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Biomedical subjects

S Arnott

Publications and source records attributed to S Arnott.

At least 19 recordsLinked to original sources
PubMed1992

Management of stage II Hodgkin's disease: 15 years experience at St. Bartholomew's Hospital.

One hundred seventy-seven consecutive patients with newly diagnosed stage II Hodgkin's disease (HD) (supradragmatic 157; infra diaphragmatic 20) were treated at St. Bartholomew's Hospital on the basis of pathologic stage (PS) in 84 (IIA 69; IIB 15) and clinical stage (CS) in 93 (IIA 33, IIB 60) between January 1968 and December 1984. The median follow up is 13 years. Overall, complete remission (CR) was achieved in 143 patients (75%) of whom 53 have had a recurrence. One hundred twenty-seven patients remain alive, the cumulative predicted survival at 15 yrs being 70%. Mantle radiotherapy was prescribed to 88 patients with supradiaphragmatic HD, of whom 75 entered CR and 9 achieved good partial remission (GPR) (95%). The duration of remission correlated strongly with ESR (greater than 50 mm/h) and mediastinal thoracic ratio (less than 33% vs. greater than 33%) in a multivariate analysis (p = 0.05 and 0.02, respectively). 46/88 patients remain in continuous first remission, the median duration of remission having not reached at 15 years. Combined modality therapy or chemotherapy alone was prescribed to 69 patients with supradiaphragmatic HD, CR being achieved in 51 patients and GPR in 8 at the completion of all therapy. 48/59 patients continue in first remission. The duration of remission of patients receiving combined modality therapy or CT alone was significantly longer (p = 0.002) than that of patients receiving RT alone, in spite of the fact that the former group comprised predominantly of patients with unfavourable features.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Ordered water in hydrated solid-state polysaccharide systems.

Water molecules within a monolayer or so of macromolecular surfaces are often located in well-defined positions and have restricted mobility. These ordered water molecules play a role in stabilizing polysaccharide ordered structures and intermolecular interactions that are the basis of the rheological properties utilized in food systems. X-ray fiber diffraction can be used to determine the three-dimensional structures of polysaccharides in solid, but well-hydrated, polycrystalline fibers. In favorable cases, difference Fourier synthesis can be used to locate ordered water molecules in these systems, allowing one to visualize their functionally important interactions. These studies provide relevant evidence regarding water interactions in more hydrated systems and in solution. The functionality of ordered water in some polysaccharides used in food systems, as well as in some connective tissue glycosaminoglycans where the ordered water has been defined in considerable detail, as determined by fiber diffraction, is described in this chapter. These structures allow one to derive some general features of the role of ordered water in such systems.

Carbohydrate Sequence↗
PubMed1991

Myeloablative therapy with autologous bone marrow transplantation as consolidation of remission in patients with follicular lymphoma.

A study has been in progress since June 1985 to evaluate the use of myeloablative therapy (cyclophosphamide [60 mg/kg x 2] and total body irradiation [200 cGy x 6]) followed by reinfusion of autologous bone marrow in patients in second or subsequent remission of B-cell non-Hodgkin's lymphoma. The marrow mononuclear cell fraction is being treated in vitro with three cycles of the monoclonal antibody anti-CD20 (anti-B1, Coulter Immunology) and baby rabbit complement (Pel-Freez). Thirty-eight patients with follicular lymphoma (age range 29-61 years, median 43) have been treated to date. At the time of treatment, 28 patients were in second remission, 7 were in third, and 3 were in more than third remission. Twenty-three patients were in complete remission, 15 had residual disease (7 had lymph nodes less than 2 cm diameter, 4 had less than 10% bone marrow infiltration, 1 had involvement of lymph nodes and bone marrow, and 3 had involvement at other sites). Of the 38 study patients, 32 are alive; 6 have died, 4 in remission. Two of the deaths were treatment related: 1 resulted from cerebral haemorrhage at 29 days; 1 resulted from systemic fungal infection at three months). One patient died from secondary acute myelogenous leukaemia at four years, and another from an unrelated cause. Two patients died following relapse. The median time to engraftment was 28 days (range 15-45 days) for neutrophils greater than 0.5 x 10(9)/L and 28 days (range 15-46 days) for platelets greater than 20 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Radiotherapy for stage I Hodgkin's disease: 20 years experience at St Bartholomew's Hospital.

