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Biomedical subjects

D Strickland

Publications and source records attributed to D Strickland.

At least 37 records · Page 2Linked to original sources
PubMed1996

Brief report: two case studies using virtual reality as a learning tool for autistic children.

The children complied with most requests. Some of our teaching goals were limited by technology or space while others were limited by the difficulty of presenting a task to the children in a way that was understandable within their environment. However, the opportunity to introduce this technology to children was an important first step in exploring the potential VR offers to understanding the perceptual processes involved in autism. Our results indicate that the will accept a VR helmet and wear it, identify familiar objects and qualities of these objects in their environment while using the helmet, and locate and move toward objects in their environment while wearing the helmet. More research is necessary to verify the potential in this area, especially to discover if learning experiences through VR generalize to other environments, but it appears virtual reality may provide a useful tool for furthering our understanding of autism and guiding efforts at treatment and intervention.

Autistic Disorder↗
PubMed1996

Descriptive epidemiology of Parkinson's disease through proxy measures.

BACKGROUND AND OBJECTIVE: In preparation for analytic study we undertook to describe areas of relative excess and deficit of Parkinson's Disease (PD) in Nebraska and tested two methodologic tools for inexpensive assessment of descriptive epidemiology of PD. METHODS: In lieu of large-scale population screening and diagnosis, we obtained sales information of anti-PD drugs in the state in 1988-1990 as well as listings of all people dying from 1984 to 1993 who had Parkinson's Disease mentioned anywhere on their death certificate. The anti-PD drug sales data are intended as a proxy for prevalence, while the death certificate data are intended as a proxy for incidence. RESULTS: Sales divided by population over age 54 indicates where anti-PD drug sales differ from expected. We found high correlation of drug sales rates with several farming exposures. Age-adjusted death rates, however, showed a low degree of association with sales or farming variables. This may be attributable to differences in death certificate completion or in underlying incidence versus prevalence. CONCLUSIONS: These techniques provide a useful tool for delineating possible differences in incidence and prevalence. While not as accurate as full community survey with expert diagnosis, they are not as expensive, and can be followed by local cluster investigations and individual-level etiologic studies to test hypotheses resulting from the initial study.

Epidemiologic Methods↗
PubMed1996

Regulation of T-cell activation in the lung: alveolar macrophages induce reversible T-cell anergy in vitro associated with inhibition of interleukin-2 receptor signal transduction.

Alveolar macrophages (AM) are recognized as archetypal 'activated' macrophages with respect to their capacity to suppress T-cell responses to antigen or mitogen, and this function has been ascribed an important role in the maintenance of local immunological homeostasis at the delicate blood:air interface. The present study demonstrates that this suppression involves a unique form of T-cell anergy, in which 'AM-suppressed' T cells proceed normally through virtually all phases of the activation sequence including Ca2+ flux, T-cell receptor (TCR) modulation, cytokine [including interleukin-2 (IL-2)] secretion and IL-2 receptor (IL-2R) expression. However, the 'suppressed' T cells fail to up-regulate CD2, and do not re-express normal levels of TCR-associated molecules after initial down-modulation; moreover, they are unable to transduce IL-2 signals leading to phosphorylation of IL-2R-associated proteins, and remained locked in G0/G1. The induction of this form of anergy is blocked by an NO-synthase inhibitor, and is reversible upon removal of AM from the T cells, which then proliferate in the absence of further stimulation. We hypothesize that this mechanism provides the means to limit the magnitude of local immune responses in this fragile tissue microenvironment, while preserving the capacity for generation of immunological memory against locally encountered antigens via clonal expansion of activated T cells after their subsequent migration to regional lymphoid organs. In an accompanying paper, we demonstrate that a significant proportion of T cells freshly isolated from lung exhibit a comparable surface phenotype.

Animals↗
PubMed1996

Regulation of T-cell activation in the lung: isolated lung T cells exhibit surface phenotypic characteristics of recent activation including down-modulated T-cell receptors, but are locked into the G0/G1 phase of the cell cycle.

Peripheral lung tissue contains large numbers of T cells, strategically located for immune surveillance at the blood-air interface. Given the intensity of antigenic exposure at this site, it is clear that local T-cell activation events require strict control, in order to maintain tissue homeostasis. How this control is achieved in this unique tissue microenvironment is unknown, and the present study sought to elucidate the process via detailed analysis of the surface phenotypic characteristics of freshly isolated lung T cells. We report below that these cells display typical characteristic of 'postactivation', notably elevated basal Ca2+ concentrations, down-modulated T-cell receptors, expression of Ia and 'late' activation antigens and concomitant CD4/CD8. However, levels of interleukin-2 receptor and CD2 expression were below those expected of 'activated' T-cell populations, and virtually all of the cells were found to be in the G0/G1 phases of the cell cycle. These properties bear a remarkable similarity to those of T cells activated in the presence of endogenous tissue (alveolar) macrophages from the lung (see accompanying paper). We hypothesize that they reflect the in vivo operation of an endogenous macrophage-mediated T-cell anergy-induction process, the function of which is to limit the local clonal expansion of T cells in peripheral lung tissue after in situ activation.

