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Biomedical subjects

J A Thomson

Publications and source records attributed to J A Thomson.

At least 127 records · Page 7Linked to original sources
PubMed1991

Angiotensin II as a potential method of targeting cytotoxic-loaded microspheres in patients with colorectal liver metastases.

Regional chemotherapy is commonly used to treat patients with colorectal liver metastases. However, improvement in survival has still not been demonstrated. Cytotoxic loaded albumin microspheres for arterial administration have been described as a means of improving the the therapeutic index, but their distribution depends upon the prevailing pattern of arterial blood-flow at the time of injection. In this study, the ability of the vasoactive drug angiotensin II to target arterially injected microspheres to colorectal liver metastases is assessed in nine patients using scintigraphic planar and tomographic imaging. The median tumour: normal ratio in nine patients with colorectal liver metastases was 3.4:1 before the administration of angiotensin II. The corresponding ratio after administration of angiotensin II was 7.3:1. The median improvement factor was 1.8 (P less than 0.05). The data suggest that worthwhile tumour targeting can be achieved with angiotensin II in patients with colorectal liver metastases.

Angiotensin II↗
PubMed1991

The effect of lithium therapy on parameters thought to be involved in the development of autoimmune thyroid disease.

This study has considered the effects of primary affective disorders and lithium therapy on a number of factors thought to be important in the development of autoimmune thyroid disease. These factors were examined in (a) controls with no history of any such disorders; (b) patients with primary affective disorders treated with drugs other than lithium and (c) patients with primary affective disorders treated with lithium alone. Eight of 40 patients who were receiving lithium therapy were found to be positive for thyroid microsomal and/or thyroglobulin antibodies, compared to only 3/40 patients who were receiving some other form of treatment for their depression. Peripheral blood mononuclear cells from patients receiving lithium were found to have significantly reduced numbers of suppressor/cytotoxic T cells (P less than 0.05). In addition, suppressor T cells from these patients showed a significantly reduced response to stimulation with concanavalin A (P less than 0.01). These effects were greatest in patients found to be antibody positive. Increased B cell activity, as measured by increased IgG and IgM release following mitogen stimulation, was seen in patients receiving lithium and in those patients receiving other forms of treatment for their depression. This would suggest that the increase is a feature of primary affective disorders and is not due specifically to lithium treatment. It would appear from this study that lithium therapy induces antibody formation in susceptible individuals and this may ultimately lead to the development of thyroid disease.

Adult↗
PubMed1991

Heterogeneity in lymphokine profiles of CD4+ and CD8+ T cells and clones activated in vivo and in vitro.

Analysis of lymphokine mRNA expression and protein secretion by about 100 short-term alloreactive T-cell clones revealed marked heterogeneity in the combinations of lymphokines synthesized. This finding argues against a simple model in which T cells express either an unrestricted (Th0) or a restricted (Th1 or Th2) lymphokine profile. Lymphokine titers appeared to be normally distributed, with the percentage of positive clones for any one product determined by the threshold of detection. Accordingly, the observation that CD4+ clones on average produced higher titers of most lymphokines than CD8+ clones indicated that apparent differences between the lymphokine profiles of these two subsets were quantitative rather than qualitative. Patterns of lymphokine gene expression detected in whole tissues or by analysis of single cells and clones were markedly influenced by in vivo priming. Relative levels of expression of IL-4, IFN-gamma and GM-CSF in lymphoid tissues differed in mice undergoing a GvHR or following contact sensitization with OX or immunization with KLH in adjuvant. Consistent with the finding that IL-4 was the major lymphokine mRNA detected in lymph nodes of KLH-primed mice, most short-term KLH-specific clones derived from such mice also expressed IL-4. A similar approach to the detection of lymphokine-secreting T-cell precursors activated late in L. major infection showed that most clones from the L. major-resistant strain, C57BL/6, secreted IFN-gamma without IL-4 whereas most clones from the susceptible strain, BALB/c, secreted IL-4 without IFN-gamma. Differences were also noted in anti-CD3-induced IL-3 production at the single-cell level between CD8+ cells activated in the GvHR or against a tumor allograft. Con A-induced, filler cell-dependent cloning of CD4+ T cells from unprimed mice gave rise both to IFN-gamma-producing and to IL-4-producing clones. A requirement for an undefined, filler cell-dependent signal for development of IL-4-secreting clones was suggested by the finding that clones of normal CD4+ and CD8+ T cells activated in an anti-CD3-induced, filler cell-free system exclusively produced IFN-gamma and IL-3 without detectable IL-4 or IL-6. With a view to developing a single-cell approach to the analysis of lymphokine profiles of in vivo-activated T cells, sensitive assays for IL-3 and other lymphokines were used to measure secreting cells activated in the GvHR or against a tumor allograft.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Children's perception of safety and danger on the road.

