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D Y Ho

Publications and source records attributed to D Y Ho.

At least 19 recordsLinked to original sources
PubMed1996

Overexpression of Bcl-2 with herpes simplex virus vectors protects CNS neurons against neurological insults in vitro and in vivo.

Previous studies have demonstrated that overexpression of the proto-oncogene bcl-2 can protect neuron and neuron-like cell lines from growth factor deprivation, calcium ionophores, glutamate excitotoxicity, hypoglycemia, free radicals, and lipid peroxidation. To determine whether Bcl-2 exhibits a similar protective effect in CNS neurons, we generated defective herpes simplex virus (HSV) vectors capable of overexpressing Bcl-2 in primary cultures and in the intact brain. Infection of hippocampal cultures with Bcl-2 vectors enhanced neuron survivorship after exposure to adriamycin, a potent oxygen radical generator. Furthermore, dichlorofluorescein measurements indicated that there was a significant reduction in the accumulation of oxygen radicals associated with this insult. Bcl-2 vectors also enhanced survival in cultured neurons after exposure to glutamate and hypoglycemia. Most significantly, the in vivo delivery of the vector protected neurons against adriamycin toxicity in the dorsal horn of the dentate gyrus and focal ischemia in the striatum.

Analysis of Variance↗
PubMed1996

Energy and glutamate dependency of 3-Nitropropionic acid neurotoxicity in culture.

3-Nitropropionic acid (3-NP) irreversibly inhibits the activity of the mitochondrial enzyme succinate dehydrogenase, leading to selective striatal lesions when administered in vivo. We studied the effects of 3-NP on dissociated cultures of neurons and glia with the following findings: (a) 3-NP killed cultured striatal neurons with a median lethal dose of 2.5 mM after 20 h of incubation in 20.0 mM glucose medium. Despite its selective toxicity in vivo, cultured striatal, hippocampal, septal, and hypothalamic neurons were similarly sensitive to 3-NP incubation. (b) 3-NP's effects were remarkably energy substrate dependent, with the median lethal dose dropping over an order of magnitude when glucose concentrations were lowered to 3.0 mM, a condition that was itself nontoxic. Cultures exposed to 3-NP had a far greater sensitivity to energy availability than those exposed to glutamate. (c) Recent work suggests that 3-NP toxicity may be partially mediated by excitotoxins. Our experiments show that neither kynurenic acid, a nonspecific glutamate receptor antagonist, nor the NMDA-receptor antagonist, DL-2-amino-7-phosphonoheptanoic acid, either in combination or alone, reduced 3-NP toxicity in striatal cultures. However, the noncompetitive NMDA antagonist MK-801 did attenuate 3-NP toxicity.

Animals↗
PubMed1996

Overexpression of the glucose transporter gene with a herpes simplex viral vector protects striatal neurons against stroke.

Herpes simplex virus vectors bearing a glucose transporter (GT) gene and a marker gene were found to protect neurons against a 1-h focal ischemic insult. Rats receiving the GT vector v alpha22beta gal alpha4GT exhibited a 67.4 +/- 35.3% survival of virally targeted neurons in the ischemic hemisphere compared with the contralateral control (n = 7), whereas rats receiving a control vector exhibited only 32.8 +/- 17.9% survival (n = 9). This significant improvement in survival (105%, p=0.022) suggests that energy failure is an important contributor to the neuropathology of ischemic damage in the striatum, and that it can be alleviated by gene transfer. This is the first demonstration of protection against ischemic cerebral injury by the direct transfer of GT genes to neurons.

Animals↗
PubMed1995

Herpes simplex virus vectors overexpressing the glucose transporter gene protect against seizure-induced neuron loss.

We have generated herpes simplex virus (HSV) vectors vIE1GT and v alpha 4GT bearing the GLUT-1 isoform of the rat brain glucose transporter (GT) under the control of the human cytomegalovirus ie1 and HSV alpha 4 promoters, respectively. We previously reported that such vectors enhance glucose uptake in hippocampal cultures and the hippocampus. In this study we demonstrate that such vectors can maintain neuronal metabolism and reduce the extent of neuron loss in cultures after a period of hypoglycemia. Microinfusion of GT vectors into the rat hippocampus also reduces kainic acid-induced seizure damage in the CA3 cell field. Furthermore, delivery of the vector even after onset of the seizure is protective, suggesting that HSV-mediated gene transfer for neuroprotection need not be carried out in anticipation of neurologic crises. Using the bicistronic vector v alpha 22 beta gal alpha 4GT, which coexpresses both GT and the Escherichia coli lacZ marker gene, we further demonstrate an inverse correlation between the extent of vector expression in the dentate and the amount of CA3 damage resulting from the simultaneous delivery of kainic acid.