Animals↗
PubMed1996

Expression of the very low-density lipoprotein receptor (VLDL-r), an apolipoprotein-E receptor, in the central nervous system and in Alzheimer's disease.

The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A beta complexes in the brain. Further characterizations of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD.

Aged↗
PubMed1996

Physical activity, trauma, and ALS: a case-control study.

AIMS: The association of trauma and physical activity with ALS is controversial. We explored the relation in a pilot case-control study. MATERIAL AND METHODS: ALS patients were selected from a university muscle disease clinic and paired with two matched controls: one from the clinic, but having different diseases, and one from the community. RESULTS: We found several strong and statistically significant differences between ALS cases and the matched controls. These included severe head, neck and back injury (OR = 5.3), the frequency of sweating in work (OR = 1.6) or leisure activity (also OR = 1.6), and earning a school letter (OR = 3.1). Other measures of trauma and activity, while not achieving statistical significance (p < 0.05), were in accord with these findings. DISCUSSION: Possible explanations include trauma and vigorous exercise precipitating ALS; trauma as an early sign of disease; or a third factor associated with ALS predisposing to injury. CONCLUSIONS: Severe head, neck, and back injury and frequency of sweating both in work and leisure activity showed a strong association with ALS. Further study could test narrower and less common exposures with greater statistical power.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Applying Watson's Theory for Caring among elders.

Caring is emerging as a significant concept for the nursing profession, and it is rapidly influencing nursing practice. In older adult care, where reductionistic medical cures are often not wanted or necessary, it seemed timely to take a closer look at Dr. Jean Watson's Theory of Human Caring. The author and a volunteer used a particular format designed by Lee Glickstein called "Laughing Spirit Listening Circles" to apply Watson's theory with six elderly women weekly over a four-week period. The main goals the volunteers had in creating this group was simply to listen to the women share their stories with one another, to be as present with them as possible, to not be directive in the group, but to be "in the flow" with whatever topics and issues emerged. Another purpose the author had in conducting these sessions was to receive feedback from the participants regarding this style of nursing practice. At the last session participants offered comments regarding their experience in this group with suggestions for how to include others. Unsolicited, the participants had much to say regarding their own personal experience at the retirement community around this issue of "presence" and "caring."

Aged↗
PubMed1995

Age-specific reference ranges for serum prostate-specific antigen.

OBJECTIVES: To assess the relationship of the distribution of serum prostate-specific antigen (PSA) to age in a population of subjects for whom PSA levels were determined as part of a health fair. METHODS: Between March 19 and March 28, 1993, 1716 men aged 40 to 79 years from eastern Nebraska who participated in "The Health Fair of the Midlands" provided blood for serum PSA determination. RESULTS: Serum PSA concentration was correlated with patient age, with the observed 95th percentile increasing from 1.5 ng/mL for subjects 40 to 44 years of age to 7.7 ng/mL for subjects 75 to 79 years of age. Variability in serum PSA concentrations increased with increasing age. Taking this heteroscedasticity into account provided the following upper limits of normal (95th percentiles) for serum PSA: age 40 to 49, 1.5; age 50 to 59, 2.6; age 60 to 69, 4.4; age 70 to 79, 7.5. CONCLUSIONS: Previously published age-specific reference ranges did not consider the increasing variability of PSA concentration with age and have upper limits of normal that are too high for subjects under age 60 and may be too low for subjects aged 70 to 79. Upper reference ranges of 1.5 ng/mL for subjects aged 40 to 49, 2.5 ng/mL for subjects aged 50 to 59, 4.5 ng/mL for subjects aged 60 to 69, and 7.5 ng/mL for subjects aged 70 to 79 years provide specificity near 95%.

Adult↗
PubMed1995

Prenatal diagnosis and management of fetal goiter caused by maternal Grave's disease.

We present a case of maternal Grave's disease associated with fetal goitrous hyperthyroidism. Fetal goiter was diagnosed by ultrasound and diagnosis of fetal hyperthyroidism was established by umbilical blood sampling. Fetus was successfully treated by increasing maternal propylthiouracil dosage. Fetal thyroid status was normal at birth. Role of sonography and umbilical blood sampling in management of fetal goiter complicated with maternal Grave's disease is discussed.

Adult↗
PubMed1995

In utero treatment of fetal goitrous hypothyroidism caused by maternal Graves' disease.

