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E J Chambers

Publications and source records attributed to E J Chambers.

11 recordsLinked to original sources
PubMed1999

Structural studies on the effects of the deletion in the red cell anion exchanger (band 3, AE1) associated with South East Asian ovalocytosis.

We have carried out a solution-state NMR study of synthetic peptides patterned on the first membrane span of normal human band 3, and the same region of the mutant band 3 present in Southeast Asian ovalocytosis (SAO) which has a nine amino acid deletion. In 1:1 (v/v) chloroform/methanol, the 42 residue normal peptide (R389-K430) consisted of three helical regions. The slow solvent exchange of backbone amide protons revealed the helix from P403 to A416 was more stable than the "cytoplasmic" N-terminal helix from P391 to A400. These helices were separated by a sharp bend at P403, which is probably located at the boundary between the cytoplasmic domain and the first transmembrane span. The SAO deletion (A400-A408) removed the bend at P403, to leave a stable helix from P391 to A416 containing the residuum of the normal first transmembrane helix and with a hydrophobic turn replaced by a polar turn in the SAO peptide. Insertion of fragments of normal band 3 and band 3 SAO into microsomal membranes was investigated using a cell free translation system. A fragment composed of the cytoplasmic domain and the putative first membrane domain of normal band 3 (B3(1)) inserted stably into the membrane. However, the corresponding fragment of band 3 SAO [SAO(1)] did not integrate stably into membranes. Our results suggest that in SAO band 3, the region of the first membrane span of normal band 3 does not integrate properly into the membrane because it lacks a sufficiently long hydrophobic segment, and the deletion also disrupts a conserved structural subdomain at the membrane surface.

Amides↗
PubMed1998

NMR solution structure of a cytoplasmic surface loop of the human red cell anion transporter, band 3.

The membrane domain of the human red cell anion transport protein, band 3, is too large to be studied by solution nuclear magnetic resonance spectroscopy (NMR), and its amphiphilic nature requires the use of detergents for solubilization. An alternative approach is to divide the protein into smaller (trans-membrane or surface loop) domains for NMR study. We report the structure of a 46-residue synthetic peptide that corresponds to the cytoplasmic surface loop connecting the putative 12th and 13th trans-membrane spans (residues 796-841) in the 14 span model of band 3. This peptide was shown by circular dichroism (CD) to be 38% helical in 30% trifluoroacetic acid. Two regions of helix (one close to the N-terminus of the peptide and one close to the C-terminus of the peptide) were identified by NMR. Long-range nuclear Overhauser effect (NOE) cross-peaks showed the two helices to be in near proximity. The helices were separated by a proline-rich loop that exhibited local order but was mobile with respect to the rest of the peptide. We discuss how the NMR structure of this loop fits the current models of band 3 structure and topology and the results of recent mutagenesis experiments. A cyclic version of this peptide was synthesized and studied by CD, but NMR studies were not possible due to the low solubility of this peptide.

Amino Acid Sequence↗
PubMed1996

Comparison of mitozantrone and epirubicin in advanced breast cancer.

Forty chemotherapy naive patients with metastatic or locally advanced breast cancer were treated in a randomized trial comparing mitozantrone 14 mg/m2 with epirubicin 75 mg/m2 given intravenously at 3-weekly intervals. There was a 40% (95% confidence interval (CI) 8-72; P = 0.013) higher partial response rate with epirubicin (11/18) than with mitozantrone (4/19). Epirubicin caused significantly more alopecia (difference 76%; 95% CI 57-96; P < 0.0001) and nausea/vomiting (difference = 38%; 95% CI 10-67; P = 0.01). Three patients who received long courses of epirubicin experienced cardiac failure; two were proved to have cardiomyopathy. The median survival for the epirubicin and mitozantrone groups were 9.5 and 8 months respectively. Thus, although epirubicin gave a higher response rate it also caused more toxicity.

Antineoplastic Agents↗
PubMed1995

Magnetic resonance imaging and magnetic resonance angiography in long term survivors of acute lymphoblastic leukemia treated with cranial irradiation.

