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Biomedical subjects

T Brown

Publications and source records attributed to T Brown.

At least 361 records · Page 20Linked to original sources
PubMed1986

Structural characterisation of the bromouracil.guanine base pair mismatch in a Z-DNA fragment.

The deoxyoligonucleotide d(BrU-G-C-G-C-G) was crystallised at pH 8.2 and its structure analysed by X-ray diffraction. The unit cell, of dimensions a = 17.94, b = 30.85, c = 49.94A contains four DNA duplexes in space group P2(1)2(1)2(1). The duplexes are in the Z conformation, with four Watson-Crick G.C base pairs and two BrU.G base pairs. The structure was refined to an R factor of 0.16 at a resolution of 2.2A with 64 solvent molecules located. The BrU.G base pair mismatch is of the wobble type, with both bases in the major tautomer form and hydrogen bonds linking 0-2 of BrU with N-1 of G and N3 of BrU with 0-6 of G. There is no indication of the presence of ionised base pairs, in spite of the high pH of crystallisation. The results are discussed in terms of the mutagenic properties of 5- bromouracil.

Bromodeoxyuridine↗
PubMed1986

Variation of SCE frequency in lymphocyte cultures from patients with Hodgkin's disease before, during, and after treatment.

Seven patients with newly-diagnosed Hodgkin's disease, having standard mustine-vinblastine-prednisolone-procarbazine therapy, had a large and regular pattern of rise in SCE frequency in their peripheral lymphocytes, which apparently started to fall before the end of the course (32 wk). In contrast, SCE frequency fell below normal in the lymphocytes of nine patients having mantle radiotherapy. Twenty-eight patients studied 2-13 yr after initial chemotherapy or radiotherapy for Hodgkin's disease had normal or near normal SCE frequencies.

Adult↗
PubMed1986

Holzman's fences. Chauvinism or confusion?

Psychiatric syndromes are defined psychologically. Why then has Holzman written that psychiatry maintains a wall between itself and psychology? Why does the Archives publish so few articles on psychological topics? And why does psychiatry neglect psychology in other ways? Holzman has suggested that chauvinism is at fault, but for Archives this is not the case. It seems more likely that the problem reflects difficulties with our understanding of the nature of teleonomic explanations.

Humans↗
PubMed1986

Lack of in vivo mutagenicity and testicular toxicity of triamterene in mice.

Triamterene (2,4,7-triamino-6-phenylpteridine), a widely used diuretic/antihypertensive agent with weak antifolate activity, has been found to be positive in several in vitro assays for mutagenicity. The present studies were undertaken to characterize the potential mutagenic and antifolate activity of triamterene in the bone marrow and testes of mice with in vivo treatment. Triamterene had no clastogenic effects on the bone marrow at 6, 16, or 24 hr after a single oral dose of 25, 125, or 250 mg/kg. No alterations in hematopoietic cell maturation characteristic of antifolate action were observed in a dose-range study in which triamterene was orally administered to mice at 5-300 mg/kg/day for 5 days. Triamterene had no adverse effects on mating or fertility and did not induce dominant lethal mutations in the germ cells of male mice when given for 5 days at 5-100 mg/kg/day. Oral exposure to mice under identical conditions had no effect on testicular weight, DNA content, or activity of the de novo pathway for thymidine synthesis from deoxy [6-3H]uridine. The present findings are consistent with an absence of mutagenic effect and antifolate action on the bone marrow and testes with in vivo administration.

Animals↗
PubMed1986

Metric analyses of the teeth and faces of South Australian twins.

Procedures are described for the acquisition and analysis of data in a study of the dental and facial characteristics of South Australian twins. Comparisons of the mesiodistal diameters of maxillary incisors in MZ and DZ twins revealed heterogeneity of total variances and evidence of inequality of mean values for some dimensions between MZ and DZ twins. Previous estimates of heritabilities for tooth size, relying on classical assumptions in twin research, may be exaggerated. A preliminary analysis of facial shape was undertaken using a procedure for shape matching based on a least squares fit of homologous coordinates. There was evidence of mirror-imaging in some MZ twin pairs and differences in facial asymmetry between male and female DZ twins. Future extensions of the study using methods for three-dimensional shape analysis are described.

Adolescent↗
PubMed1986

Molecular epidemiology of human rotavirus.

