Biomedical subjects

S Li

Publications and source records attributed to S Li.

At least 865 records · Page 48Linked to original sources

PubMed1998

Mitochondrial PEPCK: a highly polymorphic gene with alleles co-selected with Marek's disease resistance in chickens.

The gene coding for the mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M), a pivotal component in gluconeogenesis from lactate via the Cori cycle, was highly polymorphic in strains of egg-type chickens (White Leghorn) of different origins. Based on MspI restriction fragment polymorphisms a total of seven alleles could be distinguished. The allele frequencies were determined in six pairs of strains derived from different genetic base populations. Each pair consisted of two strains which differed in their susceptibility to Marek's disease (MD), a virus-induced neoplastic disease. The frequency of the most common haplotype (M2) was consistently higher in the susceptible strains than in the corresponding resistant strains (P < 0.05, Wilcoxon signed-ranks test), indicating that the observed differences were not due to random genetic drift. This result suggests that PEPCK-M may be a candidate gene which contains genetic variants affecting MD susceptibility. Variations in gluconeogenesis may affect the interplay between proliferation of neoplasia and host metabolism.

Alleles↗

PubMed1998

Influence of adrenal glands on the modulation of prolactin gene expression by the endogenous benzodiazepine ligand octadecaneuropeptide in the male rat pituitary gland.

Recently, an 86-amino acid polypeptide with high affinity for diazepam binding sites, termed diazepam-binding inhibitor (DBI), has been found in the rat brain. DBI, as well as a peptide derived from DBI, the octadecaneuropeptide DBI[33-50] (ODN), interacts with the GABA(A) receptor complex. To investigate the role of these endogenous ligands for GABA(A) receptors on prolactin gene expression, we studied the effects of acute intracerebroventricular administration (4 h before sacrifice) of ODN on prolactin mRNA levels in the male rat. Because, in some neuropeptidergic systems, glucocorticoids play a role in the response to ODN, we also studied the influence of adrenal glands and the effect of dexamethasone administration in the response of prolactin gene expression to ODN. ODN injection produced an increase in prolactin mRNA levels. Adrenalectomy performed 5 days before sacrifice resulted in an increase in prolactin gene expression and also potentiated the stimulating effect of ODN. Because castration has been shown to decrease prolactin gene expression in the male rat, we used castrated and adrenalectomized animals to study the role of dexamethasone in the response of lactotrophs to ODN. In these steroid-deprived animals, dexamethasone treatment (for 4 days) decreased prolactin mRNA levels but did not modify the response to ODN. These data indicate that an endogenous neuropeptide interacting with the GABA(A) receptor complex can stimulate prolactin gene expression and suggest that the adrenal glands may produce factor(s) capable of decreasing prolactin mRNA. On the other hand, it does not appear that glucocorticoid hormones play a role in the effect of ODN on lactotroph activity.

Adrenal Glands↗

PubMed1998

Mutagenesis of a single amino acid in the rat mu-opioid receptor discriminates ligand binding.

To investigate the role of Asp114 in the cloned rat mu-opioid receptor for ligand binding, the charged amino acid was mutated to an asparagine to generate the mutant mu receptor D114N. The wild-type mu receptor and the D114N mutant were then stably expressed in human embryonic kidney 293 cells, and the binding affinities of a series of opioids were investigated. The mu-selective agonists [D-Ala2,MePhe4,Gly-ol5]enkephalin and morphine and the endogenous peptides Met-enkephalin and beta-endorphin exhibited greatly reduced affinities for the D114N mutant compared with the wild-type mu receptor, as did the potent synthetic agonist etorphine. In contrast to the full agonists, the partial agonists buprenorphine and nalorphine and the antagonists diprenorphine and naloxone bound with similar affinities to the wild-type and D114N mutant mu receptors. The reduced affinities of the full agonists for the D114N mutant did not involve an uncoupling of the receptor from G proteins because methadone and etorphine stimulated the D114N mu receptors to inhibit adenylyl cyclase. Although the Asp114 to Asn114 mutation reduced full-agonist binding, mutation of His297 to Asn297 in the mu receptor did not but, in contrast, did reduce binding affinity of the partial agonist buprenorphine and the antagonist diprenorphine. These results indicate that some partial agonists and antagonists may have different determinants for binding to the mu receptor than do the prototypical full agonists.

