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Biomedical subjects

J Cao

Publications and source records attributed to J Cao.

At least 19 recordsLinked to original sources
PubMed2001

Human CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis.

The CED4/Apaf-1 family of proteins functions as critical regulators of apoptosis and NF-kappaB signaling pathways. A novel human member of this family, called CARD12, was identified that induces apoptosis when expressed in cells. CARD12 is most similar in structure to the CED4/Apaf-1 family member CARD4, and is comprised of an N-terminal caspase recruitment domain (CARD), a central nucleotide-binding site (NBS), and a C-terminal domain of leucine-rich repeats (LRR). The CARD domain of CARD12 interacts selectively with the CARD domain of ASC, a recently identified proapoptotic protein. In addition, CARD12 coprecipitates caspase-1, a caspase that participates in both apoptotic signaling and cytokine processing. CARD12 may assemble with proapoptotic CARD proteins to coordinate the activation of downstream apoptotic and inflammatory signaling pathways.

Animals↗
PubMed2001

Single molecule tracking of heterogeneous diffusion.

The mean square displacement of heterogeneous diffusion obeys the Einstein relation, thereby showing no sign of heterogeneities in the ensemble measurement of the diffusion constant. The signature of spatial heterogeneities appears in the time evolution of the non-Gaussian distribution and in the cross correlation between the square displacements at different times, both available from single molecule diffusional trajectories. As a quantitative measure, the non-Gaussian indicator g(t) decays asymptotically to zero according to 1/t for finite time correlation, but saturates at a plateau value for power-law correlation. In addition, the joint moment correlation function f(t,tau) provides a direct probe of the memory effect of the fluctuating rate constant. A two-state diffusion model and a stochastic Gaussian model are constructed to evaluate these quantities and are shown to yield the same result within the second cumulant expansion.

Journal Article↗
PubMed2001

Varied ecological environment and fluorosis in Tibetan children in the nature reserve of Mount Qomolangma.

To determine the extent of brick tea consumption fluorosis in children living at elevations of 2000 and 4300 m, 519 children aged 8-15 years living in Xiege'er Town at 4300 m and Zhangmu Town at 2000 m were examined for dental fluorosis, their urinary fluoride concentration was determined, their dietary structure investigated, and the fluoride concentrations of various foods, freshwaters, soils, and fuels determined. Fifteen Tibetan families living in these two areas of the nature reserve of Mount Qomolangma were studied according to UNEP, FAO, and WHO guidelines for the study of dietary intake of chemical contaminants, Horowitz's classification and examination of dental fluorosis, and Dean's dental fluorosis index. The results demonstrated that dental fluorosis in Tibetan children living at an elevation of 2000 m was significantly lower than that of children at 4300 m (P<0.01). Higher elevation can worsen the extent of fluorosis, leading to retention of fluoride in tissues as a result of hypoxia, but fluorosis can also be associated with the deterioration of the ecological environment at high elevation and a low-level economy. Beverages and foods mixed with brick tea water are responsible for the dental fluorosis in the children.

Adolescent↗
PubMed2001

Factors affecting ammonia volatilisation from a rice-wheat rotation system.

Some of the major factors influencing ammonia volatilisation in a rice wheat rotation system were studied. A continuous airflow enclosure method was used to measure NH3 volatilisation in a field experiment at an agricultural college in Jiangsu Province. The five treatments comprised application rates of 0, 100, 200 or 300 kg N ha(-1) as urea, per growing season with rice straw amendment when wheat was sown, and 200 kg N ha(-1) without rice straw amendment. There were three replicates in a randomised block design. Ammonia volatilisation was measured immediately after urea application in the three consecutive years 1995 to 1997. The results show that N losses through NH3 volatilisation accounted for 4-19% of N applied during the wheat growing season and for 5-11% during the rice growing season. Ammonia volatilisation was affected significantly by soil moisture and temperature before and after fertiliser application during the wheat growing season. The ratio of volatilised NH3-N to applied N after urea application during the rice growing season was as follows: top-dressing at the onset of tillering > top-dressing at the start of the booting stage > basal fertilization. The results also show that the amount of N lost through NH3 volatilisation increased with increasing N application rate, but the ratio to applied N was not affected significantly by N application rate. Amendment with rice straw had no significant effect on NH3 volatilisation.

