Biomedical subjects

J Huang

Publications and source records attributed to J Huang.

At least 361 records · Page 20Linked to original sources

PubMed1999

IL-12 administered during Chlamydia psittaci lung infection in mice confers immediate and long-term protection and reduces macrophage inflammatory protein-2 level and neutrophil infiltration in lung tissue.

Protection against infections with the intracellular bacterium Chlamydia spp. requires Th1-polarized CD4+ T cell immunity. In BALB/c mouse lung infections, immediate innate and nascent Chlamydia-specific immune responses following intranasal inoculation of Chlamydia psittaci strain B577 were modulated by 7-day i.p. administration of murine rIL-12, the initiation cytokine for Th1 immunity. Treatment with IL-12 reduced the severity of chlamydial pneumonia, abolished mortality (37.5% in untreated mice), and significantly reduced numbers of chlamydial organisms in lungs. On day 4 after inoculation, the neutrophil:macrophage ratio in bronchointerstitial pneumonias was 1.96 in untreated mice and 0.51 in IL-12-treated mice. This immediate, IL-12-mediated shift in innate inflammatory phenotype was correlated with a significant reduction of lung concentrations of the neutrophil chemoattractant macrophage inflammatory protein (MIP)-2 (putative murine homologue of human IL-8), monocyte chemotactic protein-1, and TNF-alpha; and a reduction in MIP-1alpha and IFN-gamma, at high-dose infection only, and IL-12-independent IL-10 levels. Chlamydia-specific Ab titers and Ig isotype ratios indicated an IL-12-dependent Th1 shift. Recall responses of IL-12-primed mice to secondary chlamydial lung infection eliminated chlamydiae more effectively and generated a lung cytokine profile conducive to perpetuation of the Th1 memory population. These data support the hypothesis that genetic differences in endogenous IL-12 production and response pathways could determine disease outcomes characterized by poor chlamydial clearance and a purulent inflammatory infiltrate vs effective elimination of chlamydiae in a macrophage-dominated response.

Administration, Intranasal↗

PubMed1999

Temporary and partial inhibition of platelets by SM-20302 prevents coronary artery thrombosis in a chronic canine model.

We proposed that temporary and partial platelet inhibition by a GPIIb/IIIa receptor antagonist, SM-20302, would provide sustained antithrombotic efficacy in a chronic model of coronary artery thrombosis. Instrumented, conscious dogs received vehicle (Group I, n = 7), low dose SM-20302 (30 microg/kg bolus + 1 microg/kg/min infusion for 6 h) (Group II, n = 7), or high dose SM-20302 (100 microg/kg bolus + 1 microg/kg/min infusion for 6 h) (Group III, n = 7). Thrombosis was initiated by electrolytic injury to the circumflex coronary artery. Coronary blood flow was monitored for 6 h on day 1 and days 2-6. Platelet aggregation was performed in platelet-rich plasma prepared from citrated or heparinized blood. At 6 h, both doses of SM-20302 inhibited adenosine diphosphate-induced platelet aggregation completely (> 90%) in citrated platelet-rich plasma, but incompletely (57-59%) in heparinized platelet-rich plasma. Platelet reactivity returned to baseline values at 24 h. Control animals developed thrombotic occlusion on Day 1. Both doses of SM-20302 maintained vessel patency during the infusion period (Day 1) and the subsequent 5 days. Myocardial infarct size and mortality in the drug treated groups were reduced compared to the vehicle group. Thus, temporary inhibition of platelet reactivity by SM-20302 is associated with sustained prevention of primary thrombus formation, and reduction in infarct size and mortality.

Animals↗

PubMed1999

Maximum solubility of cholesterol in phosphatidylcholine and phosphatidylethanolamine bilayers.