This study investigates the ability of children between 5 and 11 years to select safe places to cross the street. The children were presented with situations which were either extremely safe or manifestly dangerous and were asked to correctly identify these. In other cases, they were asked to choose for themselves routes across the road which they thought would be safe. The tasks were presented in various ways: by means of a table-top simulation on which traffic scenarios had been contrived; by means of photographs of road situations; and by taking the children to real-world sites in the streets near their schools. All the experiments showed a similar pattern of results. Five- and 7-year-olds exhibited very poor skill in identifying dangerous road-crossing sites. Their judgments relied exclusively on the visible presence of cars in the vicinity. Other factors such as blind summits, obscuring obstacles or complex junctions were never recognized as threatening situations. They also showed an unwillingness to make detours when planning their own routes, even where the direct route was manifestly dangerous. Nine-year-olds showed a higher level of ability and 11-year-olds showed quite good skill in these judgements. No sex differences were apparent. These results suggest that young children up to about 9 years must often be at considerable risk as they do not have the ability to recognize a location as dangerous, even if they know the mechanics of the Green Cross Code. The implications for road safety education are discussed.

Accidents, Traffic↗
PubMed1990

A dynamic quaternary structure of bovine alpha-crystallin as indicated from intermolecular exchange of subunits.

The structural bovine eye lens protein alpha-crystallin was dissociated in 7 M urea and its four subunits, A1, A2, B1, and B2, were separated by means of ion-exchange chromatography. Homopolymeric reaggregates of these subunits were prepared by removal of the denaturant via dialysis. It was found that subunits were exchanged upon incubation of mixtures of two homopolymers under native conditions. New hybrid species were formed within 24 h as demonstrated by isoelectric focusing. Moreover, native alpha-crystallin molecules also exchanged subunits when incubated with homopolymeric aggregates of B2 subunits. Subunit exchange between native alpha-crystallin molecules is postulated, and a "dynamic quaternary structure" is presented that allows the polydisperse protein to adapt to changes in cytoplasmic conditions upon aging of the lens tissue.

Animals↗
PubMed1990

Inhibition of alpha-crystallin aggregation by gamma-crystallin.

The transparency of the mammalian lens is primarily maintained by short range order among the major proteins of the lens fiber cells, the crystallins. Although these proteins are highly conserved at the amino acid sequence level, it has proven difficult to establish that they possess other than structural functions. We find that when non-lens proteins are added to concentrated solutions of alpha-crystallin, aggregation is induced, presumably through excluded volume effects. In contrast, the monomeric gamma-crystallins and the low molecular weight form of beta-crystallin (beta L) cause a decrease in the size of alpha-crystallin. When the naturally aggregated form of alpha-crystallin is examined, gamma- and beta L-crystallin, as well as a reducing agent, also cause partial dissociation as detected by dynamic light scattering and size exclusion chromatography, while no effect is seen with non-crystallin proteins. Furthermore, the chemical cross-linking of alpha-crystallin is inhibited by gamma- and beta L-crystallin but not by other proteins. The ability of gamma-crystallin to inhibit the association of alpha-crystallin is primarily localized to the gamma-II form which contains a high degree of exposed thiols. Only small amounts of gamma- and beta L-crystallin, however, can be cross-linked to alpha-crystallin in mixtures of the three proteins even at very high protein concentrations. These results suggest that one possible role for the lower molecular weight crystallins may be to minimize through a reductive effect the intrinsic tendency of alpha-crystallin to aggregate, an association reaction implicated in the loss of lens transparency.

Animals↗
PubMed1990

pH dependence of the urea and guanidine hydrochloride denaturation of ribonuclease A and ribonuclease T1.

