Optimum dry eye classification using questionnaire responses.
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Diagnosis, Differential↗
Biomedical subjects
A Ho
Publications and source records attributed to A Ho.
Nonlinear combination of luminance excursions during flicker, simultaneous contrast, afterimages and binocular fusion.
The changes in apparent brightness or color, induced into a test spot by a surround, can be greatly enhanced either by flickering the test spot between two luminances, or by binocularly fusing a pair of test spots of different luminances. Simultaneous contrast, in which a white surround makes a grey spot look darker, is greatly enhanced if the spot (not the surround) flickers between black and white. Colour contrast is likewise enhanced by chromatic flicker: on a blue surround, a grey spot looks slightly yellowish, but a yellow/blue flickering spot looks strongly yellow. Temporal successive contrasts, or negative afterimages, are also enhanced by flickering the test field. The negative afterimage of a half-white, half-black rectangle looked dark grey and light grey when projected on a grey test field, but it looked almost black and almost white when projected on a test field that flickered between black and white. Coloured negative afterimages were also enhanced by projecting them on a chromatic flickering test field. We examined the combination rules for pairs of luminances which were presented either successively as flicker or else dichoptically (and fused binocularly). The brightness averaging functions for spatial increments (light spots) on dark surrounds were quasi-linear for binocular fusion but quadratic for flicker. For spatial decrements (dark spots) on white surrounds, the brightness averaging functions were strongly nonlinear winner-take-all for both binocular fusion and flicker. We also found temporal analogues of Fechner's [(1860). Elements of psychophysics. New York: Holt, Rinehart, Winston, 1966] paradox and Levelt's [(1965). British Journal of Psychology, 56, 1-13] dichoptic contour effect. We conclude that the visual rules for combining luminance excursions, whether in flicker or binocular fusion, favour disproportionately the spot with the higher contrast.
Afterimage↗
Effects of "binge" pattern cocaine on stereotypy and locomotor activity in C57BL/6J and 129/J mice.
This study characterized the behavioral response to cocaine in two strains of mice, the C57BL/6J and 129/J strains, commonly utilized as host strains for transgenic and "knockout" mice. The psychomotor stimulating effects of four doses of cocaine (2.5, 5.0, 10.0, and 15.0 mg/kg/injection) with a saline control, administered in a "binge" pattern (three equal injections at hourly intervals) for 3 days were examined in adult male C57BL/6J and 129/J mice. Behavioral stereotypy in the home cage, was rated 15, 30, and 45 min following each injection. Spontaneous locomotor activity in the home cage was also monitored. Cocaine, at doses of 10.0 or 15.0 mg/kg, produced behavioral stereotypy in both C57BL/6J mice (p < 0.0001) and 129/J mice (p < 0.0001), whereas lower doses did not. The magnitude of stereotypy was significantly lower in 129/J mice than in C57BL/6J mice receiving identical doses of cocaine. C57BL/6J mice also demonstrated a dose-dependent cocaine-induced stimulation of locomotor activity following administration of 10.0 or 15.0 mg/kg of cocaine (p < 0.0005). In contrast, 129/J mice did not exhibit increased locomotion in response to any dose of cocaine tested. These results demonstrate that strain differences in drug-induced behavior may be more pronounced in one measure (i.e., locomotor activity) than in another (i.e., stereotypy) and indicate the importance of multiple behavioral measures.
Animals↗
Sustained withdrawal allows normalization of in vivo [11C]N-methylspiperone dopamine D2 receptor binding after chronic binge cocaine: a positron emission tomography study in rats.
In our previous positron emission tomography studies striatal binding for both [11C]SCH23390 and [11C]N-methylspiperone (NMSP) were decreased in the rat brain on the last day of chronic (14 days) binge cocaine administration. We have found that [11C]SCH23390 binding to dopamine D1 receptors returns to saline control levels within ten days withdrawal from chronic binge cocaine and remains at control levels after 21 days withdrawal. An 18% decrease in [11C]NMSP binding to dopamine D2 receptors was observed after ten days withdrawal. However, importantly, after 21 days withdrawal [11C]NMSP binding was at saline control levels. Changes of in vivo [11C]NMSP binding required a longer abstinence period for normalization than [11C]SCH23390 binding. The apparent recovery of dopamine D2 receptors after prolonged abstinence from chronic cocaine and the different rates of normalization for dopamine D1 versus D2 receptors may be critical information for development of pharmacotherapies for cocaine dependent patients.