In any lipid bilayer membrane, there is an upper limit on the cholesterol concentration that can be accommodated within the bilayer structure; excess cholesterol will precipitate as crystals of pure cholesterol monohydrate. This cholesterol solubility limit is a well-defined quantity. It is a first-order phase boundary in the phospholipid/cholesterol phase diagram. There are many different solubility limits in the literature, but no clear picture has emerged that can unify the disparate results. We have studied the effects that different sample preparation methods can have on the apparent experimental solubility limit. We find that artifactual demixing of cholesterol can occur during conventional sample preparation and that this demixed cholesterol may produce artifactual cholesterol crystals. Therefore, phospholipid/cholesterol suspensions which are prepared by conventional methods may manifest variable, falsely low cholesterol solubility limits. We have developed two novel preparative methods which are specifically designed to prevent demixing during sample preparation. For detection of the cholesterol crystals, X-ray diffraction has proven to be quantitative and highly sensitive. Experiments based on these methods yield reproducible and precise cholesterol solubility limits: 66 mol% for phosphatidylcholine (PC) bilayers and 51 mol% for phosphatidylethanolamine (PE) bilayers. We present evidence that these are true, equilibrium values. In contrast to the dramatic headgroup effect (PC vs. PE), acyl chain variations had no effect on the cholesterol solubility limit in four different PC/cholesterol mixtures.

Cholesterol↗

PubMed1999

Characterization of the surface proteins of influenza A (H5N1) viruses isolated from humans in 1997-1998.

Influenza A (H5N1) viruses infected humans in Hong Kong between May and December, 1997. Sixteen viruses, including 6 from fatal cases, were isolated during this outbreak. Molecular analysis of the surface proteins genes encoding the hemagglutinin (HA) and neuraminidase (NA) of these H5N1 isolates, of a subtype not previously known to infect humans, are presented. The 16 human H5 HA sequences contain multiple basic amino acids adjacent to the cleavage site, a motif associated with highly pathogenic avian influenza A viruses. The phylogenetic relationship among both avian and human H5 hemagglutinins indicates that the human isolates are related directly to isolates that circulated among chickens in the live poultry markets in Hong Kong prior to and during the outbreak in humans. HA sequences from the human isolates and a recent chicken isolate represent a separate clade, within which there are two subgroups that are distinguishable antigenically and by the presence of a potential glycosylation site. Likewise the N1 neuraminidases of the human H5 isolates represent a clade that is evolutionarily distinct from previously characterized N1 neuraminidases. The recent human H5N1 virus NA genes are avian-like, indicating direct introduction from an avian source rather than evolution of a human N1 NA. All of the 16 human NA genes encode a shortened stalk due to a 19-amino acid deletion, also found in the recent avian H5N1 isolates from Hong Kong. Two unique amino acids were identified in the N1 NAs of the recent human isolates; however, it is not known if these residues influence host range. Neither the HA nor the NA genes of the human H5N1 virus isolates show evidence of adaptive changes during the outbreak. Although analyses of the surface protein genes of the H5N1 viruses from this outbreak did not provide immediate answers regarding the molecular basis for virulence, the analyses provided clues to potentially important areas of the genes worth further investigation.

Adolescent↗

PubMed1999

High frequency of p16INK4A gene alterations in hepatocellular carcinoma.

The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) is an important component of the cell cycle and inactivation of the gene has been found in a variety of human cancers. In order to investigate the role of p16 gene in the tumorigenesis of hepatocellular carcinoma (HCC), 48 cases of HCC were analysed for p16 alterations by: methylation-specific PCR (MSP) to determine the methylation status of the p16 promoter region; comparative multiplex PCR to detect homozygous deletion; PCR-SSCP and DNA sequencing analysis to identify mutation of the p16 gene. We found high frequency of hypermethylation of the 5' CpG island of the p16 gene in 30 of 48 cases (62.5%) of HCC tumors. Moreover, homozygous deletion at p16 region were present in five of 48 cases (10.4%); and missense mutation were detected in three of 48 cases (6.3%). The overall frequency of p16 alterations, including homozygous deletion, mutation and hypermethylation, in HCC tumors was 70.8% (34 of 48 cases). These findings suggest that: (a) the inactivation of the p16 is a frequent event in HCC; (b) the p16 gene is inactivated by multiple mechanisms including homozygous deletion, promoter hypermethylation and point mutation; (c) the most common somatic alteration of the p16 gene in HCC is de novo hypermethylation of the 5' CpG island; and (d) in contrast to other studies, high frequency of genomic alterations are not uncommon in the 9p21 of the p16 gene. Our results strongly suggest that the p16 gene plays an important role in the pathogenesis of HCC.

