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Biomedical subjects

X Zhou

Publications and source records attributed to X Zhou.

At least 415 records · Page 23Linked to original sources
PubMed1998

Renal cell carcinoma with X;1 translocation in a child with Klinefelter syndrome.

Klinefelter syndrome (KS) is a sex chromosome abnormality occurring in 1 in 1,000 males. An association with leukemia, germ cell tumor, and male breast cancer has been suggested in KS. Such information is important for professionals caring for KS patients as the condition is frequently not clinically recognizable until after puberty. We report on a renal cell carcinoma (RCC) in a 10-year-old boy with KS. He developed intermittent hematuria at age 10 years and was diagnosed with a right kidney mass, which on pathology was identified as RCC. In addition, he was known to have learning disabilities and language delays. Analysis of peripheral blood chromosomes showed a 47,XXY karyotype while analysis of tumor cells demonstrated clonal abnormalities including a translocation between chromosomes X and 1, designated 47,XXYc,t(X;1)(p11.2;q21)[6]/47,XXYc,t(X;1),r(Xp)[2]/46,X XYc,-X,t(X;1)[7]. Renal cell carcinoma is rare in childhood and is not previously reported in KS. The oncogenetic significance of the chromosomal regions involved in this translocation is discussed in relation to the congenital abnormality of the patient.

Carcinoma, Renal Cell↗
PubMed1998

A mutant human beta2-microglobulin can be used to generate diverse multimeric class I peptide complexes as specific probes for T cell receptors.

Antigen-specific receptors (TCR) on CD8 T lymphocytes form relatively short-lived complexes with their natural ligands: peptides in association with major histocompatibility complex (MHC) class I molecules, which consist of a polymorphic heavy chain and a conserved light chain, beta2-microglobulin (beta2-M). To produce soluble MHC-peptide complexes in a form that would bind more stably and could be used to identify, count, and isolate CD8 T cells having the appropriate TCR, we prepared multimeric MHC-peptide complexes. Our work builds on the assembly of recombinant MHC class I peptide complexes using a mutant human beta2-M chain (Tyr 67 > Cys) which can form stable heterodimers with diverse MHC heavy chains. With biotin added to the SH group, the assembled MHC-peptide monomers formed multimers with avidin linked to a fluorochrome. The specific reactivity of the multimeric reagents with human and mouse cytotoxic T cells (CTL) is described. The present approach permits the production of class I multimers, without the necessity of genetic engineering each heavy chain, a significant advantage in view of the enormous polymorphism of MHC heavy chains. Because human beta2-M forms stable heterodimers with diverse class I heavy chains from various species (human and non human primates, mouse, etc.), this procedure is a general method for producing multimers of MHC-peptide complexes as T cell receptor-specific probes.

Animals↗
PubMed1998

In-situ self-assembling protein polymer gel systems for administration, delivery, and release of drugs.

Sequential block copolymers consisting of tandem repetition of amino acids have been constructed and genetically produced based on the natural repeating structures of silk and elastin protein. Combinations of silklike and elastinlike amino acid sequence blocks in a high molecular weight protein polymer are used to confer properties similar to those observed with hard block and soft block segmented polyurethanes. A certain subset of these silk-elastinlike protein compositions, termed ProLastins, will undergo an irreversible solution to gel transition in physiological, aqueous solution. The transition occurs over time and can be controlled by temperature, solution conditions, and additives which either prevent or promote hydrogen bond-mediated chain crystallization. The process involves no covalent crosslinking. Characterization of the gelling properties of various ProLastin compositions and their ability to release compounds which are incorporated directly into the gels are presented.

Amino Acid Sequence↗
PubMed1998

Coexisting kinetically distinguishable forms of dialkylglycine decarboxylase engendered by alkali metal ions.

