Biomedical subjects
Publications and source records attributed to A Jones.
In common with many countries throughout sub-Saharan Africa, some of the many tribes which comprise the indigenous population of Angola practise various forms of tooth mutilation. Three examples associated with distinctive tribes are described and compared with similar practices in neighbouring countries and their references from the literature.
Ion-spray triple quadrupole mass spectrometry was used to investigate the products from the solid phase synthesis of the decapeptide (H)-Val-Gln-Ala-Ala-Ile-Asp-Tyr-Ile-Asn-Gly-(OH) [acyl carrier protein(65-74)]. The target sequence was assembled in stepwise fashion from the C-terminal using Boc chemistry on a Bly-OCH2-Pam-copoly(styrenedivinylbenzene) resin. The product was deprotected and cleaved from the resin by treatment with HF/p-cresol for 1 h at 0 degrees C. The crude product was analyzed by reverse-phase HPLC and contained a single major peptide component, one significant minor (late-eluting) component and several trace-level peptide by-products. The components were separated by HPLC and the fractions directly analyzed by mass spectrometry and tandem mass spectrometry. The major product was confirmed as the desired ACP(65-74). The significant minor component was apparently from incomplete deprotection of Asp70, an artifact of this particular experiment. The trace by-products were found to arise from succinimide formation at Asp70, succinimide formation at Asn73, acylation of the Tyr71 side chain phenolic hydroxyl leading to a branched heptadecapeptide, and tert-butylation of the decapeptide. The possible origins of these by-products are discussed in light of known peptide chemistry. Also notable was the absence, to very low detection levels, of by-products frequently reported to occur in peptide synthesis, illustrating the high degree of refinement and the accuracy of currently used synthetic methods.
Intracellularly expressed cytotoxins are useful tools both to study the action of plant regulatory sequences in transgenic plants and to modify plant phenotype. We have engineered a low mammalian toxicity derivative of Pseudomonas aeruginosa exotoxin A for intracellular expression in plant cells by fusing the ADP ribosylating domain of the exotoxin gene to plant regulatory sequences. The efficacy of exotoxin A on plant cells was demonstrated by transient expression of the modified exotoxin gene in tobacco protoplasts: the exotoxin gene inhibited the expression of a co-electroporated beta-glucuronidase gene. An exotoxin with an introduced frameshift mutation was also effective at inhibiting beta-glucuronidase expression in the transient assay; the activity of the frameshifted gene was presumably a result of frameshifting during translation or initiation of translation at a codon other than AUG. When fused to napin regulatory sequences, the exotoxin gene specifically arrested embryo development in the seeds of transgenic Brassica napus plants concomitant with the onset of napin expression. The napin/exotoxin chimeric gene did not have the same pattern of expression in tobacco as in B. napus; in addition to exhibiting an inhibition of seed development, the transgenic tobacco plants were male-sterile.
The clinical and biochemical effects of combined treatment with the two aromatase inhibitors aminoglutethimide and 4-hydroxyandrostenedione were evaluated in 10 patients suffering from advanced breast cancer. All patients had become resistant to treatment with one of the drugs before having combined treatment. Seven patients progressing on 4-hydroxyandrostenedione who had aminoglutethimide added to their treatment and achieved a further suppression of plasma oestradiol by a mean of 40.0% (p < 0.05). Plasma oestrone was suppressed by a mean of 40.6% (p < 0.025) and plasma oestrone sulphate was suppressed by a mean of 63.6% (p < 0.025). Two of the patients, neither of whom had responded to 4-hydroxyandrostenedione alone, experienced objective tumour regression when aminoglutethimide was given in concert. Three patients progressing on aminoglutethimide who had 4-hydroxyandrostenedione added showed no further suppression of their plasma oestrogen levels, and no tumour regression was observed. These findings suggest a dose-response relationship between plasma oestrogen suppression at low postmenopausal levels and objective tumour response in breast cancer.
The modification responsible for the long-term synaptic potentiation (LTP) that follows a brief conditioning period is not known. To elucidate this change, we have resolved quantal levels of transmission before and after induction of LTP. We find an increase both in the number of quanta released and in quantal amplitude, consistent with combined pre- and postsynaptic modifications. On average, about 60% of LTP can be accounted for by presynaptic enhancement. The increase in either quantal amplitude or quantal content varies significantly among different experiments, but is inversely correlated with its initial value. These results may help to reconcile the different views concerning the site of LTP expression.
Peripheral aromatase activity was measured in 24 postmenopausal women suffering from advanced breast cancer. The % conversion of androstenedione to oestrone was then assessed for a significant correlation with age, weight, height, Quetelets index (weight/height2, Q.I.) and length of menopause. Serum oestradiol (E2) levels were measured in 22 of the subjects and compared with the same indices. There was no correlation between E2 or aromatase activity with the length of menopause (P = 0.3 and P = 0.5, respectively). In our data aromatase activity did not correlate with age (P greater than 0.5, n = 22). Serum E2 levels (P = 0.07, n = 20) expressed a negative correlation (i.e. decreased) with age. There was also a poor correlation between aromatase activity and weight of Quetelets index (P = 0.3, n = 20 for both). Serum E2 levels showed a statistically significant correlation with weight (P = 0.01, n = 21), but the relationship with Quetelets index just failed to attain statistical significance (P = 0.07, n = 20). In both cases the regression line was positive. When aromatase activity was correlated with serum E2 levels the regression line was positive but not statistically significant (P = 0.4, n = 22). The data indicate that aromatase activity is only one factor determining the differences in serum E2 levels between postmenopausal women.