BACKGROUND: Successful treatment of acute lymphoblastic leukemia (ALL) has resulted in an increasing number of patients whose disease is cured. This treatment includes cranial irradiation as prophylaxis against central nervous system relapse. The late effects of irradiation are well documented, but their incidence is unknown. The authors investigated the late effects of this treatment modality further by scanning 35 long term survivors of ALL who received cranial irradiation. METHODS: Thirty-five survivors of ALL with no known complication of treatment were included in this study. They were examined with magnetic resonance imaging (MRI) of the brain and magnetic resonance angiography (MRA) of the circle of Willis. A control group of 24 patients who were cured of other childhood malignancies without exposure to cranial irradiation also were scanned. RESULTS: Fifteen of 35 (43%) abnormalities were found in the study group versus 4/24 (17%) in the control group. Excluding minor atrophic changes that are known to be produced by irradiation and chemotherapy, there were 9/35 (26%) abnormalities in the study group and 1/24 (4%) in the control group (P < 0.05). These abnormalities included three tumors, a meningioma, a paranasal sinus rhabdomyosarcoma, and an anaplastic astrocytoma. In addition, there were two cases of large vessel vasculopathy, two small cystic infarcts, one diffuse white matter abnormality, and one cryptic vascular malformation. The abnormal control patient had a cerebellar infarct. CONCLUSION: Complications of cranial irradiation in the treatment of ALL appear to be more frequent than currently are appreciated. That these complications include tumors that are potentially treatable suggests that screening may be valuable for these patients.

Adolescent↗
PubMed1995

Hairpin properties of single-stranded DNA containing a GC-rich triplet repeat: (CTG)15.

Although triplet repeat DNA sequences are scattered throughout the human genome, their biological function remains obscure. To aid in correlating potential structures of these nucleic acids with their function, we propose their classification based on the presence or absence of a palindromic dinucleotide within the triplet, the G + C content, and the presence or absence of a homopolymer. Five classes of double-stranded (ds) triplet repeats are distinguished. Class I repeats, which are defined by the presence of a GC or CG palindrome, have the lowest base stacking energies, exhibit the lowest rates of slippage synthesis [Schlötterer and Tautz (1992) Nucleic Acids Res., 20, 211] and are uniquely associated with triplet repeat expansion diseases. The six single-stranded (ss) triplet repeats within Class I also have the potential to form hairpin structures, as determined by energy minimization. To explore the possibility of hairpin formation by ss Class I triplet repeats, studies were performed with a ss oligonucleotide containing 15 prototypic CTG repeats [ss (CTG)15]. Electrophoretic, P1 nuclease and KMnO4 oxidation data demonstrate that ss (CTG)15 forms a hairpin containing base paired and/or stacked thymines in the stem. Potential functions of hairpins containing Class I triplet repeats are discussed with respect to protein translation and mRNA splicing. Further, potential roles of hairpin structures in triplet repeat expansion events are discussed.

Base Composition↗
PubMed1995

Intracranial large vessel vasculopathy and anaplastic meningioma 19 years after cranial irradiation for acute lymphoblastic leukaemia.

A child was diagnosed in 1969 as having acute lymphoblastic leukaemia (ALL) and received chemotherapy. On bone marrow relapse in 1973, he was treated with cranial irradiation (20 Gy) in addition to chemotherapy. He continues in complete remission 19 years after his relapse. At age 25 years, he presented with headaches and left hemiparesis. Computerised tomograph demonstrated a large, enhancing right-sided intracranial tumour. Angiography was performed and showed the right internal carotid artery was occluded. Most of the right hemisphere was supplied from the external carotid via the middle meningeal artery. The left posterior cerebral artery and the left anterior cerebral artery were absent presumably as a result of radiation-induced arteritis. A resection of an anaplastic meningioma arising from the right sphenoidal ridge was achieved. There was a rapid improvement in function and he returned to work. Vasculopathy of the large intracranial arteries has been described after high dose radiation. It may occur as in this case after moderate dose radiation. There is a correlation with meningioma. There is a possibility that large artery vasculopathy will be present in a proportion of patients irradiated for ALL. The long lag time between irradiation and the development of meningioma may mean that, as survivors of childhood ALL enter their third decade since cure, this tumour may be seen increasingly.

Adult↗
PubMed1995

Models of care for children dying of malignant disease.

Two-thirds of children with cancer are now cured of their disease. For the majority of the remainder there is a period of terminal care. The emphasis of care at this stage is on the quality of life for both child and family. Most families prefer that their child should be cared for at home, with professional support from those known to them. This paper looks at various approaches to terminal care in children and describes the model of care for such children in the south west of the United Kingdom. From this information, key elements of an effective service are identified.

Child↗