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Biomedical subjects

L Gao

Publications and source records attributed to L Gao.

At least 37 records · Page 2Linked to original sources
PubMed2003

Fabrication of HAp-ZrO2 (3Y) nano-composite by SPS.

Nano-HAp-ZrO(2) powders and HAp-TZP(3Y) composites have been fabricated in this work. The results show that nano-HAp-ZrO(2) powders with homogeneous distribution could be synthesized by two-step precipitation method. HAp-TZP(3Y) composites with small grain size could be sintered at relatively low temperatures and very short dwelling time by using SPS technology. No reaction between HAp and ZrO(2) was found, which could be attributed to the very short sintering time of SPS.

Biocompatible Materials↗
PubMed2002

Rocuronium plasma concentrations during three phases of liver transplantation: relationship with early postoperative graft liver function.

BACKGROUND: Previous studies have suggested that neuromuscular blocking agents might be used to assess liver function during liver transplantation. This study examines changes in rocuronium plasma concentration during liver transplantation, to assess graft function. METHODS: A constant-rate infusion of rocuronium was administered to 17 adult patients undergoing liver transplantation. Blood samples were taken at 30-min intervals throughout the procedure, which was divided into three phases: paleo-, an-, and neohepatic. Assay of plasma concentrations of rocuronium was by a gas chromatographic-mass spectrometry technique. Postoperative liver function was followed for up to five days by measuring plasma aminotransferases. RESULTS: In 14 of the 15 patients who survived the transplantation procedure, there was a 7-50% decrease in rocuronium concentration during the neohepatic phase compared with the anhepatic phase. In contrast, rocuronium concentrations increased in the two patients who died after surgery, one as a result of primary non-function and one from massive bleeding. In one patient who survived there was no change in rocuronium concentration. The increase in plasma rocuronium concentration during the neohepatic phase in the two patients who died was consistent with high levels of plasma aminotransferases. CONCLUSIONS: Comparison of changes in plasma rocuronium concentration during the neohepatic phase with early postoperative liver function tests suggests the potential use of rocuronium as a pharmacokinetic probe for predicting liver function during liver transplantation. Further study of rocuronium's potential as an intraoperative pharmacodynamic probe of liver function by measuring neuromuscular paralysis is suggested.

Adult↗
PubMed2002

Improved production of Neospora caninum oocysts, cyclical oral transmission between dogs and cattle, and in vitro isolation from oocysts.

Scarce information is available about Neospora caninum oocysts and sporozoites, in part because only small numbers of oocysts have typically been produced by experimentally infected dogs. We hypothesized that I reason for low experimental production of oocysts is that dogs have been fed tissues from experimentally infected mice instead of tissues from cattle (which are natural intermediate hosts of N. caninum). In this study, 9 dogs were fed tissues from N. caninum-infected calves, and oocyst production was compared with 6 dogs that were fed infected mouse carcasses. The number of oocysts produced by dogs that ingested infected calf tissues (mean = 160,700) was significantly greater (P = 0.03) than the number of oocysts shed by dogs that ingested infected mice (mean = 5,400). The second goal of our experiment was to demonstrate cyclical oral transmission of N. caninum between dogs and cattle. As few as 300 oocysts were used to successfully infect calves, and tissues from these calves induced patent infections in 2 of 3 dogs; oocysts from I of these dogs were administered to another calf, and tissues from this calf subsequently induced a third dog to shed oocysts. Oocysts were confirmed to be N. caninum using a species-specific polymerase chain reaction technique. In addition, sporulated oocysts were used to recover N. caninum in vitro after digestion in an acid-pepsin solution and inoculation of cell monolayers.

Animals↗
PubMed2001

Effective nonlinear optical properties of metal-dielectric composite media with shape distribution.

