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Biomedical subjects

J A Mills

Publications and source records attributed to J A Mills.

At least 19 recordsLinked to original sources

Demonstration of a combined filter to improve the field uniformity of a 90 kV superficial X-ray therapy machine for different treatment field sizes.

The field uniformity of a superficial X-ray machine operating at 90 kV, 10 mA and filtered with a 1.1 mm aluminium beam hardening filter was investigated at a depth of 1 cm below the surface. Uniformity measurements were carried out using films and a densitometer to detect the relative absorbed dose across the field. Film dosimetry was assessed by comparison with ionization chamber dosimetry in a water tank. The original flat hardening aluminium filter was replaced by a combined, profiled filter to improve the uniformity across field sizes 20 cm, 5 cm and 2 cm diameter as well as hardening the beam. Flatness of the beam profile was improved for the 20 cm field size from +/-7.5% to +/-1.3% across the anode/cathode direction and from +/-7.9% to +/-4.7% in the anode/cathode direction. For the 5 cm field size the improvement was from +/-4% to +/-3% and from +/-5.3% to +/-3.6% and for 2 cm field size from +/-3.4% to +/-2.8% and from 10.5% to +/-9.7% in the same directions, respectively. Beam quality measurements were made and the original half-value-layer was reduced from 2.21 +/- 0.09 mm to 2.07 +/- 0.09 mm. The project demonstrated that it was possible to build a filter capable of flattening the beam profile for different sized applicators without significantly changing the penetrating ability of the beam.

Film Dosimetry

A philosophical approach to treatment machine maintenance and breakdown.

Planned preventative maintenance (PPM), quality control (QC) checks and breakdown all contribute to the down-time of a radiotherapy treatment machine. Low levels of machine availability are unacceptable both clinically and financially. Clinical data demonstrate that, for many tumours, interruptions to treatment will result in reduced local control. Reductions to the gaps in treatment can be achieved by patient interchange between machines. Maintaining the maximum possible machine availability will reduce the potential for errors associated with the transfer of patients between machines, and reduce the cost of treatment. Practices for routine PPM and QC vary between hospitals. In this report, a rationale for breakdown and maintenance will be described. Based on the faults experienced on a Philips SL 75-5 and a Philips SL25 over a period of 3 years, the workload associated with routine maintenance and quality control are presented and the additional work associated with breakdown discussed. Faults have been categorized on a scale between catastrophe and maintainability. A demonstration of how this analysis can be used to assess the cost-benefits of proposed changes in working patterns by the extension or reduction of maintenance periods is provided. The results indicated that no gain would be made in changing from a 1-day to a 2-day per month PPM schedule.

Cost-Benefit Analysis

Design, production and characterization of antibodies discriminating between the phenol- and monoamine-sulphating forms of human phenol sulphotransferase.

1. Phenol sulphotransferases (PSTs) are important enzymes in xenobiotic and endobiotic detoxication, and a key component of the body's chemical defence mechanism. 2. Human phenol-(P-PST) and monoamine-(M-PST) sulphating forms of PST share 93% amino acid sequence identity, and to date the various antibodies produced against PSTs all recognize both enzymes. 3. We have identified two peptides based on the cDNA-derived amino acid sequences of human P-PST and M-PST, which elicited for the first time antibodies capable of discriminating between these highly homologous enzymes. 4. These antibodies represent valuable tools for studying the expression, distribution and function of human phenol sulphotransferases.

Amino Acid Sequence

Bone scanning in the multiply injured patient.

A prospective study was undertaken to evaluate the role of radionuclide bone scanning in the management of patients with multiple injuries. During a 7 month period, 14 patients with multiple injuries underwent a bone scan in order to identify occult skeletal injuries. All of the patients had new injuries diagnosed. The majority of new injuries occurred either in a limb in which an injury had already been diagnosed at presentation, or in the chest. Such findings are consistent with previously published data. Infrequently, there was a change in management of the patients in this series following the bone scan.

Adolescent

Loci of Mycobacterium avium ser2 gene cluster and their functions.