Agriculture↗
PubMed2001

Simulation of acid-base condition and copper speciation in the fish gill microenvironment.

pH, alkalinity, and mucus content in the fish gill microenvironment of carp (Cyprinus carpio) were measured by exposing fish to copper at various water pH levels using an apparatus which separates inspired and expired water. The relationship between pH levels inside and outside of the gill microenvironment, between pH and alkalinity, and between mucus secretion, pH, and copper exposure concentration were modeled. Copper speciation in the surrounding water and in the fish gill microenvironment was simulated using MINTEQA2 chemical equilibrium calculation software. The results of the modeling for pH, alkalinity, and mucus calculation were then adopted as inputs for purposes of parameter identification in the speciation modeling. The differences observed in the copper species distribution between that of the fish gill microenvironment and the surrounding water were based on the speciation modeling. The change in copper bioavailability for fish uptake was also examined. The results indicate the presence of an experimental pH balance point at 6.9, where the pH in the fish gill microenvironment is identical to that of the surrounding water. The observed deviation range in pH levels between that found at the gills and that of the surrounding water varied from -0.4 to 0.8 units. A sinusoidal model was developed for calculation of gill pH based on the pH of the surrounding water. Models calculating alkalinity either in the gill microenvironment or in the surrounding water and for estimating mucus secretion were also developed. The results of the chemical equilibrium calculations demonstrate that, within a pH range of 6-9, the dominant species of copper in bulk solution shifted from free ions to that of the hydroxo complex. With respect to the fish gill microenvironment, the dominant species found under acidic conditions were the mucus copper complex and free ions. Because of the influence of mucus complexation and pH change, bioavailable copper species in the fish gill microenvironment were significantly lower than that in the bulk solution, especially under acidic conditions.

Acid-Base Equilibrium↗
PubMed2001

Prevention of brick tea fluorosis in rats with low-fluoride brick tea on laboratory observation.

To test whether low-fluoride brick tea can prevent the occurrence of fluorosis, rats had access only to a specially prepared low-fluoride brick tea for 1 year. The daily fluoride intake, fluoride metabolism, tissue distribution and development of tooth fluorosis were observed at 4-monthly intervals, at the end of months 4, 8 and 12, respectively. Rats drinking ordinary brick tea (F- 503.5 mg/kg) served as control. The daily intake of fluoride in the ordinary brick tea group was 0.3 mg, and this group developed dental fluorosis characterized as brown and white horizontal marks at the end of month 8, and white chalky dental fluorosis developed at the end of month 12. The total incidence was 75%. In contrast, the daily fluoride intake of the low-fluoride brick tea (F- 210 mg/kg) group was 0.19 mg, and this group did not develop any signs of dental fluorosis. Fluoride distribution was mainly retained in the bone tissue, and about half of the absorbed fluoride was excreted via urine and feces. The results suggest that this low-fluoride brick tea did not induce fluorosis in rats and can be used as an effective control measure for humans.

Age Factors↗
PubMed2001

Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum.

Acetylcholine release stimulated by nicotinic agonists was measured as radioactivity released from perfused synaptosomes prepared from mouse interpeduncular nucleus (IPN) that had been loaded with [(3)H]choline. Agonist-stimulated release was dependent upon external calcium and over 90% of released radioactivity was acetylcholine. The release process was characterized by dose response curves for 13 agonists and inhibition curves for six antagonists. alpha-Conotoxin MII did not inhibit this release, while alpha-conotoxin AuIB inhibited 50% of agonist-stimulated release. Comparison of this process with [(3)H]dopamine release from mouse striatal synaptosomes indicated that different forms of nicotinic acetylcholine receptors (nAChRs) may mediate these processes. This was confirmed by assays using mice homozygous for the beta 2 subunit null mutation. The deletion of the beta 2 subunit had no effect on agonist-stimulated acetylcholine release, but abolished agonist-stimulated release of dopamine from striatal synaptosomes. Mice heterozygous for the beta 2 subunit null mutation showed decreased dopamine release evoked by L-nicotine with no apparent change in EC(50) value, as well as similar decreases in both transient and persistent phases of release with no changes in desensitization rates.

