Biomedical subjects

L Wang

Publications and source records attributed to L Wang.

At least 1,459 records · Page 81Linked to original sources

PubMed1997

Fiber-supplemented enteral formula slows intestinal transit by intensifying inhibitory feedback from the distal gut.

Because an increase in flow rate accelerates intestinal transit, a reduction in the flow rate of formula delivery is recommended frequently for treatment of diarrhea that develops during enteral feeding. Because intestinal transit is slowed by nutrient-triggered inhibitory feedback, the rate of intestinal transit during enteral feeding may depend on a balance between the accelerating effect of flow and the inhibiting effect of the nutrient load. The addition of fiber to a formula may alter this balance. By delaying absorption of nutrients, fiber may extend the length of small intestine exposed to nutrients and thereby trigger more intense inhibitory feedback. To determine whether the addition of fiber favors nutrient-triggered inhibition over flow-driven acceleration, we studied intestinal transit after perfusion of a low-residue enteral formula compared with a fiber-supplemented formula at two perfusion rates (50 or 100 mL/h for 2 h) into the duodenum of dogs each with both a duodenal and midgut fistula. With the low-residue formula, intestinal transit accelerated when the flow rate increased from 50 to 100 mL/h (P < 0.05). With the fiber-supplemented formula, however, intestinal transit was inhibited regardless of the flow rate. To determine whether the fiber-supplemented formula inhibited intestinal transit by displacing nutrients distally, we compared intestinal transit when the two formulas, delivered at 100 mL/h, were diverted completely at the midgut fistula. Intestinal transit of the fiber-supplemented formula increased by 400%, eliminating the difference in intestinal transit speed between the two formulas. We concluded that the fiber-supplemented formula slowed intestinal transit by intensifying inhibitory feedback from the distal gut.

Analysis of Variance↗

PubMed1997

Epistasis in measured genotypes: Drosophila P-element insertions.

Transposon tagging provides an opportunity to construct large numbers of strains of organisms that differ by single insertional mutations. By scoring the phenotypes of these "measured genotypes," powerful tests of effects of mutations on phenotypic expression have been performed. Here we extend this approach by constructing with simple crosses all possible two-locus genotypes for each of eight pairs of P-element insertions. Analysis of metabolic phenotypes (fat and glycogen contents, enzyme activities, total protein, and body weight) of the resulting nine genotypes provides direct estimates of additive, dominance, and epistatic effects of the mutations. Nested two-way analysis of variance identified significant epistatic effects in 27% of the tests (35/128 of the trait x P-element combinations). Posterior contrasts were performed to partition the epistatic variance into the four orthogonal components of COCKERHAM, and the data exhibit a tendency toward additive x dominance and dominance x dominance epistasis. Mutations in this study have epistatic effects on metabolic traits that are on the same order of magnitude as main (additive and dominance) effects. Measured genotypes have been used in other contexts to quantify epistatic effects on phenotypic expression, and these results are also briefly reviewed.

Animals↗

PubMed1997

Molecular population genetics of Drosophila immune system genes.

A striking aspect of many vertebrate immune system is the exceptionally high level of polymorphism they harbor. A convincing case can be made that this polymorphism is driven by the diversity of pathogens that face selective pressures to evade attack by the host immune system. Different organisms accomplish a defense against diverse pathogens through mechanisms that differ widely in their requirements for specific recognition. It has recently been shown that innate defense mechanisms, which use proteins with broad-spectrum bactericidal properties, are common to both primitive and advanced organisms. In this study we characterize DNA sequence variation in six pathogen defense genes of Drosophila melanogaster and D. mauritiana, including Andropin; cecropin genes CecA1, CecA2, CecB, and CecC; and Diptericin. The necessity for protection against diverse pathogens, which themselves may evolve resistance to insect defenses, motivates a population-level analysis. Estimates of variation levels show that the genes are not exceptionally polymorphic, but Andropin and Diptericin have patterns of variation that differ significantly from neutrality. Patterns of interpopulation and interspecific differentiation also reveal differences among the genes in evolutionary forces.

Animals↗

PubMed1997

Intestinal transit and absorption of soy protein in dogs depend on load and degree of protein hydrolysis.