The effective linear and nonlinear optical properties have been investigated in granular metal-dielectric composites taking the geometric shape of inclusions into account. Recently derived Maxwell-Garnett-type approximations are generalized to study the spectral function for composites in which the metal inclusions have a uniform distribution of geometric shapes. The numerical results show that the spectral density function becomes a prominent peak around small spectral value s within the non-self-consistent Maxwell-Garnett approximation but a broad continuous spectrum around large s besides the prominent peak around small s within the self-consistent Maxwell-Garnett approximation. Based on the spectral representation, we investigate the optical absorption and third-order nonlinear optical susceptibility. The results indicate that the shape distribution can lead to the separation of the nonlinearity enhancement peak from the absorption peak and thereby make the figure of merit more attractive.

Journal Article↗
PubMed2001

Accessibility and activity of the promoter for a dioxin-inducible ecto-ATPase gene.

We have analyzed the core promoter for a dioxin-inducible ecto-ATPase gene in mouse hepatoma cells. The transcriptional initiation site maps to a region that contains neither a TATA sequence nor a consensus initiator sequence nor a downstream promoter element. The core promoter has constitutive activity that does not require either the aromatic hydrocarbon receptor or its heterodimerization partner Arnt. Two GC-rich regions contribute approximately equally to the constitutive activity. Proteins constitutively occupy the GC-rich regions in chromatin. The promoter assumes a non-nucleosomal configuration in its native chromosomal setting in both uninduced and dioxin-induced cells. Our findings imply that the GC-rich regions together with their cognate binding proteins carry out core promoter functions for the ecto-ATPase gene. The promoter is constitutively accessible in situ, and chromatin structure is not a limiting factor for dioxin-inducible ecto-ATPase transcription in intact cells.

Adenosine Triphosphatases↗
PubMed2001

[Study on the level of plasma calcitonin gene-related peptide and adrenomedullin in subjects with primary osteoporosis].

OBJECTIVES: To explore if there is any change of the level of plama CGRP and ADM in primary osteoporosis. METHODS: 75 female subjects complaining of back pain, aged from 34-70 years, were included in present study. The plasma level of CGRP and ADM was determined by radioimmunoassay. The bone mineral density (BMD) of lumber spine and hip of these patients was also examined by dual-energy X-ray absorptiometry (DEXA). According to the WHO osteoporosis criteria, these patients were divided into three groups: normal BMD (as control), osteopenia and osteoporosis. RESULTS: Plasma level of CGRP and ADM of lumbar osteoporosis are 37 ng/L +/- 7 ng/L and 50 ng/L +/- 11 ng/L respectfully, while those of lumber osteopenia are 38 ng/L +/- 7 ng/L and 49 ng/L +/- 11 ng/L, they are significantly higher than those of normal lumber bone mineral density, which are 29 ng/L +/- 6 ng/L and 38 ng/L +/- 8 ng/L(F = 5.60 or 9.60, P < 0.05 or 0.01). The plasma level of ADM of hip and ward's osteoporosis (49 ng/L +/- 13 ng/L and 49 ng/L +/- 11 ng/L) is also higher than that of the control (F = 5.43 and 4.66, P < 0.05). Group of lumbar osteopenia also has higher level of CGRP and ADM than the control. (37 ng/L +/- 7 ng/L) and 38 ng/L +/- 6 ng/L, P < 0.05). CONCLUSIONS: Plasma level of CGRP and ADM is significantly increased in subjects with osteoporosis. CGRP and ADM may play a role in the mechanism of etiology of primary osteoporosis.

Adrenomedullin↗
PubMed2001

[Association of 16189 variant (T-->C transition) of mitochondrial DNA with genetic predisposition to type 2 diabetes in Chinese populations].

OBJECTIVE: To assess the prevalence of 16189 variant (T-->C transition) of mitochondrial DNA in Chinese populations and to study the relation between mtDNA 16189 variant and insulin resistance and the role it plays in genetic predisposition to diabetes. METHODS: PCR and RELP techniques were used to examine 383 unrelated type 2 diabetics and 151 non-diabetic controls selected by random sampling. RESULTS: (1) The prevalence of 16189 variant among type 2 diabetics was significantly higher than that among the controls. (2) The prevalence of 16189 variant was significantly higher among type 2 diabetics with maternal family history than among those without maternal family history. (3) In comparison with the type 2 diabetics without 16189 variant, those with 16189 variant showed higher fasting serum insulin level, decreased insulin sensitivity index, and higher Homa insulin resistance index. (4) In the control group, no significant difference in age, gender, body mass index, waist to hip ratio, serum lipid level, fasting plasma glucose level, fasting serum insulin level, insulin sensitivity index, and Homa insulin resistance index was found between those with 16189 variant and those without 16189 variant. CONCLUSION: 16189 variant of mitochondrial DNA is one of the genetic predisposing factors for type 2 diabetes mellitus in Chinese populations. It might interfere with the energy metabolism and the production of ATP, thus causing insulin resistance in peripheral tissues.

