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Biomedical subjects

B A Thomas

Publications and source records attributed to B A Thomas.

At least 19 recordsLinked to original sources
PubMed1998

Rapid purification and molecular modeling of AaIT peptides from venom of Androctonus australis.

As recombinant viruses expressing scorpion toxins are moving closer toward the market, it is important to obtain large amounts of pure toxin for biochemical characterization and the evaluation of biological activity in nontarget organisms. In the past, we purified a large amount of Androctonus australis anti-insect toxin (AaIT) present in the venom of A. australis with an analytical reversed-phase column by repeated runs of crude sample. We now report 20 times improved efficiency and speed of the purification by employing a preparative reversed-phase column. In just two consecutive HPLC steps, almost 1 mg of AaIT was obtained from 70 mg crude venom. Furthermore, additional AaIT was obtained from side fractions in a second HPLC run. Recently discovered insect selective toxin, AaIT5, was isolated simultaneously from the same venom batch. It shows different biological toxicity symptoms than the known excitatory and depressant insect toxins. AaIT5 gave 100% mortality with a dose of less than 1.3 micrograms against fourth-instar tobacco budworms Heliothis virescens 24 h after injection. During the purification process, we implemented mass spectrometry in addition to bioassays to monitor the presence of AaIT and AaIT5 in the HPLC fractions. Mass spectrometric screening can unambiguously follow the purification process and can greatly facilitate and expedite the downstream purification of AaIT and AaIT5 eliminating the number of bioassays required. Further, electrospray ionization was compared with matrix-assisted desorption/ionization and evaluated as a method of choice for mass spectrometric characterization of fractions from the venom purification for it provided higher mass accuracy and relative quantitation capability. Molecular models were built for AaIT5, excitatory toxin AaIT4, and depressant toxin LqhIT2. Three-dimensional structure of AaIT5 was compared with structures of the other two toxins, suggesting that AaIT5 is similar to depressant toxins.

Amino Acid Sequence↗
PubMed1997

Interval cancers and cancers in non-attenders in the Ostergötland Mammographic Screening Programme. Duration between screening and diagnosis, S-phase fraction and distant recurrence.

The study was based on a population mammographic screening programme for women aged 40-74 years. Metastatic potential was analysed in 843 invasive breast cancers with regard to mode of detection and a number of prognostic factors. There was a higher metastatic capacity in clinically detected cases, but multivariate analyses showed that neither the mode of detection (hazard rate ratio of distant recurrence RR = 1.39, 95% CI 0.78-2.46 interval cancers and RR = 1.6, 95% CI 0.76-3.36 non-attenders) nor the duration between screening and diagnosis for true interval cancers (RR = 0.47, 95% CI 0.16-1.35 in tumours detected later than one year after screening) were independent prognostic factors. A correlation was found between metastatic potential and the SPF (RR = 2.94, 95% CI 1.57-5.50 in tumours with a high SPF), the oestrogen receptor status and the tumour stage. In conclusion, interval cancers intrinsically are not different from other breast cancers with equivalent characteristics; the duration between screening and diagnosis in interval cancers was not clearly correlated to the prognosis, but the S-phase fraction was a powerful predictor of prognosis.

Adult↗
PubMed1996

The role of rat serum carboxylesterase in the activation of paclitaxel and camptothecin prodrugs.

Paclitaxel-2-ethylcarbonate (PC) is a prototype for a family of paclitaxel prodrugs that have significant levels of antitumor activities in rodent models for human cancer. In this study, an enzyme responsible for the conversion of PC to paclitaxel was purified from rat serum. N-terminal amino acid sequence analysis indicated that the isolated enzyme was rat serum carboxylesterase. This enzyme was shown to significantly enhance the cytotoxic activities of both PC and 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), a water-soluble analogue of camptothecin, on lung carcinoma and melanoma cell lines. Rat serum carboxylesterase may have applications for the site-specific delivery of anticancer drugs to tumor masses.

Animals↗
PubMed1995

N5-methylasparagine and energy-transfer efficiency in C-phycocyanin.

