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PubMed1999

Correlation between Generated Shear Stress and Generated Permittivity for the Electrorheological Response of Colloidal Silica Suspensions.

Electrorheological response was experimentally studied by the use of silicone oil suspensions containing submicrometer-sized and supermicrometer-sized silica particles with different amounts of adsorbed water. The simultaneous measurements of dielectric permittivity and shear stress of the suspensions were carried out after the application of alternating current voltage under steady shear in ranges of shear rate (150-1400 s(-1)), electric field strength (0-4 kV/mm), its frequency (30-1000 Hz), and particle volume fraction (0.1-0.3). For the particles with small amounts of adsorbed water, steady shear stress was attained within several minutes after the application of electric field. The steady-state data for both the particles at each electric field strength showed that the shear stress generated by the application of electric field, Deltatau, varied correlatively with the generated permittivity, Deltaepsilon(r) (= epsilon(r) - epsilon(r,oil)), where epsilon(r) and epsilon(r,oil) are the permittivities of the suspension and the silicon oil, respectively. Under a wide variety of experimental conditions, the steady-state data for both the particle sizes could be correlated with a simple relationship, Deltatau ~ (Deltaepsilon(r)E)(2), where E is electric field strength. For the particles with large amounts of adsorbed water, steady state was not attained, and the evolutions of shear stress and permittivity of the suspensions were measured after the application of electric field. Remarkably, the transient values of Deltatau varied with (Deltaepsilon(r)E)(2) and fell along the same correlation line as the steady-state data. Copyright 1999 Academic Press.

Journal Article↗
PubMed1996

Ciliary neurotrophic factor enhances the rate of oligodendrocyte generation.

Although ciliary neurotrophic factor (CNTF) is a potent survival factor for many types of neurons and glial cells in vitro, there is currently no evidence that it participates in normal development. Here we show that CNTF greatly enhances the rate of oligodendrocyte generation. Proliferation of oligodendrocyte precursor cells purified from rodent optic nerves and cultured in platelet-derived growth factor-containing medium is significantly increased by CNTF. Similarly, the number of proliferating oligodendrocyte precursor cells in developing optic nerves of transgenic mice lacking CNTF is decreased by up to threefold and the number of oligodendrocytes is transiently decreased; proliferation is restored to normal by the delivery of exogenous CNTF into the developing optic nerve. Both oligodendrocyte number and myelination ultimately attain wild-type values in CNTF-deficient adult mice, indicating that CNTF is not necessary for either oligodendrocyte differentiation or myelination, although it normally accelerates oligodendrocyte development by enhancing the proliferation of oligodendrocyte precursor cells.

Animals↗
PubMed1982

Pseudo-inflammatory chorioretinal degeneration of the posterior pole. Study of a family of four affected generations, associated with tapetoretinal amaurosis (Leber) in the fifth generation.

A description is given of a large family in which a particular form of posterior pole dystrophy occurs, but in which (except for one 21-year-old patient) no symptoms occur before the age of forty. Although it is of dominant transmission through four generations with a high degree of penetrance, slight forms do occur. The disease evolves in 2-4 years and in serious cases there is total loss of the central vision. Peripheral vision is conserved, so that affected patients are never entirely disabled and dependent. Early or slight cases may be precociously detected by angiography or sensitive functional tests (EOG, VER, and perhaps colour vision). The rapid evolution is due to exudative or haemorrhagic phenomena. This observation corresponds with the description of the disease individualized by Sorsby (pseudo-inflammatory posterior pole dystrophy) and is related to colloid degeneration. In the fifth generation a case of Leber's congenital amaurosis occurs, which is difficult to relate to the late posterior pole dystrophy.

Adolescent↗
PubMed1993

Multiple brain systems generating the rat auditory evoked potential. II. Dissociation of auditory cortex and non-lemniscal generator systems.

This study addressed the issue of multiple parallel auditory processing systems and their relationship to the skull-recorded auditory evoked potentials (AEPs) in the unanesthetized, unrestrained rat. In the preceding paper (Brain Res., 602 (1993) 240-250) it has been shown that auditory cortex activity does not contribute significantly to the vertex maximal AEPs recorded from the dorsal skull of the rat. In the present study, mapping of the AEP skull distribution revealed two sets of components: one set maximal at the dorsal skull vertex, and another set at the lateral skull), but not the early (P7-P11, N15) lateral skull components generated in auditory cortex. Bilateral auditory cortex ablation eliminated the lateral skull maximal AEP components, but not the dorsal skull maximal components. These findings support extensive parallel processing of auditory inputs (reflected by the dorsal AEPs) in the absence of primary auditory cortex. Ablation of primary auditory cortex did result in a modulation of the dorsal skull AEPs, indicative of an interaction between the geniculocortical system and the parallel system which generates the dorsal AEPs.