Carcinoma, Hepatocellular↗

PubMed1999

In vivo sensitivity of human melanoma to tumor necrosis factor (TNF)-alpha is determined by tumor production of the novel cytokine endothelial-monocyte activating polypeptide II (EMAPII).

Tumor necrosis factor (TNF)-alpha is a potent anticancer agent that seems to selectively target tumor-associated vasculature resulting in hemorrhagic necrosis of tumors without injury to surrounding tissues. The major limitation in the clinical use of TNF has been severe dose-limiting toxicity when administered systemically. However, when administered in isolated organ perfusion it results in regression of advanced bulky tumors. A better understanding of the mechanisms of TNF-induced antitumor effects may provide valuable information into how its clinical use in cancer treatment may be expanded. We describe here that the release of a novel tumor-derived cytokine endothelial-monocyte-activating polypeptide II (EMAPII) renders the tumor-associated vasculature sensitive to TNF. EMAPII has the unique ability to induce tissue factor production by tumor vascular endothelial cells that initiates thrombogenic cascades, which may play a role in determining tumor sensitivity to TNF. We demonstrate here that constitutive overexpression of EMAPII in a TNF-resistant human melanoma line by retroviral-mediated transfer of EMAPII cDNA renders the tumor sensitive to the effects of systemic TNF in vivo, but not in vitro. This interaction between tumors and their associated neovasculature provides an explanation for the focal effects of TNF on tumors and possibly for the variable sensitivity of tumors to bioactive agents.

Animals↗

PubMed1999

Tissue burden of asbestos in nonoccupationally exposed individuals from east Texas.

BACKGROUND: The potential for asbestos exposure among members of the general population is appreciable, considering its widespread use in many products. This study examined tissue burden of asbestos in such a population. METHODS: A group of 33 individuals who had no work history of occupational exposure to asbestos were included in the study. Tissue sections from areas adjacent to those sites sampled for digestion were found to be without ferruginous bodies (FB) or histopathology consistent with asbestos-induced changes. All individuals had 20 or less FBs per gram of digested wet lung, a number considered to reflect general population levels. Tissue analysis of uncoated fiber burden was carried out by analytical electron microscopy. There was a trend of a higher likelihood of FB and asbestos fiber content correlated with age. RESULTS: The data are not consistent with the findings that chrysotile is readily found in lung tissue from the general population, in that none was found in 19 of the cases. It was almost as likely that one would find anthophyllite (12 of 33 cases) in this study. The commercial amphiboles (amosite and crocidolite) were occasionally found in the tissue from the general population and, when observed, were few in numbers. Twenty-six of the patients had no FBs and ten had no uncoated asbestos fibers within the limits of detectability in this study. CONCLUSIONS: The total tissue burden of asbestos in this study is much less than earlier reported observations from other general populations.

Adolescent↗

PubMed1999

Rapid iterative reconstruction for echo planar imaging.

A rapid automated method for reconstructing echo planar imaging (EPI) data has been developed and is shown to improve image quality by suppressing the troublesome ghost artifact. The algorithm can be applied without prior knowledge obtained from either reference scans or operator intervention. It first estimates, then improves iteratively, the parameters for a linear phase correction applied directly to the complex image data derived from odd and even echoes. The theory used to derive the criteria employed in the iteration provides insight into mechanisms that allow the process to work. Magn Reson Med 42:541-547, 1999.

Algorithms↗

PubMed1999

A Bayesian approach to replication of linkage findings.

A novel Bayesian approach to replication studies, allowing for locus heterogeneity, is introduced. Compared with currently used approaches to replication, it offers a natural way to accumulate evidence across independently collected data sets and yields more interpretable results. Using for replicates (one as initial study and the other three as replication studies) from Problem 2 of the Genetic Analysis Workshop 11 data, we show the performance of this method. All four disease susceptibility loci (D1G009, D1G024, D3G045, D5G035) are identified and accurately mapped, with no false positive signals.