Amino Acid Sequence↗

PubMed1998

Correlation between quantitative angiographic lesion severity and myocardial contrast intensity during a continuous infusion of perfluorocarbon-containing microbubbles.

The purpose of this study was to determine whether quantitative measurements of myocardial videointensity (MVI) during continuous intravenous infusions of microbubbles could detect differences in coronary artery stenosis severity during dobutamine stress echocardiography. Coronary artery stenoses were created in seven dogs by progressively tightening a snare around the coronary artery. Intravenous infusions of perfluorocarbon microbubbles were given during dobutamine stress. The initial rate of myocardial contrast enhancement (slope), peak myocardial contrast (peak MVI) at the longest pulsing interval, and the product (slope * peak MVI) were compared as ratios in the stenosed versus adjacent normal perfusion beds. Twenty-two coronary stenoses were compared (range 16% to 80% in diameter). There was a strong correlation between both slope ratios and slope * peak MVI ratios and percent stenosis (r = -0.89 for both, p<0.001). The rate of contrast replenishment during a continuous infusion of microbubbles can be used to determine both the presence and severity of coronary stenoses during stress echocardiography.

Animals↗

PubMed1998

Mammography use among women attending an inner-city clinic.

BACKGROUND: Low-income, minority, and inner city women have breast cancer screening rates that are below those of the general population. METHODS: The authors surveyed women who received primary care at Seattle's county hospital about their mammography behaviors in early 1995. Data were analyzed within the context of the PRECEDE framework. RESULTS: Only half (48%) of the women were obtaining regular screening. Breast cancer and mammography beliefs differed by racial group. The following factors differentiated between inner-city women who were and were not regular users: mammography beliefs concerning early detection of disease, pressure from the machine causing breast cancer, and cost (these were less important among white women than members of other racial groups); previous physician discussions, concerns about appointment scheduling, and transportation problems; and social support from physicians, family, and friends. CONCLUSION: Interventions to encourage regular screening among inner-city women should address predisposing, enabling, and reinforcing factors.

Black or African American↗

PubMed1998

Virion encapsidation of tRNA(3Lys)-ribozyme chimeric RNAs inhibits HIV infection.

Retroviruses require a specific host cellular tRNA primer for initiation of first-strand DNA synthesis. This primer is bound by viral proteins and copackaged into virions. We have exploited this property in the design and testing of an antiviral ribozyme fused to tRNA(3Lys), the primer used for lentiviral replication, including human immunodeficiency virus (HIV-1 and HIV-2). The chimera consists of tRNA(3Lys) covalently attached to a hammerhead ribozyme, which is targeted to the region immediately upstream of the primer binding site of the HIV-1 genome. The tRNA-ribozyme chimeric transcript is catalytically active in vitro and is efficiently bound by HIV reverse transcriptase with an affinity similar to that of tRNA(3Lys). We have expressed the chimeric RNAs from either the tRNA(3Lys) intragenic RNA polymerase III promoter or from a human U6 snRNA promoter. The U6 promoter results in up to 10-fold enhanced expression of the tRNA-ribozyme. Most importantly, the tRNA(3Lys)-ribozymes are encapsidated in HIV-1 virions such that they are effective in substantially reducing the level of infectious virus produced from cells cotransfected with HIV-1 proviral DNA. These results demonstrate the feasibility of using this novel strategy to reduce HIV infectivity and more generally indicate the potential power of using the retroviral primer tRNAs as tools for expressing and delivering ribozymes and other antiretroviral RNAs to the virion capsid.

Anti-HIV Agents↗

PubMed1998

Restricted TCR Valpha gene rearrangements in T cells recognizing an immunodominant peptide of myelin basic protein in DR2 patients with multiple sclerosis.