The epidemiology of human rotavirus (HRV) in north-east Scotland was investigated between 1982 and 1984. During this period 708 HRV infections were recorded. The majority (83%) of the infections were in children less than 5 years of age although some were recorded in adults. The peak incidence occurred in the winter months although a high number of HRV infections was reported during the summer of 1983. A total of 840 faecal specimens containing rotavirus were screened for HRV genome RNA by polyacrylamide gel electrophoresis. Seven hundred (83%) specimens gave RNA profiles suitable for establishing the HRV electrophoretype. Twenty-five different electrophoretypes were identified, of which 21 had 'long' RNA profiles and four had 'short' RNA profiles. There was extensive co-circulation of distinct electrophoretypes although during any one epidemic period the majority of viruses belonged to a relatively small number of types. Comparison of viruses collected from hospitalized and non-hospitalized patients showed no differences in electrophoretype distribution. HRV was identified in faecal specimens from a wide age group and no correlation was demonstrated between age of patient and electrophoretype of the infecting virus.

Adolescent↗
PubMed1986

Molecular structure of the G.A base pair in DNA and its implications for the mechanism of transversion mutations.

The synthetic deoxydodecamer d(C-G-C-G-A-A-T-T-A-G-C-G) was analyzed by x-ray diffraction methods, and the structure was refined to a residual error of R = 0.17 at 2.5-A resolution (2 sigma data) with 83 water molecules located. The sequence crystallizes as a full turn of a B-DNA helix and contains 2 purine X purine (G.A) base pairs and 10 Watson-Crick base pairs. The analysis shows conclusively that adenine is in the syn orientation with respect to the sugar moiety whereas guanine adopts the usual trans orientation. Nitrogen atoms of both bases are involved in hydrogen bonding with the N-1 of guanine 2.84 A from the N-7 of adenine and the N-6 of adenine within 2.74 A of the O-6 of guanine. The C-1'...C-1' separation is 10.7 A close to that for standard Watson-Crick base pairs. The incorporation of the purine.purine base pairs at two steps in the dodecamer causes little perturbation of either the local or the global conformation of the double helix. Comparison of the structural features with those of the G.T wobble pair and the standard G.C pair suggests a rationale for the differential enzymatic repair of the two types of base-pair mismatches.

Chemical Phenomena↗
PubMed1986

Structural features and hydration of d(C-G-C-G-A-A-T-T-A-G-C-G); a double helix containing two G.A mispairs.

Single crystal X-ray diffraction techniques have been used to characterise the molecular structure of the title compound to 2.5A resolution. The structure consists of ten standard Watson-Crick base pairs and two G.A mismatched base pairs. The purine-purine mismatches have guanine in the usual anti orientation with respect to the sugar and adenine in syn orientation. There are two hydrogen bonds formed between the mismatch bases, N-1 and O-6 of guanine with N-7 and N-6 of adenine respectively. The bulky purine-purine mismatches are accommodated with minor perturbation of the sugar-phosphate backbone. There is a slight improvement in base pair overlap at the mismatch sites. Details of the backbone conformation, base stacking interactions and hydration are presented and compared with those of the parent compound d(C-G-C-G-A-A-T-T-C-G-C-G).

Base Composition↗
PubMed1986

Biplane ventriculography in the rat.

Biplane ventriculography was performed on nine intact anesthetized rats. Images of the left ventricle large enough for analysis were obtained by placing the rats close to the radiographic tubes (direct enlargement). Sampling rates, adequate for heart rates of 500 beats/min, were obtained by filming at 500 frames/s. From the digitized silhouettes of the left ventricle the following information was obtained (means +/- SE): end-diastolic volume 0.60 +/- 0.03 ml, end-systolic volume 0.22 +/- 0.02 ml, stroke volume 0.38 +/- 0.02 ml, ejection fraction 0.63 +/- 0.02, cardiac output 118 +/- 7 ml/min, diastolic septolateral dimension 0.41 +/- 0.01 mm, diastolic anteroposterior dimension 0.40 +/- 0.01 mm, diastolic base-to-apex dimension 1.58 +/- 0.04 mm. To determine the accuracy with which the volume of the ventricle could be measured, 11 methyl methacrylate casts of the left ventricle were made. The correlation was high (r = 0.99 +/- 0.02 ml E) between the cast volumes determined by water displacement and by use of two monoplane methods (Simpson's rule of integration and the area-length method applied to the analysis of the anteroposterior films) and a biplane method (area-length). These results demonstrate that it is possible to obtain accurate dimensions and volumes of the rat left ventricle by use of high-speed ventriculography.

Animals↗
PubMed1986

Erythema infectiosum in a village primary school: clinical and virological studies.

