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Biomedical subjects

J A Thomson

Publications and source records attributed to J A Thomson.

At least 163 records · Page 9Linked to original sources
PubMed1989

The prognostic value of TSH receptor binding and thyroid stimulating antibodies following antithyroid drug treatment of Graves' disease.

Following a course of medical therapy for Graves' disease approximately 50% of patients relapse. Previous studies have tried to identify these patients by measuring antibodies to the TSH receptor using a range of assay methods. Such studies have produced widely discrepant results. The aim of the present study was to compare the accuracy with which TSH receptor binding antibodies and thyroid-stimulating antibodies could identify cases of relapse and remission. Fifty-six newly diagnosed and previously untreated Graves' disease patients were recruited into the study. At presentation 4 were negative for TSH receptor antibody and 5 negative for TS-ab. The remaining 47 were positive for TSH receptor antibody and TS-ab although correlation of the degree of abnormality between methods was poor (r = 0.13 NS). After 12 months carbimazole treatment 28 patients relapsed during the following year and 19 remained in remission. TSH receptor antibody levels obtained at the end of a 12-month course of treatment correctly identified 93% who relapsed and 95% who remained in remission. TS-ab levels could only correctly identify 68% who relapsed and 53% who remained in remission. These results have shown that the accuracy with which patients likely to relapse can be identified depends on the assay method chosen which may account for some of the discrepancies found in previously published studies.

Adult↗
PubMed1989

Comparative studies of beta s-crystallins from human, bovine, rat and rabbit lenses.

Soluble extracts from young bovine, human, rat and rabbit lenses were fractionated by high resolution size-exclusion chromatography to demonstrate the existence of three discrete size-classes of monomeric crystallins in each species. These were identified by ion exchange chromatography, amino acid analysis, SDS electrophoresis and isoelectric focusing as the beta s-, gamma A- and gamma B-crystallins. Conventional SDS electrophoretic analysis of these proteins revealed apparent Mr values of about 23kD, 22kD and 19kD, respectively. Similar analysis in the presence of 6 M urea showed the proteins all co-migrated with an apparent Mr of about 20,500, which is far more consistent with the molecular weights calculated from beta s- and gamma-crystallin sequence data. Amino acid compositions of all the beta s samples indicate a high degree of homology to the bovine protein, whose sequence is known. The different species beta s-crystallins showed other general similarities in size, charge, thiol content and secondary structural properties. On the other hand, near UV CD and fluorescence emission and energy transfer measurements indicate that these proteins have subtle yet significant differences in their tertiary structures. Unlike the gamma-crystallins, the secondary structure of all of the beta s samples is completely denatured in the presence of 8 M urea at 20 degrees C.

Amino Acids↗
PubMed1989

The "in vitro" effects of lithium on the immune system.

This study has examined the "in vitro" effects of Lithium Carbonate on the immune system at low (10(-3), 10(-2)mM) and therapeutic (0.5-1.5 mM) concentrations. Lithium, in the presence of a range of mitogens, was found to increase the incorporation of 3H-thymidine into peripheral blood mononuclear (PBM) cells. At concentrations greater than 1 mM IL2 production was also enhanced. Lithium was also found to increase IgG and IgM production--an estimate of B cell function, the effects being greatest at concentrations within the therapeutic range. However at these levels Lithium inhibited cAMP production. Whether Lithium acts individually on these processes or whether one reaction is merely the result of another is unclear at present.

B-Lymphocytes↗
PubMed1988

Conformational stability and activity of ribonuclease T1 with zero, one, and two intact disulfide bonds.

