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Biomedical subjects

K Thompson

Publications and source records attributed to K Thompson.

At least 19 recordsLinked to original sources

Posttraumatic stress disorder and service utilization among urban mental health center clients.

Although the urban poor are at high risk for exposure to trauma, community mental health clinics rarely diagnose clients with PTSD. Failure to diagnose PTSD may undermine the effectiveness of services provided. Our objectives were to (1) assess prevalence of traumatic experiences and PTSD, and (2) examine differences in service utilization between those who had PTSD and those who did not. Interview data were gathered from 181 urban psychiatric outpatients. A substantial number of clients had experienced at least one lifetime trauma (94%), and of those, 42% had PTSD during the past year. Analyses comparing service use between PTSD and nonPTSD clients supported our expectation that clients with PTSD would use more mental health services, and would be less satisfied with services than their nonPTSD counterparts.

Attitude to Health

The flat-top gene is required for the expansion and regionalization of the telencephalic primordium.

The telencephalic vesicles form in the mouse embryo by the expansion of precursor regions in the anterior neural tube. Once the vesicles have formed, discrete dorsal and ventral territories can be recognized that later give rise to cortical and subcortical structures, respectively. To investigate the mechanisms that regulate the expansion and regionalization of the telencephalon, we have carried out a screen to identify recessive mutations that disrupt these events. We isolated a mouse mutant in which an early and critical step in development of the telencephalic vesicles is disrupted. Telencephalic primordia are present in flat-top embryos but they fail to progress to form the telencephalic vesicles. An increased rate of proliferation in the forebrain neurectoderm that accompanies telencephalic expansion in wild-type embryos fails to occur in flat-top embryos. Regionalization events that would normally take place during expansion of the primordia also fail to occur. Thus the phenotype of the flat-top mouse reveals that outgrowth of the telencephalic vesicles and their regionalization are coupled processes.

Animals

Association of terminal chromosome 1 deletion with sertoli cell-only syndrome.

We report on del(1)(q44), developmental delay, cryptorchidism, and seizure disorder in a 19-year-old man. Endocrinologic evaluation showed delayed puberty and elevated gonadotropins. Testicular biopsy was consistent with Sertoli cell-only syndrome. The case illustrates a previously an unreported manifestation in males with del(1)(q44), and suggests a link between the development of germinal epithelium and genes in the 1q44 area.

Adult

Elevated intracellular calcium levels in cerebellar granule neurons of weaver mice.

Weaver mice carry a mutation in the pore domain of the Girk2 (Kcnj6) gene. The mutation causes GIRK2 containing channels to lose ion selectivity and to become constitutively active. It is not known how this alteration in ion channel activity causes in cerebellar granule cells the defects in neurite extension, cell migration and induction of cell death that are characteristic of weaver mice. One possibility is that the mutation causes an inability to regulate intracellular calcium levels properly. We tested this hypothesis by measuring intracellular calcium levels in granule cells and Purkinje cells in slices from the cerebellum of weaver mice. We report here that weaver mice have increases in resting calcium levels in their granule cells, which may account for the multiple effects of the weaver mutation upon these cells.

Animals

Estrogen replacement therapy and outcome of coronary balloon angioplasty in postmenopausal women.

Estrogen replacement therapy (ERT) in women after menopause is associated with prevention of clinical coronary artery disease. However, few studies have investigated possible benefits from ERT in postmenopausal women undergoing treatment for established coronary disease. We therefore retrospectively reviewed the clinical outcomes of 428 postmenopausal women undergoing percutaneous transluminal coronary balloon angioplasty (PTCA) to test the hypothesis that ERT has a beneficial effect in this setting. The women were divided into 2 groups based on ERT status at the time of the procedure. Estrogen users were younger (60 +/- 10 vs 68 +/- 9 years, p <0.001), more commonly had family histories of coronary heart disease (54% vs 41%, p = 0.04), had less incidence of hypertension (63% vs 76%, p = 0.02), and had slightly fewer diseased vessels per patient (1.3 +/- 0.5 vs 1.5 +/- 0.7, p = 0.03) compared with nonusers. No in-hospital deaths occurred in estrogen users compared with 5% hospital mortality in nonusers (p = 0.01). The combined outcome of death or myocardial infarction (MI) also was lower in estrogen users (4% vs 12%, p = 0.04). Of 348 women discharged after successful PTCA, 336 (97%) were able to be contacted at an average follow-up interval of 22 +/- 17 months (range 5 to 82). Estrogen users had superior event-free survival both for death as well as for death or nonfatal MI. Repeat revascularizations were similar in both groups (32% vs 24%, p = 0.15). In a Cox proportional-hazards model, nonusers had 4 times the likelihood of death after angioplasty compared with estrogen users (OR = 4.025, 95% CI = 1.3 to 13.4, p = 0.02). We conclude that estrogen replacement may offer protection against clinical coronary events in postmenopausal women who already have established coronary disease and are undergoing balloon angioplasty. The benefit was independent of age, smoking, presence of diabetes mellitus, or the number of diseased coronary vessels. However, it did not include a reduction in repeat revascularization procedures, suggesting no reduction in restenosis.