The highly antigenic glycopeptidolipids present on the surface of members of the Mycobacterium avium complex serve to distinguish these bacteria from all others and to define the various serovars that compose this complex. Previously, the genes responsible for the biosynthesis of the disaccharide hapten [2,3-di-O-methyl-alpha-L-fucopyranosyl-(1-->3)-alpha-L-rhamnopyranose] of serovar 2 of the M. avium complex were isolated, localized to a contiguous 22- to 27-kb fragment of the M. avium genome, and designated the ser2 gene cluster (J. T. Belisle, L. Pascopella, J. M. Inamine, P. J. Brennan, and W. R. Jacobs, Jr., J. Bacteriol. 173:6991-6997, 1991). In the present study, transposon saturation mutagenesis was used to map the specific genetic loci within the ser2 gene cluster required for expression of this disaccharide. Four essential loci, termed ser2A, -B, -C, and -D, constituting a total of 5.7 kb within the ser2 gene cluster, were defined. The ser2B and ser2D loci encode the methyltransferases required to methylate the fucose at the 3 and 2 positions, respectively. The rhamnosyltransferase was encoded by ser2A, whereas either ser2C or ser2D encoded the fucosyltransferase. The ser2C and ser2D loci are also apparently involved in the de novo synthesis of fucose. Isolation of the truncated versions of the hapten induced by the transposon insertions provides genetic evidence that the glycopeptidolipids of M. avium serovar 2 are synthesized by an initial transfer of the rhamnose unit to the peptide core followed by fucose and finally O methylation of the fucosyl unit.

Amino Acid Sequence

The development of an interdepartmental audit as part of a physics quality assurance programme for external beam therapy.

A cost-effective audit system has been developed that will both detect systematic error in data and procedures and evaluate the quality assurance programme provided by a physics department for radiotherapy. The audit has been developed for external beam radiotherapy and assesses one modality and one treatment machine per year. The audit is carried out on an interdepartmental basis and can be undertaken by two physicists from each department in one working day. The method of assessing the quality assurance programme and the schedule of measurements are described. The process is illustrated using the results of trial audits between the medical physics departments at Coventry and Leicester.

Electrons

Steroid secretion by human early embryos in culture.

The ability of in-vitro fertilized human embryos to secrete oestradiol in culture in the presence of precursor androgen was demonstrated in four independent cultures. Varying amounts of oestradiol were detected and secretion was observed as early as days 5-8 post-fertilization. The pattern of human chorionic gonadotrophin secretion was similar to oestradiol secretion for individual embryos. In one additional culture, secretion of oestradiol and progesterone was observed.

Chorionic Gonadotropin

Use of the linear quadratic model in order to accommodate a small reduction in the number of fractions of a standard radiotherapy treatment regime.

Use of the linear quadratic model is considered for reduction, by one or two fractions, of the number of fractions in a daily fractionated reference schedule while maintaining a continuous regime. The cases of maintaining late or early tumour reacting tissue are considered with the inclusion of time effects. The reduction of biologically effective dose (BED) to early-tumour type tissue is shown to be overestimated for both cases if time effects are not taken into account. A third option is outlined, which equates the magnitude of the fractional reduction of BED for early-tumour-reacting tissue to the fractional increase in BED for late-reacting tissue without accounting for time effects. Using this option, the resulting variations in BED for late- and early-tumour tissue are compared with the accepted tolerances in physical dose delivery and some examples presented. The overestimated prediction of the variation in BED for early-tumour tissue still applies in this option, suggesting that this is the way the linear quadratic model should be applied to such a schedule change.

Humans

Spontaneous insertion of an IS1-like element into the virF gene is responsible for avirulence in opaque colonial variants of Shigella flexneri 2a.

Colonial variation of Shigella flexneri serotype 2a from the translucent (2457T) to the opaque form (2457O) occurs spontaneously once in 10(4) cell divisions, with concomitant loss of ipa gene expression and virulence. The appearance of 2457O was associated with the insertional inactivation of virF, an invasion plasmid-encoded positive regulator of ipa gene expression. Plasmid pWR110, a Tn5-tagged invasion plasmid that restores the invasive phenotype to plasmid-cured Shigella derivatives, was conjugally transferred into 2457O. Synthesis of the invasion-associated IpaB and IpaC polypeptides, normally present on the surface of virulent shigellae, and the invasive phenotype were restored in 2457O(pWR110) transconjugants. Plasmid DNA restriction endonuclease patterns of 2457T and 2457O, along with hybridization analysis, showed that a SalI fragment carrying the virF gene in 2457O had increased in size relative to its counterpart in 2457T. Analysis of virF DNA sequences amplified by the polymerase chain reaction revealed that the virF sequence from 2457O was 780 bp larger than that amplified from 2457T. Moreover, the virF sequence amplified from 2457O hybridized to an IS1 DNA probe whereas the amplified 2457T virF sequence did not. DNA sequence analysis mapped the insertion element, designated IS1SFO, within an A.T-rich region of the virF open reading frame and identified a 9-bp virF target sequence that was duplicated at the insertion site of IS1SFO. The DNA sequence of IS1SFO was greater than 99% homologous to IS1F. Plasmid pWR600, carrying a 1,260-bp HpaII fragment encoding a wild-type virF gene, was able to restore the virulent phenotype and translucent colonial morphology to nine independently isolated 2457O hosts.