Ribonuclease T1 has two disulfide bonds linking cysteine residues 2-10 and 6-103. We have prepared a derivative of ribonuclease T1 in which one disulfide bond is broken and the cysteine residues carboxymethylated, (2-10)-RCM-T1, and three derivatives in which both disulfides are broken and the cysteine residues reduced, R-T1, carboxamidomethylated, RCAM-T1, or carboxymethylated, RCM-T1. The RNA hydrolyzing activity of these proteins has been measured, and urea and thermal denaturation studies have been used to determine conformational stability. The activity, melting temperature, and conformational stability of the proteins are: ribonuclease T1 (100%, 59.3 degrees C, 10.2 kcal/mol), (2-10)-RCM-T1 (86%, 53.3 degrees C, 6.8 kcal/mol), R-T1 (53%, 27.2 degrees C, 3.0 kcal/mol), RCAM-T1 (43%, 21.2 degrees C, 1.5 kcal/mol), and RCM-T1 (35%, 16.6 degrees C, 0.9 kcal/mol). Thus, the conformational stability is decreased by 3.4 kcal/mol when one disulfide bond is broken and by 7.2-9.3 kcal/mol when both disulfide bonds are broken. It is quite remarkable that RNase T1 can fold and function with both disulfide bonds broken and the cysteine residues carboxymethylated. The large decrease in the stability is due mainly to an increase in the conformational entropy of the unfolded protein which results when the constraints of the disulfide bonds on the flexibility are removed. We propose a new equation for predicting the effect of a cross-link on the conformational entropy of a protein: delta Sconf = -2.1 - (3/2)R 1n n, where n is the number of residues between the side chains which are cross-linked. This equation gives much better agreement with experimental results than other forms of this equation which have been used previously.

Aspergillus↗
PubMed1988

Rat lens gamma-crystallins. Characterization of the six gene products and their spatial and temporal distribution resulting from differential synthesis.

We have isolated, purified and characterized six individual gamma-crystallin polypeptides present in the rat lens. Comparison of their amino acid compositions with the known structure of the six gamma-crystallin genes permits a one-to-one correspondence to be made between each protein synthesized and the encoding gene. This demonstrates that each of the six genes is actually expressed in vivo. Two classes of three gamma-crystallins each, which we have designated classes gamma ABC and gamma DEF, are known to exist, on the basis of internal sequence homology. We have measured the temperature-dependent phase-separation characteristics of solutions of the six purified gamma-crystallins, and find that the three members of the gamma DEF class (gamma 2-2, gamma 3-1 and gamma 4-1) are all cryo-proteins with relatively high phase-separation temperatures, whereas the three gamma ABC crystallins (gamma 1-1, gamma 1-2 and gamma 2-1) do not show phase separation above -7 degrees C. We have measured the spatial distribution in rat lens of each of the alpha-, beta- and gamma-crystallins as a function of age from 1 to 420 days, using size-exclusion and ion-exchange high-pressure liquid chromatography (HPLC). Our findings in the cortical layer permit us to establish the differential synthesis of each of the crystallins during lens development. Particular attention has been devoted to the spatial and temporal distribution of the six individual gamma-crystallins. Up to birth, synthesis of the three components of the gamma DEF class predominates, and in particular that of gamma 2-2. In subsequent development the three components of the gamma ABC class assume a greater proportion of monomeric crystallins synthesized, while beta s-crystallin synthesis predominates in late development. Our analysis of different layers within single lenses provides novel information on spatial gradients of the water-soluble and water-insoluble protein fractions as a function of age. We consider the consequences of these findings for lens transparency and opacity in both rat and mouse lens. We show that the high concentrations of gamma DEF-crystallins appear to be responsible for the opacity known to occur in young rat lenses. We conclude from these observations that close control of the differential synthesis of gamma-crystallins plays an important role in maintaining lens transparency during development.

Age Factors↗
PubMed1988

Early prediction of hypothyroidism following 131I treatment for Graves' disease.

