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K C Pang

Publications and source records attributed to K C Pang.

13 recordsLinked to original sources
PubMed2005

Antisense transcription in the mammalian transcriptome.

Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.

Animals↗
PubMed2001

Cerebellar dysfunction is associated with overexpression of proinflammatory cytokine genes in lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology accompanied by central nervous system involvement in up to 60% of patients. The current study chronicles the expression of cerebellar dysfunction in SLE using MRL-lpr/lpr mice as the experimental model. These mice spontaneously develop an illness that has immunological and clinical features of human lupus. We found that MRL-lpr/lpr mice manifest severe and progressive behavioral disturbances indicative of cerebellar dysfunction beginning at 11 weeks of age. Although the lpr gene is known to induce autoimmune features, immunologically normal mice rendered congenic for lpr failed to exhibit disturbances in cerebellar function. Because lupus is a cytokine-driven disease and overexpression of certain proinflammatory cytokines has been associated with neurodegeneration, the relationship between cerebellar dysfunction and cytokine gene expression was examined. Relative to immunologically normal CBA/J mice, the cerebellum of young (11-15 weeks of age) MRL-lpr/lpr mice contained high levels of interleukin (IL)-6 and interferon-gamma (IFNgamma) mRNA, which became even more pronounced in old (22-30 weeks of age) autoimmune mice. mRNA levels for the cytokines IL-1beta and IL-10 were elevated in the cerebellum of old, but not young, MRL-lpr/lpr mice relative to CBA/J. In contrast, the levels of cerebellar transcripts for IL-3 and tumor necrosis factor-alpha were comparable in autoimmune and normal mice, indicating that enhanced gene expression of IL-6, IFNgamma, IL-1beta, and IL-10 was selective. These results suggest a potential role for certain proinflammatory cytokines in the pathogenesis of cerebellar disturbances in SLE.

Aging↗
PubMed2001

GABAergic septohippocampal neurons are not necessary for spatial memory.

The medial septum/vertical limb of the diagonal band of Broca (MSDB) provides a major input to the hippocampus and is important for spatial memory. Both cholinergic and GABAergic MSDB neurons project to the hippocampus, and nonselective lesions of the MSDB or transections of the septohippocampal pathway impair spatial memory. However, selective lesions of cholinergic MSDB neurons using 192-IgG saporin (SAP) do not impair or only mildly impair spatial memory. Previously, intraseptal kainic acid was found to reduce levels of glutamic acid decarboxylase, a marker of GABAergic neurons, but not to alter the levels of choline acetyltransferase, a marker of cholinergic neurons. The present study further characterized the effects of kainic acid on GABAergic MSDB neurons and examined the effects of intraseptal kainic acid on spatial memory. Saline, kainic acid, SAP, or the combination of kainic acid and SAP was administered into the MSDB of rats. Spatial memory was assessed in an eight-arm radial maze and a water maze. Kainic acid destroyed GABAergic septohippocampal neurons, but spared cholinergic neurons. SAP eliminated MSDB cholinergic neurons, sparing noncholinergic neurons. Coadministration of kainic acid and SAP destroyed GABAergic and cholinergic MSDB neurons. Acquisition of the radial maze task and performance on this task with 4-h delays were unimpaired by intraseptal kainic acid or SAP, but were impaired by coadministration of kainic acid and SAP. Acquisition of the water maze task was unaffected by intraseptal kainic acid, delayed slightly by SAP, and impaired severely by coadministration of kainic acid and SAP. These results provide evidence that kainic acid at appropriate concentrations effectively destroys GABAergic septohippocampal neurons, while sparing cholinergic MSDB neurons. Furthermore, lesions of the GABAergic septohippocampal neurons do not impair spatial memory. While lesions of cholinergic MSDB neurons may mildly impair spatial memory, the combined lesion of GABAergic and cholinergic septohippocampal neurons resulted in a memory impairment that was greater than that observed after a selective lesion to either population. Thus, damage of GABAergic or cholinergic MSDB neurons, which together comprise the majority of the septohippocampal pathway, cannot totally account for the spatial memory impairment that is observed after nonselective lesions of the MSDB.

Animals↗
PubMed2001

Neurons in the lateral agranular frontal cortex have divided attention correlates in a simultaneous temporal processing task.

The frontal cortex is an important brain area for divided attention. Lesions of the lateral agranular frontal cortex in rats disrupt divided attention in a simultaneous temporal processing task. In the present study, the activity of lateral agranular neurons was examined while rats performed a simultaneous temporal processing procedure. Rats were trained to time two stimuli (a light and a tone), each associated with a different fixed interval. Simple trials, in which a single stimulus was presented, and compound trials, in which both stimuli were presented simultaneously, occurred randomly in a session. Rats were able to divide attention between the two stimuli, as assessed by the pattern of lever presses. Approximately 50% of lateral agranular neurons responded to at least one phase of the task with four response patterns observed. The activity of type 1 cells (60%) was altered to compound, but not simple, stimuli. Type 2 cells (10%) responded to both types of simple stimuli and to compound stimuli. Type 3 cells (27%) had changes in firing rate to one type of simple stimulus and to compound stimuli. Type 4 cells (3%) responded to one type of simple stimulus, but were unresponsive to all other stimuli. The large proportion of type 1 cells supports the hypothesis that the lateral agranular cortex is important in divided attention. Previous studies have suggested that the lateral agranular cortex in rats is equivalent to the primary motor cortex. If so, the results from the present study provide evidence that the lateral agranular cortex may have some cognitive functions, in addition to being part of the motor system.