A posttranslationally methylated asparagine residue, N5-methylasparagine, is found at the beta-72 site in many phycobiliproteins. Two mutations (Asp and Gln) in the beta-72 position of Agmenellum quadruplicatum C-phycocyanin were investigated to clarify the role of the wild-type N5-methylasparagine near the beta-84 "fluorescing" bilin tetrapyrrole chromophore. Chemical analysis for amide modification revealed that the beta-72Q protein was partially methylated with a stoichiometry of 0.27, suggesting that either the asparagine methyltransferase is nonspecific or a glutamine methyltransferase exists. Urea denaturation studies could detect no difference in protein stability for any of the C-phycocyanin species. Steady-state spectroscopic measurements demonstrate that Asp and Gln substitution for the C-phycocyanin beta-72 NMA affects both the ground to excited state transition and the excited-state characteristics of the beta-84 chromophore, while the rate of radiative energy transfer is unaffected. Energy-transfer efficiency within phycobilisomes (represented by steady-state fluorescence quantum yields) was also negatively impacted by the beta-72 substitutions. Time-resolved fluorescence emission spectroscopic studies with C-phycocyanin reveal three distinguishable fluorescence lifetimes. The longest fluorescence lifetime is diminished 7-10% by the Asp and Gln mutations in comparison to a control sample where beta-72 is NMA. Molecular dynamics calculations implicate a change in the bilin tetrapyrrole chromophore ring geometry as a likely source of the altered photophysics induced by the mutations. We conclude that N5-methylasparagine plays a special role in establishing the environment surrounding the beta-84 chromophore which minimizes the rates of nonradiative energy losses that would otherwise defeat the high quantum yield for energy transfer within the phycobilisomes.

Asparagine↗
PubMed1995

Is psychological wellbeing impaired in long-term survivors of breast cancer?

OBJECTIVE: To measure anxiety and depression in long term survivors of breast cancer. DESIGN: Case-control study. SETTING: Follow up of the trial of early detection of breast cancer in the South West Surrey Health District. SUBJECTS: 331 patients with breast cancer aged 50-78, attending mammographic follow up, who had been invited to screening before diagnosis, and 584 controls who had attended the same clinic but did not have breast cancer. The sample included 290 pairs matched by screening attendance pattern and year of birth. MAIN OUTCOME MEASURE: Anxiety and depression scores on the Hospital Anxiety and Depression Scale. RESULTS: Significantly fewer symptoms of anxiety and depression were reported by patients with cancer than by controls and significantly fewer had high scores suggesting the presence of psychological morbidity meriting treatment. Among the patients with cancer anxiety was more common at the first annual follow up than at later visits. Symptom scores were not significantly related to the manner of detection or to the type of initial treatment. Potentially confounding social and personal factors did not account for the differences between patients with cancer and controls. CONCLUSION: The prevalence of anxiety and depression is not increased in long term survivors of breast cancer who are apparently free from disease and is not substantially affected by the manner in which a cancer is detected or by the treatment given. In the light of these findings it is difficult to justify large "quality adjustments" to the estimates of recurrence-free years of life saved by screening. Those who counsel patients with breast cancer should be aware that although the initial distress can be severe, meriting psychological treatment, patients do recover their normal ability to enjoy life.

Age Factors↗
PubMed1993

Interval cancers and sensitivity in the screening centres of the UK trial of early detection of breast cancer.

The incidence rates of interval cancers following a negative breast screen in two screening centres which offered women aged 45-64 annual screening by mammography and/or clinical examination are examined. Sensitivity of screening is estimated by comparing the incidence rate of interval cancers with that expected in the absence of screening, and the results are compared with those from alternative methods of calculating sensitivity. The incidence rate of cancers diagnosed within 12 months of a negative screen by mammography plus clinical examination was reduced by 70% for women aged 45-54, and 84% for women aged 55+. There is no indication from this that sensitivity in the UK trial was substantially lower than in other studies which have achieved larger reductions in mortality.

Breast Neoplasms↗
PubMed1991

A multivariate approach to the treatment of peripheral nerve transection injury: the role of electromagnetic field therapy.