T cell responses to myelin basic protein (MBP) are thought to play an important role in the pathogenesis of multiple sclerosis (MS). The response to the 83-99 region of MBP represents a dominant response to MBP in patients with MS and is associated with HLA-DR2 that is linked with susceptibility to MS. Although T cell clones reactive to various regions of MBP have been found to exhibit heterogeneous TCR Vbeta gene usage in patients with MS, it is unclear whether T cell clones uniformly recognizing the 83-99 peptide of MBP in the context of the same DR molecule would have restricted TCR V gene rearrangements and recognition motifs. In this study, a panel of DR2- or DR4-restricted T cell clones specific for the MBP83-99 peptide were derived from 11 patients with MS and examined for TCR V gene usage by PCR and the recognition motifs using analog peptides. Our study revealed that despite a few T cell clone pairs having similar recognition motifs and shared sequence homology in the CDR3, the overall recognition motifs of MBP83-99-specific T cells were considerably diverse. Interestingly, the DR2-restricted T cell clones displayed a biased V gene usage for Valpha3 and Valpha8, while Vbeta gene rearrangements were highly heterogeneous. This study provided experimental evidence suggesting a limited heterogeneity in TCR Valpha gene rearrangements of MBP-reactive T cells in DR2 patients with MS.

Amino Acid Sequence↗

PubMed1998

Guanidinated protein test meals with higher concentration of soybean trypsin inhibitors increase ileal recoveries of endogenous amino acids in pigs.

The amino acid concentrations of cornstarch-based guanidinated unprocessed (UGM) and autoclaved (AGM) Nutrisoy (defatted soy flour) protein test meals were compared with the respective unguanidinated Nutrisoy diets. Endogenous ileal recoveries and true digestibilities of amino acids were determined in six growing pigs, fitted with a simple T-cannula at the distal ileum, fed the guanidinated protein test meals. The UGM and AGM contained 13.4 (high) and 3.0 (low) g/kg dry matter of soybean trypsin inhibitors (SBTI), respectively. The experiment was a two-period cross-over design with each period lasting 15 d. On d 14 of each period, the pigs were fed the guanidinated test meals followed by 24 h continuous collection of digesta. Concentrations of crude protein and most of the amino acids in the test meals were higher than in the respective diets. Apparent ileal amino acid digestibilities of the test meals did not differ (P > 0.05) from reported values for the respective diets and were higher (P < 0.05) by 22.7 (cysteine) to 61.3 (tyrosine) percentage units for AGM compared with UGM. The ileal recoveries of endogenous amino acids in AGM-fed pigs were lower (P < 0.05) than UGM-fed pigs. Values ranged from -0.10 (arginine) to 0.64 (aspartate + asparagine) and from 0.84 (histidine) to 2.61 (tyrosine) g/kg dry matter intake for AGM- and UGM-fed pigs, respectively. True ileal amino acid digestibilities for AGM were higher (P < 0.05) than UGM with differences ranging from 12.7 (tyrosine) to 38.3 (leucine) percentage units. In conclusion, ileal recoveries of endogenous amino acids were increased in pigs fed guanidinated protein test meals with the higher concentration of SBTI.

Amino Acids↗

PubMed1998

Bacteriolytic activity and specificity of Achromobacter beta-lytic protease.

Achromobacter beta-lytic protease (blp), one of the bacteriolytic proteases secreted by Achromobacter lyticus, exhibited both peptidase and bacteriolytic activities at alkaline pH. The protease was strongly inhibited by 1,10-phenanthroline, and one zinc atom was detected in the molecule by ion-spray mass spectrometry. The zinc-protease specifically cleaved Gly-X bonds in peptides and possibly possessed subsites S2, S1, S1', and S2' for binding substrate [Schecter, I. and Berger, A. (1967) Biochem. Biophys. Res. Commun. 27, 157-162]. Blp lysed Staphylococcus aureus and Micrococcus luteus cells more efficiently than Achromobacter alpha-lytic protease (alp) and lysozyme, thus being responsible for the high bacteriolytic activity of A. lyticus. In the lysis of bacterial cell walls, blp hydrolyzed both the D-Ala-Gly/Ala bond at the linkage between the peptide subunit and the interpeptide and the Gly-Gly bond in the interpeptide bridge. These results indicate that blp is a highly active bacteriolytic enzyme with a broad bacteriolytic spectrum, which acts primarily by splitting the linkage between the peptide subunit and the interpeptide in the peptidoglycan.