Animals↗
PubMed1995

Multiple vectors effectively achieve gene transfer in a murine cardiac transplantation model. Immunosuppression with TGF-beta 1 or vIL-10.

The application of gene transfer techniques to organ transplantation offers the potential for modulation of immunity directly within an allograft without systemic side effects. Expression vectors and promoter elements are important determinants of gene transfer and expression. In this study, various vectors (naked plasmid DNA, retroviral vector, herpes simplex viral vector, and adenoviral vector) with various promoters (RSV-LTR, SV40, MuLV-LTR, HCMVie1) were directly compared to demonstrate the successful gene transfer and expression of beta-galactosidase in murine myoblasts in vitro and within murine heterotopic, nonvascularized cardiac isografts or allografts in vivo. Expression of transferred genes was not toxic to cells and strength of expression varied according to the type of vector. Plasmid DNA was expressed in myocytes, retroviral vector was expressed in the graft infiltrating cells, and herpes simplex and adenoviral vectors were expressed in both myocytes and graft-infiltrating cells. Preliminary studies evaluated the ability of these vectors to deliver immunologically important signals. Allografts injected with pSVTGF-beta 1, a plasmid-encoding transforming growth factor beta 1 (TGF-beta 1) under the control of the SV40 promoter, showed significant prolongation of graft survival of 26.3 +/- 2.5 days compared with 12.6 +/- 1.1 days for untreated allografts, and 12.5 +/- 1.5 days for the allografts injected with control plasmid (P < 0.05). Allografts injected with MFG-vIL-10, a retroviral vector encoding viral interleukin-10 under the control of the MuLV-LTR, showed prolongation of graft survival of 36.7 +/- 1.3 days versus 12.6 +/- 1.1 days for the untreated allograft, and 13.5 +/- 2.0 days for the allografts injected with control retroviral vector (P < 0.001). Both vectors were transcriptionally active in vivo and did not appear to have toxic effects. Gene therapy for transplantation can induce transient expression of immunologically relevant molecules within allografts that impede immune activation while avoiding the systemic toxicity of conventional immunosuppression.

Animals↗
PubMed1995

Herpes simplex virus vector system: analysis of its in vivo and in vitro cytopathic effects.

With its natural propensity to infect and establish life-long latency in neurons, herpes simplex virus type 1 (HSV-1) has been successfully employed by various laboratories as vectors for gene transfer into neurons. However, analysis of its cytopathic effects in vivo and in vitro has been limited. In this study, we examined the cytopathic effects of 2 HSV-1 alpha 4 mutants (ts756 and d120) on adult rat hippocampus and striatum and of d120 on hippocampal neurons in culture. We assessed damage by stringent counting of surviving neurons after infection and demonstrated that while neither ts756 nor d120 infection resulted in any gross anatomical or behavioral changes of the animals, ts756, but not d120, produced a significant amount of damage in the CA4 cell field and dentate gyrus of the hippocampus. Thus, since crude examination is insufficient to detect subtle but significant degrees of neuron loss, the cytopathic effects of HSV or any vector system must be carefully analyzed. Furthermore, we also observed that uninfected cell lysates damaged neurons, both in vivo and in vitro. This cytotoxicity occurred within the first 24 h post-inoculation and probably arose through the activation of glutamate receptors. For the preparation of HSV vectors, purification of the virus from soluble cellular components by a simple pelleting step can significantly decrease such acute toxicity.

Cell Count↗
PubMed1995

Defective herpes simplex virus vectors expressing the rat brain glucose transporter protect cultured neurons from necrotic insults.

Because neurons are postmitotic, they are irreplaceable once they succumb to necrotic insults such as hypoglycemia, ischemia, and seizure. A paucity of energy can exacerbate the toxicities of these insults; thus, a plausible route to protect neurons from necrotic injury would be to enhance their glucose uptake capability. We have demonstrated previously that defective herpes simplex virus (HSV) vectors overexpressing the rat brain glucose transporter (GT) gene (gt) can enhance glucose uptake in adult rat hippocampus and in hippocampal cultures. Furthermore, we have observed that such vectors can maintain neuronal metabolism during hypoglycemia and reduce kainic acid-induced seizure damage. In this study, we have developed bicistronic vectors that coexpressed gt and Escherichia coli lacZ as a reporter gene, which allows us to identify directly neurons that are infected with the vectors. Overexpression of GT from these vectors protected cultured hippocampal, spinal cord, and septal neurons against various necrotic insults, including hypoglycemia, glutamate, and 3-nitropropionic acid. Our observations demonstrate the feasibility of using HSV vectors to protect neurons from necrotic insults. Although this study has concentrated on the delivery of gt, other genes with therapeutic or protective capability might also be used.