The aim of this study was twofold. Firstly to assess the post treatment predictive value of various biochemical and immunological tests for early hypothyroidism after 131I therapy for Graves' disease, and secondly to determine whether or not pretreatment with Carbimazole protects against post treatment hypothyroidism. The early changes observed in serum T3, T4, TSH, thyroid microsomal and thyroglobulin antibody levels were found to be of no predictive value. A sharp rise, around 2 months, in TRAb levels following 131I therapy indicated that hypothyroidism was likely to occur. This rise was thought to reflect a greater degree of thyroid damage. Lower levels of thyroglobulin in patients who had become hypothyroid by 12 months after treatment would support this view. Five weeks Carbimazole pretreatment in this relatively small group of patients did not appear to protect against hypothyroidism.

Antibodies↗
PubMed1988

Hormonal responses in pubertal males to pulsatile gonadotropin releasing hormone (GnRH) administration.

Twenty-two boys (9 with delayed puberty and 13 with short stature) ages 12.3 - 17.8 yr, and 10 adult males with idiopathic hypogonadotropic hypogonadism (ages 17.3 - 41.1 yr) have been studied following pulsatile, sc GnRH therapy (240 ng/kg/pulse) over 6 days. Mean pre- and post-therapy LH and FSH concentrations were estimated by 15 min blood sampling over 3-h periods immediately before and at the end of the treatment period. There were significant correlations between the mean pre- and posttreatment LH and FSH concentrations (r = 0.82, p less than 0.001 and r = 0.51, p less than 0.02, respectively) for the 2 groups of peripubertal boys when assessed together. Nine of the 10 adults with hypogonadism showed proportionately greater gonadotropin increments following pulsatile therapy when compared with the peripubertal boys. Standard bolus GnRH tests (100 micrograms iv) did not differentiate between the three groups of patients before pulsatile GnRH therapy. Bolus GnRH tests could predict the subsequent response to pulsatile therapy in the peripubertal boys only. There was no significant change in LH increments following the GnRH bolus tests in either group, after pulsatile GnRH administration (p greater than 0.1). Early response to pulsatile GnRH administration is dependent upon the maturity of the hypothalamic-pituitary-testicular axis in males with delayed puberty or short stature. Patients with hypogonadotropic hypogonadism do not show this relationship.

Adolescent↗
PubMed1988

Heterogeneity of gamma-crystallins from spiny dogfish (Squalus acanthias) eye lens.

Mammalian lenses contain multiple gamma-crystallin gene products, which are differentially synthesized during lens development. We now report the isolation and characterization of multiple gamma-crystallins from lenses of adult spiny dogfish (Squalus acanthias) aged about 20-30 years. About 50% of total lens protein solubilized in 50 mM phosphate, pH 7.0; about 25% of this soluble fraction consists of gamma-crystallins as determined by gel filtration. These gamma-crystallins appear homogeneous with respect to molecular weight (approximately equal to 20,000) on SDS-polyacrylamide gels, but their isoelectric points range from below pH 6 to above 10. Preparative cation-exchange chromatography on SP-Sephadex at pH 4.8 resolves four major subfractions, while anion-exchange on DEAE-cellulose at pH 9.5 resolves seven subfractions. Although these procedures separate basic from acidic polypeptides, most of these gamma-crystallin subfractions still consist of polypeptide mixtures, as determined by ion-exchange HPLC and isoelectric focusing. Analytical cation-exchange HPLC on SynChropak CM300 at pH 6.0 resolves at least 10 different gamma-crystallin components. Amino acid compositions of all the subfractions are similar, yet distinct in the sense that three subclasses can be distinguished. Sulfhydryl residues range from three to six per chain, most of which are buried. The large heterogeneity of gamma-crystallins in adult lens may result from different gene products in combination with post-translational modification.

Amino Acids↗
PubMed1988

The role of visual information in control of a constrained locomotor task.