The pyridoxal phosphate (PLP) dependent enzyme dialkylglycine decarboxylase (DGD) specifically binds alkali metal ions near the active site. Large ions (Rb+, K+) activate the enzyme while smaller ones (Na+, Li+) inhibit it. Crystallographic results have shown that DGD undergoes a metal ion size dependent structural switch [Hohenester, E., Keller, J. W., and Jansonius, J. N. (1994) Biochemistry 33, 13561], but no evidence for multiple conformations in crystalline DGD was obtained. Here, evidence is presented that DGD-K+ in solution exists in two conformations differing in catalytic competence. Initial rate traces for DGD-K+ exhibit a high degree of curvature due to decreasing activity over time. DGD remains tetrameric under the assay conditions as demonstrated by gel filtration experiments, arguing against the possibility of subunit dissociation as the source of activity loss. Likewise, the mass spectrum of DGD shows a single covalent form. A hysteretic model that assumes two slowly interconverting enzyme forms accounts well for the initial rate data when kinetic parameters from biphasic pre-steady-state kinetics are employed. The fit of the model to the data yields an estimate of 59 +/- 1% for the fast form. A cooperative model cannot account for the data. Double reciprocal plots for coenzyme binding to DGD exhibit two linear phases. Similarly, two kinetic phases are observed in PLP association kinetics. The substitution of Na+ or Rb+ for K+ alters the steady-state kinetic parameters of DGD. Preincubation of DGD-K+ with the competitive inhibitor 1-aminocyclopropane-1-carboxylate (ACC) lowers both kcat and KAIB apparently by drawing the enzyme toward the less active, tighter binding form observed in the pre-steady-state kinetics. These results suggest that the structure of the protein around the alkali metal ion determines the conformational distribution. The transamination reaction with l-alanine was coupled in the pre-steady-state to the LDH-catalyzed oxidation of NADH. This experiment yields an estimate of 68 +/- 4% for the fast form, in agreement with the hysteretic fit to the steady-state data. The reaction of DGD with dithiobis(nitrobenzoate) was used to probe the preexisting forms of DGD. Preincubation of DGD with ACC, like the exchange of Na+ for K+, shifts the conformational distribution, in agreement with the steady-state kinetics. These experiments clearly demonstrate that DGD is a hysteretic enzyme whose conformational distribution is controlled by the identity of the alkali metal ion bound near the active site, and that cooperativity does not play a role in catalysis or regulation.

Alanine↗
PubMed1998

Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice.

Atherosclerosis is an inflammatory-fibrotic response to accumulation of cholesterol in the artery wall. In hypercholesterolemia, low density lipoproteins (LDL) accumulate and are oxidized to proinflammatory compounds in the arterial intima, leading to activation of endothelial cells, macrophages, and T lymphocytes. We have studied immune cell activation and the autoimmune response to oxidized LDL in atherosclerotic apo E-knockout mice. Autoantibodies to oxidized LDL exhibited subclass specificities indicative of T cell help, and the increase in antibody titers in peripheral blood was associated with increased numbers of cytokine-expressing T cells in the spleen. In addition to T cell-dependent antibodies, IgM antibodies to oxidized LDL were also increased in apo E-knockout mice. This suggests that both T cell-dependent and T cell-independent epitopes may be present on oxidized LDL. In moderate hypercholesterolemia, IgG antibodies were largely of the IgG2a isotype, suggesting that T cell help was provided by proinflammatory T helper (Th) 1 cells, which are prominent components of atherosclerotic lesions. In severe hypercholesterolemia induced by cholesterol feeding of apo E-knockout mice, a switch to Th2-dependent help was evident. It was associated with a loss of IFN-gamma-producing Th1 cells in the spleen, whereas IL-4-producing Th2 cells were more resistant to hypercholesterolemia. IFN-gamma but not IL-4 mRNA was detected in atherosclerotic lesions of moderately hypercholesterolemic apo E-knockout mice, but IL-4 mRNA appeared in the lesions when mice were made severely hypercholesterolemic by cholesterol feeding. These data show that IFN-gamma-producing Th1 cells infiltrate atherosclerotic lesions and provide T cell help for autoimmune responses to oxidized LDL in apo E-knockout mice. However, severe hypercholesterolemia is associated with a switch from Th1 to Th2, which results not only in the formation of IgG1 autoantibodies to oxidized LDL, but also in the appearance of Th2-type cytokines in the atherosclerotic lesions. Since the two subsets of T cells counteract each other, this switch may have important consequences for the inflammatory/immune process in atherosclerosis.

Animals↗
PubMed1998

Unfolding domains and tryptophan accessibility of a 59 kDa coiled-coil light meromyosin.