Adenosine Triphosphate↗
PubMed2001

Gas chromatographic-mass spectrometric assay for rocuronium with potential for quantifying its metabolite, 17-desacetylrocuronium, in human plasma.

A rapid, sensitive and selective method has been developed for the quantification of plasma concentrations of neuromuscular blocking drug, rocuronium, using gas chromatography with mass spectrometric detection. 3-Desacetylvecuronium served as the internal standard. The method involved iodide ion pair formation and a single-step liquid-liquid extraction with dicholoromethane. This method also permits simultaneous determination of its putative metabolite, 17-desacetylrocuronium, although the high detection limit for the metabolite limits the practical application of this method in pharmacokinetic study of the metabolite. The extraction efficiency was approximately 75% for rocuronium and approximately 50% for 17-desacetylrocuronium. The limit of quantification was 26 ng/ml for rocuronium and 870 ng/ml for its metabolite. The assay was used successfully in a patient undergoing liver transplantation and receiving rocuronium as a constant rate infusion and in a patient undergoing general elective surgery receiving the drug as an intravenous bolus. This assay is a time-saving alternative to published gas or liquid chromatographic methods for assaying rocuronium.

Androstanols↗
PubMed2001

Cloning and characterization of a novel Krüppel-like zinc finger gene, ZNF268, expressed in early human embryo.

With the aim of identifying genes involved in early human embryonic development, we have isolated a cDNA clone representing a novel human zinc finger gene ZNF268 from 3 week old human embryo cDNA library using a differential hybridization strategy. The complete cDNA sequence of ZNF268 contained an open reading frame of 2841 nucleotides that encodes a 947 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and 24 C-terminal zinc fingers. Northern blot analysis showed that ZNF268 mRNA is mainly expressed in 3-5 week old human embryos suggesting it could play certain roles in the embryogenesis. The gene consists of six exons spanning about 22 kb of genomic DNA. According to the genomic sequence from the HTGS database, the ZNF268 gene is assigned to human chromosome 5.

Amino Acid Sequence↗
PubMed2001

Patterns of CDKN2A gene loss in sequential oral epithelial dysplasias and carcinomas.

The CDKN2A gene locus encodes two different proteins derived from alternative splicing. p16 (exons 1alpha, 2, and 3) acts as a G1 cell cycle regulator, and p14ARF (exons 1beta, 2, and 3) acts to modulate MDM2-mediated degradation of p53. Inactivation of p16 is a common finding in many cancers; however, there is little data on CDKN2A gene abnormalities in oral precancer. In this longitudinal study, we examined changes in the CDKN2A gene locus in sequential epithelial dysplasias and oral carcinomas from 11 patients. Genomic DNA was extracted from laser-microdissected lesional tissue, and exons 1alpha, 1beta, and 2 were analyzed by duplex PCR. Immunohistochemistry was done to identify p16 and p14ARF protein expression. Two adjacent polymorphic microsatellite markers were used for allelotyping. Homozygous deletion of exon 1alpha was identified in 2 of 17 (12%) precancerous lesions. Loss of either exon 1alpha, exon 2, or both was seen in seven of nine (78%) carcinomas. In five of these carcinomas, there was loss of only exon 1alpha. No case showed deletion of exon 1beta. In 5 of 11 patients, microsatellite markers showed differing patterns of allelic imbalance in the precancerous lesions and the subsequent carcinoma, suggesting a complex genetic pattern of progression from dysplasia to carcinoma. We conclude that during oral carcinogenesis homozygous deletion of exon 1alpha of the CDKN2A gene is common but that deletion of exon 2 and 1beta is less frequent. Moreover, our results suggest that the progression from oral precancer to cancer, in some cases, is more complex genetically than predicted by linear models of carcinogenesis.

