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Biomedical subjects

K Thompson

Publications and source records attributed to K Thompson.

At least 163 records · Page 9Linked to original sources
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Effects of diazepam on cognitive processes in normal subjects.

The effects of 10 mg orally-administered diazepam on various aspects of cognition were examined in ten male subjects. Diazepam produced a subjective sense of cognitive impairment and impaired auditory vigilence, immediate recognition of twice presented words, and context-dependent free recall. There was a trend for a significant proportion of subjects to show impairment in delayed recognition of twice-presented words. There was no impairment of context-independent semantic memory, or of subjects' ability to judge how well they had performed on the free recall task. In fact, subjects' subjective sense of cognitive impairment was correlated with their performance on context-dependent memory tasks.

Adult↗
PubMed1987

Shoulder dystocia: a fetal-physician risk.

Trauma that occurs as a result of shoulder dystocia is an important cause of neonatal morbidity. If the occurrence of severe shoulder dystocia, resulting in fetal asphyxia and trauma, could be accurately predicted from maternal risk factors, then a cesarean section would be indicated to prevent the poor outcome. The information available in the obstetric literature, however, is contradictory regarding whether shoulder dystocia can be predicted. In the present study, the patients at greatest risk of shoulder dystocia (all 394 mothers delivering neonates with birth weights greater than or equal to 4000 gm over a 2-year period) were examined. A three-way discriminant analysis was used to determine if a model could be developed that could effectively predict those patients who would be included in each of the groups of no shoulder dystocia, shoulder dystocia without trauma (29 patients), and shoulder dystocia with trauma (20 patients). Three factors, including birth weight, prolonged deceleration phase, and length of second stage labor, were found individually to contribute significantly to the classification. However, when examined in detail, it was noted that while 94% of cases with no shoulder dystocia would be detected, only 16% of the cases of shoulder dystocia with trauma would be predicted by this model. We conclude that in the group of pregnancies delivering neonates greater than or equal to 4000 gm, the occurrence of shoulder dystocia cannot be predicted from clinical characteristics or labor abnormalities, and that the occurrence of shoulder dystocia is not evidence of medical malpractice.

Birth Injuries↗
PubMed1987

Mutagenic potential of a 193-nm excimer laser on fibroblasts in tissue culture.

In response to concerns regarding possible DNA damage by far ultraviolet radiation during excimer laser corneal surgery, the mutagenic potential of an argon fluoride excimer laser (193 nm) on BALB/3T3 mouse fibroblasts grown in tissue culture was investigated. The cumulative incidence of anaplastic transformation after subablative radiant exposures from 3.5 mJ/cm2/pulse to 13.4 mJ/cm2/pulse was 3.6% of all cell cultures. The incidence of anaplastic transformation in nonirradiated controls was 4.2%. Transformation after exposure to x-ray radiation (60.9 rad) was 98.8%. The difference between the incidence of transformation of nonirradiated controls or excimer-treated cultures compared with x-ray radiation-treated cells was significant P less than 0.0001 (chi square test). In this standard cell line, 193-nm laser energy does not appear to have substantial mutagenic potential.

Anaplasia↗
PubMed1987

Effects of in vivo modulation of splenic natural killer cell activity on the growth of spleen-seeking tumour variants.

A novel tumour system has been used to study the effect of natural killer cells on tumour growth by using agents which modify natural killer cell activity. The tumour cells are hybridoma cells which secrete antibody specific for red blood cells so that tumour growth can be quantitated by a haemolytic plaque assay. Spleen-seeking variants have been derived from original hybrids which are sensitive to natural killer cells. Treatment of mice with polyinosinic-polycytidylic acid substantially enhanced natural killer cell activity and correlated closely with a reduction in the growth of the hybridoma tumour cells in the spleen and life extension. Conversely, a single injection of anti-asialo GM, antibody resulted in a substantial increase in the number of plaque forming splenic tumour cells and virtual elimination of natural killer cell activity. These data demonstrate the important role of natural killer cells in constraining the growth of a tumour of B cell origin and establishes the usefulness of this tumour model in studying the biology of effects on tumour growth.

Animals↗
PubMed1987

Amino acid sequence of the human fibronectin receptor.

The amino acid sequence deduced from cDNA of the human placental fibronectin receptor is reported. The receptor is composed of two subunits: an alpha subunit of 1,008 amino acids which is processed into two polypeptides disulfide bonded to one another, and a beta subunit of 778 amino acids. Each subunit has near its COOH terminus a hydrophobic segment. This and other sequence features suggest a structure for the receptor in which the hydrophobic segments serve as transmembrane domains anchoring each subunit to the membrane and dividing each into a large ectodomain and a short cytoplasmic domain. The alpha subunit ectodomain has five sequence elements homologous to consensus Ca2+-binding sites of several calcium-binding proteins, and the beta subunit contains a fourfold repeat strikingly rich in cysteine. The alpha subunit sequence is 46% homologous to the alpha subunit of the vitronectin receptor. The beta subunit is 44% homologous to the human platelet adhesion receptor subunit IIIa and 47% homologous to a leukocyte adhesion receptor beta subunit. The high degree of homology (85%) of the beta subunit with one of the polypeptides of a chicken adhesion receptor complex referred to as integrin complex strongly suggests that the latter polypeptide is the chicken homologue of the fibronectin receptor beta subunit. These receptor subunit homologies define a superfamily of adhesion receptors. The availability of the entire protein sequence for the fibronectin receptor will facilitate studies on the functions of these receptors.

Amino Acid Sequence↗
PubMed1987

A new approach to patient indexing.

A computer based rheumatology patient index is described. Patients are indexed according to essential clinical and laboratory data without reference to Procrustean diagnostic labels. The stored information can be searched for a wide range of practical and scientific purposes. The software was devised in the windows environment for the Apricot Xen for maximum speed and intelligibility.

Humans↗
PubMed1987

Diazepam-induced amnesia: a neuropharmacological model of an "organic amnestic syndrome".

Diazepam has well-known amnestic properties. These effects, however, are selective for certain psychobiologically distinct memory functions. In this study, incremental doses of diazepam administered to 10 normal volunteers selectively impaired anterograde episodic memory and attention while totally sparing access to information in long-term memory (semantic or knowledge memory). This pattern of disruption mimics that seen in patients with organic amnesias and is in sharp contrast to the pattern seen in patients with dementia. These findings provide a framework for defining specific psychobiological determinants of cognitive failure.

Adult↗
PubMed1986

Effortful and automatic cognitive processes in depression.

Ten patients with major depression and ten age- and sex-matched normal controls were presented with two contrasting cognitive tasks: one required sustained effort and information processing, and the other required only superficial information processing that could be accomplished automatically, with little effort. Depressed patients performed more poorly only on the effort-demanding cognitive task.

Cognition↗