Bacterial Proteins

Effects of in-vitro exposure to HCG on subsequent HCG-responsiveness of human granulosa cells obtained following treatment with GnRH analogue and gonadotrophins: an in-vitro model for luteal phase support.

The pregnancy rate in patients undergoing assisted conception treatment following pituitary desensitization with GnRH analogue and ovarian stimulation with gonadotrophins has been reported to be higher when ovarian function is supported in the luteal phase by exogenous human chorionic gonadotrophin (HCG). In the present study, we have examined the effects of culturing monolayers of granulosa cells, collected from such patients at oocyte retrieval, for various time intervals in the presence or absence of HCG on their subsequent ability to secrete progesterone (P4) either spontaneously or in response to further challenge with HCG. When cultured in the absence of HCG, granulosa cells demonstrated a rapid decline in both the spontaneous P4 secretion rate and the ability to secrete P4 in response to HCG. Maintenance in the presence of HCG inhibited the rapid decline in ability to secrete P4 spontaneously and also significantly enhanced the ability to respond to subsequent HCG stimulation. These results suggest that HCG support in the luteal phase in GnRH analogue-treated patients may have a cellular basis for its action both in maintenance of P4 secretion and also in rendering the corpus luteum more sensitive to rescue by conceptus-derived HCG.

Buserelin

The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura.

Criteria for identifying Henoch-Schönlein Purpura (HSP) and distinguishing HSP from other forms of systemic arteritis were developed by comparing the manifestations in 85 patients who had HSP with those of 722 control patients with other forms of vasculitis. By the traditional format of choosing different combinations of candidate criteria and comparing the combinations for their ability to separate HSP cases from controls, 4 criteria were identified: age less than or equal to 20 years at disease onset, palpable purpura, acute abdominal pain, and biopsy showing granulocytes in the walls of small arterioles or venules. The presence of any 2 or more of these criteria distinguish HSP from other forms of vasculitis with a sensitivity of 87.1% and a specificity of 87.7%. The criteria selected by a classification tree method were similar: palpable purpura, age less than or equal to 20 years at disease onset, biopsy showing granulocytes around arterioles or venules, and gastrointestinal bleeding. These were able to distinguish HSP from other forms of vasculitis with a sensitivity of 89.4% and a specificity of 88.1%.

Adolescent

Molecular characterization of a trans-acting, positive effector (ipaR) of invasion plasmid antigen synthesis in Shigella flexneri serotype 5.

A trans-acting, positive effector of invasion plasmid antigen (Ipa) synthesis has been identified and mapped on the pWR100 invasion plasmid of Shigella flexneri serotype 5 (strain M90T-W). Recombinant plasmids carrying this regulatory gene, designated ipaR, were found to restore full virulence to a non-invasive ipaR::Tn5 insertion mutant [M90T-W(pHS1042)] that had lost the ability to synthesize four Ipa antigens (IpaA, 70 kDa; IpaB, 62 kDa; IpaC, 42 kDa; and IpaD, 37 kDa). Genetic mapping of the ipaR gene positioned the locus on a 2.6 kb PstI-AccI fragment contained within a larger 8.0 kb EcoRI molecule that also encoded IpaD, IpaA, and two small proteins (27 kDa and 28 kDa). The trans regulatory effect of the ipaR product on ipaB, ipaC, ipaD, and ipaA expression was demonstrated by transforming compatible ipaBC, ipaDA, ipaR and ipaDAR plasmid recombinants, in various combinations, into M90T-A3, an isogenic invasion plasmid mutant of M90T-W that contained a deletion of the pWR100 ipaBCDA and ipaR loci; such transformants produced wild type levels of the IpaB, IpaC, IpaD and IpaA antigens only in the presence of IpaR+ plasmids. DNA sequence analysis of the ipaR region established that the intiation codon for ipaR is 459 bp from the 3'-end of the ipaA gene and that ipaR encodes a 309 amino acid residue protein. An interesting feature of the IpaR polypeptide was its strong sequence homology with the bacteriophage P1 partition protein ParB, consisting of a 42.8% amino acid identity over a 278 residue section of the aligned proteins.

Amino Acid Sequence