Acetylcholine↗
PubMed2001

Differential regulation of hepatic bile salt and organic anion transporters in pregnant and postpartum rats and the role of prolactin.

We characterized expression and activity of the bile salt transporters Na(+)/taurocholate (TC) cotransporting polypeptide (Ntcp), and bile salt export pump (Bsep), and the expression of organic anion transporting polypeptides 1 and 2 (Oatp1 and 2) and multidrug resistance associated protein-2 (Mrp2) in pregnancy and throughout lactation in rats. The V(max) for Na(+)/TC cotransport in basolateral liver plasma membrane was increased 1.7-fold in 2 days postpartum relative to control and pregnant rats. This correlated well with an increase in Ntcp messenger RNA (mRNA) and a 2-fold increase in Ntcp protein. Ntcp mRNA remained significantly elevated until 14 days postpartum but had begun to decline by 21 days postpartum. The maximal secretory rate (nmol/min/g liver) for TC in the single pass isolated perfused liver was also increased by 10%, 31%, and 24% at 2, 14, and 21 days postpartum and correlated with increased expression of Ntcp and Bsep mRNA and protein. Infusion of ovine prolactin (oPRL) to ovariectomized rats increased expression of both Ntcp and Bsep mRNA and protein. These data indicate a coordinate increased expression of bile salt transporters postpartum and by PRL. Mrp2 mRNA was stable in pregnancy and postpartum, whereas Mrp2 protein expression decreased significantly in pregnancy, but returned to control levels postpartum. Organic anion transporting polypeptide 2 (Oatp2) mRNA was decreased in pregnancy and increased postpartum, but changes in Oatp2 protein were not significant. Oatp1 mRNA and protein were unchanged in pregnancy and postpartum.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

The use of psychoactive substances among adolescent students in an area in the south-west of China.

AIM: To survey drug/psychoactive substance use among adolescent students in a south-west province of China. DESIGN: A cluster sample was drawn from this province of nine districts or cities. Each district/city provided two schools from grade 11 senior high school, A total of 18 schools were selected randomly. FINDINGS: A total of 2649 students completed this self-report questionnaire, mean age 17.1 +/- 0.9 years. The response rate was 92.7-95.6% for each of the specific substances or drugs. The 'life-time prevalences of regular substance use' (at least 15 times during in any one month) were, in rank order of prevalence: tobacco 6.3%, non-steroid anti-inflammatory drugs (NSAID) 2.9%, alcohol 2.9%, solvent 0.3%, sedative/hypnotic 0.2% and cannabis 0.04%. The life-time prevalences of at least some use were: alcohol 66.1%, NSAID 59.3%, tobacco 27.4%, sedative/hypnotic 5.2%, heroin 3.1%, solvents 2.8%, amphetamine-type stimulants (ATS) 0.7% and cannabis 0.3%. The 'prevalences of current regular use' (at least 15 times in the past month) were: tobacco 4.2%, alcohol 1.6%, NSAID 0.8%, sedative/hypnotic 0.1%, solvents 0.1% and cannabis 0.1%. The 'prevalences of current use at any level' were: alcohol 15.2%, NSAID 9.6%, tobacco 7.1%, sedative/hypnotic 0.5%, solvents 0.4%, cannabis 0.1%, heroin 0.1%, and ATS 0.04%. The median age at onset substance use was between 10.7 and 13.4 9.6%. CONCLUSIONS: Drug misuse has appeared among teenage students in this area. The most widely used substances were alcohol and cigarettes. The rates of solvent, tobacco and alcohol use among males were substantially higher than in females.

Adolescent↗
PubMed2001

Expression of multidrug resistance-associated protein 2 in small intestine from pregnant and postpartum rats.