Anesthesia↗
PubMed2001

Use of porous glass and silica gel as support media of a surface compound for generation of analytes in gaseous standard mixtures. New method for the determination of the amount of analyte generated.

The paper presents a new method for the determination of a volatile component of a gaseous standard mixture obtained by thermal decomposition of a suitable surface compound. The amount of the analyte generated (under given conditions of thermal decomposition) per unit of mass of the chemically modified material has been determined exclusively on the basis of measuring generation time. Therefore, the total error of the determination of the amount of a standard compound depends solely on the respective errors of weighing the material and measuring its decomposition time (both being direct measurements). This new method permits obtaining a few measuring points on the basis of a single sample of the material with chemically modified surface.

Chromatography, Gas↗
PubMed1997

Minilibraries constructed from cDNA generated by arbitrarily primed RT-PCR: an alternative to normalized libraries for the generation of ESTs from nanogram quantities of mRNA.

The generation of expressed sequenced tags (ESTs) depends on the arbitrary selection of individual cDNA clones from libraries. The efficiency of this process reflects the clonal structure of the library used and can be significantly increased using size selected, directional, normalized cDNA libraries. This strategy, however, is not readily applicable when mRNA is limiting, as is the case in the study of complex microorganisms such as parasites, fetal tissues or tumor biopsies. We show here that the construction and systematic sequencing of minilibraries of cDNAs produced by arbitrarily primed PCR provides an alternative means of efficiently generating ESTs in situations where only nanogram quantities of RNA are available. This methodology greatly compensates for unequal message abundance, avoids the need for complex library construction, is equally applicable to the analysis of abundant or rare biological material and is ideally suited to multicenter programmes.

Animals↗
PubMedDate not supplied

Microwave parallel library generation: comparison of a conventional- and microwave-generated substituted 4(5)-sulfanyl-1H-imidazole library.

A methodology for the microwave parallel synthesis of libraries is described. The procedure involves the use of an array of expandable reaction vessels, which can accommodate pressure buildup within the vessel due to heating without loss of volatile solvents or reagents. A demonstration 24-membered library of substituted 4(5)-sulfanyl-1H-imidazoles was generated by both conventional and microwave procedures, achieving a reduction from 12 h to 16 min in library generation time for the microwave approach.

Combinatorial Chemistry Techniques↗
PubMed2004

Designing libraries of first generation AB3 and AB2 self-assembling dendrons via the primary structure generated from combinations of (AB)(y)-AB3 and (AB)(y)-AB2 building blocks.

Structural analysis of three libraries of up to five generations of self-assembling dendrons based on AB(3), AB(2), and combinations of AB(3) with AB(2) building blocks (Percec et al. J. Am. Chem. Soc. 2001, 123, 1302) facilitated the discovery of several nanoscale lattices previously unknown for organic compounds (3-D Pm3n cubic, 3-D P4(2)/mnm tetragonal, and a crystallographically forbidden 12-fold symmetry liquid quasicrystal) and provided fundamental correlations between the molecular structure of the dendron and the shape and the diameter of the supramolecular dendrimers which, in these experiments, were limited to less than 75 A. That study concluded that alternative design principles should be elaborated for the assembly of supramolecular dendrimers of larger dimensions. Here we report design principles, synthesis and analysis of first and higher generations AB(3) and AB(2) self-assembling dendrons, based on various primary structures, and combinations of (AB)(y)-AB(3) and (AB)(y)-AB(2) (i.e., from nondendritic AB where y = 1 to 11 and dendritic AB(3) and AB(2)) building blocks that produced the largest structural (including six new lattices) and dimensional (100 to 217 A diameter) diversity of supramolecular dendrimers.

Journal Article↗
PubMed2000

The nature of support from adult sansei (third generation) children to older nisei (second generation) parents in Japanese Canadian families.

Given the growing ethnocultural diversity of Canada's aging population and the increased research focus on the role of the family in the social support of older persons, it is important to explore the ways in which adult ethnic minority children provide assistance to older parents within the context of the family. The current study contributes to research on intergenerational support systems in later life in Japanese Canadian families by examining the factors, particularly the cultural value of oya koh koh (filial obligation), affecting the nature of support from adult children to older parents. Using data gathered from interviews with 100 older nisei (second generation) parents and 100 adult sansei (third generation) children in British Columbia, the study focuses on the frequency, quality and provision of three types of support: emotional, service, and financial. Results of logistic regression analyses indicate that oya koh koh has a significant effect on children's provision of emotional support, but no effect on financial or service support. Parent's health and socioeconomic status are found to have significant effects on children's provision of financial and service support. Child's availability is also a major determinant of financial support. Further, ordinary least squares (OLS) regression analyses results suggest that oya koh koh has a significant effect on the quality of emotional support provided by children to their parents. Findings are discussed in terms of the North American Asian "ideal" family myth and directions for future research.