Soy protein, in both intact and hydrolyzed forms, is widely used as the nitrogen source in infant and adult formulas. This protein is also consumed in vast quantities worldwide as soybean-based food products. Digestion is the rate-limiting step in the assimilation of proteins from the gut. As a result, intestinal transit must be slowed when a higher load of protein is available or when this nutrient is delivered in the intact rather than hydrolyzed form. However, little information is available on the effect of load and degree of hydrolysis of soy protein on intestinal transit and protein absorption. To test the hypothesis that inhibition of intestinal transit and protein absorption depend on the load of soy protein and the state of hydrolysis of this nutrient, we compared intestinal transit and protein absorption in dogs equipped with duodenal and midintestinal fistulas during intestinal perfusion with 0, 50, 100, or 200 g/L solutions of intact soy protein versus 0, 100, 200, 300, or 400 g/L solutions of hydrolyzed soy protein. We found that intestinal transit was slowed in a load-dependent fashion by intact (P < 0.001) and hydrolyzed (P < 0.05) soy protein. Soy protein inhibited intestinal transit more potently in the intact than hydrolyzed form (P < 0.05). A greater amount of protein was absorbed by the proximal half of the small intestine when soy protein was delivered in the hydrolyzed than intact form (P < 0.05), and the efficiency of protein absorption was maintained at a high and nearly constant level of 82.6 to 87.4% for intact soy protein and 89.0 to 92.3% for hydrolyzed soy protein. We conclude that in dogs intestinal transit and absorption of soy protein depend on the load and the degree of protein hydrolysis.

Animals↗

PubMed1997

Nucleotide compositional constraints on genomes generate alanine-, glycine-, and proline-rich structures in transcription factors.

Correlation between amino acid composition and nucleotide composition is examined. Class III POU transcription factors having higher third GC contents showed higher contents of alanine, glycine, and proline residues encoded by GC-rich nucleotides, and vice versa. This correlation was observed even among various types of transcription factors from vertebrates and invertebrates regardless of functional and structural constraints inherent to each protein. Furthermore, reptile class III POU sequences revealed no evolutionary directionality increasing the GC contents from cold- to warm-blooded vertebrates.

Alanine↗

PubMed1997

Chronic nicotine treatment enhances focal ischemic brain injury and depletes free pool of brain microvascular tissue plasminogen activator in rats.

Effects of nicotine treatment (4.5 mg/kg of nicotine-free base/day administered s.c. by osmotic minipumps for 14 days) on focal ischemic stroke and expression of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in cerebral microvessels were studied in rats in vivo using a reversible (1 h) middle cerebral artery occlusion model. Plasma levels of nicotine and its major metabolite cotinine after 14 days of treatment were 88 and 364 ng/ml, respectively. Nicotine treatment resulted in 35-40% (p < 0.001) decrease in the blood flow in the periphery of the ischemic core during reperfusion, an increase in the neurologic score of 2.6-fold (p < 0.01), and 36% (p < 0.05) and 121% (p < 0.01) increases in the injury and edema volume in the pallium, respectively. A free pool of brain microvascular t-PA antigen was completely depleted by nicotine, while the expression of the PAI-1 antigen and/or PAI-1-t-PA complexes remained unchanged. The relative abundance of cerebromicrovascular t-PA mRNA transcript versus beta-actin mRNA transcript did not change with nicotine. It is concluded that chronic nicotine treatment impairs the restoration of blood flow, worsens the neurologic outcome, and enhances brain injury following an ischemic insult. These nicotine effects are associated with depletion of brain microvascular t-PA antigen.

Animals↗

PubMed1997

Human immunodeficiency virus type 1 Vpu modifies viral cytopathic effect through augmented virus release.

We characterized two human immunodeficiency virus type 1 (HIV-1) strains, HIVMCK and HIV213, which have different cytopathic effects in infected cells. HIV213 was highly cytopathic, whereas HIVMCK was not. Biological analyses of chimeric viruses from the cloned infectious DNAs of HIVMCK and HIV213 showed that the Vpu region was responsible for the differing cytopathicity of these viruses. Although HIVMCK expressed Vpu protein, HIV213 did not because of a mutation at the start codon for Vpu. The amounts of envelope glycoprotein and virus particles associated with the cell surface were significantly increased on cells infected with Vpu-deficient viruses compared with Vpu-positive viruses. These data suggest that the highly cytopathic effects of HIV213 (Vpu-deficient) are due to an accumulation of envelope glycoprotein at the infected-cell surface, which would be caused by the retention of progeny virions in the absence of Vpu-facilitated virion release.

Base Sequence↗

PubMed1997

2006 expressed-sequence tags derived from human chromosome 7-enriched cDNA libraries.

