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Biomedical subjects

E L Mitchell

Publications and source records attributed to E L Mitchell.

At least 19 recordsLinked to original sources
PubMed2001

The angiosome concept applied to arteriovenous malformations of the head and neck.

Arteriovenous malformations remain a difficult clinical problem. There is very little understanding of the underlying pathogenesis of these lesions, and therapy frequently involves considerable risks with suboptimal outcomes. Recently, a comprehensive description of the angiosomes of the head and neck was completed in the authors' unit. It was noticed that the location of several clinically observed arteriovenous malformations in the head and neck seemed to correspond to the anatomic location of the choke anastomotic zones linking the angiosomes. Therefore, selective clinical angiograms were compared with those from the authors' previously performed fresh cadaver injection studies, in which they defined the angiosomes of the head and neck. In each patient, the location of the arteriovenous malformation corresponded directly to the choke vessel anastomotic zone linking two or more adjacent angiosomes. Clinical and pathologic ramifications of this observation are discussed.

Adolescent↗
PubMed1999

Breast conservation therapy in affiliated county, university, and private hospitals.

BACKGROUND: Breast conservation therapy (BCT) offers equivalent survival to modified radical mastectomy in patients with early-stage (I and IIa) breast cancer, but is utilized in less than 50% of eligible patients. While patient demographics have been linked to BCT rates, we suspected that physician influence was a major factor. The purpose of this study was to compare BCT at three affiliated centers staffed by similarly trained surgeons yet serving widely disparate populations, in order to assess the importance of physician influence on the utilization of BCT. METHODS: Tumor registry data were reviewed from 1993 through 1997 at affiliated city/county (CH), university (UH), and private hospitals (PH). Data were analyzed for clinical stage, treatment, and age of patient. RESULTS: The utilization of BCT for stage I and IIa breast cancer is similar at the three hospitals: 45% of patients at CH, 55% of patient at UH, and 57% of patients at PH (P>0.05). Rates of BCT were similar across all patient age groups at all sites. CONCLUSIONS: Similar BCT utilization rates can be achieved despite widely disparate patient populations. The three affiliated hospitals are staffed by surgeons with similar training, and all offer a multidisciplinary approach to breast cancer care. This suggests that physician influence may override patients' socioeconomic issues in providing optimal breast cancer therapy.

Adult↗
PubMed1998

Chromosome instability is a predominant trait of fibroblasts from Li-Fraumeni families.

Previous work has indicated a role for p53 in cell cycle control, genomic stability and cellular responses to DNA-damaging agents. However, few data are available for human fibroblasts heterozygous for defined germline mutations in TP53. We report studies on 25 strains derived from 12 families with Li-Fraumeni syndrome (LFS) and 18 strains from normal volunteers. The families include three that are classical LFS families, but in whom no TP53 mutation has been found. In the families with mutations, increased longevity and resistance to low-dose-rate ionizing radiation showed a statistically significant association with the presence of TP53 mutations. However, not all heterozygotes had increased longevity or were radioresistant, and fibroblasts from cancer-affected members of LFS families without TP53 mutations showed no significant increase in either of these end points. In contrast, all mutation-carrying strains showed evidence of genomic instability, expressed as aneuploidy, and accumulated structural chromosome aberrations in up to 100% of cells, usually accompanied by loss of the wild-type TP53 allele, immediately before senescence. Levels of aneuploidy higher than in normal cells were also observed in fibroblasts from families without TP53 mutations, suggesting that chromosome instability is a major factor in determining the cancer proneness of these families.

Adolescent↗
PubMed1997

Comparative genomic hybridisation of ductal carcinoma in situ of the breast: identification of regions of DNA amplification and deletion in common with invasive breast carcinoma.

Comparative genomic hybridisation has been used to map copy number changes in nine cases of ductal carcinoma in situ of the breast obtained from wax-embedded archive material. A wide variety of abnormalities were detected including gain of regions of 1q, 17q, 19q, 20p and 20q and loss on 13q, 14q, 17p, 16q and 22q. Amplification of areas on 10p, 8q and 20q were also observed. Chromosomal alterations were more frequent in higher grade DCIS and closely resemble those previously detected in invasive breast cancer using the same technique. These data provide strong molecular support for the view that DCIS is a precursor lesion of invasive breast carcinoma.

Aged↗
PubMed1997

G2 chromosomal radiosensitivity in fibroblasts of ataxia-telangiectasia heterozygotes and a Li-Fraumeni syndrome patient with radioresistant cells.