Journal Article↗
PubMed1989

Image generation and processing of generated images in the cerebral hemispheres.

Recent computational models describing the contribution of the cerebral hemispheres to visual imagery have suggested an exclusive capacity of the left hemisphere to generate multipart images. A brief review of relevant findings indicates that the evidence presented in support of this suggestion is not entirely compelling; this prompted a reexamination of this issue in a lateral tachistoscopic study on normal adults. Sixteen subjects participated in two experiments in which they had to decide whether or not a lowercase letter contained a segment extending above or below the main body of the letter. This decision was made directly on lowercase letters in one experiment (perceptual task) and on their generated images in the other experiment (imagery task). The quality of the letters (clear or blurred) and the retinal eccentricity of stimulus presentation (small or large) were orthogonally manipulated. The perceptual task yielded no main effect of visual field but a significant interaction of visual field and letter quality. By contrast, the imagery task resulted in a left visual-field superiority but no interaction involving the visual fields--a departure from predictions based on current models of visual imagery. In addition, the pattern of results in the imagery task corresponded to that obtained with blurred letters in the perceptual task, suggesting limitations in spatial resolution of visual images. Implications of these results for models of cerebral lateralization and visual imagery are discussed.

Adult↗
PubMed2001

Generation of adenoviruses encoding the herpes simplex virus vhs gene: a novel strategy to generate adenoviruses expressing genes toxic to producer cells.

Adenovirus vectors expressing suicide genes represent a promising approach for cancer gene therapy. We wanted to determine whether the virion host shutoff (vhs) gene of herpes simplex virus could be used as a suicide gene for gene therapy of glioblastomas. The vhs gene was cloned downstream of the glial fibrillary acidic protein promoter to direct tissue-specific expression, and recombinant adenoviruses were generated in 293 cells. Viruses, which contained the vhs gene but did not express it, could readily be isolated; however, we were unable to plaque purify viruses that expressed vhs protein. We constructed a derivative of 293 cells expressing an antisense RNA to the vhs gene and used them to generate adenovirus vectors that express vhs protein. These cells were used to complement vhs-expressing adenoviruses through three rounds of plaque purification. This approach could be generalized to produce adenovirus vectors expressing other toxic transgenes.

Adenoviridae↗
PubMed2003

In vitro co-stimulation with anti-CD28 synergizes with IL-12 in the generation of T cell immune responses to leukaemic cells; a strategy for ex-vivo generation of CTL for immunotherapy.

The existence of an immune based graft-versus-leukaemia (GvL) effect highlighted the prospect of managing relapsed leukaemias with T cell-based adoptive immunotherapy. Thus, various strategies have been explored for the in vitro expansion of acute myeloid leukaemia (AML)-specific T cells. In a popular approach, AML blasts have been genetically modified to express co-stimulatory molecules essential for effective T cell priming. One such tactic has been the modification of AML cells to express the B7/CD80 co-stimulatory molecule that binds to CD28 on T cells initiating events that culminate in enhanced cytokine production, proliferation and development of effector functions by T cells. The success of these strategies has been limited by difficulties in attaining sufficient transduction efficiencies and associated high levels of CD80 expression. We demonstrate that these problems can be circumvented by using anti-CD28 monoclonal antibody. Furthermore, we show that the synergistic relationship between CD80/CD28 pathway and interleukin 12 cytokine (IL-12), documented in the generation of cytotoxic T lymphocytes (CTL) for solid tumours, also applies to AML. CD28/IL-12 synergy facilitated the proliferation of allogeneic T cells in response to stimulation with primary AML blasts. The synergy also favoured generation of a Th1-type immune response, evidenced by gamma interferon (IFN-gamma) secretion and facilitated naive and memory T cell proliferation. Unlike some methods of in vitro T cell expansion, use of CD28/IL-12 synergy left T cells in the physiologically appropriate CD45RA-/CCR7- subsets known to be associated with immediate cytotoxic functions.

Acute Disease↗
PubMed2000

A comparison of the ERBE Erbotom ICC 200 generator and the Valleylab Force 2 electrosurgical generator in performing large loop excision of the transformation zone.