Analysis of Variance↗
Partial lung shield for TBI.
In this study, AP/PA setup was used with a 4 MV linear accelerator. The prescribed dose is 1000 cGy, with a dose per fraction of 200 cGy. One of the simplest lung dose determinations is the nomograph relating dose correction factor and patient thickness. To save time in taking port film in every treatment, lung block is used in alternating fashion: anterior blocks are used in the second and fourth fraction and posterior block is used in the third and fifth fraction. If we set the average correction factor for the lower density lung to 1.18, the six open fields will deliver an average of 708 cGy to the lung. To limit the lung dose to 10 Gy, each blocked field should deliver 73 cGy. Measurements showed that a thickness of slightly less than 1 cm of cerrobend provides approximately 65% transmission, which approximates the desired 73% broad beam transmission. The proper transmission of the partial lung shield is verified by measurements made for the patients with diodes placed at the entrance and the exit side of the lung. While we describe a particular setup, the procedure can be modified to accommodate different dose fraction. There are many ways to deliver the TBI dose, and the method of constructing the partial lung shield described here is one of the many methods that may be used to limit the dose to the lung.
Humans↗
Regional quantitation of preprodynorphin mRNA in guinea pig gastrointestinal tract.
The endogenous opioid peptide dynorphin has been shown by immunochemical studies to be widely distributed in the gastrointestinal tract. The aim of this study was to determine basal levels of preprodynorphin (ppDyn) mRNA in different regions of the gastrointestinal tract of the guinea pig. A modified sensitive and specific solution hybridization RNase protection assay was used to quantitate ppDyn mRNA, with confirmation by gel analysis of the RNase protected hybrids and PCR amplified cDNA. This method combines high sensitivity and sufficient throughput to analyze large number of samples in a single assay. Low but measurable amounts of ppDyn mRNA were detected in fundus, duodenum, jejunum, ileum, cecum, and rectum. The rectum contained significantly more ppDyn mRNA than the stomach, small bowel, and cecum. The muscularis/myenteric plexus layer of both ileum and rectum contained a higher concentration of ppDyn mRNA per microg total RNA compared to the mucosa/submucosa/submucosal plexus. However, a greater absolute amount of ppDyn mRNA (80-85%) localized to the mucosal layer. The greater absolute amount of ppDyn mRNA in the mucosal layer may indicate the presence of dynorphin in the endocrine cells of the mucosa.
Animals↗
Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kip1 induces cell migration.
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Cell Cycle Proteins↗
Localization of dystrophin isoform Dp71 to the inner limiting membrane of the retina suggests a unique functional contribution of Dp71 in the retina.
The electroretinograms (ERGs) of patients with Duchenne muscular dystrophy and an allelic variant of the mdx mouse (mdxCv3) have been shown to be abnormal. Analysis of five allelic variants of the mdx mouse with mutations in the dystrophin gene has shown that there is a correlation between the position of the mutation and the severity of the ERG abnormality. Three isoforms are expressed in the retina: Dp427, Dp260 and Dp71. Using indirect immunofluorescence and isoform-specific antibodies on retinal sections from three allelic mdx mouse strains, we have examined the localization of each of the isoforms. We show that Dp71 expression does not overlap with Dp427 and Dp260 expression at the outer plexiform layer (OPL). Instead, Dp71 is localized to the inner limiting membrane (ILM) and to retinal blood vessels. Moreover, we show that Dp260 and Dp71 differ structurally at their respective C-termini. In addition, we find that the proper localization of the beta-dystroglycan is dependent upon both Dp260 at the OPL and Dp71 expression at the ILM. Thus, Dp260 and Dp71 are non-redundant isoforms that are located at different sites within the retina yet have a common interaction with beta-dystroglycan. Our data suggest that both Dp71 and Dp260 contribute distinct but essential roles to retinal electrophysiology.
Adult↗
Nalmefene causes greater hypothalamic-pituitary-adrenal axis activation than naloxone in normal volunteers: implications for the treatment of alcoholism.