Bayes Theorem↗

PubMed1999

Spodoptera littoralis type B nucleopolyhedrovirus infection of a grasshopper cell line.

We determined that the type B nucleopolyhedrovirus of the Egyptian cottonworm, Spodoptera littoralis (SpliNPV), can infect a cell line derived from a grasshopper. We compared the infectivity of SpliNPV in two lepidopteran cell lines (Sf9 and Md210) and in a cell line (MSE4) derived from the western migratory grasshopper, Melanoplus sanguinipes (Orthoptera: Acrididae). Both Sf9 and MSE4 cells were permissive for SpliNPV replication and supported production of viable progeny. Md210 cells were nonpermissive for SpliNPV, and although the virus entered into these cells, they supported neither viral replication nor production of viable progeny. Infection of MSE4 cells with SpliNPV resulted in cytopathic effects within 48 h post infection and complete destruction of the cells within 5 days. Both virions and polyhedra were detected within virus-infected MSE4 cells by transmission electron microscopy. Extracellular virions were detected in the culture medium and were infectious to Sf9 cells, indicating that the MSE4 cells supported production of viable virus progeny.

Animals↗

PubMed1999

Determination of trace elements in tissue of human uterine cancer by instrumental neutron activation analysis.

In this article, the low-temperature freeze-drying pretreated technique and instrumental neutron activation analysis were used to determine 29 trace elements in samples of human uterine cancer tissue. The content of these trace elements in uterine cancer tissue was compared with that in cervicitis tissue and in healthy tissue, respectively. Preliminary results indicated that significant differences in contents of Au, I, and Se were observed in these tissues.

Female↗

PubMed1999

Characterization of Spodoptera littoralis type B nucleopolyhedrovirus infection in selected insect cell lines.

We have examined Spodoptera littoralis type B nucleopolyhedrovirus (SpliNPV) infections in CLS79, Sf9, and Se1 cells derived from lepidopteran insects of the genus Spodoptera (Family: Noctuidae), Ld652Y cells from Lymantria dispar (Family: Lymantriidae), and Md210 cells from Malacosoma disstria (Family: Lasiocampidae). CLS79, Sf9, and Se1 cells were permissive for SpliNPV infection as these cell lines supported complete viral DNA replication, virus-specific transcription, and production of viable progeny. Neither Ld652Y nor Md210 cells supported production of viable SpliNPV progeny. Ld652Y cells supported limited viral DNA replication and displayed reduced and delayed transcription of viral-specific RNAs. Md210 did not support viral DNA replication and displayed dramatically reduced transcription of viral-specific RNAs. We used transient expression assays as an indirect measure of the translation of SpliNPV early gene products in Sf9, Ld652Y, and Md210 cells. While transactivation of viral promoter-mediated luciferase expression occurred in SpliNPV-infected Ld652Y cells, little to no transactivation activity was detected in SpliNPV-infected Md210 cells. Our data indicated that the block to productive SpliNPV infection in Ld652Y and Md210 cells may be at the level of viral RNA transcription and further suggested that host factors play an important role in productive SpliNPV infection.

Animals↗

PubMed1999

A microscopic interaction model of maximum solubility of cholesterol in lipid bilayers.