Actins↗
PubMed2001

cDNA transfection of amino-terminal fragment of urokinase efficiently inhibits cancer cell invasion and metastasis.

Focusing of urokinase-type plasminogen activator (uPA) to the cell surface via binding to its specific receptor (uPAR, CD87) is critical for tumor invasion and metastasis. Consequently, the inhibition of uPA-uPAR interaction on the cell surface might be a promising anti-invasion and anti-metastasis strategy. We examined the effects of cDNA transfection of the human uPA amino-terminal fragment (ATF) on invasion and metastasis of cancer cells. First, a highly metastatic human lung giant-cell carcinoma cell line (PG), used as the target cell for evaluation of this effect, was demonstrated to express both uPA and uPAR. Then, ATF, which contains an intact uPAR binding site but is catalytically inactive, was designed as an antagonist of uPA-uPAR interaction and was transfected into PG cells. [(3)H]-Thymidine incorporation and cell growth curves indicated that expressed ATF did not affect the proliferation of transfected cells. However, analysis by scanning electron microscopy revealed that ATF changed the host cells from the typical invasive phenotype to a noninvasive one. Correspondingly, the modified Boyden chamber test in vitro showed that ATF expression significantly decreased the invasive capacity of transfected cells. Furthermore, in the spontaneous metastasis model, it was confirmed in vivo that expressed ATF remarkably inhibited lung metastasis of implanted ATF-transfected PG cells. In summary, autocrine ATF could act as an antagonist of uPA-uPAR interaction, and ATF cDNA transfection could efficiently inhibit the invasion and metastasis of the cancer cells. Inhibition of uPA-uPAR interaction on the cell surface might be a promising anti-invasion and anti-metastasis strategy.

Animals↗
PubMed2001

Heterogeneity within medullary-type TCRalphabeta(+)CD3(+)CD4(-)CD8(+) thymocytes in normal mouse thymus.

The functional maturation process of medullary-type CD4(-)CD8(+) [CD8 single-positive (SP)] thymocytes remains largely uncharacterized. We describe a phenotypic analysis of CD8 SP medullary-type thymocytes and find a remarkable heterogeneity within this thymic cell population. While mature CD8(+) T cells in the periphery are relatively homogeneous (TCRalphabeta(+)CD3(+)Qa-2(+) HSA(-)3G11(-)6C10(-)CD69(-)), CD8 SP medullary-type thymocytes contain discrete subpopulations that can be identified by differential expression of several cell-surface markers. We have identified at least six discrete subpopulations in the subset of TCRalphabeta(+)CD3(+) CD8 SP cells in the thymus. According to the expressed phenotypes, a linear developmental pathway is predicted among these CD8 SP subpopulations as follows: 6C10(+)CD69(+)HSA(hi)3G11(+)Qa-2(-) --> 6C10(-)CD69(+)HSA(hi/int)3G11(+)Qa-2(-) --> 6C10(-)CD69(-)HSA(int)3G11(+)Qa-2(-) --> 6C10(-)CD69(-)HSA(lo)3G11(+)Qa-2(-) --> 6C10(-)CD69(-)HSA(-/lo)3G11(-)Qa-2(-) --> 6C10(-)CD69(-)HSA(-/lo)3G11(-)Qa-2(+). This study provides a framework for understanding CD8 SP T cell maturation in the thymic medulla.

Animals↗
PubMed2001

Genetic heterogeneity of Borrelia burgdorferi sensu lato in the southern United States based on restriction fragment length polymorphism and sequence analysis.