One hundred and one consecutive patients with newly diagnosed stage I Hodgkin's disease (HD) received treatment at St Bartholomew's Hospital, between 1968 and 1987, with a median follow-up of 12 years. Eleven patients have been excluded from detailed analysis because they either received involved field radiotherapy (RT) or radiotherapy with chemotherapy or were lost to follow-up. Actuarial analysis predicts 78% to be alive and without relapse of Hodgkin's disease at 15 years. Ninety evaluable patients (clinical stage (CS) 24; pathological stage (PS) 66) received either mantle or inverted 'Y' RT and form the basis of this analysis. The median age was 33 years (63 men, 27 women). Histology at presentation was nodular sclerosing (39), lymphocytic predominant (27) or mixed cellularity (24). The presenting site was neck (78), axilla (6) groin (4) and mediastinum (2). Complete remission was achieved in all evaluable patients, the actuarial proportion in remission being 75% at 15 years. Factors predictive of a prolonged remission were pathological staging versus clinical staging (P = 0.02) and lymph node size less than 3 cm (P = 0.04). Actuarial overall survival in these 90 patients was 75% at 15 years and none of the above factors correlated with survival. Relapse of HD has occurred in 18 patients (5 within RT field, 10 without and 3 in both). Second remission was achieved in 15/18. The actuarial rate of second remission and survival was 40% at 10 years. Sixteen patients have died, 7 of Hodgkin's disease, 7 of unrelated causes and 2 of second malignancy. A further 3 patients who developed second malignancy are still alive. At 15 years the actuarial mortality related to HD was 12%. These results confirm the importance of long follow up to assess the efficacy of primary therapy.

Adolescent↗
PubMed1989

A re-examination of the crystal structure of A-DNA using fiber diffraction data.

Classical A-DNA helices with h = 0.25 nm may represent the greatest mass per unit length attainable by polynucleotide duplexes. The X-ray diffraction pattern from polycrystalline and well-oriented fibers of calf thymus DNA in its A-form has been carefully re-examined. Indexing on the basis of a C-face-centered monoclinic unit cell of dimensions a = 2.170 nm, b = 3.990 nm, c = 2.803 nm and beta = 96.82 degrees is superior to alternatives that have been proposed. Two right-handed. Watson-Crick base-paired, helical DNA chains with 2 X 11 nucleotides per 2.803 nm pitch, each carrying C3'-endo furanose rings, pass through the unit cell. The crystallography requires the two chains in the duplex to be antiparallel and conformationally identical but the 11 nucleotides in each pitch may be distinct. However, a secondary structure with a mononucleotide asymmetric unit provides as good an X-ray agreement as one with 11 distinct nucleotides. This relative lack of variability is quite different from what is observed in fibrous B-DNAs.

Animals↗
PubMed1989

Structure of the beta-form of poly d(A).poly d(U).

The crystalline beta-form of the sodium salt of poly d(A).poly d(U) trapped in oriented fibers forms a Watson-Crick base-paired, 10(1) double-helix of pitch 3.2 nm. Two molecules are present in a monoclinic unit cell apparently isomorphous with beta-poly d(A).poly d(T). The two chains in each molecule both carry C2'-endo puckered furanose rings but are conformationally not identical. The orientations of the A:U base-pairs relative to the helix-axis are distinctly different from those in classical B-DNA and the overall morphology of the duplex in which they reside resembles that of the alpha-forms of poly (purine).poly (pyrimidine) DNA duplexes previously reported.

DNA↗
PubMed1989

The synthetic DNA duplex of poly d(Abr5U).poly d(Abr5U) adopts an A-DNA-like structure.

An X-ray fiber diffraction study of the synthetic DNA duplex poly d(Abr5U).poly d(Abr5U) shows that its sodium salt adopts an unexceptional A-DNA-like structure. Similar to A-DNA, two molecules are packed in a monoclinic unit cell (a = 2.23 nm, b = 4.14 nm, c = 5.61 nm and alpha = beta = gamma = 90 degrees) of space group C2. Because of its dinucleotide chemical motif, the c-repeat is twice that in A-DNA but, notably, corresponding backbone conformation angles of adjacent nucleotides are almost identical. This is in marked contrast to many B-like conformations of polydinucleotides.

Crystallization↗
PubMed1987

Structure of the alpha-form of poly[d(A)].poly[d(T)] and related polynucleotide duplexes.

