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Biomedical subjects

C M Cheng

Publications and source records attributed to C M Cheng.

At least 19 recordsLinked to original sources
PubMed2004

Estradiol alters transcription factor gene expression in primate prefrontal cortex.

Estrogen protects neurons from a variety of experimental insults in vitro, and is thought to protect from acute and chronic neurodegenerative processes in vivo. Estrogen also enhances higher-level cognitive functions that are centered in the dorsolateral prefrontal cortex (DLPFC) in human and non-human primates. To investigate genomic mechanisms involved in estrogenic effects on the primate brain in vivo, we compared transcription factor mRNA and protein expression in the DLPFC of ovariectomized rhesus monkeys treated with either vehicle or estradiol (E2). c-FOS, E2F1, and general transcription factor IIB (TFIIB) mRNA and protein expression were altered significantly by short-term E2 treatment, as shown by DNA array, in situ hybridization, and immunohistochemical and immunoblot evaluations. C-FOS expression was increased significantly whereas E2F1 and TFIIB levels were decreased in the DLPFC of E2-treated animals. These transcription factors were concentrated in cortical pyramids, as were estrogen receptors alpha and beta. These data indicate that estrogen may have direct as well as indirect effects on neuronal gene expression in the primate prefrontal cortex.

Animals↗
PubMed2004

High-level expression of Dok-1 in neurons of the primate prefrontal cortex and hippocampus.

The docking protein p62Dok-1 (Dok-1) has a central role in cell signaling mediated by a wide range of protein tyrosine kinases, including intrinsic membrane kinases, such as the insulin-like growth factor-1 (IGF-1) receptor. To elucidate potential IGF signaling mechanisms, we used DNA array technology to investigate novel kinase targets expressed in the primate dorsolateral prefrontal cortex (DLPFC). Dok-1 transcripts were among the most abundant found in this structure. Because Dok-1 expression has not been characterized in brain, we evaluated its expression pattern using immunoblotting, in situ hybridization, and immunohistochemistry in the rhesus monkey prefrontal cortex and hippocampal formation. Dok-1 antibodies identified a 62-kDa band in lysates from the DLPFC, consistent with the known size for Dok-1. In situ hybridization showed that Dok-1 mRNA was expressed in all layers of the DLPFC and in all neuronal subregions of the hippocampal formation. Immunohistochemical analysis showed Dok-1 immunoreactivity concentrated in pyramidal neurons of cortical layers IV-V and throughout Ammon's horn and in granule neurons of the dentate gyrus. Dok-1 expression was also identified in endothelial cells of cerebral blood vessels. These expression patterns are very similar to those of the IGF-1 receptor and suggest that Dok-1 could be among the downstream targets of IGF signaling in areas of the primate brain involved in learning and memory.

Animals↗
PubMed2004

N-phosphoryl amino acids and biomolecular origins.

The possible role of phosphoryl amino acids for biomolecular origins is briefly reviewed. Peptide formation, ester formation, ester exchange on phosphorus and N to O migration occurred when the N-phosphoryl amino acid was incubated at room temperature. Short nucleotides and peptides were formed when nucleoside was reacted with N-phosphoryl amino acid at room temperature. Serine and threonine residues in their conjugate with different nucleosides (mediated with phosphorus) showed different self-cleavage activities. N-phosphoryl Histine and Ser-His dipeptide could cleave nucleic acids, proteins and esters in neutral medium. Based on a simple model, a pathway of 'co-evolution of protein and nucleic acid' was proposed.

Amino Acids↗
PubMed2004

Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth.