We present two cases of maternal Graves' disease complicated by fetal goitrous hypothyroidism. Both patients had elevated maternal thyroid-stimulating immunoglobulin and thyrotropic-binding inhibitory immunoglobulin antibody titers. Diagnosis of fetal hypothyroidism was made by cordocentesis, and serial injections of thyroxine into the amniotic fluid resulted in return to normal of fetal thyroid size and function at birth. Significance of in utero management of fetal hypothyroidism is discussed.

Adult↗
PubMed1995

Pseudomonas exotoxin-mediated selection yields cells with altered expression of low-density lipoprotein receptor-related protein.

The alpha 2-macroglobulin (alpha 2M) receptor/low-density lipoprotein receptor-related protein (LRP) is important for the clearance of proteases, protease-inhibitor complexes, and various ligands associated with lipid metabolism. While the regulation of receptor function is poorly understood, the addition of high concentrations of the 39-kD receptor-associated protein (RAP) to cells inhibits the binding and/or uptake of many of these ligands. Previously, we (Kounnas, M.Z., R.E. Morris, M.R. Thompson, D.J. FitzGerald, D.K. Strickland, and C.B. Saelinger. 1992. J. Biol. Chem. 267:12420-12423) [corrected] showed that Pseudomonas exotoxin (PE) could bind immobilized LRP. Also, the addition of RAP blocked toxin-mediated cell killing. These findings suggested that PE might use LRP to gain entry into toxin-sensitive cells. Here we report on a strategy to select PE-resistant lines of Chinese hamster ovary cells that express altered amounts of LRP. An important part of this strategy is to screen PE-resistant clones for those that retain sensitivity to both diphtheria toxin and to a fusion protein composed of lethal factor (from anthrax toxin) fused to the adenosine diphosphate-ribosylating domain of PE. Two lines, with obvious changes in their expression of LRP, were characterized in detail. The 14-2-1 line had significant amounts of LRP, but in contrast to wild-type cells, little or no receptor was displayed on the cell surface. Instead, receptor protein was found primarily within cells, much of it apparently in an unprocessed state. The 14-2-1 line showed no uptake of chymotrypsin-alpha 2M and was 10-fold resistant to PE compared with wild-type cells. A second line, 13-5-1, had no detectable LRP mRNA or protein, did not internalize alpha 2M-chymotrypsin, and exhibited a 100-fold resistance to PE. Resistance to PE appeared to be due to receptor-specific defects, since these mutant lines showed no resistance to a PE chimeric toxin that was internalized via the transferrin receptor. The results of this investigation confirm that LRP mediates the internalization of PE.

ADP Ribose Transferases↗
PubMed1995

Level of receptor-associated protein moderates cellular susceptibility to pseudomonas exotoxin A.

Pseudomonas exotoxin A (PE) enters mammalian cells via a receptor-mediated endocytic pathway. The initial step in this pathway is binding to the multiligand receptor termed the alpha 2-macroglobulin receptor/low-density lipoprotein receptor-related protein (LRP). Binding of toxin, and of the many other ligands that bind to LRP, is blocked by the addition of a 39-kDa receptor-associated protein (RAP). Here we show that approximately 40% of the cell-associated LRP is on the surface of toxin-sensitive mouse LM fibroblasts and thus accessible for toxin internalization. The remainder is located intracellularly, primarily in the Golgi region. Mammalian cells exhibit a wide range of sensitivity to PE. To investigate possible reasons for this, we examined the expression levels of both LRP and RAP. Results from a variety of cell lines indicated that there was a positive correlation between LRP expression and toxin sensitivity. In the absence of LRP, cells were as much as 200-fold more resistant to PE compared with sensitive cells. A second group of resistant cells expressed LRP but had a high level of RAP. Thus, a toxin-resistant phenotype would be expected when cells expressed either low levels of LRP or high levels of LRP in the presence of high levels of RAP. We hypothesize that RAP has a pivotal role in moderating cellular susceptibility to PE.

ADP Ribose Transferases↗
PubMed1994

Endocytosis of urokinase-plasminogen activator inhibitor type 1 complexes bound to a chimeric transmembrane urokinase receptor.

