomic locus and the corresponding portions of the unrearranged tpr and met genomic fragments. The breakpoints occur at one end of a stretch of 21 A residues that follow an Alu repetitive sequence in the tpr locus and within a group of 3 A residues in the met proto-oncogene locus. We conclude that the fusion between the tpr locus on chromosome 1 and the met locus on chromosome 7 resulted from a recombination event.

Base Sequence↗
PubMed1987

Role of myc in the abrogation of IL3 dependence of myeloid FDC-P1 cells.

We have constructed a recombinant retrovirus containing the murine c-myc and the neo gene and introduced the virus into the interleukin-3 (IL3) dependent myeloid cell line FDC-P1. Unregulated expression of the introduced c-myc gene is associated with both an increased viability and constitutive ornithine decarboxylase mRNA levels in FDC-P1 cells grown in the absence of IL3. FDC-P1 cells infected with the c-myc virus gave rise to IL3 independent lines. Three out of four independent lines have an activated endogenous c-myc or N-myc gene. We have also shown that c-myc mRNA levels are tightly regulated by IL3 in FDC-P1 cells. Taken together these results indicate that myc plays a critical role in the signal transduction pathway of IL3. Furthermore, activation of the N-myc gene may be one mechanism for myeloid cells to progress to complete IL3 independence.

Animals↗
PubMed1986

Analysis of the transforming potential of the human homolog of mos.

The human homolog, c-moshu, of the mouse cellular mos proto-oncogene (c-mosmu) transforms NIH 3T3 cells at low efficiency. Furthermore, the c-moshu-induced foci are less distinct, and transformed cells contain a high level of human mos protein. The transforming activity of hybrid mos genes derived from human and mouse sequences reveals three domains within the coding region, as well as a negative regulatory sequence upstream from the c-moshu ORF that reduces its transforming efficiency. The mos C-terminal region, however, which contains the src-kinase homology domain, appears to have the greatest influence on transforming efficiency. The low transforming efficiency of c-moshu may provide a selective advantage to the host, but it also may indicate a reduced or modified function of mos in humans.

Animals↗
PubMed1986

Regulation of c-myc transcription and mRNA abundance by serum growth factors and cell contact.

We describe effects of serum insufficiency and cell contact on the transcription and abundance of the c-myc proto-oncogene mRNA in BALB/c 3T3 fibroblasts. In exponentially growing cells, withdrawal of serum caused a 10-fold decline in c-myc mRNA within 90 min. At least part of this decline was due to a decrease in the level of myc gene transcription. These cells became quiescent at subconfluence after 36-40 h. Cells made quiescent at subconfluence or confluence contained low levels of c-myc mRNA which rose more than 20-fold 2 h after stimulation of growth by fresh serum. Thereafter, the mRNA level declined. In subconfluent cells, it declined to the level in exponentially growing cells, i.e. nearly 10-fold over the level in quiescent cells. In confluent cells, by contrast, the mRNA returned to near-quiescent levels within 18 h (by mid-S phase). However, c-myc gene transcription was regulated identically in subconfluent and confluent cultures; quiescent cells transcribed c-myc at detectable levels, and stimulation by serum caused a 5-fold increase in 1 h, followed by a decline to about 2-fold over the quiescent level within 18 h. Thus, confluence affected steady state mRNA levels without affecting the level of transcription. Our results suggest that extracellular conditions that modulate cell proliferation (serum and cell contact) exert strong and rapid control over c-myc mRNA by post-transcriptional and transcriptional mechanisms.

Actins↗
PubMed1986

Mechanism of met oncogene activation.

The met oncogene activated in vitro by treatment of a human osteogenic sarcoma (HOS) cell line with N-methyl-N'-nitronitrosoguanidine (MNNG) is related to the tyrosine kinase gene family. Probes from the met oncogene locus recognize two distinct transcripts of 9.0 kb and 10.0 kb which are independently expressed in a cell-type-specific fashion. While the met proto-oncogene locus expresses the 9.0 kb RNA and maps to human chromosome 7q21-31, the locus expressing the 10.0 kb RNA, (tpr; translocated promoter region) maps to human chromosome 1. Both MNNG-HOS cells and met NIH 3T3 transformants express a novel 5.0 kb RNA which represents a hybrid transcript with 5' sequences derived from tpr and 3' sequences from the met proto-oncogene. Treating HOS cells in vitro with MNNG, a known clastogenic carcinogen, resulted in fusion of two chromosomally disparate loci, met and tpr, generating the active met oncogene.

Cell Line↗