Light meromyosin (LMM 77), the C-terminal proteolytic peptide from myosin rod, is a 900 A coiled-coil that contains two pairs of tryptophan residues in d-positions of the heptad repeat (abcdefg)n. Previous studies showed that LMM 77 unfolded in two transitions and suggested that both Trp pairs were located in the least stable unfolding domain. Here, the thermal and denaturant unfolding properties of LMM 59, a recombinant N-terminal truncated LMM, containing only one of the Trp pairs, was compared to LMM 77. LMM 59 unfolded in two transitions with similar midpoints to the two transitions of LMM 77. However, only the second transition of LMM 59 affected the Trp fluorescence, indicating that the two pairs of Trp residues in LMM 77 are in different unfolding domains. Disulfide-crosslinked LMM 59 verified this assignment. Solute-quenching studies showed that the accessibility of the Trp in LMM 59 decreased only by 56% on forming filaments. Electron micrographs indicated that all of LMM 59 is located within the core of a bipolar tactoid with the Trp-containing region the most accessible to negative strain, in agreement with the solute-quenching studies. This suggests that part of the core of the myosin thick filament is appreciably exposed to solvent.

Circular Dichroism↗
PubMed1998

Induction of nitric oxide synthase in macrophages: inhibition by fructose-1,6-diphosphate.

Intravenous fructose-1,6-diphosphate (FDP) is reported to reverse shock and improves survival in animals given systemic lipopolysaccharide (LPS), although the mechanism is incompletely understood. Since endotoxin-related shock is associated with increased nitric oxide (NO) production, LPS-stimulated macrophages were treated with FDP, and the NO metabolite, nitrite, was measured 24 h later. Treatment of LPS-stimulated macrophages with 1, 5, or 10 mM FDP caused a dose-dependent reduction in mRNA expression for inducible NO synthase by Northern analysis and decreased the micromolar concentrations of nitrite produced by 17, 42, and 68%, respectively. Neither fructose nor sodium phosphate had these effects in LPS-exposed macrophages. Electrophoretic mobility shift assays revealed that FDP did not inhibit LPS-mediated activation of nuclear factor kappa B. Viability analysis showed that the FDP effect was not caused by cytotoxicity. Overall, these results suggest that fructose-1,6-diphosphate, a glycolytic intermediate with potential clinical use, may mitigate the adverse effects of LPS by regulating the generation of NO.

Animals↗
PubMed1998

Roles for interleukin-1beta, phorbol ester and a post-transcriptional regulator in the control of bradykinin B1 receptor gene expression.

Bradykinin B1 receptor (BKB1R) is involved in a variety of pathophysiological processes, particularly those related to inflammation. The gene for this receptor is known to be upregulated by interleukin (IL)-1beta, a proinflammatory cytokine. However, the molecular mechanisms involved in the regulation of the BKB1R gene expression have not been defined. We demonstrated that IL-1beta induces a rapid increase in BKB1R mRNA level and the binding of desArg10-kallidin in human embryo lung fibroblasts (IMR90). This increase in BKB1R mRNA level is protein synthesis-independent as indicated by treatment of cells with cycloheximide (CHX) or puromycin (PUR). By testing the IL-1beta effect on BKB1R mRNA degradation, we showed that the IL-1beta upregulation of BKB1R expression is achieved through both transcriptional activation and post-transcriptional mRNA stabilization. In addition to the IL-1beta effects, translation inhibitors, CHX and PUR increase the steady state BKB1R mRNA level by inhibiting BKB1R mRNA degradation. Removal of the CHX block with subsequent resumption of protein synthesis results in a sizable increase of desArg10-kallidin binding. Using signalling pathway inhibitors, we show that IL-1beta functions through a protein tyrosine kinase, not protein kinase C or protein kinase A. However, activation of protein kinase C by phorbol 12-myristate 13-acetate increases the level of BKB1R mRNA and the binding of desArg10-kallidin. This increase is blocked by NF-kappaB activation inhibitors.

Cell Line↗
PubMed1998

An extension of the steepest descent method for Riemann-Hilbert problems: the small dispersion limit of the Korteweg-de Vries (KdV) equation.

