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Biomedical subjects

L Hodges

Publications and source records attributed to L Hodges.

17 recordsLinked to original sources

Virtual reality: using the virtual world to improve quality of life in the real world.

Mental health professionals are increasingly integrating advances in technology to improve the health of those in their care (American Psychological Association, 2000). The authors describe the immersive properties of virtual reality and its importance for clinical purposes and then review the literature describing current clinical applications of virtual reality (VR) and research documenting its efficacy. Virtual reality has been used in the treatment of specific phobias, posttraumatic stress disorder, eating disorders, and pain management.

Feeding and Eating Disorders↗

A controlled study of virtual reality exposure therapy for the fear of flying.

Fear of flying (FOF) affects an estimated 10-25% of the population. Patients with FOF (N = 49) were randomly assigned to virtual reality exposure (VRE) therapy, standard exposure (SE) therapy, or a wait-list (WL) control. Treatment consisted of 8 sessions over 6 weeks, with 4 sessions of anxiety management training followed by either exposure to a virtual airplane (VRE) or exposure to an actual airplane at the airport (SE). A posttreatment flight on a commercial airline measured participants' willingness to fly and anxiety during flight immediately after treatment. The results indicated that VRE and SE were both superior to WL, with no differences between VRE and SE. The gains observed in treatment were maintained at a 6-month follow up. By 6 months posttreatment, 93% of VRE participants and 93% of SE participants had flown. VRE therapy and SE therapy for treatment of FOF were unequivocally supported in this controlled study.

Adult↗

Virtual reality exposure therapy for PTSD Vietnam Veterans: a case study.

Virtual reality (VR) integrates real-time computer graphics, body tracking devices, visual displays, and other sensory input devices to immerse a participant in a computer-generated virtual environment that changes in a natural way with head and body motion. VR exposure (VRE) is proposed as an alternative to typical imaginal exposure treatment for Vietnam combat veterans with posttraumatic stress disorder (PTSD). This report presents the results of the first Vietnam combat veteran with PTSD to have been treated with VRE. The patient was exposed to two virtual environments, a virtual Huey helicopter flying over a virtual Vietnam and a clearing surrounded by jungle. The patient experienced a 34% decrease on clinician-rated PTSD and a 45% decrease on self-rated PTSD. Treatment gains were maintained at 6-month follow-up.

Humans↗

Species, interindividual, and tissue specificity in endocrine signaling.

The activity of endocrine-active agents exhibits specificity at many levels. Differential responsiveness to these agents has been observed between different species and extends to interindividual differences within a species and between different tissues as well. In cases where they have been identified, the biologic and molecular mechanisms underlying this specificity are quite diverse. Determinants of species specificity include differences that exist in receptor binding, gene transcription, and cellular responses to endocrine-active compounds between species. Interindividual differences in responsiveness may be determined at the level of genetic polymorphisms in hormone-metabolizing enzymes, hormone receptors, and in those genes that are transactivated by these receptors, as well as during changing windows of susceptibility that occur as a function of age, such as prenatal and postmenopausal exposures. Extrinsic factors such as diet can also impact individual susceptibility to endocrine-active agents. Tissue-specific determinants of susceptibility are well documented, but little is known regarding the mechanisms underlying these different responses. Differences in the expression of accessory proteins for steroid hormone receptors and different patterns of receptor expression, estrogen receptor alpha and estrogen receptor beta; for example, may contribute to tissue specificity, as may differences in the pattern of expression of other genes such as hormone-metabolizing enzymes. The use of animal model systems and development of appropriate mathematical models has the potential to yield additional valuable information for elucidating the role of these determinants of specificity at low-dose exposures and for improved risk assessments for the adverse health effects of endocrine-active compounds.

Age Factors↗

Virtual reality exposure therapy.

It has been proposed that virtual reality (VR) exposure may be an alternative to standard in vivo exposure. Virtual reality integrates real-time computer graphics, body tracking devices, visual displays, and other sensory input devices to immerse a participant in a computer-generated virtual environment. Virtual reality exposure is potentially an efficient and cost-effective treatment of anxiety disorders. VR exposure therapy reduced the fear of heights in the first controlled study of virtual reality in treatment of a psychiatric disorder. A case study supported the efficacy of VR exposure therapy for the fear of flying. The potential for virtual reality exposure treatment for these and other disorders is explored, and therapeutic issues surrounding the delivery of VR exposure are discussed.