The establishment and mapping of gene-specific DNA sequences greatly complement the ongoing efforts to map and sequence all human chromosomes. To facilitate our studies of human chromosome 7, we have generated and analyzed 2006 expressed-sequence tags (ESTs) derived from a collection of direct selection cDNA libraries that are highly enriched for human chromosome 7 gene sequences. Similarity searches indicate that approximately two-thirds of the ESTs are not represented by sequences in the public databases, including those in dbEST. In addition, a large fraction (68%) of the ESTs do not have redundant or overlapping sequences within our collection. Human DNA-specific sequence-tagged sites (STSs) have been developed from 190 of the ESTs. Remarkably, 180 (96%) of these STSs map to chromosome 7, demonstrating the robustness of chromosome enrichment in constructing the direct selection cDNA libraries. Thus far, 140 of these EST-specific STSs have been assigned unequivocally to YAC contigs that are distributed across the chromosome. Together, these studies provide > 2000 ESTs highly enriched for chromosome 7 gene sequences, 180 new chromosome 7 STSs corresponding to ESTs, and a definitive demonstration of the ability to enrich for chromosome-specific cDNAs by direct selection. Furthermore, the libraries, sequence data, and mapping information will contribute to the construction of a chromosome 7 transcript map.

Brain↗

PubMed1997

Electrothermal branding for embryo labeling.

A novel embryo labeling technique based on electrothermal branding is developed. Two types of micro branding irons are fabricated and tested. One utilizes 25 microns tungsten wire as the heating element. The other utilizes surface micromachining techniques to fabricate polysilicon branding irons. The thermal behavior of the branding irons and the heat distributions in the embryos are analytically modeled. Micron-scale labels on unfertilized bovine embryos are achieved.

Animal Identification Systems↗

PubMed1997

Mapping of growth hormone releasing hormone receptor to swine chromosome 18.

The growth hormone releasing hormone receptor (GHRHR) was mapped in the pig for study as a potential candidate gene in controlling pig quantitative growth and carcass characteristics. Primers were designed from the pig GHRHR sequence to amplify a 1.65-kb intronic fragment between exons 6 and 7. By using a pig-rodent somatic cell hybrid panel, GHRHR was mapped to pig chromosome 18 (SSC18) with 100% concordance, and the regional assignment was SSC18q24 with 89% concordance. The polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs) with MseI and TaqI were developed to confirm this assignment with linkage analysis by using the European Pig Gene Mapping Project (PiGMaP) reference families. Pig GHRHR was mapped with strong linkage to SSC18 markers S0062 and S0120 (lod > 8). The GHRHR and IGFBP3 were found to map near to each other on human chromosome 7 (HSA7), and the pig IGFBP3 gene has been mapped to SSC18 by others. Our mapping of pig GHRHR increases the comparative information available on the SSC18 maps and further confirms the synteny conservation between HSA7 and SSC18.

Animals↗

PubMed1997

Effects of constant and flickering light on retinal metabolism in rabbits.

PURPOSE: To characterize the glucose metabolism in the rabbit retina. METHODS: An artery and a vortex vein were cannulated. Arteriovenous differences in oxygen, lactate and glucose concentrations, and blood flow were determined during either 1) darkness and light, or 2) light and 4 Hz flickering light. RESULTS: In darkness, oxygen consumption, glucose consumption, and lactate formation were 0.122 +/- 0.014, 0.204 +/- 0.015 and 0.160 +/- 0.023 micromol/min (mean +/- SE), respectively. Constant light reduced oxygen consumption insignificantly, and had no effect on glucose consumption. Hyperoxia did not affect the lactate formation. Flickering light increased the glucose consumption and lactate formation by 15-20%. CONCLUSIONS: In rabbits, 10% of the glucose consumed is oxidized, 40-50% is metabolized to lactate and the rest is used for other purposes. The glycolysis is primarily aerobic. Flickering light increases the glucose metabolism, constant light having little effect.

Adaptation, Ocular↗

PubMed1997

The role of nitric oxide in hyperaemic response to flicker in the retina and optic nerve in cats.

PURPOSE: To elucidate the role of nitric oxide (NO) in the eye and the flicker-induced vascular response. METHODS: The blood flow in the retina and different parts of the optic nerve was compared in cats treated with the NO-synthase blocker, N(G)-nitro-L-arginine methyl ester and in control animals. In both groups, one of the eyes was dark-adapted, the other was subjected to 8 Hz flickering light. The regional blood flow was measured with the microsphere method. RESULTS: In control animals, flickering light increased blood flow in the retina and optic nerve head by 39% and 256%, respectively. Pretreatment with N(G)-nitro-L-arginine methyl ester prevented this increase in retinal blood flow and markedly reduced the blood flow in the optic nerve heads. CONCLUSION: NO release may mediate much of the vasodilating effect of flicker in cats, and play a role in maintaining normal vascular tone in the optic nerve head.