This paper extends the steepest descent method for Riemann-Hilbert problems introduced by Deift and Zhou in a critical new way. We present, in particular, an algorithm, to obtain the support of the Riemann-Hilbert problem for leading asymptotics. Applying this extended method to small dispersion KdV (Korteweg-de Vries) equation, we (i) recover the variational formulation of P. D. Lax and C. D. Levermore [(1979) Proc. Natl. Acad. Sci. USA76, 3602-3606] for the weak limit of the solution, (ii) derive, without using an ansatz, the hyperelliptic asymptotic solution of S. Venakides that describes the oscillations; and (iii) are now able to compute the phase shifts, integrating the modulation equations exactly. The procedure of this paper is a version of fully nonlinear geometrical optics for integrable systems. With some additional analysis the theory can provide rigorous error estimates between the solution and its computed asymptotic expression.

Journal Article↗
PubMed1998

A fast spin echo technique with circular sampling.

This paper presents a fast spin echo (FSE) imaging method that employs circular sampling of k-space. The technique has been implemented on a 2 Tesla imaging system and validated on both phantoms and living animals. Experimental studies have shown that circular sampling can produce artifact-free FSE images without the need of phase correction. Although not fully explored, preliminary results also show that circular sampling may have advantages over the conventional rectilinear FSE in signal-to-noise ratio and imaging efficiency. A major disadvantage is the increased sensitivity to off-resonance effects. The authors expect that the FSE technique with circular sampling will find its applications in magnetic resonance microscopy, neuro-functional imaging, and real-time dynamic studies.

Animals↗
PubMed1998

Optimization and mechanism of step-leap respiration exercise in treating of cor pulmonale.

The interaction between cardiovascular system and the respiratory system is complicated and may be used for the rehabilitation of the cor pulmonale disease. To study the effects of different breathing mode on the cardiac and pulmonary systems, a mathematical model is established based on the previous work. Using this model, computer simulation experiments are carried out for searching an optimal respiration mode in treating of cor pulmonale disease. Results indicate that the step-leap respiration mode could provide a better assistant to the rehabilitation of the cor pulmonale patients in the sense of increasing coronary flow, reducing pulmonary arterial pressure and reducing the working load for the right heart. This result is also proven by the clinical experiments. This work may suggest that a proper directed respiration exercise can be used in the treatment of cor pulmonale disease.

Algorithms↗
PubMed1998

Moisture determination in hygroscopic drug substances by near infrared spectroscopy.

The moisture level in a hygroscopic drug substance was successfully determined by near infrared spectroscopy using coulometric Karl Fischer titration as the reference method. The importance of sample handling and proper application of the reference technique are stressed for this difficult sample type. Samples were prepared with moisture levels from 0.5 to 11.4% (w/w) and reflectance spectra were collected over the spectral range 1100-2500 nm. Calibration models were built using partial least squares (PLS) regression analysis. Optimum models were found by choosing proper spectral ranges and number of PLS factors. The best calibration models were built using first derivative spectra, a spectral range of 1850-1936 nm and 5 PLS factors. The corresponding standard error of prediction was 0.11% (w/w) water.

Calibration↗
PubMed1998

Evaluation of key sources of variability in the measurement of pharmaceutical drug products by near infrared reflectance spectroscopy.

Potential sources of variability in the measurement of solid oral drug products by near infrared reflectance spectroscopy were evaluated with statistical experimental design. Spectra were collected for two different tablet types according to the data collection and treatment parameters defined by the experimental design. Each tablet had three different dose-levels. Libraries were constructed using second-derivative spectra. Key figures-of-merit generated during internal and external library validation were used to calculate which parameters most strongly influence the library performance for dose-level discrimination. These responses and their corresponding experimental conditions were evaluated with the screening model in the JMP program. Segment value used for the second-derivative calculation was an an influential factor and had a complex effect. Orientation on the sampling platform also had an influential effect for embossed tablets. Collection of spectra over fewer days decreased variability within the library. More frequent reference spectrum collection improved the performance of libraries to a small degree. A larger sample population increased the range of spectral variability within a dose-level but apparently not the overall performance of the library. The number of scans averaged per spectrum was not an influential factor in this study. These results are summarized and used to recommend an approach to dose-level discrimination.

Evaluation Studies as Topic↗
PubMed1998

Synthesis and radioprotective effects of adamantyl substituted 1,4-dihydropyridine derivatives.