The possibility that growth hormone (GH) has effects on long bone growth independent of insulin-like growth factor-I (IGF-I) has long been debated. If this is true, then long bone growth should be more profoundly affected by the absence of GH (since both GH and GH-stimulated IGF-I effects are absent) than by the absence of IGF-I alone (since GH is still present and actually elevated). To test this hypothesis, we compared long bone growth in mice with targeted deletions of Igf1 vs growth hormone receptor (Ghr). Tibial linear growth rate was reduced by approximately 35% in Igf1 null mice and by about 65% in Ghr null mice between postnatal days 20 and 40, a time of peak GH effect during normal longitudinal growth. The Igf1 null mouse growth plate demonstrated significant enlargement of the germinal zone; chondrocyte proliferation and numbers were normal but chondrocyte hypertrophy was significantly reduced. In contrast, the Ghr null mouse germinal zone was hypoplastic, chondrocyte proliferation and numbers were significantly reduced, and chondrocyte hypertrophy was also reduced. We have previously demonstrated that IGF-II is highly expressed in growth plate germinal and proliferative zones, so we considered the possibility that GH-stimulated IGF-II production might promote germinal zone expansion and maintain normal proliferation in the Igf1 null mouse growth plate. Supporting this view, IGF-II mRNA was increased in the Igf1 null mouse and decreased in the Ghr null mouse growth plate.Thus, in the complete absence of IGF-I but in the presence of elevated GH in the Igf1 null mouse, reduction in chondrocyte hypertrophy appears to be the major defect in longitudinal bone growth. In the complete absence of a GH effect in the Ghr null mouse, however, both chondrocyte generation and hypertrophy are compromised, leading to a compound deficit in long bone growth. These observations support dual roles for GH in promoting longitudinal bone growth: an IGF-I-independent role in growth plate chondrocyte generation and an IGF-I-dependent role in promoting chondrocyte hypertrophy. The question of whether GH has direct effects on chondrocyte generation is still not settled, however, since it now appears that IGF-II may medicate some of these effects on the growth plate.

Animals↗
PubMed2001

Endogenous IGF1 enhances cell survival in the postnatal dentate gyrus.

The dentate gyrus is selectively reduced in size in the insulin-like growth factor 1 (IGF1) null mouse brain. The purpose of this study was to determine whether this defect is due to reduced granule cell numbers, and if so, to determine whether altered cell proliferation, survival, or both contribute to attenuation of dentate gyrus size. At postnatal day 10 (P10), granule cell numbers were not significantly different in IGF1 null and littermate wildtype (WT) dentate gyri. The subgranular zone cell population, however, was relatively increased, and the granule cell layer population relatively decreased in the IGF1 null dentate gyrus. By P50, total dentate cell numbers were decreased by 20% (P = 0.01) in the IGF1 null mouse, although IGF1 null subgranular zone progenitor cells remained relatively increased compared with WT (38%, P < 0.05). IGF1 null dentate cell proliferation, assessed by thymidine analogue incorporation, was actually increased at P10 (33%, P < 0.05) and P50 (167%, P = 0.001). Dentate granule cell death, assessed by the appearance of pycnotic cells and DNA fragmentation, was also significantly increased in the IGF1 null dentate (61%, P < 0.05 and 101%, P = 0.03). These data suggest that endogenous IGF1 serves an important role in dentate granule cell survival during the course of postnatal brain development. In addition, this work suggests the potential of a compensatory mechanism promoting increased dentate cell proliferation in the face of impaired cell survival during postnatal neurogenesis. J. Neurosci. Res. 64:341-347, 2001. Published 2001 Wiley-Liss, Inc.

Animals↗
PubMed2001

Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex.