In a questionnaire response to an outbreak of erythema infectiosum in a village primary school, 55 (46%) of the 121 pupils reported an illness with rash. Three of the 12 members of staff also developed a rash. Onset in most affected children was indicated by the classical ;slapped cheek' appearance of erythema infectiosum with subsequent spread of the rash to the extremities. However, in 17 (35%) of 49 children who provided additional clinical data, the rash spread either in the reverse direction or not at all. Nineteen children (39%) reported recurrence of the rash.Serological studies confirmed that human parvovirus was the cause of the outbreak. Forty-six (44%) of 104 children investigated had significant levels of virus-specific immunoglobulin (lg)M and/or lgG antibodies consistent with recent infection. Most infections occurred in older children. Human parvovirus infection was also confirmed in five of the 12 adults. These studies revealed a substantial number of subclinical episodes - 14 (22%) of 64 subjects who remained well had serological evidence of recent infection with human parovovirus. Significantly, 43 individuals (37% of those investigated) remained seronegative despite frequent exposure to infection within the school. This finding, together with the observed temporary interruption of the outbreak which coincided with school holidays substantiates the view that human parvovirus has a relatively low infectivity and requires close person-to-person contact for its transmission.

Adult↗
PubMed1985

G . T base-pairs in a DNA helix: the crystal structure of d(G-G-G-G-T-C-C-C).

The synthetic deoxyoctanucleotide d(G-G-G-G-T-C-C-C) crystallizes as an A-type DNA double helix containing two adjacent G . T base-pair mismatches. The structure has been refined to an R-factor of 14% at 2.1 A resolution with 104 solvent molecules located. The two G . T mismatches adopt the "wobble" form of base-pairing. The mismatched bases are linked by a network of water molecules interacting with the exposed functional groups in both the major and minor grooves. The presence of two mispaired bases in the octamer has surprisingly little effect on the global structure of the helix or the backbone and glycosidic torsional angles. Base stacking around the mismatch is perturbed, but the central G-T step shows particularly good base overlap, which may contribute to the relatively high stability of this oligomer.

Base Composition↗
PubMed1985

Conformations of two duplex forms of d(TCGA) in slow-exchange equilibrium characterized by NMR.

Two conformations adopted by the tetranucleoside triphosphate d(TCGA) in aqueous solution are in slow-exchange equilibrium on the NMR time scale. 1H and 31P NMR spectra obtained at temperatures below 25 degrees C contain two sets of signals that vary in relative proportions with changing temperature. High-field NMR techniques allow the conformations of these species to be examined. Both forms are right-handed double-helical structures, and their interconversion does not involve a single-stranded species since transfer of saturation is observed between corresponding imino protons held in the base pairs of each duplex. The form that predominates at higher temperatures resembles B-DNA, but the other, while of similar conformation at the ends of the molecule, is distorted at the C-G step. Shearing at the center of the duplex results in interstrand stacking of the two cytosines in a way that is reminiscent of Z-DNA. Distances between nonexchangeable protons in this model are consistent with nuclear Overhauser effects observed for resonances of the low-temperature form, while the 1H NMR spectrum shows cytidine H-2' resonances at unusually high field. The relative stabilities of the two forms are discussed in terms of base stacking and hydration, but the origin of the high activation energy for interconversion implicit in the slow-exchange rate is unclear. The conformation of the low-temperature form may represent a sequence-dependent structural feature important in natural DNA, although somewhat fortuitously exemplified by this tetramer. The suggested involvement in correct nucleosome phasing of the pentamer d(TTCGA), present in some eukaryotic genes, is noted.

Kinetics↗
PubMed1985

The crystal structure of d(G-G-G-G-C-C-C-C). A model for poly(dG).poly(dC).

The structure of the DNA oligomer d(G-G-G-G-C-C-C-C) has been determined at a resolution of 2.5 A by single-crystal X-ray methods. There are two strands in the asymmetric unit, and these coil about each other to form a right-handed double-helix of the A-type with Watson-Crick hydrogen bonds between base-pairs. The helix has a shallow minor groove and a deep, water-filled major groove; almost all exposed functional groups on the DNA are hydrated, and 106 ordered solvent molecules have been found. The two d(G-G-G-G).d(C-C-C-C) segments in the octamer exhibit similar and uniform structures, but there is a slight discontinuity at the GpC step between them. A recurring feature of the structure is the overlap of adjacent guanine bases in each GpG step, with the five-membered ring of one guanine stacking on the six-membered ring of its neighbour. There is little or no overlap between adjacent cytosine rings. Conformational parameters for these GpG steps are compared with those from other single-crystal X-ray analyses. In general, GpG steps exhibit high slide, low roll and variable twist. Models for poly(dG).poly(dC) were generated by applying a simple rotation and translation to each of the unmodified d(G-G-G-G).d(C-C-C-C) units. Detailed features of these models are shown to be compatible with various assays of poly(dG).poly(dC) in solution, and are useful in understanding the polymorphic behaviour of this sequence under a variety of experimental conditions.

Chemical Phenomena↗