Fear↗

ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson's disease.

(-)-Trans 9,10-hydroxy-2-propyl-4,5,5a,6,7,11b-hexahydro-3-thia-5- azacyclopent-1-ena[c]phenanthrene hydrochloride (A-86929) is a potent and selective full agonist at the dopamine (DA) D1-like receptor. Judging by its binding affinities to the D1 and D2 classes of receptors, the compound is approximately 20-fold D1 receptor-selective, whereas relative potencies based on functional in vitro assays indicate that A-86929 is greater than 400-fold D1-selective. A-86929 has moderate to weak (Ki > 1 microM) affinity at other monoaminergic and peptidergic receptors, at ion channels and at monoamine uptake sites. The catechol of A-86929 was bis-acetylated to produce the prodrug, (-)-trans 9,10-acetoxy-2-propyl-4,5,5a,6,7,11-b-hexahydro-3-thia- 5-azacyclopent-1-ena[c]phenanthrene hydrochloride (ABT-431), which is more chemically stable yet is rapidly converted to the parent compound with a half-life of less than 1 min in plasma. Both A-86929 and ABT-431 produced contralateral rotation in rats bearing unilateral 6-hydroxydopamine lesions, with ED50 values of 0.24 mumol/kg s.c. and 0.54 mumol/kg s.c., respectively. A-86929 and ABT-431 improved behavioral disability scores and increased locomotor activity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmoset model of Parkinson's disease in a dose-dependent manner (the minimum effective dose was 0.10 mumol/kg s.c.). When administered three times daily for 30 consecutive days to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmosets, A-86929 significantly improved disability scores throughout the duration of the study. Current Parkinson's disease therapy includes L-dopa, which stimulates both classes of DA receptors by virtue of its conversion to DA in vivo, and direct-acting D2-selective agonists. Stimulation of the D2 receptor, which is associated with all current DA agonist-based therapies, may contribute to their dose-limiting side effects. An agent such as A-86929 (or its prodrug ABT-431), which selectively stimulates the D1 receptor, may represent a novel mechanism for Parkinson's disease therapy with the potential for an improved side-effect profile and, consequently, improved patient compliance.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

CD 45 gating correlates with bone marrow differential.

In this study we assess a flow cytometric gating method and its correlation with a concurrent manual bone marrow differential in abnormal marrows. Like normal bone marrow cells, leukemic blasts fall into discrete areas when a cytogram of CD 45 expression and Right Angle Light Scatter is plotted in Log scale. We studied 50 specimens with a suspected diagnosis of leukemia. Gates were set on the eight discrete clusters typically found in normal bone marrow. We employed these gates to determine the differential of the abnormal bone marrows. Our results show a high correlation between the flow differential and the manual differential with the following r values: blasts 0.875; promyelocytes 0.914; myeloid precursors 0.879; neutrophils 0.776; lymphocytes 0.707; monocytes 0.913; and erythroid precursors 0.873. In addition some leukemic infiltrates appear to produce a characteristic pattern with the CD 45 vs. RALS cytogram. In this study, there is a total of 6 cases (3 false positives and 3 false negatives) where the flow differential does not render the same diagnosis as the manual differential, and 4 cases in which there is evidence of marked peripheral contamination leading to disagreement between the two methods. This method provides a relatively easy and powerful tool which can be applied to all bone marrow specimens that undergo flow cytometric analysis. It can greatly enhance the identification and lineage assessment of leukemic blasts in the bone marrow. The correlation with a manual differential is high, and this gating method may provide an inexpensive and easy means of obtaining an automated bone marrow differential.

Adolescent↗

Fadrozole: a potent and specific inhibitor of aromatase in the zebra finch brain.