Animals↗
PubMed1994

Filial piety, authoritarian moralism, and cognitive conservatism in Chinese societies.

In the present study, I examined the role of Confucian filial piety in relation to parental attitudes, the function of personality, and social cognition, using data assembled from 11 samples of adults and students in Hong Kong and Taiwan. Results showed that (a) filial attitudes tend to be moderately associated with parental attitudes and child training that emphasize obedience and indebtedness to one's parents, impulse control, and proper conduct; (b) people endorsing traditional filial and/or child-training attitudes tend to be poorer in verbal fluency, to adopt a passive, uncritical, and uncreative orientation toward learning, to hold fatalistic, superstitious, and stereotypic beliefs, and to be authoritarian, dogmatic, and conformist; and (c) parents' attitudes rooted in filial piety tend to result in high rigidity and low cognitive complexity in their children. The results support the contention that filial piety underlies both authoritarian moralism and cognitive conservatism.

Adolescent↗
PubMed1993

Altering central nervous system physiology with a defective herpes simplex virus vector expressing the glucose transporter gene.

Because of their postmitotic nature, neurons are difficult subjects for gene transfer. To circumvent this, we have used a defective herpes simplex virus vector to overexpress the rat brain glucose transporter (GT) gene under the control of the human cytomegalovirus ie1 promoter. This vector, designated vIE1GT, was propagated using a herpes simplex virus type 1 temperature-sensitive mutant, ts756. GT expressed from vIE1GT was readily immunoprecipitated from membrane fractions of vIE1GT-infected Vero cells. By using indirect double immunofluorescence techniques, vIE1GT was shown to be capable of enhancing GT expression in cultured hippocampal neurons and glia. Glucose transport in such vIE1GT-infected cultures was increased approximately 2-fold relative to controls. The efficacy of this system in vivo was then tested by microinjection of vIE1GT into adult rat hippocampus. When examined 2 days later, GT expression from vIE1GT was demonstrated in hippocampal neurons by in situ hybridization; a small but significant increase in glucose transport was detected in tissue immediately surrounding the injection site by 2-deoxy[14C]glucose uptake and autoradiography. Such injections did not cause marked cytopathology. Thus, this approach can be used to alter central nervous system physiology in vitro and in vivo.

Animals↗
PubMed1992

Neutralizing epitopes on herpes simplex virus-1-expressed rotavirus VP7 are dependent on coexpression of other rotavirus proteins.

We constructed a recombinant thymidine kinase-negative herpes simplex virus type 1 (HSV-1) that expressed the rotavirus major outer capsid glycoprotein, VP7. In the recombinant HSV-1, a promoter from the 5' noncoding region of the HSV-1 glycoprotein B locus regulated the expression of VP7 as a HSV-1 gamma 1 gene product. HSV-1-expressed VP7 resembled rotavirus-expressed VP7 in its SDS-PAGE mobility, high mannose-type glycosylation, disulfide bonding, perinuclear to cytoplasmic localization, intracellular retention, and reactivity with polyclonal antisera and nonneutralizing antibodies. Unlike rotavirus-expressed VP7, HSV-1-expressed VP7 lacked several neutralizing epitopes by immuno-histochemical staining and by ELISA. One neutralizing epitope identified on HSV-1-expressed VP7 by ELISA was masked by paraformaldehyde fixation of recombinant HSV-1- but not rotavirus-infected cells. Neutralizing epitopes were restored to HSV-1-expressed VP7 by coinfection of cells with the HSV-1 recombinant and a heterologous rotavirus that lack the neutralizing epitopes. The recovered neutralizing epitopes were detected on double-shelled rotavirus particles produced in the coinfected cells. This study indicates that the formation of several neutralizing epitopes on rotavirus VP7 requires interaction of VP7 with other rotavirus proteins. In addition, HSV-1 was a useful vector for studying the localization, processing, and antigenicity of an RNA virus glycoprotein.