Fifty-six strains of Borrelia burgdorferi sensu lato, isolated from ticks and vertebrate animals in Missouri, South Carolina, Georgia, Florida, and Texas, were identified and characterized by PCR-restriction fragment length polymorphism (RFLP) analysis of rrf (5S)-rrl (23S) intergenic spacer amplicons. A total of 241 to 258 bp of intergenic spacers between tandemly duplicated rrf (5S) and rrl (23S) was amplified by PCR. MseI and DraI restriction fragment polymorphisms were used to analyze these strains. PCR-RFLP analysis results indicated that the strains represented at least three genospecies and 10 different restriction patterns. Most of the strains isolated from the tick Ixodes dentatus in Missouri and Georgia belonged to the genospecies Borrelia andersonii. Excluding the I. dentatus strains, most southern strains, isolated from the ticks Ixodes scapularis and Ixodes affinis, the cotton rat (Sigmodon hispidus), and cotton mouse (Peromyscus gossypinus) in Georgia and Florida, belonged to Borrelia burgdorferi sensu stricto. Seven strains, isolated from Ixodes minor, the wood rat (Neotoma floridana), the cotton rat, and the cotton mouse in South Carolina and Florida, belonged to Borrelia bissettii. Two strains, MI-8 from Florida and TXW-1 from Texas, exhibited MseI and DraI restriction patterns different from those of previously reported genospecies. Eight Missouri tick strains (MOK-3a group) had MseI patterns similar to that of B. andersonii reference strain 21038 but had a DraI restriction site in the spacer. Strain SCGT-8a had DraI restriction patterns identical to that of strain 25015 (B. bissettii) but differed from strain 25015 in its MseI restriction pattern. Strain AI-1 had the same DraI pattern as other southern strains in the B. bissettii genospecies but had a distinct MseI profile. The taxonomic status of these atypical strains needs to be further evaluated. To clarify the taxonomic positions of these atypical Borrelia strains, the complete sequences of rrf-rrl intergenic spacers from 20 southeastern and Missouri strains were determined. The evolutionary and phylogenetic relationships of these strains were compared with those of the described genospecies in the B. burgdorferi sensu lato species complex. The 20 strains clustered into five separate lineages on the basis of sequence analysis. MI-8 and TXW-1 appeared to belong to two different undescribed genospecies, although TXW-1 was closely related to Borrelia garinii. The MOK-3a group separated into a distinct deep branch in the B. andersonii lineage. PCR-RFLP analysis results and the results of sequence analyses of the rrf-rrl intergenic spacer confirm that greater genetic heterogeneity exists among B. burgdorferi sensu lato strains isolated from the southern United States than among strains isolated from the northern United States. The B. andersonii genospecies and its MOK-3a subgroup are associated with the I. dentatus-cottontail rabbit enzootic cycle, but I. scapularis was also found to harbor a strain of this genospecies. Strains that appear to be B. bissettii in our study were isolated from I. minor and the cotton mouse, cotton rat, and wood rat. The B. burgdorferi sensu stricto strains from the south are genetically and phenotypically similar to the B31 reference strain.

Animals↗
PubMed2001

Synthetic chloride channel restores glutathione secretion in cystic fibrosis airway epithelia.

Cystic fibrosis (CF), an inherited disease characterized by defective epithelial Cl- transport, damages lungs via chronic inflammation and oxidative stress. Glutathione, a major antioxidant in the epithelial lung lining fluid, is decreased in the apical fluid of CF airway epithelia due to reduced glutathione efflux (Gao L, Kim KJ, Yankaskas JR, and Forman HJ. Am J Physiol Lung Cell Mol Physiol 277: L113-L118, 1999). The present study examined the question of whether restoration of chloride transport would also restore glutathione secretion. We found that a Cl- channel-forming peptide (N-K4-M2GlyR) and a K+ channel activator (chlorzoxazone) increased Cl- secretion, measured as bumetanide-sensitive short-circuit current, and glutathione efflux, measured by high-performance liquid chromatography, in a human CF airway epithelial cell line (CFT1). Addition of the peptide alone increased glutathione secretion (181 +/- 8% of the control value), whereas chlorzoxazone alone did not significantly affect glutathione efflux; however, chlorzoxazone potentiated the effect of the peptide on glutathione release (359 +/- 16% of the control value). These studies demonstrate that glutathione efflux is associated with apical chloride secretion, not with the CF transmembrane conductance regulator per se, and the defect of glutathione efflux in CF can be overcome pharmacologically.