Aromatase and 5 beta-reductase activity are expressed at high levels in the zebra finch brain, especially in the telencephalon. Aromatization of androgens to estrogens is thought to be a critical step in the organization and activation of avian sexual behaviors. In contrast, 5 beta-reductase is thought to be an inactivating enzyme, one that catalyzes the conversion of androgens to biologically inactive metabolites. To address the importance of aromatase activity in this system, it is necessary to find an effective and selective aromatase inhibitor, one that has little or no effect on other androgen-metabolizing enzymes. The potency and specificity of fadrozole hydrochloride as an aromatase inhibitor was tested in zebra finch telencephalon. The compound was tested in vitro in primary dissociated cell cultures made from hatching telencephalon and compared to a commonly used inhibitor, 1,4,6-androstatriene-3,17-dione (ATD). Untreated, these cultures express extremely high levels of aromatase and 5 beta-reductase activity and therefore allow sensitive measurement of the effectiveness of inhibitors. Aromatase activity was also measured in homogenates of adult telencephalon following in vivo fadrozole injection. Finally, aromatase and 5 beta-reductase activity were quantified in zebra finch telencephalon following similar intramuscular injections in 4- to 6-day-old birds. In all three cases, fadrozole was highly effective in reducing aromatase activity. Fadrozole increased 5 beta-reductase activity, presumably due to an increase in available substrate, but had no inhibitory effect on the enzyme. ATD was less effective in inhibiting aromatase, and it also inhibited 5 beta-reductase activity at high concentrations.

Androstatrienes↗

In vitro transcription from baculovirus late gene promoters: accurate mRNA initiation by nuclear extracts prepared from infected Spodoptera frugiperda cells.

Extracts prepared from nuclei of Autographa californica nuclear polyhedrosis virus-infected Spodoptera frugiperda cells were shown to support in vitro transcription from baculovirus late gene promoters. In vitro transcription was optimized for the late promoter of the 39K gene. The Mg2+ concentration was critical; concentrations higher than 1 to 2 mM did not support late transcription. Additional conditions included template (40 micrograms/ml), extract (2.5 mg/ml), and incubation time (25 min). Using a combination of runoff assays and high-resolution primer extension analyses, this system was shown to accurately initiate transcription from a variety of baculovirus late gene promoters, including those from the 39K and p39/capsid late genes and the hyperexpressed p10 and polyhedrin very late genes. In vitro transcription from the 39K late promoter was resistant to high concentrations of both alpha-amanitin (100 micrograms/ml) and tagetitoxin (4,000 U/ml), suggesting that neither RNA polymerase II nor III is responsible for the transcription of baculovirus late genes.

Animals↗

A nuclear localization signal and the C-terminal omega sequence in the Agrobacterium tumefaciens VirD2 endonuclease are important for tumor formation.

The T-DNA portion of the Agrobacterium tumefaciens tumor-inducing (Ti) plasmid integrates into plant nuclear DNA. Direct repeats define the T-DNA ends; transfer begins when the VirD2 endonuclease produces a site-specific nick in the right-hand border repeat and attaches to the 5' end of the nicked strand. Subsequent events generate linear single-stranded VirD2-bound DNA molecules that include the entire T-DNA (T-strands). VirD2 protein contains a nuclear localization signal (NLS) near the C terminus and may direct bound T-strands to plant nuclei. We constructed mutations in virD2 and showed that the NLS was important for tumorigenesis, although T-strand production occurred normally in its absence. A tobacco etch virus NLS, substituted for the VirD2 NLS, restored tumor-inducing activity. Amino acids (the omega sequence) at the C terminus of VirD2, outside the NLS and the endonuclease domain, contributed significantly to tumorigenesis, suggesting that VirD2 may serve a third important function in T-DNA transfer.

Agrobacterium tumefaciens↗

Agrobacterium tumefaciens transfers extremely long T-DNAs by a unidirectional mechanism.