One drawback of the large loop excision of the transformation zone procedure (LLETZ) is the influence of electrical current on histological interpretation through thermal artefact. The ERBE Erbotom ICC 200 unit (Surgical Technology Group, Hampshire, England, UK) compared to other standard electrosurgical generators has the theoretical advantage that it automatically regulates the output according to "demand" and therefore uses the minimum amount of power to complete the procedure, which thus should cause the minimum thermal artefact. Fifty females requiring the loop procedure were randomized to treatment with either the ERBE machine or the standard Valleylab electrosurgical generator. Although there were no significant differences in the diathermy artefact measurements between the two groups, the Valleylab unit was associated with more mucosal destruction or removal (P = 0.027) and an increased number of specimens uninterpretable due to diathermy artefact. The new technology associated with the ERBE unit had clear benefits for the clinician in terms of the time of the procedure and technical problems.

Journal Article↗
PubMed1990

The discrimination of patient-generated and randomly generated MMPIs.

A discriminant analysis was applied to 34 randomly generated and 34 patient-generated Minnesota Multiphasic Personality Inventory (MMPI) profiles. The discriminant was able to differentiate the two sets at greater than 97% accuracy. A cross validation based on derived unstandardized canonical discriminant functions was carried out on an additional 10 random and 10 patient MMPIs. It attained 95% accuracy. Eight experienced clinical psychologists attained less than 70% accuracy--six of the eight did no better than chance. The importance of including actuarial data in validity judgments was discussed.

Adult↗
PubMed2001

Effects of first generation E1E3-deleted and second generation E1E3E4-deleted/modified adenovirus vectors on human endothelial cell death.

Adenoviral vectors are promising tools for pulmonary vascular gene transfer. In first generation vectors, the viral E4 region is preserved (E4+ Ad), but E4 is deleted in second generation vectors (E4- Ad). These vectors were compared for their toxicity in human endothelial cells in terms of apoptosis and necrosis. Infection with E4+ Ad vectors reduced whereas E4- Ad vectors enhanced apoptosis under normal culture conditions. Furthermore, E4+ Ad protected against apoptosis induced by growth factor deprivation, while E4- Ad enhanced apoptosis triggered by ceramide. Ad vectors containing different E4 open reading frames, alone or in different combinations, showed similar effects to E4- Ad, leaving the viral genes that might be responsible for reducing apoptosis unidentified at the present time. As previously observed with E4+ Ad devoid of transgene, E4+ Ad carrying beta-galactosidase or green fluorescent protein under the control of either the RSV or CMV promoter also reduced apoptosis triggered by growth factor deprivation. In contrast, E4+ Ad containing a CFTR expression cassette did not reduce apoptosis, and E4- Ad with CFFR showed increased toxicity. We conclude that Ad vectors may have important effects on the control of apoptosis in transfected cells, depending on the residual expression of viral genes. This effect can be complicated by the action of transgene expression on cell survival.

Adenoviridae↗
PubMed2003

Generating evidence to inform policy and practice: the example of the second generation "atypical" antipsychotics.

The introduction of the second generation "atypical" antipsychotics has been heralded as a major advance in the treatment of schizophrenia and other psychotic disorders. Systematic reviews have revealed only modest advantages over conventional antipsychotics and uncertainty about long-term efficacy and safety, yet the second generation antipsychotic drugs have been widely accepted into clinical practice. Although the existing evidence of the benefits and harms of atypical antipsychotics can facilitate decision making about individual patients, the randomized evidence remains inadequate to make valid and fully evidence-based policy statements such as clinical practice guidelines that are designed to apply to groups of patients. Further large randomized trials are needed, but these require patients and clinicians to be in equipoise, or substantially uncertain, about alternative therapies. Premature clinical practice guidelines or expert opinion can lead to changes in clinical practice that make it difficult or impossible to conduct the required trials and are therefore a disservice to patients.

Antipsychotic Agents↗
PubMed2002

AGTR2 mutations in X-linked mental retardation.

Two angiotensin II (Ang II)-specific receptors, AGTR1 and AGTR2, are expressed in the mammalian brain. Ang II actions on blood pressure regulation, water electrolyte balance, and hormone secretion are primarily mediated by AGTR1. The function of AGTR2 remains unclear. Here, we show that expression of the AGTR2 gene was absent in a female patient with mental retardation (MR) who had a balanced X;7 chromosomal translocation. Additionally, 8 of 590 unrelated male patients with MR were found to have sequence changes in the AGTR2 gene, including one frameshift and three missense mutations. These findings indicate a role for AGTR2 in brain development and cognitive function.

Amino Acid Sequence↗