Among other actions, opioid antagonists modulate the control endogenous opioids exert on the hypothalamic-pituitary-adrenal (HPA) axis. Naloxone, nalmefene, and naltrexone are the opioid antagonists approved for use in man and are primarily mu-opioid selective. Naltrexone and nalmefene have been demonstrated to be useful in the treatment of alcoholism. Compared with naloxone, nalmefene has a longer half-life, is more potent at the mu-receptor, and has a higher affinity for kappa- and delta-opioid receptors. We conducted an inpatient study comparing the effects of 10 and 30 mg doses of intravenous naloxone and nalmefene in normal, nonsubstance nor alcohol-abusing, volunteers. Significant increases in ACTH and cortisol were observed after both antagonists, without an apparent dose-response relationship; however, both doses of nalmefene resulted in greater HPA axis activation than either dose of naloxone (ACTH: p <0.005). These results indicate that kappa- and delta-opioids may play important roles in the regulation of the HPA axis; nalmefene may be useful as both a probe to explore the HPA axis physiology and as a pharmacotherapeutic agent.
Adrenocorticotropic Hormone↗
Identification of a human immunodeficiency virus type 2 (HIV-2) encapsidation determinant and transduction of nondividing human cells by HIV-2-based lentivirus vectors.
Although previous lentivirus vector systems have used human immunodeficiency virus type 1 (HIV-1), HIV-2 is less pathogenic in humans and is amenable to pathogenicity testing in a primate model. In this study, an HIV-2 molecular clone that is infectious but apathogenic in macaques was used to first define cis-acting regions that can be deleted to prevent HIV-2 genomic encapsidation and replication without inhibiting viral gene expression. Lentivirus encapsidation determinants are complex and incompletely defined; for HIV-2, some deletions between the major 5' splice donor and the gag open reading frame have been shown to minimally affect encapsidation and replication. We find that a larger deletion (61 to 75 nucleotides) abrogates encapsidation and replication but does not diminish mRNA expression. This deletion was incorporated into a replication-defective, envelope-pseudotyped, three-plasmid HIV-2 lentivirus vector system that supplies HIV-2 Gag/Pol and accessory proteins in trans from an HIV-2 packaging plasmid. The HIV-2 vectors efficiently transduced marker genes into human T and monocytoid cell lines and, in contrast to a murine leukemia virus-based vector, into growth-arrested HeLa cells and terminally differentiated human macrophages and NTN2 neurons. Vector DNA could be detected in HIV-2 vector-transduced nondividing CD34(+) CD38(-) human hematopoietic progenitor cells but not in those cells transduced with murine vectors. However, stable integration and expression of the reporter gene could not be detected in these hematopoietic progenitors, leaving open the question of the accessibility of these cells to stable lentivirus transduction.
Antigens, CD34↗
Novelty-induced locomoter activity in Long-Evans rats pre- and post-chronic 'binge'-pattern cocaine treatment.
Incremental locomotor activity observed in behaviorally sensitized rats is associated with the activation of the mesocorticolimbic dopaminergic system and the hypothalamic-pituitary-adrenal (HPA) axis. To determine whether individual locomotor differences are altered in the behaviorally sensitized state, Long-Evans rats were placed in a novel environment and locomotor activity was recorded for 2 h. Animals, thereby, were evenly divided into two activity groups: lower- (LR) and higher- (HR) responders (LR, 367 +/- 38 cumulative beam breaks; HR, 797 +/- 43; P < 0.01). Subsequently, rats were randomly assigned to saline or chronic 'binge'-pattern (CBP) cocaine (15 mg/kg i.p., three injections/day for 14 days) treatment groups. One hour after the last injection, rats were sacrificed and trunk blood was collected for plasma corticosterone (CORT) determination. CORT levels were higher in cocaine versus saline treated animals (P < 0.01). CBP cocaine treated rats had higher locomotor activity compared to saline treated animals (P < 0.05). Moreover, rats less vulnerable to psychostimulant self-administration (LRs) appeared to have locomotor behavior resembling that of the more vulnerable phenotype (HRs) after CBP cocaine. These findings suggest that behavioral sensitization, as a result of CBP cocaine treatment, changes novelty-stress induced behavior which may reflect altered individual vulnerability to drugs of abuse.
Animals↗
Brca2 is required for embryonic cellular proliferation in the mouse.