To investigate the pH dependence of the conformational stability of ribonucleases A and T1, urea and guanidine hydrochloride denaturation curves have been determined over the pH range 2-10. The maximum conformational stability of both proteins is about 9 kcal/mol and occurs near pH 4.5 for ribonuclease T1 and between pH 7 and 9 for ribonuclease A. The pH dependence suggests that electrostatic interactions among the charged groups make a relatively small contribution to the conformational stability of these proteins. The dependence of delta G on urea concentration increases from about 1200 cal mol-1 M-1 at high pH to about 2400 cal mol-1 M-1 at low pH for ribonuclease A. This suggests that the unfolded conformations of RNase A become more accessible to urea as the net charge on the molecule increases. For RNase T1, the dependence of delta G on urea concentration is minimal near pH 6 and increases at both higher and lower pH. An analysis of information of this type for several proteins in terms of a model developed by Tanford [Tanford, C. (1964) J. Am. Chem. Soc. 86, 2050-2059] suggests that the unfolded states of proteins in urea and GdnHCl solutions may differ significantly in the extent of their interaction with denaturants. Thus, the conformations assumed by unfolded proteins may depend to at least some extent on the amino acid sequence of the protein.

Aspergillus oryzae↗
PubMed1990

Nucleotide sequence of the celA gene encoding a cellodextrinase of Ruminococcus flavefaciens FD-1.

The nucleotide sequence of a 3.6 kb DNA fragment containing a cellodextrinase gene (celA) from Ruminococcus flavefaciens FD-1 was determined. The gene was expressed from its own regulatory region in Escherichia coli and a putative consensus promoter sequence was identified upstream of a ribosome binding site and a TTG start codon. The complete amino acid sequence of the CelA enzyme (352 residues) was deduced and showed no significant homology to cellulases from other organisms. Two lysozyme-type active sites were found in the amino-terminal third of the enzyme. In E. coli the cloned Cel A protein was translocated into the periplasm. The lack of a typical signal sequence, and the results of transposon phoA mutagenesis experiments indicated that CelA is secreted by a mechanism other than a leader peptide.

Amino Acid Sequence↗
PubMed1990

Cloning, sequencing and analysis of expression of a Butyrivibrio fibrisolvens gene encoding a beta-glucosidase.

The cloning, expression and nucleotide sequence of a 3.74 kb DNA segment on pLS215 containing a beta-glucosidase gene (bglA) from Butyrivibrio fibrisolvens H17c was investigated. The B. fibrisolvens bglA open reading frame (ORF) of 2490 bp encoded a beta-glucosidase of 830 amino acid residues with a calculated Mr of 91,800. In Escherichia coli C600(pLS215) cells the beta-glucosidase was localized in the cytoplasm and these cells produced an additional protein with an apparent Mr of approximately 94,000. The bglA gene was expressed from its own regulatory region in E. coli and a single mRNA initiation point was identified upstream of the bglA ORF and adjacent to a promoter consensus sequence. The primary structure of the beta-glucosidase showed greater than 40% similarity with a domain of 237 amino acids present in the beta-glucosidases of Kluyveromyces fragilis and Clostridium thermocellum. The B. fibrisolvens beta-glucosidase hydrolysed cellobiose to a limited extent, cellotriose to cellobiose and glucose, and cellotetraose and cellopentaose to predominantly glucose.

Amino Acid Sequence↗
PubMed1990

Free radical activity in type 2 diabetes.

Free radical activity has been implicated in the development of diabetic vascular complications in Type 1 diabetes. The aim of the present study was to investigate the levels of free radical scavengers, particularly erythrocyte superoxide dismutase, plasma and erythrocyte lysate thiol, and caeruloplasmin in 22 Type 2 diabetic patients clinically free of complications, and 15 comparable non-diabetic control subjects. The concentration (median (range] of both superoxide dismutase (23 (10-39) vs 45 (25-75) mumol l-1; p less than 0.001) and plasma thiol (374 (172-523) vs 460 (386-595) mumol l-1; p less than 0.01) were reduced in the diabetic group. There were no significant differences in the concentration of erythrocyte lysate thiol (199 (114-520) vs 188 (114-328) mumol l-1) or plasma caeruloplasmin (18 (9-31) vs 24 (6-50) mumol l-1) between the groups. This reduction in superoxide dismutase and the imbalance in the redox status of the plasma and lysate thiol demonstrated is consistent with an increase in free radical activity in Type 2 diabetes.

Blood Glucose↗
PubMed1990

Thyrotropin receptor antibodies associated with post-operative relapse of thyrotoxicosis in a pregnancy complicated by neonatal thyrotoxicosis.