During crown gall tumorigenesis, part of the Agrobacterium tumefaciens tumor-inducing (Ti) plasmid, the T-DNA, integrates into plant DNA. Direct repeats define the left and right ends of the T-DNA, but tumorigenesis requires only the right-hand repeat. Virulence (vir) genes act in trans to mobilize the T-DNA into plant cells. Transfer of T-DNA begins when the VirD endonuclease cleaves within the right-hand border repeat. Although the T-DNA right-border repeat promotes T-DNA transmission best in its normal orientation, an inverted right border exhibits reduced but significant activity. Two models may account for this diminished tumorigenesis. The right border may function bidirectionally, with strong activity only in its wild-type orientation, or it may promote T-DNA transfer in a unidirectional manner such that, with an inverted right border, transfer proceeds around the entire Ti plasmid before reaching the T-DNA. To determine whether a substantial portion of the Ti plasmid is transferred to plant cells, as predicted by the unidirectional-transfer hypothesis, we examined T-DNAs in tumors induced by strains containing a Ti plasmid with a right border inverted with respect to the T-DNA oncogenes. These tumors contained extremely long T-DNAs corresponding to most or all of the Ti plasmid. To test whether the right border can function bidirectionally, we inserted T-DNAs with either a properly oriented or an inverted right border into a specific site in the A. tumefaciens chromosome. A border situated to transfer the oncogenes first directed T-DNA transfer even from the bacterial chromosome, whereas a border in the opposite (inverted) orientation did not transfer the oncogenes to plant cells. Our results indicate that the right-border repeat functions in a unidirectional manner.

Agrobacterium tumefaciens↗

Modification of glycogen deposition by priming glucose loads: the second-meal phenomenon.

Glucose priming modifies tolerance and oxidation of subsequent loads. To assess effects in glycogenesis, rats were given a D-[U14C]-glucose load, either alone or preceded by one or two unlabeled hourly doses. The incorporation of 14C into total liver glycogen was 8.6 +/- 0.4% of the glucose dose and was little changed by priming loads. Total liver glycogen was 169 +/- 10 mg after one load and 276 +/- 12 mg after two; after three it fell to 243 +/- 20 mg. In muscle, net incorporation of 14C was 9.6 +/- 0.6% of the first but fell to 6.9 +/- 0.4% of the third glucose 14C dose/100 g. Muscle glycogen concentration rose at a decremental rate with priming. Net incorporation of glucose 14C into hepatic glycogen remains constant after repeated loads even after storage is reduced. In keeping with the reported peripheral resistance to glucose uptake in the second-meal phenomenon, repeated loading is associated with reduction of 14C-glucose incorporation into muscle glycogen.

Animals↗

Potentiation of 14C-glucose oxidation by priming glucose loads: effect of starvation.

The mechanism of the Staub-Traugott effect or facilitated glucose disposal after successive glucose loads has remained elusive. In earlier publications, we have shown it can be independent of circulating hormone and free fatty acid levels. We have also proposed that it might partially depend on the rapid induction of glycolytic pathways, which are known to be depressed by prolonged fast. Mature rats were given 1.75 gm/kg glucose doses intravenously at 60-minute intervals. Respiratory CO2 was collected at 15-minute intervals over a 120-minute period following administration of the carrier glucose plus 6 microCi/100 gm rat weight of 14C-D-glucose, given either as the first, second, or third challenge. In rats fasted 14 hours there was potentiation of labeled CO2 recovered after each successive load. After three days of starvation, both relative 14C-glucose oxidation to 14CO2 as well as absolute 14CO2 increments after each load were lower. The changes in relative oxidation of an intravenous glucose load might partly account for the facilitated disposal of blood glucose seen in the second and third hours in overnight-fasted rats (Staub-Traugott effect). However, although rats fasted for three days had suppressed the Staub effect, the increments in oxidation were attenuated but still present, suggesting that alterations of other pathways must participate in the disappearance of this effect after fasting.

Animals↗

The appointment book.

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Appointments and Schedules↗

Virtual reality exposure therapy in the treatment of fear of flying: a case report.

The efficacy of virtual reality (VR) exposure therapy was examined for the fear of flying. Virtual reality exposure involved six sessions of graded exposure to flying in a virtual airplane. The specific contribution of anxiety management techniques (AMT) and the VR exposure was examined in a single case design. The subject was a 42-year-old female with a debilitating fear and avoidance of flying. All self-report measures of the fear and avoidance of flying decreased following AMT and decreased still further following VR exposure. A planned post-treatment flight was completed with anxiety measures indicating comfortable flight. The implications of this new medium for exposure therapy are discussed.

Adaptation, Psychological↗