Cell Line, Transformed↗
PubMed2001

Chlorzoxazone or 1-EBIO increases Na(+) absorption across cystic fibrosis airway epithelial cells.

Previous studies demonstrated that chlorzoxazone or 1-ethyl-2-benzimidazolinone (1-EBIO) enhances transepithelial Cl(-) secretion by increasing basolateral K(+) conductance (G(K)) (Singh AK, Devor DC, Gerlach AC, Gondor M, Pilewski JM, and Bridges RJ. J Pharmacol Exp Ther 292: 778-787, 2000). Hence these compounds may be useful to treat cystic fibrosis (CF) airway disease. The goal of the present study was to determine whether chlorzoxazone or 1-EBIO altered ion transport across Delta F508-CF transmembrane conductance regulator homozygous CFT1 airway cells. CFT1 monolayers exhibited a basal short-circuit current that was abolished by apical amiloride (inhibition constant 320 nM) as expected for Na(+) absorption. The addition of chlorzoxazone (400 microM) or 1-EBIO (2 mM) increased the amiloride-sensitive I(sc) approximately 2.5-fold. This overlapping specificity may preclude use of these compounds as CF therapeutics. Assaying for changes in the basolateral G(K) with a K(+) gradient plus the pore-forming antibiotic amphotericin B revealed that chlorzoxazone or 1-EBIO evoked an approximately 10-fold increase in clotrimazole-sensitive G(K). In contrast, chlorzoxazone did not alter epithelial Na(+) channel-mediated currents across basolateral-permeabilized monolayers or in Xenopus oocytes. These data further suggest that alterations in basolateral G(K) alone can modulate epithelial Na(+) transport.

Amiloride↗
PubMed2001

Complex gel permeation assays for screening combinatorial libraries.

Gel permeation methods have been commonly used to screen combinatorial libraries synthesized on a solid support. We report here three screens of combinatorial libraries using gel permeation assays. These include a simple enzymatic assay to identify inhibitors of the influenza enzyme neuraminidase, and two more complex assays designed to screen for inhibitors of the interleukin-8 (IL-8)-IL-8 receptor and the urokinase-urokinase receptor interactions, respectively. The IL-8 ligand-receptor assay makes use of IL-8 receptor-expressing cells attached to a membrane, thus enabling washing steps as part of the assay. The urokinase ligand-receptor assay employs an enzyme-linked immunosorbent assay-type format, previously thought to be amenable only to well-based assays. The results of these three screens are reported here, including the discovery of a novel series of acyclic inhibitors of neuraminidase. The development of complex assays in a gel permeation format allows for the routine screening of combinatorially as well as noncombinatorially made compound collections against virtually any kind of target, and is being widely used in our high throughput screening operations.

Chromatography, Gel↗
PubMed2001

[A retrospective analysis of therapeutic outcome of various types of severe virus hepatitis].

OBJECTIVE: To explore combined therapeutic schemes for severe virus hepatitis and to raise survival rate. METHODS: The therapeutic outcomes of different schemes were analyzed in 1020 cases of severe viral hepatitis treated in our hospital in recent twenty years. The treatments were classified as basic and combination of Chinese traditional and Western medicine therapies in which embryonic liver cell suspend liquid or hepatic growth factor, or/and artificial liver as blood cleaner were also used for the latter. RESULTS: The survival rate was 30.28% (33/109) treated by basic procedures and 60.15% (548/911) by combined procedures. There was obvious statistical difference in survival rate between the two groups (P<0.001). Among all the patients, 219 (21.47%) suffered from acute or sub-acute severe hepatitis, 801 (78.53%) chronic severe hepatitis; 446 started their treatment at the early stage of the disease and the survival rate was 77.13% (344/446); 404 at the mid stage and 170 at the late stage and the survival rates were 52.72% (213/404) and 14.12% (24/170), respectively. The survival rate for the patients treated at the early or the mid stage was much higher than that at the late stage (P<0.001), and had a positive correlation with the activity of prothrombin. CONCLUSION: The combined therapies used in present study are effective to raise the survival rate of the patients with severe virus hepatitis. Early treatment is extremely important for the patients' prognosis.

Adolescent↗