The incidence of bacteremia after skin surgery.
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Adult↗
Biomedical subjects
K Thompson
Publications and source records attributed to K Thompson.
The B cell system in the rheumatoid inflammation. New insights into the pathogenesis of rheumatoid arthritis using synovial B cell hybridoma clones.
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Agammaglobulinemia↗
Arrest disorders and infant brain damage.
In the past, difficult labors have been associated with maternal and infant damage. Today, changing patient management is associated with less trauma and more frequent use of cesarean births to avoid potential fetal neurologic damage. In this report, arrests of dilatation and descent and prolongation of the decelerative phase of labor were reviewed with respect to the later appearance of brain damage in infants after 2 years of age, in association with obstetric interventions including cesarean birth, forceps, and oxytocin. Charts of 413 infants born after abnormal labors were studied. Log-linear analysis was performed to determine the contribution of method of delivery and oxytocin use to the presence of neurologic abnormalities. Statistical testing ruled out the presence in the model of a three-way interaction, and excluded the two-way interactions of neurologic abnormalities-oxytocin use and neurologic abnormalities-method of delivery. Chi-square tests of partial association and marginal association for the delivery-oxytocin interaction yielded values of 33.54 (P less than .0001) and 33.78 (P less than .00001). This model asserted that method of delivery and use of oxytocin were unrelated to the presence of neurologic abnormalities, but were related to each other.
Birth Weight↗
The structural basis for insulin-like growth factor I receptor high affinity binding.
We have recently identified high and low affinity insulin-like growth factor I (IGF I) binding sites in solubilized human placental membranes and purified the high affinity IGF I receptor by IGF I affinity chromatography (Tollefsen, S. E., Thompson, K., and Petersen, D. J. (1987) J. Biol. Chem. 262, 16461-16469). To define the structural basis for high affinity IGF I binding, we have examined the effect of disulfide bond reduction on the binding parameters of the high affinity IGF I receptor. We find that the disulfide bonds linking the two alpha beta dimers of the IGF I receptor heterotetramer are reduced by incubation at pH 8.75 with 2 mM dithiothreitol (DTT) for 5 min at room temperature. Gel filtration chromatography on a Superose 12 fast protein liquid chromatography column indicates that the alpha beta dimers do not remain associated by noncovalent interactions after reduction. Scatchard plots of IGF I binding to the IGF I receptor incubated at pH 8.75 with or without DTT indicate that the IGF I receptor alpha beta dimers have a 6.1 +/- 1.6 (mean +/- S.D.) times lower affinity than the heterotetramer for IGF I. The total binding capacity of the IGF I receptor treated with DTT is 1.6 +/- 0.3 (mean +/- S.D.) times higher than that of an equal amount of receptor treated without DTT. These results are consistent with a model in which the heterotetramer binds a single IGF I molecule with high affinity, whereas each of the two alpha beta dimers binds an IGF I molecule with lower affinity after dissociation. We conclude that association of two alpha beta dimers is required for formation of an IGF I receptor with high affinity for its ligand.
Binding, Competitive↗
The effects of acute scopolamine in geriatric depression.
In an intensive multidrug, multidose study, nine elderly depressed patients were administered 0.1, 0.25, and 0.5 mg of scopolamine hydrobromide, 1 mg of oral lorazepam, and placebo in a double-blind investigation aimed at assessing the status of the central cholinergic nervous system in geriatric depression. Significant cognitive and behavioral effects of scopolamine were observed only at the high dose (0.5 mg), while lower doses and lorazepam showed no significant differences from placebo. Cognitive deficits caused by scopolamine were in the areas of new learning, access to semantic memory, vigilance, and continuous performance. Behavioral effects consisted of activation, restlessness, and anxiety, but there was no significant effect on depressed mood. These results suggest that elderly depressed patients with mild to moderate cognitive impairment seem to be more similar to previously studied elderly controls rather than to patients with Alzheimer's disease in their reaction to short-term cholinergic blockade, and suggest that the cognitive and mood changes often seen in geriatric depression may involve factors other than disturbed muscarinic cholinergic mechanisms.