The alpha-form of poly[d(A)].poly[d(T)], observed in fibers at high (greater than 80%) relative humidity, is a 10-fold double-helical structure of pitch 3.2 nm. This new X-ray analysis shows that the two strands of the double helix are of the same kind conformationally and both B-like in containing C-2'-endo-puckered deoxyribose rings. Nevertheless, the two strands are different enough for the overall morphology of the duplex to resemble that of the heteromerous model for the drier (beta) form of poly[d(A)].poly[d(T)] in which one strand has C-2'-endo rings and the other C-3'-endo. Since the orientations of the bases in poly[d(A)].poly[d(T)] are persistently different from those of classical B-DNA it is likely that there will be local bending (about 10 degrees) at the junctions between general sequence tracts and the oligo[d(A)].oligo[d(T)] tracts that occur in some native DNAs. The conclusions about the structure of alpha-poly[d(A)].poly[d(T)] are reinforced by independent analyses of similar X-ray diffraction patterns from poly[d(A)].poly[d(U)] and poly[d(A-I)].poly[d(C-T)].

Models, Molecular↗
PubMed1986

DNA-RNA hybrid secondary structures.

DNA-RNA and DNA-DNA duplexes are even more polymorphic than observed previously. DNA-RNA hybrids can have secondary structures like A-DNA or A-RNA, but double helices of the synthetic DNA-RNA hybrids poly(dA) X poly(rU) and poly(dI) X poly(rC), respectively, form 11-fold and 10-fold double-helical structures in which the two chains have quite different conformations. Extensive X-ray fiber diffraction analyses show that in both structures the DNA chains have C-2'-endo-puckered furanose rings, while the anti-parallel RNA chains have C-3'-endo-puckered rings. The bidirectional properties of such duplexes may be important in the transfer of biological information from nucleic acids.

Base Composition↗
PubMed1986

Modelling and refinement of the crystal structure of nucleoprotamine from Gibbula divaricata.

The molecular structure of nucleoprotamine from Gibbula divaricata and its packing in oriented fibers has been modelled both to fit the X-ray diffraction pattern and to avoid steric compression. The representative model consists of 51 poly (dinucleotide) B-DNA helices with 51 poly(hexapeptide) chains associated with the major grooves. The prevailing peptide conformation is beta. The four arginine residues present are hydrogen-bonded to DNA phosphates while neutral peptides protrude into the minor grooves of neighboring nucleoprotamine molecules which are packed 2.61 nm apart in a screw-disordered, quasi-hexagonal lattice. This model reconciles a number of earlier, apparently conflicting experimental results and explains the remarkable stability of nucleoprotamines.

Animals↗
PubMed1979

Bent DNA: visualization of a base-paired and stacked A-B conformational junction.

A model for the junction of contiguous DNA segments having A-DNA and B-DNA conformations is generated using a computerized linked-atom, least-squares model building program. The junction region comprises one base pair and the two neighboring internucleotide linkages and exhibits full hydrogen-bonded base-pairing, full base-stacking, and unexceptional stereochemistry. In addition, the junction has a mixed sugar ring pucker with the junction base pair adopting C2-endo and C3-endo furanose sugar rings in the complementary strands. Since the junction is fully base-stacked, the differences in base tilt between A-DNA and B-DNA result in a bend of 26 degrees in the duplex at the junction. The results of this study indicate: 1) a correlation of the B leads to A transition with several features of the initiation of RNA transcription, 2) possible structural roles of alternating AT and GC sequences in protein recognition, and 3) the possibility of dynamic conformational discontinuities in a DNA helix.

Computers↗
PubMed1979

A reinterpretation of the infrared linear dichroism of oriented nucleic acid films and a calculation of some effective partial changes on the ribose phosphate backbone.

In this paper we show, based on symmetry considerations, that structural information cannot be obtained from the linear infrared dichroism of the dioxy vibrations of the phosphate group of nucleic acids. Consequently, the discrepancies between the results of x-ray structure measurements and linear dichroism measurements are not meaningful. The linear dichroism measurements are instead important for a calculation of transition dipole moments that involve both the vibrations of all the atoms of the nucleotide and their charges. Independent information on either the atomic displacements contributing to a given vibration or the atomic charges permits a refinement of the unknown quantities. Based on the molecular dynamics calculations of Prohofsky et al., atomic charges of DNA are calculated to reproduce the observed linear dichroism results. Some of the resulting charges are unexpected and may reflect the inadequacy of the molecular dynamic calculation.

DNA↗
PubMed1978

A computer aided oligonucleotide analysis provides a model sequence for RNA polymerase-promoter recognition in E.coli.

A novel computer procedure has been used to search for homology among 17 known procaryotic promoter sequences. A model sequence, :formula: (see text), is compatible with the properties of all known promoter and operator mutations, predicts base positions for the initiation of RNA synthesis coinciding with those determined experimentally, is compatible with current models for the regulation of transcription, suggests that RNA polymerase could recognize the DNA double helix firstly in the B conformation then in the A.

Base Sequence↗