Alcaligenes↗

PubMed1998

Genetic variability in white leghorns revealed by chicken liver expressed sequence tags.

A total of 92 expressed sequence tags from chicken liver (CLEST) were searched for homology with known genes. Among the CLEST, 29% had no sequence similarities with known genes, 34% showed sequence similarity to rRNA, 9% to mitochondrial genes, 23% to known nuclear genes, and 5% to human expressed sequence tags. Among the nuclear CLEST (excluding rRNA), clones with sequence similarity to aldolase B were represented four times, whereas all the other clones represented unique genes. The presence of MspI and TaqI restriction fragment length polymorphisms (RFLP) associated with CLEST were analyzed by bulk Southern blotting in 16 strains of White Leghorn chickens derived from five different genetic bases. No RFLP were observed with rRNA CLEST and a single MspI RFLP was observed with mitochondrial CLEST. The nuclear CLEST with sequence similarity to known nuclear genes were grouped into two classes on the basis of their involvement in intermediary metabolism. Among the nine genes coding for metabolic enzymes, all but one were polymorphic at MspI and/or TaqI sites in at least one of the strains, whereas among the other genes six of nine were polymorphic. The average frequency of clones revealing RFLP per cDNA clone and restriction enzyme for the two classes were 0.7 and 0.3, respectively. The analysis indicated that in White Leghorns, RFLP markers in the vicinity of nuclear CLEST are relatively frequent. Further, RFLP in the vicinity of genes coding for metabolic enzymes were significantly more frequent than near genes coding for other proteins.

Animals↗

PubMed1998

An unusual complication associated with hard palate mucosal grafts: presumed minor salivary gland secretion.

Hard palate grafts are commonly used in eyelid reconstructive procedures as a replacement for posterior lamellar defects. Four patients are presented with an unusual complication after placement of a hard palate graft: presumed minor salivary gland secretion. They were experiencing stringy mucous discharge over the graft and along the eyelids, causing visual blurring. Removal of the graft in one patient and cryotherapy to the grafts in the others (presumably causing atrophy of the minor salivary gland tissue found within the grafts) allowed resolution of symptoms. The authors propose the application of cryotherapy to the graft surface to atrophy the salivary glands, prevent any further production of mucus, and return the tear film to a more normal consistency. Alternatively, surgical removal of the grafts can be performed. To our knowledge, this complication (saliva-like mucoid discharge) has not been previously reported.

Adult↗

PubMed1998

Effect of increasing temperature on the properties of four bone cements.

This investigation uses a laboratory model to evaluate the effects of a heated femoral stem on the biomechanical properties of four common acrylic bone cements. American Society for Testing Materials dog bone shaped acrylic cement specimens made at four test temperatures, 0 degree C, 23 degrees C, 37 degrees C and 50 degrees C, were tested for modulus, ultimate tensile strength, fracture toughness, and percent porosity. Fatigue strength was tested in Simplex P at 23 degrees C and 37 degrees C. The data allow direct comparison among four cement brands at each of the four temperature conditions. No adverse changes of the mechanical properties were found for any cement at any temperature. Modulus, fracture toughness, and fatigue strength were unaffected by increased temperature. Ultimate tensile strength increased in Simplex P and Zimmer Osteobond but was unaffected for Zimmer Regular and Palacos R cements. Percent porosity was related to temperature changes inversely in all brands studied, except for Palacos R which consistently had low porosity, unaffected by temperature variation. Fatigue strength of Simplex P was unaffected by heating to 37 degrees C. Based on this laboratory model, heating of the femoral stem could save time without sacrificing mechanical properties of acrylic bone cement.