The urokinase receptor (uPAR) is linked to plasma membranes through a glycosylphosphatidylinositol (GPI) anchor. It has been posited that the GPI anchor facilitates clearance of uPAR-bound complexes between two chain urokinase (tcuPA) and plasminogen activator inhibitor type 1 (PAI-1) by the alpha 2-macroglobulin receptor (alpha 2MR) which permits re-expression of unoccupied uPA receptors on the cell surface. To test this hypothesis we compared internalization and degradation of 125I-labeled tcuPA-PAI-1 by COS cells expressing either transfected wild-type, GPI-linked uPAR (uPAR/GPI), or a chimeric receptor composed of the extracellular domains of uPAR linked to the transmembrane and cytosolic domains of the alpha chain (p55 subunit) of the interleukin-2 receptor (uPAR/IL-2R alpha). The kinetics of binding, internalization and degradation of tcuPA-PAI-1 by COS cells expressing each form of uPAR were virtually identical. However, internalization of complexes by uPAR/IL-2R alpha was more susceptible to inhibition by recombinant soluble 39-kDa alpha 2MR-associated protein (RAP) which competes for binding of tcuPA-PAI-1 complexes to alpha 2MR (p < 0.001), and the internalization was accompanied by a greater reduction in the number of surface uPAR/IL-2R alpha, than uPAR/GPI (p < 0.05). These studies indicate that the rate of internalization of tcuPA-PAI-1 is governed primarily by the extracellular domains of uPAR, whereas the GPI anchor may facilitate internalization of complexes and re-expression of uPAR when binding sites on alpha 2MR are limiting.

Animals↗
PubMed1994

Polymerization of tubulin in apoptotic cells is not cell cycle dependent.

Prominent, specific tubulin structures were identified in human leukemic cells undergoing apoptosis following treatment with cytotoxic drugs. In order to determine whether tubulin reorganization was dependent upon the stage of the cell cycle at which apoptosis was induced, the human leukemic T-cell line CCRF-CEM was treated with cytotoxic doses of drugs known to arrest cells at different stages of the cell cycle. Apoptosis was confirmed by the detection of characteristic single and multiple nucleosome-sized fragments by agarose gel electrophoresis of isolated DNA. Cells were treated with vincristine, methotrexate, and dexamethasone, which have been shown to induce cell cycle arrest at G2-M, S-phase, and G1, respectively. Treated and untreated cells were analyzed by immunocytochemistry for beta-tubulin or Ki-67 antigen (to confirm cell cycle phase) and scored for apoptotic morphology. Dual staining for cellular tubulin and DNA content, measured by flow cytometry, was used to confirm the stage at which the cycling cells arrested. Increased total cellular tubulin immunofluorescence was observed in treated compared to untreated cells. Our results indicate that CCRF-CEM cells undergo apoptosis (identified morphologically) at all stages of the cell cycle except mitosis. We conclude that the reorganization of cellular tubulin that we have observed in apoptotic cells is independent of the tubulin involvement in cell division and thus may be an integral part of the apoptotic process.

Apoptosis↗
PubMed1994

Premature rupture of the membranes between 20 and 25 weeks' gestation: role of amniotic fluid volume in perinatal outcome.

OBJECTIVE: Our purpose was to prospectively study the relationship between amniotic fluid volume and perinatal outcome in pregnancies complicated by premature rupture of the membranes before fetal viability. STUDY DESIGN: The study population consisted of 178 singleton pregnancies with premature rupture of membranes between 20 and 25 weeks' gestation who were managed expectantly. Serial amniotic fluid volume measurements were made and their relationship to the neonatal survival rate, incidence of chorioamnionitis, and other perinatal outcomes was determined. RESULTS: Seventy-four patients were delivered before 25 weeks of gestation and only five infants (6.7%) survived. In contrast, 104 patients were delivered between 26 and 34 weeks, and 93 infants (89.4%) survived (p < 0.001). There were 107 pregnancies with adequate amniotic fluid volume after premature rupture of membranes on admission. Of these 16 patients were delivered before 25 weeks of gestation, and the remaining 91 patients were able to carry their pregnancies beyond 25 weeks of gestation. This was significantly different from 71 patients who demonstrated inadequate amniotic fluid volume on admission to the hospital, of whom 58 were delivered before 25 weeks and only 13 continued the pregnancy beyond 25 weeks (p < 0.05). At gestations between 26 and 34 weeks chorioamnionitis occurred in 22 of 91 (24.1%) patients with adequate amniotic fluid volume versus nine of 13 patients (69.2%) with inadequate amniotic fluid volume (p < 0.001). The incidence of perinatal death for pregnancies between 26 and 34 weeks with adequate versus inadequate amniotic fluid volume was 2.1% and 69.2%, respectively (p > 0.001). Overall survival rate and incidence of chorioamnionitis were 55% and 26.4%, respectively. CONCLUSIONS: Delivery of pregnancies between 20 and 25 weeks of gestation with premature rupture of membranes carries very high risk of neonatal mortality. The results of this study suggest that women with adequate amniotic fluid volume have a better chance to continue their pregnancy beyond 25 weeks of gestation and have a higher neonatal survival rate than those with inadequate amniotic fluid volume. The incidence of perinatal death and chorioamnionitis in patients who carry a pregnancy beyond 25 weeks is correlated with inadequate amniotic fluid volume.

Adult↗