Aged↗
Automatic and effortful processing in attention deficit/hyperactivity disorder.
Twenty-five boys with Attention Deficit/Hyperactivity Disorder and 23 age-matched controls were compared on verbal memory tasks differentiating automatic versus effortful information processing. Automatic processing tasks included the recognition of new or old words in a list and the recognition of frequency of occurrence of words in a list. Effortful tasks included free recall of lists of both related and unrelated words. Hyperactive boys did not differ from controls in automatic processing capabilities but demonstrated significantly poorer effortful processing. Intercorrelations of the variables revealed high correlations between scores on effortful measures and also raise questions about the purity of automaticity in some tasks employed. Stepwise discriminant analysis demonstrated that free recall of related words (an effortful task) best discriminated between groups. Effort-related processing in hyperactive and normal children is discussed in relation to variables of motivation, affect, arousal, and other higher-order cognitive processes.
Arousal↗
Child sexual abuse: inter-agency collaboration in diagnosis, investigation and management within South Glamorgan.
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Child↗
Studies on the epitopes recognized by monoclonal anti-D, anti-c and anti-E.
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Antibodies, Monoclonal↗
Immunogenic and antigenic epitopes of immunoglobulins binding of human monoclonal anti-D antibodies to FcRI on the monocyte-like U937 cell line.
Seventeen human monoclonal IgG1- or IgG3 anti-D-secreting clones have been examined for their ability to sensitise O+ red cells for Fc-receptor-mediated rosette formation with U937 cells. IgG3 but not IgG1 anti-D antibodies were able to mediate stable rosette formation with unstimulated U937 cells via interaction with the FcRI receptor. Decreasing FcRI density by incubating U937 cells with di-butyryl cAMP almost completely abolished rosette formation, whilst increasing FcRI density by incubating U937 cells with interferon-gamma increased the percentage of cells forming rosettes with IgG3- and IgG1-sensitised red cells. These data suggest that rosette formation between IgG anti-D-sensitised red cells and FcRI-expressing cells is dependent upon the density of IgG3 on the red cell surface, the density of FcRI on the effector cell, multiple FcRI/IgG interactions are required for stable rosette formation and that more FcRI/IgG1 than FcRI/IgG3 interactions are required.
Binding Sites, Antibody↗
Partial amino acid sequence analysis and variable subgroup determination (VH and VL) of a monoclonal rheumatoid factor derived from a rheumatoid arthritis patient.
Continuous cell lines secreting monoclonal rheumatoid factors (RF) were derived from rheumatoid arthritis (RA) patients by cloning Epstein-Barr virus (EBV) transformed B cells and by hybridoma techniques. We studied five different clones with stable RF secretion. All were IgM, 4 kappa and 1 lambda. One of these clones, RFAN was extensively studied, and the partial amino acid sequences of the variable regions of both heavy and light chains were determined. After affinity purification, the IgM lambda RF antibody derived from the EBV clone was run under reducing conditions on SDS-polyacrylamide gel electrophoresis. The separated heavy and light chains were blotted and then sequenced by a gas-phase sequenator. The N-terminal sequence of the lambda light chain corresponded to that of the V lambda III subgroup. The heavy chain of the same IgM RF clone had a blocked N-terminus, but a cyanogen bromide peptide starting after methionine at position 82 showed a sequence typical of the VHIII subgroup. Heavy and light chains were also prepared by gel filtration after reduction and carboxymethylation from the same EBV clone made into a hybridoma. After this preparation, the heavy chain was not blocked and the N-terminal sequence confirmed that the heavy chain variable region belonged to the VHIII subgroup. We believe this to be the first amino acid sequence study of a monoclonal RF derived from the repertoire of an RA patient.
Amino Acid Sequence↗
IgA and IgM rheumatoid factors as markers of later erosive changes in rheumatoid arthritis (RA).