PURPOSE: To investigate whether the good discrimination we previously observed between ataxia-telangiectasia (A-T) heterozygotes and normal donors for induction of chromosome aberrations by X-rays in G2 lymphocytes is also seen in G2 fibroblasts. Also to investigate the G2 radiosensitivity of a patient with the cancer-prone Li-Fraumeni syndrome (LFS) whose fibroblasts are resistant to the lethal effects of radiation. MATERIALS AND METHODS: Fibroblasts were exposed to 0.5 Gy X-rays and harvested for metaphase analysis 90 min later. RESULTS: Four A-T heterozygote cell strains were all more sensitive than seven normal controls. The LFS strain with a germline TP53 mutation was twice as sensitive as the mean control value. CONCLUSIONS: Although chromosomal, radiosensitivity is seen in A-T heterozygotes and LFS cells, the former are radiosensitive and the latter radioresistant to cell killing. Repair defects may predominate in A-T heterozygotes, inadequate genome surveillance in LFS cells.

Ataxia Telangiectasia↗
PubMed1997

Physical localisation of the breakpoints of a constitutional translocation t(5;6)(q21;q21) in a child with bilateral Wilms' tumour.

A 6 month old boy presented with bilateral Wilms' tumour. Cytogenetic analysis of the lymphocytes from the patient showed a de novo balanced translocation t(5;6)(q21;q21), which was also present in the tumour material as the sole cytogenetic abnormality. To facilitate the identification of the translocation breakpoints, we have established a lymphoblastoid cell line (MA214L) from the patient which maintains the translocation in culture. We have used Genethon microsatellite markers as sequence tagged sites (STSs) to isolate yeast artificial chromosome (YAC) clones to 5q and 6q from human genomic libraries. Using fluorescence in situ hybridisation (FISH) on metaphase preparations of MA214L, we have physically defined the translocation breakpoints between YAC clones on each chromosome arm. The genetic distance separating the flanking YACs on 6q21 is 3 cM, while that on 5q21 is 4 cM. To date this is the first report of these chromosomal regions being implicated in Wilms' tumourigenesis.

Chromosome Fragility↗
PubMed1996

A previously undescribed mutation within the tetramerisation domain of TP53 in a family with Li-Fraumeni syndrome.

We report details of a family with classic Li-Fraumeni syndrome in which there is a mutation in codon 344 of the tumour suppressor gene TP53. Codon 344 is a key residue within the tetramerisation domain, and the amino acid substitution of a proline for a leucine is predicted to have profound implications for tetramerisation and potentially DNA binding. This is the first report of a mutation at this residue in either sporadic tumours or in the germline and the first report of a germline mutation within the tetramerisation domain. The family does not appear to be remarkable in the spectrum of tumours, and there is loss of the wild-type allele in a leiomyosarcoma from the proband. A cell line has been established from the tumour of the proband and cytogenetic and molecular studies carried out, providing an extensive analysis in this family.

Adult↗
PubMed1996

Bud10p directs axial cell polarization in budding yeast and resembles a transmembrane receptor.

BACKGROUND: The budding yeast Saccharomyces cerevisiae can bud in two spatially programmed patterns: axial or bipolar. In the axial budding pattern, cells polarize and divide adjacent to the previous site of cell separation, in response to a cell-division remnant, which includes Bud3p, Bud4p and septin proteins. This paper investigates the role of an additional component of the cell-division remnant, Bud10p, in axial budding. RESULTS: The sequence of Bud10p predicts a protein that contains a single trans-membrane domain but lacks similarity to known proteins. Subcellular fractionations confirm that Bud10p is associated with membranes. Bud10p accumulates as a patch at the bud site prior to bud formation, and then persists at the mother-bud neck as the bud grows. Towards the end of the cell cycle, the localization of Bud10p refines to a tight double ring which splits at cytokinesis into two single rings, one in each progeny cell. Each single ring remains until a new concentration of Bud10p forms at the developing axial bud site, immediately adjacent to the old ring. Certain aspects of Bud10p localization are dependent upon BUD3, suggesting a close functional interaction between Bud10p and Bud3p. CONCLUSIONS: Bud10p is the first example of a transmembrane protein that controls cell polarization during budding. Because Bud10p contains a large extracellular domain, it is possible that Bud10p functions in a manner analogous to an extracellular matrix receptor. Clusters of Bud10p at the mother-bud neck formed in response to Bud3p (and possibly to an extracellular cue, such as a component of the cell wall), might facilitate the docking of downstream components that direct polarization of the cytoskeleton.

Amino Acid Sequence↗
PubMed1995

Mapping of gene loci in the Q13-Q15 region of chromosome 12.