We analyzed the expression of multidrug resistance-associated protein 2 (mrp2) in the small intestine of control female rats and in rats during late pregnancy (19-20 days of pregnancy) and lactation (2-4, 10-14, and 21 days after delivery). Western blot analysis was performed on brush-border membranes prepared from different regions of the small intestine. Expression of mrp2 was maximal in the proximal segments for all experimental groups, was preserved in pregnant rats, and increased by 100% in postpartum rats by late lactation with respect to control animals. Northern blot analysis of mrp2 mRNA revealed a positive correlation with protein levels. Transport of S-glutathione-dinitrophenol (DNP-SG) from the intestinal cell to the lumen was analyzed in the everted intestinal sac model. Secretion of DNP-SG was not altered in pregnant rats but increased in lactating animals by late lactation. Intestinal mrp2 mRNA, protein, and transport activity are increased in lactating rats, suggesting that this may represent an adaptive mechanism to minimize the toxicity of dietary xenobiotics in response to increased postpartum food consumption.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Ruscogenin glycoside (Lm-3) isolated from Liriope muscari improves liver injury by dysfunctioning liver-infiltrating lymphocytes.

The effects of ruscogenin 1-O-[beta-D-glucopyranosyl(1 --> 2)] [beta-D-xylopyranosyl(1 --> 3)]-beta-D-fucopyranoside (Lm-3) and its aglycone, ruscogenin, on liver injury induced in mice by delayed-type hypersensitivity to picryl chloride have been investigated. Lm-3 and ruscogenin significantly decreased liver injury when given during the effector phase of the delayed-type hypersensitivity reaction. The pretreatment of nonparenchymal cells, but not hepatocytes, with Lm-3 or ruscogenin in-vitro caused a concentration- and time-dependent inhibition against the damage. Lm-3 showed a stronger inhibition against the damage than ruscogenin (IC50: Lm-3 6.3 x 10(-10) M, ruscogenin 3.9 x 10(-7) M). However, neither Lm-3 nor ruscogenin blocked the hepatotoxic potential of CCl4, when used to pretreat hepatocytes. Moreover, Lm-3 and ruscogenin inhibited concanavalin A-induced lymphocyte proliferation only at high concentrations. These results suggested that Lm-3 and ruscogenin improved the immunological liver injury by selectively causing dysfunction of the liver-infiltrating cells rather than by protecting hepatocyte membranes. Such characteristics would be significant for treating immunologically related liver diseases as well as for developing new drugs.

Animals↗
PubMed2001

Effect of long-term exposure to fluoride in drinking water on risks of bone fractures.

Findings on the risk of bone fractures associated with long-term fluoride exposure from drinking water have been contradictory. The purpose of this study was to determine the prevalence of bone fracture, including hip fracture, in six Chinese populations with water fluoride concentrations ranging from 0.25 to 7.97 parts per million (ppm). A total of 8266 male and female subjects > or =50 years of age were enrolled. Parameters evaluated included fluoride exposure, prevalence of bone fractures, demographics, medical history, physical activity, cigarette smoking, and alcohol consumption. The results confirmed that drinking water was the only major source of fluoride exposure in the study populations. A U-shaped pattern was detected for the relationship between the prevalence of bone fracture and water fluoride level. The prevalence of overall bone fracture was lowest in the population of 1.00-1.06 ppm fluoride in drinking water, which was significantly lower (p < 0.05) than that of the groups exposed to water fluoride levels > or =4.32 and < or =0.34 ppm. The prevalence of hip fractures was highest in the group with the highest water fluoride (4.32-7.97 ppm). The value is significantly higher than the population with 1.00-1.06 ppm water fluoride, which had the lowest prevalence rate. It is concluded that long-term fluoride exposure from drinking water containing > or =4.32 ppm increases the risk of overall fractures as well as hip fractures. Water fluoride levels at 1.00-1.06 ppm decrease the risk of overall fractures relative to negligible fluoride in water; however, there does not appear to be similar protective benefits for the risk of hip fractures.

Aged↗
PubMed2001

CMT-3, a non-antimicrobial tetracycline (TC), inhibits MT1-MMP activity: relevance to cancer.