Animals↗

PubMed1997

Anticholinergic activity in mice and receptor-binding properties in rats of a series of synthetic tropane derivatives.

A tropane ester, three tropane ethers, atropine and mecamylamine were compared in mice for their anti-muscarinic and anti-nicotinic activity against arecoline-induced tremor and nicotine-induced convulsions, respectively. Their receptor-binding characteristics were studied in neuronal membranes prepared from rat cerebral cortex. The results showed that the tropane ester, 2 alpha R-tropanyl benzylate, was more potent than atropine in its anti-muscarinic activity, but the anti-muscarinic activity of the tropane ethers, 2 alpha-(2',2'-diphenyl-2'-hydroxy-ethoxy)tropane (alpha-DPT) and its two isomers (1R,2 alpha R- and 1S,2 alpha S-) were less potent than that of atropine. In contrast with their anti-muscarinic potency, 2 alpha R-tropanyl benzylate and the three tropane ethers were equipotent in their anti-nicotinic activities. The order of potencies of these compounds to displace the binding of [3H]quinuclidinyl benzylate to brain membranes was similar to that of their anti-muscarinic potencies. The binding of [3H]nicotine to nicotinic receptors from brain was not inhibited by these compounds. Analyses of structure-activity relationships of these compounds suggested that it is the ester groups that determine the anti-muscarinic potencies of 2 alpha R-tropanyl benzylate; their anti-nicotinic activities were independent of the structural changes and of the anti-muscarinic activities of these compounds.

Animals↗

PubMed1997

A second merozoite surface protein (MSP-4) of Plasmodium falciparum that contains an epidermal growth factor-like domain.

Merozoite surface proteins of Plasmodium falciparum play a critical role in the invasion of human erythrocytes by the malaria parasite. Here we describe the identification of a novel protein with a molecular mass of 40 kDa that is found on the merozoite surface of P. falciparum. We call this protein merozoite surface protein 4 (MSP-4). Evidence for the surface location of MSP-4 includes (i) a staining pattern that is consistent with merozoite surface location in indirect immunofluorescent studies of cultured parasites, (ii) localization of MSP-4 in the detergent phase in Triton X-114 partitioning studies, and (iii) nucleotide sequencing studies which predict the presence of an N-terminal signal sequence and a hydrophobic C-terminal sequence in the protein. Immunoprecipitation studies of biosynthetically labelled parasites with [3H] myristic acid indicated that MSP-4 is anchored on the merozoite surface by a glycosylphosphatidylinositol moiety. Of considerable interest is the presence of a single epidermal growth factor-like domain at the C terminus of the MSP-4 protein, making it the second protein with such a structure to be found on the merozoite surface.

Amino Acid Sequence↗

PubMed1997

The carboxyl-terminal 120-residue polypeptide of infectious bronchitis virus nucleocapsid induces cytotoxic T lymphocytes and protects chickens from acute infection.

Specific cytotoxic T-lymphocyte (CTL) responses to nucleocapsid of infectious bronchitis virus (IBV) were identified by using target cells infected with a Semliki Forest virus (SFV) vector. Effector cells for CTL assays were collected from chickens infected with the Gray strain of IBV or inoculated with a DNA plasmid encoding nucleocapsid proteins. IBV-specific CTL epitopes were mapped within the carboxyl-terminal 120 amino acids of the nucleocapsid protein. CTL lysis of target cells infected with SFV encoding nucleocapsid was major histocompatibility complex restricted and mediated by CD8+ T cells. In addition, splenic T cells collected from chickens inoculated in the breast muscle with a DNA plasmid encoding this CTL epitope(s) recognized target cells infected with wild-type virus or an SFV vector encoding nucleocapsid proteins. CTL activity of splenic T cells collected from chicks immunized with a DNA plasmid encoding CTL epitopes was cross-reactive, in that lysis of target cells infected with serologically distinct strains of IBV was dose responsive in a manner similar to that for lysis of target cells infected with the homologous strain of IBV. Furthermore, chickens immunized with a DNA plasmid encoding a CTL epitope(s) were protected from acute viral infection.

Animals↗

PubMed1997

Histone acetyltransferase activity is conserved between yeast and human GCN5 and is required for complementation of growth and transcriptional activation.