The nature of visually guided locomotion was examined in an experiment where subjects had to walk to targets under various conditions. Target distance was manipulated so that subjects had to (a) lengthen their paces in order to hit the target; (b) shorten their paces; (c) make no adjustments to their standard pace length at all. They did this under four visual conditions: (a) normal vision; (b) with vision restricted to a "snapshot" each time the foot that was to be placed on the target was on the ground; (c) with a snapshot each time the foot to be placed was in the swing phase; and (d) no vision after departure fro the target. The results show that the subjects succeed in reaching the target in most cases. However, the smoothness and fluidity of their movements vary significantly between conditions. Under normal vision or where visual snapshots are delivered when the pointing foot is on the ground, locomotion is smoothly regulated as the subjects approach the target. where snapshots are delivered when the pointing foot is in the swing phase, regulation becomes clumsy and ill coordinated. Where no vision is available at all during the approach, adjustments are made, but these are least coordinated of all. The results show that well-coordinated visual regulation does not require continuous visual guidance but depends on intermittent information being available at the appropriate times in the action sequence. Such timing is often more important than the total amount of information that is available for guidance.

Journal Article↗
PubMed1988

Prolonged hypogonadism in male patients with rheumatoid arthritis during flares in disease activity.

The pituitary-gonadal axis was assessed in 10 male patients during hospital admissions lasting 3-6 weeks (median 3 weeks) for flares for rheumatoid arthritis. Despite significant improvements in the Ritchie indices from median 16 (range 9-23) to 8.5 (range 5-20) (p less than 0.01) and ESR from median 67 mm/h (range 46-115 mm/h) to 58 mm/h (range 15-116 mm/h) (p less than 0.05) there were no significant changes in serum testosterone, LH, FSH, prolactin (PRL), cortisol or androstenedione during the admission periods. At follow-up (median 14 months, range 5-18 months after admission) there were further improvements in articular indices (median 7, range 3-13; p = NS) and ESR (median 20 mm/h, range 4-62 mm/h; p less than 0.05) and rheumatoid factor titres had fallen from median 1/1025 (range 1/126 to 1/1024) to median 1/512 (range 1/64 - 1/512). One patient showed biochemical features of progressive testicular failure. In the remaining patients, serum and derived free testosterone levels were significantly increased (p less than 0.01 respectively) and serum LH reduced (p less than 0.01). There were no changes, at this time, in prolactin, cortisol or androstenedione. Rheumatoid flares appear to be associated with prolonged suppression of testicular function.

Adult↗
PubMed1988

The developmental fate of androgenetic, parthenogenetic, and gynogenetic cells in chimeric gastrulating mouse embryos.

Both a maternal and a paternal genomic contribution are necessary for completion of embryonic development in the mouse. Parthenogenetic embryos, with only a maternally inherited genome, and androgenetic embryos, with only a paternally inherited genome, fail to develop to term, and these two types of isoparental embryos fail in development in characteristic ways. In this paper we describe the construction of chimeras between single androgenetic, parthenogenetic, and gynogenetic blastomeres and normal eight-cell embryos. We allow the development of the chimeras to reach the late-gastrulating-stage embryo and then analyze the tissue distributions of the isoparental component. The isoparental embryos are derived from a transgenic mouse line carrying plasmid and mouse beta-globin sequences. The isoparental cells are detected in histological sections of chimeras by DNA-DNA in situ hybridization to the transgene, using a biotinylated DNA probe with an enzymatic detection system. We found strong tissue preferences for the androgenetic, parthenogenetic, and gynogenetic cells in chimeras. Androgenetic cells contributed strongly to all trophectoderm-derived tissue, with only a rare contribution to any tissues of the embryo proper, extraembryonic mesoderm, or extraembryonic endoderm. Parthenogenetic cells shared a developmental fate similar to gynogenetic cells, contributing to all tissues of the embryo proper and to the extraembryonic mesoderm, but only rarely to the extraembryonic endoderm or to any trophectoderm-derived tissues.

Animals↗
PubMed1988

The effect of antithyroid drugs on B and T cell activity in vitro.