Young children (3.5-6.5 years of age) were tested for their comprehension of 10 common idioms in context and no-context conditions. Results revealed a significant linear trend for children to make more literal responses with increasing age. Children of this age did not find the story contexts helpful in interpreting the idioms. A range of comprehension scores was found among the individual idioms, but semantic transparency (as judged by adults) was not related to comprehension. Child-internal and methodologic variables influencing idiom comprehension are discussed.
In 1983-1988, dogs on 315 farms in Powys, mid-Wales, were purged once with arecoline acetarsol and the faecal purges were examined for cestodes. A few dogs were examined by autopsy. Ninety-seven farms had at least one infected dog, and cestodes were found in 161 of the 882 dogs examined. The ovine strain of Echinococcus granulosus was found in 41 dogs on 25 farms. Taenia hydatigena, T. pisiformis, T. multiceps, T. serialis, T. ovis and Dipylidium caninum were recovered from 85, 35, 15, 3, 19 and 29 dogs respectively. The results are compared with those of previous surveys in Powys and in other regions of Wales.
Cestodes were found in 129 of 875 foxhounds from 20 packs in Powys, mid-Wales, examined by purging in 1983-1988, in the following order of prevalence: Taenia hydatigena in 57 hounds (6.51%), Echinococcus granulosus in 27 (3.09%), Dipylidium caninum in 25 (2.86%), T. ovis in 14 (1.60%), T. pisiformis in 10 (1.14%), T. serialis in five (0.57%) and T. multiceps in four (0.46%). Of 197 foxes examined by autopsy, 22 harboured cestodes: two (1.02%) had E. granulosus, nine (4.57%) T. polyacantha, eight (4.06%) T. pisiformis, two (1.02%) T. serialis, one (0.51%) D. caninum and one (0.51%) Mesocestoides sp. This is the first definite report of T. polyacantha in British foxes. The results are compared with those of previous surveys in Powys and in other parts of Wales, and the reasons for changes in prevalence are discussed.
Tophaceous deposition of calcium pyrophosphate dihydrate (CPPD) crystals is considered unusual as is deposition within tendon sheaths. Associated tendon rupture is described but is rare. We report a lady with tophaceous CPPD deposition at the wrist, a previously unreported site. Contrary to previous cases, this occurred in the setting of symptomatic, polyarticular, pyrophosphate arthropathy. An additional point of interest was development of associated extensor tendon rupture with features favouring a non-inflammatory mechanism of tendon damage.
Mast cell numbers were quantitated in adult cases of mastocytosis demonstrating non-diffuse perivascular and upper dermal concentrations of mast cells. Using the Leder stain and computerised video image analysis, a mean of 382 (+/- 28 SE) mast cell per mm2 were counted in the superficial dermis in skin biopsies from 30 adult cases of mastocytosis, in contrast to a mean of 43 (+/- 5 SE) mast cells per mm2 in skin biopsies from 50 inflammatory dermatoses represented by subacute dermatitis, pigmented purpuric dermatosis, erythema multiforme, lichen planus and granuloma annulare. Ten skin biopsies showing no significant inflammation had a mean of 54 (+/- 7 SE) mast cells per mm2 in the upper dermis. The mean area of individual mast cells as assessed by image analysis in the mastocytosis group was 47.40 microns 2 (+/- 2.26 microns 2, SE) which was significantly different (P < 0.01) than the mast cell area (32.34 microns 2 +/- 2.22 microns 2, SE) in all other groups combined. Computerised video image analysis represents an alternative technique which is useful in assessing mast cell numbers and particularly mast cell size in adult cases of macular mastocytosis and in other dermatoses.
A system for assessing symptoms (pain, stiffness, gelling) and signs (local temperature, effusion, tenderness, synovial swelling, popliteal cyst, crepitus) of osteoarthritis of the knee has been developed. The system has been assessed for intra- and interobserver variation using normal and osteoarthritic knees. Intraobserver variability is low for all indices but interobserver variability is high for physical signs. It is suggested that the components within this system, when applied by a single observer, may provide a reasonable framework for clinical assessment of osteoarthritis of the knee.
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A 59 year old woman presented with an influenza-like illness preceding signs and symptoms strongly suggestive of systemic lupus erythematosus (SLE), which progressed over several months. Owing to these influenza-like symptoms, a viral cause of her illness was sought. Human parvovirus B19 serology was positive and antibodies to DNA were detected by two different methods. This patient is believed to be the first report of human parvovirus B19 infection coinciding with the onset of SLE. The evidence for B19 virus and the part it plays in autoimmunity and arthritis is discussed.
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Laser surgery has been advocated for treatment of many laryngeal lesions. Although the CO2 laser has many advantages, its safe use requires special education of the surgeon and operating room team, and considerable surgical skill. Several dangers inherent in laser use for laryngeal surgery must be considered. These include vocal fold scarring secondary to thermal injury, loss of histopathologically important tissue through vaporization, airway fire and others. Laser-related complications must be considered whenever use of this instrument is contemplated.
Rheumatological disease is common but is often overlooked or inadequately assessed by doctors. This may reflect training in the discipline. The results of a survey of all British medical schools by the Arthritis and Rheumatism Council and the British Society for Rheumatology show that clinical rheumatology teaching forms a small part of most courses (median 4, range 0-8 weeks), usually as a second-year specialty attachment, and that specific assessment of basic clinical skills in rheumatology is often not undertaken. The results of the survey support the idea that the current teaching of rheumatology might help to marginalise the subject rather than to promote it.
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