Biomechanical Phenomena↗

PubMed1998

Influence of contrast media on the response of rat renal arteries to endothelin and nitric oxide: influence of contrast media.

RATIONALE AND OBJECTIVES: Contrast media (CM) such as diatrizoate meglumine (DTZ) or iohexol can cause renal vasoconstriction in vivo, and this may initiate CM-induced nephropathy. Endothelin-1 (ET-1), a vasoconstrictor, and nitric oxide, a vasodilator, are key modulators of renal circulation. We tested the hypothesis that CM enhances arterial responses to ET-1, or diminishes responses to nitric oxide. METHODS: A video dimension analyzer continuously recorded changes in diameter of isolated, pressurized rat interlobar renal arteries (200-400 microm diameter) superfused with combinations of CM, ET-1, nitric oxide, and other vasoactive agents. RESULTS: Superfusion of arteries with 3.3% DTZ, but not with 3.3% iohexol, enhanced their sensitivity to ET-1 by approximately twofold, as assessed by shifts in concentration-response curves. Both DTZ and iohexol decreased the sensitivity of arteries to nitric oxide by approximately threefold. Neither DTZ nor iohexol affected arterial sensitivity to other vasoconstrictors (phenylephrine, potassium) or vasodilators (forskolin, diltiazem). CONCLUSIONS: Diatrizoate meglumine and iohexol may induce or augment renal vasoconstriction in part by causing selective alterations in arterial sensitivity to ET-1 and to nitric oxide.

Analysis of Variance↗

PubMed1998

Are estrogens carcinogenic during development of the testes?

Many chemicals in the environment mimic the female sex hormone, estrogen. Exposure to environmental estrogens during early fetal development was proposed by Sharpe & Skakkebaek as a potential risk factor for subsequent testicular disease, including neoplasia and poor semen quality. To understand the mechanisms of action of estrogenic chemicals during differentiation of the male genital tract, we have studied developmental exposure to the synthetic estrogen, diethylstilboestrol (DES). While DES is a much more potent estrogen than most environmental chemicals examined, several of these compounds share some of the same properties as DES, such as a relative lack of binding to serum estrogen carrying proteins. Prenatal exposure to DES is associated with poor semen quality, prostatic disease, cryptorchidism and testicular neoplasia in mice. A rare form of testicular cancer, rete testis carcinoma, was observed in five percent of male mice treated in utero with DES. We also demonstrated altered regulation of an estrogen responsive gene, lactotransferrin (LTF) in the seminal vesicles of treated mice, but not the controls. Likewise, LTF was irreversibly altered in the uteri of developmentally treated females; at the molecular level altered methylation of the gene appears to be involved, thus, providing a potential marker for hormonal effects during development. The induction of permanent or "imprinted" responses during the development of a relatively estrogen-free reproductive tract cell suggests that undifferentiated targets for estrogen action may be sites for subsequent growth and differentiation defects associated with neoplasia.

Animals↗

PubMed1998

Temporal gap detection measured with multiple sinusoidal markers: effects of marker number, frequency, and temporal position.

Detection thresholds were measured for silent temporal gaps within combinations of two, three, or four sinusoidal markers (i.e., combinations of one or two pre-gap markers with one or two post-gap markers). The markers were selected from the frequency range 2000-3100 Hz. Sinusoidal frequencies F1 and F4 were used as pre-gap markers, while F2 and F3 served as post-gap markers. Temporal gap detection (TGD) thresholds were measured from sets of three normal-hearing adults who tracked 70.7% correct detection thresholds adaptively across blocks of 50 two-interval, two-alternative, forced-choice trials. For symmetric marker conditions, where pre- and post-gap markers were equivalent in frequency (e.g., F1 = F2 or F1 = F2 and F3 = F4), TGD thresholds were < 10 ms. However, for asymmetric marker frequency alignments across the silent gap, including stimulus configurations where only three markers were presented on a trial (e.g., F1 = F2, F2 not equal to F3, no F4), performance was highly variable and was dramatically disrupted by the presentation of a second post-gap marker. The multiple-marker results reveal that TGD depends greatly on the number of markers presented, both in terms of the marker temporal position before and after the silent gap signal and the marker frequency alignment (symmetry) across the gap. These results, which cannot be predicted from models of the auditory periphery, may reflect perceptual mechanisms that are important in grouping and organizing auditory images.