A multivariate approach to the treatment of peripheral nerve transection injury has been used in a rat model. A pilot study (48 animals, 8 groups) examined variables associated with the method and timing of surgical repair, the arrest of wallerian degeneration, and the role of pulsing electromagnetic field therapy (PEMF) in functional recovery. A second phase (90 animals, 6 groups) then studied the timing and duration of pulsing electromagnetic field therapy as the only variable in larger groups of animals. The pilot study revealed that a vein-graft conduit did not improve functional recovery compared with standard epineurial repair. Additionally, delayed repair compared favorably with immediate repair. The use of chlorpromazine to inhibit the toxic effects of calcium influx appeared to enhance early functional recovery, and the combination of delayed nerve repair and pulsing electromagnetic field therapy seemed to consistently improve function. The second phase of the study has demonstrated (for the first time) statistical improvement in ambulation in animals treated with delayed surgical repair and prolonged pulsing electromagnetic field therapy. We postulate that future treatment of nerve transection injuries will involve a combined treatment regimen consisting of the immediate arrest of wallerian degeneration, delayed surgery, and pulsing electromagnetic field therapy.

Analysis of Variance↗
PubMed1990

Detection of methylated asparagine and glutamine residues in polypeptides.

A residue of gamma-N-methylasparagine (gamma-NMA) is found at position beta-72 of many phycobiliproteins. delta-N-Methylglutamine is present in some bacterial ribosomal proteins. gamma-NMA was synthesized by reacting the omega-methyl ester of aspartate with methylamine and delta-N-methylglutamine by reaction of pyroglutamate with methylamine. These derivatives and the omega-methyl esters of aspartate and glutamate were characterized by melting point, by thin-layer chromatography, by amino acid analysis, by NMR spectroscopy, and after conversion to the phenylthiohydantoin (PTH) derivative. The gamma-NMA residues in peptides from allophycocyanin, C-phycocyanin, and B-phycoerythrin were stable under the conditions of automated sequential gas-liquid phase Edman degradation. On HPLC, PTH-gamma-NMA co-eluted with PTH-serine and was accompanied by a minor component eluting just prior to dimethylphenylthiourea. Similar results were obtained on manual derivatization of synthetic gamma-NMA to prepare the PTH derivative. The PTH-delta-N-methylglutamine standard eluted near the position of dimethylphenylthiourea under the usual conditions employed for the identification of PTH-amino acid derivatives in automated protein sequencing.

Amino Acid Sequence↗
PubMed1984

Screening for breast cancer in Europe: achievements, problems, and future.

Several breast cancer screening programmes are being carried out in Europe. Clinical examination in combination with mammography is the screening method used in Guildford and Edinburgh (United Kingdom) as well as in Utrecht (Netherlands). Mammography is the only screening modality in the Swedish programmes of Falun (Kopparberg County), Linköping (Ostergötland county), and Malmö and in Nijmegen (Netherlands). Clinical examination is the initial screening method in Turku (Finland). The Swedish programmes are population-based, controlled, and randomised. They are designed to assess the impact of screening on the mortality of breast carcinoma. Comparing the results of all the European screening programmes is expected to give some answers to the hitherto unanswered questions concerning the screening method and ideal interval in different age groups. The results achieved so far indicate that although mammography is a sensitive method for the detection of early breast cancer, clinical examination and an aggressive biopsy policy may be necessary to reduce mortality from breast cancer in certain age groups. It is also evident that there is no universally applicable ideal screening method or rescreening interval for all age groups.

Adult↗
PubMed1983

The mammographic features of infiltrating epitheliosis.

The clinical, radiological and histological findings are described in nine cases of infiltrating epitheliosis. In seven cases the mammogram revealed 2.5-5.0 cm discoid radial scars which conformed with the histological features and there was no associated significant clinical abnormality. It can be difficult to differentiate the mammographic appearance of infiltrating epitheliosis from those of carcinoma with confidence but, taken in conjunction with the absence of clinical findings, the changes in the larger lesions are sufficiently distinctive to arouse considerable suspicion. The prevalence of the condition is estimated at 0.4/1000 women in the 45-65 years age range.

Breast↗
PubMed1983

The Guildford breast screening project.

Of the 24 069 women aged 45-64 registered with a Practitioner in the South West Surrey Health District 69% attended for breast cancer screening by clinical examination and mammography, with the resultant cancer detection rate of 5.5/1000 women screened and a cancer: benign biopsy rate of 1:1.77. These cancers represent 94% of cancers diagnosed in screened women and 84% of all cancers diagnosed in the total population of this age within one year of the screening invitation. Seventy-three percent of the cancers detected by screening and 66% of all cancers diagnosed in the total population within a year of the screening invitation were 2 cm (or less) in maximum diameter.

Biopsy↗