Stored samples from within the first year of disease of 119 patients with rheumatoid arthritis (RA) enrolled in a long-running prospective study have been studied for the presence of IgM and IgA rheumatoid factors (RF), using agglutination of rabbit IgG-coated red blood cells to detect IgMRF and an ELISA technique using rabbit IgG coated on the microtitre plates and labelled F(aB)2 fragment of goat anti-IgA. Outcome measures at a mean follow-up of 10.1 years (range 3-20) included the Steinbrocker functional grade and grading of erosive changes on hand and feet Xrays using a modification of Lawrence's method. Both IgA and IgG levels at presentation correlated significantly with outcome measured by erosive changes and functional grade at a mean of 10 years and with the time of first appearance of erosions. In patients who are IgMRF negative early in the disease, IgARF positivity indicates a greater chance of developing both erosions and impaired function than when both tests are negative. IgARF positivity seems to precede IgMRF.
Adult↗
B lymphocytes, B cell clones and rheumatoid factor antibodies in rheumatoid inflammation.
This report focuses on the B lymphocytes and plasma cells in rheumatoid inflammation, and discusses the major autoantibodies in the pathogenetic mechanisms, i.e. the rheumatoid factor (RF) antibodies. We describe ways of raising human hybridomas that produce RF antibodies in rheumatoid arthritis (RA) in order to elucidate how these antibodies differ from the RF antibodies that are part of the normal immune response in man and animals, and from those in diseases other than RA, e.g. in M-components seen in mixed cryoglobulinaemia and in Waldenström's macroglobulinaemia. The preliminary results of these studies are presented and discussed.
Animals↗
Separation of the high affinity insulin-like growth factor I receptor from low affinity binding sites by affinity chromatography.
We have identified high and low affinity insulin-like growth factor I (IGF I)-binding sites with mean dissociation constants of 0.37 and 6.25 nM, respectively, in solubilized placental membranes. We have separated these sites and purified the high affinity IGF I receptor 1,300-fold, with an overall yield of 9.9%, using wheat germ agglutinin-Sepharose chromatography, insulin affinity chromatography, and IGF I affinity chromatography. The Scatchard plot of IGF I binding to the high affinity receptor is linear, suggesting the purification of a single homogeneous class of binding sites. Insulin is two orders of magnitude less effective than IGF I in competitively inhibiting IGF I binding to this receptor. The high affinity IGF I receptor is composed of alpha and beta subunits with apparent molecular weights of 135,500 and 96,200, respectively. IGF I at concentrations of greater than or equal to 50 ng/ml stimulates autophosphorylation of the beta subunit of the purified high affinity receptor 4.6-fold. Low affinity IGF I-binding sites run through the IGF I affinity column or are eluted from the insulin affinity column. The separation of IGF I receptors with different binding affinities by sequential affinity chromatography will make it possible to examine directly the determinants of receptor affinity.
Binding Sites↗
Biochemical and biological activities of 2,3-dihydro-6-[3-(2-hydroxymethyl)phenyl-2-propenyl]-5-benzofuranol (L-651,896), a novel topical anti-inflammatory agent.
The biochemical and biological profile of a topical anti-inflammatory agent, 2,3-dihydro-6-[3-(2-hydroxymethyl)phenyl-2-propenyl]-5-benzofuranol (L-651,896 inhibited the 5-lipoxygenase of rat basophilic leukemia cells with an IC50 of 0.1 microM and leukotriene synthesis by human PMN and mouse macrophages with IC50 values of 0.4 and 0.1 microM respectively. L-651,896 also inhibited prostaglandin E2 synthesis by mouse peritoneal macrophages (IC50 = 1.1 microM). This compound inhibited ram seminal vesicle cyclooxygenase activity at considerably higher concentrations, and this effect was directly related to substrate concentration. When applied topically to the mouse ear, L-651,896 lowered elevated levels of leukotrienes associated with arachidonic acid-induced skin inflammation and delayed hypersensitivity induced by oxazolone. However, while L-651,896 inhibited the increased vascular permeability induced by arachidonic acid, it had no effect on the edema associated with the immune-based response to oxazolone in the same tissue. Thus, it is possible that leukotrienes may play a role in some but not all inflammatory responses.