This case describes the clinical, biochemical and immunological features associated with relapse of thyrotoxicosis during pregnancy in a patient who had recently undergone a subtotal thyroidectomy for Graves' disease. The baby, shortly after birth, showed clinical and biochemical features of thyrotoxicosis which responded to carbimazole therapy. Thyrotropin receptor antibodies and thyroid stimulating antibodies were present in the blood of the mother and baby. The clinical course of the neonatal thyrotoxicosis correlated with the TSH receptor antibody levels.

Adult↗
PubMed1990

Ophthalmopathy in early thyrotoxicosis--relationship to thyroid receptor antibodies and effects of treatment.

A prospective study of 25 newly diagnosed thyrotoxic patients was undertaken to determine the incidence and severity of ophthalmopathy in the early stages of the disease. A quantitative analysis of the ocular muscle changes was made using B scan ultrasonography, and the effects of treatment for the thyroid disease on the course of the eye changes was assessed. Although the majority (75%) of patients showed only mild clinical signs of ophthalmopathy (Werner Class 3 or less), 92% had ultrasonographic evidence of ocular muscle enlargement. Clinical involvement of the extraocular muscles was seen in 12% of the cases. There was an inverse correlation between the serum level of thyroid stimulating hormone receptor antibody (TR Ab) and the size of the extraocular muscles. Recovery of the euthyroid state with treatment was accompanied by a decrease in orbital infiltration in some cases, both clinically (reduced amplitude of intraocular pressure rise on elevation of the globe) and by ultrasonography, but the improvement was not statistically significant.

Adolescent↗
PubMed1990

The incidence of clinical thyroid dysfunction in an unselected group of pregnant and post partum women.

This study has examined the incidence of thyroid dysfunction during pregnancy and up to six months post partum in 65 women attending an antenatal clinic in the West of Scotland. Five were found to be positive for thyroid antibodies at presentation and in these the antibody titre fluctuated during pregnancy and in the post partum period. One patient developed thyroglobulin antibodies post partum. Mean total T3 and total T4 levels rose during pregnancy but had normalised by six weeks post partum. The changes in FT4 and TBG levels observed during pregnancy did not normalise until after six weeks post partum. Only one patient developed any biochemical evidence of thyrotoxicosis post partum and this was not found to be associated with the presence of thyroid antibodies. No patient showed any evidence of hypothyroidism.

Adult↗
PubMed1990

The effects of antithyroid drugs on intercellular mediators.

The antithyroid drugs methimazole and propylthiouracil have been shown to affect the function of monocytes and B and T lymphocytes in vitro. The aim of this study was to investigate the mechanism responsible for signalling between these various cell types. Propranolol, a drug known to have no effect on the immune system, was also included as a control against which the effects of the other drugs could be monitored. Peripheral blood lymphocytes from control subjects were stimulated with phytohemagglutinin in the presence or absence of antithyroid drugs. Propranolol was found significantly to inhibit beta 2 microglobulin production. In addition it was also found to be a very weak scavenger of free oxygen radicals. Methimazole significantly increased interleukin 2 levels (p less than 0.01), but had no significant effect on either gamma-interferon or beta 2 microglobulin production. Propylthiouracil also increased interleukin 2 levels (p less than 0.001) and significantly decreased beta 2 microglobulin production (p less than 0.01). Both drugs were found to be scavengers of free O2 radicals. It would appear that IL-2 is involved in intercellular signalling and this process may involve free radicals.

Cell Communication↗
PubMed1990

The effect of pre-operative potassium iodide therapy on antibody production.

Previous studies have suggested that iodide may increase the incidence of thyroid disease and anti-thyroid antibodies in predisposed individuals. This study has considered the effects of pre-operative potassium iodide (60 mg twice daily, for 10 days) on the immune system of patients with Graves' disease. The treatment regimen used maintained all patients in a clinically and biochemically euthyroid state prior to surgery. Potassium iodide significantly increased serum thyrotropin receptor antibody levels and B cell activity as determined by increased immunoglobulin production from mitogen stimulated peripheral blood lymphocytes. These effects were not observed in the two control groups of Graves' disease patients. Our in vivo findings would support previous in vitro work showing that potassium iodide does act on the immune system and this may be the mechanism by which iodide induces thyroid dysfunction in predisposed individuals.

Antibody Formation↗