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Biomedical subjects

K Thompson

Publications and source records attributed to K Thompson.

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

Calcium-dependent and calcium-independent protease activities in skeletal muscle during sepsis.

Sepsis was produced in rats by implanting into their abdominal cavities fecal pellets containing Escherichia coli (10(2) colony-forming units [CFU]) and Bacteroides fragilis (10(4) CFU). Control rats were implanted with sterile pellets. A febrile response and hyperlactacidemia marked the onset of the septic injury. Control and septic rats were killed 24 and 48 hr after implantations, and posterior leg muscles were removed. Muscles were homogenized to prepare soluble fractions containing calcium-independent lysosomal (cathepsins B and L) and calcium-dependent cytosolic (calpain) proteases. Cathepsin and calpain activities were then assayed using standard procedures. There were no alterations in cathepsins B or L activities during sepsis. Calpain activity in septic muscle was significantly higher than that in control muscles. In vitro calpain sensitivity to Ca2+ was also higher in septic muscle than in controls. The cysteine protease inhibitor leupeptin caused a quantitatively greater inhibition of calpain activity in septic than in control muscles. These data indicate that whereas sepsis has no effect on Ca(2+)-insensitive lysosomal proteases, it is associated with an elevation of the Ca(2+)-dependent cytosolic protease activity.

Animals↗
PubMed1990

Is the copper T 380A device associated with an increased risk of removal due to bleeding and/or pain? An analysis.

Previous studies have consistently shown that the family of the Copper T 380 devices is more effective in preventing accidental pregnancies than the inert, as well as most other, if not all, copper devices. However, a number of these studies also reported a higher removal rate due to bleeding and/or pain for the TCu 380A than for other devices. The programmatical importance of these findings prompted us to analyze the international multi-center randomized clinical trial datasets to examine this question on the new TCu 380A (ParaGard) recently marketed in the U.S. Our results, while confirming the inherent superior efficacy of the TCu 380A, did not reveal a significantly higher removal rate because of bleeding and/or pain among TCu 380A users than among users of the comparative devices, which included the Lippes Loop D, the TCu 200, the TCu 220 and the Multiload Cu 250 devices.

Adolescent↗
PubMed1990

Cytogenetic effects of extremely low doses of plutonium-238 alpha-particle irradiation in CHO K-1 cells.

CHO K-1 cells were irradiated during the G1 phase with 0.5-6 rad of alpha particles. There was no appreciable cell killing in this low dose range. Significantly increased frequencies of sister-chromatid exchanges were induced by doses as low as 0.5 rad of alpha-particle irradiation, whereas increased numbers of chromosomal aberrations were observed following exposure to 2 rad. These results suggest that very low doses of alpha radiation may lead to radiation-induced genetic alterations.

Alpha Particles↗
PubMed1990

Antioxidant-based inhibitors of leukotriene biosynthesis. The discovery of 6-[1-[2-(hydroxymethyl)phenyl]-1-propen-3-yl]-2,3-dihydro-5- benzofuranol, a potent topical antiinflammatory agent.

The leukotrienes, metabolites of arachidonic acid produced through the action of the enzyme 5-lipoxygenase, are important mediators of immediate hypersensitivity and inflammation. Among the variety of diseases in which the leukotrienes may play a symptomatic or causative role is the dermatological condition psoriasis, a chronic proliferative disease of the skin. This study reports the synthesis and comparative biological activities of various ortho-substituted phenols including 4-methoxyphenols, 6-hydroxy-1,2,3,4-tetrahydrobenzopyrans, 2,3-dihydro-5-benzofuranols, and 5-benzofuranols. The phenols prepared in this study were evaluated for their ability to inhibit the production of leukotriene B4(LTB4) in isolated human polymorphonuclear leukocytes (PMNs) and to inhibit a topical inflammatory response in the topical mouse ear (TME) model. In the former case, when the log IC50 was plotted versus the log of the octanol/water partition coefficient (log P), to eliminate the effect of lipophilicity, the 2,3-dihydro-5-benzofuranol ring system was shown to be more potent than the other ring systems examined throughout the range of partition coefficients studied. The ability to inhibit leukotriene production in vitro in human PMNs can be rationalized on the basis of a model that suggests that the observed inhibition is dependent on the kinetic ability of the inhibitor to reduce a radical species and on the fraction of inhibitor that is partitioned into the cell membrane. While the in vivo antiinflammatory activity as measured by the TME did not correlate with the in vitro data, it was felt that the TME represented a valuable measure of the ability of a compound to penetrate the skin to the site of an ongoing inflammatory response. Of the compounds synthesized in this study, 6-[1-[2-(hydroxymethyl)phenyl]-1-propen-3-yl]-2,3-dihydro-5-benzof uranol (1, L-651896) was chosen for further development.

Administration, Topical↗
PubMed1990

Implicit learning in patients with Alzheimer's disease.