Administration, Topical↗
The activation of porcine pancreatic phospholipase A2 by dipalmitoylphosphatidylcholine large unilamellar vesicles. Analysis of the state of aggregation of the activated enzyme.
Previous work from this laboratory and others has shown that the hydrolysis of pure dipalmitoylphosphatidylcholine (DPPC) liposomes by porcine pancreatic phospholipase A2 in the vicinity of the gel-to-liquid crystal phase transition is characterized by a slow initial phase followed by an apparent burst of activity. In this article we report a detailed quantitative analysis of the early time course of the hydrolysis of dipalmitoylphosphatidylcholine large unilamellar vesicles at 38 degrees C. Several kinetic models to quantitatively describe the data were considered. The most conservative model consistent with the kinetic data is one in which the enzyme initially binds the bilayer and becomes activated via a process that requires the formation of protein dimers on the surface of the membrane. The relevant kinetic parameters of the model are reported.
1,2-Dipalmitoylphosphatidylcholine↗
Decidual cell function: evidence for a role in the regulation of serum CBG and a 60 kDa protein during early pregnancy in the hamster.
Several serum proteins increase in titer during pregnancy. We tested the hypothesis that decidual cells may signal the production of certain serum proteins in the hamster. Measurement of serum CBG by equilibrium binding using either [3H]-progesterone or [3H]-cortisol in conjection with ion exchange chromatography showed that decidualization increased CBG levels. Two-dimensional gel electrophoresis revealed that a 60 kDa++ protein increases markedly in the serum of the hormonally pseudopregnant (PSP) animal soon after artificial induction of decidualization on PSP day 4. The 60 kDa serum protein remains low in the nondecidualized PSP animal, but it increases in the pregnant animal. A photoaffinity labeling procedure was used to covalently bind [3H]-androstadienolone to CBG. Fluorography of 2D gels run under denaturing conditions established that the 60 kDa protein did not bind steroid as did CBG (69 kDa). To determine whether decidual cells could induce the 60 kDa and CBG proteins, different numbers of decidual cells were injected IP into PSP recipients. A single injection of 50 x 10(6) decidual cells induced both serum proteins within 48h, whereas the same number of hamster fetal cells was ineffective. Thus, these results demonstrate that hamster decidual cells induce a 60 kDa protein of unknown function and serum CBG. Since the decidual cell itself does not appear to be the source of either protein, it follows that the decidual cell signals the synthesis and secretion of these proteins elsewhere in the body, most likely in the liver. To our knowledge, this is the first demonstration that the decidual cell regulates serum CBG and other proteins in this manner.
Animals↗
Cognitive effects of L-deprenyl in Alzheimer's disease.
Monoamine neurotransmitter systems, along with cholinergic systems, are known to play important roles in cognition, and are disrupted in at least some patients with dementia of the Alzheimer type (DAT). This suggests that monoamine-enhancing drugs might ameliorate cognitive symptoms in certain patients with DAT. L-Deprenyl is a monoamine oxidase (MAO) inhibitor which may selectively inhibit MAO-B at low doses, while at high doses it nonselectively inhibits MAO-A as well as MAO-B. We studied its effects on several types of cognitive function in 17 patients with DAT. Two doses of L-deprenyl (10 mg/day and 40 mg/day) and placebo were compared in a double-blind, serial treatment design. Episodic learning and memory, knowledge memory, attention, recognition, and performance on a continuous performance task were assessed at baseline and under these drug and placebo conditions. Statistically significant improvement was noted in performance on an episodic memory and learning task requiring complex information processing and sustained conscious effort during treatment with L-deprenyl 10 mg/day. Knowledge memory, intrusions, and other cognitive functions relevant to DAT were not altered by L-deprenyl at either dose.
Adult↗