Estrogen has many positive effects on neural tissue in experimental model systems, including stimulation of neurite growth and neurotransmitter synthesis and protection against diverse types of neural injury. In humans, estrogen treatment is reputed to protect against Alzheimer's disease. To investigate potential mediators of estrogen's action and determine whether selective estrogen receptor modulators (SERMs) such as tamoxifen have estrogen-like effects in the primate brain, we evaluated the expression of glucose transporters and insulin-like growth factor 1 (IGF1) and its receptor in the frontal cortex of ovariectomized rhesus monkeys. We treated one group for 3 days with vehicle, another with 17 beta estradiol (E2), and a third with tamoxifen. The expression of facilitative glucose transporters (Gluts) 1, 3, and 4 was investigated using in situ hybridization, immunohistochemistry, and immunoblot analysis. Gluts 3 and 4 were concentrated in cortical neurons and Glut1 in capillaries and glial cells. E2 treatment induced two- to fourfold increases in Glut3 and Glut4 mRNA levels and lesser but significant increases in Glut3 and 4 protein levels. E2 treatment induced an approximately 70% increase in parenchymal Glut1 mRNA levels, but did not appreciably affect vascular Glut1 gene expression. IGF1 and IGF1 receptor mRNAs were concentrated in cortical neurons in a distribution similar to Gluts 3 and 4. IGF1 mRNA levels were significantly increased in E2-treated animals but IGF1 receptor mRNA levels were not altered by hormone treatment. Tamoxifen increased cerebral cortical Glut3 and 4 mRNA levels, but did not affect Glut1, IGF1, or IGF1 receptor expression. This study provides novel data showing that Gluts 3 and 4 and IGF1 are coexpressed by primate cerebral cortical neurons, where their expression is enhanced by estrogen. These findings suggest that up-regulation of glucose transporter and IGF1 expression may contribute to estrogen's salutary effects on neural tissue. Tamoxifen, an antiestrogen at the breast, is shown to have estrogen-like effects on higher brain centers in the monkey, suggesting that some SERMs may share estrogen's neuroprotective potential for menopausal women.

Animals↗
PubMed2000

Insulin-like growth factor 1 regulates developing brain glucose metabolism.

The brain has enormous anabolic needs during early postnatal development. This study presents multiple lines of evidence showing that endogenous brain insulin-like growth factor 1 (Igf1) serves an essential, insulin-like role in promoting neuronal glucose utilization and growth during this period. Brain 2-deoxy-d- [1-(14)C]glucose uptake parallels Igf1 expression in wild-type mice and is profoundly reduced in Igf1-/- mice, particularly in those structures where Igf1 is normally most highly expressed. 2-Deoxy-d- [1-(14)C]glucose is significantly reduced in synaptosomes prepared from Igf1-/- brains, and the deficit is corrected by inclusion of Igf1 in the incubation medium. The serine/threonine kinase Akt/PKB is a major target of insulin-signaling in the regulation of glucose transport via the facilitative glucose transporter (GLUT4) and glycogen synthesis in peripheral tissues. Phosphorylation of Akt and GLUT4 expression are reduced in Igf1-/- neurons. Phosphorylation of glycogen synthase kinase 3beta and glycogen accumulation also are reduced in Igf1-/- neurons. These data support the hypothesis that endogenous brain Igf1 serves an anabolic, insulin-like role in developing brain metabolism.

Animals↗
PubMed2000

Role of rpoS in acid resistance and fecal shedding of Escherichia coli O157:H7.

Acid resistance (AR) is important to survival of Escherichia coli O157:H7 in acidic foods and may play a role during passage through the bovine host. In this study, we examined the role in AR of the rpoS-encoded global stress response regulator sigma(S) and its effect on shedding of E. coli O157:H7 in mice and calves. When assayed for each of the three AR systems identified in E. coli, an rpoS mutant (rpoS::pRR10) of E. coli O157:H7 lacked the glucose-repressed system and possessed reduced levels of both the arginine- and glutamate-dependent AR systems. After administration of the rpoS mutant and the wild-type strain (ATCC 43895) to ICR mice at doses ranging from 10(1) to 10(4) CFU, we found the wild-type strain in feces of mice given lower doses (10(2) versus 10(3) CFU) and at a greater frequency (80% versus 13%) than the mutant strain. The reduction in passage of the rpoS mutant was due to decreased AR, as administration of the mutant in 0.05 M phosphate buffer facilitated passage and increased the frequency of recovery in feces from 27 to 67% at a dose of 10(4) CFU. Enumeration of E. coli O157:H7 in feces from calves inoculated with an equal mixture of the wild-type strain and the rpoS mutant demonstrated shedding of the mutant to be 10- to 100-fold lower than wild-type numbers. This difference in shedding between the wild-type strain and the rpoS mutant was statistically significant (P </= 0.05). Thus, sigma(S) appears to play a role in E. coli O157:H7 passage in mice and shedding from calves, possibly by inducing expression of the glucose-repressed RpoS-dependent AR determinant and thus increasing resistance to gastrointestinal stress. These findings may provide clues for future efforts aimed at reducing or eliminating this pathogen from cattle herds.