Yeast and human ADA2 and GCN5 (y- and hADA2 and y- and hGCN5, respectively) have been shown to potentiate transcription in vivo and may function as adaptors to bridge physical interactions between DNA-bound activators and the basal transcriptional machinery. Recently it was shown that yGCN5 is a histone acetyltransferase (HAT), suggesting a link between enzymatic modification of nucleosomes and transcriptional activation. In this report, we demonstrate that hGCN5 is also an HAT and has the same substrate specificity as yGCN5. Since hGCN5 does not complement functional defects caused by deletion of yGCN5, we constructed a series of hGCN5-yGCN5 chimeras to identify human regions capable of activity in yeast. Interestingly, only the putative HAT domain of hGCN5, when fused to the remainder of yGCN5, complemented gcn5- cells for growth and transcriptional activation. Moreover, an amino acid substitution mutation within the HAT domain reduced both HAT activity in vitro and transcription in vivo. These findings directly link enzymatic histone acetylation and transcriptional activation and show evolutionary conservation of this potentially crucial pathway in gene regulation.

Acetylation↗

PubMed1997

Survey of the distribution of lesion size in multiple sclerosis: implication for the measurement of total lesion load.

OBJECTIVES: Quantitative measurement of lesion load on proton density or T2 weighted brain MRI in multiple sclerosis is a widely used marker of disease progression in treatment trials and natural history studies. However, it has proved difficult to obtain highly reproducible measurements. Several factors account for this, one of which is uncertainties in lesion identification, particularly very small white matter abnormalities. This paper aims to ascertain the significance of very small white matter abnormalities in the measurement of lesion load in multiple sclerosis. METHODS: All visible lesion areas identified by an experienced observer on proton density weighted spin echo brain MRI with 5 mm thick slices were measured by using a contouring technique in 15 patients with secondary progressive multiple sclerosis (SPMS) and 13 with relapsing remitting multiple sclerosis (RRMS). The size distribution of these lesions was analysed. RESULTS: 80% of the number of the lesions were smaller than 80 mm2. Lesions that were smaller than 10 mm2 (equivalent diameter <3.5 mm) made up nearly 20% of all lesions; their relative contribution to the total lesion load varied from 0.0-5.7% (mean=1.1%, median=0.65%) in individual patients, and was larger when the total lesion load was smaller (r = -0.65, P<0.001). Median lesion size was significantly smaller in the SPMS group than the RRMS group. CONCLUSIONS: The results suggest that it is prudent to identify and measure small lesions in evaluating treatment effects, and that measures are undertaken (for example, using thinner slices such as 3 mm) to improve their detection.

Adult↗

PubMed1997

Volume-sensitive chloride current in pigmented ciliary epithelial cells: role of phospholipases.

The whole cell recording technique was used to examine an outwardly rectifying chloride current activated by hypotonic shock in bovine pigmented ciliary epithelial (PCE) cells. Removal of internal and external Ca2+ did not affect the activation of these currents, but they were abolished by the phospholipase C inhibitor neomycin. The current was blocked by 5-nitro-2-(3-phenylpropylamino)benzoic acid, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, and 4,4'-disothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a voltage-dependent manner, but tamoxifen, dideoxyforskolin, and quinidine did not affect it. This blocking profile differs from that of the volume-sensitive chloride channel in neighboring nonpigmented ciliary epithelial cells (Wu, J., J. J. Zhang, H. Koppel, and T. J. C. Jacob, J. Physiol, Lond. 491: 743-755, 1996), and this difference implies that the volume responses of the two cell types are mediated by different chloride channels (Jacob, T. J. C., and J. J. Zhang. J. Physiol. Lond. In press). Intracellular administration of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) to PCE cells induced a transient, time-independent, outwardly rectifying chloride current that closely resembled the current activated by hypotonic shock. DIDS produced a voltage-dependent block of the GTP gamma S-activated current similar to the block of the hypotonically activated current. Intracellular neomycin completely prevented activation of this current as did incubation of the cells in calphostin C. and inhibitor of protein kinase C (PKC). Removal of Ca2+ did not affect activation of the current by GTP gamma S but extended the duration of the response. Inhibition of phospholipase A2 (PLA2) with p-bromophenacyl bromide prevented the activation of the hypotonically induced current and also inhibited the current once activated by hypotonic solution. The findings imply that the hypotonic response in PCE cells is mediated by both phospholipase C (PLC) and PLA2. Both phospholipases generate arachidonic acid, and, in addition, the PLC pathway regulates the PLA2 pathway via a PKC-dependent phosphorylation of PLA2.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