We recently reported the equilibrium maximum solubility of cholesterol in a lipid bilayer, chi*chol, to be 0.66 in four different phosphatidylcholines, and 0.51 in a phosphatidylethanolamine (Huang, J.,J.T. Buboltz, and G. W. Feigenson. 1999. Biochim. Biophys. Acta. in press). Here we present a model of cholesterol-phospholipid mixing that explains these observed values of chi*chol. Monte Carlo simulations show that pairwise-additivity of nearest-neighbor interactions is inadequate to describe all the chi*chol values. Instead, if cholesterol multibody interactions are assigned highly unfavorable energy, then jumps occur in cholesterol chemical potential that lead to its precipitation from the bilayer. Cholesterol precipitation is most likely to occur near three discrete values of cholesterol mole fraction, 0.50, 0.57, and 0.67, which correspond to cholesterol/phospholipid mole ratios of 1/1, 4/3, and 2/1, respectively. At these solubility limits, where cholesterol chemical potential jumps, the cholesterol-phospholipid bilayer mixture forms highly regular lipid distributions in order to minimize cholesterol-cholesterol contacts. This treatment shows that dramatic structural and thermodynamic changes can occur at particular cholesterol mole fractions without any stoichiometric complex formation. The physical origin of the unfavorable cholesterol multibody interaction is explained by an "umbrella model": in a bilayer, nonpolar cholesterol relies on polar phospholipid headgroup coverage to avoid the unfavorable free energy of cholesterol contact with water. Thus, at high cholesterol mole fraction, this unfavorable free energy, not any favorable cholesterol-phospholipid interaction, dominates the mixing behavior. This physical origin also explains the "cholesterol condensing effect" and the increase in acyl chain order parameter in cholesterol-phospholipid mixtures.

Biophysical Phenomena↗

PubMed1999

Pharmacokinetics of metoprolol enantiomers in Chinese subjects of major CYP2D6 genotypes.

OBJECTIVE: CYP2D6 mediates both alpha-hydroxylation and O-demethylation of metoprolol. In Chinese subjects, CYP2D6*1 (the wild-type) alleles are relatively uncommon. Subjects with P34S (C188-->T188) and S486T (G4268-->C4268) mutations (CYP2D6J or CYP2D6*10A) are more frequently seen. Recently, the CYP2D6*2 (CYP2D6L) genotype that results in R296C (C2938-->T2938) and S486T mutations was also found important. In this study, metoprolol pharmacokinetics was investigated in subjects of these 3 major genotypes. METHODS: Allele-specific polymerase chain reaction was used to differentiate CYP2D6*1 and CYP2D6*2 alleles from the common CYP2D6*10A allele in Chinese. Subjects with both CYP2D6*1 and CYP2D6*2 have homozygous C188 in the exon 1, whereas subjects with CYP2D6*10A have T188. Metoprolol pharmacokinetics was compared in 16 C188 subjects (6 homozygous CYP2D6*1 subjects and 10 heterozygous CYP2D6*1/CYP2D6*2 subjects), 12 heterozygous C/T188 subjects, and 12 homozygous T188 subjects. RESULTS: No significant difference in plasma concentration profile or urinary alpha-hydroxymetoprolol excretion could be found among subjects with R296C polymorphism (CYP2D6*1/CYP2D6*2). Therefore data from subjects with CYP2D6*1 and CYP2D6*2 were pooled to compare with data from subjects with CTP2D6*10A. The area under plasma concentration curves (AUC) of S-metoprolol was 1411+/-116 (mean +/- SEM, n = 16), 1899+/-120 (n = 12), and 3588+/-435 (n = 12) nmol x hr/L for homozygous C188, heterozygous C/T188, and homozygous T188 subjects, respectively. The urinary recovery of all 4 alpha-hydroxymetoprolol diastereomers was significantly lower in T188 subjects than in C188 subjects. CONCLUSION: The P34S polymorphism but not the R296C polymorphism resulted in higher metoprolol plasma concentrations and lower urinary metoprolol metabolite levels in Chinese subjects. This finding suggests that a lower dose of metoprolol may be used in subjects with T188 mutation (CYP2D6*10A allele).

Administration, Oral↗

PubMed1999

Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions.