Animals↗
PubMed1999

The primary immunity determinant in modulating the lysogenic immunity of the filamentous bacteriophage cf.

Bacteriophage cf is the first single-stranded DNA phage that has been shown to set up a stable lysogenic state with its genome integrated into the host chromosome. From the isolation and characterization of a virulent mutant, cf-tv2, we report the first investigation into the mechanisms of the immunity established by the filamentous bacteriophage. The mutation in cf-tv2 enables the phage to produce plaques on lawns of cf lysogenic cells. The mutation was defined as a 49-nucleotide deletion located in a 0.59 kb NcoI/KpnI fragment of cf replicative form DNA. Two messages, cM1 and cM2, transcribed from the immunity region of wild-type cf but in opposite directions, were detected. In cf-tv2, the 49-nucleotide deletion abolishes cM2 transcription. The primer extension assay suggests a possible RNA-RNA interaction directed by base-pairing of the cM1 and cM2 RNAs. A frameshift mutation of the open reading frame ORF 165, encoded by cM2, resulted in a 10(5) plating efficiency on the cf lysogen. These observations suggest that both RNA-RNA interaction and repressor protein inhibition are involved in the mechanism of cf immunity. A model is proposed for the regulation of cf immunity.

Amino Acid Sequence↗
PubMed1999

Transcription of the genome of the filamentous bacteriophage cf from both plus and minus DNA strands.

The filamentous bacteriophage cf infects the bacterium Xanthomonas campestris pv. citri. Northern blot analysis with probes derived from various restriction fragments of cf replicative form (RF) DNA has revealed the presence of five major phage-specific transcripts in infected cells. Four of these transcripts were shown to be derived from the region of the cf genome extending from gene II to gene VIII and are consistent with the cascade model of transcription proposed for Ff coliphages. These transcripts overlap with each other and terminate upstream of an efficient Rho-independent transcription terminator. Unlike the well-characterized Ff phages, in which only the minus strand of viral DNA serves as a transcription template, both strands of the RF DNA of phage cf appeared to be transcribed. Thus one of the five major cf transcripts was shown to be derived from a region of the viral minus strand that contains an open reading frame encoding a putative polypeptide of 165 amino acids. Primer extension analysis mapped the transcriptional initiation site of this RNA to a cytosine residue at position 870. A partial transcription map of phage cf revealed two independent regions of transcriptional activity. The region with the highest activity coincides with that encoding the polypeptides required in the largest amounts during the cf infection cycle.

5' Untranslated Regions↗
PubMed1999

Hemisphere differences in accessing lexical knowledge of Chinese characters.

The lateralisation of lexical knowledge of Chinese characters is investigated in this study. Three experiments were conducted in which stimuli were presented unilaterally to a visual field for recognition tests. The orthographic similarity of two alternative items for choice in Experiment 1 was manipulated, and the results showed an LVF advantage effect for legal characters in the visually similar condition and a more prominent LVF than RVF character-superiority effect. The phonological similarity of two alternative items for choice was manipulated in Experiment 2. The results showed a prominent RVF advantage effect and a significant phonological similarity effect in the RVF. In Experiment 3, the semantic similarity was manipulated, and the semantic similarity effect was observed in the RVF. These results suggest hemisphere asymmetries in accessing lexical knowledge of Chinese characters.