Mutations of the tumor suppressor gene BRCA2 are associated with predisposition to breast and other cancers. Homozygous mutant mice in which exons 10 and 11 of the Brca2 gene were deleted by gene targeting (Brca2(10-11)) die before day 9.5 of embryogenesis. Mutant phenotypes range from severely developmentally retarded embryos that do not gastrulate to embryos with reduced size that make mesoderm and survive until 8.5 days of development. Although apoptosis is normal, cellular proliferation is impaired in Brca2(10-11) mutants, both in vivo and in vitro. In addition, the expression of the cyclin-dependent kinase inhibitor p21 is increased. Thus, Brca2(10-11) mutants are similar in phenotype to Brca1(5-6) mutants but less severely affected. Expression of either of these two genes was unaffected in mutant embryos of the other. This study shows that Brca2, like Brca1, is required for cellular proliferation during embryogenesis. The similarity in phenotype between Brca1 and Brca2 mutants suggests that these genes may have cooperative roles or convergent functions during embryogenesis.
Animals↗
Reduced incidence and severity of antigen-induced autoimmune diseases in mice lacking interferon regulatory factor-1.
Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates interferon-induced genes and type I interferons. Recently, studies of IRF-l-deficient mice have revealed that IRF-I regulates the induction of molecules that play important roles in inflammation, such as inducible nitric oxide synthase (iNOS) and interleukin-l beta-converting enzyme (ICE). To study the role of IRF-1 in autoimmunity, we investigated type II collagen-induced arthritis (CIA), and experimental allergic encephalomyelitis (EAE), in mice lacking IRF-1. The incidence and severity of CIA were significantly decreased in IRF-1-/- mice compared with IRF-l +/- mice, as was the production of interferon (IFN)-gamma in lymph node cells. Both IRF-l+/- and IRF-1-/- mice exhibited mild and transient disease after adoptive transfer of a type II collagen (CII)-specific T cell line together with sera from arthritic mice, but the IRF-1-/- mice were less severely affected than the IRF-1+/- mice. In addition, the incidence of EAE in IRF-1-/- mice was decreased as compared with IRF-1 +/- mice. Reverse transcription polymerase chain reaction showed that IRF-1 mRNA was constitutively expressed in the spinal cords of IRF-1+/- mice, and was upregulated in mice with clinical EAE. Expression of iNOS was also detected in inflamed spinal cords. These results suggest that IRF-I plays a key role in promoting inflammation and autoimmunity in CIA and EAE animal models.
Animals↗
Quantitation of dopamine transporter mRNA in the rat brain: mapping, effects of "binge" cocaine administration and withdrawal.
Dopamine transporter (DAT) mRNA from selected brain regions of individual male Fischer rats was quantitated utilizing a sensitive solution hybridization assay in which the levels of RNase-protected 32P-labeled mRNA:cRNA hybrids were measured. DAT mRNA was detected in whole brain regions known to contain abundant DAT mRNA (mean picogram of DAT mRNA/microgram of total RNA +/- SEM): substantia nigra, 7.17 +/- 0.47; ventral tegmentum, 4.71 +/- 0.38. In regions known to contain low levels of DAT mRNA, these levels were detected: central grey, 0.39 +/- 0.06; hypothalamus, 0.14 +/- 0.03. In addition, DAT mRNA was detected in areas where it had not previously been identified: amygdala, 0.19 +/- 0.03; caudate-putamen, 0.15 +/- 0.03; nucleus accumbens, 0.13 +/- 0.01; pons/medulla, 0.12 +/- 0.02; globus pallidus, 0.09 +/- 0.04; pituitary 0.07 +/- 0.01; frontal cortex, 0.05 +/- 0.01. No DAT mRNA was detected in 150 micrograms of rat liver RNA. As cocaine binds to and inhibits the activity of the dopamine transporter, we sought to determine if there were differences in dopamine transporter mRNA levels between saline- and cocaine-injected rats or rats withdrawn from a chronic "binge" pattern (15 mg/kg per dose i.p.; three doses at 1 h intervals each day) cocaine injection. Using trichloroacetic acid precipitation of mRNA:cRNA hybrids from RNA extracted from whole brain regions, we found no significant differences in the substantia nigra or the ventral tegmentum following subacute (3 days) binge, chronic (14 days) binge or 10 days withdrawal from a chronic binge pattern cocaine or saline administration.
Animals↗
Regulation of astroglial-derived dopaminergic neurotrophic factors by interleukin-1 beta in the striatum of young and middle-aged mice.