The gene loci CDK4, GLI, CHOP and MDM2 have been mapped to the q13-q15 region of chromosome 12. Using fluorescence in situ hybridization onto simultaneously DAPI-banded metaphase chromosomes and interphase nuclei, we have more precisely mapped and ordered these loci, together with a number of Genethon microsatellite markers. GLI and CHOP localize to 12q13.3-14.1, CDK4 to 12q14 and MDM2 to 12q14.3-q15, and the gene order is cen-GLI/CHOP-CDK4-MDM2. The Genethon microsatellites D12S80 and D12S83 flank MDM2.

CCAAT-Enhancer-Binding Proteins↗
PubMed1995

Determination of the gene order of the three loci CD2, NGFB, and NRAS at human chromosome band 1p13 and refinement of their localisation at the subband level by fluorescence in situ hybridisation.

The three loci NRAS, NGFB, and CD2 map to human chromosome band 1p13. Using fluorescence in situ hybridisation (FISH) to simultaneously DAPI-banded metaphase chromosomes, we have further refined the localisation of these three genes to specific subbands. NRAS localises to subband 1p13.2 and CD2 and NGFB to 1p13.1. Also, with the use of multicolour FISH, we have determined the order and orientation of the three loci in relation to the centromere. The order is cen-CD2-NGFB-NRAS.

Antigens, CD↗
PubMed1994

Structural organisation and chromosomal mapping of the human Id-3 gene.

The helix-loop-helix (HLH) family of transcription factors plays a central role in the regulation of cell growth, differentiation and tumourigenesis. Members of the Id (inhibitor of DNA binding) class of these nuclear proteins are able to heterodimerise with and thereby antagonise the functions of other transcription factors of this family. We report here on the genomic organisation of the human Id3 (HLH 1R21/heir1) gene. Comparison with the two other mammalian Id genes, Id1 and Id2, reveals a highly conserved protein coding gene organisation consistent with evolution from a common, ancestral Id-like gene. In addition, by using a yeast artificial chromosome (YAC) clone of Id3, we have fine-scale mapped the gene to chromosome band 1p36.1 by fluorescence in situ hybridisation (FISH) and, using the same FISH technique, we have detected heterogeneity in tumour-associated 1p36 chromosome translocations.

Adenocarcinoma↗
PubMed1994

A transcribed polymorphism and sub-localisation of MDM2.

An NlaIV polymorphism in the 5' untranslated region of the MDM2 gene is described. MDM2 was sublocalised by fluorescence in situ hybridisation with a yeast artificial chromosome probe to 12q14.3-12q15. We demonstrate the use of the polymorphism to assess allelic imbalance in breast tumours.

Alleles↗
PubMed1993

A B cell specific immediate early human gene is located on chromosome band 1q31 and encodes an alpha helical basic phosphoprotein.

We have determined the cDNA sequence of a human B cell specific, immediate early gene, designated 1R20, which is inducible in response to several B cell activation signals. The cDNA sequence predicts a 196 amino acid open reading frame comprising numerous highly basic residues and the predicted structure contains several potential alpha helical domains together with eight consensus protein phosphorylation sites. The 1R20 gene has been localised by fluorescence in situ hybridisation to chromosome band 1q31, a region known to be implicated in the pathogenesis of haemopoietic malignancies.

Amino Acid Sequence↗
PubMed1993

The expression of aphidicolin-induced fragile sites in familial breast cancer patients.

The expression frequency of aphidicolin-induced fragile sites was examined in familial breast cancer patients to determine whether this parameter could be used as a marker of genetic susceptibility in at-risk individuals. No difference was found in expression frequency between the breast cancer patients and a group of normal individuals (p = 0.61). This indicates that the expression frequency of aphidicolin-induced fragile sites is not a suitable marker for assessing genetic susceptibility in familial breast cancer.

Adenocarcinoma↗
PubMed1992

Ring chromosomes in a retroperitoneal lipoma of childhood.

We report here the presence of ring chromosomes in a retroperitoneal lipoma from a 12-year-old male. Ring chromosomes are strongly associated with the pathological subtype "atypical lipoma" in adults. In contrast, however, the tumour described here possesses no atypical features.

Aneuploidy↗
PubMed1990

A cytogenetic study of male breast cancer.

In a direct preparation from a male breast carcinoma two populations of cells were present, one hypodiploid (range 25-34) and the other hypertriploid (range 56-84). Twenty-two marker chromosomes were recognized. One of these, dic(5:11)(p14:q23) was present in one or two copies in every cell and has not been reported in any other case of breast cancer. There was a consistent monosomy of chromosome 7 and, in the hypertriploid cells, a gain of one to three copies of chromosome 3. The breakpoint 11q23 is a rare, folate-sensitive fragile site but was not expressed in peripheral blood cell lymphocytes from the patient.

Aged↗