We examined implicit memory using priming and procedural learning tasks in patients with probable Dementia-Alzheimer's Type (DAT) to examine whether priming and procedural processes could be dissociated and whether task specificity was a factor in DAT patient performance. Priming was tested using a word recognition paradigm (perceptual priming) and by repeated administrations of a fragmented objects test (long term priming). Procedural learning was tested using repeated and random sequences on a choice serial reaction time task and by repeated administration of a puzzle map of the United States. DAT patients were compared to hospitalized depressed patients, patients suffering from Progressive Supranuclear Palsy (PSP), and normal controls. We found that DAT patients demonstrated marginal but significant implicit learning on both procedural learning and perceptual priming tasks. DAT patients performed relatively better on the procedural learning task than a perceptual priming task compared to PSP patients, suggesting that priming of meaningful stimuli is subserved by cortical structures whereas procedural motor responses to simple serial visual stimulus patterns can be maintained by subcortical systems. Furthermore, our findings suggest that priming and procedural processes can be dissociated and that task specificity is a factor in interpreting the results of implicit learning paradigms in DAT patients. The implications of these results for models of knowledge representation and memory processes as well as the way they can serve as models for testing nootropic drug effects are discussed.

Aged↗
PubMed1990

The complete nucleotide sequences of the heavy chain variable regions of six monospecific rheumatoid factors derived from Epstein-Barr virus-transformed B cells isolated from the synovial tissue of patients with rheumatoid arthritis. Further evidence that some autoantibodies are unmutated copies of germ line genes.

Structural studies of human monoclonal rheumatoid factors (RF) derived from patients with monoclonal gammapathies have revealed a restriction in the usage of heavy and light chain variable regions. These studies have suggested that germline genes with little if any somatic mutation can generate RF specificity. However, there is no information presently available regarding the primary structure and genetic origin of RF in rheumatoid arthritis. In this study, we have isolated and sequenced the VH regions of six monoclonal RF derived from the synovial membranes of two patients with rheumatoid arthritis and one with the juvenile polyarticular form of the disease. We found the same VH families as previously reported among monoclonal paraproteins with RF activity. However, our sample was diverse regarding the VH, DH, and JH gene segments used. Among VHI RF there was conservation in the length of CDRIII as well as restriction in the amino acid generated at the V-D junction, as opposed to VHIII RF and non-RF VHI molecules that are highly heterogeneous in these two aspects. We also found that different JH gene segments may contribute to RF specificity. The VH, DH, and JH elements of one RF in our study all had clearly identifiable germline counterparts. This RF displays a nearly germline configuration throughout its entire heavy chain and represents another example of an autoantibody encoded by one of the VH gene segments from the preimmune fetal repertoire.

Arthritis, Rheumatoid↗
PubMed1990

Cognitive effects of corticosteroids.

In three independent studies with different designs and groups of subjects, the authors found that 1) depressed patients who did not suppress cortisol when given dexamethasone (compared to suppressors and normal control subjects), 2) healthy volunteers given a single 1-mg dose of dexamethasone (compared to those given placebo), and 3) healthy volunteers given 80 mg/day of prednisone for 5 days (compared to those given placebo) all made significantly more errors of commission in verbal memory tasks, with no significant change in their rates of errors of omission. These findings raise the possibility of specific corticosteroid-related cognitive impairments.

Adrenal Cortex Hormones↗
PubMed1990

Cross-sectional echocardiographic characterization of atelectatic lung segments. Differentiation from extracardiac tumors.

This report describes a unique series of patients who, during routine cross-sectional echocardiographic examination, were each noted to have a large echo-dense extracardiac mass adherent to the lateral aspect of the left ventricle. While this echo-dense mass was considered initially to represent an extracardiac tumor, this mass was shown subsequently to be an atelectatic segment of the left lower lobe of the lung. The salient echocardiographic findings that were considered to be helpful in terms of differentiating these adherent pulmonary atelectatic lung segments were that the lung segments always occurred in the presence of a moderate to large left pleural effusion; in real-time examination, the atelectatic lung masses generally appeared solid, as opposed to cystic, with a characteristic brightly reflective ground-glass appearance; there was never any evidence of extrinsic compression of the heart by the lung mass.

Aged↗
PubMed1990

Human monoclonal antibodies to C, c, E, e and G antigens of the Rh system.

A panel of heterohybridomas secreting human IgG and IgM monoclonal antibodies to the C, c, G, E, and e antigens of the Rh system has been established. Both classes of antibody have been shown to react with red blood cells carrying their respective antigens; those of the IgM class being able to directly agglutinate unmodified red blood cells in saline. The heterohybridomas have been shown to be suitable for bulk culture and produce levels of antibody in the range of 15-73 micrograms/ml in the spent culture supernatant.

Antibodies, Monoclonal↗
PubMed1989

Cerebral interferon entry in mice after osmotic alteration of blood-brain barrier.

Systemically administered interferon (IFN) is not readily detected in the central nervous system (CNS) due to the presence of the blood-brain barrier (BBB). A method of osmotic BBB alteration in a mouse model was established in this laboratory. IFN's entry into the normal and osmotically altered brain after its intracarotid injection was investigated. Significant IFN levels (100-1,000 units) in the brain can be achieved by this method. The highest IFN activity was found in the brain hemisphere ipsilateral to the injection site within 20 min to 1 h after injection. IFN activity in the brain was detectable up to 4 h. Animals injected in this manner with murine IFN-alpha/beta (MuIFN-alpha/beta) and observed for a 6-month time interval showed no signs of neurological dysfunctions and resumed their normal activities. The therapeutic value of this method will be tested in a murine model of malignant glioma.

Animals↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