Journal Article↗
PubMed1999

Vulnerability of rural hospitals to Medicare outpatient payment reform.

Because the Balanced Budget Act (BBA) of 1997 requires implementation of a Medicare prospective payment system (PPS) for hospital outpatient services, the authors evaluated the potential impact of outpatient PPS on rural hospitals. Areas examined include: (1) How dependent are rural hospitals on outpatient revenue? (2) Are they more likely than urban hospitals to be vulnerable to payment reform? (3) What types of rural hospitals will be most vulnerable to reform? Using Medicare cost report data, the authors found that small size and government ownership are more common among rural than urban hospitals and are the most important determinants of vulnerability to payment reform.

Aged↗
PubMed1998

Biochemical and morphometric analyses show that myelination in the insulin-like growth factor 1 null brain is proportionate to its neuronal composition.

To elucidate the role of insulin-like growth factor 1 (IGF1) in the normal development of brain myelination, we used behavioral, biochemical, and histological analyses to compare the myelination of brains from Igf1(-/-) and wild-type (WT) littermate mice. The studies were conducted at postnatal day 40, at which time the Igf1(-/-) mice weighed approximately 66% less than wild-type mice. However, the Igf1(-/-) brain weight was only reduced by approximately 34%. Formal neurological testing showed no sign of central or peripheral myelinopathy in Igf1(-/-) mice. Myelin composition was not significantly different, and myelin concentration, normalized to brain weight or protein, was equal in Igf1(-/-) and WT mice. Likewise, concentrations of myelin-specific proteins (MBP, myelin proteolipid protein, MAG, and 2',3'-cyclic nucleotide,3'-phosphodiesterase) were not significantly different in Igf1(-/-) and WT mice. The myelin-associated lipids galactocerebroside and sulfatide were modestly reduced in Igf1(-/-) brains. Regional oligodendrocyte populations and myelin staining patterns were comparable in Igf1(-/-) and WT brains, with the notable exception of the olfactory system. The Igf1(-/-) olfactory bulb was profoundly reduced in size and was depleted of mitral neurons and oligodendrocytes, and its efferent tracts were depleted of myelin. In summary, this study shows that myelination of the Igf1(-/-) brain is proportionate to its neuronal composition. Where projection neurons are preserved despite the deletion of IGF1, as in the cerebellar system, oligodendrocytes and myelination are indistinguishable from wild type. Where projection neurons are depleted, as in the olfactory bulb, oligodendrocytes are also depleted, and myelination is reduced in proportion to the reduced projection neuron mass. These data make a strong case for the primacy of axonal factors, not including IGF1, in determining oligodendrocyte survival and myelination.

Animals↗
PubMed1998

Initiation and maintenance of a hospital-based parent group for parents of premature infants: key factors for success.

The impact of a premature birth can be very traumatic for parents. They are usually not prepared for this event, and their sense of grief and loss is so intense that they often have difficulty coping with the situation. A parent group can help parents adapt to the crisis of prematurity by providing information and family support. This article describes the development of a parent group at a regional perinatal center in Ontario and identifies key factors for its successful initiation and maintenance.

Adaptation, Psychological↗
PubMed1997

Sequence of a human E2F-4 pseudogene with shortened AGC trinucleotide repeats.

We have isolated a human genomic DNA fragment of 0.7 kb by polymerase chain reaction (PCR) using human E2F-4 gene primers. Sequence analysis indicates that this DNA comes from a processed E2F-4 pseudogene. Its sequence is 75% identical to the human E2F-4 cDNA, and bears several deletions and insertions. A 30 bp deletion shortens the 13 AGC repeats in the E2F-4 gene by 10 repeats. The sequence data also suggest that another 65 bp deletion and some small insertions may be generated by replication errors on template pairing.

Amino Acid Sequence↗