Tetracyclines (TCs) and their non-antimicrobial analogs (CMTs) have therapeutic potential to inhibit tissue destructive disease processes, such as cancer invasion and metastasis, by inhibiting certain matrix metalloproteinases. Enhanced matrix metalloproteinase-2 (MMP-2; gelatinase A) activity has been correlated to cancer invasiveness, and membrane type MMP (MT1-MMP) expressed by tumor cells is involved in localizing and activating pro-MMP-2, a pathway believed to mediate cancer induced tissue breakdown. CMT-3 (6-demethyl, 6-deoxy, 4-dedimethylamino TC) has been shown to experimentally suppress prostate cancer, colon adenocarcinoma and melanoma invasiveness in cell culture and to inhibit tumor growth and metastasis in vivo and was used in the current in vitro study. Confluent MT1-MMP transfected COS-1 cells were harvested, washed thoroughly, subjected to N(2) cavitation and cell membrane enriched fractions were isolated by sequential centrifugations. This MT1-MMP preparation exhibited (i) pro-MMP-2 activating activity as shown by molecular weight shift of this gelatinase from 72 kDa to 62 kDa using gelatin zymography, and (ii) the ability to degrade both [(3)H-methyl] gelatin and casein at 37 degrees C. Adding CMT-3 at final concentrations of 5--20microM inhibited MT1-MMP gelatinolytic and caseinolytic activity, blocked MT1-MMP activation of pro-MMP-2, and decreased invasiveness (using the Matrigel system) of HT-1080 fibrosarcoma cells. The inhibition of MT1-MMP by CMT-3 may partially explain the inhibition of cancer cell -mediated tissue breakdown and invasiveness by this non-antimicrobial tetracycline analog.

Animals↗
PubMed2001

Reversal of multidrug resistance by the P-glycoprotein modulator, LY335979, from the bench to the clinic.

Multidrug resistance may be conferred by P-glycoprotein (Pgp, ABCB1) or the multidrug resistance associated protein (MRP). These membrane proteins are members of the ATP binding cassette transporter superfamily and are responsible for the removal from the cell of several anticancer agents including doxorubicin. Modulators can inhibit these transporters. LY335979 is among the most potent modulators of Pgp with a Ki of 59 nM. LY335979 is selective for Pgp, and does not modulate MRP-mediated resistance by MRP1 (ABCC1) and MRP2 (ABCC2). LY335979 significantly enhanced the survival of mice implanted with Pgp-expressing murine leukemia (P388/ADR) when administered in combination with either daunorubicin, doxorubicin or etoposide. Coadministration of LY335979 with paclitaxel compared to paclitaxel alone significantly reduced the tumor mass of the Pgp-expressing UCLA-P3.003VLB lung carcinoma in a xenograph model and delayed the development of tumors in mice implanted with the parental drug-sensitive UCLA-P3 tumor. LY335979 was without significant effect on the pharmacokinetics of these anticancer agents. This may be due impart to its poor inhibition of four major cytochrome P450 isozymes important in metabolizing doxorubicin and other oncolytics. The selectivity and potency of this modulator allows the clinical evaluation of the role of Pgp in multidrug resistance. LY335979 is currently in clinical trials.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Chemical characteristics and relative bioavailability of supplemental organic copper sources for poultry.

Five commercially available organic Cu products and reagent-grade CuSO4 x 5H2O (Cu Sulf) were evaluated by polarographic analysis and solubility in 0.1 M K2HPO4-KH2PO4 buffer (pH 5), 0.2 M HCl-KCl buffer (pH 2), or deionized water. Fractions from these solubility tests were evaluated by gel filtration chromatography for structural integrity. The organic sources were Cu lysine complex (Cu Lys), Cu amino acid chelate (Cu AA), Cu proteinate A (Cu ProA), Cu proteinate B (Cu ProB), and Cu proteinate C (Cu ProC). Separation of peaks in the chromatograms for the soluble Cu fraction from deionized water indicated that 77, 31, 69, 94, and 16% of the Cu remained chelated for the above sources, respectively. Two experiments were conducted to estimate the relative bioavailability of Cu from the organic Cu supplements for chicks when added at high dietary concentrations to practical corn-soybean meal diets. Liver Cu concentration increased (P < 0.0001) as dietary Cu increased in both experiments. When Cu Sulf was assigned a value of 100% as the standard, linear regression slope ratios of log10 liver Cu concentration regressed on added dietary Cu concentration gave estimated relative bioavailability values of 124 +/- 5.1, 122 +/- 5.3, and 111 +/- 6.0 for Cu Lys, Cu AA, and Cu ProC, respectively, in Exp. 1. The bioavailability estimates for Cu Lys and Cu AA were greater (P < 0.05) than that for Cu Sulf. Values in Exp. 2 were 111 +/- 7.6, 109 +/- 8.4, and 105 +/- 7.5 for Cu Lys, Cu ProA, and Cu ProB, respectively, and all sources were similar in value for chicks. Solubility of Cu in pH 2 buffer provided the best prediction of bioavailability (r2 = 0.924). Other indicators of chelation integrity and solubility had little value as predictors of bioavailability (r2 < or = 0.445).