Adult

Metastatic papillary oncocytic carcinoma of the pancreas to the liver diagnosed by fine-needle aspiration.

A 37-year-old white male with a large pancreatic mass was referred to our institution with a hypodense liver lesion detected on CT scan. A fine-needle aspiration (FNA) was performed on the liver lesion. Diff-Quik smears demonstrated scattered papillary structures and single neoplastic cells with abundant well-defined dense granular cytoplasm. Eccentrically located nuclei were noted with single prominent nucleoli. Cell block preparations showed papillary structures lined by cells with abundant pink granular cytoplasm, hyperchromatic nuclei, and prominent single nucleoli. Electron microscopic examination displayed numerous but poorly preserved mitochondria. The diagnosis of papillary carcinoma with oncocytic features was made. Only two previous cases of pancreatic oncocytic tumors diagnosed by FNA have been reported in the literature. We present an additional case, notable in that the diagnosis was made in a metastatic liver nodule.

Adult

Endothelial and serum factors which include apolipoprotein A1 tether elastin to smooth muscle cells inducing serine elastase activity via tyrosine kinase-mediated transcription and translation.

We previously reported that serine elastase activity is induced in cultured porcine pulmonary artery (PA) smooth muscle cells (SMC) following serum stimulation by a mechanism involving adhesion of elastin to an elastin binding protein and tyrosine kinase activity. The present study demonstrates that a PA endothelial cell factor also promotes a fourfold increase in elastin adhesion to PA SMC and a twofold increase in serine elastase activity. The mechanism involves tethering of the factor to SMC, since [3H]-elastin pre-incubated with serum or endothelial cell (EC)-conditioned medium or SMC pre-treated with serum accelerates binding of elastin and tyrosine-kinase related elastase activity. The serum factor appears to interact with integrins as elastase induction is partially inhibited by RGD peptides. The elastase-inducing properties of serum could not, however, be attributed to several RGD-containing proteins. While a 120 kD fibronectin fragment partially reproduced the effect, it was not found in the serum fraction containing elastase-inducing activity. Instead, a 27 kD serum protein was enriched by elastin affinity chromatography, identified as apolipoprotein (Apo) A1 by microsequence analysis, and found to have about 50% of the elastase-inducing activity of serum. Elastase induction is inhibited by actinomycin and cycloheximide, suggesting a requirement for mRNA transcription and protein synthesis. Our results suggest a novel cell-extracellular matrix interaction whereby a soluble factor, in this case a lipoprotein, binds and tethers a matrix component to the cell surface and induces tyrosine kinase-dependent transcription of mRNA culminating in substrate proteolysis.

Animals

Interleukin-10 expression and function in experimental murine liver inflammation and fibrosis.

Kupffer cells (KC) play a central role in the initiation and perpetuation of hepatic inflammation, which, if uncontrolled, can result in tissue damage, fibrosis, and cirrhosis. Interleukin-10 (IL-10) can inhibit a range of macrophage functions. We hypothesized that the transcription, synthesis, and release of IL-10 may influence the development of liver injury. Rat KC were activated in vitro with lipopolysaccharide (LPS), and expression of IL-10 mRNA compared with IL-13 and IL-1beta by reverse-transcription polymerase chain reaction (RT-PCR). The effects of pretreatment with recombinant IL-10 (rIL-10) on KC phagocytosis, production of superoxide (SO), and tumor necrosis factor (TNF-) were examined by fluorescent activated cell sorter (FACS), reduction of ferricytochrome C, and bioassay, respectively. Rats were administered intraperitoneal carbon tetrachloride (CCl4), and expression of IL-10 mRNA and protein in vivo compared with IL-13 and IL-1beta by RT-PCR and immunoblotting. Results were correlated with histological inflammatory changes. Finally, IL-10 gene-deleted (IL-10-/-) mice and wild-type (WT) controls were administered intraperitoneal CCl4 biweekly for up to 70 days, and the development of inflammation and fibrosis compared by scoring histological changes. IL-10 mRNA was up-regulated early, both in KC in vitro and in whole liver in vivo, concurrent with that of IL-1beta. IL-10 was able to inhibit KC production of both SO and TNF- in vitro, and this was achieved more effectively than IL-4 or IL-13; no such effects were seen on KC phagocytosis. After 70 days of treatment with CCl4, IL-10-/- mice showed significantly more severe fibrosis and exhibited higher hepatic TNF- levels than WT controls. These results suggest that IL-10 synthesized during the course of liver inflammation and fibrosis may modulate KC actions, and influence subsequent progression of fibrosis.