Interleukin-1 beta (IL-1 beta) can induce dopaminergic axonal sprouting in the denervated striatum of parkinsonian animals. In order to determine whether IL-1 beta effects on dopaminergic axonal sprouting are mediated by the induction of astroglial-derived dopaminergic neurotrophic factors, effects of IL-1 beta treatment on acidic and basic fibroblast growth factor (aFGF and bFGF) and glial cell line-derived growth factor (GDNF) gene expression were examined in primary striatal astrocyte cultures and after in vivo administration. We found a selective induction of bFGF mRNA synthesis but not aFGF or GDNF mRNA after IL-1 beta treatment both in vitro and in vivo. This suggests that bFGF may be the putative endogenous dopaminergic neurotrophic factor mediating lesion-induced plasticity of dopamine neurons. In addition, to determine why recovery from injury becomes reduced with age, we examined whether there was an aging-associated decline in the ability of IL-1 beta to induce the synthesis of neurotrophic factors in middle-aged animals compared to young mice. Interestingly, IL-1 beta stimulated a greater induction in bFGF mRNA levels in the middle-aged mice compared to young mice. These results suggest that the regulation of bFGF and possibly its receptor signaling efficacy may vary as the brain ages.
Age Factors↗
Basal total opioid peptide release in the striatum of rats with cholestasis from bile duct resection: a study by the use of in vivo microdialysis.
The opiate withdrawal-like reaction experienced by patients with cholestatic liver disease after the ingestion of the opiate antagonist nalmefene led to the hypothesis that increased opioidergic neurotransmission/neuromodulation in the central nervous system (CNS) contributes to the pathophysiology of cholestasis. The state of antinociception, which is stereospecifically reversed by naloxone, documented in rats with cholestasis from bile duct resection supports this hypothesis. To further study the opioid system in this animal model of cholestasis, we studied the release of endogenous opioid peptides into the extracellular fluid of the dorso-lateral striatum by the technique of in-vivo microdialysis. Total opioid peptide concentration in the dialysate was measured by a solid phase radioimmunoassay with an antibody directed against the N-terminus of the Tyr-Gly-Gly-Phe-X amino acid sequence after acetylation. Basal total opioid peptide release was significantly higher after surgery in both sham resected and bile duct resected animals. However, basal (unstimulated) total opioid peptide release in the striatum of rats was not altered by cholestasis. It is inferred that the opioidergic abnormalities of cholestasis are not associated with an appreciable increase in the release of endogenous opioids into the extracellular fluid of the striatum. Abnormal processing of specific opioid peptides in cholestasis however, cannot be excluded.
Acetylation↗
Cocaine impairs maternal nest building in pregnant rats.
The present study investigated the onset of maternal nest building in pregnant Fischer rats following chronic repeated cocaine administration. Pregnant Fischer rats were injected with saline or cocaine, 15 mg/kg, three times daily at 1-h intervals for 10 days starting on gestation day 8. Cocaine-exposed females incorporated less material into their nests and built fewer fully completed circular nests than control animals. The overall quality of the nest in cocaine exposed dams was significantly lower than that of control animals. Furthermore, cocaine exposed dams gained less weight than control females. However, no difference in number of pups, weight, or length of pups was observed between groups. Thus, it seems that cocaine disrupts the interest and skill in nest building of pregnant rats.
Animals↗
Behavioral stereotypies induced by "binge' cocaine administration are independent of drug-induced increases in corticosterone levels.
Cocaine administration causes dramatic stereotypic behavior and elevation of circulating corticosterone levels in rodents. The present study tested the possible role of increased corticosterone in mediating stereotypic behavior caused by "binge' pattern cocaine administration. Animals were administered saline or cocaine intraperitoneally for 3 days, with or without pretreatment with a D1 (SCH 23390, 2 mg/kg) or D2 (sulpiride, 50 mg/kg) dopamine receptor antagonist. Three days of cocaine "binges' significantly increased corticosterone levels in vehicle pretreated rats (P < 0.01). Both SCH 23390 and sulpiride pretreatment daily significantly attenuated this increase (P < 0.01). Cocaine administration caused stereotypic behaviors in vehicle pretreatment rats (P < 0.01). These behavioral responses were blocked by the D1 dopamine receptor antagonist SCH 23390, but not by the D2 antagonist sulpiride. These findings reaffirm the dominant role of the D1 receptor in mediating behavioral stereotypy caused by elevations of extracellular dopamine in the synaptic cleft. The fact that the dose of sulpiride used in these studies prevented the elevation of plasma corticosterone caused by cocaine, without blocking the stereotypy caused by cocaine, indicates that this stereotypic behavior does not require drug-induced elevation in circulating levels of corticosterone.
Animals↗