Animals↗
PubMed2001

Inhibition of TNF-alpha-induced sickle RBC retention in retina by a VLA-4 antagonist.

PURPOSE: Patients with sickle cell disease have elevated circulating levels of cytokines including tumor necrosis factor (TNF) alpha. TNF-alpha stimulates expression by endothelial cells of adhesion molecules, including vascular cell adhesion molecule (VCAM) 1. Others have demonstrated that VLA-4 (alpha(4)beta(1)), a ligand for VCAM-1 or fibronectin, is present on a fraction of sickle reticulocytes. The intent of this study was to determine, using a rat model, if TNF-alpha increases retention of sickle erythrocytes in retina and if that retention can be inhibited. METHODS: TNF-alpha was given intraperitoneally to rats 5 hours before IV administration of FITC-labeled, density-separated sickle erythrocytes. After 5 minutes, rats were exsanguinated, and retinas were excised and incubated for ADPase activity, permitting the determination of the number and location of retained cells. RESULTS: TNF-alpha caused a three- to fourfold increase in retention of sickle erythrocytes in retinal capillaries (P < 0.05) but not of normal human erythrocytes. Preincubation of sickle erythrocytes with TBC772, a peptide that blocks the binding of alpha(4)beta(1) and alpha(4)beta(7), or a monoclonal antibody against VLA-4 (19H8), significantly inhibited the TNF-alpha-induced retention (P < or = 0.02), whereas a control cyclic peptide and antibody had no effect. IV TBC772 also inhibited sickle erythrocyte retention (P = 0.01). Two intravenously administered anti-fibronectin antibodies inhibited sickle cell retention as well, but an anti-rat VCAM-1 antibody did not inhibit retention. CONCLUSIONS: The authors conclude that TNF-alpha stimulates retention of sickle erythrocytes in the retinal vasculature. This increased retention can be blocked by a VLA-4 antagonist, suggesting that the cells retained after cytokine stimulation are reticulocytes. The counter-receptor for VLA-4 in this rat retina model appears to be fibronectin and not VCAM-1, based on data obtained using antibodies against these molecules.

Anemia, Sickle Cell↗
PubMed2000

Conversion of threonine 757 to valine enhances Stat5a transactivation potential.

The growth hormone family of cytokines transduces intracellular signals through the Jak2-Stat5 pathway to activate the transcription of target genes. Amino acids within the C termini of Stats constitute the transactivation domain but also regulate the time course of tyrosine phosphorylation and extent of DNA binding. We mutated Thr(757) in the C-terminal of Stat5a (Thr-Stat5) to Val (Val-Stat5) and Asp (Asp-Stat5) and examined the effect on nuclear translocation, DNA binding, and prolactin-induced transcriptional activation of a Stat5-responsive luciferase reporter gene. Val-Stat5 produced a 5-fold higher increase in transcriptional activity relative to Thr-Stat5; Asp-Stat5 produced a similar response to Thr-Stat5. The increased transactivation was ligand induced and was not due to differences in basal expression of Val-Stat5 or to a constitutively activated Stat5 protein. Similar rates of loss of DNA binding ability and phosphorylation of Val- and Thr-Stat5 were observed following a single pulse of prolactin, indicating that the dephosphorylation pathways were unaltered. The serine-threonine kinase inhibitor H7 inhibited the transactivation potential of Thr-, Val-, and Asp-Stat5 to a similar extent, eliminating phosphorylation of Thr(757) as a regulatory mechanism. The results suggest that Thr(757) modulates the transactivation potential of Stat5 by a mechanism(s) that is dependent on the formation of Stat5 dimers and/or their nuclear translocation.

Aspartic Acid↗