Animals

Immunohistochemical identification of epithelial and mesenchymal cell types in the chorioallantoic and yolk sac placentae of the guinea-pig.

To define the epithelial and mesenchymal cell types of the guinea-pig placenta, immunostaining patterns were determined for the intermediate filament proteins cytokeratin and vimentin. Chorionic and yolk sac placentae were studied at 15, 20, 25, 29-30, 44-45, 55 and 65 days of gestation. Immunohistochemistry was performed on 5-microm thick sections of paraffin embedded tissue using specific antibodies against cytokeratin, a marker for epithelial cells, including trophoblast, and vimentin, a marker for mesenchymal cells and stromal decidua. Immunostaining was identified by the avidin-biotin-peroxidase technique with diaminobenzidine as the chromogen. Most of the surface of the placenta is covered by the columnar epithelium of the parietal yolk sac, beneath which is found a layer of chorionic giant cells. In the guinea-pig, a sheet of mesenchymal cells interposed between these cell layers immunostained for vimentin, a protein that is expressed only intracellularly, and had nuclei orientated parallel to the surface of the placenta. This cell layer is quite different from Reichert's membrane in the rat or mouse, which is acellular. Within the main placenta, cytokeratin immunostaining demonstrated that the trophoblasts lining the large maternal blood sinuses are different in character from the surrounding syncytiotrophoblast, confirming earlier ultrastructural observations. In the subplacenta, some trophoblast did not immunostain for cytokeratin and there was non-specific staining of cellular debris, so that immunostaining for vimentin provided the clearest indication of the maternal-fetal interface. In later stages of gestation (30-55 days), trophoblasts invading the walls of maternal arteries immunostained for cytokeratin and were vimentin negative. In early gestation, however, trophoblast invasion of the maternal vessels was indicated by cells that were immunoreactive for both cytokeratin and vimentin.

Allantois

Hippocampal stimulation produces neuronal death in the immature brain.

We re-examined the proposed resistance of the immature brain to seizure-induced damage. In awake, freely moving rat pups, intermittent perforant path stimulation produced selective hippocampal cell loss and reduction in paired-pulse inhibition. During 16 h of stimulation, animals showed frequent wet dog shakes and hind-limb scratching movements but no convulsive motor activity. In situ end-labelling performed 2 h after the end of stimulation showed an intense band of positively-labelled eosinophilic cells with condensed profiles bilaterally in the dentate granule cell layer of stimulated animals. Control animals showed no in situ end-labelling positivity in the dentate gyrus. These cells were not observed 24 h later, suggestive of rapidly scavenged apoptotic cells. One day after the end of stimulation, many necrotic interneurons with eosinophilic cytoplasm and pyknotic nuclei were observed in the hilus of the stimulated dentate gyrus in all rats tested. Hippocampal pyramidal cells in CA1, CA3 and subiculum showed bilateral damage greater on the side of stimulation, and prepiriform cortex sustained bilateral symmetrical lesions. One month after perforant path stimulation, Cresyl Violet staining showed the number of large hilar interneurons (>15 microm) was reduced on the stimulated side (54.1 +/- 12.2) compared to the non-stimulated side (100.5 +/- 10.2 cells, P<0.01). Immunohistochemical analysis showed significant losses in somatostatin (8.5 +/- 1.6 stimulated side, 22.8 +/- 3.8 unstimulated side, P<0.05) and neuropeptide Y (12.8 +/- 3.2 stimulated side, 17.0 +/- 4.1 unstimulated side, P<0.05) immunoreactive cells in the stimulated hilus but no loss of parvalbumin-immunoreactive cells. Significant reductions in paired-pulse inhibition were found after stimulation but there was some return of inhibition by one month. These combined data demonstrate that the immature brain can incur damage as a result of prolonged seizure-like hippocampal activity mimicking status epilepticus in immature rats. The hippocampal damage produced by perforant path stimulation is associated with the immediate loss of physiological inhibition suggesting important modification of excitatory control in an extremely epileptogenic region of the brain.

Animals

Determinants of four functional tasks among older adults: an exploratory regression analysis.

Functional ability declines in later life. The purpose of this project was to determine if strength, postural control, and joint pain predict performance of four functional tasks among older adults. A sample of 28 older adults completed assessments of strength, postural control, joint pain, and four functional tasks. The duration to complete the functional tasks of: 1) getting out of bed, going to a chair, and then returning to bed; 2) crossing a street and getting onto a bus; 3) exiting the passenger side of a car; and 4) climbing a flight of 27 stairs was recorded. Step-wise regression equations indicated that seated row strength and dynamic postural control were significant predictors of all of the tasks and accounted for the largest proportion of the variance in each equation. These results indicate that measures of physical fitness may be more important predictors of functional tasks among older adults than chronological age.