Animals↗
PubMed1991

An investigation of the calendar calculation ability of a Chinese calendar savant.

A Chinese calendar savant was investigated on his exceptional proficiency in calendar calculation and his culture-specific talent of converting the Gregorian calendar to the Chinese calendar. Results did not support any one of the hypotheses of eidetic imagery, high-speed calculation, rote memorization, keying-off (anchoring) strategy, use of calendar regularities or monthly configuration as the only explanation proposed in earlier investigations. The savant's calculation ability is hypothesized to be brought about by his familiarity of the 14 calendar templates and the knowledge of matching the templates to every year. For dates that are beyond the 20th century, the calculation is by regressing the date to a corresponding year in the 20th century by additions or subtractions of 28 or 700 years with his accurate use of the simple operations in arithmetic.

Adult↗
PubMed1989

Community psychology in Hong Kong: past, present, and future.

The expansion of mental health services during the 1960s from a single remote mental hospital to centers and clinics in mainstream communities fostered the development of community psychology in Hong Kong. Few psychologists were initially involved in the local community mental health movement, but its momentum resulted in increasing numbers of practitioner psychologists working in community-based service settings. Community psychology in Hong Kong today consists primarily of service delivery, but also includes applied research, community organization/consultation, and community education. Despite having many parallels with the American situation, key concepts underpinning the practice of community psychology in the Territory possess their own character as a reflection of nuances in the local scene. Prospects for the continued development of community psychology in Hong Kong appear favorable. Of special relevance is the field's potential contribution to a better understanding of the psychological phenomena associated with the Territory's sociopolitical transformation in 1997.

Community Mental Health Services↗
PubMed1989

Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse.

During latent infection by herpes simplex virus (HSV), an abundant latency-associated transcript (LAT) that is antisense to a predominant viral alpha gene (ICP0) is found localized in the nucleus of sensory neurons. We disrupted both copies of the LAT gene in the HSV-1 genome by insertion of the Escherichia coli lacZ gene under LAT promoter control. The resulting recombinant virus, RH142, does not express any detectable LAT in either latently or productively infected cells, although beta-galactosidase expression is readily detectable in sensory neurons of latently infected mice. Expression was first detectable 3 days postinoculation and continued at approximately the same level for the entire experimental period (56 days). beta-Galactosidase expression was not detectable at any time during RH142 replication in Vero cells. Thus, the kinetics of expression and cell-type specificity of the LAT gene are distinct from other HSV-1 genes that are expressed during productive growth. When latently infected trigeminal ganglia were explanted, RH142 reactivated from latency with the kinetics and an efficiency indistinguishable from the parental wild-type virus. These studies argue against any possible antisense regulatory mechanism of LAT in the regulation of viral gene expression or any role of LAT-encoded protein during the establishment or maintenance of latency in the mouse.

Animals↗
PubMed1988

Beta-galactosidase as a marker in the peripheral and neural tissues of the herpes simplex virus-infected mouse.

We have inserted a modified Escherichia coli lacZ gene, placed under the control of herpes simplex virus alpha 4 or beta 8 regulatory signals, into the HSV-1 genome disrupting the viral thymidine kinase gene. Using beta-galactosidase as an in situ indicator of viral gene expression, we detected expression from these recombinant HSV in dermal and neural tissues of the BALB/c mouse. Our detection of beta-galactosidase expression in neuronal cells indicates that TK-deficient viruses are capable of invading mouse neuronal cells and expressing up to the beta class of gene product.

Animals↗
PubMed1978

The conception of man in Mao Tse-tung thought.

In 1940, long before the People's Republic of China came into being, Mao Tse-tung declared: The aim of all our efforts is the building of a new society and new nation of the Chinese people. In such a new society and new nation, there will be not only a new political organization and new economy, but a new culture as well. Twenty-six years later, the world witnessed the Great Cultural Revolution (GCR), in which Mao himself took an active leading role. The very idea of a cultural revolution is revolutionary enough. Never before in history has there been such an ambitious attempt to create a new man, with a new culture, in a new society. Unparalleled in both its scope and intensity, the GCR is a unique social experiment that has directly involved a fifth of mankind, and has profound implications for mankind as a whole. What are the philosophic assumptions about man embodied in Mao Tse-tung Thought, the guide to action in the Chinese revolution? How are these assumptions linked to Mao's political ideology? What is the relevance that Mao's conception of man has for contemporary psychology? The present essay is an attempt to answer these questions.

China↗