A series of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diesters substituted at the N-1 and/or C-4 positions of the dihydropyridine ring was synthesized. The in vitro cytotoxicity and in vitro and in vivo radioprotective efficacy of these agents were evaluated in Chinese hamster (V-79) cells and CD2F1 male mice, respectively. Compounds with at least one adamantyl substituent afforded better radioprotection than those without this substituent. Substitution of an aromatic ring at the C-4 position of the dihydropyridine ring did not enhance the radioprotectant action of the compounds.

Adamantane↗
PubMed1998

Prevalence and correlates of early smoking among elementary schoolchildren in multiethnic, low-income inner-city neighborhoods.

PURPOSE: The prevalence and correlates of early smoking were investigated among schoolchildren in grades 4-6 living in multiethnic, low-income neighborhoods in Montreal. METHODS: As part of the evaluation of a school-based heart health promotion program, baseline data on the prevalence of early smoking were collected from 2285 students aged 9-13 years in 24 inner-city elementary schools during May-June 1993. RESULTS: Overall, 28.7% of boys and 20.3% of girls had smoked. Girls began trying later than boys, but by age 13 the prevalence of experimental or regular smoking by girls overtook that of boys. Univariately, ever smoking varied considerably by family origin, from 2.1% among Vietnamese girls, to 35.8% among Portuguese boys. In multivariate analysis, age, perceived smoking habits of friends, and smoking by family members, were strong correlates of smoking. Being of Asian family origin was negatively associated with smoking. None of the indicators of social class were significantly associated with ever smoking. CONCLUSIONS: Smoking prevention should begin with children even younger than age 9 in multiethnic, low-income, inner-city neighborhoods. With the exception of a lower prevalence of smoking among Asian children, ethnicity and social class were not strong influences on early smoking behavior in this population.

Adolescent↗
PubMed1998

Genetic variation in sympatric Ascaris populations from humans and pigs in China.

It has recently been shown using genetic markers that Ascaris in humans and pigs in Central America comprise reproductively isolated populations. We present a similar analysis for a region of China in which close association between pigs and humans has been the norm for thousands of years, and agricultural practices will result in frequent exposure to eggs from both sources. DNA fragments from selected regions of mitochondrial and ribosomal DNA were amplified by PCR and allelic forms identified following digestion with a panel of restriction enzymes, using DNA from a total of 115 individual worms from both people and pigs from 2 neighbouring villages. Significant frequency differences in both mtDNA haplotypes and the rDNA spacer were found between the 2 host-associated populations, indicating that they represented reproductively isolated populations. Mitochondrial haplotype frequencies were different from those observed in Guatemala and also from other Asian Ascaris populations, suggesting low levels of gene flow between populations. However, we found no evidence for significant heterogeneity in the genetic composition of Ascaris infrapopulations in either humans or pigs, possibly indicative of agricultural practices in China which have resulted in a random distribution of alleles within the parasite populations.

Animals↗
PubMed1998

Pharmacokinetics of (R,S)-Albuterol after aerosol inhalation in healthy adult volunteers.

The pharmacokinetics of inhaled (R,S)-albuterol following pulmonary absorption were studied in healthy human subjects. Ten subjects (5 females and 5 males) inhaled two puffs (180 microg) of albuterol via a metered-dose inhaler and spacer device. All subjects were nonsmoking and had normal pulmonary function. Charcoal slurries were ingested to block gastrointestinal absorption of drug. Venous samples were obtained from each subject at thirteen time points from 0 through 12 h post dose. (R,S)-Albuterol concentration in plasma was measured using a gas chromatography-mass spectrometry (GC-MS) assay. The plasma concentration-time profiles conformed to a two-compartment extravascular model with first-order absorption kinetics. The drug levels reached maximum in 12.6 +/- 2.2 (SD) minutes, which is in contrast with previous reports that maximum plasma concentrations occur within 2 to 4 h. The mean peak plasma level was 1469 +/- 410 pg/mL. The mean half-life of distribution was 17.9 +/- 8.2 min. The mean half-life of elimination was 4.4 +/- 1.5 h. Female subjects achieved peak concentration more rapidly than male subjects (10.4 vs 14.8 min, p = 0.01) and had a higher mean peak concentration (1778 vs 1159 pg/mL, p = 0.04).

Absorption↗