Activities of Daily Living

Histopathological features of lepromatous iridocyclitis; a case report.

A peripheral iridectomy specimen which included a portion of the ciliary body from an advanced lepromatous leprosy patient was studied histopathologically. The lepromatous granuloma in the iris was similar in content and appearance to that of skin lesions. It appeared that even in this advanced lepromatous patient the dilator muscles of the iris were preserved. This study agrees with the earlier observation that the dysfunction of the iris in lepromatous disease is most probably the result of autonomic nerve destruction. Further, it is possible that the lepromatous involvement of the iris may reflect the histopathological changes in the ciliary body.

Aged

Lithium-pilocarpine status epilepticus in the immature rabbit.

Although status epilepticus in children is associated with neuronal pathologies, there are few developmental models of status epilepticus which produce damage in the immature brain. We have developed a new model of status epilepticus using systemically injected pilocarpine in immature rabbits pretreated with lithium. Injected animals demonstrated behavioral and electrographic seizures. Behavioral seizures were characterized by sustained or recurrent bouts of clonus in all limbs. The pilocarpine-induced seizures had a 40% mortality. All animals surviving the status epilepticus had hippocampal lesions when evaluated 48 h after the SE. Within the hippocampus, CA1 pyramidal cells were the most vulnerable cell population. Extrahippocampal damage was seen in the majority of animals. Our results show that severe seizures cause hippocampal lesions in the absence of hypoxemia and suggest that the presumed resistance of the immature brain to seizure-induced damage is not a general rule which can be applied to all models or species.

Animals

In vivo production of A-protein, lipopolysaccharide, iron-regulated outer membrane proteins and 70-kDa serine protease by Aeromonas salmonicida subsp. salmonicida.

Using specific immunostaining of Western blots, the in vivo expression of several putative virulence factors of Aeromonas salmonicida subsp. salmonicida was demonstrated in infected muscle tissue of Atlantic salmon and rainbow trout. Three virulent isolates of A. salmonicida were used. One isolate was chosen because in vitro it was apparently a non-producer of the 70-kDa serine protease. Infected furuncle tissue was centrifuged and samples of the pellet and supernatant probed for evidence that the components of interest were bacterial cell-associated or secreted. The A-protein was detected in pelleted furuncle material but not in the supernatant. Lipopolysaccharide, both high and low molecular mass, was present in the pellet but only high molecular mass lipopolysaccharide was detected in the furuncle supernatant. Iron-regulated outer membrane proteins were detected in the furuncle pellet. The 70-kDa serine protease was detected in the furuncle supernatant of both protease-producing strains. However, whilst the protease-deficient isolate was demonstrated to produce low levels of the 70-kDa protease when grown in vitro under iron restricted conditions, none could be detected in vivo.

Aeromonas

Partial protection of hippocampal neurons by MK-801 during perforant path stimulation in the immature brain.

We investigated whether the non-competitive NMDA receptor antagonist, MK-801, could protect neurons in the immature brain from the excitotoxic affects of perforant path stimulation. A high dose of MK-801 reduced the number of injured hilar interneurons in the stimulated hippocampus from 30.0 +/- 5.2 in unmedicated rats to 12.2 +/- 9.6 in MK-801 treated animals (P < 0.05). MK-801 injection also protected the animals from the scattered dentate granule cell injury observed in non-medicated animals 1 day after stimulation. Other effects of drug injection included exacerbated damage in limbic cortices, retrosplenial cortical damage, and reduced inhibition in a highly epileptogenic region of the dentate gyrus. Our results show that a subpopulation of hilar interneurons is vulnerable to NMDA-induced damage in the immature hippocampus but that non-competitive blockade of the NMDA receptor may be a dangerous therapeutic strategy.

Age Factors

Minimal effects of dextroamphetamine on scopolamine-induced cognitive impairments in humans.

The central anticholinergic drug scopolamine has been used to model aspects of the memory impairment that occurs in Alzheimer's disease and in aging. To determine whether nonspecific stimulant effects can attenuate the cognitive impairment induced by scopolamine, we studied the effects of scopolamine and the stimulant dextroamphetamine in 17 young normal volunteers. After a baseline day of cognitive testing, subjects participated in two study days, in which they received dextroamphetamine (d-AMP) (0.25 mg/kg p.o.) + scopolamine (0.5 mg i.v.) and placebo + scopolamine, in randomized order under double-blind conditions. There were no statistically significant differences in cognitive test performance between the two drug conditions with the exception of one of the category retrieval tasks. Stimulant effects were documented to occur by other measures. We conclude that d-AMP at the dose used does not attenuate the memory impairment induced by scopolamine.

Adult