Acoustic Stimulation↗
PubMed1999

Interactions between 192-IgG saporin and intraseptal cholinergic and GABAergic drugs: role of cholinergic medial septal neurons in spatial working memory.

Rats were administered 192-IgG saporin (SAP) or vehicle into the medial septum-vertical limb of the diagonal band (MS-vDB). Starting 1 week later, the effects of intraseptal scopolamine, oxotremorine, and muscimol were tested in a T-maze alternation task. Choice accuracy in the absence of infusions did not differ between control and SAP-treated rats. Intraseptal scopolamine or muscimol impaired the choice accuracy of SAP-treated but not control rats. Oxotremorine impaired accuracy similarly in control and SAP-treated rats. The enhanced effects of scopolamine and muscimol produced by SAP are consistent with the hypothesis that cholinergic MS-vDB neurons are used in spatial working memory. The finding that SAP alone did not alter choice accuracy provides further evidence that cholinergic MS-vDB neurons are not necessary for spatial working memory. Thus, cholinergic MS-vDB neurons are involved in but not necessary for spatial working memory.

Animals↗
PubMed1999

Subthalamic stimulation-induced synaptic responses in substantia nigra pars compacta dopaminergic neurons in vitro.

The subthalamic nucleus (STN) is one of the principal sources of excitatory glutamatergic input to dopaminergic neurons of the substantia nigra, yet stimulation of the STN produces both excitatory and inhibitory effects on nigral dopaminergic neurons recorded extracellularly in vivo. The present experiments were designed to determine the sources of the excitatory and inhibitory effects. Synaptic potentials were recorded intracellularly from substantia nigra pars compacta dopaminergic neurons in parasagittal slices in response to stimulation of the STN. Synaptic potentials were analyzed for onset latency, amplitude, duration, and reversal potential in the presence and absence of GABA and glutamate receptor antagonists. STN-evoked depolarizing synaptic responses in dopaminergic neurons reversed at approximately -31 mV, intermediate between the expected reversal potential for an excitatory and an inhibitory postsynaptic potential (EPSP and IPSP). Blockade of GABA(A) receptors with bicuculline caused a positive shift in the reversal potential to near 0 mV, suggesting that STN stimulation evoked a near simultaneous EPSP and IPSP. Both synaptic responses were blocked by application of the glutamate receptor antagonist, 6-cyano-7-nitroquinoxalene-2,3-dione. The confounding influence of inhibitory fibers of passage from globus pallidus and/or striatum by STN stimulation was eliminated by unilaterally transecting striatonigral and pallidonigral fibers 3 days before recording. The reversal potential of STN-evoked synaptic responses in dopaminergic neurons in slices from transected animals was approximately -30 mV. Bath application of bicuculline shifted the reversal potential to approximately 5 mV as it did in intact animals, suggesting that the source of the IPSP was within substantia nigra. These data indicate that electrical stimulation of the STN elicits a mixed EPSP-IPSP in nigral dopaminergic neurons due to the coactivation of an excitatory monosynaptic and an inhibitory polysynaptic connection between the STN and the dopaminergic neurons of substantia nigra pars compacta. The EPSP arises from a direct monosynaptic excitatory glutamatergic input from the STN. The IPSP arises polysynaptically, most likely through STN-evoked excitation of GABAergic neurons in substantia nigra pars reticulata, which produces feed-forward GABA(A)-mediated inhibition of dopaminergic neurons through inhibitory intranigral axon collaterals.

Animals↗
PubMed1998

Type I IFNs enhance the terminal differentiation of dendritic cells.

This study identifies type I IFNs as activating cytokines in a serum-free system in which human dendritic cells (DC) were generated from CD34+ progenitor cells. After 14 days of culture in GM-CSF, TNF-alpha, and IL-4, CD34+ progenitors gave rise to a population of large, immature DC expressing CD1a and CD11b but lacking CD14, CD80, CD83, CD86, and CMRF44. During the next 2 wk, this population spontaneously matured into nonadherent, CD1a(low/-), CD11b(low/-), CD14-, CD80+, CD83+, CD86+, CMRF44+ DC with high allostimulatory activity in the MLR. To examine which factors influenced this maturation, 25 different cytokines or factors were added to the immature DC culture. Only type I IFNs (alpha or beta) accelerated this maturation in a dose-dependent manner, so that after only 3 days the majority of large cells acquired the morphology, phenotype, and function characteristics of mature DC. Furthermore, supernatants from cultures containing spontaneously maturing DC revealed low levels of endogenous IFN production. Because of the similarity of the activation of DC in our culture system with the phenotypic and functional changes observed during Langerhans cells activation and migration in vivo, we investigated the effect of IFN-alpha on human Langerhans cell migration. IFN-alpha also activated the migration of human split skin-derived DC, demonstrating that this effect was not limited to DC derived in vitro from hemopoietic progenitor cells. DC activation by type I IFNs represents a novel mechanism of immunomodulation by these cytokines, which could be important during antiviral responses and autoimmune reactions.