OBJECTIVES: We tested the hypothesis that pravastatin (PRA) activates endothelial nitric oxide synthase (eNOS). BACKGROUND: Pravastatin has been found to have clinical benefits beyond those predicted by its actions in reducing plasma low density lipoprotein cholesterol (LDL). Both PRA and simvastatin (SIM) are equally effective in reducing LDL, but only PRA reduces platelet aggregation and is an effective vasodilator. Nitric oxide (NO) also inhibits platelet aggregation and vasodilates. METHODS: We determined PRA and SIM effects on vasorelaxation in aortic rings and NO production by cultured bovine aortic endothelial cells. Nitric oxide was measured by using a NO electrode and by an assay for conversion of hemoglobin to methemoglobin. Specificity of NOS activation was tested by using the NOS inhibitor nitro-L-arginine methyl ester (L-NAME, 1 mmol/liter) in the presence or absence of excess L-arginine (L-ARG, 1 mmol/liter). RESULTS: Endothelium-dependent vasorelaxation was maximal with acetylocholine (ACH, 100%), followed by PRA (62.8%) and then SIM (37.1%). Direct measurement of NO confirmed that vasorelaxation is due to NO release and showed that PRA and ACH had similar dose-dependent effects on NO production, while SIM was only 25% to 30% as effective. Methemoglobin assay confirmed these results and demonstrated their specificity for NOS activity. The L-NAME blunted the responses to 45% of initial values. Excess L-ARG reversed this effect and potentiated NO production to 133% of initial levels. CONCLUSIONS: Both PRA and SIM activate eNOS, but SIM is much less effective. Clinical benefits with PRA not explained by LDL reductions may be the result of an independent action of PRA on eNOS activation.

Animals↗

PubMed1999

Pure-phase two-dimensional niobium-93 nutation spectroscopic study of lead metaniobate and the piezoelectric lead magnesium niobate.

An NMR technique to measure pure-phase two-dimensional nutation NMR spectra, that yields higher resolution than traditional nutation experiments is reported. Using this technique 93Nb nutation NMR spectra of PbNb2O6 and the technologically important Pb(Mg1/3Nb2/3)O3 (PMN) have been measured and the quadrupolar coupling constant of the niobium site in PbNb2O6 (C(Q) = 19 +/- 2 MHz) determined. Estimates of the quadrupolar coupling constants for three different resonances associated with different niobium(V) sites in PMN (C(Q) < 1.2 MHz, approximately 17 MHz, and > 62 MHz) are also reported.

Lead↗

PubMed1999

Chinese traditional medicine and abnormal sex ratio at birth in China.

A study of the abnormal sex ratio at birth in China reveals that it is not an entirely new phenomenon that emerged since the 1980s, but is simply more visible at present. Deliberate intervention to determine the sex of children has existed in the past few decades, at least in certain groups. Apart from modern medical methods, traditional Chinese medical practice is shown to be highly accurate in identifying the sex of a fetus. This may lead to sex-selective abortion and an abnormal sex ratio at birth. The possible causes of the abnormal sex ratio at birth include not only the real imbalance due to the disturbance of social factors, but also a spurious one attributable to the undercounting of female births. The real magnitude of the imbalance has been exaggerated by statistical error. The phenomenon is a complicated one reflecting the comprehensive socioeconomic setting. Among these factors, the stage of the fertility transition is one of the most decisive.

Child↗

PubMed1999

Genetic anticipation and breast cancer: a prospective follow-up study.

Genetic anticipation is characterized by an earlier age of disease onset, increased severity, and a greater proportion of affected individuals in succeeding generations. The discovery of trinucleotide repeat expansion (TRE) mutations as the molecular correlate of anticipation in a number of rare Mendelian neurodegenerative disorders has led to a resurgence of interest in this phenomenon. Because of the difficulties presented to traditional genetics by complex diseases, the testing for genetic anticipation coupled with TRE detection has been proposed as a strategy for expediting the identification of susceptibility genes for complex disorders. In the case of breast cancer, a number of previous studies found evidence consistent with genetic anticipation. It is known that a proportion of such families are linked to either BRCA1 or BRCA2, but no TRE mutations have been identified. It has been shown that the typical ascertainment employed in studies purporting to demonstrate genetic anticipation combined with unadjusted statistical analysis can dramatically elevate the type I error. We re-examine the evidence for anticipation in breast cancer by applying a new statistical approach that appears to have validity in the analysis of anticipation to data ascertained from a recent follow-up of a large prospective cohort family study of breast cancer. Using this approach, we find no statistically significant evidence for genetic anticipation in familial breast cancer. We discuss the limitations of our analysis, including the problem of adequate sample size for this new statistical test.

Adult↗