This study examined the abilities of methimazole, propylthiouracil (PTU) and propranolol to exert an immunosuppressive effect in vitro. Incubation of peripheral blood lymphocytes (PBL) with propranolol showed the drug to have no effect on either B- or T-cell activity. Methimazole or PTU at concentrations of greater than or equal to 10(-5)M resulted in significantly lower amounts of IgG and IgM being released into the culture medium. Both drugs were also found to have a direct effect on T-cell function as they caused the percentage of total and suppressor cells to increase towards normal levels. The three drugs were all found to have some free radical scavenging ability. These ranked PTU greater than methimazole greater than propranolol. These in-vitro findings would suggest that both methimazole and PTU have some direct effect on the immune system. It would seem more likely however that these effects are mediated via interleukin 2 rather than by their ability to act as free radical scavengers.

Antithyroid Agents↗
PubMed1988

Colonization of Tomato Plants by Two Agrocin-Producing Strains of Agrobacterium tumefaciens.

For a bacterium to be a successful biocontrol agent against crown gall disease, it must produce an effective agrocin specific for Agrobacterium tumefaciens and be able to colonize host plants efficiently. The colonization abilities of K84 and J73, successful and potential biocontrolling strains, respectively, were compared both in vivo and in vitro. Both strains produced fibrils attaching them to tomato root surfaces and had similar colonization efficiencies up to 14 days after inoculation. However, the ability of J73 to colonize plants for longer periods was significantly less than that of K84. Thus, the presence of fibrils is not sufficient to ensure colonization. No correlation was found between hydrophobicity and colonization.

Journal Article↗
PubMed1988

Treatment of hypercalcaemia in thyrotoxicosis with aminohydroxypropylidene diphosphonate.

Two patients had symptomatic hypercalcaemia accompanying thyrotoxicosis, despite initial treatment with volume repletion, beta blockade and antithyroid drugs. They were further managed with intravenous infusions of aminohydroxypropylidene diphosphonate resulting in rapid normalization of the serum calcium, with relief of symptoms. Aminohydroxypropylidene diphosphonate effectively suppressed the increased bone resorption of thyrotoxicosis without any undesirable adverse effects.

Adult↗
PubMed1988

On the structure of alpha-crystallin: the minimum molecular weight.

alpha-crystallin can be isolated in two forms depending on the temperature at which the lens is extracted. At 4 degrees C, alpha c-crystallin is obtained while at 37 degrees C, a smaller molecule, alpha m-crystallin can be isolated. The apparent molecular weight of bovine foetal alpha m- and alpha c-crystallins were determined in 5 different ways using sedimentation velocity, sedimentation equilibrium and intensity fluctuation spectroscopy analyses and the experimentally determined diffusion coefficients, intrinsic viscosity and partial specific volume. Values ranged from 291,000 to 369,000 for alpha m and from 604,000 to 760,000 for alpha c due to the differential effects of the protein's polydispersity on the different methods. Subfractionation of the protein by gel filtration yielded much less polydisperse minimum species populations with molecular weights of 280,000 and 529,000 for alpha m and alpha c respectively. It was concluded that alpha-crystallin is probably synthesized as a symmetrical dodecamer and that the polydispersity of most preparations can be attributed to age-related modification in vivo as well as in vitro supra-aggregation due to variations in experimental conditions.

Animals↗
PubMed1988

Absence of gradient of thyrotropin receptor antibody and T cell subset distribution between thyroid and peripheral venous blood in patients with Graves' disease prepared for surgery with carbimazole and potassium iodide.

The aim of the study was to examine tri-iodothyronine, thyroxine, thyroid antibody and thyrotropin receptor antibody levels in thyroid and peripheral venous blood at the time of surgery in patients with Graves' disease. T cell subset patterns in peripheral and thyroidal venous blood were compared to the distribution of T cell subset patterns within the thyroid gland itself. The results showed that at the time of surgery there were no significant differences in any of the parameters measured between thyroidal and peripheral venous samples. T cell subset patterns within the thyroid gland were subjectively similar to those in the venous samples.

Autoantibodies↗