Adult↗

PubMed1998

Suppressor scanning at positions 177 and 236 in the Escherichia coli lactose/H+ cotransporter and stereotypical effects of acidic substituents that suggest a favored orientation of transmembrane segments relative to the lipid bilayer.

Acidic substituents for Ala-177 (helix 6) or Tyr-236 (helix 7) in LacY cause effects on sugar recognition and cosubstrate coupling that are stereotypical of neutral substituents. Thus, helices 6 and 7 are probably oriented to produce little side-chain contact with the low dielectric lipid bilayer at positions 177 and 236.

Carrier Proteins↗

PubMed1998

Escherichia coli strains lacking protein HU are UV sensitive due to a role for HU in homologous recombination.

hupA and hupB encode the alpha and beta subunits of the Escherichia coli histone-like protein HU. Here we show that E. coli hup mutants are sensitive to UV in the rec+ sbc+, recBC sbcA, recBC sbcBC, umuDC, recF, and recD backgrounds. However, hupAB mutations do not enhance the UV sensitivity of resolvase-deficient recG ruvA strains. hupAB uvrA and hupAB recG strains are supersensitive to UV. hup mutations enhance the UV sensitivity of ruvA strains to a much lesser extent but enhance that of rus-1 ruvA strains to the same extent as for rus+ ruv+ strains. Our results suggest that HU plays a role in recombinational DNA repair that is not specifically limited to double-strand break repair or daughter strand gap repair; the lack of HU affects the RecG RusA and RuvABC pathways for Holliday junction processing equally if the two pathways are equally active in recombinational repair; the function of HU is not in the substrate processing step or in the RecFOR-directed synapsis action during recombinational repair. Furthermore, the UV sensitivity of hup mutants cannot be suppressed by overexpression of wild-type or mutant gyrB, which confers novobiocin resistance, or by different concentrations of a gyrase inhibitor that can increase or decrease the supercoiling of chromosomal DNA.

Bacterial Outer Membrane Proteins↗

PubMed1998

CCR5 expression correlates with susceptibility of maturing monocytes to human immunodeficiency virus type 1 infection.

The chemokine receptor CCR5 and to a lesser extent CCR3 and CCR2b have been shown to serve as coreceptors for human immunodeficiency virus type 1 (HIV-1) entry into blood- or tissue-derived macrophages. Therefore, we examined the expression of the chemokine receptors CCR1, CCR2b, CCR3, CCR5, and CXCR4 as RNAs or as membrane-expressed antigens in monocytes maturing into macrophages and correlated these results with the susceptibility of macrophages to HIV-1 infection, as measured by their concentrations of extracellular p24 antigen and levels of intracellular HIV DNA by quantitative PCR. There was little change in levels of CCR1, CCR2b, and CCR5 RNAs. CCR3 RNA and surface antigen were undetectable throughout maturation of adherent monocytes over 10 days. CXCR4 RNA and membrane antigen were strongly expressed in newly adherent monocytes, but their levels declined at day 7. The amounts of CCR5 RNA remained stable, but the amounts of CCR5 antigen increased from undetectable to peak levels at day 7 and then declined slightly at day 10. Levels of susceptibility to laboratory (HIV-1BaL) and clinical strains of HIV-1 showed parallel kinetics, peaking at day 7 and then decreasing at days 10 to 14. The concordance of levels of HIV DNA and p24 antigen suggested that the changes in susceptibility with monocyte maturation were at or immediately after entry and correlated well with CCR5 expression and inversely with CXCR4 expression.

Base Sequence↗