Adjuvants, Immunologic↗
PubMed1998

A serum-free culture model for studying the differentiation of human dendritic cells from adult CD34+ progenitor cells.

The antigen-presenting capacity of dendritic cells (DCs) makes them attractive potential cellular adjuvants for vaccination strategies. Currently, most in vitro culture systems for the production of these DCs include serum. However, this is undesirable because serum contains growth factors that vary between individuals and could affect DC development. Unless the patient's own serum is used, foreign antigens and the risk of infection will detract from the usefulness of these cells in clinical strategies. In this study we investigated the production of DCs from CD34+ progenitor cells of cancer patients or normal donors under serum-free conditions. We have established a model system for the investigation of DC development and maturation. Dendritic cells that developed from myeloid precursors accumulated after 2 weeks in an intermediate CD1a , CD80-, CD83-, CD86- stage. Intermediate DCs adhered to plastic surfaces, expressed Birbeck granules, and were negative for CD2 and CD14. In the presence of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha, interleukin-4 promoted the development of these stages. Spontaneous maturation of intermediate DCs into fully activated DCs expressing CD83 and costimulatory molecules occurred asynchronously over the ensuing 2 to 3 weeks. This maturation involved increased expression of CD80, CD83, CD86, CMRF-44, HLA-A, -B, -C, and -DR as well as downregulation of CD1a and CD11b. Activated DCs are characterized by the lack of adherence to plastic surfaces and the absence of Birbeck granules. By day 28, these cells were nonphagocytic, potent antigen-presenting cells with an irreversible phenotype. This serum-free system offers advantages in that the process of differentiation and maturation of committed DCs is extended over a period of more than 28 days, allowing investigators to study the effects of individual cytokines or other supplements during distinct phases of DC development in a defined environment.

Adult↗
PubMed1995

The trefoil peptides spasmolytic polypeptide and intestinal trefoil factor are major secretory products of the rat gut.

Spasmolytic polypeptide (SP) and intestinal trefoil factor (ITF) are trefoil peptides expressed by gut mucus cells. Using specific antisera we have quantified and characterized the molecular forms and distribution of these peptides in the rat gut. SP predominates in the gastric antrum as a 12 kDa form. ITF (7 kDa) is highly expressed throughout the small intestine. Both peptides are distributed in the apical secretory compartment of antral mucus cells (SP) and goblet cells (ITF), and on the lumenal surface. This study quantifies SP and ITF for the first time, and confirms them as major secretory products of the rat gut.

Amino Acid Sequence↗
PubMed1991

Individual differences in aging: behavioral and neural analyses.

Aged populations have remarkable variability in recent memory and cognitive mapping. Although some individuals may have substantial age-related impairments, others perform almost as well as young individuals. This paper reviews the relevant data on aged rats and indicates two challenges for biomarkers of aging. The first is to provide an appropriate quantitative description of these individual differences. The second is to use them effectively as markers for age-related changes in psychological functions and their neural substrates.

Aging↗
PubMed1989

Differential effect of norepinephrine upon granule cells and interneurons in the dentate gyrus.

The effect of locally applied norepinephrine upon dentate granule cells and neighboring interneurons was examined in urethane-anesthetized rats. Norepinephrine inhibited the spontaneous firing of physiologically identified granule cells, but excited interneurons. These results demonstrate that two coexisting hippocampal cell types, which have many physiological properties and behavioral correlates in common, may be differentiated using a pharmacological criterion.

Action Potentials↗
PubMed1983

Characteristics of mononuclear phagocytes mediating antilisterial resistance in splenectomized mice.

The characteristics of mononuclear phagocytes mediating resistance to infection with Listeria monocytogenes during the early phase (up to 48 h) of the response were investigated in mice of the A strain that had undergone splenectomy. Although irradiation in the sham-operated host had no effect on its antilisterial response when administered immediately before infection, it markedly reduced the ability of the splenectomized host to resist listerial challenge. This effect of radiation was demonstrable in the high-dose range (600 r) and could not be reversed immediately by repopulation with 20 x 10(6) syngeneic nucleated bone marrow cells. Administration of silica 24 h before infection profoundly enhanced the growth of L. monocytogenes in the liver of splenectomized mice. Shielding of the liver, but not the bone marrow, protected the splenectomized host against the effects of radiation, indicating that the cell population responsible for mediating the enhanced antilisterial resistance resides in the liver. The enhanced antilisterial resistance of splenectomized mice was specifically because of the absence of the spleen and not merely because of the removal of a favorable replicating environment for listeria organisms.

Animals↗